Coronary vasospasm in the setting of perioperative anaphylaxis: A case report

Anaphylaxis is a severe systemic hypersensitivity response requiring urgent medical attention, with respiratory, cardiovascular, cutaneous or gastrointestinal manifestations associated with exposure to a trigger. The clinical presentation of acute coronary syndrome (ACS) due to coronary vasospasm in the background of allergic or anaphylactic reactions was first described in 1991 and such a phenomenon has often been termed as allergic angina or Kounis syndrome. ¹ Over 90% of the cases of Kounis syndrome reported so far have been associated with serious manifestations, and of these 37% followed the intravenous administration of medications, particularly antibiotics. ² With specific reference to anaesthesia, previous presentations have been described in the context of administration of midazolam, morphine and muscle relaxants, including rocuronium and cisatracurium.^3–6 Most presentations have been described in males, between 40 and 80 years of age, and occurring within an hour of exposure to the trigger. ⁷ We present a case of anaphylaxis that manifested intraoperatively with concurrent features of coronary vasospasm following the administration of rocuronium. The patient has provided consent for publication of the case report and images, and hospital ethics approval was obtained (Human research ethics committee Ref ID: 77433). This report complies with the applicable Enhancing the QUAlity and Transparency Of health Research (EQUATOR) publishing guidelines. ⁸

A 59-year-old man (171 cm; 79 kg) was scheduled to have an emergency laparoscopic appendicectomy at a major cardiothoracic referral centre in Brisbane, Australia. His past medical history included smoking, and hypertension treated with amlodipine 10 mg daily and candesartan/hydrochlorothiazide 32 mg/25 mg daily. He had undergone nasal sinus surgery 35 years earlier without complications. He did not have any known allergies. Following pre-oxygenation, general anaesthesia was induced with intravenous doses of midazolam 1 mg, fentanyl 100 µg, oxycodone 4 mg, and an initial bolus of propofol 200 mg followed by an additional 100 mg. The patient coughed soon after the administration of intravenous rocuronium 50 mg. Once the coughing episode subsided, his trachea was intubated with an 8.5 mm internal diameter cuffed oral endotracheal tube. Bilateral air entry was confirmed with the absence of added sounds. Immediately, significant ST elevation was noticed on the electrocardiographic trace (lead II), Profound hypotension (blood pressure 58/28 mmHg) and a drop in end-tidal carbon dioxide was noticed along with a series of rhythm disturbances, including tachycardia followed by multiple ventricular ectopic complexes, bigeminy and then finally atrial fibrillation. External cardiac massage was commenced at this stage, due to the suspicion that cardiac output was absent. As per Australian and New Zealand Anaesthetic Allergy Group guidelines, initial management with a bolus of intravenous adrenaline 1 mg was followed by adrenaline infusion titrated to response through the peripheral venous line. A radial intra-arterial line and a triple lumen internal jugular venous line were then inserted, while 4 l of intravenous crystalloid and 1 l of albumin were administered. The adrenaline infusion was then continued via the central venous line. Throughout the event, there were no respiratory allergic manifestations, no reduction in oxygen saturations and no cutaneous signs other than a generalised flushing. As the ST elevation persisted even after the return of more stable haemodynamics, intraoperative myocardial ischaemia was suspected, and transoesophageal echocardiography was performed. This confirmed normal myocardial contractility and valvular function. The on-call cardiologist was contacted, and aspirin 300 mg was administered through a nasogastric tube upon his advice. In addition, intravenous hydrocortisone 100 mg, calcium chloride 10 mmol and sodium bicarbonate 50 mmol were administered. A decision was made to abort the surgery and proceed to immediate coronary angiography in an adjacent hybrid operating suite, to rule out any ACS. The angiogram identified no significant coronary disease; however, vasospasm of the proximal right coronary artery (RCA) and mid left anterior descending artery was found, which resolved following injection of intracoronary nitroglycerine (Figure 1). Intravenous magnesium sulphate 10 mmol and amiodarone 300 mg were administered while the angiography was performed. A provisional diagnosis of Kounis syndrome was made and the patient was transferred to our intensive care unit (ICU) for further haemodynamic and ventilatory support for the following 24 h. The patient was treated with antibiotics, was extubated uneventfully the next day and was subsequently discharged without any surgical intervention and made a full recovery.

Figure 1.

Coronary angiogram illustrating the coronary vasospasm with Kounis syndrome and the effect of GTN on RCA ((a) and (b)); LCx and LAD artery ((c) and (d)). (a) RCA ostium: pre GTN. (b) RCA ostium: post GTN. (c) Mid LCx and LAD: pre GTN. (d) Mid LCx and LAD: post GTN.

The tryptase level taken while in the operating theatre at approximately 30 min after the episode commenced was found to be elevated (77.1 µg/l; normal <13.5 µg/l). A subsequent sample sent from the ICU 8 h post reaction was 12.9 µg/l. The initial troponin level 1 h post-induction was within normal limits (cTnI: 18 ng/l; normal <20 ng/l), although a repeated troponin at 12 h was found to be elevated at 346 ng/l. Approximately two months after the event, anaesthetic allergy skin testing with skin prick testing (SPT) and intradermal testing (IDT) (3 mm wheal; positive reaction ≥6 mm) were performed. ⁹ SPT showed positive reactions to rocuronium (10 mg/ml), vecuronium (4 mg/ml) and pancuronium (2 mg/ml). Hence, further IDT was not performed for these drugs. A negative SPT to cisatracurium (2 mg/ml) and a positive IDT to cisatracurium (2 µg/ml) was observed. A positive SPT reaction was noticed with undiluted suxamethonium and mivacurium (50 mg/ml and 2 mg/ml, respectively). The patient had negative skin reaction to IDT for midazolam (10 µg/ml), fentanyl (0.05 µg/ml), propofol (0.1 mg/ml), oxycodone (10 µg/ml) and chlorhexidine (0.2 µg/ml). Radioimmunoassays (Phadia ImmunoCAP TM, ThermoFisher Scientific Inc., MA, USA) showed a moderate response to quarternary ammonium muscle relaxants, morphine (10.5 kU/l) and pholcodine (38.7 kU/l). The allergy clinic had organised a MedicAlert bracelet and issued a letter explaining the need to avoid muscle relaxants with future anaesthetics and pholcodine-containing cough and cold medications. A report of the adverse drug reaction was submitted to the Therapeutic Goods Administration (TGA) in Canberra, Australia (TGA Identifier: AU-TGA-0000479750).

The recommended laboratory investigations with this presentation of anaphylaxis include serum levels of tryptase, histamine, C-reactive protein, eosinophil count, cardiac enzymes and inflammatory markers. ⁷ Coronary angiography may show coronary vasospasm or stenosis with the RCA affected in more than 50% of cases. ⁷ In the description of Kounis syndrome, three variants of presentations had been discussed. ¹⁰ Type I variant (the most common variant) presents in patients with no cardiac risk factors or history of ischaemic heart disease, type II involves patients with pre-existing coronary artery disease and type III presents as allergic coronary stent thrombosis. ¹⁰ Management of anaphylaxis may resolve cardiac symptoms in patients with type I, while type II patients need conventional management of their ACS features. Type III also requires urgent aspiration of intrastent thrombotic materials and histological examination of the stent materials to confirm the diagnosis.^7,10 The key challenge in the management is the simultaneous treatment of both the anaphylaxis and ACS based on the initial presentation and the variants. ¹¹ Pre-existing coronary artery disease and administration of intravenous adrenaline for anaphylaxis management may worsen the myocardial ischaemia. Coronary symptoms should be managed conventionally, and early coronary angiography is mandatory to rule out coronary vasospasm.

Coronary vasospasm resulting in an ACS is an unusual but serious and potentially fatal manifestation of anaphylaxis. While anaesthetists should be aware of the potential for coronary vasospasm during an allergic reaction, standard management of both the allergic reaction and an ACS are required, until the diagnosis of coronary vasospasm is confirmed by coronary angiography. It is imperative for physicians involved in perioperative care to be aware of this unusual condition for effective and timely management.