Anaphylaxis, Allergy, and Adverse Drug Reactions: Important Considerations for Perioperative Management. Jerrold H. Levy, MD, FAHA, FCCM

Transcription

1 Anaphylaxis, Allergy, and Adverse Drug Reactions: Important Considerations for Perioperative Management Jerrold H. Levy, MD, FAHA, FCCM Professor of Anesthesiology Associate Professor of Surgery CoDirector Cardiothoracic ICU Duke University School of Medicine Durham, NC

2 Disclosures for Jerrold H Levy, MD, FAHA, FCCM Research Support/P.I. Employee Consultant Major Stockholder Speakers Bureau Honoraria Scientific Advisory Board DoD, Lilly, ViroPharma No relevant conflicts of interest to declare No relevant conflicts of interest to declare No relevant conflicts of interest to declare No relevant conflicts of interest to declare No relevant conflicts of interest to declare CSL Behring, Baxter, Boehringer-Ingelheim, Johnson&Johnson, Merck

3 Objectives 1) Review different adverse drug reactions and life threatening anaphylactic and allergic reactions a clinician may encounter 2) Understand different mechanisms of anaphylaxis and agents often responsible for reactions including drugs, blood products, and environmental agents including latex 3) Discuss therapeutic approaches to treating and preventing anaphylactic reactions and cardiopulmonary dysfunction that occurs

4 ADVERSE DRUG REACTIONS

5 PREDICTABLE REACTIONS Overdosage or toxicity Side effects Secondary/Indirect effects Drug interactions

6 UNPREDICTABLE REACTIONS Dose-independent Not related to drug s actions Related to immune response (allergy)

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8 ANAPHYLAXIS Acute inflammatory response Inter-relationships with CV system, endothelium, and coagulation Mast cell/basophil activation by IgE Complement activation by IgG Non-immunologic mast cell/complement activation

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10 DIAGNOSING ANAPHYLAXIS: SIGNS AND SYMPTOMS

11 SYMPTOMS Difficulty breathing Chest discomfort Dizziness, malaise Burning, tingling, itching

12 CARDIOVASCULAR Hypotension, cardiac arrest Dysrhythmias Decreased SVR Pulmonary vasoconstriction

13 MEDIATORS THAT PRODUCE VASODILATION Prostaglandins: PGI 2, PGE 1, PGE 2, PGD 2 Histamine: (H 1 and H 2 effects) Kinins: bradykinin, kallikrein Leukotrienes Nitric oxide Platelet-activating factor, Substance P

14 VASCULAR ENDOTHELIUM Huraux C et al: Circulation 1999;99:53-59

15 Angioedema Well demarcated non pitting edema caused by pathological factors that cause urticaria Reaction occurs deeper in dermis and subcutaneously Face, tongue, lips, eyelids most commonly affected May cause respiratory distress if larynx involved

16 RESPIRATORY Bronchospasm/wheezing Airway edema High airway pressures Acute pulmonary edema

17 Asthma: Pathological changes

18 Asthma and Airway Inflammation Inflammatory mediators Cellular infiltration Normal Asthma Inflammation Adapted from Holgate ST, Peters-Golden M J Allergy Clin Immunol 2003;111(1 suppl):s1-s4; Holgate ST et al J Allergy Clin Immunol 2003;111(1 suppl):s18-s36; Henderson WR Jr et al Am J Respir Crit Care Med 2002;165: ; Peters-Golden M, Sampson AP J Allergy Clin Immunol 2003;111(1 suppl):s37-s42; Varner AE, Lemanske RF Jr. In Asthma and Rhinitis. Oxford, UK: Blackwell Science, 2000:

19 CLINICAL FINDINGS Bronchospasm was most difficult feature to treat 3/4 deaths occurred in these patients Postmortem showed acute emphysema and pulmonary edema

20 CAUSES OF WHEEZING Reactive airways Pulmonary edema Pneumothorax Anaphylaxis Aspiration

21 CAUSES OF WHEEZING Endobronchial intubation Airway obstruction ETT obstruction Pulmonary emboli

22 CLINICAL SIGNS Circulatory collapse 68% Cardiac arrest 11% Bronchospasm 23% Widespread flush 55% Edema 26%

23 DIFFERENTIAL DIAGNOSIS OF ANAPHYLAXIS Administration of sedative, hypnotic, or anesthetic drugs Asthma/bronchospasm Cardiogenic shock Disconnection or overdosage of vasoactive drug infusions Dysrhythmias Tension pneumothorax

24 DIFFERENTIAL DIAGNOSIS OF ANAPHYLAXIS Pericardial tamponade Postextubation stridor Pulmonary edema Pulmonary embolus Septic shock/sirs Vasovagal reactions Venous air embolism

25 MECHANISMS OF ANAPHYLAXIS Mast cell/basophil activation by IgE Complement activation by IgG and direct activation Non-immunologic inflammatory activation

26 GRANULOCYTES Complement Activation Leukoagglutinins AGGREGATION PULMONARY LEUKOSTASIS Prostaglandins Leukotrienes Lysosomal Enzymes O 2 Free Radicals ENDOTHELIAL DAMAGE INCREASED PERMEABILITY PULMONARY HYPERTENSION Levy JH. Anaphylactic Reactions in Anesthesia and Intensive Care. 2nd ed. Stoneham Mass. : Butterworth-Heinemann;1992: 103.

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28 DRUGS THAT RELEASE HISTAMINE Antibiotics: vancomycin Hyperosmotic agents Muscle relaxants Opioids Polybasic compounds Thiobarbiturates

29 Levy JH: Anesthesiology 1989;70:756

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32 Agents most often implicated in perioperative anaphylaxis Antibiotics Blood products Muscle relaxants Proteins (aprotinin, latex and protamine)

33 NMBAs and Allergy Complete antigens Some are mirror molecules Potential histamine release Potential for false positive skin tests

34 How to make a muscle relaxant Take 2 bisquarternary ammonium ions, and separate nm (Å) with 8-10 molecules Linear molecule is depolarizing (decamethonium, succinylcholine) Add bulky side groups (benzylisoquinolines) or insert into steroidal ring

35 STEROID MUSCLE RELAXANTS: Molecular Structure N CH 3 O C=O CH 3 N + N N + CH 3 CO O Vecuronium

36 NMBAs Benzylisoquinolines Amino steroids Acetylcholine homologues

37 Levy JH: Anaphylactic reactions to NMBAs: are we making the correct diagnosis? Anesth Analg 2004;98: French reports use undiluted drug in prick testing; ROC, VEC are 10 and 1 mg/ml. Dhonneur showed if French prick test validity were applied, all reacting volunteers would have fulfilled criteria of allergy. (Moneret-Vautrin DA:Allerg Immunol (Paris) 2002; 34:233) and (Rev Fr Allergol 1997;42:776).

38 LATEX ALLERGY Preoperative considerations: Allergy to bananas, avocados, kiwis, mangos, stone fruits Chronic care (latex-based products) Spina bifida with multiple ops Intraop anaphylaxis:?etiology Repeated surgical procedures (>9) Intolerance to latex-based products Healthcare workers

39 Guidelines for managing potential drug reexposures: 3) Initial (test) doses may produce anaphylaxis, thus clinicians must be cautious during a re-exposure. Test doses should be administered intravenously at least 10 min before the loading dose Levy, Adkinson: Anesth Analg. 2008;106:

40 THERAPY(1) Stop antigen Maintain airway / 100% O2 Discontinue anesthetic agents Volume expansion Epinephrine

41 THERAPY(2) Catecholamines/AVP Antihistamines Bronchodilators Corticosteroids Bicarbonate Airway evaluation

42 THERAPY(3) If hypotension persists, consider Vasopressin Echo: TEE/TTE RV failure? hour ICU/PACU observation Steroid coverage

43 ARGININE VASOPRESSIN Peptide from the posterior pituitary V 1 -receptor: pressor response V 2 - receptor: ADH effect During CPR, plasma AVP levels higher in ROSC pts IIb recommendation in ACLS 2000

44 VASOPRESSIN Inhibits product of cgmp by IL- 1 and ANP Inhibits ATP-activated potassium channels of VSM Counteracts pathologically activated vasodilation

45 Contraction (%) EPINEPHRINE VASOPRESSIN Histamine Histamine Epinephrine (log M) Vasopressin (log M) Tsuda, Tanaka, Levy: Anesth Analg 2001;93:1453

46 VASOPRESSIN Landry DW: Vasopressin deficiency contributes to the vasodilation of septic shock. Circulation 1997;95:5:1122 Argenziano: Management of vasodilatory shock after cardiac surgery. JTCS 1998;116:973. Argenziano: vasopressin in the treatment of vasodilatory shock after LVAD placement. Circulation 1997;96:9:286 Landry DW: The pathogenesis of vasodilatory shock. N Engl J Med. 2001;345:588.

47 THERAPY(4): RV FAILURE Reassess ventilation: I/E ratios? Treat bronchospasm Phosphodiesterase inhibitors Vasodilators: NO, PGE 1,PGI 2 LA norepinephrine Mechanical support: IABP,VAD, CPB

48 SUMMARY Understanding the spectrum of ADRs and anaphylaxis is important when evaluating potential reactions. If you have a reaction, draw blood for Tryptase-within 1-2 hrs, then 24 hrs later

49 SUMMARY (2) Skin testing with NMBAs and opioids need to be performed with appropriate dilutions to avoid false positive responses Rapid diagnosis, and aggressive therapy is important to avoid a disastrous outcome.

50 AnaphylaxisWeb.com