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   Introduction
   Case Report
   Discussion
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Table of Contents
CASE REPORT  
Year : 2017  |  Volume : 20  |  Issue : 3  |  Page : 376-378
Sugammadex to reverse neuromuscular blockade in a child with a past history of cardiac transplantation


1 The Ohio State University College of Medicine, Ohio, USA
2 Department of Anesthesiology and Pain Medicine, Nationwide Children's Hospital, Ohio, USA
3 Department of Anesthesiology and Pain Medicine, Nationwide Children's Hospital; Department of Anesthesiology and Pain Medicine, The Ohio State University College of Medicine, Columbus, Ohio, USA

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Date of Web Publication12-Jul-2017
 

   Abstract 

Sugammadex is a novel agent for the reversal of neuromuscular blockade. The speed and efficacy of reversal with sugammadex are significantly faster than acetylcholinesterase inhibitors, such as neostigmine. Sugammadex also has a limited adverse profile when compared with acetylcholinesterase inhibitors, specifically in regard to the incidence of bradycardia. This adverse effect may be particularly relevant in the setting of a heart transplant recipient with a denervated heart. The authors present a case of an 8-year-old child, status postcardiac transplantation, who required anesthetic care for laparoscopy and lysis of intra-abdominal adhesions. Sugammadex was used to reverse neuromuscular blockade and avoid the potential adverse effects of neostigmine. The unique mechanism of action of sugammadex is discussed, previous reports of its use in this unique patient population are reviewed, and its potential benefits compared to traditional acetylcholinesterase inhibitors are presented.

Keywords: Cardiac transplant, neostigmine, neuromuscular blocking agents, rocuronium, sugammadex, vecuronium

How to cite this article:
Miller K, Hall B, Tobias JD. Sugammadex to reverse neuromuscular blockade in a child with a past history of cardiac transplantation. Ann Card Anaesth 2017;20:376-8

How to cite this URL:
Miller K, Hall B, Tobias JD. Sugammadex to reverse neuromuscular blockade in a child with a past history of cardiac transplantation. Ann Card Anaesth [serial online] 2017 [cited 2020 Sep 28];20:376-8. Available from: http://www.annals.in/text.asp?2017/20/3/376/210401





   Introduction Top


Sugammadex (Bridion ®, Merck and Co., Whitehouse Stations, NJ, USA) was approved for clinical use by the United States Food and Drug Administration in December 2015.[1] Its mechanism of action for the reversal of a neuromuscular blockade is entirely different from the commonly used acetylcholinesterase inhibitors such as neostigmine. Sugammadex is a modified γ-cyclodextrin that encapsulates the steroidal neuromuscular blockade agents (rocuronium and vecuronium), resulting in a reduction of the free plasma concentration, thereby terminating neuromuscular blockade.[2] Preliminary data have demonstrated the complete reversal of neuromuscular blockade with limited residual blockade when compared to neostigmine.[3] In addition, in specific clinical scenarios, the parasympathomimetic effects of acetylcholinesterase inhibitors may lead to bradycardia or asystole. The authors present a case of an 8-year-old child, status postcardiac transplantation, who required anesthetic care for laparoscopy and lysis of intra-abdominal adhesions. Sugammadex was used to reverse neuromuscular blockade and avoid the potential adverse effects of neostigmine. The unique mechanism of action of sugammadex is discussed, previous reports of its use in this unique patient population are reviewed, and its potential benefits compared to traditional acetylcholinesterase inhibitors are presented.


   Case Report Top


Institutional Review Board approval for publication is not required for single case reports at Nationwide Children's Hospital (Columbus, Ohio). An 8-year-old, weighing 25.5 kg, male was transferred from an outside hospital with a 3–4-month history of decreased oral intake, abdominal pain, nausea, and abdominal distention. His past medical history was significant for Hirschsprung's disease, constipation, delayed gastric emptying, congenital heart disease (pulmonary atresia) requiring orthotopic heart transplantation, and vesicoureteral reflux. Current medications included tacrolimus (1 mg in the morning and 0.5 mg at bedtime). An echocardiogram, performed before surgery, was unremarkable with no valvular abnormalities and normal left and right ventricular function. An upper gastrointestinal endoscopy performed several days before the surgery revealed no evidence of pathology. Preoperative laboratory findings were normal except for a mild elevation of the blood urea nitrogen. Based on the clinical findings, it was decided to perform a gastrocutaneous fistula takedown, diagnostic laparoscopy, and upper endoscopy. After being transported to the operating room, routine American Society of Anesthesiologists' monitors were placed. A modified rapid sequence intubation with cricoid pressure was performed after the administration of propofol (4 mg/kg), fentanyl (2 μg/kg), and rocuronium (0.6 mg/kg). A second dose of rocuronium (0.4 mg/kg) was administered. Maintenance anesthesia was provided by desflurane. No intraoperative complications were reported. Surgical findings included an esophagus with decreased vasculature and mild erythema in distal esophagus. Ulceration was found on the great curvature of the stomach, and biopsies were taken around the ulceration, greater curvature, and antrum. Intraoperative fluids included 400 mL of lactated ringers. Prophylactic antiemetic therapy was provided by dexamethasone (0.15 mg/kg) and ondansetron (0.15 mg/kg). Postoperative analgesia was provided by hydromorphone (0.02 mg/kg). After 2 out of 4 twitches were assessed with train of four, neuromuscular blockade was reversed with sugammadex (2 mg/kg). Within 2–3 min, there was spontaneous movement, and the patient's trachea was extubated in the operating room. He was transported to the postanesthesia care unit. Total anesthesia time was 1 h 39 min. The remainder of the postoperative course was unremarkable except for a slow return of gastrointestinal function and resumption of normal oral intake. The patient was discharged home on postoperative day 8.


   Discussion Top


Although the time-honored agent for reversal of neuromuscular blockade is acetylcholinesterase inhibitors such as neostigmine, the accumulation of acetylcholine at sites away from the neuromuscular junction may result in the expected adverse effect profile of bradycardia, bronchospasm, hypersalivation, increased gastrointestinal motility, nausea, and vomiting. These may not be prevented by the concomitant administration of an anticholinergic agent (atropine or glycopyrrolate). These concerns may be magnified in the setting of a denervated heart where profound bradycardia or asystole has been reported following the administration of neostigmine. Neostigmine is thought to cause bradycardia following heart transplantation as a result of either variable parasympathetic reinnervation or direct stimulation of nicotinic cholinergic receptors on the postganglionic parasympathetic neurons. This results in the release of acetylcholine from their terminals and subsequent activation of inhibitory cardiac receptors.[4] The cardiac allograft may also develop denervation hypersensitivity of both the postganglionic neurons and the muscarinic myocardial receptors to the cholinergic effects of neostigmine. These factors combined with intrinsic allograft sinoatrial node dysfunction may produce severe dysfunction or sinus arrest after acetylcholinesterase inhibitors are administered to heart transplant recipients.[5],[6]

Regardless of the mechanisms involved, profound bradycardia or asystole has been reported following the administration of neostigmine in heart transplant recipients [Table 1].[7],[8],[9],[10],[11],[12] These outcomes have occurred even with the concomitant administration of an anticholinergic agent. In many instances, the bradycardia was unresponsive to atropine. Pharmacological, theoretical, and anecdotal clinical data suggest the potential utility of the novel agent, sugammadex, to reverse neuromuscular blockade and avoid the parasympathomimetic effects of acetylcholinesterase inhibitors. However, till now, there are only four previous reports involving a total of six patients which report the use of sugammadex in patients who have undergone cardiac transplantation.[13],[14],[15],[16] In five patients, reversal of neuromuscular blockade with sugammadex was successful without the occurrence of hemodynamic effects including bradycardia. Similar results were noted in our patient, adding further evidence to this anecdotal experience. Although the sample size is limited in number and anecdote, the results are promising for avoiding the potential for bradycardia and asystole with the use of acetylcholinesterase inhibitors for the reversal of neuromuscular blockade in patients who have undergone cardiac transplantation.
Table 1: Cardiovascular effects of acetylcholinesterase inhibitors in the transplanted heart

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Sugammadex reverses neuromuscular blockade directly by encapsulating the neuromuscular blocking agent rather than indirectly, such as acetylcholinesterase inhibitors, by increasing the concentration of acetylcholine at the neuromuscular junction. In addition to having limited muscarinic effects, sugammadex has been shown to be safe and effective in patients with cardiovascular disease with a limited adverse effect profile on hemodynamic function.[2], 3, [13],[14],[15],[16] However, as noted in the package insert, marked bradycardia with the occasional progression to cardiac arrest has been observed within minutes after administration during preclinical trials. No mechanism has been postulated for this response. Administration of an anticholinergic agent (atropine) or a catecholamine (epinephrine), depending on the progression of the heart rate, is recommended if clinically significant bradycardia is observed. Future studies to clearly define the role of this novel agent for reversal of neuromuscular blockade are needed, especially in specific clinical scenarios, such as patient who has undergone cardiac transplantation.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
   References Top

1.
Tobias JD. Current evidence for the use of sugammadex in children. Paediatr Anaesth 2017;27:118-25.  Back to cited text no. 1
    
2.
Bom A, Hope F, Rutherford S, Thomson K. Preclinical pharmacology of sugammadex. J Crit Care 2009;24:29-35.  Back to cited text no. 2
    
3.
Naguib M. Sugammadex: Another milestone in clinical neuromuscular pharmacology. Anesth Analg 2007;104:575-81.  Back to cited text no. 3
    
4.
Backman SB, Bachoo M, Polosa C. Mechanism of the bradycardia produced in the cat by the anticholinesterase neostigmine. J Pharmacol Exp Ther 1993;265:194-200.  Back to cited text no. 4
    
5.
Samuels SI, Kanter SF. Anaesthesia for major surgery in a patient with a transplanted heart. Br J Anaesth 1977;49:265-7.  Back to cited text no. 5
    
6.
Gómez-Ríos MÁ. Anaesthesia for non-cardiac surgery in a cardiac transplant recipient. Indian J Anaesth 2012;56:88-9.  Back to cited text no. 6
    
7.
Backman SB, Ralley FE, Fox GS. Neostigmine produces bradycardia in a heart transplant patient. Anesthesiology 1993;78:777-9.  Back to cited text no. 7
    
8.
Backman SB, Fox GS, Stein RD, Ralley FE. Neostigmine decreases heart rate in heart transplant patients. Can J Anaesth 1996;43:373-8.  Back to cited text no. 8
    
9.
Beebe DS, Shumway SJ, Maddock R. Sinus arrest after intravenous neostigmine in two heart transplant recipients. Anesth Analg 1994;78:779-82.  Back to cited text no. 9
    
10.
Bertolizio G, Yuki K, Odegard K, Collard V, Dinardo J. Cardiac arrest and neuromuscular blockade reversal agents in the transplanted heart. J Cardiothorac Vasc Anesth 2013;27:1374-8.  Back to cited text no. 10
    
11.
Bjerke RJ, Mangione MP. Asystole after intravenous neostigmine in a heart transplant recipient. Can J Anaesth 2001;48:305-7.  Back to cited text no. 11
    
12.
Sawasdiwipachai P, Laussen PC, McGowan FX, Smoot L, Casta A. Cardiac arrest after neuromuscular blockade reversal in a heart transplant infant. Anesthesiology 2007;107:663-5.  Back to cited text no. 12
    
13.
Gómez-Ríos MÁ, López LR. Use of combination of rocuronium and sugammadex in heart transplant recipients. Anaesth Intensive Care 2012;40:903-4.  Back to cited text no. 13
    
14.
Varela N, Golvano M, Pérez-Pevida B. Safety of sugammadex for neuromuscular reversal in cardiac transplant patients. J Cardiothorac Vasc Anesth 2016;30:e37.  Back to cited text no. 14
    
15.
Tezcan B, Saylan A, Bölükbasi D, Koçulu R, Karadeniz Ü. Use of sugammadex in a heart transplant recipient: Review of the unique physiology of the transplanted heart. J Cardiothorac Vasc Anesth 2016;30:462-5.  Back to cited text no. 15
    
16.
Hashimoto M, Sakaguchi H, Sadanaga M. Anesthetic management for endoscopic sinus surgery in a patient with transplanted heart – A case report. Masui 2015;64:160-3.  Back to cited text no. 16
    

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Correspondence Address:
Karen Miller
Department of Anesthesiology and Pain Medicine, The Ohio State University College of Medicine, Columbus, Ohio, 43205
USA
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/aca.ACA_15_17

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