Anaphylaxis Anaphylactoid reaction

ANAPHYLACTIC REACTION VS
ANAPHYLACTOID REACTION
[CEACCP 2004 Vol 4(4) "Anaphylaxis"]

Anaphylactic reaction
 Exaggerated response to a foreign substance
 Previous exposure/sensitisation necessary
 Subsequent exposure triggers massive degranulation by mast cells, mediated by specific
IgE antibodies
 Response is not related to quantity of the triggering allergen

Anaphylactoid reaction
 Triggered by
* Direct stimulation on mast cells, causing histamine release
* Complement activation (classical or alternative pathways)
 No prior exposure necessary
 No IgE antibody involvement

Example of anaphylactoid reaction

 Common in reactions to contrast media

Non-immunological histamine release

Drug directly acting on mast cells
--> release of histamine
 Response is related to quantity of the triggering allergen
 Tend to be confined to skin
 Occurs in up to 30% of anaesthesia

Examples of drugs directly stimulating mast cells

 Atracurium
 Mivacurium
 Morphine
 Meperidine
 TREATMENT OF ANAPHYLAXIS
[CEACCP 2004 Vol 4(4) "Anaphylaxis"]

Immediate management
1. Stop administration of all agents likely to have caused the anaphylaxis
2. Call for help
3. Maintain airway, give 100% O2, lie patient flat with leg elevated
4. Give epinephrine
* IM dose = 0.5 - 1mg (0.5-1mL of 1:1000)
* IV dose = 50 - 100mcg (0.5 - 1 mL of 1:10,000) over 1 min in case of CVS collapse
* Never give undiluted 1:1000 epinephrine IV
5. Give IVF
* Adults may require 2 - 4 L

Subsequent management
1. Give antihistamines
* Role of H2 antagonist is controversial
2. Give corticosteroid (100 - 500 mg hydrocortisone slowly IV)
3. Consider bronchodilator if necessary
4. Catecholamine infusion
* CVS instability may last several hours
* Epinephrine infusion = 0.05 - 0.1 mcg/kg/min = 3 - 6 mcg/kg/hr
* For 70kg adult, roughly 4 mL of 1:10,000 per hour
5. Check ABG
6. Consider bicarbonate 0.5 - 1 mmol/kg
* 8.4% of NaHCO3 = 1 mmol/mL

Investigation
3 blood samples to be taken:
1. Immediately after the reaction has been treated
2. About 1 hour after the reaction
3. About 6 hours or up to 24 hours after the reaction
These bloods are to be stored at 4C if analysis within 48 hours, otherwise store at -20C

Tryptase
 Tryptase is found almost exclusively in mast cells
 Released during anaphylaxis and anaphylactoid reaction
 Peak after about 1 hour
 Blood test needs to be taken at about 1 hour after the reaction to confirm the presence of
tryptase
 Later investigations
 Full investigation and referal to allergist
For example,
 Skin prick tests
 Measurement of specific IgE
* By radio-allergosorbent test (RAST) or by CAP test (??)

Screening
Screening for anaphylaxis has no value
* History of previous exposure is often not necessary

Management of patient with previous

anaphylaxis
 Avoid causative agent
 Consider inhalational induction
 Premedication
* Hydrocortisone
* Inhaled beta-agonist
* H1 and H2-receptor antagonists
 Preoxygenation
 Vasopressor immediately available

1 2

Table of contents | Index

Anaphylaxis_treatment.html
Part of study notes by LD99
Revised at 02/02/2007 00:17
Version 1
S

Anaphylaxis

Dr Sara Rees
Cardiff
UK

Case History

You are anaesthetising a fit and well 40 year old woman for total abdominal hysterectomy for
menorrhagia. You induce with fentanyl, propofol and atracurium. Following intubation you note she
appears flushed and the lungs are difficult to inflate. The pulse is very faint and you cannot record a
blood pressure.

Complete these questions before reading the tutorial

1. What would be your immediate reaction?

2. What are the possible diagnoses?
3. Once stabilised what other therapies would you consider?
4. Would you carry on with the surgery?
5. What initial investigations would you carry out?
6. What is the difference between anaphylactic and anaphylactoid reactions?
7. Name 2 common presenting features of anaphylaxis
8. What is the most important drug in the treatment of anaphylactic shock?
9. What are the most common group of drugs to cause anaphylaxis in anaesthesia?
10. Name 3 vasoactive substances released into the plasma in anaphylaxis
11. How would you investigate to find the causative agent?

Introduction

Anaphylactic reactions during anaesthesia are extremely rare but can be fatal if not promptly
recognized and treated. Reactions can vary in severity and presentation.

Incidence in the UK is unknown; in France suspected anaphylaxis is estimated to be 1 in 13000

anaesthetics whereas true anaphylaxis to neuromuscular blocking agents is approximately 1 in 6500.

Pathophysiology

An anaphylactic reaction is an exaggerated immunological response to an exogenous agent (antigen)

to which an individual has been previously sensitized. The antigen binds to the specific IgE antibodies
which are found on mast cells and basophils. This is classed as a Type 1 hypersensitivity reaction.
The IgE antibodies are produced by T cells as a result of the sensitization. This binding of antigen to
antibody causes breakdown and degranulation of these cells to release into the plasma vasoactive
and bronchospastic substances including:-

· Histamine

· Leukotrienes

· Serotonin

· Tryptase

These reactions are not dose related and can occur even with a minute dose of drug administered.
They tend to become more severe on re-exposure.

Anaphylactoid reactions are clinically indistinguishable from anaphylaxis but are IgG mediated and
require no prior exposure or immunological sensitization, but result by direct action from the drug.
Common Trigger agents

· Neuromuscular blocking agents are responsible for 60-70% of anaphylactic reactions under
anaesthesia. The antigen is the quaternary ammonium group which is found in other drugs, food,
cosmetics and hair products. Therefore a reaction can occur without previous exposure to the agent.
Most common precipitants in decreasing order vecuronium, atracurium, suxamethonium,
pancuronium, rocuronium, mivacurium. Female to male ratio 2.5:1

· Antibiotics. Predominantly penicillin type drugs containing a beta lactam ring. 8% cross reactivity
with cephalosporins which is often incomplete.

· Thiopentone reported as 1 in 14,000

· Latex 12-17% of reactions

· Plasma expanders: dextrans, starches, gelatins

Recognition

Over 90% of anaphylaxis will occur at or shortly after induction but reactions can occur at any time.
Clinical manifestations are not consistent and therefore diagnosis can be difficult. The most common
life-threatening presenting feature is cardiovascular collapse. Presenting clinical features and
percentage frequency are:

 Cardiovascular collapse 88%

 Erythema 45%
 Bronchospasm 36%
 Angio-oedema 24%
 Rash 13%
 Urticaria 8.5%

Management
Immediate Management Subsequent Management
Stop injection or infusion in process Antihistamines
Summon help and inform surgeon
· Chlorpheniramine 10-20mg iv
Switch to 100% O2 with low conc of slow injection
volatile agent
Give EPINEPHRINE (adrenaline) Steroids

if unrecordable BP · Hydrocortisone 200mg iv slow

injection
0.5-1ml of 1 in 10,000
Persistent bronchospasm

titrate to response
· Salbutamol

if milder reaction consider

MDI or nebulised via breathing
ephedrine/metaraminol
circuit
Start rapid intravascular volume
expansion 250microgram slow bolus iv
with Hartmann’s or saline solution
plus
IV infusion 3-20 micrograms /
 elevate legs minute

external chest compressions if · Aminophylline

cardiac arrest
Loading dose 5mg/kg iv

Infusion 0.5mg/kg/hr

Check ABG if
severe ACIDOSISafter 20 minutes
consider
SODIUM BICARBONATE 0.5 - 1
mmol/kg

8.4% solution 1mmol/ml

Catecholamine infusions for
persistent CVS instability

Dose range
ADRENALINE
0.1-0.5
NORADRENALINE
mcg/kg/min
Vasopressin may
be effective
Clotting screen
Consider possibility of coagulopathy

Note: epinephrine is adrenaline

As previously mentioned the range and severity of presentation and response to treatment is
extremely variable. The above algorithm is used as a guide only as some reactions can be mild with
some bronchospasm, flushing and mild hypotension requiring only IV fluid and ephedrine, and in
these cases use of adrenaline would be inappropriate.

Other cases can be life threatening immediately and need aggressive treatment with subsequent ICU
admission and organ support for some days.

Consider ICU admission if:

Airway

 Oedema – check for laryngeal oedema by checking for a leak around ETT

Breathing

 Persistent bronchospasm
 Hypoxia
 Pulmonary oedema
 ARDS

Circulation
  Ongoing CVS instability and dependence on inotropes to maintain BP
 Severe metabolic acidosis

Investigations

Immediate

Serum Tryptase levels

Mast cell tryptase is the main protein of mast cell granules. 99% of this enzyme is found in mast
cells and it is not found in red or white blood cells so plasma levels not affected by haemolysis. The
half life is 2.5 hours with peak levels occurring rapidly and within 1 hour. In countries with the facility
to measure serum tryptase it is recommended to take 3 blood samples:-

 Immediately after initial treatment

 1 hour post exposure (for the peak)
 6 hours

All samples should be carefully labeled with timings. Samples should be stored at -20 degrees C.
Even post mortem serum tryptase may give meaningful results to aid diagnosis. Raised serum
tryptase merely indicates there has been mast cell degranulation which occurs in both anaphylactic
and anaphylactoid reactions. Basal level 0.8-1.5ng/ml

Levels up to 15ng/ml seen in anaphylactoid reactions and mild anaphylaxis. A higher value is more
likely to be an IgE response i.e. >20ng/ml. It is important at the time of the event to make sure that
the event is well documented with accurate timings and all drugs administered. Later tests are used
to try and identify the causative agent to prevent reactions in the future.

Skin Prick testing

· Should be done > 4 weeks after reaction to allow regeneration of IgE

· Usually diagnostic in anaphylactic but not in anaphylactoid reactions

· Should test for wide range of anaesthetic drugs plus suspected agents

· Positive and negative controls: histamine and saline

· A drop of drug is applied to the forearm and a lancet pricked through it to break skin

· This is done with neat drug, interpreted at 15 min and if wheal >2mm repeated with drug diluted to
1 in 10 - if wheal present, this is a true positive reaction

· True reactions may have positive tests at much greater dilutions

Other tests

 RAST: radioallergosorbent test which measures antigen-specific IgE antibodies in the serum
 CAP test is more sensitive than RAST and is a fluoro-immunoassay.
 These tests are currently helpful in only confirming allergy to suxamethonium and latex
allergy and have a low sensitivity, therefore negative results still require skin prick tesing

After Testing
  Explanation to patient and issue a medicalert bracelet
 Make note in hospital notes and inform GP
 If in UK Report to the Committee on the Safety of Medicines “yellow card”

New developments

Vasopressin- there have been successful case reports on vasopressin used in severe anaphylaxis
which has been unresponsive to epinephrine. Vasopressin is a very potent vasoconstrictor and should
be considered if there is a limited response to epinephrine

Summary

Anaphylaxis is a rare but serious event and is diagnosed clinically. All anaesthetists should be familiar
with an algorithm for treatment of anaphylaxis. Epinephrine should be given early in severe
reactions. Delay in diagnosis or treatment can be fatal.

Further reading

The Association of Anaesthetists of Great Britain and Ireland (2003) Suspected anaphylactic
reactions associated with Anaesthesia. www.aagbi.org

ArticleDate:20061029
SiteSection: Article

Related Articles:
Anaphylaxis

Anaphylaxis

NMBAs and anaphylaxis