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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
other
               opioid colloid
      hypnotics        4%        1%
                1%
         3%

ATB
15%




                                        NMBAs
                                         59%
NRL
17%
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
9%         3% 1%


20%                                 44%




           23%    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.

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Perioperative Anaphylaxis

  • 2. scope Prevalence and incidence Cause of perioperative anaphylaxis Diagnosis Management
  • 3. 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
  • 4.
  • 5. other opioid colloid hypnotics 4% 1% 1% 3% ATB 15% NMBAs 59% NRL 17%
  • 6.
  • 7.
  • 8.
  • 9. 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
  • 10. 1.Extent of sign of anaphylaxis In most cases perioperative anaphylaxis is characterized by severe respiratory and cardiovascular manifestration !
  • 11.
  • 12.
  • 13.
  • 14. 2.Drugs and related compounds The most common is NMBAs Others are latex, antibiotics
  • 15.
  • 16. 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
  • 17. 4.Previous allergies from drugs or related compounds Careful retrospecive assessment of medical history and record Identify risk of patients during preanesthetic visit
  • 18. 5.Underlying conditions itentified underlying condition can also help to identify causative compounds Atopic individual are risk of anaphylaxis from NRL Mastocytosis, HAE
  • 19. 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
  • 20.
  • 22.
  • 23. 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)
  • 24.
  • 27.
  • 28. 9% 3% 1% 20% 44% 23% rocuronium succinylcholine atracurium vacuronium pancuronium other
  • 29. 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
  • 30. Rocuronium :high risk anaphylaxis British j anasthesia 2001: 86; 678-82
  • 31.
  • 32. 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.
  • 33.
  • 34.
  • 35. 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%
  • 36. Avoid NMBAs for such patient in future anesthesia whenever possible!
  • 37. Local anesthetic agents divide into benzoic acid esters and amide
  • 38. 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
  • 39. 1.181 1.181
  • 40.
  • 41. Challenge test remain the gold standard !
  • 42. 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
  • 43.
  • 44. 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)
  • 45. 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
  • 46. NRL Devide into 2 group - atopic - significant exposure=>HCP, Neural tube defect 20% of perioperative anaphylaxis Use questionaire Rx => avoidance
  • 47.
  • 48.
  • 49.
  • 50.
  • 51.
  • 52.
  • 53. Plasma volume expanders 4% of perioperative anaphylaxis 20% severe reaction 20 min after administration Gelatin allergy - Skin test (phadiac74) , BAT HES - skin test
  • 54. Drextran => DIAR - IgG immune complex dis - prevent by hapten dextran (1Kd) infusion - skin test is not established Albumin anaphylaxis is anectodal case
  • 55. 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
  • 56.
  • 58.
  • 59.
  • 60.
  • 61. 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
  • 62.
  • 63. 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
  • 64.
  • 65. 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
  • 66. Thank you for your attention.