This content has been generated for SALG by the Perioperative Allergy Network

Case 1

A patient underwent general anaesthesia for urgent laparoscopic cholecystectomy. Following a modified rapid sequence induction with propofol, remifentanil and rocuronium, it was noted the patient’s heart rate had increased from ~100 to ~150bpm, with a fall in blood pressure from 127/63 to 65/33. Mild erythema over the upper chest and face was noted. A clinical emergency was declared resulting in assistance from several consultant anaesthetists. IV adrenaline (1x 100mcg IV) was given with resolution of the hypotension and tachycardia. Ephedrine was subsequently given for a further episode of hypotension.   Following discussion with the surgical team, the case was cancelled. The patient was successfully extubated after a period of monitoring under general anaesthesia. Recovery was uneventful with resolution of the erythema and tachycardia and the patient was subsequently discharged to the ward.  Samples were taken for mast cell tryptases and the patient referred to immunology for further investigation.

The differential diagnoses included anaphylaxis (potential causative agents rocuronium or cefazolin) or relative overdose of induction agents in an obese and anxious patient, with possible underlying hypovolaemia.

Case 2

A patient attended for their second total knee replacement 3 months after the first was undertaken uneventfully. Teicoplanin and midazolam were administered prior to spinal anaesthesia. The patient reported nausea, became bradycardic and hypotensive and developed hypoxia and erythema. A diagnosis of anaphylaxis secondary to teicoplanin was made. The patient was intubated, ventilated and given an adrenaline infusion. Mast cell tryptases were sent and the procedure cancelled.

Case 3

A patient underwent uneventful induction of anaesthesia using propofol, fentanyl and rocuronium. After a central venous catheter was inserted, the patient was transferred to theatre and anaesthesia maintained with isoflurane. Following skin preparation and administration of cefuroxime and teicoplanin the blood pressure was noted to be low. The patient was placed head down and intravenous fluids were increased to no effect. Immediate review of ventilation revealed a poor end tidal CO2 trace. Anaphylaxis was declared.

Case 4

Intravenous co-amoxiclav and metronidazole were administered to a cardiovascularly stable, anaesthetised patient prior to surgery. Rising airway pressures, falling end tidal CO₂ , decreased tidal volumes and a significant drop in invasively monitored blood pressure led to an anaesthetic emergency being declared. The position of the endotracheal tube and patency of breathing circuit were confirmed and a bolus of metaraminol was given with no response. Cardiopulmonary resuscitation (CPR) was commenced. The presenting rhythm was PEA. Adrenaline 1mg was given. The metronidazole infusion was stopped. Blood gas analysis revealed good oxygenation, normal potassium with no obvious cause for the cardiac arrest. A brief period of return of spontaneous circulation (ROSC) occurred after 15 minutes but this was short lived despite further boluses of IV adrenaline. The rhythm alternated between PEA and VF. Bilateral surgical thoracostomies were performed for suspected tension pneumothorax. A central venous catheter was inserted and adrenaline and noradrenaline infusions administered. An echocardiogram revealed a moderate pericardial effusion considered not to be amenable to drainage with no right ventricle collapse.  After 90 minutes of CPR and a total of 23mg adrenaline, resuscitation efforts were abandoned.

Commentary

Perioperative anaphylaxis can be challenging to identify due to the wide range of differential diagnoses, including exaggerated physiological responses to induction agents, airway manipulation and surgical interventions. Anaphylaxis should be considered whenever unexpected and significant cardiovascular or respiratory compromise occurs and treated promptly.¹ The Perioperative Allergy Network (PAN) in collaboration with the Resuscitation Council UK (RCUK) have published an algorithm for the emergency management of peri-operative anaphylaxis¹ which aligns with the Quick reference handbook.²  Emergency guidance should be used to improve outcomes in the management of infrequent challenging scenarios.³

First-line treatment of peri-operative anaphylaxis is intravenous adrenaline (epinephrine). An initial dose of 50 micrograms (0.5 ml of 1 mg/ 10 ml [1:10,000]) is recommended in adults and children aged 12 years and over.¹ Adrenaline must be supported by intravenous crystalloid fluid. Multiple large volume fluid boluses may be required (up to 3-5L in adults).¹

If signs of anaphylaxis persist despite boluses of adrenaline, an adrenaline infusion should be initiated. A low-dose adrenaline infusion, given via a peripheral venous line, is an effective alternative if central venous access is not immediately available. If there is a poor clinical response to an adrenaline infusion and appropriate fluid resuscitation, a second-line vasopressor should be given, in addition to adrenaline.¹

Intravenous adrenaline should be administered as per advanced life support protocols if cardiac arrest occurs. Prolonged cardiopulmonary resuscitation (including extrapulmonary life support, if available) should be considered, as anaphylaxis is a potentially reversible cause of cardiac arrest.⁴

Fatal cases of anaphylaxis should be referred as soon as possible to the UK Fatal Anaphylaxis Registry. Local laboratories should be advised to retain all peri-mortem samples to facilitate post-mortem investigation.

Peri-operative anaphylaxis occurs most commonly following induction. During this period multiple drugs are given over a short period of time making it difficult to identify the causative agent. All patients with suspected peri-operative hypersensitivity reactions should be referred to a specialist allergy service for formal allergy testing, irrespective of tryptase results, to identify the causative agent(s) and facilitate safe future anaesthesia. ⁵

Teicoplanin is the most common cause of perioperative anaphylaxis. It is 17 times more likely to cause anaphylaxis than alternative antimicrobials (Case 2: patient may have had a sensitising event to teicoplanin during their first knee replacement, leading to anaphylaxis with their second exposure). Teicoplanin should be given by infusion or a slow bolus over 3-5 minutes. There is cross reactivity with vancomycin. Both can cause ‘red man’-type reactions that may mimic anaphylaxis, if given rapidly.⁶

Chlorhexidine accounts for 9% of perioperative anaphylactic reactions and must be considered as a potential causative agent.³ Chlorhexidine is a so-called hidden allergen with patients often experiencing multiple exposures (e.g. Case 3: skin preparation for peripheral and central cannulation & surgical skin preparation).

We would like to encourage anaesthetists to report incidents of suspected or confirmed perioperative allergy and to ensure that the results of investigations are added to the report when available, to enable better understanding of these incidents.

References:

1. Dodd A, Turner PJ, Soar J, Savic L; representing the UK Perioperative Allergy Network. Emergency treatment of peri-operative anaphylaxis: Resuscitation Council UK algorithm for anaesthetists. Anaes. 2024 May;79(5):535-541.
2. Association of Anaesthetists. Section 3.1 Anaphylaxis (v5). Quick Reference Handbook. April, 2022 [Accessed 10 April, 2025]
3. Simmons WR, Huang J. Operating Room Emergency Manuals Improve Patient Safety: A Systemic Review. Cureus 2019 Jun;11(6):e4888.
4. Garvey LH et al. Management of suspected immediate perioperative allergy reactions: an international overview and consensus recommendations.
   BJA 2019 Jul; 123(1): E50–E64.
5. Harper NJN et al. Anaesthesia, surgery, and life-threatening allergic reactions: epidemiology and clinical features of perioperative anaphylaxis in the 6th National Audit Project (NAP6). BJA 2018 ;121(1):159-171.
6. Electronic Medicines Compendium. Datapharm