NAP 6 Perioperative Anaphylaxis CLINICAL FEATURES Dr KL

NAP 6: Perioperative Anaphylaxis CLINICAL FEATURES Dr K-L Kong, MD MBBS FRCA, Consultant Anaesthetist Dr Surendra Karanam, BSc MBBS MRCP FRCPath, Consultant Immunologist

NAP 6: Perioperative Anaphylaxis WHAT WE ALREADY KNOW • Early recognition and prompt treatment of perioperative anaphylaxis vital. • Clinical diagnosis at presentation. • Knowledge of clinical features and high index of suspicion essential. • Recognition of anaphylaxis often delayed. • Key clinical features more commonly have non-allergic cause during perioperative period.

NAP 6: Perioperative Anaphylaxis NAP 6 ANALYSIS – PRESENTING FEATURE Cardiac arrest Nausea/vomiting Allergic Anaphylaxis Laryngeal oedema/Stridor All Patients Urticaria Bradycardia Decreased/Absent CO 2 trace Patient feeling unwell Cyanosis/Oxygen desaturation Flushing/non-urticarial rash Tachycardia Bronchospasm/High airway pressure Hypotension 0% 5% 10% 15% 20% 25% 30% 35% 40% 45% 50%

NAP 6: Perioperative Anaphylaxis NAP 6 ANALYSIS – ALL CLINICAL FEATURES Itching Nausea/vomiting Absent CO 2 trace Allergic Anaphylaxis All Patients Patient feeling unwell Bradycardia Cardiac arrest Urticaria Decreased CO 2 trace Cyanosis/Oxygen desaturation Tachycardia Bronchospasm/High airway pressure Flushing/non-urticarial rash Hypotension 0% 20% 40% 60% 80% 100% 120%

NAP 6: Perioperative Anaphylaxis NAP 6 ANALYSIS – OTHER FEATURES • • • Airway problems rarely seen. Isolated cardiovascular features: 15 (5. 6%) patients. Bronchospasm more common in asthma patients. Bronchospasm more common in morbidly obese patients. No difference in presenting or clinical features in patients with/without history of coronary artery disease. • Hypotension main presenting feature in patients taking betablockers or ACE inhibitors.

NAP 6: Perioperative Anaphylaxis NMBAs – Presenting features 80% 70% 60% 50% Bronchospasm/High airway pressure Flushing/Nonurticarial Rash 40% Hypotension Urticaria 30% 20% 10% 0% Atracurium rocuronium Suxamethonium

NAP 6: Perioperative Anaphylaxis ANTIBIOTICS – Presenting features 80% Bronchospasm/High airway pressure 70% Flushing/Nonurticarial Rash 60% 50% Hypotension 40% Reduced/Absent CO 2 Trace 30% 20% 10% 0% co-amoxiclav teicoplanin

NAP 6: Perioperative Anaphylaxis CHLORHEXIDINE & PATENT BLUE – Presenting features 60% 50% Cyanosis/Oxygen Desaturation 40% Flushing/Nonurticarial Rash Hypotension 30% Laryngeal Oedema/Stridor Other Tachycardia 20% Urticaria 10% 0% chlorhexidine patent blue

NAP 6: Perioperative Anaphylaxis Time from exposure to presenting feature (mins) Number (Percentage) of patients 0– 5 176 (66. 2%) 6 – 10 44 (16. 5%) 11 – 15 13 (4. 9%) 16 – 30 19 (7. 1%) 31 – 60 7 (2. 6%) 61 – 120 3 (1. 1%) > 120 2 (0. 75%) Blank 2

NAP 6: Perioperative Anaphylaxis Time from exposure to presentation - NMBAs 30 25 20 Atracurium Mivacurium 15 Rocuronium Suxamethonium 10 5 0 0 to 5 mins 06 to 10 mins 11 to 15 mins 16 to 30 mins Greater than 120 mins

NAP 6: Perioperative Anaphylaxis Time from exposure to presentation - Antibiotics 40 35 30 0 to 5 mins 06 to 10 mins 11 to 15 mins 16 to 30 mins 25 20 15 10 5 0 Cefuroxime Co-amoxiclav Flucloxacillin Gentamicin Metronidazole Piperacillin and Tazobactam Teicoplanin Vancomycin

NAP 6: Perioperative Anaphylaxis Time from exposure to presentation – Chlorhexidine and Patent Blue dye 8 7 6 0 to 5 mins 5 6 to 10 mins 11 to 15 mins 4 16 to 30 mins 31 to 60 mins 3 61 to 120 mins Greater than 120 mins 2 1 0 chlorhexidine patent blue

NAP 6: Perioperative Anaphylaxis Time to suspect and treat anaphylaxis • Speed of response by anaesthetist varies. • Response <10 mins when presenting feature was cardiac arrest, bradycardia, reduced/absent CO 2 trace, laryngeal oedema. • Longer delays when presenting feature was hypotension, bronchospasm/high airway pressure, cyanosis, nonspecific flushing.

NAP 6: Perioperative Anaphylaxis Reduced capnograph trace and unrecordably low oxygen saturation • Reduced/absent capnograph trace in 30% of cases. No clear correlation with grade of reaction. • Unrecordably low oxygen saturation reported in 31 cases. These reactions more likely grade 4 or 5, more rapid onset, and anaphylaxis more promptly suspected and treated.

NAP 6: Perioperative Anaphylaxis DISCUSSION (1) • More women with perioperative anaphylaxis proportional to more women undergoing surgery and anaesthesia. – NMBA anaphylaxis: twice as many women – Chlorhexidine anaphylaxis: preponderance of men • Hypotension universal during perioperative anaphylaxis. Consider anaphylaxis as differential diagnosis during unexplained perioperative hypotension. • Perioperative anaphylaxis can present as isolated organ system involvement.

NAP 6: Perioperative Anaphylaxis DISCUSSION (2) • Hypotension commonest presenting feature in anaphylaxis: – Atracurium (bronchospasm/high airway pressure with suxamethonium) – Chlorhexidine, Patent Blue dye and antibiotics, – Patients taking beta-blockers or ACE inhibitors. • Rapid onset for most culprit agents – Exceptions: chlorhexidine, Patent Blue dye, oral drugs

NAP 6: Perioperative Anaphylaxis DISCUSSION (3) • Clinical features of immediate concern and prompt recognition of anaphylaxis: cardiac arrest, reduced/absent CO 2 trace, laryngeal oedema. • Other relatively frequent clinical features during anaesthesia with causes unrelated to anaphylaxis – delay in recognition and treatment. • Bronchospasm/high airway pressure may be presenting feature of anaphylaxis in asthma patients.

NAP 6: Perioperative Anaphylaxis DISCUSSION (4) • Gouel-Cheron A et al. Br J Anaesth 2017; 119: 908 -17 – End-tidal CO 2 value <2. 6 k. Pa useful independent marker of severe anaphylaxis. – Potentially useful in early diagnosis of anaphylaxis as capnography readily/continuously monitored with routine GA. – Findings not confirmed by NAP 6 data. • NAP 6 data – Patients with unrecordably low O 2 saturation experienced severe reactions with early recognition and treatment by anaesthetist.

NAP 6: Perioperative Anaphylaxis KEY FINDINGS/RECOMMENDATIONS • Presenting features of perioperative anaphylaxis may have many other causes. • Early recognition key to successful treatment. • Anaphylaxis should be considered in unexpected perioperative hypotension. • Likewise in bronchospasm (asthmatic patients). • Perioperative anaphylaxis can present as isolated organ system involvement. • Cutaneous signs uncommon presenting features. • Majority of reactions present rapidly. • Education and training in recognition/treatment of anaphylaxis recommended.

NAP 6: Perioperative Anaphylaxis Thank you

NAP 6: Perioperative Anaphylaxis Urticaria and grade of anaphylaxis 40% 35% 30% Axis Title 25% Grade 3 20% Grade 4 Grade 5 15% 10% 5% 0% Urticaria No Urticaria Axis Title

NAP 6: Perioperative Anaphylaxis Grade vs age 35 30 25 20 Grade 3 Grade 4 15 Grade 5 10 5 0 01 to 5 06 to 15 16 to 25 26 to 35 36 to 45 46 to 55 56 to 65 66 to 75 76 to 85 86 to 95

NAP 6: Perioperative Anaphylaxis Grade vs ASA 70% 60% 50% 40% Grade 3 30% Grade 4 Grade 5 20% 10% 0% ASA 1 ASA 2 ASA 3 Figure 1. Grade of Anaphylaxis as per ASA status ASA 4