Anaphylaxis in Anesthesiology, it's incidence and what to do

2. Introduction to anaphylaxis…
Charles Robert
Richet
1850-1935
Paul Portier
1866-1962
• Nobel laureates - Charles Robert Richet and
Paul Portier coined the term “anaphylaxis” in 1902
• Death of a dog following repeated injection of
jellyfish toxin, which was tolerated well on first
administration prompted the first insight.
• Word has its origins in the Greek language as
“opposite of prophylaxis”
• Generally occurs on re-exposure to specific
antigen and requires release of specific pro-
inflammatory mediators.
• Re-exposure is not always a pre-requisite and
may be seen on first exposure thanks to cross
reactivity as well.

3. Pathophysiology of anaphylaxis…
• Type I immediate hypersensitivity
Initial exposure: IgE is produced and binds to mast cells and basophils
Re - exposure: Antigen cross-links between two IgE receptors
Induces the tyrosine phosphorylation of cytoplasmic tyrosine
activation motifs.
This sets up a signal-transduction cascade which results in increase of
intracellular Ca2+.

4. Pathophysiology contd…
This causes a release of preformed mediators such as histamine,
proteases, proteoglycans and platelet activating factor.
Vascular permeability changes, flushing, urticaria
angioedema, hypotension and bronchoconstriction.
Phospholipid metabolism further leads to synthesis of
leukotrienes (LTC4, LTE4 & LTD4) and Prostaglandins
(PGD2).

5. Pathophysiology of anaphylactoid reaction…
• Initial event is similar but differs in terms of activation of complement or
bradykinin cascade.
• Not mediated by IgE.
• There is direct activation of mast cells and basophils.
Symptoms seen in both..
• Pruritis, flushing, urticaria, angioedema, conjunctivitis, rhinitis, wheezing,
dyspnea, cyanosis, abdominal pain, nausea, vomiting, diarrhea, tachycardia,
hypotension, shock.

6. Diagnosis under normal circumstances…
Retrospective diagnosis:
* Serologic and skin tests * Human α and β tryptase
* Histamine is not preferred as half life is few mins.
In Vitro tests:
* To detect IgE antibodies * by radioallergosorbent test or RAST
• Measures specific IgE antibodies to a disk coated with specific drugs.
• Sensitization to muscle relaxants may remain for 3 decades, whereas
sensitization to β – lactam antibiotics may fade over time.
• Basophil histamine release assay.
In Vivo tests
* Skin tests to be done 4 – 6 weeks after anaphylactic episode.

7. What impedes diagnosis under anaesthesia..…?
1. Patient is draped - masks skin rashes. Therefore respiratory system and
cardiovascular system signs may be better indicators.
2. Anaesthetic drugs alter vasoactive mediator’s release, delaying possible
early recognition of anaphylaxis.
3. Some anaesthetic drugs (eg: propofol) mimic vasodilatation by causing
hypotension.
4. Scenarios which may mimic anaphylaxis are:
a. pulmonary embolism
b. myocardial infarction
c. aspiration
d. vasovagal reaction

8. Management of perioperative anaphylaxis
Principles involved
1. Withdraw the offending drug.
2. Interrupt the effects of preformed mediators
3. Prevent further release of mediators
4. Give 100 % oxygen.

9. Management of perioperative anaphylaxis..contd
•Careful history regarding adverse drug reactions
•Identification of risk patients (atopic individuals, female health care
workers with exposure to latex etc.)
•Premedicating with histamine blockers and steroids is controversial
as they may blunt the early signs of anaphylaxis and hence should be
reserved exclusively for early treatment of anaphylaxis.
•Desensitization of the individual is one approach which affords
some degree of temporary tolerance.
Prevention of perioperative anaphylaxis

10. Management of perioperative anaphylaxis..contd
•Administration of epinephrine
* effect on α1 (supports blood pressure) and β2 (provides smooth muscle
bronchial relaxation)
* 5 – 10 μg kg-1 (0.2 μg/kg) I.V. bolus for hypotension.
* 0.1 – 0.5 mg I.V. in presence of cardiovascular collapse.
•Airway support with 100% oxygen
•I.V.crystalloid (2-4 L)
•Histamine H1 blockers (diphenhydramine 0.5 – 1.0 mg kg-1) and
Histamine H2 blockers (ranitidine 150 mg or cimetidine 400 mg IV
bolus)

11. Management of perioperative anaphylaxis..contd
•Of late research shows that blockade of Histamine H3 receptor
results in improvement of left ventricular systolic function and heart
rate.
•Bronchodilators (albuterol and ipratropium bromide nebulizers)
•Corticosteroid – hydrocortisone (preferred due to earlier onset).
•Delay extubation (there may be airway swelling and inflammation
upto a day)

12. Anaphylaxis & specific anaesthesia drugs….
Local anaesthetics
•Anaphylactic reactions to amide local anaesthetics (lidocaine,
mepivacaine, prilocaine, bupivacaine, levobupivacaine and ropivacaine)
are extremely rare.
•Metabisulfite in local anaesthetics can cause reactions.
•Vasovagal response, tachycardia, light-headedness, metallic taste and
perioral numbness.
•Most common is a delayed hypersensitivity reaction (type IV reaction)
or contact dermatitis.
Prevention:
•Use preservative free preparations * Skin challenge tests

13. Anaphylaxis & specific anaesthesia drugs….
Muscle Relaxants
•Most common anaesthetic mediators of anaphylaxis.
•Account for 69.2 % of anaphylactic reactions under anaesthesia.
•Inciting factors are the 2 quaternary or tertiary ammonium ions.
•Suxamethonium causes more commonly than NDMRs.
•Primary exposure is explained by sensitisation to quaternary or tertiary
ammonium ions present in over the counter cosmetic preparations.
•Neostigmine and morphine also contain ammonium ions which can
cross react with muscle relaxants.

14. Anaphylaxis & specific anaesthesia drugs….
Muscle Relaxants…contd..
•Direct mast cell degranulation is mediated by D-tc,
atracurium, cisatracurium, doxacurium and mivacurium.
•Increased incidence of anaphylactic reactions and deaths with
use of rocuronium warrant further study.
•Radioimmunoassay and skin challenge tests can help
avoid these reactions.

15. Anaphylaxis & specific anaesthesia drugs….
Muscle Relaxants…contd..
Muscle Relaxants Incidence
Rocuronium 98%
Suxamethonium 78%
Atracurium 71%
Vecuronium 59%
Pancuronium 20%
Mivacurium 9%
Cisatracurium 1%

16. Anaphylaxis & specific anaesthesia drugs….
Opoids….
•Anaphylactic reactions are rare.
•Morphine and meperidine most commonly implicated.
•Fentanyl is deemed to be the safest.
Barbiturates….
•Incidence of anaphylactic reactions with thiopental is 1 in 30, 000.
•Best detected by detection of IgE antibodies by RAST method.
Propofol….
•Incidence of anaphylactic reactions with propofol is 1 in 60, 000.
•Reaction may be due to egg lecithin component of propofol.
•But overall, propofol is not contraindicated in egg allergy patients

17. Anaphylaxis & specific anaesthesia drugs….
Other induction agents….
•Etomidate is the most immunologically safe induction agent.
•Next is ketamine.
Benzodiazepines….
•Very rare
•More likely with diazepam.
Volatile anaesthetics….
No reports of anaphylaxis have been reported.
However immune mediated hepatic injury (halothane) can present as
rash, fever, arthralgias, eosinophilia and increased liver enzymes.

18. Anaphylaxis & specific anaesthesia drugs….
Aprotinin….
•Derived from bovine lung, antigenic in humans.
•Reactions are more common if administered within 6 months of
primary exposure.
•Seen in cardiac surgeries
Heparin….
•Derived from bovine or porcine lung.
•Antigenic in humans.
•Reactions are in the form of heparin induced thrombocytopenia (HIT)
•HIT is less common with LMWH.

19. Anaphylaxis & specific anaesthesia drugs….
Protamine Sulfate….
•Derived from salmon sperm.
•Used to reverse anticoagulant effect of heparin.
•Reactions are more common in patients who have received insulin
preparations containing protamine-zinc.
•Urticaria, systemic hypotension with pulmonary vasoconstriction
Antibiotics….
•Penicillins, cephalosporins and β-lactam antibiotics
•Vancomycin (red man syndrome), bacitracin
•Clindamycin, metronidazole, gentamicin

20. Anaphylaxis & specific anaesthesia drugs….
Other agents….
•Povidone-Iodine
•Iodinated contrast material
•Chlorhexidine.
•Latex.
•Colloids. ( albumin, dextran, hetastarch and gelatin)
•Isosulfan blue dye.

21. In Summary….
•Anaphylactic reactions can occur with just about any of the day to day
preparations used in the OR
•Early recognition of signs & symptoms and prompt management alter
the outcome successfully.
•Prevention is always preferred.
•For prevention to be effective, prior detection is essential.
•Meticulous history, skin allergy testing and perioperative preparedness
can make the difference.

22. References….
1. Miller’s Anaesthesia, 7th Edition, Vol 1:pP1378 -80
2. Anaesthesia by Aitkenhead, p423
3. “Anaphylaxis during the perioperative period” by David.L.Hepner and
Mariana.C.Castells – A Review in Anaesthesia & Analgesia; 2003 –
Nov
4. Internal Medicine by Harrison – 17th Edition
5. CMDT – 2010
6. “Anaphylaxis & adverse drug reactions in anaesthesia” by
Dr Akkamahadevi.P, Dr Archana.K.N and Dr Chowdary Sriram.B–
Karnataka Journal of Anaesthesia, Vol 12; No.1, sept 2011, p21-31