ALLERGIC REACTIONS TO ANAESTHETIC DRUGS

Philippe SCHERPEREEL

TARGU MURES 2009

Professor Emeritus of Anaesthesiology Centre Hospitalier Rgional Universitaire 59037 LILLE FRANCE p-scherpereel@chru-lille.fr

ALLERGIC RISK IN ANESTHESIA

IS SUBJECT TO CONTROVERSY BUT SEEMS RELATIVELY

FREQUENT: 9 19 % OF THE ACCIDENTS LINKED TO ANESTHESIA REPRESENTING IN FRANCE (2002)

1/22,500 Anesthesia 1/6,500 anesthesia implicating a myorelaxant

SEVERE: 5 17 % OF DEATHS

DEFINITIONS

ALLERGIC REACTION (HYPERSENSITIVITY) Immune pathological reaction In an individual previously sensitized Linked to the production of

Specific antibodies (IgE: humoral immunity) Sensitized cells (T lymphocytes: cell immunity)

ANAPHYLACTIC REACTION (Anaphylaxy) Immune specific response Induced by IgE antibodies (immediate hypersensitivity) Producing a mast cell and basophiles degranulation ANAPHYLACTOID REACTION (non specific histamine release) Pharmacological effect on mast cells and basophiles Histamine release proportional to the speed of injection and the drug concentration Not an immune reaction

ANAPHYLACTIC REACTION MECHANISM

FIRST SENZITIZING CONTACT

Production of IgE antibodies

HISTAMINE

TRYPTASE

BASOPHILES MAST CELLS

ANAPHYLACTIC REACTION MECHANISM

SECOND FIRING CONTACT

Dgranulation of mast cells IgE Specific histamine release

HISTAMINE

TRYPTASE

RECEPTORS H1 H2

ANAPHYLACTIC REACTION MECHANISM

FIRST CONTACT

Dgranulation of mast cells

HISTAMINE

Non specific histamine release

RECEPTEURS H1 H2 TRYPTASE

THE COMPLEMENT PATHWAY

CLASSICAL PATHWAY ALTERNATIVE PATHWAY

C1
C4 C2 C3 b
Opsonin LYTIC PATHWAY

C 3 (H2O)
Properdin Factors D et B

C3 C5
C5 b 6789
Membrane Attack Complex

C3 a
anaphylatoxin

C5 a
anaphylatoxin

BJA 1995;74:217-28

CLINICAL SYMPTOMS
STAGES OF INCREASING SEVERITY 1. GENERALIZED SKIN AND MUCOUS SYMPTOMS
Rasch, urticaria with or without angioneurotic edema

2. MILD MULTIVISCERAL ATTACK

Skin and mucous symptoms Hypotension, tachycardia Bronchial hyper reactivity : cough, dyspnea

3. SEVERE MULTIVISCERAL, ATTACK LIFE THREATENING

Collapse, tachy or bradycardia, dysrthymias Bronchspasm Skin symptoms sometimes missing appearing after tension recovery

4. CIRCULATORY INEFFICIENCY, CARDIAC ARREST 5. DEATH BY CPR FAILURE

CLINICAL SYMPTOMS OF ANAPHYLAXY DURING ANESTHESIA ACCORDING TO THE MECHANISM

from PM Mertes et al. Ann Fr Anesth Reanim 2004;23:1133-43

Clinical symptoms
Skin symptoms - Rash - Urticaria - Angioneurotic edema Cardiovascular symptoms - Hypotension - Collapse - Cardiac arrest - Bronchospasm

Anaphylactic reaction (n=491)

326 (66,4 %) 209 (42.6 %) 101 50 386 (78.6 %) 127 (25.9 %) 249 (50.7 %) 29 (5.9 %) 196 (39.9 %)

Anaphylactoid reaction (n=221)

206 (93.6 %)* 151 (68.3 %) 54 (24.5 %) 16 (7.2 %) 70 (31.7 %)* 50 (22.6 %) 12 (5.4 %) 0 43 (19.5 %)

* P <0.05

GRADES OF SEVERITY OF REACTIONS DURING ANAESTHESIA ACCORDING TO THE MECHANISM

from PM Mertes et al. Ann Fr Anesth Reanim 2004;23:1133-43

%
60 50 40 30 20 10 0

Anaphylactic (n=491) Anaphylactoid (n=221)

II

III

IV

GRADES OF SEVERITY

COMPLEMENTARY INVESTIGATIONS
IMMEDIATE:

during and immediately after the accident Histamine (blood) Tryptase IgE specific antibodies 6 weeks after the accident Skin tests

DELAYED:

Prick tests Intra dermal reactions (IDR)* Histamine release from leucocytes Specific allergens detection (RAST) Basophil Activation Test (BAT) with triple labelling

Biological dosages

PLASMA TRYPTASE MEASUREMENT Tryptase concentration (u.liter-1) 26 20 14 8 2

1 2 4 8 16 32 64

- Enzyme . Exclusively stored in mast cells . In favour of anaphylactic reactions . Blood peak (>25 g/l): 30 min-2 h . Half life time in plama = 90 min

Hours after reaction

According to MATSON et P et al. 1991;33:211-12

ANAPHYLAXY DURING ANAESTHESIA

Casal agent % Myorelaxants Latex Hypnotics Opiods Colloids Antibiotics Miscellaneous 1989* 5n=821) 81.0 0.5 11.0 3.0 0.5 2.0 2.0 1992* (n=813) 70.2 12.5 5.6 1.7 4.6 2.6 2.8 1994* (n=1030) 59.2 19.0 8.0 3.5 5.0 3.1 2.2 1996* 1998** 2002*** (n=734) (n=571) (n=712) 61.6 16.6 5.1 2.7 3.1 8.3 2.6 69.1 12.1 3.7 1.4 2.7 8.1 2.9 54.0 22.3 0.8 2.4 2.8 14.7 3.0

*Ann Fr Anesth Reanim

**Br J Anaesth 2001

*** Ann Fr Anaesth Reanim 2004

CAUSAL AGENTS INVOLVED IN ANAPHYLACTIC REACTIONS DURING ANAESTHESIA IN FRANCE IN 2001 - 2002
daprs PM MERTES Ann Fr Anesth Reanim 2004;23:1133-43

Collodes 2,8% (n=14) Hypnosdatifs 0,8% (n=4) Antibiotiques 14,7% (n=74)

Morphiniques 2,4% (n=12) Autres 3%

Curares 54% (n=271)

Latex 22,3% (n=112)

MYORELAXANTS INVOLVED IN ANAPHYLACTIC REACTIONS DURING ANAESTHESIA IN FRANCE IN 2001 - 2002

according to PM MERTES Ann Fr Anesth Reanim 2004;23:1133-43

Atracurium 23,7% (n=64)

Pancuronium 2,6% (n=7)

Rocuronium 26,2% (n=71)

Mivacurium 1,1% (n=3)

Vcuronium 7% (n=19)

Suxamethonium 37,6% (n=102)

Cisatracurium 1,8% (n=5)

COMPARISON BETWEEN THE PERCENTAGE OF EXPOSED PATIENTS AND ANAPHYLACTIC REACTIONS TO THE MYORELAXANTS IN 2001 2002 according to PM Mertes and al Ann Fr Anesth reanim 2004;23:1133-43

EXPOSED PATIENTS* (n = 5.721. 172) % ATRACURIUM CISATRACURIUM SUCCINYL CHOLINE ROCURONIUM VECURONIUM PANCURONIUM MIVACURIUM 60,3 14,7 8,2 6,5 4,9 1,9 3,5

ANAPHYLACTIC REACTIONS (n=271) % 23,7 1,8 37,6 26,2 7,0 2,6 1,1

100 %
* Data obtained from GERS Hospitals and Hospital Panel - MAP 1

100 %

ANAPHYLAXY TO LATEX DURING ANAESTHESIA

PREVALENCE

22,3 % OF ANAPHYLACTIC REACTIONS DURING ANAESTHESIA 72.9 FEMALES / 27.1 MALES COMPARED TO ANAPHYLAXY DUE TO MYORELAXANTS Younger patients Less severe reactions PATIENTS WITH HIGH RISK OF LATEX ALLERGY 1. History of latex allergy
- unexplained shock during a previous anaesthesia - pruitus, rash, edema after contact with latex (gloves, condoms, balloons)

2. Repeated exposures to Latex

- Health care providers - Urologic malformations (spina bifida : 40%) - multiple surgical interventions +atopy
3.

Food allergy
- bananas, avocados, kiwis, exotic fruits

HISTORY OR ALLERGY IN PATIENTS WITH ANAPHYLACTIC REACTION TO LATEX AND MYORELAXANTS, IN FRANCE IN 2001 - 2002
according to PM MERTES Ann Fr Anesth Reanim 2004;23:1133-43

MYORELAXANTS (n=271) % ATOPY 10,3

LATEX (n=112) % 26,0

p <0,005

ASTHMA FOOD ALLERGY

7,4

21,4

< 0,005

1,5

26,8

< 0,0001

ANAPHYLAXY TO LATEX DURING ANAESTHESIA

MECHANISMS
EQUIPMENTS FOR ANAESTHESIA AND SURGERY CAN EXPOSE PATIENTS TO ANAPHYLACTIC REACTIONS BY : DIRECT CONTACT WITH: Skin (facial mask, tourniquet) Mucuous tubes, drains) Organs (gloves, instruments) Vessels (catheters) INHALATION OF LATEX PARTICLES: Anesthetic circuit: 1.5 to 2.8 of Latex natural proteins in suspension in the rubber Air in the operating theater : adsorption of Latex natural proteins on the starch powder of surgical gloves

ANAPHYLAXY TO LATEX DURING ANAESTHESIA

DIAGNOSTIC
PATIENTS WITH HIGH RISK OF LATEX ALLERGY SKIN TESTS: PRICK TEST - At the forearm - With fresh latex extract standard - Compared with a solution of codeine and a negative control after 15 minutes - Prefered to IDR and scratch tests DOSAGES OF LATEX SPECIFIC IgE - Less the: rast tests (time consuming, expensive) last (Latex allergo sorbent test not reliable: 18.8 % - But the coated allergen particule test (CAP) positive for Latex specific IgE>0.35 kUI-1 - Reliable: 56.0 %

ANAPHYLAXY TO LATEX DURING ANAESTHESIA

PROPHYLAXY
INFORMATION + + + - In all the sites: O.R., recovery room, ward - To all the people: surgeons, anesthetists nurses - By all means: chart, bracelet, strap LATEX FREE EQUIPMENT: LATEX FREE KITS - Gloves - Circuits, ventilation devices DRUGS AND MATERIAL TO TREAT AN ANAPHYLACTIC SHOCK READY TO USE SCHEDULED FIRST OF THE LIST

DECISIONAL TREE ALGORITHM

PREVIOUS ANAPHYLACTIC REACTION DURING ANESTHESIA EMERGENCY

PLANNED SURGERY
SEARCH FOR ANESTHETIC PROTOCOL

UNKNOWN
CONSULTATION OF ALLERGY IN ANESTHESIA

IDENTIFIED
CLINICAL HISTORY COMPATIBLE

YES
CONSULTATION OF ALLERGO IN ANESTHESIA

NO
OTHER DIAGNOSTIC TO BE CONSIDERED

LATEX FREE ENVIRONMENT AVOID MYORELAXANTS HISTAMINERELEASING DRUGS

HISTORY OF ATOPY, ALLERGY SKIN TESTS: ALL SUSPECTED DRUGS AND RELATED (CROSS SENSITIZATION) BLOOD MEASUREMENTS IgE.

TREATMENT OF ANAPHYLACTIC SHOCK DURING ANESTHESIA 1. STOP INJECTION OR INFUSION WHEN POSSIBLE 2. ADVISE THE SURGICAL TEAM DECISION
Abstention Simplification Acceleration or arrest of surgery

3. OXYGEN: FiO2 = 1 4. CONTROL OF THE AIRWAY, IF NOT YET DONE VENOUS ACESS 5. EPINEPHRINE IV
Grade 1 Not necessary Grade 2 Bolus 10 20 g by titration Grade 3 Bolus 100 200 g by titration Grade 4 cardiac arrest chest compressions epinephrine: 1 mg IV AT EACH PHASE OF CPR FOLLOWED BY IV INFUSION (0.005-0.1 g.kg-1min-1) vascular filling: cristalloids (30 ml.kg-1) ethylstarch (30 ml.kg-1)

SPECIAL CASES
BRONCHOSPASM

Salbutamol by nebulizer When severe or resisting to the treatment

Salbutamol IV Bolus 100 200 g Infusion 5 - 25 g.min Epinephrine by IV infusion Corticosteroids are not immediately efficient PREGNANT WOMAN

Ephephrine 10 g IV every 1-2 minutes up to 0.7 mg/kg-1 If insufficient Epinephrine

PATIENTS TREATED BY BETA BLOCKERS

Increased doses of epinephrine x 2- 5 times Add eventualy glucagon 1 2 mg IV In case of severe cardiovascular collapse refractory to Epinephrine Norephnephrine 0.1 g.kg-1.min-1

CONCLUSIONS
EVEN RARE AND SOMETIMES SUBJECT TO CONTROVERSIES THE ANAPHYLAXY DURING SURGERY IMPLIES :

1. To test all patients and only the patients having an history of anaphylactic reaction
specialised consultations of allergy in anaesthesia

2. When there is an allergy suspected to one myorelaxant test all

risk of cross sensitization

3. Be prepared to treat:
protocols of treatments (posters in or simulators) kits of blood sampling drugs ready to use

4. Prophylaxy is based exclusively on:

anesthesia without myorelaxant latex free equipment and material information + + + patient (card), team there is no efficient premedication