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.