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Profound Bradycardia and Cardiac Arrest After Sugammadex Administration in a Previously Healthy Patient: A Case Report

Sanoja, Ivanna A. MD; Toth, Kenneth S. MD, PhD

doi: 10.1213/XAA.0000000000000834
Case Reports

We report the case of a 60-year-old man who underwent open radical prostatectomy for prostate adenocarcinoma. He had no known cardiac disease or symptoms other than controlled hypertension and remote history of cocaine use. The patient was given sugammadex for reversal of neuromuscular blockade and, within 1 minute, developed severe, drug-resistant bradycardia followed by pulseless electrical activity arrest. Advanced cardiac life support was initiated and continued for 15 minutes before the return of spontaneous circulation. Subsequent cardiac workup showed no abnormalities. We believe the cause of arrest was sugammadex, considering the time of administration, the absence of cardiac disease, and stable operative course.

From the Department of Anesthesiology and Pain Management, John H. Stroger Jr. Hospital of Cook County, Chicago Illinois.

Accepted for publication May 24, 2018.

Funding: None.

The authors declare no conflicts of interest.

Address correspondence to Ivanna A. Sanoja, MD, Department of Anesthesiology and Pain Management, John H. Stroger Jr. Hospital of Cook County, 1969 Ogden Ave, Chicago, IL 60612. Address e-mail to

Sugammadex (Bridion, Merck & Co, Whitehouse Station, NJ) is a modified γ-cyclodextrin that is routinely used as an effective reversal agent to rocuronium and vecuronium-induced neuromuscular blockade by binding and shifting the concentration gradient of these neuromuscular blockade agents away from the neuromuscular junction.1 However, since its introduction, serious side effects have been reported including hypersensitivity, anaphylaxis,2,3 and arrhythmias.4–7 Here, we present the case of a previously healthy 60-year-old man undergoing radical prostatectomy, who developed profound bradycardia followed by cardiac arrest immediately after the administration of sugammadex. The patient has provided written consent to publish this case.

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A 60-year-old American Society of Anesthesiologists physical status II, 82-kg man with body mass index of 28.4 was scheduled for an open prostatectomy for cT2c, Gleason 4 + 3 prostate cancer under general anesthesia. His medical history was significant for well-controlled hypertension, prediabetes, and prostate adenocarcinoma. In addition, the patient had a remote history of cocaine abuse. Electrolytes and hemoglobin were within normal limits. The patient had been enrolled in the enhanced recovery after surgery (ERAS) protocol and received preoperative gabapentin, celecoxib, and acetaminophen, but refused epidural catheter placement. He was then taken to the operating room where standard monitors were placed, before induction and an arterial catheter was placed, after uneventful endotracheal intubation. The patient’s preoperative heart rate was 70 bpm. Ketamine and lidocaine infusions were begun and maintained at 0.1 and 1.5 mg/kg/h, respectively, according to our institutional ERAS protocol. General anesthesia was maintained with 1 minimum alveolar concentration of sevoflurane, fentanyl and boluses of vecuronium were given to facilitate surgery. The total dose of vecuronium administered during surgery was 17 mg.

The surgical procedure was uneventful and lasted approximately 7 hours, which is an average time for our institution. Arterial blood gas 2 hours before the end of surgery showed pH: 7.39, Pco2: 38.7, Po2: 44, base excess: −1, HCO3: 23.6, Na: 140, K: 3.8, ionized calcium: 1.14, Glu: 117, and Hgb: 10.9. The lidocaine and ketamine infusions were discontinued about 40 minutes before complete wound closure, according to our departmental practice. The total dose of lidocaine received was 180 mg and ketamine was 150 mg. Sevoflurane was stopped and ondansetron was given for postoperative nausea and vomiting prophylaxis. Stimulation of the right ulnar nerve with a peripheral nerve stimulator resulted in 4 of 4 twitches of the adductor pollicis muscle without fade, after which 200 mg of sugammadex was administered corresponding to 2.4 mg/kg. For over 2 hours before administration of sugammadex, the patient’s heart rate was consistently in the range of 75–80 bpm. Within the first minute after sugammadex administration, the patient’s heart rate became sinus bradycardic to 35 bpm. Immediately thereafter, the mean arterial pressure dropped to the mid-30s. Peak airway pressure remained 18 cm H2O; end-tidal CO2 38 mm Hg, and body temperature 36.1°C. No rash or urticaria was observed, bilateral breath sounds were present and clear. Initially, a single bolus of atropine 1 mg was given to treat severe bradycardia, without effect. Shortly after, end-tidal CO2 fell to 10 mm Hg, carotid pulses were not palpable, and advanced cardiac life support protocol for pulseless electrical activity was initiated with chest compressions, and bolus of 1 mg epinephrine intravenous, without change in underlying rhythm. Central venous access was obtained and resuscitation was continued with additional administration of 1-mg boluses of epinephrine every 3 minutes for a total of 7 mg and 1 g of calcium chloride until return of spontaneous circulation, with heart rate >100 bpm and mean arterial pressure >90 mm Hg. The patient was transferred to the surgical intensive care unit, for observation, where his cardiopulmonary status remained stable overnight. He was extubated the following morning. Postoperative cardiac workup including transthoracic echocardiogram, electrocardiogram, chest X-ray, computed tomography chest, and urine toxicology were all unremarkable. A tryptase level was not obtained, owing to a lack of signs or symptoms of allergic reaction noted earlier. He was discharged on day 7 with no discernible sequelae.

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Sugammadex was first approved in Europe for reversal of neuromuscular blockade induced by rocuronium and vecuronium in 2008. On December 2015, Sugammadex was approved by the Food and Drug Administration (FDA) for use in the United States; this delay was due to concerns regarding its safety profile including the risk of life-threatening anaphylaxis and bradycardia.8 The most common adverse reactions reported are vomiting, dry mouth, tachycardia, and hypotension.2,3 However, data from recent case reports indicate more serious side effects associated with sugammadex administration including third-degree atrioventricular block, persistent bradycardia, QT interval prolongation, and coronary vasospasm leading to cardiac arrest.4–7,9 Consequently, the FDA recommended that patients be closely monitored for hemodynamic changes during and after sugammadex administration.8 In our case, not only did the patient experience severe drug-resistant bradycardia, but also quickly progressed to pulseless electrical activity arrest, temporally related to the administration of sugammadex in an essentially healthy individual, with no underlying cardiac disease.

In this case, a decrease in heart rate was seen within the first minute after administration of sugammadex with further progression to pulseless electrical activity arrest. The only other medication administered approximately 5 minutes before sugammadex was ondansetron. Ondansetron has been reported to be associated with several arrhythmias including severe bradycardia and cardiac arrest.10 However, there were no changes in hemodynamics immediately after administration of ondansetron, making sugammadex a more likely culprit.

Another distinctive feature of this case was the use of ERAS protocol that includes continuous infusion of ketamine and lidocaine. Based on the duration of infusion and time of discontinuation, plasma concentrations were possibly within therapeutic range at the time of sugammadex administration; therefore, we cannot rule out the possibility that ketamine or lidocaine might have had a role in the dysrhythmia or the subsequent arrest. However, the cases of arrest seen with ketamine or lidocaine are immediately after bolus administration or toxic doses, respectively,11,12 making either drug a less probable candidate.

Previously cited case reports have described sugammadex-related cardiac arrest in patients with previous cardiac conditions such as undiagnosed variant angina, preoperative sinus bradycardia, and a pediatric patient with a transplanted heart in cases where muscle relaxation was maintained with rocuronium and operative times were significantly shorter. Bilgi et al5 reported a case of atropine-resistant bradycardia in a healthy patient after sugammadex but without cardiac arrest. This patient had no history of bradycardia, arrhythmias, or coronary disease and underwent a lengthy procedure where vecuronium was used for muscle relaxation; all distinguished factors that have not been described and need to be considered when hypothesizing possible drug-relevant mechanisms.

Other possible causes of sudden cardiac arrest such as venous air embolism, coronary thrombosis, pulmonary embolism were low in differential and were ruled out in the immediate postoperative period by subsequent workup.

The mechanism of sugammadex-induced bradycardia is not due to cholinergic effects as cited by Booij et al13 and further reported by King et al14 in a case of severe bradycardia with a denervated, transplanted heart; however, no other mechanism has been postulated and the administration of an anticholinergic agent to treat bradycardia is still being recommended.15

The cardiovascular effects of sugammadex might be associated with the amount of free sugammadex plasma molecules. Bhavani16 reported 2 cases of sugammadex-induced bradycardia and cardiac arrest where the doses of sugammadex exceeded the recommended 2 mg/kg to reverse the respective train of four response, as was the case in our anesthetic report.

Considering that sugammadex has become an increasingly important reversal agent and adverse events will likely continue to be observed, we have to be vigilant of possible sugammadex-related side effects and follow the FDA recommendations to closely monitor patient hemodynamics during administration. We also suggest considering the use of low-dose epinephrine instead of anticholinergics to treat bradycardia that might result from sugammadex, given the lack of known muscarinic effect from sugammadex with in vivo animal experiments13 and several case reports previously cited with inadequate atropine response, including this case. We should always consider sugammadex as 1 possible cause of cardiac arrest in the operating room.

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Name: Ivanna A. Sanoja, MD.

Contribution: This author helped review the literature and elaborate the manuscript.

Name: Kenneth S. Toth, MD, PhD.

Contribution: This author helped in the conception of the article and provided critical revision including grammar and spelling.

This manuscript was handled by: Ken B. Johnson, MD.

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