Abstract
Sugammadex-induced bradycardia is well known and the incidence is quoted to be around 0.6–1%.1,2 While the mechanism is unknown, sugammadex-induced bradycardia can be resistant to the administration of anticholinergics 3 and may degenerate to pulseless electrical activity 4 or asystole, 5 warranting management with vasopressors and inotropes alongside standard cardiopulmonary resuscitation (CPR) measures. We report a patient who developed asystole immediately after administration of 200 mg (2.7 mg/kg) of sugammadex, which then evolved into complete heart block (CHB) requiring temporary transvenous pacing over 24 h.
An 84-year-old male weighing 73 kg with features of acute acalculous cholecystitis was scheduled for an emergency laparoscopic cholecystectomy. Significant past medical history included hypertension, hypercholesterolaemia, ischaemic heart disease with moderate systolic dysfunction (ejection fraction 37%), stable angina and chronic kidney disease with an estimated glomerular filtration rate of 45 ml/min/1.72 m2. He was independent with his activities of daily living; however, he described New York Heart Association Class 2 dyspnoea. His medications included isosorbide mononitrate, candesartan, aspirin, atorvastatin and pantoprazole. His baseline troponin level during this admission was elevated to 66 ng/l, a change from 43 ng/l (reference range ≤16 ng/l) measured three weeks prior, and this was attributed to his gallbladder inflammation and renal dysfunction. A preoperative electrocardiogram (ECG) showed sinus rhythm with a heart rate (HR) of 66/min and left bundle branch block.
Anaesthesia was induced with intravenous (IV) propofol, fentanyl and rocuronium and maintained with desflurane and oxygen–air mixture. Monitoring included a five-lead ECG, SpO2, invasive arterial blood pressure, and end-tidal CO2. Intraoperative haemodynamic parameters were unremarkable. The duration of surgery was 3 h owing to difficulties attributed to the gallbladder pathology. Intraoperative analgesia was titrated with fentanyl IV to a total of 450 µg. Rocuronium 30 mg IV was administered for tracheal intubation and a further three incremental doses of 10 mg were delivered with the last dose 40 min before neuromuscular blockade reversal with sugammadex 200 mg.
Haemodynamic parameters at the time of sugammadex administration were HR 66/min and blood pressure (BP) 108/48 mmHg. Approximately 30 s post-injection, the patient was noted to be in asystole. CPR was commenced immediately. Return of spontaneous circulation was achieved after 1 min of CPR and an adrenaline 100 µg IV bolus. His ECG showed a 2:1 block with a ventricular rate of 60/min and his BP was 124/40 mmHg. Considering the quick haemodynamic improvement and satisfactory ventilatory parameters, and with the patient becoming awake, we decided to proceed to tracheal extubation.
Within a couple of minutes post-extubation, his HR dropped to <30/min and BP declined to 70/30 mmHg. Atropine 600 µg IV and further boluses of adrenaline IV in 100 µg increments to a total of 1100 µg were administered over the next 20 min. During this time frame, his HR fluctuated between 30 and 60/min and the systolic BP between 70 and 200 mmHg, this being HR dependent. Thereafter, the patient’s conscious state deteriorated slowly, and tracheal reintubation was accomplished after administering propofol and atracurium. A 12-lead ECG revealed CHB with a ventricular rate of 29/min. Atropine 600 µg IV was repeated with no effect. Subsequently, transcutaneous external pacing was instituted with 100 mA, at a rate of 80/min, that achieved a good capture, and his BP improved and stabilised around 128/40 mmHg. An isoprenaline infusion at 4 µg/kg per min and a low dose adrenaline infusion 0.03 µg/kg per min did not increase the ventricular rate when the external pacing was momentarily ceased. Due to the ongoing requirement of external pacing, the cardiology team advised temporary transvenous pacing that was accomplished in the cardiac catheterisation laboratory uneventfully. A transthoracic echocardiogram revealed findings similar to his preoperative echocardiogram and was not suggestive of an acute coronary syndrome. Isoprenaline and adrenaline infusions were discontinued in the intensive care unit (ICU) within 30 min of patient’s arrival and vasoactive agents were not required thereafter. Transvenous pacing was continued for 24 h in ICU, intermittently reducing the pacing rate to observe any evolving native rhythm. After 24 h, the patient had an intrinsic sinus rhythm with a HR above 60/min with stable BP and was extubated. The patient was discharged home on day 5 and was advised to have follow-up with his cardiologist.
There was no significant rise in the troponin T level, (33 ng/l post-event). Anaphylaxis to sugammadex was ruled out based on serial serum tryptase measurements and an intradermal skin test. There were no significant biochemical or electrolyte derangements noted during the events surrounding the haemodynamic compromise.
The asystole followed by sustained CHB in our patient was attributed to a temporal association with sugammadex, potentiated by other contributory factors. Possible contributory factors included underlying impaired cardiac function, conduction defect, vagal response related to deflation of pneumoperitoneum, possible drug effect from co-administered fentanyl and possibly unrecognised hypercarbia and acidosis. Other rare differential diagnosis possibilities include venous air embolism and local anaesthetic toxicity from wound infiltration. While the understanding of the exact mechanism is still unknown, the absence of endogenous targets/receptors for sugammadex 6 and the real-world experience of bradycardia not responding to anticholinergics suggest a non-cholinergic idiosyncratic mechanism. The persistence of CHB in our case, long after sugammadex would have been cleared from the plasma, is difficult to explain. It can possibly be attributed to the underlying cardiac risk factors contributing to delayed resolution of the rhythm insult.
Use of isoprenaline and temporary pacing have been rarely reported in the management of sugammadex-induced bradycardia. In our patient, temporary pacing was found to be the most effective intervention to restore cardiac conduction when pharmacological options were ineffective. While external transcutaneous pacing can be quickly established, it can only be used as a transient measure and needs to be converted to a superior transvenous pacing modality if there is ongoing dependency as per our case.
In conclusion, we describe a patient with an underlying cardiac comorbidity who developed asystole followed by sustained CHB after sugammadex administration. Along with standard treatment for cardiovascular collapse, transvenous pacing was required for 24 h. Practitioners should be vigilant for this rare adverse event, especially in patients with cardiac risk factors, and should consider employing transcutaneous/transvenous pacing early, particularly if the cardiac conduction abnormality fails to improve with conventional pharmacological treatments.
