ACUTE RESPIRATORY FAILURE

Respiratory factors

Acute pulmonary vascular occlusion can result in ventilation-perfusion mismatch and respiratory failure
due to insufficient blood flow to functioning alveoli. Massive pulmonary artery embolisation may cause
high right-sided after-load pressures leading to cardiac dysfunction and inability of the heart to circulate
adequate blood volume.

Pneumothorax can lead to respiratory failure if there is not enough lung reserve to compensate for the
collapsed lung or lung segment. This would typically occur in the setting of pre-existing pulmonary
dysfunction. Bilateral pneumothoraces can cause catastrophic respiratory failure and rapid cardiac
arrest.

Fluid or blood accumulation in the pleural space (pulmonary effusion) may lead to compression of
pulmonary tissues and loss of pulmonary function, causing respiratory failure. Effusion can occur
secondary to infection, malignancy, trauma, cardiac failure, and collagen vascular disease, as well as
many other conditions.

Destruction or infiltration of alveoli reduces the surface area available for gas exchange. Emphysema
causes alveolar destruction, and the bullae that are formed occupy intra-thoracic space without
contributing to gas exchange. Respiratory failure results from acute or eventual loss of the baseline
number of alveolar units. Infiltration or filling of alveoli with fluid is a frequent cause of acute respiratory
failure. Conditions that cause alveolar filling include pneumonia, pulmonary oedema, and pulmonary
haemorrhage. Alveolar haemorrhage can occur with Goodpasture's syndrome, Wegener's
granulomatosis, and trauma. Fluid-filling of alveoli leads to inability of these alveoli to provide gas
exchange with the blood. Acute respiratory distress syndrome resulting from trauma, hypo-perfusion, or
direct insult is a form of alveolar infiltration and injury.

Acute upper airway obstruction (e.g., from foreign body aspiration, acute epiglottitis, anatomical
abnormalities, anaphylaxis) can inhibit air flow into the lungs and cause respiratory failure. Lower
airway obstruction (e.g., from asthma, chronic obstructive pulmonary disease, cystic fibrosis) is more
common and involves constriction or mucous blockage of intermediate-size bronchioles.

Pulmonary embolus can occur as a result of hypercoagulability from clotting cascade diseases or
abnormalities.

Exposure to toxic fumes can lead to damage of the upper airway, lower airway, or alveoli. Industrial
gases such as chlorine are an example. The most common inhalation injury is smoke inhalation, where
particulate matter and gases are intermixed and can cause upper airway and lower airway inflammation
resulting in respiratory failure. Toxic gases such as carbon monoxide and hydrogen sulfide are
exchanged in the lungs, yet result in asphyxia by inhibiting the ability of the blood to effectively extract
oxygen from the lungs, as well as causing cellular metabolic damage (cellular asphyxia).

Non-respiratory factors

Poor perfusion of the brain, heart, and lungs (e.g., from haemorrhagic hypovolaemia, dehydration
hypovolaemia, septic shock, cardiogenic shock, severe anaemia) can result in respiratory failure by
reducing blood oxygenation and depressing CNS respiratory centres.

Ventilation with pulmonary gas exchange is dependent on diaphragm and chest wall muscle
functioning. Neurological disorders inhibiting respiratory muscle function limit ventilation and can cause
respiratory failure. Examples include Guillain-Barre syndrome and myasthenia gravis. Muscular
dystrophy is an example of a disorder that results in muscle function abnormalities that limit ventilation
and can result in respiratory failure.

Opiate and sedative medicines decrease respiratory drive in the CNS, with resulting limited ventilatory
effort.

Injuries, disease, or insult of the CNS can result in loss of respiratory drive and secondary respiratory
failure. Examples include infiltrating and mass cancers of the CNS, head injury with haemorrhagic mass
effect, direct brain injury, infections, primary CNS disorders, and cerebrovascular accident.

Traumatic causes

Direct thoracic injury may result in a number of abnormalities that can lead to respiratory failure.

Direct brain injury can result in loss of respiratory drive.

 Spinal injury can result in loss of peripheral nerve function and the lack of ability to ventilate due to
inadequate respiratory muscle function.

Acute Respiratory Failure:

Definition:

The loss of the ability to ventilate adequately or to provide sufficient oxygen to the blood and systemic organs.
The pulmonary system is no longer able to meet the metabolic demands of the body with respect to
oxygenation of the blood and/or CO2 elimination.
Classification:

Type 1 (Hypoxemic ) - PO2 < 50 mmHg on room air. Usually seen in patients with acute pulmonary edema
or acute lung injury. These disorders interfere with the lung's ability to oxygenate blood as it flows through the
pulmonary vasculature.
Type 2 (Hypercapnic/ Ventilatory ) - PCO2 > 50 mmHg (if not a chronic CO2 retainer). This is usually seen
in patients with an increased work of breathing due to airflow obstruction or decreased respiratory system
compliance, with decreased respiratory muscle power due to neuromuscular disease, or with central
respiratory failure and decreased respiratory drive.
Type 3 (Peri-operative). This is generally a subset of type 1 failure but is sometimes considered separately
because it is so common.
Type 4 (Shock) - secondary to cardiovascular instability.

Etiologies:

ARF can result from a variety of etiologies. It can result from primary pulmonary pathologies or can be initiated
by extra-pulmonary pathology. Causes are often multifactorial. Acute respiratory failure can be caused by
abnormalities in:

CNS ( drugs, metabolic encephalopathy, CNS infections, increased ICP, OSA, Central alveolar
hypoventilation)
spinal cord (trauma, transverse myelitis)
neuromuscular system ( polio, tetanus, M.S., M.Gravis, Guillain-Barre, critical care or steroid myopathy)
chest wall ( Kyphoscoliosis, obesity)
upper airways ( obstruction from tissue enlargement, infection, mass; vocal cord paralysis, tracheomalacia)
lower airways ( bronchospasm, CHF, infection)
lung parenchyma ( infection, interstitial lung disease)
cardiovascular system

Hypoxemic Respiratory Failure (Type 1):

Physiologic Causes of Hypoxemia

Low FiO2 (high altitude)

Hypoventilation
V/Q mismatch (low V/Q)
Shunt (Qs/Qt)
Diffusion abnormality
Venous admixture ( low mixed venous oxygen)

Low FiO2 is the primary cause of ARF only at altitude. However, it should be kept in mind that any patient who
suddenly desaturates while on oxygen may have had their oxygen source disconnected or interrupted.
Hypoventilation can be ruled in or out with the use of the alveolar-air gas equation. A normal A-a gradient
indicates that hypoventilation is the cause.

PAO2 = FIO2 (PBarometric - 47) - 1.25PaCO2)

Occasionally a patient with a sub-clinical intra-pulmonary shunt may become hypoxemic due to venous
admixture. In this situation inadequate oxygen delivery to the periphery results in increased peripheral oxygen
extraction and thus the return of blood with a very low mixed venous oxygen saturation. The relatively small
shunt in the lungs is normally not clinically obvious, but is great enough so that if extremely desaturated blood
returns to the lungs it will not be adequately re-oxygenated. Thus patient hemodynamics and the possibility of
a low-flow state should be kept in mind as a possible cause of hypoxemia.

However, the two most common causes of hypoxemic respiratory failure in the ICU are V/Q mismatch and
shunt. These can be distinguished from each other by their response to oxygen. V/Q mismatch responds very
readily to oxygen whereas shunt is very oxygen insensitive. A classic cause of V/Q mismatch is a COPD
exacerbation. In shunt, alveolar capillary perfusion is much greater than alveolar oxygenation due to collapse
and derecruitment of alveoli. This means that venous blood does not come in contact with oxygen as it is
"shunted" by the collapsed or fluid -filled alveoli. Therapy for shunt is directed at re-opening or recruiting
collapsed alveoli, preventing derecruitment, diminishing lung water, and improving pulmonary hypoxic
vasoconstriction. Some causes of shunt include ;

Cardiogenic pulmonary edema

Noncardiogenic pulmonary edema (ARDS)
Pneumonia
Lung hemorrhage
Atelectasis

Therapies for acute hypoxemic respiratory failure include;

Oxygen
PEEP
Diuresis
Prone Position
Permissive hypercapnia
Inverse Ratio Ventilation or Pressure Control Ventilation
Nitric oxide
ECMO / ECCOR / Partial Liquid Ventilation

Type 2 ( Ventilatory /Hypercapnic Respiratory Failure):

Physiologic causes of Hypercapnia:

Increased CO2 production (fever, sepsis, burns, overfeeding)

Decreased alveolar ventilation

decreased RR
decreased tidal volume (Vt)
increased dead space (Vd)

The cause of hypercapnia is often independent of hypoxemia. Hypercapnia results from either increased CO2
production secondary to increased metabolism (sepsis, fever, burns, overfeeding), or decreased CO2
excretion. CO2excretion is inversely proportional to alveolar ventilation (VA). VA is decreased if total minute
ventilation is decreased - secondary to either a decreased respiratory rate (f) or a decrease in tidal volume (Vt);
or if the deadspace fraction of the tidal volume is increased (Vd/ Vt).

PACO2 = k x VCO2 / VA, therefore....

PACO2 = k x VCO2 / VE(1 - Vd/ Vt) = k x VCO2 / (Vt x f) (1- Vd/ Vt)

since VA = (Vt - Vd)f

where VCO2 is carbon dioxide production, VA is alveolar ventilation, VE is total minute ventilation, and Vd/Vt is
the fraction of dead space over tidal volume.
Causes of decreased alveolar ventilation:

Decreased CNS drive ( CNS lesion, overdose, anesthesia). The patient is unable to sense the increased
PaCO2. The patient "won't breathe".
Neuromuscular disease ( Myasthenia Gravis, ALS, Guillian-Barre , Botulism, spinal cord disease,
myopathies, etc.). The patient is unable to neurologically signal the muscles of respiration or has significant
intrinsic respiratory muscle weakness. The patient "can't breathe".
Increased Work Of Breathing leading to respiratory muscle fatigue and inadequate ventilation.
Asthma/ COPD
Pulmonary fibrosis
Kyphoscoliosis
Increased Physiologic Dead Space (Vd). When blood flow to some alveoli is significantly diminished, CO2 is
not transferred from the pulmonary circulation to the alveoli and CO2 rich blood is returned to the left atrium.
Causes of increased dead space ventilation include pulmonary embolus, hypovolemia, poor cardiac output,
and alveolar over distension. Dead space can be quantified using the Bohr equation and a Douglas bag, or
with the use of a "metabolic cart".

Evaluation of Hypercapnia:

The physiologic reasons for hypercapnia can be determined at the bedside.

Minute Ventilation, RR, Vt,

 Assessment of patient's work of breathing - accessory respiratory muscle use, indrawing, retractions,
abdominal paradox.
NIF (negative inspiratory force). This is a measure of the patient's respiratory system muscle strength. It is
obtained by having the patient fully exhale. Occluding the patient's airway or endotracheal tube for 20 seconds,
then measuring the maximal pressure the patient can generate upon inspiration. NIF's less than -20 to -25 cm
H2O suggest that the patient does not have adequate respiratory muscle strength to support ventilation on his
own.
P0.1 max. This measurement of the degree of pressure drop during the first 100 milliseconds of a patient
initiated breath is an estimate of the patient's respiratory drive. A low P0.1 max suggests that the patient has a
low drive and a central hypoventilation syndrome.

central hypoventilation vs. Neuromuscular weakness

"wont breathe vs. cant breathe"
central = low P0.1 with normal NIF
Neuromuscular weakness = normal P0.1 with low NIF

Metabolic cart

calculates VCO2, and Vd/ Vt

ICU Alveolar Hypoventilation:

Central / Brainstem depression (drugs, obesity)

Neuropathic (MG, Guillian-Barre, MS, Botulism, Phrenic nerve injury, ICU polyneuropathy)
Myopathic (Mg, PO4, ICU myopathy)

Abnormalities in Lung Mechanics:

There are many possible etiologies for acute respiratory failure and the diagnosis is often unclear or uncertain
during the critical first few minutes after presentation. Since it is often necessary to initiate treatment before a
clear diagnosis can be established, taking a pathophysiologic approach towards the patient can be useful. To
that end, the "respiratory equation of motion" can provide a useful conceptual framework in determining why
the patient is unable to sustain adequate minute ventilation.

Work Of Breathing (WOB) = Resistance + Elastance + Threshold load + Inertia

Pmuscle + Papplied = E(Vt) + R(V)+ threshold load + Inertia

Pmuscle is the pressure supplied by the Inspiratory respiratory muscles; Papplied is the inspiratory pressure
provided by mechanical means (i.e., a ventilator); E is the elastance of the system; R is the respiratory system
resistance; Threshold load is the amount of PEEPi or intrinsic PEEP the patient must overcome before
inspiratory flow can begin; Vt and V are the tidal volume and the flow rate respectively; Inertia is a property of
all mass and has minimal contributions and thus can be ignored clinically.

More simply put, acute respiratory failure results when there is an imbalance between the respiratory muscle
power available (supply) versus the muscle power needed (demand). This usually occurs when the respiratory
loads are increased to the point where the respiratory muscles begin to fatigue and fail. As examples, acute
bronchospasm due to asthma or COPD places an increased resistive load on the respiratory system, acute
pulmonary edema decreases lung compliance and thus places an increased elastance load on the system,
and in COPD intrinsic PEEP increases the threshold load. The object of medical therapy is to decrease or
reverse these acute respiratory loads thereby decreasing demand on fatiguing respiratory muscles. If this is
not successful, then ventilation needs to be aided by mechanical means. Recruitment of accessory muscles of
respiration and abdominal paradox are clinical signs that the respiratory muscles do not have enough power on
their own to meet demand. Any patient with these signs will need to have the loads reduced or eventually,
ventilation aided by mechanical means.
Type 3 (Peri-operative) Respiratory Failure:

Type 3 respiratory failure can be considered as a subtype of type 1 failure. However, acute respiratory failure is
common in the post-operative period with atelectasis being the most frequent cause. Thus measures to
reverse atelectasis are paramount.In general residual anesthesia effects, post-operative pain, and abnormal
abdominal mechanics contribute to decreasing FRC and progressive collapse of dependant lung units.

Causes of post-operative atelectasis include:

decreased FRC
Supine/ obese/ ascites
anesthesia
upper abdominal incision
 airway secretions

Therapy is directed at reversing the atelectasis.

Turn patient q1-2h

Chest physiotherapy
Incentive spirometry
Treat incisional pain (may include epidural anesthesia or patient controlled analgesia)
Ventilate at 45 degrees upright
Drain ascites
Re-expansion of lobar collapse
Avoid overhydration

Type 4 (Shock);

Hypoperfusion can lead to respiratory failure.Ventilator therapy is often instituted in order to minimize the steal
of the limited cardiac output by the overworking respiratory muscles until the etiology of the hypoperfusion
state is identified and corrected.

cardiogenic
hypovolemic
septic

Clinical Signs and Symptoms of Acute Respiratory Failure

Clinical manifestations of respiratory distress reflect signs and symptoms of hypoxemia, hypercapnia, or the
increased work of breathing necessary. These include

Altered mental status (agitation, somnolence)

Peripheral or central cyanosis or decreased oxygen saturation on pulse oximetry
Manifestations of a "stress response" including tachycardia, hypertension, and diaphoresis
Evidence of increased respiratory work of breathing including accessory muscle use, nasal flaring,
intercostal indrawing, suprasternal or supraclavicular retractions, tachypnea
Evidence of diaphragmatic fatigue (abdominal paradox)
Abnormal arterial blood gas results

ARF : CXR Findings

Clear CXR with hypoxemia and normocapnia.- Pulmonary embolus, R to L shunt, Shock
Diffusely white (opacified) CXR with hypoxemia and normocapnia - ARDS, NCPE, CHF, pulmonary fibrosis
Localized infiltrate - pneumonia, atelectasis, infarct
Clear CXR with hypercapnia - COPD, asthma, overdose, neuromuscular weakness

Acute Respiratory Failure with COPD: Differential Dx.:

Bronchitis
Pneumonia
LV failure (pulmonary edema)
Pneumothorax
Pulmonary embolus
Drugs ( beta blockers )

Management of Acute Respiratory Failure

The management of acute respiratory failure can be divided into an urgent resuscitation phase followed by a
phase of ongoing care. The goal of the urgent resuscitation phase is to stabilize the patient as much as
possible and to prevent any further life-threatening deterioration. Once these goals are accomplished the focus
should then shift towards diagnosis of the underlying process, and then the institution of therapy targeted at
reversing the primary etiology of the ARF.
Urgent resuscitation

Oxygenation
Airway control
Ventilator management
Stabilization of the circulation
Bronchodilators/ Steroids

Ongoing care
 Differential diagnosis and investigations
Therapeutic plan tailored to diagnosis

Oxygenation

Almost all patients with ARF require supplemental oxygen. All should be placed on a pulse oximeter and
oxygen saturation should generally be maintained above 90%. Oxygen diffuses from the alveolus across the
alveolar membrane into capillary blood. The rate of diffusion is driven by the oxygen partial-pressure gradient.
Therefore increasing the PAO2 with supplementary oxygen should improve the transfer of oxygen into the
pulmonary capillary blood.

There are several different devices that can be used to deliver oxygen. They differ in terms of whether the are
open or closed systems, whether they deliver low or high oxygen concentrations, and whether they are low or
high flow systems. Their effectiveness depends upon whether they can deliver enough oxygen at a sufficient
flow rate to meet the patients demands. Non-intubated patients spontaneously breathing through an open
system will "entrain" some room air from their environment with each breath. Thus the ultimate oxygen
concentration delivered to them will depend upon how much was delivered by the oxygen device and how
much was entrained room air. The lower the flow delivered by the oxygen device, and the higher the patient's
own inspiratory flow is, the more room that will be entrained resulting in a lower oxygen concentration. For
example, a tachypneic patient will likely have a high respiratory drive and high inspiratory flows. He will require
a high flow system in order to prevent significant entrainment of room air and thus dilution of the delivered
oxygen.

a. Nasal cannula; Low-flow, low oxygen concentration, open device. 100 % oxygen is delivered through
cannulae at 0.5 to 6 L/min. Higher flow rates do not increase the FIO2 significantly and lead to drying of
the mucosa and patient discomfort. The resulting FIO2 depends upon the patient's minute ventilation
and how much room air is entrained. Thus it cannot be precisely controlled. The maximal oxygen
concentration at the trachea is not likely to exceed 40 to 50 %. Nasal prongs are generally used for
relatively stable patients who do not require high FIO2 or precise control of their FIO2.
b. Venturi masks. These are variable oxygen concentration, low to moderate flow, open devices. These
air entrainment masks deliver 100% oxygen through a jet-mixing device that causes a controlled
entrainment of air and thus allows for deliver of precise oxygen concentrations from 24 to 50 %. These
masks are useful in patients with COPD in whom a precise titration of oxygen concentration may be
desirable in order to minimize an increase in PCO2.
c. Reservoir Face Masks. These are high flow, high oxygen, open devices designed to minimize
entrainment of air in patients with high inspiratory flow demands. These masks incorporate a reservoir
bag that is filled with 100% oxygen. If the patient makes an inspiratory effort generating a flow higher
than the wall circuit can deliver, the reservoir of oxygen will be emptied to minimize entrainment of room
air.. The use of "tusks" on the facemask is a similar principle. The bag should be at least partially
distended throughout the respiratory cycle.
d. Resuscitation Bag-Mask-Valve Unit. High oxygen, high flow device. The oxygen flow should be kept
high (15 L/min) when this device is used. When the mask is held firmly over the face with a good
facemask seal, entrainment of room air is minimized.
e. Non-Invasive Positive Pressure Ventilation (NPPV). NPPV provides ventilatory assistance, positive
pressure, and a controlled oxygen concentration using a tight-fitting facemask as the interface between
the patient and the ventilator instead of an endotracheal tube. It can be used in order to avoid or
prevent intubation in carefully selected patients.
f. Introduction to Mechanical Ventilation

Hypercapnic ARF Pathophsiology in Asthma and COPD more

CNS disorders complex
Stroke, brain tumor, spinal cord lesions, Hypercapnic respiratory failure
drug overdose Increase dead space
Peripheral nerve disease Upper airway obstruction
Guillain-Barre syndrome, botulism, Asthma, COPD
myasthenia gravis Foreign body aspiration (check-valve)
Muscle disorders Chest wall disorder
Muscular dystropHy, respiratory muscles Kyphoscliosis, thoracoplasty etc
fatigue Hypercapnic respiratory failure
Chest wall abnormalities
Scoliosis, kyphosis, obesity Increase CO2 production
Metabolic abnormalities
Myxedema, hypokalemia Fever, sepsis, seizure, obesity, anxiety
Increase work of breathing (asthma,
Airway obstruction COPD)
High carbohydrate diet with underlying
Upper airway obstruction, Asthma, COPD lung disease (high RQ)