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Allergy and anesthesia
- 1. Immune Function and Allergic Response Karim Maasri PGY1 April 30, 2010 Karim Maasri MD-AUBMC
- 2. Basic Immunologic Principles HOST Humoral DEFENSE Cellular Antibody-Mediated Antigen (1st exposure) immune response Engulfed by Free Antigens Display of Antigens by infected cells Activation Macrophage Activation Becoming B Cell Cytotoxic T cell Giving rise Antigen Presenting Cell Stimulating Plasma Cell Helper T Cell Secretion Memory helper T Cell Active Cytotoxic Antigen T cells Memory B Cells Karim exposure) Memory T Cells (2nd Maasri MD-AUBMC Antibodies
- 3. The antigen Molecule stimulating an immune response Anesthesiologists Polypeptides Protamine Use of few antigens Large macromolecules Dextrans Other drugs Simple organic compounds with low molecular weight Immunogenic Stable bond with Hapten- circulating proteins / macromolecular tissue micromolecules Karim Maasri MD-AUBMC complex
- 4. Thymus – Derived (T – Cell) Lymphocytes Thymus of Immature Fetus T-Cells lymphocytes Subpopulations No specific Regulatory of T cells stimulation Cells Suppressor cells Helper cells Killer cells Destruction of myobacteria, Transplant fungi, viruses rejection In HIV infection Defense against Cytotoxic cells tumor Karim Maasri MD-AUBMC cells
- 5. Bursa – Derived (B – Cell) Lymphocytes Important in producing cells responsible for Ab synthesis Helper T-cell lymphocytes Suppressor T-cell lymphocytes Specific Specific lymphocyte plasma line cells Karim Maasri MD-AUBMC
- 6. Antibodies Ag binding to Fab Antigen Binding Sites Variable region on heavy chain Conformational Light Variable region on change Chain light chain Disulfide Bridges Constant region on light chain Activation of Fc receptor Heavy Chain Constant region on heavy chain Karim Maasri MD-AUBMC
- 7. Monocytes and Macrohpages Circulating monocytes Confined to specific organs (Lungs) Macrophages Ingesting Ag Presenting Ag Mediator Inflammatory Synthesis Tumorocidal Facilitating B-Lymphocyte and T-Lymphocyte response Microbicidal Karim Maasri MD-AUBMC
- 8. Polymorphonuclear Leukocytes (Neutrophils) First cells appearing in acute inflammatory reaction Containing Activation Hydrolases Neutral Proteases Hydroxyl radicals Lysosomes Superoxide Microbial Hydrogen peroxide killing Karim Maasri MD-AUBMC
- 9. Eosinophils Function in host defense UNCLEAR Presence at Parasitic infections Tumors Allergic reactions Karim Maasri MD-AUBMC
- 10. Basophils 0.5% - 1% of circulating granulocytes in blood Surface with IgE receptors Similar function to those on mast cells Karim Maasri MD-AUBMC
- 11. Mast Cells Important in immediate hypersensitivity responses Tissue Fixed Location in perivascular space Skin Lung Intestine Release of active mediators Surface with IgE receptors Activation important to hypersenitivity responses Immune Nonimmune Stimuli Stimuli Karim Maasri MD-AUBMC
- 12. Proteins – Cytokines / Interleukins Synthesis by macrophages Activation Endothelial cells Secondary messengers White cells IL-1 Fever TNF Neuropeptide release Endothelial cell activation Increased adhesion molecule expression Important in infection and inflammatory responses Neutrophil priming Hypotension Myocardial suppression Catabolic state Karim Maasri MD-AUBMC
- 13. Proteins – Cytokines / Interleukins Activation Extravasation into alveolar space Adherence of neutrophils to pulmonary capillaries IL1, IL8, TNF Karim Maasri MD-AUBMC
- 14. Proteins – Complement Primary humoral response Activation of to Ag-Ab binding complement system Important effector system of inflammation Activated Ab 20 different proteins Binding to Other complement proteins Cell membranes Activation of complement system Classic Pathway Alternate Pathway IgG / IgM binding to Ag Endotoxins or drugs Karim Maasri MD-AUBMC
- 15. Proteins – Complement Antigen + C3a + C4A + C5a Antibody C1 Complex C2a + C4b fragments Important humoral and chemotactic Classic Pathway C3 convertase properties Alternate Pathway C3 hydrolysis C3b + C3a fragments Recognizing bacteria C5 cleaved into C5a directly and indirectly and C5b by attracting phagocytes Swelling of cell C5b + C6 + C7 + C8 + C9 formation of membrane Increasing adhesions And attack complex of phagocytes to Ag busting Cell Lysis Karim Maasri MD-AUBMC
- 16. Proteins – Complement Regulation of complement system by series of inhibitors Angioneurotic edema Hereditary (autosomal dominant) Acquired (lymphoma, lymphosarcoma, CLL, macroglobulinemia) C1 esterase deficiency Recurrent increased vascular permeability of Trauma Surgery No cause specific subcutaneous and serosal tissues (angioedema) Laryngeal obstruction Respiratory abnormalities Cardiovascular abnormalities Pathologic manifestation of complement activation Protamine administration Karim Maasri MD-AUBMC Acute pulmonary vasoconstriction
- 17. Effects of Anesthesia on immune system Transfused Anesthesia Depression of blood + nonspecific host products resistance mechanisms Surgery Coincident infections Immunologic Direct and effects of hormonal other drugs effects of used anesthetic drugs Karim Maasri MD-AUBMC
- 18. Type I Reactions Independent of Complement Antigen Binding of IgE Ab to Fc receptors + Antigen IgE - Ag Fc receptor IgE Cross-linking of IgE Degranulation Intracellular activation Mast cell / Release of mediators Anaphylaxis Basophil cell Extrinsic Asthma Allergic rhinitis Karim Maasri MD-AUBMC
- 19. Type II Reactions Antigen Complement activation and cell lysis IgG or IgM Killer T Cell Fc receptor Individual ABO – incompatible transfusion reactions own cell Drug – induced anemia Heparin – induced thrombocytopenia Karim Maasri MD-AUBMC
- 20. Type III Reactions Antigen IgG or IgM Soluble protein Insoluble Protein – Ab complex Complement activation Recruitment of Inflammatory cells Tissue Injury Classic Serum sickness after snake antisera Immune complex vascular injury ? Protamine mediated pulmonary vasoconstruction Karim Maasri MD-AUBMC
- 21. Type IV Reactions Second contact with same antigen Lymphocyte Antigen regulation Macrophage Lymphokines activation Mononuclear cell infiltration Delayed tissue injury Sensitized Tissue rejection T -cell Graft-versus-host reactions Contact dematitis Tuberculin immunity Karim Maasri MD-AUBMC
- 22. Intraoperative Allergic Reactions Once in every 5,000 to 25,000 anesthetics Mortality rate of 3.4% Allergic reactions due to an IV drug 90% Time (minutes) 5 Vasodilation Most dangerous manifestation Circulatory collapse Venous return May be the only manifestation Refractory hypotension Karim Maasri MD-AUBMC
- 23. Recognition of Anaphylaxis during Regional and General Anesthesia Respiratory System Coughing Dyspnea Wheezing Chest Discomfort Sneezing Laryngeal Edema Pulmonary Compliance Fulminant Pulmonary Edema Acute Respiratory Failure Karim Maasri MD-AUBMC
- 24. Recognition of Anaphylaxis during Regional and General Anesthesia Cardiovascular System Disorientation Diaphoresis Dizziness Loss of Consciousness Malaise Hypotension Retrosternal Oppression Tachycardia Dysrhythmias SVR Cardiac Arrest Pulmonary HTN Karim Maasri MD-AUBMC
- 25. Recognition of Anaphylaxis during Regional and General Anesthesia Cutaneous System Urticaria (Hives) Itching Flushing Burning Periorbital Edema Tingling Perioral Edema Karim Maasri MD-AUBMC
- 26. Arachidonic Acid Metabolites Activation Arachidonic Mast Acid Cell Metabolism Lipoxygenase pathway Cylco-oxygenase pathway Leukotrienes Prostaglandins Classic slow reacting Substance C4, D4, E4 PG D2 of anaphylaxis Bronchoconstriction Bronchospasm Capillary permeability Vasodilation TX B2 Vasodilation Coronary vasoconstriction Pulmonary HTN Myocardial depression Capillary permeability Protamine Karim Maasri MD-AUBMC reactions
- 27. Kinins Kinins Small Peptides Vasodilation Mast Cell Capillary permeability Kinins Bronchoconstriction Basophil Cell Stimulation of vascular endothelium Release of vasoactive factors Prostacyclin EDRF (NO) Karim Maasri MD-AUBMC
- 28. Platelet – Activating Factor Activation Mast Cell Unstored Lipid Platelet – Activating Factor Very potent ? Aggregation of PAF Physiologic effect at 10-10 M Leukocytes’ Platelets’ Activation Activation Release of inflammatory Capillary permeability products Smooth muscle contraction Intense Wheal and flare response Karim Maasri MD-AUBMC
- 29. Non-IgE Mediated Reactions – Complement Activation Complement Activation Immunologic pathway: Ab mediated (Classic) Non-immunologic pathway (Alternative) Multimolecular self assembly proteins Release of biologically active fragments of C3, C5 C3a, C5a ANAPHYLATOXINS Histamine Smooth Increase in release from Interleukin muscle capillary mast/basophil synthesis contraction permeability cells Karim Maasri MD-AUBMC
- 30. Non-IgE Mediated Reactions – Complement Activation Directed against C5a antigenic determinants IgG Interaction with high or granulocyte surfaces affinity receptors on PMNs and platelets Leukocyte Chemotaxis LEUKOAGGLUTININS Aggregation Activation Embolus Microvascular occlusion Clinical Expression Transfusion reaction Liberation of Pulmonary vasoconstriction inflammatory (protamine transfusion) products ARDS Septic Shock Karim Maasri MD-AUBMC
- 31. Non-IgE Mediated Reactions – Non Immunologic Release of Histamine Molecules administered Histamine release in a during the dose-dependent, perioperative period nonimmunologic fashion Mechanism Not well understood What is know Basophils not involved Only cell population responding Human cutaneous mast cells to drugs and endogenous stimuli Equimolar basis Atracurium, d-Tubocurarine, Same ability for metocurine degranulation Clinically Newer aminosteroidal agents Minimal effect on recommended dose (Rocuronium, Rapacuronium) Karim Maasri MD-AUBMC histamine release
- 32. Treatment Plan Anaphylactic Reaction Vasodilation Hypotension Capillary permeability + Hypoxia Bronchospasm Severe reactions Aggressive therapy Lower respiratory obstruction Pulmonary hypertension Persistent hypotension Laryngeal obstruction Persistence of symptoms 5h-32h ICU 24h for observation Karim Maasri MD-AUBMC
- 33. Treatment Plan Airway maintenance 100% Oxygen Intravascular volume expanders Epinephrine Karim Maasri MD-AUBMC
- 34. Treatment Plan Airway maintenance + Oxygen Administration Anaphylactic Reaction Ventilation / Perfusion abnormalities 100% O2 Hypoxemia Ventilatory Support Follow Up response with ABGs Karim Maasri MD-AUBMC
- 35. Treatment Plan Discontinuation of all anesthetic drugs Hypotension induction Not bronchodilators of choice Anaphylactic Reaction Inhalational drugs Bronchospasm Hypotension Interference with body’s compensatory mechanism to cardiovascular collapse Halothane Stop all Sensitization of Inhalational myocardium to drugs epinephrine Karim Maasri MD-AUBMC
- 36. Treatment Plan Providing volume expansion Anaphylactic Reaction Intravascular space Interstitial space 40% Quick Process Acute Hypotension Persistence of Hypotension No advantage for any Lactated Ringer’s Colloid 2L – 4L + 25 ml/kg – 50 ml/kg Normal Saline Karim Maasri MD-AUBMC
- 37. Treatment Plan Providing volume expansion Accurate assessment of intravascular volume TEE Guidance of intervention After anaphylaxis Fulminant noncardiogenic pulmonary edema + Loss of intravascular volume Careful hemodynamic monitoring while replenishing volume Karim Maasri MD-AUBMC
- 38. Treatment Plan Epinephrine Drug of choice during resuscitation in anaphylactic shock -adrenergic effect Vasoconstriction Reversal of hypotension 2 receptor stimulation Bronchodilation Inhibition of mediator release from mast cells and basophils Hypotensive patient Volume 5g – 10g IV + + Epinephrine Cardiovascular collapse 0.1mg – 1 mg IV Epinephrine Laryngeal edema without hypotension Maasri MD-AUBMC Epinephrine Karim S/C
- 39. Secondary Treatment Antihistamines Unclear indication Diphenhydramine 0.5mg/kg – 1mg/kg Competing with histamine over receptor No inhibition of anaphylactic reaction ? antidopaminergic effects Slow infusion to prevent potential hypotension Karim Maasri MD-AUBMC
- 40. Secondary Treatment Catecholamines Resuscitation Persistent hypotension Bronchospasm Patient with Give anaphylactic Catecholamine reaction Epinephrine Titrate according to response 0.05g/kg/min - 0.1g/kg/min Norepinephrine Those with refractory hypotension to SVR Karim Maasri MD-AUBMC
- 41. Secondary Treatment Bronchodilators Bronchospasm as major feature Ipratropium Patients receiving -adrenergic blockers Karim Maasri MD-AUBMC
- 42. Secondary Treatment Corticosteroids Anti-inflammatory effects Infusion of corticosteroids Time (hours) 4 6 12 24 Anaphylactic Reaction Benefits of Attenuation of corticosteroids late phase reactions IgE mediated reactions 0.25g - 1g IV methylpredisone Complement mediated reactions 1g - 2g IV methylpredisone Catastrophic pulmonary vasoconstriction after protamine transfusion reactions Karim Maasri MD-AUBMC
- 43. Secondary Treatment Bicarbonate Persistent hypotension Rapid Acidosis Reduction in epinephrine effect on heart and systemic vasculature Sodium Bicarbonate 0.5meq/kg – 1 meq/kg Every 5 minutes according to response Karim Maasri MD-AUBMC
- 44. Airway Evaluation Profound Facial Time for laryngeal edema extubation edema Deflation of Evaluation Airway ET tube cuff of trachea edema Reassess before extubation Leak No Leak WAIT Extubate Keep Intubated Karim Maasri MD-AUBMC
- 45. Vasopressin Important drug for refractory shock Hypotension Vasodilatory Shock Cardiac Output Inability of - Activation of adrenergic vasodilatory + mechanisms to mechanisms compensate Infusion: 0.01units/min Karim Maasri MD-AUBMC
- 46. Perioperative management Allergic Reactions Drugs: 1% - 3% risk of allergic reaction 6% - 10% Americans: 5% with allergy to 1 or 2 drugs Adverse Reactions Adverse Reactions Pharmacological action of drug Opioid Dose dependant Allergy Nausea Predictable Vomiting Mild Serious Local release Overdose of histamine Unintentional route of administration Karim Maasri MD-AUBMC
- 47. Perioperative management Side effects Most common adverse drug reactions Undesirable pharmacologic actions occuring at usual prescribed dose Morphine Dilatation of venous capacitance bed Effect depending Heart Rate on patient’s blood volume Sympathetic Tone In depleted patients Karim Maasri MD-AUBMC Rapid Hypotension
- 48. Perioperative management Drug interactions Predictable Dose Dependant IV Benzodiazepine IV Fentanyl + HYPOTENSION Sedative – Hypnotic Drug Karim Maasri MD-AUBMC
- 49. Perioperative management Unpredictable adverse drug reactions Dose Dependant Related to Allergic genetic reactions differences Small percentage Enzyme of patients deficiency Clinical manifestations not Sulfa Drugs in resembling known G6PD deficient pharmacologic action patients TIME SPAN Exposure to drug Manifestations Karim Maasri MD-AUBMC
- 50. Immunologic Mechanisms of Drug mechanism Different Any Immunologic Antigen Responses Different reactions in different patients Penicillin Different reactions 1 patient Type I Type II Type III Type IV Anaphylaxis Hemolytic Serum Contact Anemia Sickness Dermatitis Angio- Localized neurotic Rash edema Karim Maasri MD-AUBMC
- 51. Evaluating a patient with allergic reactions Hard Identifying the drug Relying on Temporal sequence circumstantial of drug evidence administration Allergic Reaction ANY DRUG Direct challenge of patient with the drug Only way to prove an allergic reaction DANGEROUS NOT REOMMENDED Karim Maasri MD-AUBMC
- 52. Agents implicated in Allergic Reactions Allergy to 1 muscle relaxant Multiple Agents Potential of allergy to other muscle relaxants Antibiotics Cross-reactivity because Induction Agents similarity of the active site Muscle Relaxants NSAIDs Quaternary ammonium molecule Protamine Colloid Volume Expanders Blood Products Vecuronium Pancuronium Karim Maasri MD-AUBMC
- 53. Latex Important cause of perioperative anaphylaxis Derived from the tree Hevea brasiliensis Preservatives Milky sap + Accelerators Antioxidants Increased risk Health care workers Children with spina bifida Children with urogenital abnormalities Banana Children with certain food allergies Avocado Karim Maasri MD-AUBMC Kiwi
- 54. Latex Anesthesiologists 24% with irritation / contact dermatitis Of those 12.5% with Latex – specific IgE positivity Pretreatment with antihistamine No data for prevention No data for decreasing severity Karim Maasri MD-AUBMC
- 55. Muscle Relaxants 62% - 81% of anaphylactic reactions Unique molecular features Potential allergens Divalent More in steroid derived agents Capable of cross-linking cell- Cross surface IgE linking Muscle IgE Relaxant Mediator release from mast cells / basophils Mast Cell No need for haptenating to large carrier molecules Karim Maasri MD-AUBMC
- 56. Thank You Karim Maasri MD-AUBMC