Efficacy and safety of adamgammadex for reversing rocuronium-induced deep neuromuscular blockade: A multicenter, randomized, phase IIb study.

The rapid reversal of deep neuromuscular blockade (NMB) is important but remains challenging. This study aimed to evaluate the efficacy and safety of adamgammadex versus sugammadex in reversing deep rocuronium-induced NMB. This multicenter, randomized, phase IIb study included 80 patients aged 18-64 years, American Society of Anesthesiologists (ASA) grade 1-2, undergoing elective surgery under general anesthesia with rocuronium. Patients were randomized to the adamgammadex 7, 8, and 9 mg/kg group or the sugammadex 4 mg/kg group. The primary efficacy variable was the time to recovery of train-of-four ratio (TOFr) to 0.9. The secondary efficacy variables were the time to recovery of TOFr to 0.7, antagonistic success rate of the recovery of TOFr to 0.9 within 5 min, and incidence rate of recurarization within 30 min after drug administration. The explorative efficacy variable was the time to recovery of the corrected TOFr to 0.9 (actual/baseline TOF ratio). Adamgammadex 7, 8, and 9 mg/kg and sugammadex 4 mg/kg groups did not significantly differ in all efficacy variables. Importantly, adamgammadex 9 mg/kg permitted reversal within a geometric mean of 2.9 min. According to the safety profile, adamgammadex achieved good tolerance and low incidence of drug-related adverse events compared with the 4 mg/kg sugammadex. Adamgammadex 7, 8, and 9 mg/kg facilitated rapid reversal of deep rocuronium-induced NMB and had good tolerance and low incidence of drug-related adverse events. Therefore, adamgammadex is a potential and promising alternative to sugammadex.

A randomized trial evaluating the safety profile of sugammadex in high surgical risk ASA physical class 3 or 4 participants.

BACKGROUND: The aim of this randomized, double-blind trial was to evaluate the safety and tolerability profile, including cardiac safety, of sugammadex-mediated recovery from neuromuscular block in participants undergoing surgery who met the American Society of Anesthesiologists (ASA) Physical Class 3 or 4 criteria. Specifically, this study assessed the impact of sugammadex on cardiac adverse events (AEs) and other prespecified AEs of clinical interest. METHODS: Participants meeting ASA Class 3 and 4 criteria were stratified by ASA Class and NMBA (rocuronium or vecuronium) then randomized to one of the following: 1) Moderate neuromuscular block, sugammadex 2 mg/kg; 2) Moderate neuromuscular block, neostigmine and glycopyrrolate (neostigmine/glycopyrrolate); 3) Deep neuromuscular block, sugammadex 4 mg/kg; 4) Deep neuromuscular block, sugammadex 16 mg/kg (rocuronium only). Primary endpoints included incidences of treatment-emergent (TE) sinus bradycardia, TE sinus tachycardia and other TE cardiac arrhythmias. RESULTS: Of 344 participants randomized, 331 received treatment (61% male, BMI 28.5 ± 5.3 kg/m2, age 69 ± 11 years). Incidence of TE sinus bradycardia was significantly lower in the sugammadex 2 mg/kg group vs neostigmine/glycopyrrolate. The incidence of TE sinus tachycardia was significantly lower in the sugammadex 2 and 4 mg/kg groups vs neostigmine/glycopyrrolate. No significant differences in other TE cardiac arrythmias were seen between sugammadex groups and neostigmine/glycopyrrolate. There were no cases of adjudicated anaphylaxis or hypersensitivity reactions in this study. CONCLUSIONS: Compared with neostigmine/glycopyrrolate, incidence of TE sinus bradycardia was significantly lower with sugammadex 2 mg/kg and incidence of TE sinus tachycardia was significantly lower with sugammadex 2 mg/kg and 4 mg/kg. These results support the safety of sugammadex for reversing rocuronium- or vecuronium-induced moderate and deep neuromuscular block in ASA Class 3 or 4 participants. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03346057 .

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.

Relationship of perioperative anaphylaxis to neuromuscular blocking agents, obesity, and pholcodine consumption: a case-control study.

BACKGROUND: The observation that patients presenting for bariatric surgery had a high incidence of neuromuscular blocking agent (NMBA) anaphylaxis prompted this restricted case-control study to test the hypothesis that obesity is a risk factor for NMBA anaphylaxis, independent of differences in pholcodine consumption. METHODS: We compared 145 patients diagnosed with intraoperative NMBA anaphylaxis in Western Australia between 2012 and 2020 with 61 patients with cefazolin anaphylaxis with respect to BMI grade, history of pholcodine consumption, sex, age, comorbid disease, and NMBA type and dose. Confounding was assessed by stratification and binomial logistic regression. RESULTS: Obesity (odds ratio [OR]=2.96, χ2=11.7, P=0.001), 'definite' pholcodine consumption (OR=14.0, χ2=2.6, P<0.001), and female sex (OR=2.70, χ2=9.61, P=0.002) were statistically significant risk factors for NMBA anaphylaxis on univariate analysis. The risk of NMBA anaphylaxis increased with BMI grade. Confounding analysis indicated that both obesity and pholcodine consumption remained important risk factors after correction for confounding, but that sex did not. The relative rate of rocuronium anaphylaxis was estimated to be 3.0 times that of vecuronium using controls as an estimate of market share, and the risk of NMBA anaphylaxis in patients presenting for bariatric surgery was 8.8 times the expected rate (74.9 vs 8.5 per 100 000 anaesthetic procedures). CONCLUSIONS: Obesity is a risk factor for NMBA anaphylaxis, the risk increasing with BMI grade. Pholcodine consumption is also a risk factor, and this is consistent with the pholcodine hypothesis. Rocuronium use is associated with an increased risk of anaphylaxis compared with vecuronium in this population.

Early Skin Test after Anaphylaxis during Induction of Anesthesia: A Case Report.

BACKGROUND: It is recommended that a skin test be performed 4-6 weeks after anaphylaxis. However, there is little evidence about the timing of the skin test when there is a need to identify the cause within 4-6 weeks. CASE REPORT: A 57-year-old woman was scheduled to undergo surgery via a sphenoidal approach to remove a pituitary macroadenoma. Immediately after the administration of rocuronium, pulse rate increased to 120 beats/min and blood pressure dropped to 77/36 mmHg. At the same time, generalized urticaria and tongue edema were observed. Epinephrine was administered and the surgery was postponed. Reoperation was planned two weeks after the event. Four days after the anaphylactic episode, rocuronium was confirmed to be the cause by the skin prick test. Cisatracurium, which showed a negative reaction, was selected as an alternative agent for future procedures. Two weeks later, the patient underwent reoperation without any adverse events. CONCLUSIONS: The early skin test can be performed if there is a need even earlier than 4-6 weeks after anaphylaxis.

Effects on Postoperative Gastrointestinal Motility After Neuromuscular Blockade Reversal With Sugammadex Versus Neostigmine/Glycopyrrolate in Colorectal Surgery Patients.

BACKGROUND: Neuromuscular blockers (NMBs) used during surgery have historically been reversed with acetylcholinesterase inhibitors and anticholinergic agents, which can slow gastrointestinal motility. Sugammadex (SUG) provides NMB reversal with minimal effects on gastrointestinal motility. OBJECTIVE: The purpose of this study was to determine if SUG for reversal of NMB is associated with decreased time to first bowel movement (BM) following laparoscopic colorectal surgery. METHODS: A retrospective cohort analysis divided 224 patients undergoing laparoscopic colorectal surgeries based on whether they received SUG or a combination of neostigmine and glycopyrrolate (NG) for NMB reversal. The primary outcome was time (in hours) from NMB reversal until first recorded BM. Secondary end points were postoperative ileus, postoperative nausea and vomiting, prevalence of residual NMB, and hospital length of stay. The relationship between NMB reversal agent and outcomes were analyzed using multivariable linear regression and Cox proportional hazards model. RESULTS: There were 128 patients who received NG and 96 who received SUG. Time to first BM was faster in the SUG group by 11.7 hours (P = 0.004). SUG maintained the effect in a multiple regression model (P = 0.012). A Cox Proportional Hazards regression model found 50% increased odds of a BM across time for the SUG group (P = 0.003). No adverse effects were noted. CONCLUSION AND RELEVANCE: This represents the first report demonstrating faster return of BM following colorectal surgery with SUG when compared with NG. Application of these data may add another tool to enhance recovery after colorectal surgery.

The efficacy of Antipyretic Analgesics administration intravenously for Preventing Rocuronium-Associated Pain/Withdrawal Response: a systematic review and meta-analysis.

BACKGROUND: Rocuronium-associated injection pain/withdrawal response (RAIPWR) was non-ideal but occurred frequently when injection intravenously during anesthesia induction. Many studies had reported that pretreating with antipyretic analgesics (AAs) could reduce the occurrence of RAIPWR, but there was no consensus yet. Therefore, this meta-analysis was designed to systematically evaluate the benefits of AAs on RAIPWR in patients. METHODS: PubMed, Cochrane Library, Ovid, EMbase, Chinese National Knowledge Infrastructure (CNKI), Wan Fang Data were searched by January 1st 2019 for randomized controlled trials (RCTs) applying AAs to alleviate RAIPWR in patients who underwent elective surgery under general anesthesia. Two investigators assessed quality of RCTs and extracted data respectively and the meta-analysis was carried on Revman 5.3 software. Moreover, we compared AAs in pros and cons directly with lidocaine, the most reported medicine to prevent RAIPWR. RESULTS: Data were analyzed from 9 RCTs totaling 819 patients. The results of Meta-analysis showed that compared to the control group, pretreating with AAs could prevent the total occurrence of RAIPWR [Risk ratio (RR), 0.52; 95% confidence interval (CI), 0.42 to 0.66; P < 0.0001], and took effect on moderate (RR, 0.56; 95%CI, 0.43 to 0.73; P < 0.0001) and severe RAIPWR (RR = 0.14; 95%CI, 0.08 to 0.24; P < 0.00001). When compared to lidocaine, the preventive effect was not so excellent as the latter but injection pain induced by prophylactic occurred less. CONCLUSION: The currently available evidence suggested that pretreating with AAs intravenously could alleviate RAIPWR. TRIAL REGISTRATION: PROSPERO CRD42019129776.

Hypoxic ventilatory response after rocuronium-induced partial neuromuscular blockade in men with obstructive sleep apnoea.

Obstructive sleep apnoea and residual neuromuscular blockade are, independently, known to be risk factors for respiratory complications after major surgery. Residual effects of neuromuscular blocking agents are known to reduce the hypoxic ventilatory response in healthy volunteers. Patients with obstructive sleep apnoea have impaired control of breathing, but it is not known to what extent neuromuscular blocking agents interfere with the regulation of breathing in such patients. In a physiological study in 10 unsedated men with untreated obstructive sleep apnoea, we wished to examine if partial neuromuscular blockade had an effect on hypoxic ventilatory response (isocapnic hypoxia to oxygen saturation of 80%) and hypercapnic ventilatory response (normoxic inspired carbon dioxide 5%). The hypoxic ventilatory response was reduced by 32% (p = 0.016) during residual neuromuscular block (rocuronium to train-of-four ratio 0.7), but the hypercapnic ventilatory response was unaffected. We conclude that neuromuscular blockade specifically depresses peripheral chemosensitivity, and not respiratory muscle function since the hypercapnic ventilatory response was unaffected.

Drug Challenge Tests With General Anesthetics: Predictive Value of Skin Tests.

BACKGROUND: The study of perioperative drug reactions remains a major challenge for both diagnosis and therapy. The lack of a standard assessment of allergy to general anesthetics and of data establishing the true value of skin tests for most drugs used in induction and maintenance of anesthesia, as well as the lack of commercially available reagents for in vitro tests, renders the study of these reactions problematic. The aims of this study were to provide a diagnostic protocol for drug challenge testing with general anesthetics, to establish an etiological diagnosis that is as specific as possible, and to determine the predictive value of skin tests. METHODS: Twenty-nine patients with perioperative drug reactions were included in the study from November 2008 to December 2018. RESULTS: We confirmed the high negative predictive value of the tests (96%-100%) in the case of propofol, rocuronium, and fentanyl. To our knowledge, this is the first study to describe drug challenge testing with general anesthetics and, therefore, to establish the true negative predictive value of skin tests, which leads to a definitive diagnosis and safer surgery. CONCLUSIONS: After assessing risks and benefits and considering the importance of this group of drugs, we conclude that drug challenge testing with general anesthetics is necessary. We propose a protocol for perioperative drug reactions that enables us to make a highly accurate etiological diagnosis with minimum risk for the patient.

An urgent open surgical approach for left ventricle venting during peripheral veno-arterial extracorporeal membrane oxygenation for refractory cardiac arrest: case report.

The objective of the study is to describe an emergency procedure for left ventricle venting during veno-arterial extracorporeal life support for refractory cardiac arrest. Veno-arterial extracorporeal membrane oxygenation is widely used in refractory cardiac arrest but is characterized by an increase in left ventricle afterload, which may impair cardiac contractility improvement. Different left ventricle venting techniques are available. We report the use of a surgical approach with sternotomy for left ventricle venting in a 21-year-old patient who was placed under veno-arterial extracorporeal membrane oxygenation for refractory cardiac arrest with severe pulmonary edema, respiratory failure, and left ventricle stasis. A 21-year-old woman was admitted for laparoscopic sleeve gastrectomy. In the recovery room, she developed a refractory circulatory shock. Transthoracic echocardiography revealed a dilated cardiomyopathy with severe left ventricle systolic dysfunction (left ventricle ejection fraction at 20%). Coronary angiogram was normal. On day 2, she underwent laparotomy for sepsis and she presented cardiac arrest secondary to ventricular tachycardia. We proceeded to peripheral veno-arterial extracorporeal membrane oxygenation as the cardiac arrest was refractory. A miniaturized veno-arterial extracorporeal membrane oxygenation system was implanted into the right femoral vessels onsite .The low flow duration was 40 minutes. Veno-arterial extracorporeal membrane oxygenation blood flow was set to 3 L min-1, resulting in a closed aortic valve and a massive pulmonary edema. Transesophageal echocardiography showed left ventricular ejection fraction at 5% without aortic valve opening. We first implanted an intra-aortic balloon pump without clinical improvement. Transesophageal echocardiography revealed massive thrombus formation into the aortic root. We decided to perform an open surgical approach for left ventricle unload using a transmitral cannula (22 Fr) via the right superior pulmonary vein connected to the inflow tube of the veno-arterial extracorporeal membrane oxygenation with Y connection. Transesophageal echocardiography showed a full opening of aortic valve and elimination of valve aortic thrombus. Chest radiography showed a significant decrease of pulmonary congestion. We were able to withdraw extracorporeal life support organization on day 10 and discharged on day 54. Clinical explorations reveal a fulminant rocuronium-related hypersensitivity myocarditis. This salvage surgical technique using a modified central veno-arterial extracorporeal membrane oxygenation cannulation technique has efficiently decreased blood stasis and permitted rapid recovery.

Effect of Sugammadex on Postoperative Myasthenic Crisis in Myasthenia Gravis Patients: Propensity Score Analysis of a Japanese Nationwide Database.

BACKGROUND: In myasthenia gravis (MG) patients, postoperative myasthenic crisis, and residual neuromuscular blocking agent (NMBA) can cause respiratory failure that requires mechanical ventilation. However, it remains unclear whether the use of sugammadex for NMBA reversal reduces postoperative myasthenic crisis in MG patients undergoing surgery. We analyzed the association between use of sugammadex and postoperative myasthenic crisis in patients with MG using a national inpatient database. METHODS: Adult patients with MG who received thymectomy under general anesthesia were identified in the Japanese Diagnosis Procedure Combination database from July 1, 2010 to March 31, 2016. Patients who received sugammadex (sugammadex group) were compared with those who did not receive sugammadex (control group). The primary outcome was postoperative myasthenic crisis, and the secondary outcomes were postoperative pneumonia, tracheostomy, 28-day mortality, total hospitalization costs, and length of stay after surgery. Propensity scores were estimated by logistic regression based on the following variables: age; sex; body mass index (BMI); smoking index; history of cancer; Charlson comorbidity index (CCI); type of thymectomy; time from hospital admission to surgery; use of plasma exchange, immunosuppressants, corticosteroids, anticholinesterase, and oral benzodiazepine before surgery; type of hospital; and treatment year. The outcomes were compared using stabilized inverse probability of treatment weighting (IPTW) analyses to obtain good between-group balance. RESULTS: Of 795 patients identified, 506 patients received sugammadex and 289 patients did not. After stabilized IPTW, the sugammadex group was associated with a decrease in postoperative myasthenic crisis (22/507 [4.3%] vs 25/288 [8.7%]; odds ratio [OR], 0.48; 95% confidence interval [CI], 0.25-0.91), but not associated with a decrease in postoperative pneumonia (5/507 [1.0%] vs 7/288 [2.4%]; OR, 0.44; 95% CI, 0.17-1.14) or tracheostomy (7/507 [1.4%] vs 10/288 [3.5%]; OR, 0.38; 95% CI, 0.12-1.22) compared with the control group. The sugammadex group had significantly lower median (interquartile range) total hospitalization costs ($13,186 [$11,250-$16,988] vs $14,119 [$11,713-$20,207]; P < .001) and median length of stay after surgery (10 [8-15] vs 11 [8-18] days; P < .001), compared with the control group. CONCLUSIONS: In this retrospective observational study, sugammadex was associated with reductions in postoperative myasthenic crisis and total hospitalization costs in adult patients with MG who received thymectomy. Given the present findings, sugammadex should be routinely administered for MG patients undergoing thymectomy.

A Prospective, Randomized Trial Comparing Respiratory Status During Anesthesia for Airway Stenting: Spontaneous Respiration Versus Controlled Ventilation With Muscle Relaxants.

BACKGROUND: Airway stenting is a procedure in which a stent is inserted into a stenotic site of the airway. The safest method of ventilation for airway stenting is controversial. A prospective randomized interventional study was conducted on airway stenting. We conducted this study to investigate whether controlled ventilation with muscle relaxants (MR) during airway stenting reduces the incidence of desaturation events (percutaneous oxygen saturation [SpO2] <95%) in comparison with spontaneous respiration (SP). METHODS: Sixty-four patients were enrolled at our hospital between April 2016 and August 2018, and were randomly assigned to the controlled ventilation with MR group or SP group. For anesthesia, total intravenous anesthesia with propofol target-controlled infusion and remifentanil was performed. In the SP group, SP was maintained. In the MR group, a rigid bronchoscope was inserted after the administration of MR to perform controlled ventilation. The incidence of desaturation events was analyzed by logistic regression adjusted by the preoperative respiratory state and stenotic site of the airway. RESULTS: The incidence of desaturation events in the SP and MR groups was 75.0% (24/32) and 9.7% (3/31), respectively, with an odds ratio of 0.04 (95% confidence interval, 0.01-0.16, reference = SP group; P < .001). In the SP group, the mean intraoperative pH was lower than that in the MR group (7.2 ± 0.1 vs 7.4 ± 0.1, respectively; P < .001). In this group, the mean partial pressure of arterial carbon dioxide (PaCO2) was higher (70.2 ± 17.0 mm Hg vs 40.5 ± 8.0 mm Hg, respectively; P < .001) and the mean partial pressure of oxygen in the arterial blood/fraction of the inspiratory oxygen ratio was lower (263.1 ± 64.2 mm Hg vs 396.4 ± 69.4 mm Hg, respectively; P < .001). CONCLUSIONS: Controlled ventilation with MR during airway stenting reduced the incidence of desaturation events, maintaining a favorable respiratory status.

Anaphylaxis induced by sugammadex and sugammadex-rocuronium complex -a case report.

BACKGROUND: In sugammadex-induced anaphylaxis, sugammadex and/or sugammadex-rocuronium complex have possible allergenic epitope. CASE: We report a case of sugammadex-induced anaphylaxis during general anesthesia in a 60-year-old male undergoing orthopedic hand surgery, manifesting as profound hypotension and urticaria. The timing of onset was closely associated with sugammadex administration. The patient recovered after extensive therapy including fluid, epinephrine, other vasopressors, steroid, and antihistamine administration. By intradermal skin test which was done at four weeks after anaphylaxis, we confirmed positive reactions to both sugammadex and sugammadex-rocuronium complex. CONCLUSIONS: This is a rare case of sugammadex-induced anaphylaxis that both sugammadex and sugammadex-rocuronium complex were confirmed as allergenic epitopes.

The Effects of Postoperative Residual Neuromuscular Blockade on Hospital Costs and Intensive Care Unit Admission: A Population-Based Cohort Study.

BACKGROUND: Postoperative residual neuromuscular blockade continues to be a frequent occurrence with a reported incidence rate of up to 64%. However, the effect of postoperative residual neuromuscular blockade on health care utilization remains unclear. We conducted a retrospective cohort study to investigate the effects of postoperative residual neuromuscular blockade on hospital costs (primary outcome), intensive care unit admission rate, and hospital length of stay (secondary outcomes). METHODS: We performed a prespecified secondary analysis of data obtained in 2233 adult patients undergoing surgery under general anesthesia. Postoperative residual neuromuscular blockade was defined as a train-of-four ratio <0.9 in the postanesthesia care unit (PACU). Our confounder model adjusted for a variety of patient, surgical, and anesthesia-related factors. We fitted truncated negative binomial regression models for hospital cost and hospital length of stay analyses and a logistic regression model for our intensive care unit admission analysis. RESULTS: Overall, 457 (20.5%) patients in our cohort had residual neuromuscular blockade on admission to the PACU. Postoperative residual neuromuscular blockade was not independently associated with increased hospital costs (adjusted incidence rate ratio, 1.04, CI, 0.98-1.11; P = .22). There were significantly higher odds of intensive care unit admission in those with postoperative residual neuromuscular blockade compared to those without (adjusted odds ratio, 3.03, CI, 1.33-6.87; P < .01). Further, we found a trend toward increased hospital length of stay in patients with postoperative residual neuromuscular blockade (adjusted incidence rate ratio, 1.09; P = .06). Sensitivity analysis using the same model in the day of surgery admissions and ambulatory surgery confirmed our findings. CONCLUSIONS: Postoperative residual neuromuscular blockade at PACU admission was not significantly associated with increased hospital costs, but was associated with higher rates of intensive care unit admission. These findings support the view that clinicians should continue to work to reduce the rate of postoperative residual neuromuscular blockade.

Extracorporeal membrane oxygenation support in refractory perioperative anaphylactic shock to rocuronium: a report of two cases.

In recent years, extracorporeal membrane oxygenation has become increasingly common in the treatment of in-hospital cardiac arrest in non-cardiac surgery patients. This includes cardiac arrest secondary to perioperative anaphylactic shock refractory to standard advanced life support protocols, which is a rare but catastrophic event associated with significant mortality. Neuromuscular blocking drugs are most commonly implicated in perioperative anaphylaxis, with rocuronium playing a major role. In this article, we report two cases of young and otherwise fit and well patients who experienced a perioperative arrest secondary to rocuronium anaphylaxis before elective surgery; both patients did not respond to conventional advanced life support, but survived neurologically intact after institution of urgent veno-arterial extracorporeal membrane oxygenation.

Comparison of rocuronium requirement in children with continuous infusion versus intermittent bolus: A randomised controlled trial.

BACKGROUND: Minimising rocuronium administration during paediatric surgery helps to reduce the incidence of residual muscular blockade. OBJECTIVE: To determine whether intermittent bolus injection (Bolus group) or continuous infusion (group) requires the lesser amount of rocuronium. DESIGN: A randomised, single-blind controlled trial. SETTING: A single university hospital from March to June 2017. PATIENTS: Sixty-six children undergoing general anaesthesia. INTERVENTIONS: Dose of rocuronium for maintenance of muscle relaxation in either Bolus or continuous infusion group. Train-of-four (TOF) count of two was maintained during surgery. When TOF count reached three, 0.1 mg kg of rocuronium was administered in Bolus group or infused at an increased rate of 0.1 mg kg h in continuous infusion group. MAIN OUTCOME MEASURES: Primary outcome was the dose of rocuronium given (µg kg min). The recovery time from the TOF count four to TOF 0.7 (RT0.7), and 0.9 (RT0.9) were recorded. All adverse events were recorded up to 30 min after extubation. RESULTS: Mean (SD) rocuronium dose in the Bolus group was 6.1 (0.9), [95% confidence interval (95% CI) 5.7 to 6.4] µg kg min and 4.9 (1.0), (95% CI 4.6 to 5.3) µg kg min in the continuous infusion group (P = 0.001). RT0.7 was 24.0 (13.7), 95% CI 19.3 to 28.7) min in the Bolus group, and 25.7 (16.0), (95% CI 20.2 to 31.2) min in the continuous infusion group (P = 0.73). RT0.9 was 30.7 (17.1), (95% CI 24.9 to 36.5) min in the Bolus group, and 30.0 (17.6), (95% CI 24.0 to 36.0) min in the continuous infusion group (P = 0.91). The incidence of adverse events was not significantly different between two groups. CONCLUSION: In children undergoing general anaesthesia, the dose of rocuronium given by continuous administration was less than that with intermittent bolus. TRIAL REGISTRATION: ClinicalTrials.gov (identifier: NCT03060707).

Sugammadex Reversal of a Large Subcutaneous Depot of Rocuronium in a Dialysis Patient: A Case Report.

Sugammadex is a modified gamma cyclodextrin that encapsulates rocuronium. We report the successful use of sugammadex in the management of an elderly man with end-stage renal failure who sustained an infiltration of subcutaneous rocuronium during rapid sequence induction of general anesthesia. Given the erratic absorption of subcutaneous rocuronium from the tissue, sugammadex was chosen to reverse the neuromuscular block at the end of the procedure. This report demonstrates the efficacy of sugammadex to reverse neuromuscular block in elderly patients with poor renal function. Moreover, the duration of action for sugammadex was sufficient to neutralize the ongoing absorption of subcutaneous rocuronium.

Prevention of rocuronium induced mast cell activation with prophylactic oleuropein rich diet in anesthetized rabbits

Abstract Purpose: The effect of a prophylactic oleuropein-rich diet before anesthesia accompanied by the widely-used steroid-based neuromuscular drug rocuronium on mast cell activation was investigated in the study. Methods: 14 rabbits used in the study. The rabbits in the oleuropein group were given oleuropein-rich extract added to the animals' water at doses of 20 mg/kg oleuropein for 15 days orally. After 15 days, all rabbits in the two groups were given general anesthesia with rocuronium of 1 mg/kg. After 1 day, animals were sacrificed and the liver tissue sections stained with H&E, toluidine blue and tryptase for immunohistochemical study. Results: There was no statistically significant difference between ALT, AST and albumin averages of the oleuropein and control groups (p> 0.05). The tryptase average of the control group was higher than the tryptase average of the oleuropein group and this difference was statistically significant (p=0.003). The T. blue average in the oleuropein group was higher than the control group. However, there was no statistically significant difference between groups (p=0.482). Conclusions: Rocuronium adverse effects, like hypersensitivity and anaphylaxis, may limit routine use of this substance. The use of oleuropein reduced the number of inflammatory cells and prevented degranulation.

Effectiveness of sugammadex versus neostigmine on restoration of neuromuscular function in surgical patients with myasthenia gravis undergoing rocuronium-induced neuromuscular blockade: a systematic review protocol.

REVIEW QUESTION/OBJECTIVE: The objective of this systematic review is to identify the effectiveness of sugammadex versus neostigmine on the reversal of rocuronium-induced neuromuscular blockade in surgical patients with myasthenia gravis undergoing general anesthesia.

Management of rocuronium neuromuscular block using a protocol for qualitative monitoring and reversal with neostigmine.

BACKGROUND: Neuromuscular block using subjective monitoring and neostigmine reversal is commonly associated with postoperative residual neuromuscular block. We tested whether a protocol for the management of neuromuscular block that specified appropriate dosing and optimal neostigmine reversal was associated with a reduction in postoperative residual neuromuscular block. METHODS: Rocuronium administration was guided by surgical requirements and based on the ideal body weight, with dose reductions for female sex and age >55 yr. Neostigmine was administered in adjusted doses after a train-of-four count of four was confirmed at the thumb. The protocol ensured a minimum of 10 min between neostigmine administration and tracheal extubation. We measured the postoperative residual neuromuscular block in patients undergoing abdominal surgery before and after introduction of the protocol. Pre-specified primary and secondary endpoints were incidence of postoperative residual neuromuscular block and severe postoperative residual neuromuscular block at the time of tracheal extubation, defined as normalised train-of-four ratios <0.9 and <0.7, respectively. RESULTS: The incidence of postoperative residual neuromuscular block at tracheal extubation was 14/40 (35%) for patients managed according to the protocol compared with 22/38 (58%) for patients in the control group, odds ratio of 0.39, and 95% confidence interval of 0.14-1.07; P=0.068. The incidence of severe postoperative residual neuromuscular block at tracheal extubation showed a highly significant difference, odds ratio=0.06, and confidence interval of 0.00-0.43; P=0.001. CONCLUSIONS: The incidence of severe postoperative residual neuromuscular block was significantly reduced after the protocol was introduced. Given the limitations inherent in this before-and-after study, further research is needed to confirm these results. CLINICAL TRIAL REGISTRATION: NCT02660398.