perioperative anaphylaxis-Anaphylaxis is a severe, potentially fatal systemic allergic reaction that occurs suddenly (minutes to hours) after contact with an allergy-causing substance

Anaphylaxis is a severe, potentially fatal systemic allergic reaction that occurs suddenly (minutes to hours) after contact with an allergy-causing substance

Fatal

Death can occur in minutes, usually due to closure of airways

Type I Hypersensitivity reaction.

1. PERIOPERATIVE ANAPHYLAXIS Dr. Sanjaya Kr. Gupta Classified Specialist & Professor, Department of Anaesthesiology , Military Hospital, Prayagraj

2. → Brief intro -2021 guidelines → How will I know if its Anaphylaxis ? → Management –what is time critical ?

3. CASE HISTORY 24yrs female ASA I for Hemi Thyroidectomy (RT) on 09 Sep 22. Inv - WNL. No Comorbidities Induced with 120mg Propofol,100mcg Fentanyl,30mg Atracurium – intubated with 7mm ID ETT(O) After 5 min, BP 80/30mmHg. Inj Mephentermine 3mg administered-BP rises to 90/60mm Hg, drops to 70/50 mm Hg in 1 min- ongoing hypotension. Ventilating pressure is 45 cm H2O. Saturation 80%,tidal volume 200ml. Chest- bilateral wheeze.

4. PRESENTING SIGNS Hypotension Difficult inflating lungs Skin reaction After IV injection

5. WOULD YOU GIVE ADRENALINE? What factor will prevent you from adrenaline to treat these situation? Uncertain Diagnosis Adrenaline ,may cause harm How much would you give? What are the advantages? What are the risk?

6. MANAGEMENT ABCDE protocol 100% O2 Deepening of anaesthesia- sevoflurane Inj Adrenaline (1:10000) 1ml+1ml+1ml IV fluids 1ltr NS Salbutamol MDI puff via ETT Inj Hydrocortisone 200mg IV Started Noradrenaline infusion surgery postponed →extubated → shifted to ICU

7. HAVE AN ANAPHYLAXIS TRIGGER If hypotension is refractory to vasopressor OR If bronchospasm is ongoing after salbutamol IS THIS ANAPHYLAXIS ? 100 mcg Adrenaline may have much benefit and minimal harm.

8. DEFINITION Anaphylaxis is a severe, life-threatening, generalized or systemic hypersensitivity reaction Anaphylaxis vs Anaphylactoid Incidence ? Mortality?

9. SKIN - Urticaria , Angioedema, Pruritus, Erythema RESPIRATORY - Rhinitis, Cough, Dyspnea, Wheeze, Stridor, Voice change GI – Throat Swelling or Tightness, Dysphagia, Vomiting, Diarrhea, Cramps CVS – Hypotension, Dizziness, Syncope, Cyanosis URTICARIA ANGIOEDEMA CLINICAL MANIFESTATIONS OF ANAPHYLAXIS

10. MANAGEMENT – EPINEPHRINE Prompt administration of epinephrine with Hemodynamic monitoring is the main stay of treatment. The main factor associated with mortality is delay in epinephrine administration. Dosage &route.. Additional dose if required . Bronchodilators ( salbutamol )   Ref ; liewWK , Williamson E, Anaphylaxis fatalities and out comes in Australia, J Allergy clin immunol 2000. Pumphery.RS lesion for management of anaphylaxis from a study of fatal reactions clic exp allergy J Br soc immunol 2000.  

11. Call for help Stop all medications Maintain airway and give 100% O2 A ( Emergency drug cart & Airway cart) Adrenaline IM/ IV B Activate CPR team (Code Blue ) IV fluids C MANAGEMENT

12. INTRA VENOUS FLUID RESUSCITATION Repeated bolus of 15-25 ml per kg intravenous crystalloids to fill the dilated peripheral vessels also to compensate leakage into extra vascular space.   Ref ; Longrois D, Lejius , treatment of hypersensitivity reactions anaphylactic shock occurring during anaesthesia , Ann Fr Anaesthesia Reanimation 2017;30. Galvano VR, peri operative anaphylaxis.curr Allergy Asthma Rep 2014;14(8 )  

13. OTHER THERAPIES → Steroids Hydrocortisone 200mg bolus, followed by 100mg 6 th hrly → Antihistamine Chlorpheneramine 10mg slow iv and ranitidine 50mg IV → Bronchodilator Salbutamol-bronchospasm Ipratropium bromide Mg → Nor adrenaline → Vasopressin → Glucagon Ref; woeser KM immunol Allergy clin north Am2013 Ref ; longrois Ann Fr Anaesthesia Reanimation 2011;30 Ref; Thomas M, Crawford glucagon infusion in refractory anaphylactic shock in patients with beta blockers,Emer Med J 2005;22 (4)

14. POST RESUSCITATION CARE ICU Investigation – ABG, LFT, Urea , S Cr, T ryptase immediately,1 hr & 6-24 hrs Plasma/Urine histamine Allergy referral for testing Inform patient/report adverse event.

15. DIFFERENTIAL DIAGNOSIS Perioperative anaphylaxis should be differentiated from Exacerbation of asthma, Tension pneumothorax Myocardial infarction Pulmonary embolism C ardial tamponade C1estarase deficiency

16. PERI-OPERATIVE TRIGGERS → A small quantity of allergen is sufficient to cause anaphylaxis. The common Agents involved in lgE mediated anaphylaxis are IV Drugs –Antibiotics, Muscle Relaxants, hypnotics, opioids Blood Products & Plasma substitutes Contrast media Latex Chlorhexidine. → Outside Hospital –Food (Peanut, Seafood's) ,insects stings [[ Ref; harper NJN Dixon, et al, suspected anaphylaxis associated with anaesthesia. Analgesia 2013,64;(2)199-211

17. ANAPHYLAXIS: CAUSES OF DEATH Upper and/or Lower Airway Obstruction (70%) Cardiac Dysfunction (24%)

18. TAKE HOME MESSAGE Anaphylaxis is severe, potentially life threatening systemic hypersensitivity reaction . It can be caused by immunological, non-immunological mechanism or be idiopathic . Anaphylaxis is a clinical diagnosis and the management remains same irrespective of cause . It is difficult to diagnose intra operatively as covered by drapes , under sedation, and unable to reports pruritus. Immediate management priorities Adrenaline A 100% Oxygen B Fluids C

19. 2021 guidelines

20. crash cart trolley

21. Code blue bag

22. Code blue box

23. REFERENCES Hepner DL, Castellis MC. Anaphylaxis during the perioperative period. Anesth Analg 2003;97:1381-95 Ryder S, Waldmann C.Anaphylaxis . Continuing Education in Anaesthesia, Critical Care and Pain. Vol 4 number 4 2004 pp 111-113 Association of Anaesthesia, Critical Care and Pain. Vol 4 number 4 2004 pp111-113 Association if Anaesthesia of Great Britain and Ireland. Suspected anaphylaxis reactions associated with anaesthesia .Anaesthesia 2009;64:pages199-211

24. Thank you

25. PERIOPERATIVE TRIGGERS Non lgE Mediated anaphylaxis may be associated with drugs as NSAIDs, iodinated contrast agents.        Ref ; woosnerKM , Anaphylaxis during anaesthesia, immunol allergy clin north Am.2013;33(2 )-49  

26. INVESTIGATION Tryptase A protease released from mast cell degranulation. Tryptase level above 25mic gm per lit. Half life 1-2hrs. Max 24 hrs     Ref ; ebo DG, Fisher mm, anaphylaxis during anaesthesia, diagnostic approach. Allergy2007;62(5)471-87. Schwartz Lb at al, time course pf appearance and disappearance of human mast cell tryptase in the circulation after anaphylaxis, J clininvest 1989;89(5):1551 .

27. INVESTIGATION Plasma histamine Early increase in plasma histamine observed 60-90 minutes after anaphylaxis early elevated levels is important. Short plasma half life of histamine limits its diagnostic importance.            Ref; vadas P Perelman B, platelet activating factor, histamine and typtase levels in human anaphylaxis. J Allergy clic immunol,2013;131(1):141-9.    

28. INVESTIGATION Urine histamine Histamine and its metabolites can be detected in the urine after anaphylaxis and increased levels are more specific than the increased in the plasma histamine for anaphylaxis.     Ref; current and future approaches. J allergy clin immunol 2007:120.

29. ANAPHYLAXIS

30. DEFINITION Anaphylaxis is a severe , potentially fatal systemic allergic reaction that occurs suddenly (minutes to hours) after contact with an allergy-causing substance Fatal Death can occur in minutes , usually due to closure of airways Type I Hypersensitivity reaction.

31. MEDIATED BY TH2 cells IgE antibodies Mast cells PATHOPHYSIOLOGY

32. Bone marrow derived cells. Widely distributed near blood vessels, nerves & subepithelial tissues. Have cytoplasmic membrane bound granules that contains biologically active mediators. MAST CELLS

33. MECHANISM

34. MEDIATORS

35. EFFECTS OF EPINEPHRINE Increases BP, reverses peripheral vasodilation , ( alpha-adrenergic activity) Reduces urticaria and angioedema by vasoconstriction (alpha) Bronchodilation – relaxes bronchial smooth muscle (beta-2 adrenergic activity) Increases cardiac contractility – force and volume, increasing heart rate & BP (beta-1) Prevents further mast cell degranulation (beta)

36. MANAGEMENT cont … H1 & H2 Blockers : Chlorpheniramine (Adult:10mg, Child: 2.5-5mg), Diphenhydramine (Adult:25 – 50 mg, Child: 1mg/kg up to 50mg), Ranitidine (1mg/kg) Steroids : Hydrocortisone (200mg Adult, 100mg child), Methylprednisolone (1mg/kg)

37. Management of anaphylaxis: Bronchospasm Inhaled bronchodilators eg salbutamol. Oxygen Intubation and ventilation if needed

38. Management of anaphylaxis: Laryngeal edema Epinephrine via nebulizer Intubation or cricothyrotomy or tracheostomy

39. Management of anaphylaxis: Hypotension Trendelenberg position Volume expansion with fluids Vasopressors eg dopamine, norepinephrine, vasopressin

40. HYPERSENSITIVITY REACTIONS Type 2 Hypersensitivity : caused by antibodies that react with antigens present on cell surface or in extracellular matrix. Mediated by IgG & IgM . Examples: Autoimmune hemolytic anemia, Transfusion reactions, Haemolytic disease of new born, Myasthinia gravis.

41. HYPERSENSITIVITY REACTIONS Type 3 Hypersensitivity : Characterised by deposition of antigen-antibody complexes in tissue,activation of complement & infiltration of PMNL leading to tissue damage. Mediated by IgG & IgM Examples: Arthus reaction, serum sickness, SLE

42. HYPERSENSITIVITY REACTIONS Type 4 Hypersensitivity: Mediated by sensitized T- lymphocytes which on contact with specific antigen, release lymphokines that causes biological effects on macrophages, leucocytes & tissue cells. Occurs within 48-72 hrs of antigen challenge. Examples: Type 1 DM, Multiple sclerosis, rheumatoid arthritis.