Prevention of Postoperative Events Following Reversal With Sugammadex or Neostigmine (The P- PERSoN Trial) – Pilot Data Following Early Termination of a Prospective, Blinded, Randomised Trial.

Background: Residual paralysis following anaesthesia is common and can lead to postoperative morbidity. While sugammadex has been shown to be effective in minimising residual paralysis, uncertainty exists as to whether its use reduces any associated morbidity. We designed this trial to determine if the use of sugammadex for the reversal of intraoperative aminosteroid neuromuscular blockade results in improvements in postoperative pulmonary complications, complications in the recovery unit, postoperative nausea and vomiting, and patient satisfaction, when compared to reversal with neostigmine. Methods: A prospective, double-blind, randomised controlled trial in adult patients admitted for surgical operations at two Australian hospitals between December 2018 and March 2019 was performed comparing the reversal of neuromuscular paralysis using sugammadex 2mg/kg versus neostigmine 50mcg/kg. Statistical analysis of continuous data was performed using two tailed t-tests, with categorical and ordinal data was assessed by Chi-squared analysis. Results: The trial was terminated due to a combination of resource constraints and the 2019 novel coronavirus disease (COVID-19) pandemic. Of 51 patients screened, 33 were eligible for participation and 30 subsequently recruited and randomised. All patients received the intended treatment allocated. Data for the primary outcome was obtained in all patients. There was no difference in the rates of postoperative pulmonary complications between the sugammadex and neostigmine groups (0% (0/19) vs 9% (1/11) RR 5.0 (95%CI 0.22-113) p=0.37. There was no difference in any of the secondary outcomes between the groups. Conclusions: The P-PERSoN trial showed no difference in post operative pulmonary complications between sugammadex and neostigmine based reversal of aminosteroid neuromuscular block, but was underpowered to show any difference due to early trial termination. The randomisation and data collection was feasible. We support the need for an adequately resourced and funded randomised controlled trial to address this important clinical question. Trial Registration: The P-PERSoN trial is registered at the Australian and New Zealand Trial Registry (www.anzctr.org.au) # ACTRN12616000063415 and The U.S. National Library of Medicine (www.ClinicalTrials.gov) #NCT02825576

Residual paralysis caused by 50 mg rocuronium after reversal with 4 mg/kg sugammadex: a case report

Background Rocuronium-induced neuromuscular blockade can be quickly and completely reversed by administration of an optimal dose of sugammadex. Sugammadex antagonizes rocuronium-induced neuromuscular blockade by encapsulating rocuronium. Herein, we report a case of residual neuromuscular paralysis in which the recommended dose of sugammadex (4 mg·kg− 1) failed to antagonize a rocuronium-induced blockade. Case presentation A 71-year-old man (body mass index: 26.7 kg·m− 2) underwent endoscopic submucosal dissection of early-stage gastric cancer. He had no known factors that may have affected the effects of rocuronium and sugammadex. He received rocuronium (50 mg; 0.7 mg·kg− 1) for anesthesia induction. No additional rocuronium was administered during the 71-min procedure. Ninety-four minutes after rocuronium administration, neuromuscular monitoring showed 20 twitches in response to post-tetanic count stimulation. The train-of-four (TOF) ratio was not measurable despite sugammadex (280 mg; 4 mg/kg) administration, although four weak twitches in response to TOF stimulation appeared in 3 min. The TOF ratio became detectable following administration of an additional dose of sugammadex (120 mg; 1.7 mg·kg− 1), and it recovered to 107% 8 min after the second dose. The patient opened his eyes; moved his neck, arms, and limbs; and regained consciousness. The trachea was extubated and the patient was transferred to the ward. Conclusions Neuromuscular monitoring should be used if a neuromuscular blockage agent is administered, even if the recommended dose of sugammadex is administered.

A Comparative Study between Sugammadex versus Neostigmine as Regards Efficiency of Reversal of Rocuronium and Bleeding Tendency Effect after Septoplasty

Backround Sugammadex is a reversal agent with well-known advantages but its effects on coagulation profile, reversal time and hemodynamic parameters have been a topic of interest. Septoplasty is a common surgical procedure with postoperative respiratory complications and bleeding. Aim of the Work the purpose of this study was to compare the efficacy of different doses of sugammadex versus neostigmine for rocuronium reversal in septoplasty surgery regarding its effects on the reversal time, occurrence of residual paralysis, incidence of adverse events, hemodynamic parameters and effect on coagulation profile. Patients and Methods this study was conducted in Ain Shams University Hospital. After obtaining approval of research ethical committee and patients’ informed consents. Sixty (60) patients of both sexes, aging between 25- 50 years old, with ASA status I – II. Induction of anesthesia was achieved by intravenous injection of fentanyl 1-2 mcg/ kg and propofol 2-2.5 mg/ kg. Rocuronium 0.6 mg/ kg was administered intravenously. At the end of the surgical procedure, when spontaneous recovery of neuromuscular blockade occurs with the appearance of T2, anesthesia was withdrawn and the neuromuscular block was reversed using IV injection of 1, 2 or 4 mg/ kg sugammadex or neostigmine sulfate 0.04 mg/kg with atropine sulfate 0.02mg/ kg. Results as regards gender, age, weight, height and ASA stat, signs of residual paralysis, incidence of adverse effects there was no statistically significant differences found between groups. Regarding the comparison between the reversal times of the 4 groups, a highly statistical significance was found between the 4 groups. The heart rate showed a high statistical significance between the four groups at 2 and 10 minutes but they showed a lesser significance at 30 minutes. Mean arterial pressure increased in neostigmine group 2min, 10 min after the medication. Sugammadex group had lower heart rate when compared to neostigmine group, (N>S1>S2>S4). Lastly, considering the coagulation profile, At 30 minutes after drug administration, there was a mild increase in PT and PTT in S2 group with moderate increase in S4 group that return to normal values again at 120 minutes. Conclusion we have designed a study to compare the efficacy of different doses of sugammadex versus neostigmine for rocuronium reversal and studied its effects on hemostasis in septoplasty surgery regarding the reversal time, occurrence of residual paralysis, incidence of adverse events, hemodynamic parameters and effect on coagulation profile. Sugmmadex proved to have a lesser reversal time in all its studied doses compared to neostigmine with a TOF (T4:T1) ratio 0.9. We studied the effect of sugammadex for neuromuscular blockade in terms of PONV, we found no differences regarding this issue between both drugs. Although there were increases on hemodynamic parameters in both N and S groups, this increase was more prominent in patients receiving neostigmine. Finally, our study demonstrated that sugammadex caused mild and transient elevation in PT and aPTT values within 30 minutes then returned to their normal levels within 120 minutes.