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Peri-operative
anaphylaxis
w. pongsak
scope
�Prevalence and incidence
�Cause of perioperative anaphylaxis
�Diagnosis
�Management
prevalence
�Difficult to determine incidence and prevalence
� 1 in 3500 to 1 in 13000 in french study
� IgE and non IgE mediated reaction
�Mortality 3-6 %
�Multiple drug during anesthesia
� no available diagnostic test that absolute accuracy
�NMBA usually result skin test +ve for long time
NMBAs
59%
NRL
17%
ATB
15%
hypnotics
3%
opioid
1%
colloid
4%
other
1%
history
1. Extent of sign of anaphylaxis
2. Drugs and related compounds
3. Time elapsed between administration and
onset of symptom
4. Previous allergies from drugs or related
compound
5. Underlying conditions
1.Extent of sign of
anaphylaxis
�In most cases
perioperative anaphylaxis is
characterized by severe respiratory
and cardiovascular manifestration !
2.Drugs and related
compounds
�The most common is NMBAs
�Others are latex, antibiotics
3.Time elapsed between administration
and onset of symptom
�Clinical sign usually start within 5-10 min after IV
administration but may occur in second
�NRL and antiseptics exhibit more delay onset and
generally occur in maintenance anesthesia or
recovery room
�Colloid may immediated reaction or delay onset
4.Previous allergies from drugs
or related compounds
�Careful retrospecive assessment of medical
history and record
�Identify risk of patients during preanesthetic
visit
5.Underlying conditions
�itentified underlying condition can also help
to identify causative compounds
�Atopic individual are risk of anaphylaxis
from NRL
�Mastocytosis, HAE
tryptase
�Neural serine proteinase
�Mature β-tryptase reflect mast cell activation
� Pro β-tryptase reflect mast cell number
�Mast cell or basophil
� 60-120 min collection after event
�Compare 2 sample in the same person
� Persistent elevate in…..
� False –ve & false +ve
etiology
�NMBAs
�NRL
�Antibiotics
�Colloid
�Hypnotics
�Opioids
�Local anesthetic agent
�miscellaneous
NMBAs
�All NMBAs can elicit anaphylaxis
�Short acting depolarizing is greatest risk
succinylcholine !�Induce 2 type of reactions
- IgE dependent => NH4+ main antigenic epitope
- direct mast cell activation => benzylisoquinolinium
( cisatracurium is lowest risk of mast cell activate)
aminosteroid
benzylisoquinolinium
44%
23%
20%
9% 3% 1%
rocuronium
succinylcholine
atracurium
vacuronium
pancuronium
other
�Data controversy in rocuronium
�Cross reactivity between NMBAs is 65% by skin test
and 80% by RIA
� Pattern of cross reactivity vary between person
�Cross reactivity depend on configuration,
flexibility,inter-ammonium distant
�Unusual to allergic to all NMBAs
�But keep in mind some pt. might suffer from multiple
allergies
� Subsequent anesthesia
Rocuronium :high risk anaphylaxis
British j anasthesia 2001: 86; 678-82
Skin test
�Undiluted drug except
succinylcholine,atracurium,mivacurium
� 0.03-0.05 cc for IDT
�+ve IDT => 8 mm wheal or double in size
SPT or IDT
�rocuronium and cisatracurium can elicit non
specific IDT +ve in non allergic pt.
�no currently available NMBAs for in vitro
except suxamethonium (low sensitivity)
�May use choline chloride,PAPC,morphine –
base solid phase sIgE
�Histamine release test
�BAT sen 60% spec 90%
Avoid NMBAs for such patient in future
anesthesia whenever possible!
Local anesthetic agents
�divide into benzoic acid esters and amide
�Side effect usually from vasovagal or
anxiety reaction
�Usually add epinephrine
�Anaphylaxis is very rare
�Amide-rare , ester< 1% for anaphylaxis
�Ester metabolite=> PABA usually cause
type I reaction
�Preservative => methylparaben,paraben
1.181
1.181
Challenge test remain the gold standard !
Hypotics
�Cross reactivity between thiopental sodium
barbitone,methohexital( rare anaphylaxis)
�Propofol => alkyl phenol that bear 2 isopropyl
groups that act as antigenic epitopes
- cross react with eggs ,soy and lechitins in
propofol vehicle ?
upto now no evidence support this postulate
opioids
�generalized reaction to opioids usually result
from nonspecific mast cell activation
�Skin mast cell are sensitive to nonspecific
activation , in contrast to heart,GI,lung
�How about basophil?
�Classification of opioid
- phenanthrene (morphine,codeine)
- phenylpiperedine(phentanyl,meperidine)
- diphenylheptane(methadone,propoxyphene)
�Most of reaction are not life-treatening reaction
�Fentanyl appear not to activate mast cell
�Data in cross reactivity of opioid subclass is
inconclusive
�SPT for opioids is not useful
�Placebo controlled chalenges may be required to
diagnose opioid allergy
NRL
�Devide into 2 group
- atopic
- significant exposure=>HCP, Neural tube
defect
�20% of perioperative anaphylaxis
�Use questionaire
�Rx => avoidance
Plasma volume expanders
�4% of perioperative anaphylaxis
�20% severe reaction
�20 min after administration
�Gelatin allergy
- Skin test (phadiac74) , BAT
�HES
- skin test
�Drextran => DIAR
- IgG immune complex dis
- prevent by hapten dextran (1Kd) infusion
- skin test is not established
�Albumin anaphylaxis is anectodal case
Chlorhexidine and other antiseptics
�Cationic biguanide
�Chlorhexidine salt can trigger irritant
dermatitis
�SPT 10 fold dilution of chlorhexidine
digluconate in 70% alcohol
�sIgE (c8,Phadia)
�Povidone iodine => anaphylaxis is rare
Other agent
�Hyaluronidase
�Oxytocin
�dyes
�Aprotinin
�Protamine and heparin
protamine
�Isolate from the sperm of fish
�Antidote for heparin
�Significant histamine release
�Previous exposure (NPH),heparin
neutralization, vasectomy,fish allergy may
risk for anaphylaxis
�But these finding not confirm
�Skin test ,sIgE may be helpful
Increased risk of severe protamine reactions in NPH
insulin-dependent diabetics undergoing cardiac
catheterization
� 886 cases in 20 mths 651 cases received protamine
� Received NPH 15/651
� Major reaction 4/15 in NPH group
� Major reaction 3/636 in non NPH group
Significant different in rate of reaction!
Circulation 1984 ;vol 70 : 788-792
conclusion
�Prevance of peri-operative anaphylaxis
�Diagnostic approach
� NMBAs is MCM cause
�Diagnostic test
�Anaphylaxis and anaphylactoid
�Almost procedure and medication can cause
peri-operative anaphylaxis
Thank you for
your attention.