Occurrence of Kounis syndrome under anesthesia.

Sir,

The occurrence of anaphylactic reaction during anesthesia has variable manifestations. Although frequently reported in emergency medicine,[1] allergic reaction manifesting as coronary artery spasm or acute coronary syndrome (ACS) under anesthesia has been rarely described. We report a case of anaphylaxis following intramuscular (IM) injection of diclofenac sodium under anesthesia where the hemodynamic instability rapidly progressed to acute myocardial infarction without any cutaneous or respiratory involvement.

A 47-year-old male was scheduled for the left parotid gland excision under general anesthesia (GA). On preanesthetic evaluation, he was found to be in American Society of Anesthesiologists class I physical status. He denied the history of asthma, any drug, or food allergy. The routine laboratory investigations and 12 lead electrocardiogram (ECG) were unremarkable. GA was induced in a standard manner using midazolam, fentanyl and propofol and endotracheal intubation were accomplished by intravenous (IV) vecuronium. For maintenance of anesthesia sevoflurane in oxygen – nitrous mixture was administered. After 30 min the parotid gland was excised, and surgical closure was started. At this point, IM diclofenac 75 mg was administered intragluteally. Ten minutes later, the noninvasive blood pressure (NIBP) fell to 78/40 from 112/70 mmHg, and the heart rate increased to 114/min from 90/min. A second NIBP reading taken immediately confirmed significant hypotension. Rapidly IV fluids were pushed, and sevoflurane was switched off. However, the significant fall in NIBP and tachycardia continued despite administering fluids and ECG in started showing significant ST depression. The 12 lead ECG was done which revealed ST depression and T-wave inversion in lead II, III and a ventricular fibrillation and from V2 to V5 suggestive of inferior and lateral wall myocardial infarction. As the patient had no underlying cardiac disease and there was a temporal relation between events and drug administration, anaphylactic reaction to IM diclofenac was suspected. The lips of patients were noticed to be swollen. IV hydrocortisone 100 mg, chlorpheniramine maleate 10 mg, and ranitidine 50 mg were administered immediately. IV adrenaline was not administered due to the concern of aggravation of ECG changes or precipitation of arrhythmias. In view of refactory hypotension, dopamine infusion at 10 mcg/kg/min was started. No skin involvement, an increase in airway pressure or desaturation was observed at any time.

The blood pressure of patient gradually improved with vasopressor support over 30-45 min and the in ECG ST depression decreased in magnitude. He was shifted to Intensive Care Unit (ICU) and laboratory investigations including serum tryptase, serum electrolytes, cardiac biomarkers CPK-MB, and troponin I were sent. The values of serum tryptase and cardiac enzymes were found to be raised. The cardiologist opinion was taken who suggested a diagnosis of Kounis syndrome (KS). The coronary angiography was done urgently which revealed normal coronary vasculature. The patient was electively ventilated in ICU, the ECG changes reverted back to normal within 10-12 h and dopamine was gradually tapered off. He was extubated next day and kept under observation. The patient was offered an intradermal test for diclofenac sensitivity 3 weeks later which he declined.

KS, also known as the “allergic angina syndrome” is a concurrence of coronary artery spasm or ACS with an allergic reaction. Under anesthesia, KS has been reported after administration of rocuronium[2] and cisatracurium.[3] KS has three variants,[4] type 1 includes patients with normal coronary arteries in whom acute allergic reaction induces coronary artery spasm. Patients with quiescent preexisting atheromatous disease in whom allergic insult induces plaque erosion/rupture leading to ACS comprises type II variants whereas type III involves patients with coronary thrombosis (including stent thrombosis). The present case belongs to type I variant. Pathophysiologically, KS results from degradation of mast cells in settings of allergic reaction with subsequent release of inflammatory mediators. These mediators lead to coronary spasm or plaque rupture. IM diclofenac has previously implicated in KS in nonanesthetic settings.[5] Adverse cardiac effects following administration of diclofenac and other nonsteroidal anti-inflammatory drugs are attributed to anti-prostacyclin effects of these drugs. The diagnosis of KS intraoperatively is made clinically without definite markers. There is usually short time interval between the culprit drug administration and occurrence of events. This temporal association under anesthesia is complicated by the fact that many drugs are given in rapid succession especially during the induction phase. Sometimes, the patient may have past medical history of atopy, asthma, or food allergy. The measurement of inflammatory mediators helps in supporting an allergic etiology to the event. The mediators which can be determined are histamine and mast cell tryptase in serum and N-methylhistamine in urine. As patient develops both allergic and cardiac symptoms, treatment of KS is challenging. The drugs administered can worsen allergic manifestations or aggravate cardiac involvement. There are no definitive treatment guidelines. Table 1 summarizes the concerns in the treatment of KS from Cevik et al.[6]

Table 1

Concerns with drugs used for treatment of Kounis syndrome

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