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iGuide 2009

iGuide
intensive care medicine 2009

From an idea by Tom Woodcock.


"Diseases desperate grown,
By desperate appliance are relieved,
Or not at all."

King Claudius in 'Hamlet' 4.3, Shakespeare,

quoted by Patrick Shackleton, Lancet  1958

"Vel parvo, vel magno, in stercore semper."

MS Neilsen

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iGuide 2009

Table of Contents
Good clinical practice in Critical Care .......................................................................................5
Defining Critical Care .......................................................................................................5
Care bundles ....................................................................................................................5
Outreach ..........................................................................................................................5
Quality assurance in ICU practice ......................................................................................5
Practical Procedures ................................................................................................................7
Precautions for all staff; .......................................................................................................7
Infected health workers ....................................................................................................7
Procedures ..........................................................................................................................7
Any vascular access ..........................................................................................................7
Taking samples ................................................................................................................7
Read The Instructions. ......................................................................................................7
Use 2D Ultrasound to visualise the vessel before and after catheterising it .......................8
Arterial lines. ....................................................................................................................8
Central lines. ....................................................................................................................9
Cardiac output measurement .........................................................................................10
Pulmonary artery (right heart) catheters .........................................................................10
Haemofiltration; vascular access. ...................................................................................12
Endotracheal intubation. ................................................................................................12
Tracheostomy ................................................................................................................12
Setting up a ventilator ....................................................................................................13
Patient transport ............................................................................................................13
Thoracostomy ................................................................................................................13
Metabolic measurements ...............................................................................................13
Radiology .......................................................................................................................13
Management of self poisoning .......................................................................................14
Consent to treatment. ....................................................................................................14
Withholding and withdrawing life sustaining treatments in the Critical Care Unit; a few
practical and legal points. ..............................................................................................14
General care ..........................................................................................................................16
Body position .................................................................................................................16
Acute Gastric dilatation ..................................................................................................16
Peptic ulceration ............................................................................................................16
Nutrition ........................................................................................................................16
“Renal dose” dopamine ...................................................................................................16
Neither wet nor dry ........................................................................................................17
Thrombo-embolism prophylaxis ....................................................................................17
Hospital acquired infections ...........................................................................................17
Breaking the cycle of infection ........................................................................................18
Nosocomial, or Ventilator associated, pneumonia ..........................................................18
Urinary tract infections ...................................................................................................19
Catheter-related sepsis ..................................................................................................19
Gut permeability and systemic sepsis .............................................................................19
Systemic inflammatory response and septic shock ..........................................................19
Anti-inflammatory therapies in severe sepsis. ................................................................21
Organ dysfunction or failure. ..........................................................................................21
Neuromuscular changes .................................................................................................22
Circulatory support ................................................................................................................23
Resuscitation. .................................................................................................................23
Do Not attempt Resuscitation (DNAR) instructions .........................................................23
Shock ................................................................................................................................23
Cardiogenic shock ..........................................................................................................23
Hypovolaemic shock .......................................................................................................23
Distributive or hyperdynamic shock ................................................................................24
Assessing shock state ....................................................................................................25
Principles of shock reversal ................................................................................................25
ANAPHYLAXIS; a special case ..........................................................................................26
Sequential resuscitation phase 1 ....................................................................................26
Sequential resuscitation phase 2a ...................................................................................26
Sequential resuscitation phase 2b ..................................................................................26
Sequential resuscitation phase 3 ....................................................................................27
Sequential resuscitation phase 4 ....................................................................................28

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Side effects ....................................................................................................................28


MODS; the multi-organ dysfunction syndrome. ..................................................................28
Small print .....................................................................................................................29
Metabolic Acidosis .............................................................................................................29
Arrhythmias .......................................................................................................................29
Hypertension .....................................................................................................................30
The Vascular Pedicle ..........................................................................................................30
Respiratory Support ...............................................................................................................32
Prophylactic respiratory support .....................................................................................32
Therapeutic respiratory support .....................................................................................32
The ventilator care bundle .................................................................................................33
Tracheostomy; if, when, how. .........................................................................................33
Type 1 Respiratory failure ..................................................................................................33
Acute lung injury ............................................................................................................34
Therapy of type 1 respiratory failure ...............................................................................35
Severe acute respiratory failure. .....................................................................................35
Small print .....................................................................................................................38
Type II Respiratory Failure .................................................................................................38
Therapy of Type II respiratory failure ..............................................................................38
Humidification, secretions etc. ...........................................................................................40
Weaning from Mechanical Ventilation .................................................................................40
Weaning check-list .........................................................................................................40
Rapid wean ....................................................................................................................40
Slow wean ......................................................................................................................40
‘Classic’ wean ................................................................................................................40
“Progressive care programme” ........................................................................................41
Minitracheostomy ...........................................................................................................41
Fibreoptic Bronchoscopy (FOB) .......................................................................................41
Intubation. .....................................................................................................................41
Fluids, solutes, acid/base balance .........................................................................................42
Essential physiology. ......................................................................................................42
Natraemia ......................................................................................................................43
Chloraemia ....................................................................................................................43
Kalaemia ........................................................................................................................43
Hypomagnesaemia .........................................................................................................43
Therapeutic hypermagnesaemia .....................................................................................43
Calcaemia .......................................................................................................................44
Phosphataemia ...............................................................................................................44
Albuminaemia ................................................................................................................44
Colloid osmotic pressure ................................................................................................44
Glycaemia .......................................................................................................................44
Crystalloid Vs Colloid .....................................................................................................46
Comparing available colloids ..........................................................................................46
Maintenance fluids, and deficits. ....................................................................................46
Resuscitation fluids ........................................................................................................48
Blood and clotting factors ..............................................................................................48
Acid-base balance ..........................................................................................................49
Renal Support ........................................................................................................................51
Pathophysiology of Acute Renal Failure ..........................................................................51
Management of oliguria .................................................................................................52
Renal Replacement therapy (RRT) ...................................................................................52
Unphysiologic anions .....................................................................................................54
Nutrient balance .............................................................................................................54
Drug clearance ...............................................................................................................54
Outcome ........................................................................................................................54
Liver Failure ..........................................................................................................................55
Unconjugated hyper-bilirubinaemia ...............................................................................55
Conjugated hyper-bilirubinaemia, ..................................................................................55
Acute Liver Failure (ALF) .................................................................................................55
Ascites ...........................................................................................................................56
Upper GI tract Bleeding and Portal Hypertension. ............................................................56
Nutritional Support ................................................................................................................57
Vitamins .........................................................................................................................57

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Feeding acutely ill patients .............................................................................................57


Feeding starved patients ................................................................................................58
Disease-specific considerations .....................................................................................58
Enteral Feeding ..............................................................................................................58
Parenteral nutrition ........................................................................................................58
Small print. ....................................................................................................................59
Sleep, sedation and mood .....................................................................................................60
Features of sleep ............................................................................................................60
Disorders of sleep ..........................................................................................................60
Hypnosis ........................................................................................................................61
Hypoxaemia during sleep ...............................................................................................61
Pathophysiology of mood and consciousness .................................................................61
Sedation in Intensive Care ..............................................................................................63
Mu receptor agonists .....................................................................................................64
GABAA receptor agonists binding the gamma subunit (Benzodiazepine receptor) ...........64
GABAA receptor agonists binding the beta subunit. ........................................................65
NMDA receptor antagonists ............................................................................................65
Mixed action anaesthetics. .............................................................................................65
Two-pore-domain potassium channel activators. ...........................................................65
Alpha-2 c receptor agonists. ..........................................................................................66
Anaesthesia ...................................................................................................................66
Mood. .............................................................................................................................66
Cerebral Support and Determination of Brain Stem Death ......................................................67
Principles of ICP control. ................................................................................................67
Continuous processed electro-encephalography ............................................................68
Jugular bulb venous oximetry .........................................................................................68
Status epilepticus ...........................................................................................................68
Coma after cerebral ischaemia .......................................................................................69
Death determined by brain stem tests. ...........................................................................69

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Chapter 1

Good clinical practice in Critical


Care
 

Defining Critical Care


The Department of Health's vision for the future of Critical Care within the National Health
Service is described in a key document called Comprehensive Critical Care which you can find
on the Department of Health’s world wide web pages
Clinical Standards Committee of ICS have refined the definitions of levels of critical care and
these too can be found on-line. Other useful standards documents are provided by the
Intensive Care Society, the world's oldest professional Intensive or critical care society.
http://www.ics.ac.uk
and by the Society of Critical Care Medicine, the world's largest.
http://www.sccm.org/

Care bundles
The NHS Modernisation Agency’s “High Impact Change” number 6 is “Increase the reliability of
performing therapeutic interventions through a Care Bundle approach” and several Care
Bundles were identified for Critical Care in about 2003. Originally proposed by the United
States Institute for Health Improvement, they are described as evidence-based protocols but
are not immune from criticism. Typically they include Ventilator Bundle, Central Line Bundle,
Sepsis Resuscitation Bundle, Sepsis Management Bundle and Optimal Glucose Control.
The following are the current “Areas of Focus” for the IHI:
• Eliminate inappropriate days in the ICU
• Reduce infections resulting from mechanical ventilation and central lines
• Implement early identification and optimal treatment of sepsis
• Institute intensive glucose management
• Shorten weaning times from ventilators
• Reduce sedation costs for patients on mechanical ventilation
• Reduce adverse events in the ICU
• Implement multidisciplinary rounds and daily goals sheets
• Decrease delays in discharge by improving throughput of ICU patients
• Improve efficiency by focusing on value-added processes and removing waste
Their ambitious goals are to reduce ICU mortality by at least 20% and adverse events by 75%!
This Guide is IHI-compatible, so read and digest…

Outreach
'Critical care without walls' was a slogan underlying the introduction of teams, often nurse-
led, which support non-critical care professionals in recognizing and treating patients who are
at risk or who become critically-ill. Though the benefits of this service have not yet been
established, they are widely presumed to be self-evident.

Quality assurance in ICU practice


You should familiarize yourself with the various instruments for estimating 'predicted
mortality' in a cohort of patients, which allows comparison with the actual or 'observed'
mortality. The ratio of observed / predicted is called the Standardised Mortality Ratio and can
be used to monitor ICU performance and compare it to other ICUs. Commonly used systems
are 'Acute Physiology and Chronic Health Evaluation' (APACHE), 'Simplified Acute Physiology
Score' (SAPS) and Mortality Prediction Model (MPM).

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The Intensive Care National Audit and Research Council are able to monitor standards of care
in participating services; see the ICNARC website to see what can be done with good-quality
information;
http://www.icnarc.org/
The Societe Francaise d’Anesthesie et de Reanimation publish some ‘international’ pages in
English which include some on-line risk-stratifying scoring systems which you may want to
use on real patients;
http://www.sfar.org/

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Chapter 2

Practical Procedures
Precautions for all staff;
have vaccination and boosters against do not resheath needles
hepatitis B dispose of all sharps in approved
cover cuts and abrasions with container
waterproof dressing disposables and waste into yellow
do not pass sharps hand to hand clinical waste bag for incineration.
do not use hand needles
do not guide needle with fingers
Additionally, when caring for HIV, hepatitis, and high risk patients;

mark all specimens as high risk; notify high level discipline


laboratory staff; experienced carers only
special arrangements for blood gases double glove, gown, mask, eye
(Ask technicians) protection
use minimum invasive procedures disposable anaesthetic and respiratory
remove unnecessary equipment care
equipment
refer to current local policies

Infected health workers


The GMC and Department of Health recommends that staff who think they have been at risk of
infection should be confidentially counselled and tested.  If the worker is HIV or Hepatitis B e-
antigen positive he/she should stop performing invasive procedures.  Observation of these
recommendations is regarded as mandatory by the Medical Defence Societies.  The Trust are
required to take active steps to ensure staff performing invasive procedures are not infected;
in the near future it may be routine to check your hepatitis B e-antigen status, so your career
is at risk if you are careless.
Methicillin-resistant staphylococci are an expanding problem in ICUs. Be careful to wash your
hands before and after patient contacts and wear protective clothing (gloves, gown) when
required by infection control policy. Frequent use of antiseptic gel-dispensers is encouraged.
The NHS has adopted a ‘bare below the elbows’ policy even though there is no evidence that
dress or uniform policy affects hospital-acquired infections. You should cooperate with staff
screening procedures (a series of three nose swabs) when these are requested.

Procedures
Any vascular access
Observe policies on skin preparation, technique, dressing and audit in order to minimize
complications including catheter-related sepsis.

Taking samples
Specimen containers must only be labeled AFTER the specimen has been taken; prelabelling
invariably leads to occasional errors, sometimes with catastrophic consequences.

Read The Instructions.


Whenever you perform a procedure with a kit, whether a central venous line, dialysis catheter,
or tracheostomy tube, be sure you are familiar with the Manufacturers note for the Operator. 
When things go wrong, and you have omitted to do something recommended by the
manufacturer, it is very difficult to defend you from litigation.

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Use 2D Ultrasound to visualise the vessel before and after


catheterising it
2DUS is available on the ICU. Check the anatomy, and confirm patency, before attempting
vascular catheterization. Confirm correct placement and absence of haematomas after
placement. You can periodically inspect indwelling vascular catheters for evidence of
thrombus formation.

Arterial lines.
Radial or dorsalis pedis arteries are usually used for safety and convenience, but brachial and
femoral lines are better sites to measure the ‘central’ arterial pressure in hypotensive patients. 
In norepinephrine treated shocked patients radial artery pressure usually underestimates
central arterial pressure and may lead to unnecessarily high doses of vasopressor being used.
The depth of the femoral artery from the skin demands a longer catheter than the standard
20G; remember to cannulate the femoral artery (if absolutely necessary) just below the
inguinal ligament, lower approaches are traumatic.  Axillary artery cannulation is described
but rarely used.
Blood gas analysis.
Important decisions are taken on the basis of arterial and/ or venous blood gas results.  Take
steps to prevent contamination of your samples due to flush solution or air.  Cap the syringe.
Analyse straightaway, or else keep sample “on ice” if there is an unavoidable delay.
Ensure sample is well mixed
before introducing to the blood
gas machine.  Use the “mixing
wire” provided for this purpose
when analysing capillary
samples (see instruction sheet
for details).
In ICU practice it is not
necessary to adjust for patient
temperature.
The isoshunt method is
recommended for choosing the
next FIO2 after arterial blood
analysis. (The diagram shown
here is in Torr rather than kPa,
and you do have to calculate
the alveolar oxygen tension;
clinical approximation (in kPa)
PAO2 = FIO2(PB-6.2) - 1.2
(PaCO2).) And once you have estimated the PAO2 you can easily calculate the A-a gradient!
Blood Cultures.
Bacteraemia is common in Intensive Care patients and mortality can only be reduced if we use
blood culture techniques appropriately. When septicaemia is suspected (temperature spike,
hypotension, tachycardia) a sample must be drawn using aseptic technique (iodine prep, gown
& glove) from an uncatheterised vein. If catheter-related sepsis is suspected, draw "isolator"
samples for semi-quantitative results from the suspect vascular catheters.

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Central lines.
Uses;
measuring/ monitoring CVP,
measuring/ monitoring venous gases, acid-base, electrolytes etc.
injecting indicators for haemodynamic investigations,
infusing/ administering drugs,
infusing/ administering fluids, nutrition.
Triple or quadruple lumen catheters are often preferred.   Heparin bonded and antibiotic
impregnated catheters can be used in selected cases.   A dedicated tunnelled feeding line
(usually subclavian) is preferred for longer-term parenteral nutrition. CV catheters with
continuous venous oximetry are available; see below on mixed venous oximetry for rationale.
Central venous access routes;
NICE Technology Appraisal No 49 relates to Ultrasound Locating Devices for placing Central
Venous Catheters. Please learn both landmark and US-guided techniques for application in
your practice, and make a note in patient record which you used for each procedure.
Pre-insertion imaging of the vein reveals its anatomy and patency at that point;

Post-insertion imaging can be used to confirm intravascular position;

Right internal jugular is preferred for routine central venous access.   Be aware of different
approaches; 'high' depends upon palpation of carotid artery medial to sternomastoid and is
widely taught by UK anaesthetists, while 'low' locates the vein at the apex of the triangle
formed by sternal and clavicular heads of the muscle (clavicle at base of this triangle) and is
preferred in US/ Canadian practice. The 'low' approach is used for retrograde jugular bulb
catheterization. Left subclavian is the route of second choice, but should be preserved if
parenteral nutrition may be needed.  Left internal jugular and right subclavian veins are technically
more difficult to cannulate.  Infraclavicular axillary vein cannulation is a possible alternative to
traditional approaches and can be ultrasound-guided. Supraclavicular approach to the
subclavian vein is popular in some centres.  Basilic vein can be catheterised in the arm using
2DUS and is suitable for ‘long’ multi-lumen central venous catheters. Antecubital fossa long
lines should only be used for acute short-term cannulation or when other approaches are
contraindicated (e.g. profound coagulopathy).  Femoral venous cannulation looks deceptively
simple, but a common mistake is attempt cannulation too far below the inguinal ligament. 
You may then hit the long saphenous vein or one of its tributaries.  Note the position of the
inguinal ligament, and attempt to puncture the vein no more than 1 inch below the ligament.
It is best practice to avoid femoral vascular access as far as possible!

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Insertion
Use whichever route and technique of insertion you have been taught and are most confident
with, and always ensure that you have read the manufacturers recommendations for the
specific catheterisation kit you choose.  After placement of a subclavian or jugular catheter
please get CXR within the hour and inspect carefully for pneumothorax and to check tip
position (do not leave tip within the right atrium). 
After connecting a CV line to the transducer, examine the trace for
waveform; SVC placement? tricuspid incompetence?
pressure; referred to mid-axillary line is traditional, and note response to fluid challenge
pressure variability with positive pressure ventilation; minimal when blood volume is
'filled'.
At earliest opportunity, draw and analyse a venous blood gas (VBG). A poor man’s substitute
for ‘mixed’ venous blood from the pulmonary artery, but seems to have value for decision-
making. Oxyhaemoglobin saturation 65-75% is about normal, but less than this suggests
tissue hypoxia and need for urgent resuscitation.
There is no benefit in "routine" line changing, but when a line must be changed it is acceptable
to perform a change at the same site over a guide wire so long as the site is not evidently
inflamed or infected.  Use aseptic technique, and send the tip of the old catheter for culture. 
Take steps to avoid air embolism during insertion, changing or removal of central venous
catheters.  Antiseptic surface treated catheters are now in common use.

Cardiac output measurement


Indicator dilution (indocyanine green, lithium, thermal etc) and aortic blood flow (oesophageal
Doppler) techniques predominate in bedside measurement/ monitoring. Care is needed to
obtain reliable results. See manufacturer's instructions.
Calculated 'Vascular resistance'
Instantaneous ratio of intravascular pressure to flow. Expressed as Wood Units (mmHg divided
by L/min) or SI units (Wood multiplied by fudge factor 79.92 gives dyne sec cm-5). In practice,
the haemodynamic relationship between flow and pressure is non-linear, and depends upon
cardiac output, blood viscosity, and laminar/ turbulent flow characteristics. Therefore you can
rationally treat pressure and flow measurements, but not their calculated ratio (see for
example the Surviving Sepsis Campaign guidelines). Further logical complexities follow when
you use cardiac index in place of cardiac output to calculate 'vascular resistance index'.
Calculated ‘Arterial elastance’
If you can monitor stroke volume, an alternative way to assess vascular ‘tone’ is to look at the
ratio of the proportionate change in arterial pressure to the proportionate change in arterial
volume during an inspiratory – expiratory cycle. For example, if the arterial pressure variation
is 5% and the arterial stroke volume variation is 5%, the arterial elastance is 1. When the
elastance is less than 1 (volume change greater than pressure change), consider
vasoconstrictor therapy. When the elastance is greater than 1 (pressure change greater than
volume change), consider vasodilators.

Pulmonary artery (right heart) catheters


If you believe that you need information about the cardiac output, pulmonary venous and
arterial pressures to provide effective care for your patient you will use a pulmonary artery
flotation catheter (PAFC). Proposed indications include the monitoring of patients
undergoing major surgery,
with acute cardiovascular failure
with severe acute respiratory failure
A PAFC is expensive and can cause fatal complications; if you decide to use a PAFC you should
make every effort to get maximum information from it and be prepared to treat any
abnormalities detected; nobody gets better simply because you put in a ‘Swan’.  The best sites
of insertion are right internal jugular, left subclavian or left antecubital fossa.  “Keep the curve
of the catheter” and from these sites it will go easily to the right pulmonary artery.
Wedging

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Remember the FOUR CRUCIAL STEPS in measuring pulmonary artery wedge pressure.

1/ check PA waveform; is it of good quality? note PA systolic/mean/diastolic.


2/ inflate the balloon SLOWLY until the trace ‘wedges’then lock the syringe port.  DEFLATE if
there is undue resistance or ‘overwedge’ (steadily rising pressure)
3/ PAOP is the mean pressure during expiration (the Servo ventilator features an ‘expiratory
hold’ button to facilitate a steady trace).  Is the trace good? “acv” waves should be evident, and
the ‘wedge’ should be lower than PA diastolic.
4/ Deflate the balloon slowly; does the PA waveform return?
What does the wedge pressure tell us?
If the catheter is in “West zone 3” when the artery is occluded, flow ceases up to the junction
with the first venous tributary from a non-occluded arterial branch. Thus the occlusion
pressure is a measure of pulmonary venous pressure. A special problem with measuring
intravascular pressures in the chest is that they should be referenced to intrathoracic pressure
(the transmural pressure gradient) but for expedience we reference them to extrathoracic
pressure (usually the mid-axillary line). Positive pressure ventilation is an additional
confounding factor. Do not disconnect patients with Type 1 respiratory failure from PEEP or
CPAP in an attempt to get a truer wedge pressure; lung units collapse quickly as FRC falls and
may be slow to recruit.
“Left ventricular preload” would ideally be measured as the left ventricular end-diastolic
volume. To correlate pressure to volume assumptions have to be made about ventricular
compliance and the pressure gradient between the ventricle and pulmonary veins will depend
upon heart rate and mitral valvular function.
“Pulmonary capillary pressure” is a determinant of fluid flux across the capillary and is always
higher than pulmonary venous. In health, the Garr formula gives a reasonable approximation
of pulmonary capillary pressure;
PCAP=PAOP+(0.4(mean PPA-PAOP)
This presumes that 40% of the pulmonary vascular resistance is venular; in critical illness
however there is substantial variability.
Non-invasive assessment of left ventricular end-diastolic pressure.
Spontaneously breathing patients with PAOP or LVEDP >15cmH2O consistently show a square
wave response during the strain phase of Valsalva manoeuvre, while patients with low PAOP/
LVEDP (<8cmH2O) have exaggerated systolic pressure drop. In ventilated patients, look out for
systolic pressure swing with IPPV as a marker of hypovolaemia. To mimic the Valsalva
manoeuvre, examine effect of inspiratory pressure pause at about 30-40cmH2O on systolic BP
to further assess adequacy of  LV preload.
If the vascular pedicle width on the chest radiograph is greater than 70mm, the PAOP is likely
to be >15. Sequential changes in the VPW reflect changes in the intravascular volume and
PAOP.
Mixed venous blood analysis
Venous blood streams are fully mixed by the time they get to the pulmonary artery, so oxygen
consumption calculations use sVO2. By drawing back very gently with the catheter 'wedged'
you can obtain true pulmonary capillary blood, but too dangerous to recommend in clinical
practice! Fibreoptic catheters can be used for continuous mixed venous oximetery. Low values
suggest tissue hypoxia and should be treated if possible.
Cardiac output measurement by thermistor catheter
1. Refer to manufacturers guidance to prevent technical errors relating to injectate volume
and temperature, and correction factors for various thermistors. Errors will produce
potentially dangerous miscalculations.  You should be consistent when making repeated
measures of cardiac output in the timing of injectate. Synchronisation to the respiratory
cycle   may give more reproducible results than unsynchronised injections, but will

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overestimate the mean Qt if synchronised to the ventilators expiration, as is sometimes


advocated, or underestimate if the patient is breathing spontaneously. You should note
that tricuspid regurgitation is common in patients under mechanical ventilation, and this
can cause either underestimation or overestimation of the cardiac output by
thermodilution. PA catheters should be removed as soon as practicable and always by 72
hours.

Haemofiltration; vascular access.


The preferred access is a double lumen catheter inserted into a subclavian vein.  The standard
pack includes Seldinger wire and a rigid dilator to assist placement.  It may sometimes be
necessary to use a femoral vein just below the inguinal ligament but this limits patient
mobility and is more prone to contamination than other sites.
If high volume haemofiltration is to be used as an adjunct to shock reversal, a larger double
lumen catheter is required (consult with ICU technicians).

Endotracheal intubation.
Anaesthetists seem to prefer general anaesthesia and muscle relaxation for intubation, but in
the critically ill patient be prepared for exaggerated hypotension on induction and initiation of
positive pressure ventilation.  It is also necessary to take precautions against regurgitation,
but suxamethonium is a very dangerous drug in the presence of acidosis and/or
hyperkalaemia, and in the presence of burns or denervation (e.g. spinal cord injury).   A
modified rapid sequence induction with a non-depolarising agent such as vecuronium or
rocuronium is often safer.  Awake fibreoptic guided intubation under local anaesthesia has
advantages and is probably underused. The cuff of the tube should be liberally lubricated with
gel in order to prevent leakage of pharyngeal liquids into the trachea. Even with lubrication,
standard low-pressure cuffs become leaky after 24 hours.
Croup;
Epiglottitis commonly affects children aged 3-7 years, but adults are sometimes severely
affected. The onset is typically rapid with high fever (>38.5C), dyspnoea and sore throat. 
Swallowing is so painful the patient sits up and drools.  In suspected epiglottitis summon the
on-call ENT Registrar to theatre, then an experienced anaesthetist performs intubation under
inhalational anaesthesia with emergency tracheotomy equipment to hand.   Place nasogastric
tube. 
Prolonged tracheal intubation
If patients are to be intubated for more than 72 hours give consideration to nasotracheal
route; an oral tube may be changed for a nasal one when convenient.  Contraindications to
nasal intubation include basal skull fractures and coagulopathy.  Complications are said to
include maxillary sinusitis, but evidence suggests sinusitis is is just as common with other
routes of intubation. Nasotracheal intubation in ICU seems to have gone out of fashion, but
remains a useful option.

Tracheostomy
The evidence base is equivocal, but consideration should be given to tracheostomy if long
term tracheal intubation is anticipated.  Bedside ‘percutaneous’ techniques include sequential
or one-stage dilators (Ciaglia), one-stage forceps dilation (Portex), and a translaryngeal dilator
which is pulled from the outside instead of pushed (Mallenkrodt). Do not attempt these
procedures without prior supervised training.  Percutaneous tracheostomies are preferred to
open surgical techniques in most cases.
Minitracheostomy is actually performed through the cricothyroid membrane and is useful in
emergencies.   Also used for airway toilet in patients unable to cough adequately, and
occasionally used to allow jet ventilation.
For any percutaneous tracheostomy technique, an ultrasonographic examination of the
proposed tracheostomy site to reveal aberrant arteries or veins is recommended by some.
Infiltration with local anaesthetic plus epinephrine provides post-procedure analgesia and
reduces blood loss. A 1.5-2cm transverse incision must be made below the cricoid cartilage,
and blunt dissection to the pre-tracheal fascia performed, BEFORE any attempt is made to
puncture the trachea at the first-second or second-third tracheal ring space. Fibre-optic
confirmation of atraumatic puncture of the trachea and suitable level is recommended before
dilation begins.

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Drugs and endotracheal tubes for formal intubation should be readily to hand in case of
serious complications.

Setting up a ventilator
A machine will usually be provided assembled and ready for use when a patient is intubated. 
However, the responsibility for prescribing ventilator settings and checking the safe
performance of the ventilator is yours. Modern ventilators feature assist/control (A/C),
support and synchronised intermittent mandatory ventilation (SIMV) modes. Familiarise
yourself with the ventilators and how to set them early in your attachment.

Patient transport
The principles of safe secondary transfer are simple but too often neglected.   Critically-ill
patients should be intubated and mechanically ventilated for transport. An adequate blood
volume must be assured, and this will usually require monitoring of CVP.  Arterial pressure
monitoring and continuous pulse oximetry are usual.  Only when the patients condition is
stable should he be moved.  Nonetheless, equipment for resuscitation should be carried by
the attending doctor.

Thoracostomy
Complications of this procedure can be life-threatening, so please be meticulous in your
technique. Patients with coagulopathy, poorly compliant lungs and pleural pathology are
common in ICUs and are at special risk. Ultrasonographic localisation of fluid collections is
recommended.

1. Position patient, ideally sitting up 6. Blunt dissection with curved


or semi-recumbent in order to forceps up and over that rib, then
lower the diaphragm. into the pleural space.
2. Check physical signs and confirm 7. Enlarge tract by opening the jaws
indication for drain insertion. of the forceps.
3. Identify site for insertion 8. Digital exploration of the pleural
(recommended, the “TRIANGLE OF cavity to ensure the lung is not
SAFETY” in front of the midaxillary adherent.
line, behind the posterior border 9. Use no trochar or other rigid
of pectoralis major, and above the device; if possible, have ventilator
level of the nipple (T4 vertebra). disconnected while you introduce
4. Prep with iodine or alcoholic tube; pass tube into space and
chlorhexidine, drape, infiltrate direct it appropriately (superior/
with lignocaine & epinephrine anterior for air, posterior for fluid).
(down to pleura, confirming 10. Connect to drainage bottle.
pleural air or fluid by aspiration
11. Secure by sutures and adhesive
into syringe).
dressing.
5. Horizontal skin incision at lower
12. Check CXR.
border of chosen rib, purse string
suture placed if you have time.

Metabolic measurements
A Metabolic monitor can be connected to the patients ventilator circuit (or hood if extubated)
to assess patients metabolic rate and therefore calorific feeding requirement.   It monitors
inspired gas concentrations and draws the expired gas into a fixed flow rate generator,
measures the mean PCO2 in the generator by infrared analysis and so calculates VCO2.  FECO2
is also measured, and the expired minute volume derived (VE=VCO2/FECO2).  This eliminates
errors intrinsic in trying to measure VE.  Respiratory Quotient is calculated by the Haldane
transformation; RQ=(1-FIO2)/([FIO2-FEO2]/FECO2)-FIO2.   VO2 is derived from the formula
VO2=VCO2/RQ. 

Radiology
You must particularly familiarise yourself with the interpretation of chest and cervical spine
radiographs.

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iGuide 2009

Portable AP Chest X rays are ordered;

after intubation and ventilation of daily in acutely ill ventilated patients to


acutely ill patients (including monitor vascular pedicle width, CTR,
tracheostomy), consolidation, collapse, oedema of
after central venous cannulation to lung parenchyma; such routine
check position of catheter tip radiography may be done at longer
intervals in stable but ventilated
after any other procedure with risk of
patients,
pneumothorax,
following acute cardiorespiratory
changes.
Portable lateral cervical spine X rays can be performed in the A&E department or Intensive
Care Unit when injuries are suspected. Assess AABCS; Adequacy (C1-C7/T1), Alignment,
Bones, Cartilage and joints, Soft tissues. To exclude bony injury, request a "full cervical spine
series" which will include lateral, AP, AP peg view and (only if needed to show C7/T1)
swimmers view. Get Radiologists report.
A normal cervical X-ray series does not exclude the possibility of significant ligamentous
injury with the potential for spinal cord injury. Before cervical immobilisation can be
discontinued, the conscious patient must be examined for spinal stability and absence of
signs of cord injury. If patient cannot cooperate, discuss with Consultant Radiologist; options
include MRI scan or dynamic lateral screened flexion and extension views.

Management of self poisoning


Intensive care involvement is usually requested for patients with serious obtundation of
consciousness with risk of aspiration pneumonia. Patients with no gag reflex should be
intubated. Patients who retain their gag reflex need careful assessment as to intubate them
will require administration of anaesthesia, which is dangerous in patients with a full stomach.
Gut decontamination techniques.
Activated charcoal and gastric lavage are only of value up to one hour after ingestion. Emesis
should rarely be used. Whole-bowel irrigation with polyethylene glycol solution may have a
place in certain poisonings.
Carbon monoxide poisoning
should be treated with 100% oxygen inhalation to maximize PO2 in blood and at the
mitochondrion in order to shorten the elimination half life of the poisonous gas. Despite some
controversial trials, hyperbaric oxygen therapy is recommended for patients who have been
unconscious, or if CO concentration has exceeded 40%, or if there are neurological changes.
However, availability and the logistics of transfer to a chamber may make treatment
impracticable.

Consent to treatment.
The Mental Capacity Act gives power to consent to treatment to adults who are not shown to
be incapacitated, or (when they are found to lack capacity) to a donee under a Lasting Power
of Attorney or to a Court-appointed Deputy. A new Court of Protection exists for those rare
cases that go to law for determination. The role of kin (or of an Independent Mental Capacity
Advocate where no friends or family can be identified) in the care of the incapacitated adult is
to advice what the patient might hold to be important when a best interests judgment is made
by the decision maker, who is usually the patient’s Consultant. Where nobody can be found to
represent the interests of the incapax adult facing major treatment decisions, the local IMCA
must be approached.

Withholding and withdrawing life sustaining treatments in


the Critical Care Unit; a few practical and legal points.
Legal
UK law puts the highest priority on the protection and preservation of life…
…but does not require a doctor to “strive officiously to keep alive” patients who are dying.
(What does the law mean by ‘dying’? It is a medical judgment.)

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A doctor’s duty to preserve life can be overruled by a patient’s freely-made and explicitly-
stated decision to refuse life-sustaining treatment.
A doctor who takes active steps to end a life is guilty of attempting murder, even if the patient
has requested the lethal treatment.
A medical treatment which has as an unintended side effect the shortening of life may be
given with consent or on the principle of necessity; this can be seen as an example of the
‘doctrine of double effect’. It includes the palliative use of opioid agonists even though they
may suppress respiratory drive.
Treatments being used to preserve the life of a patient who is incapable of making a decision
about his treatment and who is not ‘dying’ may only be withdrawn if there can be no doubt
that death is in the patient’s best interest. Perceptions of poor quality of life are not grounds
for withholding or withdrawing life-sustaining treatments. Courts are keen to protect disabled
people from negative attitudes to their quality of life.
Where there is dispute or uncertainty over a decision to withhold or withdraw life-sustaining
treatment, the final decision lies with the Court of Protection. It is a breach of a patient’s
European Convention Rights (Article 8) to fail to seek the decision of a Court in reasonable
time.
Practical
Sometimes requests are made for treatment of dying patients in critical care units because the
patient or family are insisting that ‘everything’ possible is done. Situations like this can usually
be defused by diplomatic explanation that ‘everything’ does not include treatments which
have no prospect of saving life, and by negotiation of a more realistic treatment plan with
clear end of life arrangements. A Department of Health criterion for ICU admission and
treatment is a reasonable expectation that the patient’s life can be saved.
In most cases, the reason for WH/WD will be that the patient is dying in spite of all reasonable
attempts to save the life.
TW recommends that the patient’s family is informed of, and accepting of, a decision to
withdraw life-sustaining treatment in anticipation that the patient will die. They should be
advised that, just occasionally, patients survive after treatments intended to prolong life are
withdrawn.
Withdraw inotropes and pressors first; just occasionally these drugs seem to be doing more
harm than good.
In unstoppable haemorrhage, withhold all fluids and monitor the haemodynamic consequence;
just occasionally, bleeding stops as blood pressure becomes very low and the condition
stabilises.
There has been some interesting debate about the ethics of withdrawing assisted ventilation
from patients who are under the influence of muscle relaxant drugs. TW recommends that
muscle relaxants are discontinued and their effect allowed to wear off before discontinuing
ventilation.

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Chapter 3

General care
Body position
Critically ill patients are often limited in mobility and posture is chosen by attending staff.
Supine position seems to be the default norm. It is however known to be associated with
reduced functional residual capacity even in healthy anaesthetised patients. If the ventilated
patient has sufficient blood pressure to tolerate it, the semi-recumbent position (45% head up)
is associated with lower incidence of ventilator-associated pneumonia. Intermittent prone
positioning improves oxygenation in some patients with acute lung injury but the effect on
outcome is not established. Specialised beds for prevention of decubitus ulcer or hypostatic
pneumonia are expensive.

Acute Gastric dilatation


is associated with trauma or acute respiratory failure (air swallowing) and occurs in children
and adults.   Made worse by CPAP or PPV with a face mask.   May cause hypotension or
regurgitation, it requires decompression with a gastric tube.

Peptic ulceration
It is held that critically ill patients are at risk of stress ulceration, though it is likely that with
the modern awareness of the importance of maintaining cardiac output and tissue
oxygenation, the risk (about 5% in patients ventilated for 48 hours or more) is less than it used
to be.   In the past, antacids and sucralfate have been used for stress ulcer prophylaxis. In a
large Canadian RCT intravenous ranitidine 50mg 8 hourly (frequency reduced in renal failure)
gave protection against gastrointestinal bleeding with relatively little adverse effect on
ventilator associated pneumonia. It should therefore be the routine prophylactic for patients
who are expected to be ventilated for more than 48 hours. Proton pump inhibitors (PPIs) are
generally superior to H2 antagonists and so are a reasonable alternative for critically-ill
patients. Omeprazole and lansoprazole use the hepatic cytochrome P450 metabolic pathway
and interfere with the metabolism of numerous other drugs, especially in patients with hepatic
and renal dysfunction, which are common in critical illness. Pantoprazole is, in theory at least,
pharmacokinetically superior and can be considered in certain cases. Pantoprazole infusion is
used to control severe GI haemorrhage. Once enteral nutrition is fully established, no
prophylaxis is required unless there are other risk factors such as heparinisation,
coagulopathy, chronic non-steroidal anti-inflammatory drug administration or steroids.

Nutrition
Start at the earliest opportunity, aiming to provide 25-75% of the calculated energy
expenditure every day while the patient is critically-ill.   The preferred route is enteral, and
studies show that the presence of bowel sounds is not necessary. Maintain good fluid and
electrolyte balance and reduce opioids if there is ileus.  Remember that dopamine inhibits
peristalsis and may cause nausea.  You are reminded that neuromuscular blocking drugs have
no effect on visceral smooth muscle and so they do not prevent peristalsis.
Gastric stasis sometimes prevents food being passed to the small bowel and some units use
jejunal feed.   We prefer to try metoclopromide if stasis occurs, considering cisapride or
domperidone if that fails.  Note that the antibiotic erythromycin is a very effective promotility
agent.   Give feeds ‘full strength’, as there is no benefit in diluting them.   Diarrhoea is
common, and is not an indication to suspend feeding. Even very small amounts of enteral feed
(10ml/h) may be beneficial as nutrients of the intestinal mucosa.

“Renal dose” dopamine


... should not be used.   Dopamine 1-3microg/kg/minute has been   used “to   promote
splanchnic blood flow” in shocked patients and as a mild diuretic in spite of a lack of evidence
for clinical benefit.
Dopamine depresses the circulating concentrations of all the anterior pituitary-dependent
hormones except for cortisol. Important consequences include the “sick euthyroid syndrome”,
growth hormone deficiency (metabolic) and prolactin deficiency (immune problems).

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Remember that it may make patients feel nauseated, and inhibit gastric motility. It also
attenuates hypoxic drive.
Dopexamine combines dopaminergic properties with beta-2 and norepinephrine-1 uptake
inhibition. It shares dopamine's hormonal effects.

Neither wet nor dry


Fluid and solute balance is crucial to a good outcome. The Danish Study on Perioperative Fluid
Therapy suggests that as positive fluid balance (body weight) increases, the incidence of
cardiac, pulmonary and even infectious complications rises. Daily input of more than 3.5 litres
of fluid, or weight gain of more than 2.5kg from baseline is dangerous. Fluid balance charts
must be scrutinised but are imprecise over the longer term. Daily weighing is recommended if
possible. Learn to measure the vascular pedicle width on chest radiograph and follow
sequential changes. Diuretics (e.g. furosemide up to 80mg/day or spironolactone enterally)
can be used to counter the tendency of ventilated critically ill patients to accumulate excess
body water.

Thrombo-embolism prophylaxis
Patients with normal clotting and platelet counts who are immobilised for more than 72 hours,
or who have undergone major pelvic or abdominal surgery, are at risk of thrombosis and
embolism.  Prescribe unfractionated Heparin 5,000 iu sc  tds (bd in small patients) unless
there are contra-indications.  Low molecular weight heparins accumulate in renal insufficiency,
and monitoring their effect is difficult, so they are not to be regarded as first-line therapy for
newly-admitted and unstable critically ill patients, especially when bleeding complications
would be undesirable. Compression stockings or devices can be used as an alternative to or to
supplement the effects of heparin.   Active or passive mobilisation by nursing and
physiotherapy staff helps prevent thrombosis, disuse atrophy and contractures.

Hospital acquired infections


The important causes of infection in the ICU include the following organisms;
Staphylococcus Aureus;
Gram-positive coccus carried by normal people and spread both airborne and via staff-patient
contact.  Methicillin-resistant strains (MRSA) are increasingly common.  Patients staying more
than a few hours in a hospital ward were MRSA is known to be present must be isolated on
Intensive Care and carefully screened.   In some instances, infected areas may have to be
closed to admissions in order to eradicate MRSA from the environment. There are worrying
reports of MRSA with intermediate resistance to vancomycin and teicoplanin.
Coagulase-negative Staphylococci (CNS);
CNS such as Staph. epidermidis are normal skin flora and are often only sensitive to
vancomycin or teicoplanin.   They are responsible for much catheter-related sepsis as they
produce a “biomatrix” or “slime” which enables colonies to attach to and thrive on inert
surfaces.  Infected lines must usually be removed.
Enterococci;
Ent. faecalis and Ent. faecium are normal gut and vaginal Gram-positive flora which can cause
urinary tract infections, wound infections, endocarditis and bacteraemia in critically-ill
patients.  Widespread use of cephalosporins, to which they are often resistant, may account
for the increasing importance of Enterococci.   Ampicillin or vancomycin with a second
antibiotic is the first line of treatment, though resistance is increasing (glycopeptide-resistant
enterococci, GRE).
Pseudomonas spp and Xanthomonas;
These Gram-negative bacilli are not normal flora, but are widespread in the environment and
flourish in moist areas.   In infected patients we usually use two antibiotics from amongst
aminoglycosides, ceftazidime, ciprofloxacin and meropenem.
Acinetobacter spp;
Gram-negative cocco-bacilli which flourish in moist areas, and are also part of normal skin
flora.  Treat according to sensitivities.
Other Gram negative opportunist bacteria;

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Escherichia, Klebsiella, Proteus and Enterobacter spp (collectively known as the


enterobacteriaceae) are increasingly showing resistance to cephalosporins, quinolones and
trimethoprim.
Clostridium difficile
C. diff. associated diarrhoea (CDAD) is the major cause of antibiotic-associated diarrhoea and
colitis, a healthcare associated intestinal infection that mostly affects elderly patients with
other underlying diseases. Diagnosis is confirmed by finding toxins A & B in the stool.
Metronidazole is the treatment of choice, but vancomycin may be more effective against the
more virulent strains of the bacterium.
Basis of resistance to antimicrobials
Resistance arises via mutation of the organism, gene transfer from one organism to another,
or by selection. Mechanisms of resistance include inactivation of the antimicrobial outside the
cell wall (by penicillinases, beta-lactamases, carbapenemases etc), impermeability of the cell
wall to the antimicrobial, active excretion of the antimicrobial by the bacterium, changes to
the antimicrobials target protein, and alternate metabolic pathways to bypass blocks produced
by the antimicrobial. Intensive Care Units are recognised as danger areas for development of
resistant organisms.
Yeasts
Difficult to isolate, can contribute to high mortality multiple organ system failure.  Risk factors
include severe illness, prolonged tracheal intubation or other body cavity catheterisation, use
of broad spectrum antibiotics, parenteral nutrition and immunosuppression.   Positive
diagnosis is made if the patient develops endophthalmitis or organisms are isolated from a
normally sterile organ such as kidney,  lung or blood. Empiric therapy should be considered in
patients with multiple site colonisation, or in single site colonisation if the patients condition
is deteriorating. Commonest species Candida albicans is often sensitive to fluconazole or
voriconazole. Flucytosine is an adjunctive therapy. Candida glabrata and others may
necessitate amphoteracin B or caspofungin therapy. C. parapsilosis forms biofilms, lives on
health workers hands, and has a predeliction to settle in central lines; mostly sensitive to
fluconazole.

Breaking the cycle of infection


Prevention of secondary infections can be considered under four main headings;
Surveillance
Vigilance to detect outbreaks and take appropriate action. The Department of Health has
surveillance systems in place for MRSA, CDAD and GRE.
Interrupting the spread
Hand washing, protective clothing, good design of the ICU, cleaning & disinfection of surfaces.
Modifying risk factors
Rational use of appropriate antibiotics, rotation of antibiotic policies, avoid using unnecessary
catheters and cannulae, good patient nutrition, restrictive use of drugs which impair immunity
(e.g steroids, opiates, inotropes).
Diminishing the reservoir;
Selective Decontamination of the Digestive Tract (SDD) with oropharyngeal and gastric
antibiotics, plus systemic antibiotics and microbiological surveillance (also called selective
parenteral and enteral antibiotic regimen, SPEAR) has been proposed as a strategy for
prevention of nosocomial infections.   A randomized controlled trial involving nearly 6000
patients in 13 ICUs in the Netherlands (NEJM 2009) confirmed 28-day mortality benefit. The
odds ratio for death at d28 for SDD was 0.83. Selective oropharyngeal decontamination alone
(SOD) was almost as good, odds ratio 0.86. SOD can also be used in the treatment of patients
with difficult Gram-negative pneumonias.  These patients should preferably be nursed in a
side room.   The non-absorbable oropharyngeal and enteral drugs are polymixin,
amphoteracin and tobramicin. 

Nosocomial, or Ventilator associated, pneumonia


VAP should be suspected in a patient with new or persistent radiologic features of pneumonia
without other cause, plus two of; pyrexia, abnormal white cell count, purulent tracheal

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iGuide 2009

secretions or growth of potentially pathogenic micro-organisms from them, and increasing


oxygen requirements. Alkalinisation of the stomach facilitates passage of potentially
pathogenic microorganisms (PPMs) within the intestinal tract to the oropharynx with the risk
of respiratory tract infection.   Using upright or semi-recumbent posture reduces
oropharyngeal contamination and subsequent ventilator-associated pneumonia (VAP). Fibre-
optic guided broncho-alveolar lavage is not superior to standard tracheal suction specimens
in the management of VAP.

Urinary tract infections


are presumed to be due to perineal soiling with PPMs in catheterised patients.  It is often
necessary to replace the catheter as part of the treatment.

Catheter-related sepsis
is often due to coagulase-negative staphylococci which form a protective layer of slime and
are difficult to treat.  Prevention is better than cure.  If suspected;
inspect site and remove catheter if obviously  inflamed or infected, but if site is clean then;
discontinue dextrose or TPN solutions down the suspect catheter and
send isolator specimen (for semi-quantitative culture) from the line plus standard venous
blood culture sample (draw these samples yourself to ensure there is no contamination,
notify lab).
It is acceptable to change lines over a wire if the site looks clean, but send tip of the old
catheter for culture, and remove the ‘new’ line if results suggest it may have been
contaminated during wire change.

Gut permeability and systemic sepsis


Shock is presumed to reduce the effectiveness of the bowel wall as a barrier to bacterial
invasion, and so toxinaemia and bacteraemia may occur (by ‘translocation’ from the bowel
lumen) even in ‘cardiogenic’ shock.  Minor portal vein bacteraemia or endotoxinaemia is easily
mopped up by hepatic reticulo-endothelial cells (Kupffer cells) facilitated by opsonisation with
plasma fibronectin, but when these defences are overwhelmed systemic sepsis occurs.   A
hypothesis which provides justification of the practice of selective decontamination of the
digestive tract. Good evidence in support of this theory is awaited, and the practice is not
widely adopted.

Systemic inflammatory response and septic shock


TERM ACCP/SCCM DEFINITION
Infection Local inflammatory response to micro-organisms or invasion of normally sterile host tissue
by micro-organisms
Bacteraemia, Presence of viable micro-organisms in the blood.
viraemia, fungaemia,
parasitaemia etc.
Systemic May be due to infective or non-infective insults such as trauma, burns and pancreatitis. Two
Inflammatory or more of the following;
Response Syndrome
(SIRS) 1 Temperature >38C or <36C
2 Heart rate >90 beats per minute
3 Respiratory rate > 20 breaths per min.
4 White Cell Count >12,000/ml or <4,000/ml or >10% immature (band) forms.
Sepsis Systemic inflammatory response to infection. Criteria as for SIRS.
Severe sepsis Sepsis associated with organ dysfunction, perfusion abnormality, or hypotension.
Septic shock Sepsis with hypotension (unresponsive to adequate fluid resuscitation) and perfusion
abnormality (e.g. lactic acidosis, oliguria, acute alteration in mental status).
Hypotension Systolic blood pressure <90mmHg or <40mmHg below baseline for the patient.
Multiple organ Presence of altered organ function in an acutely ill patient such that homeostasis cannot be
dysfunction maintained without intervention.
syndrome (MODS)

Not all that is pyrexial and leucocytotic is sepsis.


Changes in temperature, white cell count and multi-system organ dysfunction are seen in
both sepsis and a number of non-septic conditions such as trauma, burns, pancreatitis and
drug rash with eosinophilia and systemic symptoms (DRESS syndrome).  Even some of our

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common "therapeutic" interventions, like positive pressure ventilation with supranormal tidal
volumes and the administration of morphine may predispose to inflammation. The unifying
feature appears to be stimulation of cytokine production by macrophages and other tissues;
among the more important inflammatory cytokines
seem to be tumour necrosis factor (TNF-alpha) and
interleukin-1 (IL-1).   Toll-like receptors (TLRs) in
cell membranes appear to be an important part of
the immune response to bacteria and toxins and
trigger a variety of chemical responses which are of
research interest.
Cytopathic hypoxia; the Warburg effect
In 1931 Otto Warburg won a Nobel Prize for his
work on the generation of adenosine triphosphate
(ATP) by cancer cells, which rely heavily on
anaerobic pathways, and so generate large amounts
of lactate. More recent research is elucidating the
role of mitochondrial damage, and it seems that
similar changes may occur in ‘septic’ cells. Under
cytokine stimulation or after severe hypoxia many
tissues appear to undergo a transformation in the
way they generate ATP. Glycolysis (glucose ->
pyruvate -> lactate) is increased while
mitochondrial respiration is impaired. Clinical
studies show that tissue oxygen tensions may be
normal or even high. The condition has been called cytopathic hypoxia and it can be modeled
in in-vitro laboratory studies. Cytopathic hypoxia is an acquired, potentially reversible,
intrinsic derangement in cellular respiration. Laboratory studies show that it develops after
prolonged exposure to a pro-inflammatory milieu (at least 8-48 hours) and is caused by
structural damage to mitochondria (Complex I). The mechanism of mitochondrial damage is
superoxide and peroxynitrite reactions with DNA, which trigger the poly (ADP-Ribose)
polymerase-1 (PARP) repair mechanism, which in turn uses NAD+ and depletes its availability
for respiration.
Two important clinical management principles emerge from insight into the condition known
as cytopathic hypoxia. Firstly, that there is a short ‘window of opportunity’ to prevent
cytopathic hypoxia and MODS by rapid resuscitation and treatment. Secondly, that once
cytopathic hypoxia is established, therapies that are intended to increase blood flow/ oxygen
delivery/ tissue oxygen tension become unlikely to be effective, and may even become
harmful. Lactate becomes an important fuel during cytopathic hypoxia and lactataemia will
only resolve as cells revert to predominantly aerobic respiration. Clinical studies to date
appear to support these hypotheses.
Immunological and haematological changes
Interferon (IFN-gamma) is a stimulator of macrophages but its importance in the
pathophysiology of systemic inflammation is not clear.   Other mediators of systemic
inflammatory response include circulating and endothelial components of the coagulation
cascades, platelet activating factor (PAF), the arachadonic acid metabolites (cyclooxygenase
pathway leads to prostaglandins (PG), prostacyclin and thromboxane(TXA); lipoxygenase
pathway produces leukotrienes (LT)), complement cascade, proteases, and the endorphins.  In
addition to these circulating factors, the vascular endothelium expresses adhesion molecules
(P, E and L selectins) which hold leukocytes plus intercellular adhesion molecules (ICAM 1 & 2)
to bind neutrophils, and vascular cell adhesion molecule (VCAM 1) to bind lymphocytes.  The
relatively low shear forces on white cells passing through the pulmonary circulation may make
the lung particularly vulnerable to attack when neutrophil activation occurs.
Activated Protein C exerts an antithrombotic effect by inhibiting Factors Va and VIIIa and  has
indirect profibrinolytic activity through its ability to inhibit plasminogen activator inhibitor-1
(PAI-1) and limiting generation of activated thrombin-activatable-fibrinolysis-inhibitor.
Additionally, Activated Protein C may exert an anti-inflammatory effect by inhibiting human
tumor necrosis factor production by monocytes, by blocking leukocyte adhesion to selectins,
and by limiting the thrombin-induced inflammatory responses within the microvascular
endothelium.

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Investigating cellular processes which occur in the interstitial space is especially challenging.
Research is showing how the structural molecules of the extracellular matrix modify tissue
macrophage function.
Erythropoetin modulates a broad array of cellular processes in ischaemia and hypoxia and may
prove to be an effective cytoprotective agent. Clinical trials strongly suggest a survival benefit
in critically-ill trauma patients which cannot be accounted for by transfusion requirements.
In an attempt to standardise the definitions of sepsis, the systemic inflammatory response,
and shock, the Society of Critical Care Medicine and American College of Chest Physicians has
proposed the criteria outlined in the above table. In 2004 an International collaboration of
professional organisations (sponsored by Eli Lilly) published the first 'Surviving Sepsis
Campaign Guidelines' for care of patients with sepsis. A checklist is provided as an appendix
to the Guide. The full current document can be downloaded from http://www.sccm.org/ and
other web sites.
SIRS/CARS & MARS?
Failure of clinical trials utilising specific antagonists of the mediators of SIRS has prompted
some “experts” to reassess the theory of SIRS and to propose that in critical illness the balance
between pro-inflammatory and anti-inflammatory mediators may be more important than just
the suppression of SIRS. 
The late Roger Bone has proposed to label the anti-inflammatory response CARS
(compensatory anti-inflammatory response syndrome) in which the HLA-DR expression on
monocytes is <30% and there is a diminished ability of monocytes to produce inflammatory
cytokines. In most patients there will be a mixed antagonists response (MARS) with SIRS or
CARS predominating.
Bones mnemonic for the consequences of SIRS/CARS/MARS is CHAOS;
Cardiovascular compromise (SIRS dominant)
Homeostasis (perfect balance of SIRS/CARS, return to health).
Apoptosis (cell death with minimal inflammation)
Organ dysfunction (SIRS dominant)
Suppression of immune system (CARS dominant).
“Double hit” theory
A single insult such as cardiogenic shock or pneumonia only infrequently progresses to MODS,
but multiple insults are much more likely to be complicated by MODS. This observation has
lead to a suggestion that the first insult in some way primes the immune system to overreact
to the second insult leading to MODS, and has been called the double hit theory.

Anti-inflammatory therapies in severe sepsis.


A randomised controlled trial of recombinant human activated protein C (called Drotrecogin
alfa (activated)) was terminated because of 28 day mortality benefit, relative risk of death
reduced by about 20%; the number needed to treat for an additional survivor is of the order of
15, more effective than thrombolysis in myocardial infarction. Licensed as an adjuvant therapy
for severe sepsis.
A French collaborative study of hydrocortisone plus fludrocortisone in severe sepsis has
shown survival benefit in patients with poor response to a corticotrophin stimulation test, but
an International trial called CORTICUS failed to find any survival benefit.
More research is needed to establish indications for these therapies in UK intensive care units.

Organ dysfunction or failure.


Outcome is strongly correlated to the number of failing organ systems.  Various definitions of
multiple organ system dysfunction or failure have been proposed.   In general, the “organ
systems” and “markers of dysfunction” are as the example given below;

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Vincent JL et al. The SOFA (Sepsis-related Organ Failure Assessment) score to describe organ
dysfunction / failure. Intensive Care Med. 1996;22:707-710.
1 2 3 4
Respiratory; < 53 (with or < 40 (with or < 27 and < 13 and
PaO2/FIO2 without support) without support) mechanically mechanically
ventilated ventilated
Nervous; GCS 13, 14 12, 11, 10 9, 8, 7 <7
CVS; MAP or >70 Dop<5 or dob Dop>5 or norepi Dop>15 or norepi
pressors mic/kg/ (any) <0.1 or epi <0.1 >0.1 or epi >0.1
min
Liver; bili 20-32 33-101 102-204 >204
micmol/L
Coag (platelets) <150 <100 <50 <20
Renal 110-170 171-299 300-440 or u/o >440 or u/o
<0.5L/d <0.2L/d

Neuromuscular changes
A number of complications may occur during prolonged critical illness leading to profound
weakness and delayed recovery. Monitor strength by simple parameters, such as;
1. full strength in legs/ arms/ hand grip
2. unable to raise arm at shoulder, leg at hip
3. unable to bend elbow, knee
4. unable to move hand/ foot, fingers/ toes.
DISUSE atrophy of the diaphragm can be seen on histological, biochemical and gene-
expression studies after as little as 18 hours disuse on mechanical ventilation. CATABOLIC
atrophy is common.  CRITICAL ILLNESS NEUROMYOPATHY (CINM) is an axonal degeneration of
sensory and motor nerves.  It is often associated with sepsis; CPK is essentially normal and
muscle biopsy shows denervation changes.  Recovery may be slow, and ventilator support may
be needed after oxygenation has recovered.  Patients given prolonged muscle relaxant therapy
may suffer from PROLONGED BLOCKADE upon termination, or MOTOR NEUROPATHY/
MYOPATHY with raised CPK especially when steroids have also been used (called acute
quadriplegic myopathy, AQM).   Rarely, patients may suffer from ACUTE MYOSITIS or
PYOMYOSITIS with raised CPK, and necrosis seen on biopsy.

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iGuide 2009

Chapter 4

Circulatory support
Resuscitation.
You are expected to be familiar with, and capable of practising, basic and advanced life
support for children and adults.  The resuscitation guidelines are frequently updated by the
many expert bodies who issue them. The International Liaison Committee on Resuscitation
(ILCOR) has representatives from the European Resuscitation Council, the American Heart
Association, the Heart and Stroke Foundation of Canada, the Australian Resuscitation Council,
the Resuscitation Council of South Africa and the Resuscitation Council of Latin America. They
have also published guidelines for research into resuscitation.
Post-resuscitation care is important. Patients who do not regain consciousness within a few
minutes of restoring their circulation can benefit from a period of induced hypothermia.

Do Not attempt Resuscitation (DNAR) instructions


are made on Consultant responsibility after discussion with the patient or (in patients lacking
decision-making capacity) next-of-kin.  May include “Do Not Escalate” (DNE, where survival is
still possible and current support is continued, but no increase or addition would be made) or
“Allow Natural Death” (AND, where the focus of treatment is on a comfortable dying). DNAR
orders should be reviewed periodically and can be rescinded in the light of changing
circumstances. Compliance with BMA/UKCC guidelines is expected in UK practice.

Shock
is said to be an acute syndrome of circulatory insufficiency leading to inadequate tissue
perfusion and cellular dysfunction. There are three conceptual categories and the patient may
fall into any one, or more, of them.  Patients present with hypotension (systolic BP < 90 mmHg
or <individual “normal”-40mmHg) and a perfusion abnormality (impaired mentation, oliguria,
lactic acidosis).

Cardiogenic shock
Low cardiac output due to intrinsic pump failure often associated with high central venous
pressure. Diagnosis vital as early appropriate interventions can be life saving.
MYOCARDIAL INFARCTION; history, ECG, troponin, cardiac enzymes; consider
thrombolysis.
TENSION PNEUMOTHORAX; CXR (but don’t wait if strongly suspected); intercostal drainage.
PULMONARY EMBOLISM; usually underdiagnosed especially in chronically sick patients;
anticoagulate, consider thrombolysis or embolectomy.
VALVULAR DYSFUNCTION, TAMPONADE, CARDIOMYOPATHY; echocardiography; consider
surgery in acute mitral incompetence, centesis for tamponade.

Hypovolaemic shock
Low cardiac output due to inadequate cardiac preload usually with low central venous
pressure.     Differential diagnosis includes haemorrhagic shock, fluid deprivation, and
conditions causing compartmental shifts such as pre-eclampsia, sepsis and anaphylaxis.
Initially, rapid resuscitation equivalent to 15% of blood volume (500-750 colloid, 1000-1500
crystalloid) is indicated to restore an adequate stroke volume, but full replacement of lost
fluids should be staged and slower to allow compensatory adaptations to re-adjust.
Resuscitation in uncontrolled haemorrhage.
It is now generally accepted that it is pointless or even harmful to attempt to restore normal
circulation by aggressive transfusion while the site of haemorrhage is uncontrolled. For out-
of-hospital trauma patients, NICE (Technology Appraisal Guidance 74, 2004) recommends “no
fluid” so long as the patient has a palpable radial pulse (systolic pressure >70mmHg), or
central pulse in patients with penetrating torso injury (systolic pressure >50mmHg). The
principle can be extended to emergency care of haemorrhagic shock within hospitals, and has
been called “delayed resuscitation”, “low-volume resuscitation” or “permissive hypotension”. In

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the hospital setting, it should be possible to monitor arterial pressure rather than rely on the
presence or absence of a pulse.

Distributive or hyperdynamic shock


Hyperdynamic shock is often presumed due to sepsis, but think of and check for some rarer
causes of distributive shock, such as;
PANCREATITIS; check serum amylase & get abdominal ultrasound examination.
FULMINANT HEPATIC FAILURE; check serum transaminases and monitor coagulation
indices, especially INR.   If these are very high, ultrasound examination of the liver and
urgent opinion of hepatologist.  (NB bacteraemia and/or endotoxinaemia occur in many
FHF patients).
ANAPHYLAXIS; check serum tryptase immediately and at 12 and 24 hours if suspected. 
ACUTE ADRENOCORTICAL FAILURE; suggested by hyponatraemia and hyperkalemia, may
be due to auto-antibodies, DIC, anticoagulant therapy or drugs such as etomidate,
rifampicin or spironolactone. 
PITUITARY FAILURE (eg Sheehans syndrome).
SEVERE ANAEMIA is associated with low vascular resistance due to low blood viscosity
rather than vasodilation.
PREGNANCY, THYROTOXICOSIS, BERI-BERI and A-V SHUNTS are also associated with high
resting cardiac output.
Meningococcal septicaemia & purpura fulminans
The severest form of endotoxin-induced shock; patients are young and the mortality high at
about 25-50%, with a high proportion of survivors requiring amputation of gangrenous
extremities. Patients with rapidly developing purpura, coagulopathy   (INR, platelet
abnormality) or perfusion abnormality (base deficit, oliguria) must be admitted to ICU for
shock reversal even if the patient is not yet hypotensive. A substantial number of strategies
are recommended by different authorities in the care of this disease so get early Consultant
opinion.
choose ketamine instead of morphine for sedation/ analgesia for better haemodynamic
stability and reduction of TNF levels.
resist the temptation to give plasma proteins or albumin solutions until the inflammatory
process is controlled, you may just aggravate intravascular coagulation and proteolysis.
early veno-venous haemofiltration in shocked patients.
replenish the natural anticoagulant activated protein C.
tissue plasminogen activator thrombolysis to salvage ischaemic limbs.
Consider ECMO for severe cardiovascular failure.
Trauma & Burns
The management of acute traumatic injuries poses some special challenges. Advanced Trauma
Life Support (ATLS) training is a didactic approach to trauma resuscitation designed for non-
specialist American practitioners. Though it has not been found to improve outcome it is
widely taught and commended in the U.K.  After a sensational report in 1988 that “up to” 33%
of deaths following trauma could have been avoided with better care, a Regional Trauma
Centre was established in the North West Midlands. Unfortunately, it has had no effect on the
outcome from major trauma. Detailed study of services in the USA revealed that in patients
with penetrating injuries immediate fluid resuscitation was harmful and this has inspired a
theory of hypotensive resuscitation. Low blood pressure is tolerated while action is taken to
prepare the patient for surgery to control the source of haemorrhage, so long as the patient
remains conscious.
Assessment, analgesia and fluid resuscitation are important cornerstones of initial burns
management. Be familiar with the Rule of Nines for estimation of surface area, and a guide to
fluid replacement such as the Parkland Formula for initial resuscitation;
for >15% burns give 4 x (%2nd & 3rd degree burns) x (body weight kg) ml balanced salt
solution, half in first 8 hours and half in next 16 hours.

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Early excision and grafting of burns, topical antimicrobial therapy, and multidisciplinary
intensive care are said to be important features of modern burns management. Three major
prognostic factors were identified from experience in New England; age >60 years, burn area
>40%, and evidence of inhalation injury. Prognosis related to number of factors present (0, 1,
2 or 3) is approximately 0.3%, 3%, 33% and 90%.

Assessing shock state


The endpoints for shock reversal are indicators of the adequacy of perfusion. Look for clinical
evidence of organ dysfunction. Feel the peripheries for temperature distribution. Take blood
for indices of   global oxygen utilisation; arterial acid-base status (including lactate), mixed
venous (or caval venous if no RHC) oxygenation and acid-base status. Be aware, however, that
lactataemia is an unreliable indicator of tissue hypoxia. Novel techniques to monitor regional
acid/base status (e.g. gastric or colonic tonometry) may have a role. Adequacy of   oxygen
delivery to the gut is said to determine the intramucosal gastric pH; gastric pHi is said to be
calculable with a silicone balloon tonometer in the gastric lumen to measure PCO2 and a
simultaneous arterial blood gas sample for arterial bicarbonate estimation.   A modified
Henderson-Hasselbach equation is then used to estimate pHi.   Whether this is a clinically
useful measurement remains unknown. The regional-arterial carbon dioxide tension gradient
has been preferred to pHi calculations.
Cardiac output has little correlation with adequacy of tissue perfusion and oxygen utilization,
but it’s measurement may be of value for diagnosis and physiological monitoring. Dye dilution
techniques (Stewart-Hamilton equation) use thermistors for thermal indicator detection in the
pulmonary artery or a systemic artery, or detection of Lithium or indocyanine green curves
fom arterial blood. A number of continuous cardiac output monitoring systems have been
developed and have their enthusiasts. These include aortic Doppler flow probes, thermistor PA
catheters, thoracic electrical bio-impedance and arterial pulse contour analysers. Good results
have been claimed in perioperative patients who are fluid-challenged against their stroke
volume (by oesophageal Doppler technique) or cardiac output (by dye dilution).

Principles of shock reversal


Sequential resuscitation continues until you achieve shock reversal. Resuscitation can be
considered in four main phases;
1. Oxygen therapy
2. Cardiac output restoration by
o fluid resuscitation
o inotrope therapy
3. Perfusion pressure restoration by pressor therapy
4. Optimisation of tissue blood flow and oxygenation by drug therapy; this last is widely
practised in different ways by different Intensive Care specialists but no good evidence
exists for a benefit.
Controversy continues over what constitutes an adequate cardiac output. Shoemaker’s so
called “optimal” therapeutic goals for oxygen delivery and consumption in post-surgical and
post-traumatic patients seem to be associated with better outcomes when applied before the
onset of organ failure in very high risk (mortality >20%) cases. Jean-Louis Vincent and others
have suggested ‘oxygen flux testing’ in which a vasodilator (typically dobutamine or
epoprostenol) is administered to discover whether oxygen consumption is delivery dependent
(which would suggest concealed tissue ischaemia).   However, there has been considerable
concern that VO2 and DO2 derived from the same PA catheter thermodilution cardiac output
are not independent variables and any apparent dependence may well be artefactual. An
Italian national randomised controlled trial of three “haemodynamic therapy goals” for PA
catheter guided treatment (supranormal cardiac index vs normal cardiac index vs normal SvO2)
failed to show any benefit of one over another.  However, patients who achieved their assigned
goal had a better outcome than those who failed, and failures were commoner amongst older
patients. An audit group in the USA have identified right heart catheterisation in the first 24
hours of intensive care as a major independent risk factor for death, and offered some
possible explanations for their findings. A Canadian national randomized controlled trial
found that pulmonary artery catheterization in critically ill patients was associated with
increased incidence of pulmonary embolism, but did not otherwise alter patient outcome. A

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multicentre RCT in the United Kingdom also failed to demonstrate a benefit for pulmonary
artery cathetersation. The Surviving Sepsis Campaign consensus opinion is that the pursuit of
an elevated cardiac output goal is not recommended in the treatment of sepsis (see
Appendix). In sepsis, there is evidence that time is of the essence. Liberal resuscitation in the
first six hours may prevent progression to cytopathic hypoxia state, followed by restrictive
fluids because a positive fluid balance at 72 hours is associated with poorer outcome.

ANAPHYLAXIS; a special case


In anaphylactic shock epinephrine may have to be given before i.v. access or monitoring is
available; intramuscular or subcutaneous dose is 0.01ml 1:1000 per kg, or 0.5ml for an adult,
repeated as needed every 5 minutes.   When iv access and continuous monitoring are
established, use intravenous epinephrine 0.1ml/kg 1:10 000, 3-5 ml for an adult.  Expect to
need up to 30ml/kg of colloid solution as immediate fluid resucitation.

Sequential resuscitation phase 1


Give OXYGEN.
Short exposure to 100% oxygen (raising alveolar, arterial and tissue oxygen tensions) is almost
always beneficial and very rarely harmful for acutely ill patients. For the ventilated patient,
manipulate FIO2 and mean airway pressure. Surgical patients benefit from administration of
80% oxygen during and for two hours after surgery. Wound infection rate and the incidence of
post-operative nausea and vomiting may be reduced.

Sequential resuscitation phase 2a


“Volume load” with appropriate FLUIDS to correct half the estimated deficit. If patient is
tachycardic with adequate blood pressure, blood volume deficit is no more than about 15%
(about 700ml). 30% deficit of the blood volume (i.e 1500ml) causes marked hypotension.
Crystalloids initially; only use colloids, albumin, and blood products where a strong indication
exists as liberal use of these seems to be harmful (see Chapter 6).
At this point monitoring of the patient should include:
Regular BP (automated if possible)
Regular pulse recording
Regular temperature recording (core - peripheral difference may be useful especially in the
child)
Urinary catheter with hourly measurement of urine output
If the patient does not respond to replacement of estimated deficit and there is no pulmonary
oedema then proceed to insert a CVP line, draw blood for venous blood gas analysis, and give
a FLUID CHALLENGE;
reduced venous oxygen saturation (less than 70%) suggests tissue hypoxia and demands
rapid correction if possible;
if CVP is initially low then aggressive fluid challenge eg 500 ml of appropriate colloid stat.
if CVP is high but not rising then a more cautious fluid challenge should be given eg.
250-500 ml crystalloid in 30 minutes.
assess arterial and venous pressure response to a Valsalva manoeuvre (or to the rising and
falling pleural pressure of positive pressure ventilation) as an index of left ventricular
preload.
Target CVP is 8 to 12mmHg in non-ventilated or 12 to 15mmHg in ventilated patients.
If the venous oxygen saturation remains low and if Valsalva response is square wave and if the
CVP is high and rises after cautious fluid loading then restrict fluids and procede to …

Sequential resuscitation phase 2b


All patients requiring inotropic / pressor support should, if possible, be admitted to ICU. Table
below shows commonly used drugs.
AGENT & RECEPTORS DILUTION DOSE RANGE µg/kg/min
(ml/h for adult)
Dobutamine, mostly β 500 mg in 100ml 2-25+ (2-21ml/h+)

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AGENT & RECEPTORS DILUTION DOSE RANGE µg/kg/min


(ml/h for adult)
Dopamine, DA, β, α 400mg in 100ml 5-20+ (6-24ml/h+)
Norepinephrine 4 mg in 50ml 0.02-0.2 (1-10ml/h)
...profound shock, mostly α ...’neat’ 1mg/ml ...0.1-1.25+ (0.4-5ml/h+)
Epinephrine 5mg in 50ml 0.02-0.1 (1-4ml/h)
...profound shock, α, β ...’neat’ 1mg/ml ...0.1-1+ (0.4-4ml/h+)
Isoprenaline,  β 4mg in 50ml 0.05-0.2
Milrinone, Phosphodiesterase inhibitor 100mg in 50ml 0.375-0.75
Dopexamine, DA1 and β2 50mg in 50ml 0.5-5µg/kg/min
Vasopressin , V1 40u/40ml via central venous cath 0.01-0.08 u/min
(0.6-4.8ml/h)
Glucose/ insulin/ potassium.   According to metabolic state.

Insert arterial catheter before or soon after starting inotropes/ pressors; check arterial gases
and anions including lactate and chloride; dobutamine is the inotrope of first choice if systolic
blood pressure is >90mmHg, but in hypotension dopamine gives more reliable blood pressure
support. In tachycardic patients it may be preferable to use norepinephrine. Glucose/ insulin/
potassium improves cardiac function in patients with acute coronary syndromes and might be
of benefit in septic shock.
Consider bedside cardiac assessment techniques.
Echocardiography is useful for examining valves, ventricular wall thickness, motion
abnormalities and contractility. It is the method of choice for demonstrating fluid in the
pericardium.
Consider cardiac output assessment by indicator dilution;
If cardiac output is subnormal (<2.5 L/m2/min) try to normalise it with an appropriate
inotrope (normal range 2.5-3.5 L/m2/min) and monitor changes in perfusion indicators
(e.g. lactate, venous oxygen saturation).
In the immediate perioperative or post-traumatic phase and before organ dysfunction is
established inotrope therapy to achieve supranormal cardiac output targets (>3.5 L/m2/
min) may benefit selected high risk patients, but once organ dysfunction occurs
supranormal goals are harmful.
Right heart (PA) catheterisation is more invasive and potentially dangerous. See Section 2 for
techniques of right heart catheterisation. If used for guiding shock reversal;
Aim to get PAOP (wedge pressure) 12 - 16 mmHg with normal saline and colloid.
Using continuous mixed venous oximetry
SvO2 is an index of global tissue oxygenation and haemodynamic stability and enables us to
reduce the number of blood gas and cardiac output determinations necessary to ensure the
patients well-being.  Normal SvO2 (70% or more) is dependent upon arterial blood oxygen
content (and SaO2 while Hb is constant), cardiac output and oxygen consumption (which is not
subject to rapid fluctuation so long as delivery is maintained).  Therefore rapid falls in SvO2
are almost always due to either falling SaO2 or falling cardiac output; the differential should be
easy.  Conversely, rising SvO2 usually signifies improving cardiac output.  Watch the change in
SvO2 as you change inotrope doses, and you will find that the new equilibrium point for SvO2 is
reached within a few minutes.  SvO2 is also a rapid way to find ‘Best PEEP’; as you increase
PEEP, SaO2 may rise continuously, but SvO2 only rises until the cardiac output reduction
outweighs the improved arterial oxygen content (mirrored by SaO2).  Therefore, you can adjust
PEEP to obtain the best SvO2. If you do not have mixed venous oximetry, cardiac output and
oxygen delivery studies should be performed 20 min after instituting any inotrope or PEEP
changes to assess their effectiveness.

Sequential resuscitation phase 3


Like inotropes, vasopressors appear to have a narrow therapeutic window. In trials which have
lower target mean arterial pressures there may be benefit from vasopressor support. Trial
protocols which have set higher target pressures have shown harm from the investigational
pressor. Before using vasopressors you should be confident that the patient is fully volume
resuscitated and has an adequate cardiac output. Alpha-1 adrenergic agonists are the

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mainstay of pressor therapy; epinephrine seems appropriate when the heart rate is lower,
norepinephrine when it is higher.
Target MAP 65-70 mmHg. In hyperdynamic septic shock norepinephrine alone may provide
optimal adrenergic support. Norepinephrine is started at 1.3mcg/min and is titrated up
to 15mcg/min in 40 min. Excessive use of pressors can be counter-productive; resist
the temptation to increase arterial pressure to over 80mmHg in an attempt to squeeze
urine from failing kidneys.
Consider the perfusion pressure if there is cause to suspect raised venous pressure; e.g.
measure intracranial pressure in brain injury, or intra-abdominal pressure when the
abdomen is distended and urine output low.
In the patient refractory to inotropes or vasopressors, particularly in “septic” shock;
Short tetracosactrin test to exclude primary or secondary Addisonian crisis.
“short synacthen” test; take blood for basal cortisol (T0) then immediately give 250 µg
tetracosactrin iv.  Take further samples for stimulated cortisol 30 and 60 minutes later (T30
and T60); cortisol level should double after stimulation.  Baseline cortisol concentration <100
nmol/L, peak <400 nmol/l suggestive of adrenocortical failure.
if Addison’s clinically suspected give hydrocortisone 100mg (1mg/kg) without awaiting
results.
If shock and dependence on vasopressors persist after treatment of infection (or 48 hours
from onset) and Addison’s has been excluded there is no benefit in further tests of
ACTH response, nor any evidence of benefit from physiologic doses of hydrocortisone.
Vasopressin can increase urine output and reduce norepinephrine dose requirement in
vasodilated shock states. In the VASST study, vasopressin was beneficial when started
while the needed norepinephrine dose was less than 15mcg/minute, but of no benefit
to patients needing more than 15 mcg/minute of norepinephrine. Vasopressin was
started at 0.0026 units/min and titrated up to 0.03 units/min in 40min.
Results from RCTs of terlipressin are awaited.

Sequential resuscitation phase 4


A varied group of theoretically attractive drugs which might augment tissue blood flow and
oxygenation, or modulate the cytokine response.  There is no convincing evidence for any of
them. Examples;
“Renal dose dopamine” or dopexamine to promote splanchnic blood flow
N-acetyl cysteine to alleviate oxidative stress and facilitate nitric oxide activation of
guanylate cyclase
Glyceryl trinitrate or epoprostenol to promote flow in pressor-treated shock
Pentoxifilline to inhibit TNF synthesis and promote microvascular perfusion.
Chlorpromazine to preserve splanchnic blood flow, inhibit TNF synthesis, inhibit inducible
NO synthase and protect against secondary infection.

Side effects
Adrenergic agents predispose to catabolism, hyperglycaemia, lactataemia and hypokalaemia.
An insulin infusion may be required to keep blood glucose <8.3mmol/L. Additionally,
dopamine causes nausea, gastric stasis, and inhibits anterior pituitary hormone secretion. It
should not be continued for more than 24-48 hours. Adrenoceptors show the phenomenon of
down regulation with tachyphylaxis. Thus inotrope infusions may need to be increased at
regular intervals to maintain their effectiveness.  Steroids inhibit down-regulation, but are not
indicated in acute shock states.

MODS; the multi-organ dysfunction


syndrome.
After resuscitation from acute tissue anoxia or septic shock many patients enter a phase of
MODS, which may be a clinical manifestation of cytopathic hypoxia at the cellular level. There
is generalised vasoparesis in which the arterial tone is typically reduced (pressure to flow
ratios low) and tissue oxygen tensions are normal or even higher than normal. Continued

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attempts to push higher blood flows and higher blood pressures with inotropes and pressors
can become counter-productive, and a Consultant may choose to reduce cardiac output and
pressure goals of therapy in order to reduce the harmful side-effects of these drugs. In a few
cases, patients have been observed to improve when inotropes and pressors are withdrawn.

Small print
Animal and in vitro evidence shows ketamine analgesia suppresses TNF blood concentration
and confers survival benefit compared to morphine and may be the analgesic of choice in
profound septic shock. In cases of septic shock refractory to norepinephrine or in profuse and
uncontrollable haemorrhage consider vasopressin infusion; Methylene blue 1-3mg/kg inhibits
guanylate cyclase and has also been reported to improve refractory vasodilation in profound
sepsis.  Analogues of Arginine (such as N-methyl L-arginine) reduce NO production by NO
synthetase and have been shown raise the blood pressure in septic shock, but clinical trials
have been suspended because of increased mortality.  Cross-linked hemoglobins, designed as
blood substitutes, scavenge free NO   in shock but may be associated with myocardial
ischaemia. Dexamethasone inhibits the inducible NO synthetase and sometimes assists shock
reversal, but overall the deleterious side effects of steroids weigh against their uncritical use. 
An ingenious device which applies synchronised systolic lower body positive pressure has
been tested and found to augment cardiac output and blood pressure in human septic shock.

Metabolic Acidosis
If the patient has non-repiratory acidosis, examine;
Plasma [Na]; hyponatraemia causes a degree of alkalosis, but more importantly examine
the strong ion difference.
Plasma [Cl]; hyperchloraemia is common in patients resuscitated with sodium chloride
solutions.
Blood [lactate]
Plasma [albumin]; if the [alb] is half normal (i.e about 18G/L) this will account for about
6mEq of the base excess of arterial blood.
Metabolic acidosis due to lactate or unmeasured anions is a sign of profound shock. We can
readily measure blood lactate levels in order to follow the effectiveness of resuscitation.
Extracellular acidosis alone does not seriously compromise myocardial contractility or cellular
viability, therefore treat acidosis due to tissue hypoxia by improving tissue O2 tension;
uncritical use of bicarbonate may worsen the situation by reducing intracellular pH even
further and alters the Hb-O2 affinity curve in the “wrong” direction. Note that catecholamines
(especially epinephrine infusions) raise blood lactate and pyruvate as part of their
physiological effect on carbohydrate metabolism.
Bicarbonate therapy (NaHCO3 1.26%, or 150ml 8.4% added to 5% Dex) is appropriate for
bicarbonate-losing or hyperchloraemic acidosis, eg in renal acidosis or high volume
haemofiltration or during crystalloid resuscitation. For rapid emergency improvement of very
high hydrogen ion concentration/ low pH, use hyperventilation and NaHCO3 8.4%. NaHCO3
8.4% is 1mmol/ml, therefore dose calculation is simple but it is very hypertonic.

Arrhythmias
First get a 12 lead EGG to diagnose the type of arrhythmia predominating. Check electrolyte
levels and correct any [K+] deficiency to above 4.0 mmol/L with KCl 30mmol/hour and, if the
patient is not hypotensive or oliguric, magnesium sulphate 50% 10ml in one hour - this will
often terminate recurrent ventricular ectopics. Correct hypovolaemia and check acid-base
status which may indicate the need for increasing oxygen delivery by increasing FIO2 and/or
using inotropic support. If the above measures are unsuccessful then treat the arrhythmia
appropriately.  Amiodarone should be used with caution in patients receiving supplementary
oxygen as a number of case reports and series imply that this combination can cause or
aggravate acute lung injury in as many as 30% of patients.
The treatment of choice for patients with narrow complex tachyarrhythmia (except atrial
fibrillation) is ADENOSINE starting at 3mg given rapidly and followed by a saline flush; if
unsuccessful give increasing doses (6mg, 12mg, 12mg); remember that theophylline is an
adenosine antagonist. If there is no response, or if patient is in A.F. then;

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IF PATIENT IS HAEMODYNAMICALLY COMPROMISED treat by  SYNCHRONISED CARDIOVERSION


(100J:200J:360J) followed by AMIODARONE 300mg/15minutes and 300mg/1hour. If required,
you can repeat cardioversion after amiodarone loading.
IF PATIENT IS NOT SHOCKED then choose from various drug therapies; 
if the patient has not already received it for treatment of hypokalaemia, MAGNESIUM (as
sulphate) 0.15mmol/L over 5 minutes, then infusion at 0.1mmol/kg/hour.   (For 70kg this
equates to 2.5G bolus (5ml 50% MgSO4) then 1.75G (3.5ml 50% MgSO4) per hour). Check
plasma magnesium concentrations daily on therapy, aiming for a “therapeutic” level of around
2mmol/L.  Do not use magnesium in hypotensive or renal failure patients.
AMIODARONE can also be used to slow, convert, or protect against atrial tachyarrhythmias;
300mg over one hour, and repeat once if needed.
DIGOXIN up to 500mg in 30 minutes, may be repeated once. 
ESMOLOL  boluses 40mg over 1 minute and infusion at 4-12mg/min.
VERAPAMIL 5-10mg.
Broad complex tachyarrhythmias should be treated initially with LIGNOCAINE 50mg boluses up
to 200mg, and infuse at 2mg/minute. If this fails, or if the patient is haemodynamically
compromised, consider CARDIOVERSION and AMIODARONE as above. Other anti-arrhythmics
which may be effective include flecainide, procainamide or bretylium.
PACING is indicated in all inferior myocardial infarctions with heart block as this
improves prognosis.

Hypertension
Systemic hypertension after surgery is often due to pain which should be treated.  Careful
control of hypertension is necessary after cardiac or major vascular surgery, and SODIUM
NITROPRUSSIDE is the drug of choice. Hydroxocobolamine may protect against cyanide
poisoning for prolonged use.  GLYCERYL TRINITRATE is adequate for mild hypertension or left
ventricular failure especially in the presence of coronary artery disease, but the patient soon
develops tachyphylaxis unless n-acetyl cysteine is co-administered.   If tachycardia is a
problem, use LABETALOL. CLONIDINE is sometimes useful for young patients who are difficult
to sedate.  It can be given by slow i.v injection (150 microgram bd or tds) or into the stomach
in initial dose of 100 micrograms tds, rising to 600-900 micrograms per day.  It is an alpha 2
agonist which inhibits endogenous epinephrine and norepinephrine release.  Effects include
reduced blood pressure and heart rate, sedation and analgesia.
In isolated pulmonary hypertension the agent of choice to reduce the pulmonary pressure is
EPOPROSTENOL. Inhaled NITRIC OXIDE is a powerful short-acting pulmonary vasodilator but is
too toxic to be recommended.

The Vascular Pedicle


Using the portable CXR to monitor blood volume changes. The vascular pedicle width (VPW) is
the horizontal distance between the origin of the left subclavian artery (1) and the point at
which the shadow of the superior vena cava crosses the right main bronchus (2). The
cardiothoracic ratio (CTR) is the ratio of maximum cardiac width to maximum thoracic width.
Patients with VPW >70mm and CTR >0.55 are likely to have pulmonary artery occlusion
pressure >18, i.e to be “fluid overloaded” (Eli & Haponik 2002). A change of 5mm in the VPW
is said to reflect a change of about 1 litre blood volume, 3 to 4 litres of body water (assessed
by fluid balance or weighing).

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Chapter 5

Respiratory Support
Respiratory support may be provided PROPHYLACTICALLY or THERAPEUTICALLY.
Clear evidence of the rapidity of diaphragmatic disuse atrophy in fully-ventilated patients
strongly supports the use of respiratory support that preserves diaphragmatic work.
Histological, biochemical and gene-expression changes can be detected after less than 24
hours.

Prophylactic respiratory support


Used after major surgery; most patients have essentially normal lung function pre-operatively.
Once haemodynamically stable and warm (core temp. > 35oC) with a reasonable urine output
sedation can be discontinued and the patient allowed to wake up and wean rapidly from
ventilation. Many of the patients in this category will require less than 24 hours support and
are the group of patients in which it is very reasonable to use propofol for sedation.

Therapeutic respiratory support


used in the management of acute and acute-on-chronic respiratory failure. The level and type
of support needed depends on the aetiology of the respiratory failure.
CONTROLLED MECHANICAL VENTILATION (CMV)   is only appropriate for apnoeic or
pharmacologically paralysed patients. On modern intensive care ventilators, the control modes
also allow the patient to trigger the inspiration and to receive more control breaths than the
set rate. Such modes are more appropriately termed Assist/Control (A/C) and are more
comfortable for the patient than older style CMV. They reduce the work of breathing
substantially. Typically, A/C modes can be delivered with Volume control (VC), Pressure
control (PC) or Pressure-regulated Volume control (PRVC). The patient who experiences air-
hunger may benefit from increasing the inspiratory flow rate to satisfy his dyspnoea. It must
be emphasised that, used properly, A/C modes are very acceptable to patients who are lightly
sedated and able to trigger the ventilator; it is not necessary to switch to IMV or pressure
support.
SUPPORT MODES are used for the patient who   is capable of triggering the ventilator
consistently and with an efficient pattern. Typically we use pressure support (IPS) but an
alternative is volume support (VS) in which the ventilator calculates and varies the pressure
support needed to attain prescribed tidal volumes; in theory, as the patients strength recovers
he can take on increasing proportions of the work of breathing (WOB) with this mode, but in
practice many patients just let the machine do the work!
BILEVEL features on some modern ventilators with suitable valve technology and can be
prescribed in three main ways.
Pressure controlled ventilation; the higher and lower pressure levels are set as the
inspiratory and expiratory pressures, the time in each set to provide a traditional respiratory
rate and I:E ratio. Suitable for fully ventilated patients. Typical prescription might be higher
pressure 20 for 1.2 seconds, lower pressure 5 for 1.8 seconds (therefore respiratory rate 20,
I:E ratio 1:1.5). Pressure support can be set to 0.
BIPAP; the higher and lower pressure levels are both treated as expiratory pressures,
with the patient triggering inspiratory efforts which are pressure supported from either. The
cycling from higher to lower causes some mandatory alveolar ventilation with no work on the
patient’s part. Equivalent to CPAP/ IPS. Typical prescription high 8 for 3 seconds, low 4 for 3
seconds, pressure support as needed.
Airway Pressure Release (APRV): the higher level is used as the baseline from which
the patient can trigger supported inspirations, with very short mandatory drops to the lower
level to provide supplementary alveolar ventilation with no effort by the patient. The time at
lower level is deliberately set to be shorter than the time to zero flow, so there is autoPEEP.
Potentially a dangerous mode, especially for patients with predominantly resistance pathology
(and raised FRC) like asthma. Suitable for lightly-sedated triggering patients with reduced FRC
but only after expert assessment and prescription with careful and frequent monitoring.
SYNCHRONISED INTERMITTENT MANDATORY VENTILATION (SIMV) modes deliver a prescribed
number of control breaths and allow unsupported or   supported breaths to be taken in

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between. IMV valves were added to older CMV ventilator circuits to allow spontaneous
breathing, and SIMV is the electronic descendant of that modification. However, trials show
that SIMV is associated with higher work of breathing than A/C modes and does not, contrary
to expectations, help patients to wean from sedation or mechanical ventilatory support. If the
triggered breaths are not supported, the lower intrathoracic pressures generated by
inspiratory effort would be expected to enhance venous return and so increase cardiac output
when compared to other modes.
Jet ventilation, high frequency oscillation, and external oscillation or cuirass ventilators are
occasionally used in special cases after Consultant review.

The ventilator care bundle


Initiatives from the USA and UK are promoting five standards of care for ventilated patients
which are established to reduce the duration of ventilator dependency and improve survival.
They are;
1. Elevating the head of the patient s bed (HOB) to 30 degrees or higher. Most VAP episodes are
thought to develop from the aspiration (inhalation) of secretions containing potentially
pathogenic organisms. Being on mechanical ventilation interrupts the body s defenses against
aspiration, thus increasing the risk of its occurrence.
2. Giving some patients on ventilation prophylactic treatment for deep venous thrombosis (DVT).
3. Giving patients prophylactic treatment for peptic ulcer disease (PUD), which reduces the risk of
upper-GI bleeding.
4. Conducting a daily sedation vacation for patients on ventilation, an interruption of sedative
drug infusion until the patient reaches a point of alertness. This is important because over-
sedation further complicates and extends the patient s care.
5. Conducting a daily screening of respiratory function, followed by trials of spontaneous
breathing, which can reduce the LOS as well as the length of time a patient is on mechanical
ventilation (speed the weaning ).

Tracheostomy; if, when, how.


It has become fashionable in the UK to perform tracheostomy on patients needing more than a
few days of assisted ventilation, but the technique is not without complications, which include
late tracheal stenosis. We believe that patients are more comfortable with a tracheostomy. We
tend to consider tracheostomy for periods of assisted ventilation which exceed ten days, but
this number is arbitrarily chosen, and now happens to be the average time that UK intensive
care physicians perform a tracheostomy. A large UK randomised controlled trial showed no
advantage for tracheostomy earlier than ten days.
Tracheostomy can be performed on the ICU and does not require transfer to theatre. The
patient is sedated, and lidocaine/ epinephrine infiltration provides analgesia with
vasoconstriction. After making a skin incision and blunt dissecting to the pretracheal fascia, a
Seldinger wire-based dilational technique is used and is at least as safe and effective when
performed by skilled operators as the traditional ‘surgical’ tracheostomy.

Type 1 Respiratory failure


characterised by
rapid onset
often previously normal lungs
hypoxemia with hypocapnia progressing to hypercapnia
initially a reduced functional residual capacity (FRC)
Notes on ARDS
Initially labelled “adult” to differentiate it from “infant” respiratory distress syndrome, though
it can of course occur in infants and children.  Sometimes therefore called “acute” respiratory
distress syndrome, and more recently the popular term is acute lung injury.   Diagnosis
requires a suspected cause of the lung injury, radiologic appearance of bilateral infiltrates,
hypoxaemia, and reduced lung compliance. It is no longer considered necessary to exclude

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hydrostatic or cardiogenic pulmonary oedema by measurement of the pulmonary artery wedge


pressure.   Almost all cases proceeding to "ARDS" have positive fluid balance and
hyoalbuminaemia, so careful attention to fluid balance is strongly recommended. Studies
suggest targeting low central venous pressure with avoidance of positive fluid balance
(especially following acute circulatory resuscitation with crystalloids). The vascular pedicle
width has been found to reflect intravascular volume status in patients with acute lung injury,
and can be used to track the response to diuretics. Recognising there is a spectrum of lung
injury severity, Murray has proposed a lung injury scoring system.
Acute Lung Injury Score. Murray JF et al Am Rev Respir Dis. 1988;138:720-3.Score
for CXR, PaO2/FIO2 and PEEP each day the patient is on more than 50% oxygen. Acute
Lung Injury Score is the average of the three point scores.  Include Compliance score if
severe ARDS; ALI is then the average of the four scores
POINTS CXR alveolar PaO2/FIO2 kPa PEEP Compliance* ml/cmH20
consolidation cmH2O
0 no consolidation 40+ 0-5 80+
1 1 quadrant 30-39 6-8 60-79
2 2 quadrants 23-29 9-11 40-59
3 3 quadrants 13-22 12-14 20-39
4 4 quadrants <13 15+ <20

 *static respiratory system compliance measured in an apnoeic patient with a super


syringe at about 10ml/kg above FRC.
The threshhold at which ARDS is diagnosed has been suggested to be LIS 2.5 or higher, or
PaO2/FIO2 ratio >26.6kPa.
Following the lung injury tachypnoea and hypoxaemia may occur while the chest X-ray is still
essentially normal.  During this “pre-ARDS” phase, there is capillary leak with increased fluid
flux from the capillaries to the interstitial space, but the total lung water remains normal (circa
500 ml in an adult) so long as it can be cleared, predominantly via the lymphatic system. 

Acute lung injury


Once the drainage capacity is exceeded, lung water increases rapidly to 2,000ml or more, and
the CXR shows the typical appearance of early ARDS.   This early phase is termed the
EXUDATIVE PHASE.   Electron microscopy reveals cellular damage to both the alveolar
epithelium and capillary endothelium.   Hyaline membranes (eosinophilic bands of fibrin,
cellular debris and exuded plasma proteins) form in the distal airspaces.   Resident
macrophages have, in many cases, been stimulated to secrete cytokines which intitiate or
amplify the inflammatory response directly or via activation of neutrophils, with release of
cytotoxic proteases and oxygen radicals.   Over-activation of the coagulation cascade
(particularly platelets and the contact system) leads to platelet micro-emboli and
microthromboses, and thromboxane-induced vasoconstriction.  As type 1 pneumocytes (the
flat, gas-exchanging cells) are lost from the alveolar capillary membrane, they leave areas of
denuded basement membrane.  CAT scanning of the thorax (vide infra) shows graded areas of
poor aeration and consolidation in dependent zones of the lung, and these gradients are
inverted within minutes of turning the patient from supine to prone position.  If the patient
does not rapidly recover or die during the first 3-4 days, he enters the second phase of ARDS,
PROLIFERATION AND FIBROSIS.   Mesenchymal cells replicate within the intimal and medial
layers of pulmonary vessels, narrowing the lumen and contributing to pulmonary
hypertension.   Proliferating type 2 pneumocytes cover the gaps left by the necrosis of type 1
pneumocytes.  Fibroblasts proliferate, laying down fibrin within the interstitium and airspaces. 
Fibrosis becomes significant 8-10 days after the initial lung injury.   RESOLUTION occurs when
type 2 pneumocytes differentiate into type 1 in sufficient quantities to restore adequate gas
exchange.
Mortality from ALI/ARDS is consistently found in some series to exceed 50% but experience in
some specialist units suggests an improving outlook.
It seems to be possible to minimise ventilator-induced lung injury (VILI) by intelligent
prescription of ventilator settings (called “protective mechanical ventilation”). Excessive
distension of vulnerable lung units during inspiration (volutrauma rather than barotrauma)
and repeated collapse and re-expansion (RECOREX or atelectrauma) of vulnerable units in
expiration have been cited as important mechanisms, leading to speculation   that careful
selection of PEEP and avoidance of high tidal volume positive-pressure breaths may improve

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evolution of lung injury and final outcome. The third aspect to VILI the inflammatory response
(biotrauma).
Transfusion-related acute lung injury (TRALI) is recognised as a complication of transfusion of
plasma containing antibodies to the patient’s white blood cells, especially associated with FFP
transfusions donated by women who have experienced pregnancy. Onset of dyspnoea within
24 hours of exposure.

Therapy of type 1 respiratory failure


Is aimed at preventing extreme hypoxemia with PaO2> 7kPa. Where possible pH should be
>7.25; FIO2 should be  <0.6. The cause of respiratory failure should be treated appropriately. 
In mild cases of type I respiratory failure added oxygen via a Venturi type face mask will be
sufficient to correct the hypoxemia.  In co-operative patients mask positive airway pressure
(CPAP) may be of benefit with up to 10 cm H2O CPAP which increases FRC; beware, however,
the development of gastric distension.  Any patient who is unable to protect their airway must
be intubated; CPAP may then be applied via the endotracheal tube.
Ventilation is necessary when hypoxemia and hypercapnia are present. Initially try A/C mode
rate 12 - 15 and positive end expiratory pressure (PEEP)  up to 10 cm H2O. High tidal volumes
(12ml/kg ideal body weight in the NIH study) are known to have excess mortality compared to
"normal" (6ml/kg ideal body weight). Therefore, restrict tidal volume as best you can and
never exceed 700ml in an adult for more than a very short period. The I:E ratio is set to
achieve an inspiratory time of 0.8-1 second for most patients; at the highest rates (30-35) I:E
ration must be 40-50%, but at more normal rates (12-15) much smaller I:E ratios are needed.
As the patient improves the control ventilation rate may be reduced. When the patient is ready
to wean inspiratory pressure support (IPS) of the patient’s own breaths should chosen; IPS may
initially be high; 20 - 25 cm H2O above PEEP but can be reduced as the patient improves.
Try not to curarise ventilated patients since there is always the problem of awareness with too
little sedation; a level of sedation can usually be found at which the patient is comfortable and
arousable in order to communicate wherever appropriate.     Indications for neuromuscular
block in Intensive Care are few. 
for intubation under general anaesthesia
to minimise O2 consumption in severe hypoxaemia (dubious)
to minimise ICP in brain injury (also dubious)
to prevent spasms in severe tetanus
to control patients whose circulation will not tolerate the side effects of adequate sedation
(cruel-to-be-kind; should be rare).
Pancuronium in intermittent doses is recommended by SCCM, but infusion of vecuronium or
atracurium is a commoner practice.

Severe acute respiratory failure.


PaO2 of 7-9kPa (SaO2 circa 90%) is quite adequate while the FIO2 is greater than 0.5, and
10kPa is unnecessarily high.   Sedation is often used to inhibit dyspnoea and optimise
ventilation control.  It is widely held that the peak inspiratory pressure should not exceed
35-40cmH2O. Curarisation may also be required. Curarised patients should be sedated, but
anaesthesia is impracticable so do talk to them and give reassurance. An appealing alternative
approach is APRV with minimal sedation, encouraging patient-triggered inspirations. This
mode needs expert prescription and monitoring.
A balloon-tipped flow-directed pulmonary artery catheter (PAC) is sometimes used to check
for excessive hydrostatic pressure (as estimated from PAOP) and to optimise oxygen delivery,
though the benefits of this are controversial.  Indeed, superior vena cava pressure may be a
more important factor than wedge pressure in controlling pulmonary oedema, as it influences
lymphatic drainage from the thoracic duct. The objective of care is to achieve adequate
oxygen delivery to the tissues with minimal FIO2 and mean airway pressure. Attention must be
paid to blood volume and inotropic cardiac support as well as lung ventilation.  After adequate
intravascular resuscitation PEEP can be selected in one of three ways;
empirically choosing the lowest PEEP which enables you to keep the PaO2 above 8kPa; the
NIH study used a scale linking PEEP to the FIO2; rule of thumb is that appropriate PEEP is
O2%/5.

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adjusting the PEEP to get the best SvO2; the rational approach for shocked patients when
you are using a PAC, but no evidence of outcome benefit.
adjusting the PEEP to the thoracic compliance curve (oesophageal-pressure guided).  A
randomized controlled trial has shown substantial benefit for oxygenation and
compliance, but effects on outcome remain unknown.
Remember that PEEP can be both extrinsic (ePEEP, the PEEP we set in the PEEP dial on the
ventilator) or intrinsic (expiratory gas flow still occurring at end expiration; iPEEP is revealed
after an expiratory hold). Intrinsic PEEP is also known as “auto-PEEP”.
From computerised axial tomography radiological studies Gattinoni hypothesises that in ARDS
the number of ventilatable lung units is greatly reduced; a variable proportion are collapsed
but ‘recruitable’ by appropriate posture change or ventilation, and the rest are collapsed and
‘non-recruitable’.  Amato and his colleagues recommend frequent periodic application of high
continuous positive airway pressure (30-35 cmH2O for 10-20 seconds; or up to 40 cmH2O for
40 seconds in extreme cases) to re-recruit collapsed lung units, especially after interruption of
ventilation with PEEP. The success or otherwise of this manoeuvre is revealed by a step change
in the PaO2/FIO2 ratio.
If possible, try changes in POSTURE   (especially prone) for their effects on lung unit
recruitment and so gas exchange. Typically patients develop air leaks (pneumo-thorax or
peritoneum or mediastinum) in the second week of respiratory failure when higher airway
pressures are being used to maintain gas exchange, and patchy lung necrosis is occurring.  It
can be very difficult to differentiate intraparenchymal lung cysts from loculated
pneumothoraces.  Intercostal drainage is dangerous because the lung is very fragile and easily
traumatised by the tube.  Moreover, it loses elasticity and may be difficult to re-expand.  It is
probably preferable to use ventilation techniques that maintain lung expansion even if air
leaks persist rather than accept lung collapse.   There are hypothetical reasons why HIGH
FREQUENCY JET VENTILATION might improve and sustain lung unit aeration. HFJV has been
superimposed on conventional lung ventilation (combined high frequency ventilation) and
sometimes improves gas exchange.   HIGH FREQUENCY OSCILLATION is still undergoing
evaluation in adult respiratory failure. INDEPENDENT LUNG VENTILATION is occasionally used
on patients with markedly unilateral pathology, such as contusion or pneumonia.  The object
is to apply higher airway pressures via a double lumen tracheal tube to the diseased lung
while protecting the good lung.  Obviously two ventilators are required, but they do not need
to be synchronised.   Check the CXR within a few hours of starting, to exclude excessive
mediastinal shift. With modern ventilators with the ability to let the patient breath
spontaneously from lower or higher airway pressures, modes with names like bi-level and
airway pressure release have been proposed and tried, but no evidence for benefit has been
published yet.
Studies suggest that ventilation techniques should aim to prevent hypoxemia but not
necessarily reduce hypercapnia; Hickling’s so-called ‘PERMISSIVE HYPERCAPNIA’ technique
(originally described in Intensive Care Medicine 1990) uses pressure-limited ventilation to
achieve adequate oxygenation (PaO2 >7kPa) regardless of PaCO2 which may be allowed to rise
as high as 12kPa. There is not enough biological evidence to convince us that hypercapnia is
beneficial, but enough evidence to believe patients can tolerate hypercapnia when better
alveolar ventilation is difficult or dangerous to achieve. Particular attention to ventilating the
injured lung over the steepest section of its compliance curve is believed to be the key to
success, but the hypothesis has not been convincingly confirmed by randomised controlled
trials. A NIH trial of standardised ventilation strategies comparing "normal" tidal volume (6ml/
kg ideal body weight for height) versus high tidal volume (12ml/kg ideal body weight for
height) in the USA was stopped because of excess mortality in the 12ml/kg group. A further
multicentre Canadian/ Australian/ Arabian trial (JAMA 2008) showed additional benefit from
the use of intermittent lung recruitment procedures (halved the need for hypoxaemia rescue
therapies and halved the number of hypoxaemia deaths).
In severe acute respiratory failure fluid retention is commonly found partly as a result of leaky
capillaries and partly due to the hormonal response to prolonged positive pressure ventilation
and opioid sedation. This fluid-overload   impairs gas exchange and can be controlled by
FLUID AND SOLUTE RESTRICTION, PHARMACOLOGICAL DEHYDRATION (e.g. frusemide
infusion) and, in desperate cases, HAEMOFILTRATION.   Circulating blood volume must be
maintained while shrinking the extracellular fluid volume.
O2 consumption can be reduced by avoiding pyrexia, or COOLING to subnormal temperature
(minimum 34C, chlorpromazine is used to help reset the temperature regulatory centre).

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NITRIC OXIDE added to the inspired gases selectively vasodilates ventilated lung units, acutely
reducing PA pressure, improving V/Q match and so improving arterial oxygenation, but meta-
analysis of the published experience to date is that it has no effect on outcome, and may even
be harmful.   iNO does appear to be effective in some cases of neonatal pulmonary
hypertension and respiratory failure and may reduce the need for neonatal ECMO. Delivery,
monitoring, scavenging and health and safety issues must be addressed before iNO is used.
STEROIDS are proven to be ineffective or even counter-productive when administered in high
dose early in the exudative phase of ALI, but there is some randomised controlled trial
evidence that they can speed recovery when used in lower doses. There is no evidence to
support steroid therapy in ‘late’ (after 14 days) ARDS. Response is judged by improvement in
the elements of the acute lung injury score (PaO2/FIO2, compliance, need for PEEP, radiology)
and may take 7-10 days to manifest.
VIRAL PNEUMONIA is a rarer cause of type 1 respiratory failure. Anti-viral therapy may be
exhibited, though outcome benefit is not established. Similarly, steroid therapy is sometimes
resorted to for suppression of inflammatory cytokines, but with no evidence base. Other
unproven therapies to consider include immunoglobulin therapy, immunosupportive sedatives
such as phenothiazine plus ketamine rather than opiate plus benzodiazepine, methylene blue
for multiple organ failure, and early ECLS for severe hypoxaemia.
Extra-Corporeal Lung Support (ECLS).
The first adult ECMO trial (USA) in severe acute respiratory failure resulted in 95% mortality in
both treated and untreated groups.   Gattinoni (Italy) proposed the use of low blood flow
(approximately 25% cardiac output) veno-venous ECMO designed primarily to excrete CO2
while the lungs were used for almost apnoeic oxygenation (low frequency positive pressure
ventilation).   He called it LFPPV/ECCO2R and claims 50% survival in ECMO-entry criteria
patients, but refuses to undertake a controlled trial.  A controlled trial of Gattinoni’s protocol
conducted in Salt Lake City, USA, found 70% mortality in control and treatment groups so
throwing grave doubt on the benefits of LFPPV/ECCO2R. There are now few ECMO centres
around the world with limited capacity, but the threat of large numbers of patients with H1N1
viral pneumonia and severe hypoxaemia is forcing consideration of greater provision.  Patients
facing imminent hypoxaemic or hypercapnic death can be supported by high flow veno-
venous or veno-arterial ECMO but the technique is difficult and it is impossible to predict
whether the lungs will eventually recover.    The entry criteria of the ECMO trials were:
’FAST’ ENTRY: PaO2 less than 6.7 kPa (50 mmHg) for more than 2 hours on FIO2 of 1.0 and
PEEP 5 cmH2O
’SLOW’ ENTRY:- PaO2 less than 6.7 kPa (50 mmHg) for 12 hours with FIO2 0.6 and PEEP 5
cmH2O.
CESAR criteria: 4-parameter Murray score at least 3.0, or respiratory acidosis pH <7.2.
Patients will only be considered if they have potentially reversible lung pathology. Early ECMO
for very severe acute lung injury (<48 hours ALI) is likely to be the most effective use of ECMO.
Patients in ARDS (Murray 2.5+) for more than 10 days and patients who have been subjected
to high-pressure ventilation or high-oxygen exposure (plateau >35, FiO2 >0.8) for more
than 7 days are not suitable candidates.  Complications are mostly related to anticoagulation
therapy, so contra-indications include head injury, liver failure, coagulopathy and
thrombocytopaenia (<100,000). Preference will be given to patients with greater life
expectancy before the onset of ALI and with fewer comorbidities. Patients considered
moribund will not be offered ECMO.
ECMO centres often target normal haematocrit (Hb 140g/L) and plasma oncotic pressure, so
consider transfusion therapy before proceeding to ECMO. Objectives are to maximise oxygen
delivery at lower oxygen tensions and to inhibit extravascular lung water accumulation. Other
possible benefits include oxygen and NO radical scavenging and increased pressure/ flow
ratio (higher calculated SVR). Patients are kept euvolaemic and ‘dry’ by liberal use of diuretics,
haemofiltration and colloid/ RBC transfusion. Haemofiltration capability can be included in the
ECMO circuit.
Reliable arterial access is needed. A central arterial cannula (i.e. Axillary, brachial or femoral)
of at least 18G before heparinisation is recommended.
The decision to go onto ECMO will be made by the consultant in charge; the cannulae used are
large (21 FG) and a significant volume of blood may be lost upon their insertion. Right internal
jugular and a femoral (or bilateral femoral) access is needed. 2DUS guided percutaneous

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technique is preferred, but surgical cutdown is an alternative. Blood is drained from the right
atrium and returned to the IVC. Blood is also used to prime the extracorporeal circuit so
ensure at least 12 units of blood have been cross matched if ECMO is imminent. Use of two
membranes makes for easier changes during prolonged perfusion. The circuit must be
capable of blood flows up to 0.12L/kg/min. Heparin bonded tubing is available which makes
full anti-coagulation  unnecessary although if haemofiltration is also required then this circuit
must be heparinised.   Aprotinin is sometimes used to reduce haemorrhage.   Thrombin
solution can be applied to the cannulation sites.
Systemic heparinisation is used to achieve activated clotting time (ACT) 160-220s. Be
prepared for cardiovascular instability at the start of ECMO. Slowly increase the blood flow rate
to approximately 25% of the cardiac output, stabilise and assess. Use the lowest
extracorporeal flow compatible with the preservation of life during lung rest (FiO2 no more
than 40%, inspiratory and expiratory pressures less than 20, respiratory rate 10 or less).
Arterial oxygen tension 85-90% is adequate, especially as haemoglobin concentration will be
higher than non-ECMO practice. Oxygenation will require higher blood flows, usually 50-75%
of the cardiac output. Changes in cardiac output will cause changes in ‘shunting’ of the
venous return which has not been oxygenated and must be considered when interpreting
arterial blood samples. Cardiac output management is essential. The other phenomenon to
consider is recirculation of already-oxygenated venous blood into the ECMO circuit.
Body temperature is kept at 35-37C; lower temperatures may be attractive for suppression of
metabolic rate, but coagulation considerations make this risky.
After heparinisation, it is impractical to provide new vascular access. Haemofiltration can be
incorporated into the ECMO circuit, and drugs including parenteral nutrition can be
administered downstream of the membrane oxygenator.

Small print
Replenishment of the anti-oxidant amino-acids glutathione and cysteine (e.g with Acetyl
cysteine (Parvolex) seems to improve DO2 in ARDS, and may “protect” the lungs if given early
reducing the number of organ failure free (OFF) days but has not been shown to change
mortality. KETOCONAZOLE (an imidazole antifungal agent which is also a thromboxane
synthetase inhibitor) and LISOPHYLLINE failed to produce benefit in definitive RCTs.
EPOPROSTENOL (prostacyclin, PGI2) has been demonstrated to be an effective (if expensive)
nebulised pulmonary vasodilator.  ALPROSTADIL (PGE1) showed some promise either alone or
in a liposomal carrier in reversing early ARDS but trials have failed to find a substantial
benefit. ALMITRINE  might be a complementary agent to NO as it is given intravenously and
augments hypoxic pulmonary vasoconstriction.  SURFACTANT therapy has been disappointing.
PARTIAL LIQUID VENTILATION (also called perfluorocarbon associated gas exchange, PAGE) is
practicable and has theoretical mechanical benefits, opening and keeping open lung units in
dependent zones, but whether it will help patients either alone or in combination with other
therapies (like surfactants or nitric oxide) awaits study.

Type II Respiratory Failure


Characterised by
Previously diseased lungs
Slower onset
Hypoxemia, hypercapnia
Increased FRC
e.g. COPD, asthma

Therapy of Type II respiratory failure


Increase FIO2 and humidification.  Antibiotics only if bacterial infection is likely.  Nebulised
salbutamol 5mg or terbutaline 10mg should be given at 15-30 minute intervals until
improvement is seen. Alternatively use a continuous nebuliser delivering up to 10mg/ hour
salbutamol. Add nebulised Ipratropium bromide (0.5mg adults).
Asthmatics benefit from steroids; prednisolone 40mg od orally or hydrocortisone 100mg qds
intravenously for adults. 

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A single dose of magnesium 1.2-2G over 20 minutes can help in patients who have not
responded to salbutamol and steroids, but should not be repeated.
In severe cases iv salbutamol (slow loading dose 250µg then 3-20µg/minute under ECG
monitoring). Patients normally taking theophylline can receive intravenous aminophylline
infusion at 0.5-0.7mg/kg/hour.   If theophylline loading dose is needed give 5mg/kg over 20
minutes. Therapeutic levels should be measured in serum (10 ml clotted blood before next
dose or >1 h after starting infusion). Therapeutic level is 55 - 110 µmol/l (10 - 20 mg/l). 
Convulsions are a sign of toxicity so avoid paralysis if possible.
In some of the chronically hypercarbic chronic obstructive pulmonary disease (COPD) patients
(typically the ‘blue bloaters’) use of high FIO2  may worsen hypercapnia by increasing dead
space in patients unable to increase minute ventilation or by reducing “hypoxic” respiratory
drive. Thus regular blood gases should be used to monitor the effectiveness of therapy. Avoid
all sedative medication. 
NIPPV (non-invasive positive pressure ventilation) is proven to be an effective supportive
intervention for patients with acute exacerbations of COPD.   Indications are acidaemia
(pH<7.35) and tachypnoea (RR >30 breaths/min). NIPPV can be performed with special
ventilators on the respiratory wards at SGH.  Alternatively, a flow triggered ICU ventilator can
be used in pressure control mode (20cmH2O) with 0-5cmH2O PEEP, but the sensitivity of the
alarms on such ventilators makes it impractical to use them for NIPPV for more than a short
period of time.
The decision to intubate and ventilate a patient with COPD is often difficult and such a
decision should have been made after discussion with both ICU and Respiratory consultants.
Ideally when such patients are admitted there should be early discussion over the patient’s
suitability for ventilation before their condition deteriorates. Such decisions are based on
health prior to the acute episode, examination, investigation, and social history. The number
of acute admissions in the previous year and previous episodes requiring ventilation should
also be considered. Patients who are at best house-bound by their respiratory insufficiency
should not be ventilated.
DOXAPRAM infusion may be of benefit in those patients not considered suitable for
ventilation.
Indications for intubation and ventilation are:
exhaustion
inability to cough
decreasing conscious level
rising PaCO2
persistently low PaO2
It may be most appropriate to intubate these patients awake to avoid the cardiovascular
instability associated with induction of anaesthesia; such patients are often very dehydrated.
Pressure support ventilation is then appropriate with pressures up to 30 cm H2O above a low
PEEP (2.5 cm H2O). Aim for normal PaCO2 of 5.3 kPa with PaO2 > 8 kPa. A novel variant of
pressure support/ PEEP is pressure support/ bi-level PEEP. Some mandatory tidal excursion
occurs as the ventilator cycles between the low and high PEEP levels. With persistently high
HCO3- levels correction with acetazolamide may be of benefit (250 mg bd). Salbutamol will
cause a lowering of plasma potassium which should be corrected if < 3.5 mmol/l. As the
patient improves so the pressure support may be reduced. Once support is minimal a ‘T’ piece
cross-flow circuit should be used prior to extubation. Avoid high levels of PEEP and CPAP. 
Asthma poses some special challenges. Most patients presenting to ICU with acute severe
asthma have chronic moderate to severe airflow obstruction with deterioration over several
days. They have been treated with increased beta agonists and steroids and the
pathophysiology seems to be mucosal oedema and hypertrophy with plugging of secretions
which contain eosinophils. These patients could benefit from bronchial lavage.
In the asthmatic patient requiring ventilation there is a risk of tension pneumothorax if airway
pressures exceed   45 cm H2O. Inflation pressures are often high and pressure controlled
ventilation may be the best mode with a slow respiratory rate and prolonged expiration.
Permissive hypercapnia may be necessary in such circumstances until bronchospasm subsides. 
A number of further techniques have been used in extreme asthma; they all have the potential
to cause complications and are not invariably successful.

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HELIOX (oxygen in helium) has a lower viscosity than air and is easier to breath.
ANAESTHETIC AGENTS have been reported to improve bronchospasm.  Ketamine is probably
the anaesthetic of choice in asthma.  The inhalational agents may cause sudden hypotension
when given in acute severe asthma.
BRONCHOALVEOLAR LAVAGE   is sometimes used to clear mucus plugging,   Transient
deterioration in blood gases should be anticipated.
FORCED EXHALATION  uses a nurse kneeling astride the patient to press on his chest to aid
exhalation in order to overcome air trapping.  Only used in extremis!

Humidification, secretions etc.


Heat-moisture exchangers (filter humidifiers) are adequate for most cases. Heated water
humidifiers can become contaminated with bacteria such as Pseudomonas. Nebulised
salbutamol (5mg) is both a bronchodilator and anti-inflammatory agent. Nebulised heparin
(50,000 units in 5ml) reduces the elasticity of viscid bronchial secretions. N-acetyl cysteine is
a mucolytic which can be nebulised in 20% solution (but smells and tastes of rotten eggs) or
given intravenously. Nebulised hypertonic saline (5ml of 3-7%) is more effective than isotonic
saline (0.9%) at assisting expectoration, but both can acutely increase airway resistance.

Weaning from Mechanical Ventilation


Before weaning starts, the patient should be at his/her best.

Weaning check-list
1.       Ensure that acid-base status, electrolyte and PCV values are normal. Abnormal levels of K+, Mg++,
PO4-- and Ca++ may impair muscle function.
2.       Circulation stable; weaning can start if only a low level of inotropic support is required.
3.       Gas exchange is satisfactory: PaO2 >8kPa; FIO2 <0.4; PEEP <5cmH2O. Areas of atelectasis should
have been re-expanded (CXR).
4.       Respiratory rate should be <35/min with a minute volume >200 ml/kg/min. A widely quoted test for
adult patients is frequency (breaths per minute) divided by tidal volume (litres) two minutes after
disconnection from mechanical support; values of 100 or more suggest the patient still needs support.
5.       The patient is awake and co-operative; respiratory drive must be optimal; respiratory muscles should
be working normally (vital capacity should be >15 m/kg and maximal inspiratory pressure more
negative than -16). Gag and cough reflexes must be intact.
6.       Empty stomach prior to extubation; abdominal distension may hinder weaning.
Decide what form of weaning is appropriate for the patient;

Rapid wean
is often suitable for patients who were ventilated prophylactically after major surgery where
lung function was normal prior to that surgery. Some asthmatics may also do well with a rapid
wean when bronchospasm has resolved. These patients should be put onto a cross-flow ‘T’
piece with humidified gas at an FIO2 of 40% once awake and fully co-operative. If respiratory
pattern is acceptable and comfortable for the patient then if SaO2 remains in the low 90s or
above then proceed to extubation as soon as indicated.

Slow wean
is used for patients with pre-existing lung disease or in those who have undergone prolonged
periods of ventilation.  After prolonged critical illness profound weakness is common and has
been attributed to a polyneuropathy, whose aetiology is unclear.  Weakness may affect even
the respiratory muscles, but most patients eventually recover.
Weaning starts with a reduction in ventilatory support by a reduction in the control rate.
Switch to pressure support when the patient has adequate respiratory drive at an acceptable
arterial CO2 tension.  Pressure support is then reduced in small steps. A poor prognostic sign
is a fall in tidal volume with progressive reduction in the support level above PEEP. Arterial
blood gas monitoring is essential in the early phase of weaning such patients; progress should
be slow but steady.

‘Classic’ wean

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Some patients who have had prolonged periods of ventilation or who have severe pre-existing
COPD with poor cardiorespiratory reserve whose respiratory muscles may not be able to
function adequately in the weaning modes described above may successfully wean by the
classic method. Instead of switching to IPS, patients are allowed to breathe spontaneously via
T-piece or continuous-flow CPAP circuit for a short period at regular intervals: e.g. 5 min
every hour. This period of spontaneous ventilation is gradually increased until extubation is
possible.

“Progressive care programme”


In some difficult-to-wean patients an alternative is the BiPap machine (available through the
senior physiotherapist). In some COPD patients this may make weaning easier and more rapid;
this machine can also be used in the extubated patient using a tightly fitting face-mask. Some
patients may require prolonged ventilatory support on discharge to the ward or even from
hospital.

Minitracheostomy
Has a limited place in respiratory support but may be of use in the mildly obtunded patient
whose major problems are of impaired cough with subsequent sputum retention. In such
patients it may avoid formal intubation or re-intubation in a patient who has been weaned and
extubated. There are several complications associated with minitracheostomy of which
bleeding and malplacement may cause additional problems. Minitracheostomies should
therefore be inserted only by someone familiar with the technique.  The Seldinger insertion
method is prefered.   Jet ventilation can be applied through a Minitrach, but displacement
causes dramatic problems so take care.

Fibreoptic Bronchoscopy (FOB)


Please handle the Flexible Fibreoptic Bronchoscope (FFB) with care, and always with permission
of Consultant.  Indications include; aid to intubation, confirmation of correct tube positioning,
airway toilet, and obtaining specimens from selected parts of the bronchial tree.  A catheter
mount with a diaphragm through which the FFB is passed while ventilation proceeds is
available.   Administer 100% oxygen and ensure somebody is monitoring the patients vital
signs.

Intubation.
Apply topical local anaesthesia (with vasoconstrictor if nasal intubation).   It is sometimes
useful to pass the ET tube to pharynx and then pass FFB through.  When cords are seen, inject
local anaesthetic onto them and wait a moment before advancing to trachea.  The patient will
often cough on intubation even with good analgesia.  Slide tube over FFB to trachea.
Down the tube you will see (1)  inside of the endotracheal tube (ETT), (2) the Murphy eye, (3)
the trachea and carina. If the ETT is coated with inspissated secretions, change it!  Recheck
position of new tube by FOB.  The carina is sometimes haemorrhagic if the patient has been
intubated for several days and suctioned frequently.  Examine the ‘good’ side first, if there is
one, to minimise contamination.  The right bronchus is usually more obvious as it is more ‘in
line’ with the trachea.  Going down the right bronchus you will notice almost immediately the
right upper lobe bronchus.  This has three segmental bronchi, apical, posterior and anterior. 
Continuing down the right bronchus you will find the middle lobe bronchus which has two
segmental bronchi, the medial and lateral.  The continuation of the right bronchus is the lower
lobe bronchus which has five segmental bronchi, apical, medial, lateral, anterior, posterior. 
Now, coming back to the carina and going 45cm down the left bronchus, you will first see the
upper lobe bronchus which has four or five segmental bronchi in two groups; apical bronchi
are  the apicoposterior (or apical and posterior) and anterior, lingula bronchi are the superior
lingula and inferior lingula.  The continuation of the left bronchus is the lower lobe bronchus
and terminates in four (or five) segmental bronchi, apical, anterior, posterior, lateral (the
medial is greatly reduced on the left by the heart).
Secretions from specific parts of the lower respiratory tract can be collected in a sterile
sputum trap to confirm a diagnosis of pneumonia.  If necessary, 10ml saline can be used to
obtain a lavage specimen, but without specialised protected suction apparatus contamination
from the trachea cannot be excluded.

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Chapter 6

Fluids, solutes, acid/base balance


Maintenance compensates for obligatory salt and water loss in urine, stool, evaporation while
Nil By Mouth and preserves homeostasis.
Deficit is added to maintenance to compensate for extra losses.
Resuscitation compensates for extreme losses of blood, water and/ or electrolytes which are
causing organ dysfunction.
Parenteral nutrition. Specialist advice.
Therapeutic uses of IV fluids, Specialist advice.

Essential physiology.
Bio fluids are aqueous solutions of;
• Strong ions, e.g. Na+, K+, Cl-, lactate etc
• Carbon dioxide/ carbonic acid/ bicarbonate equilibrium (enzyme carbonic anhydrase)
• Weak ions (mostly weak acids), e.g. Albumin, phosphate, amino acids etc.
• Non-electrolyte molecules.
All membranes are permeable to water; hypothalamic – pituitary – renal axis maintains body
fluid osmolarity at about 285 m.osmol/litre. In a 70kg man (42 litres total body water);

RBC ICF 1 litre Plasma 3 litres ISF 14 litres ICF 24 litres

Na+ 19 140 135 10

Cl- 50 105 110 10

K+ 95 4 3 155

Weak anions A- 42 15 - 115

Mg++ 5 2 2 10

Other anions 10 1 1 35

HCO3- 15 25 30 12

pH 7.2 7.4 7.4 7.0

Daily renal excretion approximately 500 mosmol nitrogen-containing molecules plus


electrolytes, an active person takes in about 2.5 litres water per day, produces about 1.8 litres
urine with about 700 mosmol (390 mosmol / L), but under restrictive fluid input can easily
excrete the 700 mosmol in about 1000ml concentrated urine / 24 hours.
Stress and systemic inflammation increase proteolysis and so increase the nitrogen load to be
excreted, but the hormonal environment inhibits increase in urine output, and maximal
concentrating ability is reduced from about 1200 to perhaps only 500 mosmol/L. Expect
therefore to see transient rise in plasma urea and urine output reduced to about 1000ml / day
after surgery or in acute illness. Giving liberal intravenous fluids has only small effect on urine
output but may reduce plasma urea by dilution. Unless the patient was depleted, most of the
extra water and electrolytes are retained as oedema (“fluid overload”). Patient gains weight
(1litre = 1kg). Weight gain > 4kg (fluid balance > 4 litres) increases complications including
ileus, infection, and arrhythmias. Transient hypoalbuminaemia and hypomagnesaemia (and
low urea) are common after major surgery and acute illness for which liberal intravenous
therapy has been used. It is not necessary to ‘correct’ them by giving albumin or magnesium
unless severe or unless the patient is symptomatic.
Evaporative loss as sweat may be as little as 10-20ml/ hour in a temporate climate, but much
greater in summer heat or in pyrexial illness or after exercise. Water (and carbon dioxide)

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produced by metabolism matches water lost by exhalation. (The partial pressures of CO2 and
water in exhaled air are similar).

Natraemia 
Hyponatraemia is the commonest electrolyte abnormality and is usually due to water overload
(sometimes inappropriate antidiuretic hormone secretion).  Restrict fluid volume if possible. 
Pseudo-hyponatraemia is due to lipaemic serum (especially patients on parenteral nutrition). 
Severe hyponatraemia and its treatment can cause irreversible neurological injury (typically
central pontine myelinolysis).  Treatment is controversial.  In acute hyponatraemia (less than
24 hours) use fluid restriction and 2xnormal saline therapy to get [Na+] 120-130mmol/l
(maximum daily increase 20mmol/l).  In chronic hyponatraemia due to overload restrict fluids
and consider frusemide; if diuretic induced use potassium/insulin/glucose infusion.  In either
case give normal saline to replace urinary sodium losses (which should be measured).  Limit
plasma sodium increase to 12mmol/l/day.
Mild hyponatraemia sometimes develops during continuous haemofiltration; this can be
corrected by increasing [Na] of HF Replacement solution.
Hypernatremia is usually due to water deficit, restrict Na and rehydrate.

Chloraemia
Needs to be assessed relative to sodium concentration, see Balasubramanian’s worksheet at
the end of this chapter.

Kalaemia
Hypokalaemia is common and may be associated with a metabolic alkalosis. It can be
aggravated by beta2 agonist therapy   or magnesium deficiency.   Replace aggressively to
maintain 4-4.5 mmol/l.    Monitor ECG continuously for signs of adequacy of replacement. 
NEVER ADMINISTER CONCENTRATED POTASSIUM SOLUTION THROUGH A PERIPHERAL IV
CANNULA.
Hyperkalaemia is treated by restriction, chelating agents when practicable, or insulin/glucose
therapy (20 units to 50ml 50% Glucose).  Treat metabolic acidosis if present.  Salbutamol or
dopexamine may also be beneficial.

Hypomagnesaemia
... by dilution is a common coincidental finding in acutely ill patients, and is associated with
changed albumin and other electrolyte concentrations rather than true magnesium deficiency.
There is no evidence that 'correction' of dilutional hypomagnesaemia is beneficial. True
deficiency is usually associated with hypokalaemia and/ or hypophosphataemia. Can occur in
severe chronic malnutrition.

Therapeutic hypermagnesaemia
Specific indications include pre-eclampsia, tetanus, cardiac arrythmias and acute severe
asthma. See disease-specific protocols. Monitor ankle jerks and regular serum magnesium
levels. Magnesium is both a muscle relaxant and an anaesthetic agent, so close supervision is
needed. CaCl is used to treat intoxication.
Specialist therapy; magnesium sulphate for acute severe asthma
2g Magnesium sulphate (20ml of 10% MgSO4) over Caution in oliguria.
ten minutes.

Specialist therapy; magnesium sulphate for pre eclampsia or tetanus


4g Magnesium sulphate in twenty minutes then Careful regular examination of knee and
maintain at 1g magnesium sulphate per hour. ankle jerk reflexes, respiratory rate,
Target plasma concentration magnesium 1.5 - 3.5 muscle strength.
mmol/ L

Specialist therapy; severe hypomagnesaemia.


5g Magnesium sulphate over five hours. Caution in oliguria.

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Calcaemia
Hypocalcaemia is seen in hypoalbuminaemia and after parathyroid surgery. Trousseau’s or
Chvostek’s signs may be positive. Correct carefully with CaCl 10% by slow i.v injection.
Hypercalcaemia is associated with dehydration; in severe cases, forced diuresis may be
necessary.

Phosphataemia
Hyperphosphataemia ocurs in renal failure or lactic acidosis and may have significant acid-
base consequences. Treat underlying cause.
Mild hypophosphatamia does not need active correction.
Specialist therapy; moderate to severe hypophosphataemia (phosphate deficiency).
Hypophosphataemia due to redistribution is seen in alkalosis, diabetic ketoacidosis, insulin/ glucose
therapy and recovery from burns.
Moderate, PO4 < 0.5 mmol/l.
10mmol as sodium phosphate or dipotassium hydrogen phosphate in 500ml Glucose 5% or
Sodium Chloride 0.9% over 12 hours.
Severe, PO4 <0.3 mmol/l.
10mmol as sodium phosphate or dipotassium hydrogen phosphate 17.42% in 500ml Glucose 5%
or Sodium chloride 0.9% over 6-8 hours and recheck.

Albuminaemia
Hypoalbuminaemia is common and probably of little consequence for most patients.  It is,
however, an index of severity of illness and strongly associated with increased risk of death. In
the SAFE study, using albumin to treat hypovolaemia produced no overall advantage or
disadvantage when compared to crystalloid resuscitation, but albumin resuscitation was
HARMFUL in patients with traumatic brain injury. Albumin replacement in the acutely-ill
patient is not indicated, except perhaps in profound (<15 mmol/l. by BCP method)
symptomatic hypoalbuminaemia.
Hyperalbuminaemia occurs in acute dehydration. Treat by rehydration.

Colloid osmotic pressure


Very controversial in therapeutics. While it is generally accepted that albumin therapy offers
little benefit, some clinicians use synthetic colloids to maintain plasma oncotic pressure and
preserve plasma volume in hypoalbuminaemic patients. Excessive use of colloids is probably
harmful to renal function.

Glycaemia
Hyperglycaemia is common in stressed patients, even those who are not diabetic, and sound
evidence exists for improved clinical outcome using intensive insulin therapy (with adequate
carbohydrate provision) to achieve normoglycaemia in patients with acute myocardial
infarction, acute brain injury, and following major surgery. DO NOT treat hyperglycaemia by
withholding glucose.
Hypoglycaemia is an occasional complication of over-enthusiastic insulin therapy. Give
aliquots of 50% glucose i.v.

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Some Crystalloids; ions (mmol) and glucose (g) per litre.


Na+ K+ Cl- HCO3- Gluc
Sodium chloride 0.9% 154 154
Potassium chloride 0.15% or 154 20 or 40 175 or 195
0.3% / Sodium chloride 0.9%

Sodium chloride 1.8% 310 310


Glucose 5% (280 mmol/L) 50g
Potassium chloride 0.15% or 20 or 40 20 or 40 50g
0.3% / Glucose 5%
Glucose 4% / Sodium chloride 31 31 40g
0.18%
Potassium chloride 0.15% or 31 20 or 40 51 or 71 40g
0.3% / Glucose 4% / Sodium
chloride 0.18%
Glucose 5% / Sodium chloride 77 77 50g
0.45%
Glucose 10% 100g
Sodium bicarbonate 1.26% 150 150

Sodium bicarbonate 8.4% 1000 1000


Compound sodium lactate 131 5 111 Lactate metabolised to
HCO3 and glucose.
Calcium.

Fluids for ECF and blood volume expansion,


these solutions have little or no potassium or glucose.
ions mmol / l
Na+ Cl- / HCO3- Other molecule
Balanced salt solution (e.g. 140 105 / 35 K+ , some have Ca++ and/ or
Sterofundin (Braun) or (Acetate, malate, Mg++ in plasma
Plasmalyte (Baxter) gluconate as bicarb concentration
substitute.)
Gelofusine 4% 154 120 / 34 (OH) Gelatine 40g
Voluven 6% in balanced salt 137 110 / 34 (acetate) Hydroxyethyl starch 60g
solution (Volulyte) Mg 1.5
Plasma, Human Albumin 140 105 / 35 Albumin 45g
Solution 4.5%.
Human Albumin Solution 20% 140 105 / 35 Albumin 200g

Fluids for ECF expansion in patients with hyperchloraemic acidosis or for alkaline
diuresis
Ions mmol / l. Select according to plasma sodium.
Bag of… Add… Na+ Cl-/ HCO3- Gluc g/L
Sodium bicarbonate 150 0 / 150
1.26% 1000ml
Glucose 5% 1000ml Sodium Bicarbonate 8.4% 130 0 / 130 43
150ml “Sodium bicarbonate 1.1% / glucose
4.3%”
Glucose 5% / Sodium Sodium bicarbonate 8.4% 162 71 / 91 43
chloride 0.45% 500ml 50ml “Sodium bicarbonate 0.76% / sodium
chloride 0.41% / glucose 4.3%”
Glucose 4% / Sodium Sodium Bicarbonate 8.4% 118 27 / 91 36
chloride 0.18% 500ml 50ml “Sodium bicarbonate 0.76% / sodium
chloride 0.16% / glucose 3.6%”

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Crystalloid Vs Colloid
  CRYSTALLOIDS COLLOIDS
Distribution extracellular mostly intravascular
 Haemodynamic effects transient  rapid, sustained
 Volume required  at least  x2  smaller
 Risks  oedema (reduced COPmv)  i/ oedema  (increased Pmv)
ii/ anaphylaxis (esp
gelofusine), renal failure
(dose-dependent effect of
HES in sepsis)
III/ excess mortality risk?
 Cost  Cheap  Expensive

Comparing available colloids


  GELATIN DEXTRAN  70 HE STARCHES
CONC. 3.5% 6% 6%-10%
MOL WT (1000) 35 70 130-450
VOL EFFECT% 80% 120% 100%-140%
PLASMA T½ H 3 6 6-8
ELIMINATION very rapid rapid Larger MW solutions are very slow
ELECTROLYTES Na 154 various various
Cl 120
COMMENTS Gelofusin is Ca Possible anaphylaxis, Hyper-amylasaemia.
free and pH platelet inhibition, cell Overload the reticulo-endothelial system?
balanced. wash before cross Coagulopathy? (binds clotting factors).
Anaphylaxis matching. Fewer hydroxyl groups (lower degree of
risk 1:2000 Does it protect against substition) may be advantageous (0.4-0.6)
  DVT, ARDS?

Maintenance fluids, and deficits.


Assess needs carefully.
Before any intravenous fluid is prescribed, whether for replacement or maintenance, the
following should be considered:
• Clinical assessment of the patient’s fluid status, i.e. is there a deficit requiring replacement
or does the patient need maintenance fluids only.
• Where a fluid deficit is identified (e.g. haemorrhage or vasodilatation, diarrhoea or vomitus,
insensible or renal losses) the nature of the fluid deficit must be identified.
• The type of fluid which will best treat the deficit.
• The appropriate rate of fluid administration guided by clinical assessment and safety limits.
• The proposed clinical endpoint.
• Continued monitoring of fluid and electrolyte status.
Dehydration (whole body water depletion; repletion is a necessarily slow process)
Estimate water deficiency from degree of hypernatraemia and replace with Glucose 5%
100-250ml/hour. Monitor Na+ concentration and avoid change of more than 20mmol / 24h.
Monitor glucose and consider insulin.

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Diabetes insipidus Measure hourly urine volume and match with Glucose 5%
plus Potassium chloride or Glucose 4% / Sodium chloride
0.18% according to electrolytes. Consider insulin to prevent
hyperglycaemia. Consider V1 agonist to control polyuria.
Understanding typical constitution of some GI losses.
Body Secretion & Na+ mmol/L K+ mmol/L Cl- mmol/L HCO3- mmol/L
typical ions.
Gastric 20-60 15 140 0 – 15
Pancreatic 130 10 50 85
Bile & small 145 5 105-135 8-30
intestinal
Diarrhoea 30 – 140 30 – 70 20 – 80

When allowing for nutritional volume, remember that lipid solutions are not entirely aqueous. 
You can assess lipaemia by inspecting the plasma of a small saved sample once the cells have
settled.  If present, reduce lipid administration.

Daily maintenance prescriptions.

Restrictive prescription; the “1ml/kg rule” for adults. Flow rate 1ml/kg IBW/h
Daily volume 24ml/kg IBW
Adult Female typically 60ml / h, 1.42 litres per day.
Adult Male typically 70 ml / h, 1.68 litres per day.
Liberal prescription; the “4-2-1 rule” for children and adults. Flow rate is 4ml/kg up to 10kg,
2ml/kg 11-20kg, then 1ml/kg. For >20kg patient, 1ml/kg +40ml/hour. Daily volume 24ml/
kg IBW + 960ml.
Adult Female typically 100 ml / hour, 2.4 litres per day.
Adult Male typically 110 ml/ hour, 2.64 litres per day.
Remember that many drugs come as sodium salts, so that total sodium input may be much
higher than fluid prescription. For most adults Glucose 4% / Sodium chloride 0.18% with
Potassium chloride 0.15% at 60-80ml/h.
Na+ K+ Cl- Gluc
Daily requirement mmol/kg 1-2 1-2
2000ml / day of following prescriptions provides;
Prescription Na+ mmol / K+ Cl- Gluc
(83ml / hour = 2000ml / day) day mmol / day mmol / day g / day
Glucose 4% / Sodium chloride 0.18% 83ml/h 62 62 80g
Glucose 5% 83ml/h x 2, 0.9% Sodium 103 103 33.5g
chloride 83ml/h x1
Glucose 5% 83ml/h alternating 154 154 50g
0.9% Sodium chloride 83ml/h
Glucose 5% / Sodium chloride 0.45% 83 ml/ 154 154 100g
h
… + Potassium chloride 20mmol / l (0.15%). + 40 + 40
… + Potassium chloride 40mmol / l (0.3%). + 80 + 80

Specialist service maintenance preference at SUHT; hepatobiliary surgery


Prescription Na+ mmol / K+ Cl- Gluc
day mmol / day mmol / day g / day
Glucose 4% / Sodium chloride 0.18% 62 62 80g
80ml/h
Gelofusine 30ml/h 95 6 86
Human Albumin Solution used for correction of hypovolaemia.

Specialist service maintenance preference at SUHT; neurosurgery


Prescription Na+ mmol / K+ Cl- Gluc
day mmol / day mmol / day g / day
Sodium chloride 0.9% 80ml/h 300 300
Enteral feeding when possible. Emphasis on avoiding free water which adds to brain swelling.

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Resuscitation fluids
Meta-analysis of published RCTs finds no obvious advantages for the more expensive and
risky colloids over sodium-containing crystalloids in trauma resuscitation and surgical
patients. Crystalloids are preferred for trauma and surgery in US but at possible cost of
peripheral oedema.   Healthy lungs are partly protected by low reflection co-efficient to
albumin and high lymph flow capacity.   Choose synthetic colloid and blood (if indicated) for
very rapid resuscitation in profound hypovolaemic shock.  Rapid infusion cannulae and giving
sets and fluid heat exchanger should be used when available.  Published studies suggest that
excessively-aggressive fluid resuscitation can be harmful, so an estimate of the likely deficit,
and care not to exceed that volume, could be helpful.
Albumin for fluid resuscitation in patients with traumatic brain injury is NOT SAFE. This
subgroup from the SAFE study had reduced survival compared to saline-resuscitated patients.

Low extra-cellular fluid volume / adequate blood volume


Dry membranes, reduced skin turgor, oliguria (or polyuria as cause of ECF volume depletion
as in diabetes mellitus). Plasma sodium often low. Need frequent reassessment especially for
rising venous pressure/ pulmonary oedema. Do not use colloids.
Immediately;
(chemistry not known) Sodium chloride 500ml in thirty minutes.
After blood (and urine if possible) chemistry results;
Plasma sodium normal or high, balanced salt solution 150-250ml/h
no acidosis,
Plasma sodium low, no acidosis, 0.9% Sodium chloride at 150-250ml/h
Plasma sodium low, acidosis 1.26% Na Bicarbonate at 150-250ml/h
Continue until response (improved urine output, rising venous pressure etc). Use insulin
sliding scale when blood sugar > 8.3 mmol/L (N.B. diabetes mellitus)

Low blood volume (haemorrhage or extreme ECF depletion).


Falling BP, rising heart rate, low venous pressure, oliguria, altered mental state.
THIS IS AN EMERGENCY, do not leave patient unattended until circulation restored.
Balanced Salt Solution 1000ml (or 20ml / kg) immediately then second 1000ml
(preferred) or 0.9% Sodium bolus
chloride.
Plasma substitute; Colloid in 500ml boluses
Balanced salt solution or 0.9%
Sodium chloride.
Plasma; Human Albumin 4.5% Expensive, no benefit over BSS or plasma substitute in acute
resuscitation. Only use in very hypoalbuminaemic patients.
RBC transfusion Blood loss >30% blood volume or > 1000ml or Hb <70g/l
FFP Blood loss > 50% blood volume or Bleeding and INR >2
Platelets Bleeding and platelets <50

Experimental studies suggests a possible future for hypertonic saline (up to 7.5% NaCl) with or
without a colloid for rapid resuscitation. Hypertonic saline is postulated to have benefits
beyond the anticipated expansion of ECF from intracellular fluid redistribution; these include
vasodilation, deswelling of intravascular and endothelial cells, and central sympathetic
nervous system activation.

Blood and clotting factors


There is no optimal haemoglobin concentration, but for critically ill adults somewhere in the
range 70-120g/L is acceptable.  A Canadian RCT found that most patients benefit from a
‘restrictive’ approach to transfusion (70-90g/L). However, there remains a concern that there
may be subgroups who would benefit from keeping the Hb higher. Though recently transfused
RBCs transport relatively small quantities of oxygen, transfusion increases blood viscosity with
possible improvement of tissue perfusion.
RBC transfusion may cause minor allergic or pyrexial reactions, which can be diminished by
co-administration of chlorpheniramine and paracetamol. Rarely the patient can experience
acute and severe haemolysis, anaphylaxis or bacteraemia. Delayed haemolysis can occur in

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patients previously transfused. Post-transfusion purpura occurs 5-9 days after blood
transfusion and is due to PLA-1 positive platelets given to a PLA-1 negative patient.
Evidence suggests erythropoietin (Epoitin Alfa 40,000 units weekly up to three doses) have
little if any effect on transfusion requirements for critically-ill patients, but there is a survival
benefit for trauma patients.
Platelet count below 20,000 or INR   >5 should usually be treated to minimise the risk of
bleeding.  In the presence of bleeding, check Hb, platelet count and INR regularly.  If platelet
count is low and INR prolonged, request fibrinogen levels and fibrin degradation products. In
the presence of ACTIVE HAEMORRHAGE, treat;
platelet count <100,000 with platelet transfusion,
INR >1.8 with fresh frozen plasma,
fibrinogen <0.8g/L with cryoprecipitate.
A rare cause of thrombocytopenia is an immune reaction to heparin. The “4T score” estimates
the a priori likelihood of this diagnosis;
Thrombocytopenia: the fall exceeds 50% of baseline or nadir count is 20-100 = 2 points,
the fall is 30-50% or nadir count is 10-19 = 1 point.
Timing: 5-10 days after heparin treatment initiated or 1 day if prior exposure to heparin
within 30 days = 2points, more than 10 days after treatment initiated or more than 30
days from prior exposure = 1point
Thrombosis: new proven thrombosis or skin necrosis or systemic reaction = 2points,
progressive or recurrent thrombosis or red skin lesions = 1 point.
By exclusion: no alternative cause = 2 points, possible alternative cause = 1 point.
If 4T score is 1-3 (HIT unlikely), continue heparin while awaiting results of investigations. If 4T
score 6-8 (HIT probable), withdraw heparin and use alternatives. First request ELISA test for
antibodies to heparin and platelet factor 4 (PF4). ELISA-positive patients may then be offered
serotonin-release assay (SRA) to confirm or refute diagnosis.
Aprotinin ("Trasylol") is a protease inhibitor which appears to protect platelet glycoprotein 1b
(GP1b) receptors from damage thereby reducing blood loss due to platelet dysfunction during
extracorporeal blood circulation or major surgery.
Severity of illness correlates with the extent of depletion of the natural anti-coagulants
antithrombin III (ATIII) and activated protein C (APC). In severe sepsis, cytokines induce
coagulopathy via the protein C and S pathway so APC replacement is a rational approach.
Indiscriminate administration of pro-coagulation factors in an attempt to correct coagulopathy
before the DIC is terminated can make things worse; “throwing coals on the fire”. Indeed,
evidence exists for a harmful effect of fresh frozen plasma in acute septic shock from animal
experiments and clinical audit.
In refractory haemorrhagic states, treatment with recombinant activated tissue factor
(NovoSeven) can be life-saving; get haematology advice and assistance. Clotting factors
activities are increased by alkalaemia.

Acid-base balance
Reinterpretations of the mechanisms of acid-base balance suggest an important role for the
liver. There has also been a recent return to fashion of Peter Stewart’s approach to acid base
balance; in essence this focuses on “strong ions” and the “strong ion difference” (particularly
Na and Cl) rather than bicarbonate as determinative of hydrogen ion concentration in plasma. 
In shock mixed venous or central venous blood probably gives a better indication of the
severity of derangements of acid/base balance than arterial.  Respiratory acidosis is treated by
controlled ventilation if possible, but may have to be tolerated if high lung resistance (eg
severe asthma) or low compliance (eg severe ARDS) limit the attainable alveolar ventilation
('permissive hypercarbia').  Extreme respiratory acidosis is countered by sodium bicarbonate
infusion.
Metabolic acidosis is treated by correction of the underlying cause.   Note that a common
cause of post-operative base deficit is narrowing of the strong ion difference by
hyperchloraemia; this acidosis is does not appear to be harmful but can be prevented by
attention to chloride input. Sodium bicarbonate is of limited value in lactic acidosis or diabetic

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ketoacidosis and should not be used without careful consideration unless pH <7.15 and care
to avoid sodium overload.  In profound refractory acidosis haemofiltration and bicarbonate-
based filtrate replacement fluids may be indicated.
Balasubramanian worksheet for bedside assessment of acid – base status.
Print out and take with you to the bedside. After you have done the calculation a few times,
you will no longer need the worksheet. You need to know the base excess, Na, Cl and
albumin. Lactate is useful too.
From the blood gas machine’s calculation Base excess
calculated from
pH/ PCO2
Na

Calculate the base excess due to free water Befw =


0.3 (Na – 140)
Cl

Calculate the base excess due to chloride BECl =


(adjusted for the Na concentration)
102 – (Cl x 140/Na)
Alb

Calculate the base excess due to albumin BEAlb =


0.34 x (45 – alb)
Calculate the BE due to unmeasured anions Beua =
BE – Befw – BECl –BEAlb
Lactate

Lactate can be considered a strong ion and you can also BELact =
calculate base excess due to lactate;
-Lact

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Chapter 7

Renal Support
URINE physiologic oliguria oliguric renal failure
Protein nil +
Specific gravity >1020 1010
Osmolality >500mmol/l  200-350mmol/l
U. sodium <15mmol/l  >60mmol/l
Urine/plasma osm. >1.3 <1.1
U. urea >250mmol/l  <160mmol/l
Fe Na (fractional excretion of <1 >1
sodium) U.Na/(U/P creat)
 sediment normal granular or epithelial cell
casts
 response to volume always  Occasionally

Definitions
• OLIGURIA is a urine output averaging less than 15ml/hour (400ml/day or 200ml/12h)
in any patient older than 8 years.  It may be a physiological response to renal
hypoperfusion or dehydration.
• ANURIA suggests urinary tract obstruction or severe acute parenchymal disease.
• ACUTE RENAL FAILURE is an abrupt decline in renal function associated with retention
of water, hydrogen and potassium ions, and nitrogenous waste products.  Usually
oliguric, may sometimes feature normal or even high urine volume (polyuric renal
failure).  The mortality is high.
• ACUTE TUBULAR NECROSIS is the morphological feature in 75% of cases.
• ACUTE KIDNEY INJURY in severe sepsis usually has no morphological features at
autopsy.
Acute kidney injury stratification; Risk, Injury, Failure, Loss, and End-stage Kidney (RIFLE)
classification. (proposed by the “AKI Network”).

Class Glomerular filtration rate criteria Urine output criteria


Risk (AKIN stage Serum creatinine × 1.5 < 0.5 ml/kg/hour × 6 hours
1)
Injury (AKIN Serum creatinine × 2 < 0.5 ml/kg/hour × 12 hours
stage 2)
Failure (AKIN Serum creatinine × 3, or serum creatinine ≥ < 0.3 ml/kg/hour × 24 hours,
stage 3) 4 mg/dl with an acute rise > 0.5 mg/dl. or anuria × 12 hours
RRT.
Loss Persistent acute renal failure = complete loss of kidney function > 4 weeks
End-stage kidney End-stage kidney disease > 3 months
disease
Author’s note; I have tried but failed to find the authority behind “half a mil per kilo” as a urine
output criterion. Is this actual or lean body weight, do age or gender matter? Need we worry
about just one or two hours of oliguria? My advice is that any female passing less than 120ml
of urine in any four hours, and any male passing less than 160 ml in any four hours, deserves
investigation. Giving a loop diuretic to increase urine volume before measuring urine and
plasma chemistry is lazy and dangerous practice. Diagnosis and appropriate treatment of
oliguria can prevent renal failure, but frusemide does not.

Pathophysiology of Acute Renal Failure


Normally renal blood flow is very high (approx. 25% of cardiac output) and cortical flow (4ml/
g/min) predominates over medullary (2ml/g/min).  Tissue PO2 in the cortex is around 6kPa,
but only 2kPa in the medulla. Relative medullary ischaemia/hypoxia is necessary to maintain

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osmolality gradients (built up by the countercurrent exchange mechanism) which enable us to


produce concentrated urine.  The major O2 demand in the medulla is for active reabsorption in
the thick ascending limb; inhibition of active transport by a loop diuretic such as frusemide
increases medullary PO2 to 4kPa.   A complex system of intrinsic renal vasodilators and
vasoconstrictors exists to maintain renal homeostasis.   Of importance are the eicosanoid
vasodilators such as PGE2, dopamine (a medullary vasodilator), adenosine (which causes
cortical vasoconstriction and medullary vasodilation), urodilatin (same as atrial natriuretic
peptide but produced by renal distal tubular cells) and the potent vasoconstrictors endothelin
and angiotensin II.  Tuboglomerular feedback (via the macula densa) diminishes GFR if sodium
reabsorption diminishes, limiting the oxygen demand. Though hyperaldosteronism is seen in
critical illness (sodium retention and potassium wasting), in some series approximately half
the hospital patients with renal insufficiency show hyperreninaemic hypoaldosteronism (low
aldosterone=renin ratio) and have a worse prognosis for renal failure. The actions of
aldosterone gave been described as a cardiovascular assault, with vascular endothelial
dysfunction and reduced fibrinolysis damaging the heart, the brain and the kidneys.
Mineralocorticoid receptor blockade with spironolactone appears to be beneficial.
While the healthy kidney can concentrate urine to about 1200mosmol/L, under stress and
critical illness this ability is severely diminished. With more than 500mosmol of nitrogen-
carrying molecules to excrete every day, the capacity to excrete other solutes/ electrolytes
(such as a sodium load with a salt solution or colloid) is limited and patients are susceptible to
iatrogenic fluid overload.
In acute injury, tubular cells swell and lose their villi.   Adhesion molecules, expressed by
vascular endothelial cells, predispose to aggregation of neutrophils and platelets.  Glomeruli
and collecting ducts are relatively resistant to ischaemia.

Management of oliguria
Get a urine sample for chemistry analysis.  Microscopy of a fresh urine sediment may give
valuable clues to the aetiology of oliguria.   Optimise blood and extracellular fluid volume,
protect renal perfusion pressure. The kidneys have powerful intrinsic autoregulation and renal
perfusion may improve when an adequate arterial pressure (MAP at least 60mmHg, up to
80mmHg) is achieved, if necessary by the use of vasoconstrictors like norepinephrine.   If
oliguria persists in spite of adequate blood volume resuscitation, blood pressure and flow,
recheck the urinary Na and osmolality and arterial blood pH, Na and Cl.  If urinary sodium is
low and arterial pH and chloride normal, use normal saline to “salt load” the patient; this
reduces the work of renal concentration and stimulates intrarenal prostaglandin and dopamine
synthesis.  If the pH is low or the chloride high, prefer sodium bicarbonate 1.26%. Give a bolus
of the sodium (chloride or bicarbonate) solution and continue at, e.g, 200ml/hour until urine
output picks up or obvious signs of overload (eg fast-rising CVP or PAWP) force you to stop. 
When you are confident the patient is adequately salt-loaded, stop sodium loading and
consider diuretic drugs. Furosemide (bolus 20mg and infuse at 3 mg/hour) further reduces
medullary oxygen consumption and increases urine output. Metolozone (enteral
adminstration) is a thiazide-like diuretic which inhibits the sodium-chloride symporter in the
distal convoluted tubule and potentiates the effect of loop diuretics, even in renal failure.
Spironolactone (enteral administration) will inhibit aldosterone-induced salt and water
retention and potassium excretion, so useful in patients needing potassium supplements.
Furosemide dose can be escalated if necessary to a maximum of 250mg in five hours.
Ultrasound of the kidneys is indicated if post renal obstruction is possible.
Dopamine infusions do more harm than good in oliguric critically ill patients.
In established renal failure conservative management consists of meticulous attention to fluid
and electrolyte balance, nutrition and monitoring of pH and K+.  Try frusemide 20-80 mg
boluses or infuse 250mg over 30 minutes.  Treat hyperkalaemia with calcium resonium and
glucose/insulin infusion (50G/10iu), repeated as necessary.   A b2 agonist like salbutamol or
dopexamine may sometimes buy time.   Actual or anticipated failure of conservative
management are the indications for filtration or dialysis.  Patients without cardiorespiratory
failure should be refered to the Renal team at the earliest convenience.  If there is doubt over
the diagnosis of acute renal failure, ask for renal consultation.

Renal Replacement therapy (RRT)


In acute renal failure the indications for continuous renal replacement therapy (CRRT) are;

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fluid overload
hyperkalaemia
acidosis
symptomatic uraemia.
Occasionally we will use haemofiltration in the treatment of refractory oedema (especially in
severe acute respiratory failure), lactic acidosis, and poisoning.  Research suggests a possible
but unproven benefit in sepsis or liver failure.
Why do we need haemodiafiltration?   What's wrong with good old fashioned peritoneal
dialysis?  The major drawback of PD is that clearance rates sufficient to sustain a severely
catabolic critically ill patients are difficult to achieve.  Other problems are the need for an
intact peritoneum (excludes many surgical patients), protein loss, and elevation of the
diaphragm causing some respiratory embarrassment.
Haemofiltration.
Plasma water is filtered through a semi-permeable membrane along with small molecules
(including urea) and the lost volume is replaced with a suitable electrolyte solution.  
Clearance of filterable molecules is by CONVECTION; there is no concentration gradient across
the membrane and clearance is entirely dependent on the volume of the filtrate.   Modern
filters will also convect larger molecules of about 500 Daltons ('middle molecules'), which
include some cytokines and mediators of the sepsis syndrome. 
• The clearance of a filterable molecule (e.g. urea) is proportionate to the amount of
filtrate produced.
• The amount of filtrate produced is proportionate to the amount of blood circulated
through the filter …
• … so that clearance by haemofiltration is regulated by increasing or reducing blood
flow to the filter.
• By balancing filtrate volume against replacement solution volume one has powerful
control over the patients extracellular fluid volume.
EXTERNAL BLOOD PUMP enables us to draw blood from, and return blood to, the central venous
system rather than use arterial to venous pressure gradients. Higher filter blood flows are
easily achieved and so proportionately increases the filtrate production and urea clearance. 
Expensive electrical equipment with fail-safe devices is necessary to protect the patient from
air embolism if the circuit is inadvertently opened.  Standard filtration therapy is continuous
veno-venous pumped haemofiltration (CVVH).  With dedicated double-lumen catheters only
one venepuncture is necessary. 
The higher the blood urea, the more moles will be removed by filtration; when the plasma urea
concentration is 40mmol/L, each litre of filtrate will contain 40mmol urea. If the rate of urea
production is 600mmol/24h, then 15 litres of filtration per day will prevent a rise in plasma
urea. More than 15 litres per day will cause the plasma urea to fall. When the plasma urea
concentration is 20, 30 litres of filtration will prevent a rise.
Optimal HF dosage seems to be of the order of 35ml/kg/hour (2-2.5 litres per hour). With a
urea production rate of 600mmol/24h, the plasma urea concentration will settle at about
12mmol/L after a few days. HIGH VOLUME HAEMOFILTRATION uses higher blood flow rates,
demands bigger catheters, and results in larger filtration volumes (75 litres/ day or more)
which have to be replaced with larger volumes of filtrate replacement solutions. More rapid
correction of chemical abnormalities and haemodynamic instability, but outcome benefit
remains to be established.
Haemodiafiltration
A dialysis solution flows along the semi-permeable membrane countercurrent to the blood
flow.  If the outflow volume is constrained to be the same as inflow then solutes are cleared
entirely by DIFFUSION across the membrane.   Small molecules like urea (60 Daltons) are
efficiently cleared, larger molecules like creatinine (113 Daltons) less so, and the middle
molecules (500 Daltons or more) are not significantly cleared.  In practice, the outflow volume
usually exceeds inflow during dialysis, the difference being due to some haemofiltration;
hence the compound term 'haemodiafiltration' (HDF).
• The clearance of a diffusible molecule (e.g. urea) by dialysis is proportionate to the
amount of dialysate passed over the semipermeable membrane.

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• The amount of dialysate is limited by the characteristics of the filter, but 48 litres per
day (two litres per hour) is adequate in continuous RRT on ICUs.
• Clearance by haemodiafiltration is regulated by increasing or reducing dialysate flow
• … and a relatively small extracorporeal blood circulation can achieve more urea
clearance than by filtration alone.
Summarising, continuous veno-venous haemodiafiltration includes elements of both filtration
(solutes up to middle molecule size cleared by convection, clearance proportional to filtrate
volume) and dialysis (mostly small molecules cleared by diffusion, clearance proportional to
dialysate flow).   For control of refractory oedema low volume haemofiltration alone is
satisfactory.  To control urea concentrations in catabolic patients it may be necessary to use a
dialysate or to increase extracorporeal blood flow for higher volume haemofiltration.
Too much RRT...
is not good for you. The efficiency of solute removal falls as the abnormally high
concentrations are brought down, prolonged extracorporeal circulation damages the blood
cellular elements and activates complemement, cytokines, coagulation cascades etc, and
“trace” elements and small molecules are removed to the detriment of normal homeostasis.
When the volume, pH and urea status has been stabilised, give your patient breaks from RRT,
and just see if the urine output will pick up.
Anticoagulation
is usually necessary to prevent filter clotting.  For an adult with normal coagulation it is our
practice to give a bolus dose of 5,000 I.U. heparin before starting HDF, then infuse heparin
10,000 I.U. in 1000ml saline at about 10 I.U (=1ml)/kg body weight/hour into the 'arterial'
limb of the circuit.  If the filter lasts more than 48 hours and the patient does not bleed we are
satisfied!  Citrate infusion is a viable alternative to systemic anticoagulation for patients at
high risk of bleeding. Rare patients become thrombocytopenic when heparinised, and the filter
fails prematurely with a distinctive white clot.  The condition is called heparin associated (or
induced) thrombocytopenia (HIT or HAT). Calculate the “4T score” (see section on blood
transfusion). The Consultant will consider further investigations and whether to use
epoprostenol or citrate infusion. Leprirudin is a direct thrombin inhibitor.

Unphysiologic anions
Cheaper filtrate replacement solutions may contain lactate or acetate as an anion.  Bicarbonate
is therefore filtered out and replaced with lactate or acetate, sometimes in excess of the
patients ability to convert the unphysiologic anions.   This is a particular problem for the
shocked patient.  If the arterial base deficit during HDF is 6mmol/L or worse, or if lactate
>3mmol/L, prescribe only bicarbonate-based filtrate replacement fluid.

Nutrient balance
is not a serious problem during HDF, but there will be some loss of amino-acids (including
carnitine incriminated in muscle breakdown) and phosphate.  There is evidence that early HDF
permits adequate TPN in critically ill patients and shows some survival benefit. 
Hyperphosphataemia often develops during treatment, and is controlled by enteral aluminium
hydroxide (Aludrox).

Drug clearance
is predictable by molecular size, protein binding, adherence to the filter, and the ratio of
convective to diffusive clearance.  Obviously it is complex and in practice it is advisable to
measure levels of drugs like antibiotics periodically.  Beware of angiotensin converting enzyme
inhibitors (anaphylactoid reaction with certain types of filter) and clonidine (poorly cleared).

Outcome
of haemodiafiltration in an Intensive Care Unit depends upon the severity of illness.  Intensive
Care patients in acute renal failure have survival rates of less than 50% in published studies.
“More is not better”; a trial conducted by the VA/NIH Acute Renal failure Trial Network showed
no survival benefit for more intensive RRT over less intensive.

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Chapter 8

Liver Failure
Jaundice is a marker of hepatic dysfunction in critically ill patients. The different patterns of
jaundice are all seen in “SIRS” but the commonest is an intrahepatic cholestasis. Consider pre-
existing liver disease when assessing a critically ill patient.

Unconjugated hyper-bilirubinaemia
Typically indicates haemolysis (anaemia, reticulocytosis, LDH) and may be due to transfusion,
drugs, sepsis or high flow extracorporeal circulation (e.g. ECMO with blood transfusion).

Conjugated hyper-bilirubinaemia,
Cholestatic jaundice (high alkaline phosphatase) is due to extrahepatic obstruction if dilated
bile ducts are seen on abdominal ultrasound examination.   If bile ducts are normal then
cholestasis may be associated with severe illness, drugs, TPN, sepsis or ischaemia. Curiously,
alkaline phosphatase inhibits iNOS and could afford some protection against SIRS-induced
vasoparesis.
Hepatocellular jaundice (high transaminases) can follow severe hypotension and ischaemia
(confirmed by ultrasound appearances), sepsis, drugs (including halothane) or viral hepatitis.
You will need to be familiar with the up-to-date recommendations on the management of
paracetamol poisoning.  Patients with end-stage liver disease and portal hypertension of all
forms are increasingly being referred for specialist opinion and treatment.  Massive upper GI
tract haemorrhage associated with liver disease may precipitate admission to ICU.

Acute Liver Failure (ALF)


… is a rare syndrome characterised by abrupt loss of function with hepatic encephalopathy
and coagulopathy within 6 months of first symptoms of liver disease (usually jaundice).
Hyperacute liver failure (fulminant hepatic failure) when jaundice to encephalopathy interval is
less than 7 days. Commonest causes are paracetamol poisoning, idiosyncratic drug reaction
and viral hepatitis. Rare causes with specific therapies include Amanita mushroom poisoning
(give continuous i.v Penicillin G or cephalosporin) or acute fatty liver of pregnancy (deliver the
baby) or Wilson’s disease (zinc and trientine). Subacute liver failure when jaundice to
encephalopathy interval is more than 28 days. Clinical picture includes ascites and azotaemia.
Prognosis is poor.
Glutathione depletion is common in critical illness. Glutathione levels are replenished by n-
acetyl cysteine (NAC) treatment. Glutathione scavenges the reactive paracetamol metabolite N-
acetyl-p-benzoquinoneimine. There is some, albeit small, benefit from NAC even in non-
paracetamol ALF.
Steroids have been tried in auto-immune hepatitis with no benefit and possible harm from
immunosuppression.
Up to 90% of all ALF patients suffer sepsis, the common organisms being Gram negative
bacilli, gram positive cocci, and candida spp. Prophylactic antibiotics, including SDD
strategies, are not effective. Empiric broad-spectrum antibiotics are indicated in
encephalopathy or acute renal failure. Remember possibility of spontaneous bacterial
peritonitis.
Hyperacute ALF patients are at particular risk of cerebral oedema as rapidly-rising
ammonaemia leads to osmotically-active glutamine accumulation in astrocytes, which then
take up water and swell. In subacute ALF compensatory fall in other intracellular osmolytes
reduces the risk of oedema. Watch for signs of raised ICP in encephalopathic patients
(especially pupillary light reflexes and high BP). Nurse head up with neutral neck position and
minimise stimuli which cause coughing and straining. Mild hyperventilation, either
spontaneous or supported, is probably optimal. Care with fluid balance, consider ICP
monitoring with mannitol therapy and hypertonic saline to achieve slight hypernatraemia
(145-155). Prevent pyrexia, consider hypothermia. Consider heavy sedation, barbiturate coma.
Attend to the coagulopathy. Vitamin K may be given but is probably not helpful. Monitor INR
and other clotting tests; remember INR is one of the best measures of the progress of liver

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failure, only treat with FFP if bleeding is a problem or invasive procedures with bleeding risk
are to undertaken,
Check for hyperammonaemia and use a non-absorbable disaccharide (lactulose) to promote
colonic non-urease-producing lactobacilli.
Hepato-renal failure may be precipitated by shock or hypovolaemia.   The urinary sodium
excretion is low (fractional excretion <1%, urinary concentration <10mmol/L) until ATN sets
in. Use early haemodiafiltration in renal failure but take care to prevent rapid fall in serum
osmolarity during dialysis; measure osmolarity and if necessary keep it up with 20% mannitol.
Restrict (but no need to entirely withhold) amino-acid or protein nutrition.
Extra-Corporeal Albumin Dialysis (ECAD) s an experimental holding therapy for pre-transplant
patients and occasionally used in ICUs.

Ascites
Diagnostic paracentesis includes serum to ascites albumin gradient and microbiology
examination. In portal hypertension the ascitic fluid has low albumin concentration and the
portal and hepatic veins should be imaged by abdominal ultrasound. Large-volume
paracentesis (>5L) may cause hypovolaemia; treat with albumin infusion.

Upper GI tract Bleeding and Portal Hypertension.


Intensive Care is indicated if there is severe shock or concomitant respiratory failure.
Resuscitate carefully. Arrange endoscopic assessment by GI team. Prescribe pharmacologic
reduction of portal blood flow with vasopressin (vasoconstriction) or somatostatin (less
vasoconstriction). Consider Sengstaken-Blakemore tube (inflated gastric balloon is impacted
into gastro-oesophageal junction by traction with a fluid bag or similar weight: oesophageal
balloon may be inflated (typically 40mmHg pressure) to tamponade oesophageal varices.
Consider endoscopic sclerotherapy or rubber band ligation of varices. If refractory to this
therapy, patients can be considered for transjugular intrahepatic portal-systemic shunt (an
invasive radiology procedure sometimes done under GA). Final resort is to surgical portal-
systemic shunt or oesophageal transection.

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Chapter 9

Nutritional Support

"Give me neither poverty nor riches, but feed me with food that is needful
to me."
PROVERBS 30.8
Basic daily requirement is 25-30 KCALS/ KG as;

carbohydrate (4kcal/G) 2-4G/kg,


protein (4kcal/G) 1-2G/kg (or 11-22 G nitrogen per day),
fat (9kcal/G) 1-2G/kg. 

Protein-energy malnutrition (PEM) is common in critically-ill patients. Measures of


malnutrition fall into three broad categories; anthropometric, immune responsivity and blood
chemistry.   However, these are of limited value in complicated critical illness. HARRIS
BENEDICT EQUATIONS are an accepted way of estimating the basal energy expenditure (wt in
kg, ht in cm, age in years);

Male BEE = 66+(13.7*wt)+(5*ht)-(6.8*age)


Female BEE = 655+(9.6*wt)+(1.8*ht)-(4.7*age)
Fever increases the metabolic rate by 13% per C. 
Finally, apply the 'stress factor;
*1.25(mild), *1.5(moderate) or *1.75(severe).

SCHOFIELD EQUATIONS are another option. Equations tend to overestimate the need for
energy in Intensive Care patients; preferably measure energy expenditure and RQ with a
metabolic monitor, input should match expenditure and should never exceed it by more than
15%.  Outcome data suggest patient benefit for “underfeeding” during critical illness; no more
than 75% of the calculated basal energy requirement, and no less than 25%. It should be
unusual to have to feed more than 2,000 kcal/day. 
Oxygen consumption as calculated by PA catheter studies does not include the lungs, where in
critical illness metabolism can be substantial. 
Patients should ideally be in positive nitrogen balance. Nitrogen Balance = input – output.

Output calculation requires a urine collection for total urinary urea nitrogen (UUN).
UUN = [UUN] * urine volume.
Nitrogen output = 1.2*UUN + 2G.

Influences on metabolism
Critical illnesses and the adrenergic therapies that are widely applied are associated with net
catabolism and loss of lean body mass in spite of feeding, so an intervention which enhances
anabolism and improves recovery would be attractive. A trial of growth hormone showed net
harm from treatment and was terminated. A trial of ‘aggressive’ insulin therapy to keep the
blood sugar concentration within the normal range produced substantial improvement in
morbidities (septicaemia, renal failure, ventilator dependence, polyneuropathy) and mortality.
A trial of propranolol in children with severe burns showed dramatic metabolic benefits which
we must now wait to see confirmed in larger trials of a broader cohort of patients.

Vitamins
Deficiency is rare in Britain but sometimes associated with critical illness in poorly nourished /
alcoholic / liver disease patients. Beri-beri and Wernickes encephalopathy should be
considered. Vitamin K deficiency is common in critical illness; prolongation of INR is a late
stage.  Older patients with haemodynamic problems may be given B12 and folate supplements.

Feeding acutely ill patients

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Nutrition is poorly tolerated because of insulin resistance and complex changes in


micronutrient fluxes. It is impractical and even harmful to attempt full nutrition until shock
reversal has been achieved.

Feeding starved patients


Adaptations to starvation include a decrease in activity of the Na/K exchange pump in cell
membranes, reduced intracellular magnesium levels and reduced manufacture of high energy
phosphates such as ATP. Sudden return to normal feeding in starved patients may precipitate
life-threatening hypokalaemia, hypomagnesaemia and hypophosphataemia (the refeeding
syndrome). Therefore, recommence nutrition cautiously in starved patients.

Disease-specific considerations
In all the following, benefits compared to "standard" feeds are at best modest.
VENTILATORY FAILURE; shift to fat as primary energy source reduces RQ and lessens CO2
production.
RENAL FAILURE; volume, sodium, potassium, nitrogen may need to be restricted in the
absence of dialysis, but standard feed can be used in filtered/dialysed patients.
HEPATIC FAILURE; volume and sodium may need to be restricted.   Amino acids are better
tolerated than the equivalent enteral protein feed.   Encephalopathy is associated with
abnormal ratio of aromatic to branched chain amino acids, and BCAA enriched feeds can
improve encephalopathy but do not affect mortality.
Early restoration of full nutrition may be associated with improved survival; nutrition for
critically-ill patients should not be withheld for more than 72 hours.  Parenteral nutrition is
expensive, and dangerous because of catheter-related trauma and sepsis, and immune
suppression and free radical production by i.v lipids.   Additionally, TPN solutions lack
glutamine and butyrate, and suppress ketone production, which are important intestinal
metabolic substrates.  This may lead to mucosal atrophy and bacterial translocation from the
gut to the portal venous system. Enteral nutrition is therefore greatly preferred.

Enteral Feeding
Try early.  Bowel sounds are a poor indicator of ability to tolerate enteral feeding.  Use full
strength feeds (there is no benefit in diluting them).  Even very small volumes (eg 10ml/hr)
may benefit the patient if absorption is poor and should be persisted with. Gastric stasis may
respond to reducing the level of sedation (especially opioids) and correcting electrolyte
abnormalities.   Otherwise, try metoclopromide, followed if necessary by cisapride.   Jejunal
feeding has its advocates, but is difficult to perform other than by surgically placed
jejunostomy.   Percutaneous endoscopic gastrostomy (PEG) is another option.   Diarrhoea
should be treated with codeine phosphate; consider enterocolitis (if stool is bloody or slimy
send for toxin analysis and culture).   Do not discontinue feed.   Sometimes correction of
hypoalbuminaemia improves diarrhoea. 
Formulas may be polymeric or elemental.  Specialist feeds include high fat (Pulmocare, for
ventilatory failure), high arginine, RNA and omega-3 fatty acids for "immune-
enhancement" (Impact) and high glutamine (Alitraq). The 'immunonutrition' feeds may be
HARMFUL in acutely-ill patients.

Parenteral nutrition
does not improve the outcome of acute severe illness. The reason is not clear, but intravenous
lipids may amplify the prostaglandin response and are potentially hazardous.  In the longer
term intravenous lipids may cause fatty liver with abnormal LFTs, and should be restricted if
this occurs.
 Consider every day;
the acceptable fluid volume load
nitrogen requirement (usual range 9-18 G)
caloric requirement
electrolytes Na+, K+ (circa 10mmol/G N2), Mg++ (circa 1mmol/G N2), Zn++ (circa
40-80μmol) and PO4--(circa 10-20mmol)
trace elements (Cu, Se, Cr, Fe, Mn, I, Mb).

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vitamins (water & fat soluble).


Measure DAILY urea, creatinine, PO4, electrolytes, glucose, ABG, FBC.   Examine serum for
lipaemia. “Metabolic cart” if available.
At least TWICE PER WEEK measure LFT, albumin, Ca++, PO4--, Mg++, Zn++.coagulation profile.

Small print.
Sulphhydryl donor amino acid depletion may impair the bodies protection against oxidising
radicals.  If the plasma and red cell glutathione levels are low there may be some benefit in
infusing N-acetyl cysteine (NAC; "Parvolex"). Possible indications include severe sepsis, ALI
with high FIO2, and hepato-renal syndrome.

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Chapter 10

Sleep, sedation and mood


ICU patients are usually too ill, too sedated, or too disturbed to get REM sleep. Deprivation is
probably harmful, and most patients get their compensatory REM sleep after discharge from
the ICU. A detailed description of normal sleep is given here to help you appreciate the fact
that comatose or anaesthetized patients with their eyes closed are not sleeping.

Features of sleep
Circadian Rhythm
Without external indicators of time ("Zeitgebers" from German, literally time-givers) the
circadian rhythm is about 25 hours.  Within the cycle there exist two “sleep gates” during
which sleep can be initiated, separated by a “forbidden zone” when sleep is almost impossible. 
The normal gates are mid afternoon and late evening.  The forbidden zone is about 9pm; after
late nights on Friday and Saturday, you may   push back your forbidden zone on Sunday
(“Sunday night insomnia”).   The wake/sleep cycle is dependent upon numerous chemical
mediators.   Interleukin-1 has a reciprocal rhythm to beta-endorphin, and influences the
hypothalamic-pituitary-adrenal hormone axis.       Melatonin supports normal sleep, and
deficiency leads to insomnia which is improved with replacement therapy.   Major illnesses
which disrupt circadian rhythm will impair the normal wake/sleep cycle.
Non-REM (NREM)
Sleep onset is characterised by EEG spindle activity.  Spindles are high-voltage bursts of EEG
activity in the 12-14Hz range ("K-complexes").  Slow waves (1-4Hz) become intermixed with
spindles as sleep progresses, and the four stages of non-REM sleep are defined by the
proportion of spindles to slow waves;
Stage 1; drowsiness/wakefulness
Stage 2; sleep with K-complexes
Stages 3 and 4 are slow wave sleep (SWS) with increasing delta wave activity, stage 4 having the
greatest proportion of slow waves.
In NREM sleep, cerebral blood flow and glucose utilisation fall, though autonomic regulation of
temperature and respiration is preserved.  Muscle tone is reduced but present.
REM
REM is characterised by simultaneous presence of desynchronised low voltage EEG (typical of
an 'active' brain), absence of tone in the antigravity muscles (interrupted by occasional
twitches), and periodic bursts of rapid eye movement.  It usually follows a period of NREM and
recurs typically 4-5 times a night.  In infants REM sleep is not seen, though phasic muscle
twitches and eye movements are seen instead (a state called 'active sleep').   While the cortical
EEG of REM is desynchronised, subcortical EEG recordings shows very synchronised patterns in
the hippocampus (theta waves) and ponto-geniculo-occipital region (spikes).  Atonia is due to
active inhibition (hyperpolarisation) of the affected motorneurones, and in contrast to NREM
the sympathetic nervous system is inhibited. Miosis of the pupil and changes in control of
respiration and the circulation occur.  Most people awoken suddenly from REM sleep report
that they were dreaming.
Why do we sleep?
It is obvious that occasional sleep is necessary for alertness during wakefulness and for our
psychological wellbeing.  The role of NREM may be  to enforce inactivity and conserve energy,
and it has been suggested that a beneficial effect of IL-1, released in sepsis, may be to induce
NREM and reduce hypermetabolism.  Growth hormone levels are high during SWS and it has
been suggested that “growth and repair” are maximal during sleep.  NREM is also a necessary
precursor to REM and dreaming, which "..permits each and every one of us to be quietly and
safely insane every night of our lives." (WC Dement).  Sleep deprivation is not entirely harmful,
however, as depressed patients seem to be improved by it!

Disorders of sleep
Four main categories are
1.      disorders of initiating and maintaining sleep (DIMS) which includes insomnia,

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2.      disorders of excessive somnolence (DOES) including narcoleptic syndrome and sleep apnoea syndromes,
3.      disorders of the sleep/wake cycle such as shift-working and jet-lag, and
4.      parasomnias such as night terrors and sleep walking.

Hypnosis
Patients complaining of insomnia are frequently prescribed benzodiazepines which shorten
the time taken to get to sleep and prolong sleep.  Tolerance to this effect occurs within a few
nights, but patients seem happy to continue the drug.  REM sleep is diminished.

Hypoxaemia during sleep


Apnoea (cessation of airflow at the mouth >10 seconds) during sleep with some HbO2
desaturation is common, especially amongst men.   Apnoea is classified as obstructive
(thoracoabdominal movement present), central or mixed. 
Hypersomnia sleep apnoea syndrome (HSA)
Characterised by excessive daytime somnolence, >30 sleep apnoeas per night, and few or no
other clinical signs.  Loud snoring is common. Arterial blood gases are normal.
Obese hypoventilation syndrome (OHS, Pickwickian)
Features hypersomnolence and multiple sleep apnoeas, but the patients are by definition
obese and have arterial hypercapnia.  They may also be cyanosed, and suffer from pulmonary
hypertension and right heart failure.  The vital capacity is reduced.  Sudden nocturnal death is
a risk.
Chronic obstructive pulmonary disease
is often associated with severe nocturnal HbO2 desaturation.  Desaturation is profoundest and
longest in these patients during REM sleep.  An important mechanism in these patients may be
the loss of muscle tone during REM sleep leading to FRC (and so V/Q mismatch) changes.
Post surgical hypoxaemia
has been shown to be very common especially during sleep. It is speculated that sleep
hypoxaemia may be responsible for postoperative cerebral or myocardial morbidity.  Morphine
prolongs sleep time and may worsen apnoeas.   Detailed sleep studies are difficult in
postoperative patients, but it has been shown that morphine analgesia abolishes REM sleep,
and that withdrawal of morphine leads not only to recovery of REM but overshoot and excess
REM.  Stress, whether surgical, traumatic or exercise-induced also inhibits REM sleep, perhaps
mediated by IL-1, and may also produce increased REM-associated HbO2 desaturation during
recovery.
There seems to be little knowledge of the problems of sleep in the Intensive Care Unit.  It is
generally held that sleep deprivation occurs due to disturbance and that 'sedation' is
beneficial.   However, few people have addressed the fact that sedatives like opioids,
benzodiazepines, and general anesthetics given in sub-anaesthetic concentration may cause
drowsiness but they do not promote normal sleep.   REM deprivation, sleep/ wake cycle
disturbance, and parasomnias are common.

Pathophysiology of mood and consciousness


The tuberomammillary nucleus is a
subnucleus of the posterior third of the
hypothalamus. Mostly histamine-
secreting neurons involved with the
control of arousal, sleep and circadian
rhythm. Axons project to the cerebral
cortex, thalamus, basal ganglia, basal
forebrain, and hypothalamus. The
histaminergic projections to the cerebral
cortex directly increase cortical activation
and arousal (H1 receptors), and
projections to acetylcholinergic neurons
of the basal forebrain and dorsal pons do
so indirectly, by increasing the release of
acetylcholine in the cerebral cortex. Slow
wave sleep occurs when TMN

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histaminergic neurons firing rate falls to about 0.5Hz so that cortical activation is greatly
diminished.
The ventrolateral preoptic nucleus is a group of neurons in the hypothalamus. Active during
sleep, and inhibit other neurons that are involved in wakefulness.
The VLPO neurons release the inhibitory neurotransmitters galanin and GABA to inhibit the
monaminergic cell groups in the locus ceruleus, the raphe nucleus, and the tuberomammillary
nucleus. VLPO is activated by various somnogens (substances inducing sleep). A2A receptor
(adenosine) is an important activator. VLPO is inhibited by arousal transmitters such as
norepinephrine and acetylcholine. Rapid eye movement sleep occurs when the TMN is turned
off by the VLPO which is activated by various somnogens including adenosine (A2A receptors).
The locus ceruleus is in the dorsal wall of the rostral pons in the lateral floor of the fourth
ventricle. This nucleus is the principal site for synthesis of norepinephrine in the brain
The norepinephrine from the LC has an excitatory effect on most of the brain, mediating
arousal and priming the brain neurons to be activated by stimuli, while inhibiting the VLPO.
The Raphe nuclei are
cluster of nuclei found
in the brain stem. They
release serotonin to
the rest of the brain,
modulating mood,
memory, sleep and
cognition. Projections
to dorsal horn of
spinal cord grey matter
modulate pain
perception through
enkephalin release.
The glycine receptor
chloride channel (GlyR)
is a member of the
nicotinic acetylcholine
receptor family of
ligand-gated ion
channels. GlyRs are
involved in motor reflex
circuits of the spinal
cord and provide
inhibitory synapses
onto pain sensory
neurons.
Enkephalin-releasing
interneurons in the
dorsal horn grey matter
stimulate mu opioid
receptors and thereby
inhibit pain pathways.
Encephalopathy /coma
can be induced by a
variety of means
including;
•I n t e r l e u k i n - 1
induction and intense
IL-1 receptor activation
induces drowsiness and
pyrexia in sepsis.
•Prostaglandin D2
enhances adenosine
release (A2A agonist).

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• Kynurenic acid (NMDA antagonist) in tick-borne encephalitis and HIV infection.


• Allopregnanolone (tetrahydroprogesterone), an endogenous neurosteroid (GABA agonist) in
hepatic encephalopathy.
• LC destruction causes encephalitis lethargica, a rare complication of influenza.
It is believed that arousal/consciousness is not possible when brain stem function ceases, so
patients with irreversible loss of brain stem function (permanent apnoeic coma) are regarded
by most people as dead even if other parts of the brain remain functional.

Sedation in Intensive Care


Sedation/anaesthesia can be induced by a variety of means including;
• Two-pore potassium channel activators which stabilise the resting membrane potential of all
neurons (e.g. isoflurane, halothane).
• GABA receptor agonists (e.g. propofol and etomidate on the gamma subunit increase pore
opening duration, benzodiazepines on the beta subunit increase pore opening frequency.
Isoflurane, halothane).
• NMDA receptor antagonists (e.g. ketamine, cyclopropane, nitrous oxide)
• Thiopentone, a short acting barbiturate, works at both GABA and NMDA sites.
• Mu opioid receptor agonists which are inhibitory, especially on pain pathways (e.g.
morphine, fentanyl).
• Alpha 2 receptor agonists which inhibit norepinephrine release, especially in the LC (e.g.
clonidine, dexmedetomidine)
• Facilitation of GlyR activation to suppress spinal cord reflexes (most anaesthetic drugs).
Etomidate was an anaesthetic with minimal cardiorespiratory side effects thought to be safe
for sedation in Intensive Care; audit showed, however, a large increase in mortality associated
with (but emphatically not due to) inhibition of adrenal hydroxylases preventing synthesis of
cortisol.
Objectives are freedom from anxiety and relief from pain.  Sedation has only a minor role to
play in 'settling the patient on the ventilator'.
Natural sleep and hormonal changes of the circadian rhythm are impaired in critical illness. 
While small doses of analgesics and sedatives may improve the conditions for natural sleep to
occur in the recovering patient, larger doses cause coma but not sleep. 
There have been almost as many proposed 'Sedation scales' as there have been papers on
sedation.  Many are modifications of the Glasgow Coma Scale, but the most widely accepted
are;

Ramsey sedation scale; Richmond agitation-sedation scale;

1.      agitated, +4 combative

+3 very agitated

+2 agitated

+1 restless

2.      cooperative, 0

3.      responds  to  voice, -1 responds to voice & maintains eye contact

-2 responds to voice, eye contact <10 sec.

4.           brisk response to loud noise/ -3 responds to voice


touch,

5.      sluggish response, -4 responds to physical stimulation

6.      no response. -5 unrousable

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Optimal level of sedation is Ramsay 2 or 3.  Daily reduction or discontinuation of sedatives


(with restart as needed) is recommended to guard against cumulative intoxication. In Care
Bundle terminology, sedation breaks.
Prolonged deep sedation or anaesthesia has several side effects or complications.  Almost all
such drugs DEPRESS THE MYOCARDIUM leading to hypotension and perhaps reduced oxygen
delivery to the tissues.  Though most anaesthetics reduce the metabolic oxygen demand, they
have a disproportionately large depressant effect on supply.   Sedation lowers endogenous
catecholamine production, so exogenous sympathomimetics may be necessary to support the
circulation in the deeply sedated patient. The immune system is compromised by sedation so
special care is needed to reduce the risk of nosocomial infections.
The immobility of heavy sedation has several consequences.  MUSCLE WASTING, DEEP VEIN
THROMBOSIS, PERIPHERAL OEDEMA, DECALCIFICATION OF BONE AND SKIN BREAKDOWN are
among the more common.  The FUNCTIONAL RESIDUAL CAPACITY FALLS due to poor muscle
tone and supine position (except in ketamine anaesthesia), while lack of cough leads to
ATELECTASIS and SPUTUM RETENTION which require intensive physiotherapy and suction to
prevent or treat. ACALCULOUS CHOLECYSTITIS (sludging, obstruction of the biliary tree and
sepsis) and POLYNEUROPATHY OF THE CRITICALLY ILL are two ICU syndromes which may be in
part due to sedatives. Tolerance occurs progressively to most sedatives; cancer patients taking
1000mg or more of morphine per day are quite capable of driving a car safely!  After two to
three weeks of high dose opioids and benzodiazepines physical dependence becomes a
problem, and recovering patients will need a program of gradually reducing dosage.  Signs of
withdrawal are sometimes seen.   Twitching and involuntary movements can occur after
midazolam or propofol.  Morphine withdrawal leads to sweating, fever, diarrhoea, piloerection
('goose pimples' or 'cold turkey'), nausea and insomnia. The pupils are dilated. Clonidine is
reported to help.
Late complications (seen after hospital discharge) attributable to sedation practice are POST-
TRAUMATIC STRESS DISORDER and DEPRESSION. They are particularly associated with higher
benzodiazepine dose.

Mu receptor agonists
MORPHINE is a reliable sedative and analgesic, and for most patients is the 'drug of choice'. 
However in oliguria the active metabolites morphine-3-glucuronide and morphine-6-
glucuronide are not excreted.  Morphine pretreatment of rodents makes them susceptible to
bacterial, fungal and viral infections. There is concern that immune suppression by morphine
or other mu-receptor agonists could also contribute to human disease, but this should not
deter you from prescribing adequate analgesia. Hypotension (nitric oxide synthase stimulation
via mu-3 receptor) commoner than with more potent opioids.
FENTANYL is very potent and so is the preferred opioid in shock, oliguria and renal failure. 
Can be delivered transcutaneously. Prolongs elimination half-time of midazolam.
ALFENTANIL is a shorter acting but more expensive alternative which competes for the same
hepatic cytochrome P450 enzyme as midazolam, so when used together elimination may be
prolonged.
REMIFENTANYL is the shortest-acting mu receptor agonist and must be given by continuous
infusion.
Naloxone is the standard mu-receptor antagonist. At very low dose (0.25mcg/kg/hour) in
combination with epidural or systemic morphine it reduces opiate side effects (itching,
nausea) without reducing analgesia. In higher doses, it is antanalgesic. Was trialled in high
dose to antagonise endogenous opioids in septic shock without success.

GABAA receptor agonists binding the gamma subunit


(Benzodiazepine receptor)
Gamma-aminobutyric acid (GABA) is the major inhibitory neurotransmitter in man (and indeed
in all vertebrates). The GABAA receptor is linked to chloride channels in cell membranes, and
its stimulation increases chloride conductance thereby stabilizing the resting membrane
potential. Many sedatives and anaesthetics have now been shown to work in part or wholly
through the GABAA receptor. The agonist effect of benzodiazepines is through binding to the
gamma sub-unit of the receptor and to increase pore opening frequency. The major sites of
binding are the cerebral cortex and the limbic system.

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MIDAZOLAM is the benzodiazepine of choice for short-term sedation due to its water
solubility, rapid onset and shorter elimination half time (<8h), but clearance can be greatly
reduced in critical illness or by drugs sharing metabolism by cytochrome P450 3A (CYP3A).  To
some extent clearance depends on hepatic blood flow, but extrahepatic metabolism (e.g. in
the intestinal mucosa) does occur.  In oliguria, the active metabolite alpha-hydroxymidazolam
glucuronide accumulates (t1/2 50-80h) and so midazolam should be used sparingly if at all in
renal failure. Doses greater than 75mg/day (3mg/hour) predispose to depression in survivors,
so alternatives should be considered for deep or prolonged sedation.
LORAZEPAM is slower in onset than midazolam, and is intermediate in duration of action.
However, its metabolism is less susceptible to inhibition than midazolam, and recovery from
lorazepam may be quicker than from midazolam in critical illness. SCCM consensus regards it
as the benzodiazepine of choice in protracted critical illness. Has been used in high doses to
terminate status epilepticus.
DIAZEPAM is used occasionally for its anticonvulsant properties.
Flumazenil is the standard benzodiazepine receptor antagonist. Occasionally used to diagnose
or exclude benzodiazepine “overdose”.

GABAA receptor agonists binding the beta subunit.


Propofol and etomidate both bind to and interfere with the beta subunit of the GABAA receptor
to prolong pore opening. Minor changes to the beta subunit can greatly alter the susceptibility
of an animal to etomidate or propofol.
PROPOFOL is suitable for patients required to wake quickly from a short period of sedation. 
Maximum dose 4mg/kg/hour (or about 30ml/hour). Use in children is controversial. There
have been reports of refractory metabolic acidosis and circulatory collapse (propofol infusion
syndrome) and the Committee for Safety of Medicines advise against propofol infusions for
sick children, but some paediatric intensive care units continue to use it. There are also
reports of adult deaths from propofol infusion syndrome.
ETOMIDATE should not be used because of its lethal side-effects.

NMDA receptor antagonists


N-methyl d-aspartate is an excitatory amino acid and antagonists suppress wakefulness in a
peculiar way. Nitrous oxide and ketamine are used in clinical practice, while the rare gas
Xenon is too rare for routine use and cyclopropane is too explosive!
KETAMINE is an N-methyl d-aspartate (NMDA) receptor and mu-opioid receptor antagonist
and a strong analgesic which is used in asthma, burns, or haemodynamically unstable adults
or children. It does not appear to reduce gastrointestinal motility, and enhances opioid
analgesia by inhibiting "wind-up" of dorsal horn nociceptive neurones.  Theoretical beneficial
effects for reperfusion injury have not been proven in trials. Suppresses Tumour Necrosis
Factor response to acute sepsis but not proven to improve outcome. Benzodiazepines can
prevent hallucinations which occur during emergence from ketamine anaesthesia. Has been
used to terminate status epilepticus refractory to conventional anti-convulsants. Is shown to
be a rapid and powerful anti-depressant. In severely depressed patients 0.5mg/kg produced
improvement of symptoms within 2 hours of slow i.v. administration, and at 24 hours two
thirds were still improved, with remission of symptoms in one third.

Mixed action anaesthetics.


THIOPENTONE and PENTOBARBITONE are sometimes used to induce ‘flat EEG’ as a brain
protection strategy. Modes of action include effects on both the GABAA receptor (agonists) and
NMDA receptor (antagonists). There are endogenous neurosteroids like pregnenolone, but
synthetic neurosteroids have been used as anaesthetics. Minaxolone was one of the first, and
Althesin (alphaxalone/ alphadolone) was very popular once.   Though none are currently
available for human anaesthesia, future developments may see a return.

Two-pore-domain potassium channel activators.


The two-pore-domain potassium channels (K2P channels, also known as leak channels)
regulate the currents generated by ions moving across a membrane. They are influenced by
oxygen tension, hydrogen ion concentration, mechanical stretch and various G-proteins. The
commonly-used anaesthetic vapours have recently been found to activate potassium channels
as well as having an agonist effect at the GABAA receptor.

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ISOFLURANE 0.5% has been used successfully for short term sedation but nephrotoxic levels of
fluoride have been reported after 50 MAC hours. Scavenging can be a problem in Intensive
Care. The anaesthetic vapours may have beneficial side effects including myocardial protection
by preconditioning. There is evidence that sub-anaesthetic concentrations of SEVOFLURANE
prevent ‘emotive’ memories.

Alpha-2 c receptor agonists.


The sedative effect of these drugs is very specifically within the tiny locus coerulius (LC) where
alpha-2 agonism inhibits noradrenaline release. The VLPO is thereby disinhibited and sleep is
facilitated.
CLONIDINE is an alpha-2 adrenergic agonist occasionally used as an adjunct in patients who
are hypertensive and tachycardic in spite of high doses of sedative medication (tetanus being
an excellent example).  It appears to enhance the effects of opioids at spinal cord level.  Start
at 100-150 micg 4-8 hourly.   Not cleared in renal failure even by filtration.
DEXMEDETOMIDINE has fewer haemodynamic effects and has been found to be superior to
lorazepam for sedation of ventilated patients (MENDS trial) but is not currently available in the
UK.

Anaesthesia
Is a drug-induced condition in which the patient shows no response to noxious stimulus
(usually a surgical operation) and has no explicit recall of the noxious stimulus. Immobility is a
result of spinal cord obtundation and can be brought about by a skilled anaesthetist using a
variety of drugs. About one patient in every thousand experiences some degree of ‘awareness’
because there is a wide variation in people’s susceptibility to the cerebral effects of
anaesthesia. Spectral analysis of the EEG has been shown ineffective in preventing awareness.
Very rarely a cock-up leaves a patient curarised but unanaesthetised.

Mood.
Sadness (reactive depression) is common after acute illness. It does NOT respond to ant-
depressants, which have serious side effects and should not be given to acutely-ill patients
without psychiatric consultation and careful consideration about drug safety. For recovering
patients experiencing pain and insomnia, a nocte dose of amitriptiline seems to be safe and
effective.
Cognitive dysfunction following surgery, trauma or major illness is particularly common in
older patients and is made worse by the use of benzodiazepines, pethidine and anti-
cholinergic medications.
Delirium is associated with poorer outcomes for critically ill patients. If it is troubling enough
to demand treatment, use a dopamine-antagonist tranquiliser such as haloperidol or
levomepromazine. Recent retrospective data from Pittsbugh even suggested an outcome
benefit for haloperidol treatment in ventilated patients, but note that droperidol was
withdrawn from the market following case reports of lethal cardiac arrhythmias including
torsades des pointes, and haloperidol shares this unfortunate ability to prolong the QT
interval.

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Chapter 11

Cerebral Support and


Determination of Brain Stem
Death
You must be conversant with the Glasgow Coma Scale. A number of modified scales suitable
for younger children have been proposed.
G l a s g o w1 2 3 4 5 6
C o m a
Scale
Eyes Does not Opens eyes in Opens eyes in Opens eyes N/A N/A
open eyes response to response to spontaneously
painful stimuli voice
Verbal Makes no Incomprehensible U t t e r s C o n f u s e d , O r i e n t e d , N/A
sounds sounds inappropriate disoriented converses
words normally
Motor Makes no Extension to A b n o r m a l Flexion /L o c a l i z e sO b e y s
movements painful stimuli flexion to Withdrawal to p a i n f u l Commands
painful stimuli painful stimuli stimuli

Following any type of brain injury, further damage must be prevented by normalising the
blood pressure, arterial blood oxygen content, and carbon dioxide tension. Resuscitation must
be achieved before interhospital transfer.   Hyperglycaemia is known to be dangerous and
should be avoided. Pyrexia is associated with increased metabolic rate and should be treated.
Anticonvulsant therapy has no influence on the incidence of late post traumatic epilepsy.
Steroids are of no benefit in acute traumatic brain injury. Patients presenting with other
conditions in which ICP monitoring may be indicated include fulminant hepatic failure and
Reyes syndrome.
Computerised axial tomography is performed in severe traumatic brain injury (Glasgow coma
scale (GCS) 4-8) and accessible mass lesions estimated to be greater than 25ml are usually
evacuated.  Intracranial pressure monitoring may then be instituted to guide therapy aimed at
reducing intracranial pressure (ICP) to less than 20mmHg.

Principles of ICP control.


cardiorespiratory resuscitation.  The mean arterial pressure should be high enough for a
cerebral perfusion pressure of 70mmHg.
sedation and controlled endotracheal hyperventilation.  The PaCO2 should be lowered in
steps, and should never be less than 3.5kPa.  Morphine and/or midazolam are suitable
sedatives.  Propofol can have a detrimental effect on cerebral perfusion pressure. 
Softening doses of muscle relaxants are said to help prevent coughing and straining
which may raise ICP.
nurse the patient 'head up', free of neck constrictions, and use maintenance fluids only
sparingly (30-50ml/kg/day for children and adults, 100ml/kg/day for infants).
prevent pyrexia.  Mild hypothermia (to 35C) may offer worthwhile reduction in CMRO2
without adverse circulatory effects. Early cooling to 33C maintained for 24 hours
hastened recovery from traumatic coma (GCS 5-7) in one RCT.
transient increases in ICP to over 20mmHg often respond to a brief period of manual
hyperventilation (bagging).  Sustained rises should be treated by lowering PaCO2 if
possible, and increasing sedation.  Is a repeat scan indicated? Neurosurgical opinion.
If ICP remains higher than 20mmHg and surgically remediable lesions have been excluded
by scan, consider jugular bulb oximetry for rational prescription of pressure-reducing
therapy (see below).
if a ventricular pressure monitor is in place, consider controlled CSF drainage.  Mannitol
0.5G/kg should also be considered (monitor serum osmolality).  Non-osmotic diuretics
reduce CSF formation but are of limited clinical value.

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finally consider 'barbiturate coma'; EEG monitoring is valuable if this is to be used. 


Thiopentone is given as a loading dose and infusion (taking care to maintain the mean
arterial pressure and cerebral perfusion pressure with dopamine or norepinephrine if
necessary) to achieve "burst suppression" (periods of isoelectricity), at which point
functional O2 consumption is minimal.
In trauma, early rises of ICP are thought to be more significant and are treated more
aggressively than later rises which can occur during weaning from ventilation (so take out the
monitor after 48-72 hours!) RCTs on the management of ATBI are mostly inconclusive.
A novel protocol for the management of acute traumatic brain injury is reported from Lund
(Sweden) in which the emphasis is towards brain volume regulation by anti-hypertensive and
anti-stress pharmacotherapy. Published clinical experience to date is encouraging, but
adoption of this unconventional therapy should await results of controlled trials.

Continuous processed electro-encephalography


The electrodes must be placed with careful prior skin preparation to achieve a low impedance
In many devices the EEG is broken down by Fourier analysis into its harmonic components
which are then displayed by amplitude (up; scale 50-200 microV, selectable) and frequency
(along; 0.5-30 Hz), with the time scale (5-30 minutes, selectable) stretching back. When
assessing the processed EEG trace think SAFE;
Symmetry? (if not, something is obviously wrong on at least one side!)
Amplitude? the highest amplitudes should be in the lower frequency bands, at about 100-200
microV.  Absence of activity may be due to deep anaesthesia (though NOT opiates alone) or
death.
Frequency spread? Only low frequency waves are seen in deep opiate sedation or brain injury.
Edge? (Spectral edge or median power frequency)
Epileptic discharges show up as very high amplitude waves right across the frequency range,
often followed by a transient reduction in EEG activity.

Jugular bulb venous oximetry


Offers a valuable insight into the effects of therapy in head injury.  The catheter is passed
retrogradely from the internal jugular vein and its position is confirmed radiographically.  A
continuous oximetric trace is monitored, and periodically recalibrated against samples. 
Lactate measurements can also be made intermittently.
Low SjO2 (<40%) implies global ischaemia, and venous lactate will be raised. However, cerebral
ischaemia may be present even with normal SjO2 (54-75%) so the Lactate Oxygen Index (LOI)
can be estimated.
ajD.lact(mmol / l)
LOI = * 2.24
aj DO2 (ml / dl)
LOI is normally less than 0.03 but rises to over 0.08 in the presence of ischaemia. Raised
intracranial pressure with ischaemia is rationally treated by increasing mean arterial pressure
and reducing cerebral oedema with diuretics.
SjO2 is greater than 75% in the presence of inappropriately high cerebral blood flow
(hyperaemia), or cessation of oxygen consumption (brain death). Raised intracranial pressure
with hyperaemia is rationally treated by further hyperventilation plus thiopentone (monitor
EEG and titrate thiopentone to achieve burst suppression).

Status epilepticus
Patients are usually admitted to ICU if boluses of diazepam with loading and maintenance
doses of phenytoin have failed to control the fits.  EEG monitoring is helpful.  Any anaesthetic
agent (thiopentone, methohexitone, propofol, isoflurane) will temporarily stop the fitting, but
it will often return on recovery unless anticonvulsants are given effectively. Watch the blood
pressure!  Intubation and ventilation are the only safe way to care for anaesthetised patients
on ICU.  In refractory status epilepticus there are reports of ketamine being used successfully
as a supplementary agent to block the effects of excitatory amino acids. We have used
intravenous paraldehyde in a weak 4% solution from syringe and tubing suitable for sodium

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nitroprusside (though no manufacturer will recommend such use!) but the major complication
is acute heart failure.

Coma after cerebral ischaemia


Patients who do not wake up after cardiopulmonary resuscitation should be admitted to ICU. 
Induced hypothermia – initiated within 2 hours of arrest, and continued for at least 24 hours -
has been found to improve neurological recovery. Normal sedative medication may be used if
ventilation is required.  Patients in coma (GCS<6) at 72 hours are unlikely to leave hospital
alive. 

Death determined by brain stem tests.


(Academy of Medical Royal Colleges (70 Wimpole Street, London, W1G 8AX). A Code of Practice
for the Diagnosis and Confirmation of Death, October 2008)
A Code of Practice was first issued by the Royal Colleges in 1983 and was updated in 1998
and 2008. They define death in the United Kingdom as
"the irreversible loss of capacity for consciousness, combined with the irreversible loss of the
capacity to breath"
and emphasise that it does not imply death of the whole brain. The diagnosis can be
considered in a patient aged two months or older who is in deep coma and showing no
spontaneous movement.  You must know the cause of the brain injury, and be satisfied that
coma is not due to drugs, circulatory, endocrine or metabolic abnormality, or hypothermia. 
Some patients will have diabetes insipidus, and will require water supplementation (5%
Dextrose with KCl) to prevent dehydration.  Extreme polyuria (>200ml/hour) can be controlled
with small doses of DDAVP or vasopressin infusion.  In brain dead patients the heart beat is
remarkably steady with little 'beat to beat variation'.  The metabolic rate is also reduced, so
relatively small minute volume ventilation is all that is needed to maintain normocapnia, and
active warming is often needed to prevent hypothermia. 
A detailed neurological examination is performed. After the first examination the relatives
should be informed of the findings, and it must be explained that the examination will be
repeated.  If the findings are the same at the second examination then the patient will be
confirmed to have been diagnosed dead at the first examination (i.e. time of death is time of
the first determination).  If the relatives understand this, and have had an opportunity to ask
questions, this is a good moment to ask them to "consider whether John would have wished to
help other people by organ donation in the event of his sudden death".  Phrased this way, the
emphasis is on what the patient would have wanted.   The "will you give us his organs?"
approach puts an unnecessary burden of responsibility on the relatives, who may reply that
John was generally in favour of organ donation, but "we do not want to put him through any
more suffering".  Give them time to consider your approach about organ donation; most know
immediately one way or the other what Johnny would have wanted, but sometimes a family will
want to consult amongst themselves and talk to you again.
Perform the second examination at a suitable time 1-24 hours later.
ELECTIVE VENTILATION is a misleading title for the practice of   admitting near-terminal
patients (typically with intracranial haemorrhage) to ICU so that they can be intubated and
ventilated just as apnoea is judged to occur.  This scheme to increase the number of potential
organ donors was pioneered in Exeter and enthusiastically backed by the Department of
Health but has obvious ethical problems and was later ruled to be an assault upon the patient
which must not be undertaken. Though many people hope it will soon be forgotten, the British
Transplantation Society continue to push for law reform to enable its implementation.
PRESUMED CONSENT describes a system in which people are presumed to have consented to
be donors unless they have registered as objectors or their families can prove they were
objectors. Also intended to increase the donor pool. Now advocated by the BMA after a change
of heart in 1999 but opposed by public opinion, by Scottish Parliament (twice), the UK Organ
Donation Taskforce (2008) and the British Organ Donation Association (BODY). Should 'a gift
of life' be swapped for a 'tax on death’?

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