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Immune Function        andAllergic Response                           Karim Maasri                               PGY1     ...
Basic Immunologic Principles                                                    HOST             Humoral                  ...
The antigenMolecule stimulating an immune responseAnesthesiologists                                             Polypeptid...
Thymus – Derived (T – Cell) Lymphocytes                            Thymus of      Immature                Fetus           ...
Bursa – Derived (B – Cell) Lymphocytes                    Important in producing                    cells responsible for ...
AntibodiesAg binding to Fab                                    Antigen Binding Sites                                      ...
Monocytes and MacrohpagesCirculatingmonocytes                               Confined to                              speci...
Polymorphonuclear Leukocytes (Neutrophils)First cells appearing in acute inflammatory reactionContaining                  ...
EosinophilsFunction in host defense                                     UNCLEARPresence at              Parasitic infectio...
Basophils0.5% - 1% of circulating granulocytes in bloodSurface with IgE receptorsSimilar function to those      on mast ce...
Mast Cells  Important in immediate hypersensitivity responses   Tissue Fixed      Location in  perivascular space         ...
Proteins – Cytokines / InterleukinsSynthesis by macrophages                                    Activation                 ...
Proteins – Cytokines / Interleukins                                              Activation                               ...
Proteins – ComplementPrimary humoral response                                         Activation of    to Ag-Ab binding   ...
Proteins – Complement  Antigen                                              +     C3a + C4A + C5a      Antibody           ...
Proteins – Complement Regulation of complement system by series of inhibitorsAngioneurotic edema                          ...
Effects of Anesthesia on immune system                                                                   TransfusedAnesthe...
Type I ReactionsIndependent of  Complement                 Antigen                                                      Bi...
Type II ReactionsAntigen                                                                  Complement                      ...
Type III ReactionsAntigen                          IgG or IgM                                                        Solub...
Type IV ReactionsSecond contact with same antigen                                                            Lymphocyte An...
Intraoperative Allergic ReactionsOnce in every 5,000 to 25,000 anesthetics                      Mortality rate of 3.4%Alle...
Recognition of Anaphylaxis during Regional and             General AnesthesiaRespiratory System                           ...
Recognition of Anaphylaxis during Regional and               General AnesthesiaCardiovascular System                      ...
Recognition of Anaphylaxis during Regional and              General AnesthesiaCutaneous System                            ...
Arachidonic Acid Metabolites     Activation                                               Arachidonic                     ...
KininsKinins     Small Peptides                                             Vasodilation         Mast         Cell        ...
Platelet – Activating FactorActivation                 Mast                 Cell                                          ...
Non-IgE Mediated Reactions – Complement Activation                                Complement ActivationImmunologic pathway...
Non-IgE Mediated Reactions – Complement Activation                                                   Directed againstC5a  ...
Non-IgE Mediated Reactions – Non Immunologic Release of Histamine  Molecules administered              Histamine release i...
Treatment PlanAnaphylactic Reaction                           Vasodilation                                                ...
Treatment PlanAirway maintenance100% OxygenIntravascular volume expandersEpinephrine         Karim Maasri MD-AUBMC
Treatment PlanAirway maintenance + Oxygen Administration   Anaphylactic Reaction        Ventilation / Perfusion abnormalit...
Treatment PlanDiscontinuation of all anesthetic drugs                                                             Hypotens...
Treatment PlanProviding volume expansion             Anaphylactic Reaction Intravascular space             Interstitial sp...
Treatment PlanProviding volume expansion                      Accurate assessment of intravascular volume      TEE        ...
Treatment PlanEpinephrine    Drug of choice during resuscitation in anaphylactic shock -adrenergic effect           Vasoc...
Secondary TreatmentAntihistamines   Unclear indication   Diphenhydramine              0.5mg/kg – 1mg/kg   Competing with h...
Secondary TreatmentCatecholamines       Resuscitation               Persistent hypotension                                ...
Secondary TreatmentBronchodilators      Bronchospasm as major feature      Ipratropium       Patients receiving -adrenerg...
Secondary TreatmentCorticosteroids    Anti-inflammatory effects          Infusion of        corticosteroids               ...
Secondary TreatmentBicarbonate    Persistent hypotension                               Rapid                              ...
Airway EvaluationProfound      Facial                         Time forlaryngeal    edema                          extubati...
VasopressinImportant drug for refractory shock                                                            Hypotension     ...
Perioperative management                    Allergic Reactions                                                     Drugs: ...
Perioperative managementSide effects           Most common adverse drug reactions           Undesirable pharmacologic acti...
Perioperative managementDrug interactions               Predictable               Dose Dependant                       IV ...
Perioperative management                         Unpredictable adverse drug reactions                                 Dose...
Immunologic Mechanisms of Drug mechanism                                                        Different                 ...
Evaluating a patient with allergic reactions                      HardIdentifying   the   drug                    Relying ...
Agents implicated in Allergic Reactions                                                  Allergy to 1 muscle relaxantMulti...
LatexImportant cause of perioperative anaphylaxisDerived from the tree Hevea brasiliensis                                 ...
LatexAnesthesiologists 24% with irritation / contact dermatitis       Of     those        12.5% with Latex – specific IgE ...
Muscle Relaxants62% - 81% of anaphylactic reactions Unique molecular features                        Potential allergens  ...
Thank You Karim Maasri MD-AUBMC
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Allergy and anesthesia

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Allergy and anesthesia

  1. 1. Immune Function andAllergic Response Karim Maasri PGY1 April 30, 2010 Karim Maasri MD-AUBMC
  2. 2. Basic Immunologic Principles HOST Humoral DEFENSE Cellular Antibody-Mediated Antigen (1st exposure) immune response Engulfed byFree 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. 3. The antigenMolecule stimulating an immune responseAnesthesiologists 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. 4. Thymus – Derived (T – Cell) Lymphocytes Thymus of Immature Fetus T-Cells lymphocytes Subpopulations No specific Regulatory of T cells stimulation CellsSuppressor 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. 5. Bursa – Derived (B – Cell) Lymphocytes Important in producing cells responsible for Ab synthesis Helper T-cell lymphocytes Suppressor T-cell lymphocytes Specific Specificlymphocyte plasma line cells Karim Maasri MD-AUBMC
  6. 6. AntibodiesAg binding to Fab Antigen Binding Sites Variable region on heavy chainConformational 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. 7. Monocytes and MacrohpagesCirculatingmonocytes 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. 8. Polymorphonuclear Leukocytes (Neutrophils)First cells appearing in acute inflammatory reactionContaining Activation Hydrolases Neutral Proteases Hydroxyl radicals Lysosomes Superoxide Microbial Hydrogen peroxide killing Karim Maasri MD-AUBMC
  9. 9. EosinophilsFunction in host defense UNCLEARPresence at Parasitic infections Tumors Allergic reactions Karim Maasri MD-AUBMC
  10. 10. Basophils0.5% - 1% of circulating granulocytes in bloodSurface with IgE receptorsSimilar function to those on mast cells Karim Maasri MD-AUBMC
  11. 11. Mast Cells Important in immediate hypersensitivity responses Tissue Fixed Location in perivascular space Skin Lung Intestine Release of active mediatorsSurface with IgE receptors Activation important to hypersenitivity responses Immune Nonimmune Stimuli Stimuli Karim Maasri MD-AUBMC
  12. 12. Proteins – Cytokines / InterleukinsSynthesis by macrophages Activation Endothelial cells Secondary messengers White cellsIL-1 FeverTNF Neuropeptide release Endothelial cell activation Increased adhesion molecule expressionImportant in infection and inflammatory responses Neutrophil priming Hypotension Myocardial suppression Catabolic state Karim Maasri MD-AUBMC
  13. 13. Proteins – Cytokines / Interleukins Activation Extravasation into alveolar space Adherence of neutrophils to pulmonary capillaries IL1, IL8, TNF Karim Maasri MD-AUBMC
  14. 14. Proteins – ComplementPrimary humoral response Activation of to Ag-Ab binding complement systemImportant effector system of inflammation Activated Ab20 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. 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 phagocytesSwelling of cell C5b + C6 + C7 + C8 + C9 formation of membrane Increasing adhesions And attack complex of phagocytes to Agbusting Cell Lysis Karim Maasri MD-AUBMC
  16. 16. Proteins – Complement Regulation of complement system by series of inhibitorsAngioneurotic 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 activationProtamine administration Karim Maasri MD-AUBMC Acute pulmonary vasoconstriction
  17. 17. Effects of Anesthesia on immune system TransfusedAnesthesia 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. 18. Type I ReactionsIndependent 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. 19. Type II ReactionsAntigen 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. 20. Type III ReactionsAntigen IgG or IgM Soluble protein Insoluble Protein – Ab complexComplement 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. 21. Type IV ReactionsSecond 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. 22. Intraoperative Allergic ReactionsOnce 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. 23. Recognition of Anaphylaxis during Regional and General AnesthesiaRespiratory System Coughing Dyspnea Wheezing Chest Discomfort Sneezing Laryngeal Edema  Pulmonary Compliance Fulminant Pulmonary Edema Acute Respiratory Failure Karim Maasri MD-AUBMC
  24. 24. Recognition of Anaphylaxis during Regional and General AnesthesiaCardiovascular System Disorientation Diaphoresis Dizziness Loss of Consciousness Malaise Hypotension Retrosternal Oppression Tachycardia Dysrhythmias  SVR Cardiac Arrest Pulmonary HTN Karim Maasri MD-AUBMC
  25. 25. Recognition of Anaphylaxis during Regional and General AnesthesiaCutaneous System Urticaria (Hives) Itching Flushing Burning Periorbital Edema Tingling Perioral Edema Karim Maasri MD-AUBMC
  26. 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 D2of anaphylaxis Bronchoconstriction Bronchospasm  Capillary permeability Vasodilation TX B2 Vasodilation Coronary vasoconstriction Pulmonary HTN Myocardial depression  Capillary permeability Protamine Karim Maasri MD-AUBMC reactions
  27. 27. KininsKinins 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. 28. Platelet – Activating FactorActivation Mast Cell Unstored Lipid Platelet – Activating Factor Very potent ? Aggregation of PAF Physiologic effect at 10-10 MLeukocytes’ Platelets’ Activation Activation Release of inflammatory  Capillary permeability products Smooth muscle contraction Intense Wheal and flare response Karim Maasri MD-AUBMC
  29. 29. Non-IgE Mediated Reactions – Complement Activation Complement ActivationImmunologic 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. 30. Non-IgE Mediated Reactions – Complement Activation Directed againstC5a 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. 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. 32. Treatment PlanAnaphylactic 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. 33. Treatment PlanAirway maintenance100% OxygenIntravascular volume expandersEpinephrine Karim Maasri MD-AUBMC
  34. 34. Treatment PlanAirway maintenance + Oxygen Administration Anaphylactic Reaction Ventilation / Perfusion abnormalities 100% O2 Hypoxemia Ventilatory Support Follow Up response with ABGs Karim Maasri MD-AUBMC
  35. 35. Treatment PlanDiscontinuation 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. 36. Treatment PlanProviding volume expansion Anaphylactic Reaction Intravascular space Interstitial space 40% Quick Process Acute Hypotension Persistence of HypotensionNo advantage for any Lactated Ringer’s Colloid 2L – 4L + 25 ml/kg – 50 ml/kg Normal Saline Karim Maasri MD-AUBMC
  37. 37. Treatment PlanProviding 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. 38. Treatment PlanEpinephrine 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 5g – 10g IV + + EpinephrineCardiovascular collapse 0.1mg – 1 mg IV EpinephrineLaryngeal edema without hypotension Maasri MD-AUBMC Epinephrine Karim S/C
  39. 39. Secondary TreatmentAntihistamines 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. 40. Secondary TreatmentCatecholamines Resuscitation Persistent hypotension Bronchospasm Patient with Give anaphylactic Catecholamine reaction Epinephrine Titrate according to response 0.05g/kg/min - 0.1g/kg/min Norepinephrine Those with refractory hypotension to  SVR Karim Maasri MD-AUBMC
  41. 41. Secondary TreatmentBronchodilators Bronchospasm as major feature Ipratropium Patients receiving -adrenergic blockers Karim Maasri MD-AUBMC
  42. 42. Secondary TreatmentCorticosteroids 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. 43. Secondary TreatmentBicarbonate 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. 44. Airway EvaluationProfound Facial Time forlaryngeal edema extubation edema Deflation ofEvaluation Airway ET tube cuffof trachea edema Reassess beforeextubation Leak No Leak WAIT Extubate Keep Intubated Karim Maasri MD-AUBMC
  45. 45. VasopressinImportant drug for refractory shock Hypotension Vasodilatory Shock  Cardiac Output Inability of - Activation of adrenergic vasodilatory + mechanisms to mechanisms compensateInfusion: 0.01units/min Karim Maasri MD-AUBMC
  46. 46. Perioperative management Allergic Reactions Drugs: 1% - 3% risk of allergic reaction 6% - 10% Americans: 5% with allergy to 1 or 2 drugs AdverseReactions 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. 47. Perioperative managementSide effects Most common adverse drug reactions Undesirable pharmacologic actions occuring at usual prescribed doseMorphine 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. 48. Perioperative managementDrug interactions Predictable Dose Dependant IV Benzodiazepine IV Fentanyl + HYPOTENSION Sedative – Hypnotic Drug Karim Maasri MD-AUBMC
  49. 49. Perioperative management Unpredictable adverse drug reactions Dose Dependant Related to Allergic genetic reactions differences Small percentage Enzyme of patients deficiency Clinical manifestations notSulfa Drugs in resembling knownG6PD deficient pharmacologic action patients TIME SPAN Exposure to drug Manifestations Karim Maasri MD-AUBMC
  50. 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. 51. Evaluating a patient with allergic reactions HardIdentifying the drug Relying on Temporal sequence circumstantial of drug evidence administration Allergic Reaction ANY DRUGDirect challenge of patient with the drug Only way to prove an allergic reaction DANGEROUS NOT REOMMENDED Karim Maasri MD-AUBMC
  52. 52. Agents implicated in Allergic Reactions Allergy to 1 muscle relaxantMultipleAgents 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. 53. LatexImportant cause of perioperative anaphylaxisDerived from the tree Hevea brasiliensis Preservatives Milky sap + Accelerators AntioxidantsIncreased 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. 54. LatexAnesthesiologists 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. 55. Muscle Relaxants62% - 81% of anaphylactic reactions Unique molecular features Potential allergens Divalent More in steroid derived agentsCapable of cross-linking cell- Cross surface IgE linking Muscle IgE RelaxantMediator release from mast cells / basophils Mast Cell No need for haptenating to large carrier molecules Karim Maasri MD-AUBMC
  56. 56. Thank You Karim Maasri MD-AUBMC

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