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8/12/2019 Allergic Reactions to Anaesthetic Drugs[1]
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ALLERGIC REACTIONS TO
ANAESTHETIC DRUGS
Philippe SCHERPEREEL
Professor Emeritus of AnaesthesioloCentre Hospitalier Rgional Universit59037 LILLE FRAN
[email protected] MURES 2009
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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
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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 andthe drug concentration
Not an immune reaction
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FIRST SENZITIZINGCONTACT
BASOPHILEMAST CELLTRYPTASE
Production ofIgE antibodies
HISTAMINE
ANAPHYLACTIC REACTION MECHANISM
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SECOND FIRINGCONTACT
RECEPTORS H1 H2
Dgranulationof mast cells
IgE
ANAPHYLACTIC REACTION MECHANISM
Specific histaminrelease
TRYPTASE
HISTAMINE
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FIRST CONTACT
RECEPTEURS H1 H
ANAPHYLACTIC REACTION MECHANISM
TRYPTASE
HISTAMINE
Dgranulationof mast cells
Non specifichistamine releas
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THE COMPLEMENT PATHWAY
CLASSICAL PATHWAY
LYTIC PATHWAY
ALTERNATIVE PATHWA
ProperdinFactors D et B
C3 aanaphylatoxin
C5 a
anaphylatoxin
C5 b 6789Membrane Attack Complex
C 3
C 5
C 1
C3 bOpsonin
C2
C4
BJA 1995;74:217
C 3 (H2O)
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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, dyspnea3. SEVERE MULTIVISCERAL, ATTACK LIFE THREATENING
Collapse, tachy or bradycardia, dysrthymias
Bronchspasm
Skin symptoms sometimes missing appearing after tensionrecovery
4. CIRCULATORY INEFFICIENCY, CARDIAC ARREST
5. DEATH BY CPR FAILURE
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CLINICAL SYMPTOMS OF ANAPHYLAXY DURING ANESTHESIAACCORDING TO THE MECHANISM
from PM Mertes et al. Ann Fr Anesth Reanim 2004;23:1133-43
Clinical symptoms Anaphylactic
reaction (n=491)
Anaphylactoid
reaction (n=221)
Skin symptoms
- Rash
- Urticaria
- Angioneurotic edema
326 (66,4 %)
209 (42.6 %)
101
50
206 (93.6 %)*
151 (68.3 %)
54 (24.5 %)
16 (7.2 %)Cardiovascular symptoms
- Hypotension
- Collapse
- Cardiac arrest
386 (78.6 %)
127 (25.9 %)
249 (50.7 %)
29 (5.9 %)
70 (31.7 %)*
50 (22.6 %)
12 (5.4 %)
0
- Bronchospasm 196 (39.9 %) 43 (19.5 %)
* P
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GRADES OF SEVERITY OF REACTIONS DURING ANAESTHESIAACCORDING TO THE MECHANISM
from PM Mertes et al. Ann Fr Anesth Reanim 2004;23:1133-43
0
10
20
Anaphylactic (n=491)Anaphylactoid (n=221)
30
I II III IV
40
50
60
V
GRADES OF SEVERITY
%
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COMPLEMENTARY INVESTIGATIONS
IMMEDIATE: during and immediately after the accident
Histamine (blood)
Tryptase
IgE specific antibodies
DELAYED: 6 weeks after the accident
Skin tests
Prick tests
Intra dermal reactions (IDR)*
Biological dosages
Histamine release from leucocytes Specific allergens detection (RAST)
Basophil Activation Test (BAT) with triple labelling
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PLASMA TRYPTASE MEASUREMENT
2
8
14
20
26
1 2 4 8 16 32 64Hours after reaction
Tryptaseconcentration
(u.l
iter-1)
According to MATSON et P et al. 1991;33:211-1
- Enzyme. Exclusively stored in mast cells
. In favour of anaphylactic reaction
. Blood peak (>25 g/l): 30 min-2 h
. Half life time in plama = 90 min
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ANAPHYLAXY DURING ANAESTHESIA
Casal agent % 1989*
5n=821)
1992*
(n=813)
1994*
(n=1030)
1996*
(n=734)
1998**
(n=571)
2002*
(n=71
Myorelaxants 81.0 70.2 59.2 61.6 69.1 54.0
Latex 0.5 12.5 19.0 16.6 12.1 22.3
Hypnotics 11.0 5.6 8.0 5.1 3.7 0.8
Opiods 3.0 1.7 3.5 2.7 1.4 2.4
Colloids 0.5 4.6 5.0 3.1 2.7 2.8
Antibiotics 2.0 2.6 3.1 8.3 8.1 14.7
Miscellaneous 2.0 2.8 2.2 2.6 2.9 3.0
*Ann Fr Anesth Reanim **Br J Anaesth 2001 *** Ann Fr Anaesth Reanim 2004
CAUSAL AGENTS INVOLVED IN ANAPHYLACTIC REACTIONS DURING
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Autres
3%
Hypnosdatifs
0,8% (n=4)
Latex
22,3% (n=112)
Curares
54% (n=271)
Antibiotiques14,7% (n=74)
Collodes
2,8% (n=14)
Morphiniques
2,4% (n=12)
CAUSAL AGENTS INVOLVED IN ANAPHYLACTIC REACTIONS DURING
ANAESTHESIA IN FRANCE IN 2001 - 2002daprs PM MERTES Ann Fr Anesth Reanim 2004;23:1133-43
MYORELAXANTS INVOLVED IN ANAPHYLACTIC REACTIONS DURING
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MYORELAXANTS INVOLVED IN ANAPHYLACTIC REACTIONS DURING
ANAESTHESIA IN FRANCE IN 2001 - 2002according to PM MERTES Ann Fr Anesth Reanim 2004;23:1133-43
Atracurium
23,7% (n=64)
Cisatracurium
1,8% (n=5)
Rocuronium
26,2% (n=71)
Pancuronium2,6% (n=7)
Mivacurium
1,1% (n=3)
Suxamethonium
37,6% (n=102)
Vcuronium
7% (n=19)
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COMPARISON BETWEEN THE PERCENTAGE OF EXPOSED PATIENTS AN
ANAPHYLACTIC REACTIONS TO THE MYORELAXANTS IN 2001 2002according to PM Mertes and al Ann Fr Anesth reanim 2004;23:1133-43
* Data obtained from GERS Hospitals and Hospital Panel - MAP 1
EXPOSED PATIENTS*(n = 5.721. 172) % ANAPHYLACTICREACTIONS (n=271)
ATRACURIUM 60,3 23,7
CISATRACURIUM 14,7 1,8
SUCCINYL CHOLINE 8,2 37,6
ROCURONIUM 6,5 26,2
VECURONIUM 4,9 7,0
PANCURONIUM 1,9 2,6
MIVACURIUM 3,5 1,1
100 % 100 %
ANAPHYLAXY TO LATEX DURING ANAESTHESIA
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ANAPHYLAXY TO LATEX DURING ANAESTHESIA
22,3 % OF ANAPHYLACTIC REACTIONS DURINGANAESTHESIA
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
PREVALENCE
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HISTORY OR ALLERGY IN PATIENTS WITH ANAPHYLACTIC REACTIO
TO LATEX AND MYORELAXANTS, IN FRANCE IN 2001 - 2002according to PM MERTES Ann Fr Anesth Reanim 2004;23:1133-43
MYORELAXANTS(n=271) %
LATEX(n=112) % p
ATOPY 10,3 26,0
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EQUIPMENTS FOR ANAESTHESIA AND SURGERY CANEXPOSE 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 insuspension in the rubber
Air in the operating theater : adsorption of Latex naturalproteins on the starch powder of surgical gloves
MECHANISMS
ANAPHYLAXY TO LATEX DURING ANAESTHESIA
ANAPHYLAXY TO LATEX DURING ANAESTHESIA
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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 controlafter 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 %
DIAGNOSTIC
ANAPHYLAXY TO LATEX DURING ANAESTHESIA
ANAPHYLAXY TO LATEX DURING ANAESTHESIA
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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 USESCHEDULED FIRST OF THE LIST
PROPHYLAXY
ANAPHYLAXY TO LATEX DURING ANAESTHESIA
DECISIONAL TREE ALGORITHM
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DECISIONAL TREE ALGORITHM
EMERGENCY
SEARCH FOR ANESTHETIC PROTOCOL
CONSULTATION OFALLERGY IN ANESTHESIA
CLINICAL HISTORYCOMPATIBLE
LATEX FREEENVIRONMENTAVOIDMYORELAXANTSHISTAMINE-RELEASINGDRUGS
CONSULTATION OFALLERGO IN ANESTHESIA
OTHER DIAGNOSTTO BE CONSIDERE
HISTORY OF ATOPY, ALLERGYSKIN TESTS: ALL SUSPECTED DRUGS AND
RELATED (CROSS SENSITIZATION)
BLOOD MEASUREMENTS IgE.
YES NO
IDENTIFIEDUNKNOWN
PLANNED SURGERY
PREVIOUS ANAPHYLACTIC REACTION DURING ANESTHESIA
TREATMENT OF ANAPHYLACTIC SHOCK
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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 ACES
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 FOLLOWEDBY IV INFUSION (0.005-0.1 g.kg-1min-1)
vascular filling: cristalloids (30 ml.kg-1)ethylstarch (30 ml.kg-1)
SPECIAL CASES
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SPECIAL CASES
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
BRONCHOSPASM
Ephephrine 10 g IV every 1-2 minutes up to 0.7 mg/kg-1
If insufficient Epinephrine
PREGNANT WOMAN
Increased doses of epinephrine x 2- 5 times
Add eventualy glucagon 1 2 mg IV
In case of severe cardiovascular collapse refractory to EpinephrineNore hne hrine 0.1 .k -1.min-1
PATIENTS TREATED BY BETA BLOCKERS
CONCLUSIONS
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CONCLUSIONS
EVEN RARE AND SOMETIMES SUBJECT TO CONTROVERSIESTHE ANAPHYLAXY DURING SURGERY IMPLIES :
1. To test all patients and only the patients having an history of
anaphylactic reactionspecialised consultations of allergy in anaesthesia
2. When there is an allergy suspected to one myorelaxant test allrisk 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