Reversal Of Deep Neuromuscular Blockade Research Articles

785: EVALUATION OF SUGAMMADEX DOSING FOR DEEP NEUROMUSCULAR BLOCKADE REVERSAL IN THE EMERGENCY DEPARTMENT

Introduction: Neuromuscular blocking agents (NMBAs) are often administered to facilitate rapid sequence intubation (RSI). The effects of neuromuscular blockade may be prolonged in the setting of organ dysfunction or need for rapid attainment of a neurological examination may be necessary. The primary objective of this study is to evaluate low (2 mg/kg) versus standard dose (4 mg/kg) sugammadex for reversal of deep neuromuscular blockade in the emergency department (ED) to facilitate neurological examination. Methods: A single-center, retrospective cohort study was performed and approved by the local Institutional Review Board. Patients were identified using sugammadex charge codes between 01/01/2017 - 07/15/2022. Adult patients were included if they received sugammadex in the ED to facilitate neurological examination, were given rocuronium or vecuronium for RSI, and had a documented train-of-four (TOF) before and after sugammadex administration. Patients were excluded if records were incomplete, initial sugammadex dose other than 2 mg/kg or 4 mg/kg was used and if initial TOF was 1 – 4. The primary outcome of this study was successful deep neuromuscular blockade reversal defined by achieving a post-treatment TOF of 4. Results: Of 36 sugammadex doses administered in the ED, 26 patients were included in the final analysis, with 10 in the low-dose group and 16 patients in the standard-dose group. The median dose was 2.28 mg/kg and 4.09 mg/kg for low- and standard-dose, respectively. The overall cohort was predominantly male (65.4%) with a median age of 68.4 years (49.7-76.9). Most patients presented for intraparenchymal hemorrhage (53.8%), with 57.7% of bleeds being traumatic in origin. Median initial Glasgow Coma Score was 3, and all initial TOF were zero. Paralytics were administered in the pre-hospital setting in 85% of patients, with rocuronium use predominating (92.3%). No significant difference in success rate of NMBA reversal was found between low-dose versus standard-dose sugammadex (100.0% vs. 93.8%, P = 1.000). Conclusions: Low-dose sugammadex did not result in a significantly different success rate of NMBA reversal when compared to standard-dose. Low-dose sugammadex may be a viable option for deep NMBA reversal in the ED to facilitate neurological examinations.

Sugammadex for reversal of neuromuscular blockade in pediatric patients: Results from a phase IV randomized study

Few randomized studies have assessed recovery from rocuronium- or vecuronium-induced moderate or deep neuromuscular blockade with sugammadex in pediatric participants. To assess sugammadex for reversal of neuromuscular blockade in pediatric participants. This was a randomized, phase IV, active comparator-controlled, double-blind study. Participants aged 2 to <17years, under moderate or deep neuromuscular blockade, were administered sugammadex (2 or 4mg/kg) or neostigmine (50µg/kg; for moderate neuromuscular blockade only). Predefined adverse events of clinical interest, including clinically relevant bradycardia, hypersensitivity, and anaphylaxis, were monitored. The primary efficacy endpoint was time to recovery to a train-of-four ratio of ≥0.9 in participants receiving sugammadex 2mg/kg versus neostigmine for reversal of moderate neuromuscular blockade, analyzed by analysis of variance adjusted for neuromuscular blocking agent and age. Of 288 randomized participants, 272 completed the study and 276 were included in the analyses. Clinically relevant bradycardia was experienced by 2.0%, 1.6%, and 5.9% of participants in the sugammadex 2mg/kg, sugammadex 4mg/kg, and neostigmine groups, respectively. No hypersensitivity or anaphylaxis events were observed. Recovery to a train-of-four ratio of ≥0.9 with sugammadex 2mg/kg was faster than neostigmine (1.6min, 95% CI 1.3 to 2.0 vs. 7.5min, 95% CI 5.6 to 10.0; p<.0001) and was comparable to sugammadex 4mg/kg (2.0min, 95% CI 1.8 to 2.3). Pediatric participants recovered from rocuronium- or vecuronium-induced moderate neuromuscular blockade significantly faster with sugammadex 2mg/kg than with neostigmine. Time to reversal of deep neuromuscular blockade with sugammadex 4mg/kg was consistent with that of moderate neuromuscular blockade reversal. No meaningful differences in clinically relevant bradycardia, hypersensitivity, or anaphylaxis were seen with sugammadex vs neostigmine. These results support the use of sugammadex for reversal of moderate and deep rocuronium- and vecuronium-induced neuromuscular blockade in patients aged 2 to <17years. NCT03351608/EudraCT 2017-000692-92.

Sugammadex, the Guardian of Deep Muscle Relaxation During Conventional and Robot-Assisted Laparoscopic Surgery: A Narrative Review.

High intra-abdominal pressure induced by artificial pneumoperitoneum can obviously impair respiratory and circulatory functions and has a negative effect on the prognosis of patients undergoing conventional and robot-assisted laparoscopic surgery. The application of deep neuromuscular blockade during the operation is reported to lower the intra-abdominal pressure and improve patients’ outcome. However, concern lies in the risks of postoperative residual muscular paralysis with the use of deep neuromuscular blockade. Sugammadex, a specific antagonist for aminosteroids muscle relaxants, can effectively and rapidly reverse rocuronium and vecuronium induced neuromuscular blockade of different depths. Thus, sugammadex allows the ability to safeguard the application of deep neuromuscular blockade in laparoscopic operations and helps to alleviate the adverse complications associated with pneumoperitoneum. Here, we review the application of deep neuromuscular blockade in different laparoscopic surgeries and discuss the benefits and possible risks of sugammadex administration in the reversal of deep neuromuscular blockade in these operations.

Efficacy and safety of sugammadex doses calculated on the basis of corrected body weight and total body weight for the reversal of deep neuromuscular blockade in morbidly obese patients.

ObjectiveWe investigated the efficacy and safety of sugammadex doses calculated using corrected body weight (CBW) for reversing deep rocuronium-induced neuromuscular blockade (NMB) in morbidly obese patients undergoing laparoscopic bariatric surgery.MethodsOne hundred and twenty-five morbidly obese patients were randomly assigned to three groups: (1) a CBW group, n = 50; (2) a total body weight (TBW) group, n = 50; and (3) a control group, n = 25. Deep NMB was maintained using a continuous infusion of rocuronium. At the reappearance of 1 to 2 post-tetanic counts (PTCs), 4 mg/kg sugammadex, calculated using CBW or TBW, were administered.ResultsAll the participants in the CBW and TBW groups recovered to a train-of-four (TOF) ratio of 0.9 within 5 minutes. The recovery times from the start of sugammadex administration to a TOF ratio of 0.9 were 2.2 ± 0.7 and 2.0 ± 0.7 minutes in the CBW and TBW groups, respectively. Thus, a sugammadex dose calculated using CBW was not inferior to that calculated using TBW for the reversal of rocuronium-induced deep NMB in morbidly obese patients.ConclusionA dose of 4 mg/kg of sugammadex calculated using CBW is efficient and safe for the reversal of deep NMB after a continuous infusion of rocuronium in morbidly obese patients.Clinical Trial Registration Number ChiCTR1900028652 (Chinese Clinical Trial Registry, www.chictr.org.cn)

Deep Neuromuscular Blockade: Does the Data Support Its Use in Surgical Patients?

This review aims to provide an update about the role of deep neuromuscular blockade (NMB) in surgery by providing an overview the literature of the last 3 years. Since the approval of sugammadex for the reversal of deep NMB, the influence of deep NMB on facilitation of surgery as well as postoperative patient outcome has become the focus of increased interest in research. Though deep NMB is still predominantly investigated in the setting of laparoscopic surgery, some recent publications have also investigated deep block in other patient populations. Deep NMB has become increasingly popular and intensely researched. Mounting evidence has documented that surgical conditions are improved when deep (vs. moderate) neuromuscular blockade is used. Though this is true for many, it may not be applicable to all surgical procedures. Previously not well documented, deep vs. moderate NMB may also influence postoperative patient outcome by a reduction in surgical complication rates and/or decreased postoperative pain after certain procedures.

Is there an interaction between dexamethasone and sugammadex in real clinical conditions? A randomized controlled trial in patients undergoing laparoscopic cholecystectomy.

Background and Aims:There is evidence that sugammadex can encapsulate other substances except rocuronium, such as dexamethasone. The aim of this study was to investigate the possible clinical interaction between dexamethasone and sugammadex, in patients undergoing laparoscopic cholecystectomy.Material and Methods:This was a randomized, double-blind controlled trial, performed in patients aged 18–75 years, American Society of Anesthesiologists (ASA) I–III, who underwent a laparoscopic cholecystectomy under deep neuromuscular blockade with rocuronium. Patients received 5 mg of dexamethasone or placebo (N/S 0.9%) during induction of anesthesia. Sugammadex 4 mg/kg was administered at the end of surgery at post-tetanic count 1–2. The outcome measures assessed were the time from sugammadex administration until train-of-four (TOF) 0.9, and until patient's extubation, postoperative pain (measured by numeric rating scale 0–10), nausea and vomiting, as well as rescue analgesics and antiemetics required during the first 24 hours postoperatively. The total dose of rocuronium required in both groups was also recorded.Results:Overall, 44 patients were studied. No difference was detected regarding the demographic and surgical characteristics of patients. The time from sugammadex administration until TOF 0.9 and until patients' extubation did not differ significantly between the groups (P = 0.21 and 0.17). Operating conditions, pain scores, nausea/vomiting, and rescue analgesics and antiemetics during the first 24 hours postoperatively, did not differ between the groups. The total dose of rocuronium, however, was significantly more in patients who received dexamethasone (P = 0.01).Conclusion:No significant clinical interaction was revealed between dexamethasone and sugammadex during reversal of deep neuromuscular blockade in patients undergoing laparoscopic cholecystectomy.

Train-of-four recovery precedes twitch recovery during reversal with sugammadex in pediatric patients: A retrospective analysis.

After reversal of a rocuronium-induced neuromuscular blockade with sugammadex, the recovery of train-of-four ratio to 0.9 is faster than recovery of first twitch of the train-of-four to 90% in adults. These findings after reversal of neuromuscular blockade with sugammadex have not yet been investigated in pediatric patients. The aim of this retrospective analysis was to investigate the relationship of the recovery of first twitch of the train-of-four height and train-of-four ratio after reversal of rocuronium-induced neuromuscular blockade with sugammadex in pediatric patients. Patients ASA I-III, aged 2-11years, and who underwent abdominal and/or perineal surgery were included in the analysis. After extracting the necessary data from the hospital database, the patients were divided into 2 groups based on the dose of sugammadex received: group A: 2mg.kg-1 for reversal of moderate neuromuscular blockade and group B: 4mg.kg-1 for reversal of deep neuromuscular blockade. The relationship of the recovery of first twitch of the train-of-four height and train-of-four ratio in these 2 groups were analyzed. Data from 43 pediatric patients aged 2-11years could be analyzed. The first twitch of the train-of-four height at the recovery of train-of-four ratio to 0.9 in group B was statistically significantly lower compared with group A. This height 3 and 5minutes after the train-of-four ratio reached 0.9 showed no statistically significant differences between groups. The results were in line with the results found in adults and showed that the train-of-four ratio recovered to 0.9 was faster than first twitch of the train-of-four height recovered to the same level.

Efficacy, Safety and Pharmacokinetics of Sugammadex 4 mg/kg for Reversal of Deep Neuromuscular Blockade in Patients With Severe Renal Impairment

Panhuizen, I. F.*; Gold, S. J. A.†; Buerkle, C.‡; Snoek, M. M. J.*; Harper, N. J. N.†; Kaspers, M. J. G. H.§; van den Heuvel, M. W.§; Hollmann, M. W.∥ Author Information

Efficacy, safety and pharmacokinetics of sugammadex 4 mg kg−1 for reversal of deep neuromuscular blockade in patients with severe renal impairment

This study evaluated efficacy and safety of sugammadex 4 mg kg(-1) for deep neuromuscular blockade (NMB) reversal in patients with severe renal impairment (creatinine clearance [CLCR] <30 ml min(-1)) vs those with normal renal function (CLCR ≥80 ml min(-1)). Sugammadex 4 mg kg(-1) was administered at 1-2 post-tetanic counts for reversal of rocuronium NMB. Primary efficacy variable was time from sugammadex to recovery to train-of-four (T4/T1) ratio 0.9. Equivalence between groups was demonstrated if two-sided 95% CI for difference in recovery times was within -1 to +1 min interval. Pharmacokinetics of rocuronium and overall safety were assessed. The intent-to-treat group comprised 67 patients (renal n=35; control n=32). Median (95% CI) time from sugammadex to recovery to T4/T1 ratio 0.9 was 3.1 (2.4-4.6) and 1.9 (1.6-2.8) min for renal patients vs controls. Estimated median (95% CI) difference between groups was 1.3 (0.6-2.4) min; thus equivalence bounds were not met. One control patient experienced acceleromyography-determined NMB recurrence, possibly as a result of premature sugammadex (4 mg kg(-1)) administration, with no clinical evidence of NMB recurrence observed. Rocuronium, encapsulated by Sugammadex, was detectable in plasma at day 7 in 6 patients. Bioanalytical data for sugammadex were collected but could not be used for pharmacokinetics. Sugammadex 4 mg kg(-1) provided rapid reversal of deep rocuronium-induced NMB in renal and control patients. However, considering the prolonged sugammadex-rocuronium complex exposure in patients with severe renal impairment, current safety experience is insufficient to support recommended use of sugammadex in this population. NCT00702715.

PSU6 Economic Impact of Using Sugammadex for the Reversal of Deep Neuromuscular Blockade in the Swedish Health Care Setting

PSU6 Economic Impact of Using Sugammadex for the Reversal of Deep Neuromuscular Blockade in the Swedish Health Care Setting

A Randomized, Dose-Response Study of Sugammadex Given for the Reversal of Deep Rocuronium- or Vecuronium-Induced Neuromuscular Blockade Under Sevoflurane Anesthesia

Sugammadex is the first of a new class of selective muscle relaxant binding drugs developed for the rapid and complete reversal of neuromuscular blockade induced by rocuronium and vecuronium. Many studies have demonstrated a dose-response relationship with sugammadex for reversal of neuromuscular blockade in patients induced and maintained under propofol anesthesia. However, sevoflurane anesthesia, unlike propofol, can prolong the effect of neuromuscular blocking drugs (NMBDs) such as rocuronium and vecuronium. We designed this randomized, open-label, dose-response trial to explore the dose-response relationship of sugammadex for the reversal of deep neuromuscular blockade induced by rocuronium or vecuronium under propofol-induced and sevoflurane-maintained anesthesia. As a secondary objective, the safety variables of sugammadex were evaluated. After anesthesia induction with propofol, 102 patients aged > or = 20 and < 65 yr were randomized to receive a single bolus dose of rocuronium 0.9 mg/kg (n = 50) or vecuronium 0.1 mg/kg (n = 52), followed by maintenance doses (rocuronium 0.1-0.2 mg/kg or vecuronium 0.02-0.03 mg/kg) as needed. Neuromuscular blockade was monitored using acceleromyography. After the last dose of NMBD, at 1-2 posttetanic counts, a single bolus dose of sugammadex 0.5, 1.0, 2.0, 4.0, or 8.0 mg/kg was administered. The primary efficacy variable was time from start of sugammadex administration to recovery of the T(4)/T(1) ratio to 0.9. The per-protocol population consisted of 48 patients in the rocuronium group and 47 in the vecuronium group. A dose-response effect was demonstrated for decreased mean time to recovery of the T(4)/T(1) ratio to 0.9 with increasing sugammadex dose in both NMBD groups (per-protocol population): rocuronium group, 79.8 (SD 33.0) min (sugammadex 0.5 mg/kg) to 1.7 (0.7) min (4.0 mg/kg) and 1.1 (0.3) min (8.0 mg/kg subgroup); vecuronium group, 68.4 (31.9) min (0.5 mg/kg) to 3.3 (3.5) min (4.0 mg/kg), and 1.7 (0.8) min (8.0 mg/kg subgroup). Neuromuscular monitoring showed recurrent neuromuscular blockade in 5 patients, all in the rocuronium group (2 given sugammadex 0.5 mg/kg and 3 given 1.0 mg/kg), but there were no clinical events attributable to recurrent or residual neuromuscular blockade. Sugammadex at doses of > or = 4 mg/kg provides rapid reversal of deep rocuronium- and vecuronium-induced neuromuscular blockade under sevoflurane maintenance anesthesia.