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PERIOPERATIVE MANAGEMENT

           OF

 ANAPHYLACTIC REACTIONS
PROF. MRIDUL M. PANDITRAO


           CONSULTANT
DEPARTMENT OF ANESTHESIOLOGY AND
           CRITICAL CARE
      RAND MEMORIAL HOSPITAL
            FREEPORT
          GRAND BAHAMA
  THE COMMONWEALTH OF BAHAMAS
1.   Importance of Diagnosis.
2.   Goals of Diagnosis
3.   Risk factors in patients.
4.   Suppression of Mediators Release.
5.   Tests to be done at the time of
     reaction.
6.   Tests to be done 4-6 weeks after
     reaction.
7.   Documentation & Medico legal
     Implications.
8.   Pre anesthetic testing.
IMPORTANCE OF DIAGNOSIS

1. Epidemiological.

2. Medico legal.

3. To prevent reactions in subsequent
  anesthetics.
GOALS OF DIAGNOSTIC TESTING


1.Cause of reaction.

 2. To pinpoint a specific drug.

3. Which other drug could produce similar
  reaction.
RISK FACTORS IN PATIENTS
 1. Rare in neonates and Geriatrics

 2. Rare in Shock states

 3.Behavioral changes in mast cells

 4. Low levels of Renin Angiotensin systems

 5. Relation with h/o Atopy or Allergy
RISK FACTORS IN PATIENTS (CONTD)

 6. Female : Male – 4:1
    ↑ IgA, IgM, IgG → Polio virus & bovine albumine
    Female Sex hormones- Prolactin ↑ses Cell
                                mediated responses
       Androgenic hormones- Immunosuppressive

 7. Previous exposure- not important

 8. β blocked patients – Difficult to treat
                          Needs ↑ doses
SUPPRESSION OF MEDIATOR RELEASE
1.   Adenyl cyclase- ↑ cAMP synthesis →↓ mast cell
     degranulation. Prostaglandins, histamine ( small
     doses ) & β agonists ↑ adenyl cyclase. Epinephrine
     acts via β receptors.

2.   Corticosteroids act → cytokines →↓ mast cell activity.

3.   Phosphodiesterase inhibitors→ ↑cAMP by
     inhibiting its breakdown.

4.   Disodium cromoglycate inhibits
     Ca influx into cell & prevents initiation of response.
TESTS PERFORMED DURING REACTION
1.Plasma histamine: 0-1ng/ml. Half life is only 10 minutes.
  Level > 20ng/ml shows histamine involved reaction.

2. Urinary Methyl Histamine : 0-118mcg/24hours sample
   10 in 10 patients →↑ plasma histamine.
   4 in 10 patients →↑ urinary methyl histamine.

3. Immunoglobulin E levels-↑ indicates reaction.
     * Drug specific IgE.

4. Complement levels is serum : 55-110ng/ml.

5. Mast Cell Tryptase- 10ng/ml (2-23ng/ml).
   25% of Mast Cell protein- degranulation – liberated.
   Half life- 90 min. 1 hrs, 6 hrs & 24 hrs- sensitive test.
TESTS DONE 4-6 WEEKS AFTER THE REACTION


   Time allowed to normalize.

   All drugs used should be tested.

   Patient to be made aware.
SKIN TESTING
 Main stay in our hands as labs are distant.
 Skin of back and anterior face of forearm.

 ho anaphylaxis- positive for plasma
  H, Tryptase, Urinary Methyl H.
 Operation Theatre Complex- Resuscitation
  measures , Drugs, IV fluids, Equipment.
 Monitors – pulse, BP, resp,
  O2 saturation.
 Sweating /discomfort.
CONTD.



 0.4% phenol in saline- negative - < 2-4mm dia
 9% codeine phosphate- positive- > 15mm dia
 Drug test positive- wheal > 7-8mm dia
 Each prick test – observed 15 minutes .
 Next drug- 30 mins after previous.
 2 drugs on each forearm/ day.
 Injection site examined 12-24 hrs- late reaction.
 Not useful for colloids & contrast media.
 Cross sensitivity should also be tested.
2 TYPES OF SKIN TESTING

    Intra dermal injection-1 in 100 con of drug
    used - flare or wheal. If negative- Less
    dilutions may be tried in strongly suggestive
    case with caution.

   Prick test- drop of undiluted drug placed on
    forearm- prick with sterile needle through
    drop.

   Moderate to severe reactions-seen & treated.
RADIO IMMUNO ASSAY


   Reflects IgE bound to mast cells.

   Antigen ( drug) + patient’s serum –
    incubated- antigen antibody complex
    formed.

   Complex + radio labeled anti IgE –
    incubated bound radioactivity assessed.
SKIN TEST+ RIA- CONCLUSIONS

 ST more specific than RIA- particular drug.
 Drug specific RIA – not available for all
  drugs.
 ST+RIA- preferable.

 Cross sensitivity – better with RIA.

                      Thio and NMBD.



      LEUCOCYTE & BASOPHIL- H - not specific.
MEDICO LEGAL IMPLICATIONS
                    CLEAR DUTIES
1.   Diagnose & treat.
2.   Investigations in immediate, postop 4-6
     weeks as per availability.
3.   Skin testing – 4-6 weeks. All drugs and
     cross.
4.   Documentation: all events – intra - post –
     late post op on case paper& main hospital
     records.
5.   Communicate results to patients and
SUBSEQUENT ANAESTHESIA
•   After listening to these tests - All patients- skin test &
    RIA.
•   No predictive value. Not practical.

PRE-ANAESTHETIC TESTING:
• Done in patients with positive H/O reaction during
  anaesthesia or any treatment.
• Possible in elective- but not in emergency.
• Testing schedule:
       History, previous records – study & document.
       Skin testing planned – all precautions . All drugs to be
        used, cross sensitivity.
       All testing negative – does not rule out possibility. All
        precautions & resuscitative measures -ready.
PREFERENCES

•   Premedication- fentanyl, pethidine over
    morphine.
•    Induction- ketamine/ propofol /thiopentone.
•   Inhalational anaesthesia preferred over TIVA.
•   Regional anaesthesia- lesser no. of drugs, less
    sensitivity to local anaesthetic.
•   Prefer Starches over Haemacoel.
•   Preventive measures – corticosteroids,
    disodium cromoglycate, β agonists, epinephrine.
EMERGENCY CASES


 No time for testing.
 If previous records available – avoid those
  drugs
 other preferences as per the routine cases.

 ketamine / propofol / thiopentone

 Mivacurium / pancuronium / vecuronium

 Inhalational better than TIVA.

 Regional anaesthesia better than general
  anaesthesia.
Thank You
FUTURE DEVELOPMENTS

•   Rare event so simulated anaphylaxis drill – practical
•   Desensitization by exposure to increasing doses still
    inconclusive.
•   More efficient H receptor blockers & other mediator
    blockers.
•   Safer drug designing eliminating anaphylaxis
    component.
•   Methods to measure trigeriness of mast cell.
•   Measurement of circulating IL-4,5, still distant
    possibility.

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Perioperative management of anaphylactic reactions

  • 1. PERIOPERATIVE MANAGEMENT OF ANAPHYLACTIC REACTIONS
  • 2. PROF. MRIDUL M. PANDITRAO CONSULTANT DEPARTMENT OF ANESTHESIOLOGY AND CRITICAL CARE RAND MEMORIAL HOSPITAL FREEPORT GRAND BAHAMA THE COMMONWEALTH OF BAHAMAS
  • 3. 1. Importance of Diagnosis. 2. Goals of Diagnosis 3. Risk factors in patients. 4. Suppression of Mediators Release. 5. Tests to be done at the time of reaction. 6. Tests to be done 4-6 weeks after reaction. 7. Documentation & Medico legal Implications. 8. Pre anesthetic testing.
  • 4. IMPORTANCE OF DIAGNOSIS 1. Epidemiological. 2. Medico legal. 3. To prevent reactions in subsequent anesthetics.
  • 5. GOALS OF DIAGNOSTIC TESTING 1.Cause of reaction. 2. To pinpoint a specific drug. 3. Which other drug could produce similar reaction.
  • 6. RISK FACTORS IN PATIENTS 1. Rare in neonates and Geriatrics 2. Rare in Shock states 3.Behavioral changes in mast cells 4. Low levels of Renin Angiotensin systems 5. Relation with h/o Atopy or Allergy
  • 7. RISK FACTORS IN PATIENTS (CONTD) 6. Female : Male – 4:1 ↑ IgA, IgM, IgG → Polio virus & bovine albumine Female Sex hormones- Prolactin ↑ses Cell mediated responses Androgenic hormones- Immunosuppressive 7. Previous exposure- not important 8. β blocked patients – Difficult to treat Needs ↑ doses
  • 8. SUPPRESSION OF MEDIATOR RELEASE 1. Adenyl cyclase- ↑ cAMP synthesis →↓ mast cell degranulation. Prostaglandins, histamine ( small doses ) & β agonists ↑ adenyl cyclase. Epinephrine acts via β receptors. 2. Corticosteroids act → cytokines →↓ mast cell activity. 3. Phosphodiesterase inhibitors→ ↑cAMP by inhibiting its breakdown. 4. Disodium cromoglycate inhibits Ca influx into cell & prevents initiation of response.
  • 9. TESTS PERFORMED DURING REACTION 1.Plasma histamine: 0-1ng/ml. Half life is only 10 minutes. Level > 20ng/ml shows histamine involved reaction. 2. Urinary Methyl Histamine : 0-118mcg/24hours sample 10 in 10 patients →↑ plasma histamine. 4 in 10 patients →↑ urinary methyl histamine. 3. Immunoglobulin E levels-↑ indicates reaction. * Drug specific IgE. 4. Complement levels is serum : 55-110ng/ml. 5. Mast Cell Tryptase- 10ng/ml (2-23ng/ml). 25% of Mast Cell protein- degranulation – liberated. Half life- 90 min. 1 hrs, 6 hrs & 24 hrs- sensitive test.
  • 10. TESTS DONE 4-6 WEEKS AFTER THE REACTION  Time allowed to normalize.  All drugs used should be tested.  Patient to be made aware.
  • 11. SKIN TESTING  Main stay in our hands as labs are distant.  Skin of back and anterior face of forearm.  ho anaphylaxis- positive for plasma H, Tryptase, Urinary Methyl H.  Operation Theatre Complex- Resuscitation measures , Drugs, IV fluids, Equipment.  Monitors – pulse, BP, resp, O2 saturation.  Sweating /discomfort.
  • 12. CONTD.  0.4% phenol in saline- negative - < 2-4mm dia  9% codeine phosphate- positive- > 15mm dia  Drug test positive- wheal > 7-8mm dia  Each prick test – observed 15 minutes .  Next drug- 30 mins after previous.  2 drugs on each forearm/ day.  Injection site examined 12-24 hrs- late reaction.  Not useful for colloids & contrast media.  Cross sensitivity should also be tested.
  • 13. 2 TYPES OF SKIN TESTING  Intra dermal injection-1 in 100 con of drug used - flare or wheal. If negative- Less dilutions may be tried in strongly suggestive case with caution.  Prick test- drop of undiluted drug placed on forearm- prick with sterile needle through drop.  Moderate to severe reactions-seen & treated.
  • 14. RADIO IMMUNO ASSAY  Reflects IgE bound to mast cells.  Antigen ( drug) + patient’s serum – incubated- antigen antibody complex formed.  Complex + radio labeled anti IgE – incubated bound radioactivity assessed.
  • 15. SKIN TEST+ RIA- CONCLUSIONS  ST more specific than RIA- particular drug.  Drug specific RIA – not available for all drugs.  ST+RIA- preferable.  Cross sensitivity – better with RIA. Thio and NMBD. LEUCOCYTE & BASOPHIL- H - not specific.
  • 16. MEDICO LEGAL IMPLICATIONS CLEAR DUTIES 1. Diagnose & treat. 2. Investigations in immediate, postop 4-6 weeks as per availability. 3. Skin testing – 4-6 weeks. All drugs and cross. 4. Documentation: all events – intra - post – late post op on case paper& main hospital records. 5. Communicate results to patients and
  • 17. SUBSEQUENT ANAESTHESIA • After listening to these tests - All patients- skin test & RIA. • No predictive value. Not practical. PRE-ANAESTHETIC TESTING: • Done in patients with positive H/O reaction during anaesthesia or any treatment. • Possible in elective- but not in emergency. • Testing schedule:  History, previous records – study & document.  Skin testing planned – all precautions . All drugs to be used, cross sensitivity.  All testing negative – does not rule out possibility. All precautions & resuscitative measures -ready.
  • 18. PREFERENCES • Premedication- fentanyl, pethidine over morphine. • Induction- ketamine/ propofol /thiopentone. • Inhalational anaesthesia preferred over TIVA. • Regional anaesthesia- lesser no. of drugs, less sensitivity to local anaesthetic. • Prefer Starches over Haemacoel. • Preventive measures – corticosteroids, disodium cromoglycate, β agonists, epinephrine.
  • 19. EMERGENCY CASES  No time for testing.  If previous records available – avoid those drugs  other preferences as per the routine cases.  ketamine / propofol / thiopentone  Mivacurium / pancuronium / vecuronium  Inhalational better than TIVA.  Regional anaesthesia better than general anaesthesia.
  • 21. FUTURE DEVELOPMENTS • Rare event so simulated anaphylaxis drill – practical • Desensitization by exposure to increasing doses still inconclusive. • More efficient H receptor blockers & other mediator blockers. • Safer drug designing eliminating anaphylaxis component. • Methods to measure trigeriness of mast cell. • Measurement of circulating IL-4,5, still distant possibility.