Association between reversal agents (sugammadex vs. neostigmine) for neuromuscular block and postoperative pulmonary complications: A retrospective analysis.

AIMS: Residual neuromuscular blockade has been linked to pulmonary complications in the postoperative period. This study aimed to determine whether sugammadex was associated with a lower risk of postoperative pulmonary complications (PPCs) compared with neostigmine. METHODS: This retrospective cohort study was conducted in a tertiary academic medical center. Patients ≥18 year of age undergoing noncardiac surgical procedures with general anesthesia and mechanical ventilation were enrolled between January 2019 and September 2021. We identified all patients receiving rocuronium and reversal with neostigmine or sugammadex via electronic medical record review. The primary endpoint was a composite of PPCs (including pneumonia, atelectasis, respiratory failure, pulmonary embolism, pleural effusion, or pneumothorax). The incidence of PPCs was compared using propensity score analysis. RESULTS: A total of 1786 patients were included in this study. Among these patients, 976 (54.6%) received neostigmine, and 810 (45.4%) received sugammadex. In the whole sample, PPCs occurred in 81 (4.54%) subjects (7.04% sugammadex vs. 2.46% neostigmine). Baseline covariates were well balanced between groups after overlap weighting. Patients in the sugammadex group had similar risk (overlap weighting OR: 0.75; 95% CI: 0.40 to 1.41) compared to neostigmine. The sensitivity analysis showed consistent results. In subgroup analysis, the interaction P-value for the reversal agents stratified by surgery duration was 0.011. CONCLUSION: There was no significant difference in the rate of PPCs when the neuromuscular blockade was reversed with sugammadex compared to neostigmine. Patients undergoing prolonged surgery may benefit from sugammadex, which needs to be further investigated.

Under-dosing and over-dosing of neuromuscular blocking drugs and reversal agents: beware of the risks.

The phenomena of residual curarisation and recurarisation after the use of long-acting non-depolarising neuromuscular blocking drugs such as tubocurarine and pancuronium were well recognised 60 years ago. But the incidence seemed to decline with the introduction of atracurium and vecuronium. However, recently there have been an increasing number of reports of residual and recurrent neuromuscular block. Some of these reports are a result of inappropriate doses of rocuronium, sugammadex or both, together with inadequate neuromuscular monitoring. We urge clinicians to review their practice to ensure the highest standards of clinical care when using neuromuscular blocking drugs and reversal agents. This includes the use of quantitative neuromuscular monitoring whenever neuromuscular blocking drugs are administered.

Is adamgammadex the brother of sugammadex or the next generation of reversal agent?

Sugammadex is now in widespread use to reverse the neuromuscular blocking effects of rocuronium. Adverse effects from sugammadex are rare, but anaphylactic and cardiovascular reactions to the drug have been reported. In an attempt to reduce such side-effects, a modified gamma-cyclodextrin, adamgammadex, has been developed. Phase 3 clinical trials suggest that it is slightly less potent than sugammadex and has a non-inferior speed of onset. In a multicentre trial of 310 patients, there was a suggestion of a lower incidence of allergic responses and recurarisation after adamgammadex compared with sugammadex. The clinical implications of this study are discussed in this editorial.

Phase III clinical trial comparing the efficacy and safety of adamgammadex with sugammadex for reversal of rocuronium-induced neuromuscular block.

BACKGROUND: Preliminary clinical trials of adamgammadex, a new cyclodextrin-based selective reversal agent, have demonstrated its efficacy in reversing neuromuscular block by rocuronium. METHODS: This multicentre, randomised, double-blind, positive-controlled, non-inferiority phase III clinical trial compared the efficacy and safety of adamgammadex and sugammadex. We randomised 310 subjects to receive adamgammadex (4 mg kg-1) or sugammadex (2 mg kg-1) at reappearance of the second twitch of the train-of-four (TOF), and standard safety data were collected. RESULTS: For the primary outcome, the proportion of patients with TOF ratio ≥0.9 within 5 min was 98.7% in the adamgammadex group vs 100% in the sugammadex group, with a point estimate and 95% confidence interval (CI) of 1.3% (-4.6%, +1.3%); the lower limit was greater than the non-inferiority margin of -10%. For the key secondary outcome, the median (inter quartile range) time from the start of administration of adamgammadex or sugammadex to recovery of TOF ratio to 0.9 was 2.25 (1.75, 2.75) min and 1.75 (1.50, 2.00) min, respectively. The difference was 0.50 (95% CI: 0.25, 0.50); the upper limit was lower than the non-inferiority margin of 5 min. In addition, there were no inferior results observed in secondary outcomes. Adamgammadex had a lower incidence of adverse drug reactions compared with sugammadex (anaphylactic reaction, recurarisation, decreased heart rate, and laryngospasm; P=0.047). CONCLUSIONS: Adamgammadex was non-inferior to sugammadex with a possible lower incidence of adverse drug reactions compared with sugammadex. Adamgammadex may have a potential advantage in terms of its overall risk-benefit profile. CLINICAL TRIAL REGISTRATION: Chinese Clinical Trial Registry, ChiCTR2000039525. Registered October 30, 2020. https://www.chictr.org.cn/showproj.html?proj=56825.

The effect of sugammadex on patient morbidity and quality of recovery after general anaesthesia: a systematic review and meta-analysis.

BACKGROUND: Residual neuromuscular block is associated with increased patient morbidity. Therefore prevention of residual neuromuscular block is an important component of general anaesthesia where neuromuscular blocking agents are used. Whereas sugammadex improves reversal based on neuromuscular twitch monitoring parameters, there have been no prospective, adequately powered definitive studies demonstrating that sugammadex is also associated with less patient morbidity. METHODS: We performed a systematic review of randomised trials comparing sugammadex with anticholinesterase-based reversal or placebo reversal that reported important patient outcomes beyond the postanaesthesia care unit. RESULTS: We identified 43 articles, including 5839 trial participants. Only one trial reported days alive and out of hospital to 30 days (DAOH-30), which showed that the number of DAOH-30 was similar in those allocated to sugammadex compared with neostigmine-based reversal (25 days [19-27] vs 24 days [21-27], median difference 0.00 [-2.15 to 2.15]). Pooled analyses of data from 16 trials showed an estimated odds ratio (OR) for postoperative pulmonary complications of 0.67 (95% confidence interval 0.47-0.95) with sugammadex use. Pooled analysis showed that pneumonia (eight trials OR 0.51 [0.24-1.01] with sugammadex use), hospital length of stay (23 trials, mean difference -0.31 [-0.84 to 0.22] with sugammadex use), and patient-reported quality of recovery (11 trials, varied depending on metric used) are similar in those allocated to sugammadex vs control. The difference seen in mortality (11 trials, OR 0.39 [0.15-1.01] with sugammadex use) would be considered to be clinically significant and warrants further investigation, however, the rarity of these events precludes drawing definitive conclusions. CONCLUSION: Although few trials reported on DAOH-30 or important patient outcomes, sugammadex is associated with a reduction in postoperative pulmonary complications, however, this might not translate to a difference in hospital length of stay, patient-reported quality of recovery, or mortality. CLINICAL TRIAL REGISTRATION: PROSPERO database (CRD42022325858).

Sugammadex Versus Neostigmine for Reversal of Neuromuscular Blockade in Patients With Severe Renal Impairment: A Randomized, Double-Blinded Study.

BACKGROUND: Sugammadex is not advised for patients with severe renal impairment, but has been shown in a variety of other populations to be superior to neostigmine for reversal of neuromuscular blockade. The objective of this study was to determine if reversal of rocuronium-induced neuromuscular blockade with sugammadex versus reversal of cisatracurium-induced neuromuscular blockade with neostigmine results in a faster return to a train-of-four ratio (TOFR) ≥90% in patients with severe renal impairment. METHODS: We conducted a prospective, randomized, blinded, controlled trial at a large county hospital. A total of 49 patients were enrolled. Inclusion criteria included patients age ≥18, American Society of Anesthesiologists (ASA) physical status III and IV, with a creatinine clearance <30 mL/min, undergoing general anesthesia with expected surgical duration ≥2 hours and necessitating neuromuscular blockade. Subjects received either cisatracurium 0.2 mg/kg or rocuronium 0.6 mg/kg for induction of anesthesia to facilitate tracheal intubation. Subjects were kept at moderate neuromuscular blockade during surgery and received either 2 mg/kg sugammadex or 50 µg/kg neostigmine with 10 µg/kg glycopyrrolate for reversal of neuromuscular blockade. Neuromuscular monitoring was performed with electromyography (TwitchView), and the TOFR was recorded every minute after administration of the reversal agent. The time from administration of neuromuscular reversal until the patient reached a TOFR ≥90% was recorded as the primary outcome. RESULTS: The mean time to recovery of TOFR ≥90% was significantly faster with sugammadex at 3.5 (±1.6) min compared with neostigmine at 14.8 (±6.1) min ( P < .0001; mean difference, 11.3 minutes; 95% confidence interval [CI], 9.0-13.5 minutes). There were no major adverse events in either group. CONCLUSIONS: In patients with severe renal impairment, neuromuscular blockade with rocuronium followed by reversal with sugammadex provides a significantly faster return of neuromuscular function compared to cisatracurium and neostigmine, without any major adverse effects.

Analysis of the factors contributing to residual weakness after sugammadex administration in pediatric patients under 2 years of age.

BACKGROUND: Sugammadex reverses the neuromuscular blockade induced by rocuronium and vecuronium and is approved by the U.S. Food and Drug Administration for use in patients aged over 2 years. There is, however, a paucity of data regarding its dosing profile in infants and children younger than 2 years. AIMS: The aim of this study was to assess the risk of recurarization, or re-paralysis, in children under 2 years of age to increase awareness on the importance of appropriate neuromuscular blocked monitoring and reversal. METHODS: All patients aged ≤24 months who underwent an operative procedure at a tertiary medical center between January 1, 2018, and December 31, 2021, and received both rocuronium for neuromuscular blockade and sugammadex for neuromuscular blockade reversal, were identified in the electronic medical record. Patients were excluded from analysis if they (1) received vecuronium, cisatracurium, atracurium, or succinylcholine for neuromuscular blockade, (2) received neostigmine for reversal, or (3) underwent more than one operation within 24 h. We performed a survival analysis of sugammadex redose using a Cox proportional hazards model. RESULTS: We reviewed 2923 records. Sugammadex was redosed in 123 (4.2%) cases. The median [IQR] time to redose was 7 [4-17] min, and the median [IQR] amount of redose administered was 2.74 [1.96-3.99] mg/kg. Increasing patient age (p < .01) and weight (p < .01) were associated with reduced hazard rate of sugammadex redose. For a patient of median weight, increasing age from 3 to 13 months was associated with a 53% risk reduction (HR: 0.47; 95% CI: 0.24-0.91). For a patient of median age, increasing weight from 4.7 to 9.2 kg was associated with 41% risk reduction (HR: 0.59; 95% CI: 0.32-1.07). We failed to detect any other associations. CONCLUSIONS: In this single-center, retrospective cohort study of pediatric surgery patients, there was an association between the hazard of sugammadex redose with both increased age and weight.

Extravascular injection of neuromuscular blocking drugs: A systematic review of current evidence and management.

Extravascular injection of neuromuscular blocking drugs (NMBDs) can cause a neuromuscular block because of systemic absorption. Currently, there are no guidelines available on managing extravasation of NMBDs. This article reviews the available literature on extravasation of NMBDs. Medline and Embase databases were searched for studies concerning the paravenous or subcutaneous injection of NMBDs. Nine articles were included consisting of seven case reports, one case series and one clinical trial. Rocuronium was used as primary NMBD in nine cases, vecuronium in two cases and pancuronium in one case. Although there exists significant heterogeneity between the reported information in the included studies, the majority of the case reports describe a slower onset, with a median delay of 20 min and prolonged duration of the neuromuscular block. Nine patients had a residual neuromuscular block at the end of the surgery. Postoperative monitoring in the recovery room was prolonged (median time 4 h). Most studies suggest that the delay in NMBD onset and recovery is caused by the formation of a subcutaneous depot, from which the NMBD is slowly absorbed into the systemic circulation. According to the current literature, extravasation of NMBDs results in an unpredictable neuromuscular block. Strategies to prevent potentially harmful side effects, such as frequent train-of-four (TOF) monitoring, the use of NMBD reversal agents and prolonged length of stay in the postanaesthesia care unit (PACU), should be considered. This article suggests a clinical pathway that can be used after extravascular injection of NMBDs.

Evaluation of a Protocol for the Management of Maintenance and Reversal of Rocuronium Block Using Neostigmine or Sugammadex.

BACKGROUND: Postoperative residual neuromuscular blockade (PRNB) is defined as an adductor pollicis train-of-four ratio (TOFR) <0.9. It is a common postoperative complication when nondepolarizing muscle relaxants are either not reversed or reversed with neostigmine. PRNB has been reported in 25% to 58% of patients who receive intermediate-acting nondepolarizing muscle relaxants, and it is associated with increased morbidity and decreased patient satisfaction. We conducted a prospective descriptive cohort study during the implementation of a practice guideline that included the selective use of sugammadex or neostigmine. The primary study aim of this pragmatic study was to estimate the incidence of PRNB at arrival to the postanesthesia care unit (PACU) when the practice guideline is followed. METHODS: We enrolled patients undergoing orthopedic or abdominal surgery requiring neuromuscular blockade. Rocuronium administration was guided by surgical requirements and based on ideal body weight, with dose reductions for women and/or age >55 years. Only qualitative monitoring was available to the anesthesia providers, and selection of sugammadex or neostigmine was guided by tactile assessments of the response to train-of-four (TOF) stimulation by a peripheral nerve stimulator. Neostigmine was administered if no fade was detected in the TOF response at the thumb. Deeper blocks were reversed with sugammadex. The prespecified primary and secondary end points were the incidence of PRNB at arrival to the PACU, defined as a normalized TOFR (nTOFR) < 0.9, and severe PRNB, defined as nTOFR <0.7 on arrival to the PACU. Anesthesia providers were blinded to all quantitative measurements made by research staff. RESULTS: Analysis included 163 patients, and 145 underwent orthopedic and 18 abdominal surgeries. Of the 163 patients, 92 (56%) were reversed with neostigmine and 71 (44%) with sugammadex. The overall incidence of PRNB at PACU arrival was 5 of 163 or 3% (95% confidence interval [CI], 1-7). The incidence of severe PRNB in PACU was 1% (95% CI, 0-4). Three of the 5 subjects with PRNB had TOFR <0.4 at time of reversal but were given neostigmine since anesthesia providers detected no fade by qualitative assessment. CONCLUSIONS: The use of a protocol that specifies rocuronium dosing and selective use of sugammadex versus neostigmine based on qualitative assessment of TOF count and fade allowed us to achieve an incidence of PRNB of 3% (95% CI, 1-7) at PACU arrival. Quantitative monitoring may be needed to further reduce this incidence.

Use of neuromuscular blockade for neck dissection and association with iatrogenic nerve injury.

BACKGROUND: Cranial nerve injury is an uncommon but significant complication of neck dissection. We examined the association between the use of intraoperative neuromuscular blockade and iatrogenic cranial nerve injury during neck dissection. METHODS: This was a single-center, retrospective, electronic health record review. Study inclusion criteria stipulated patients > 18 years who had ≥ 2 neck lymphatic levels dissected for malignancy under general anesthesia with a surgery date between 2008 - 2018. Use of neuromuscular blockade during neck dissection was the primary independent variable. This was defined as any use of rocuronium, cisatracurium, or vecuronium upon anesthesia induction without reversal with sugammadex prior to surgical incision. Univariate tests were used to compare variables between those patients with, and those without, iatrogenic cranial nerve injury. Multivariable logistic regression determined predictors of cranial nerve injury and was performed incorporating Firth's estimation given low prevalence of the primary outcome. RESULTS: Our cohort consisted of 925 distinct neck dissections performed in 897 patients. Neuromuscular blockade was used during 285 (30.8%) neck dissections. Fourteen instances (1.5% of surgical cases) of nerve injury were identified. On univariate logistic regression, use of neuromuscular blockade was not associated with iatrogenic cranial nerve injury (OR: 1.73, 95% CI: 0.62 - 4.86, p = 0.30). There remained no significant association on multivariable logistic regression controlling for patient age, sex, weight, ASA class, paralytic dose, history of diabetes, stroke, coronary artery disease, carotid atherosclerosis, myocardial infarction, and cardiac arrythmia (OR: 1.87, 95% CI: 0.63 - 5.51, p = 0.26). CONCLUSIONS: In this study, use of neuromuscular blockade intraoperatively during neck dissection was not associated with increased rates of iatrogenic cranial nerve injury. While this investigation provides early support for safe use of neuromuscular blockade during neck dissection, future investigation with greater power remains necessary.

Peri-operative management of neuromuscular blockade: A guideline from the European Society of Anaesthesiology and Intensive Care.

Recent data indicated a high incidence of inappropriate management of neuromuscular block, with a high rate of residual paralysis and relaxant-associated postoperative complications. These data are alarming in that the available neuromuscular monitoring, as well as myorelaxants and their antagonists basically allow well tolerated management of neuromuscular blockade. In this first European Society of Anaesthesiology and Intensive Care (ESAIC) guideline on peri-operative management of neuromuscular block, we aim to present aggregated and evidence-based recommendations to assist clinicians provide best medical care and ensure patient safety. We identified three main clinical questions: Are myorelaxants necessary to facilitate tracheal intubation in adults? Does the intensity of neuromuscular blockade influence a patient's outcome in abdominal surgery? What are the strategies for the diagnosis and treatment of residual paralysis? On the basis of this, PICO (patient, intervention, comparator, outcome) questions were derived that guided a structured literature search. A stepwise approach was used to reduce the number of trials of the initial research ( n  = 24 000) to the finally relevant clinical studies ( n  = 88). GRADE methodology (Grading of Recommendations, Assessment, Development and Evaluation) was used for formulating the recommendations based on the findings of the included studies in conjunction with their methodological quality. A two-step Delphi process was used to determine the agreement of the panel members with the recommendations: R1 We recommend using a muscle relaxant to facilitate tracheal intubation (1A). R2 We recommend the use of muscle relaxants to reduce pharyngeal and/or laryngeal injury following endotracheal intubation (1C). R3 We recommend the use of a fast-acting muscle relaxant for rapid sequence induction intubation (RSII) such as succinylcholine 1 mg kg -1 or rocuronium 0.9 to 1.2 mg kg -1 (1B). R4 We recommend deepening neuromuscular blockade if surgical conditions need to be improved (1B). R5 There is insufficient evidence to recommend deep neuromuscular blockade in general to reduce postoperative pain or decrease the incidence of peri-operative complications. (2C). R6 We recommend the use of ulnar nerve stimulation and quantitative neuromuscular monitoring at the adductor pollicis muscle to exclude residual paralysis (1B). R7 We recommend using sugammadex to antagonise deep, moderate and shallow neuromuscular blockade induced by aminosteroidal agents (rocuronium, vecuronium) (1A). R8 We recommend advanced spontaneous recovery (i.e. TOF ratio >0.2) before starting neostigmine-based reversal and to continue quantitative monitoring of neuromuscular blockade until a TOF ratio of more than 0.9 has been attained. (1C).

Traumatic brain injury and RSI is rocuronium or succinylcholine preferred?

PURPOSE OF REVIEW: Traumatic brain injury is widespread and has significant morbidity and mortality. Patients with severe traumatic brain injury often necessitate intubation. The paralytic for rapid sequence induction and intubation for the patient with traumatic brain injury has not been standardized. RECENT FINDINGS: Rapid sequence induction is the standard of care for patients with traumatic brain injury. Historically, succinylcholine has been the agent of choice due to its fast onset and short duration of action, but it has numerous adverse effects such as increased intracranial pressure and hyperkalemia. Rocuronium, when dosed appropriately, provides neuromuscular blockade as quickly and effectively as succinylcholine but was previously avoided due to its prolonged duration of action which precluded neurologic examination. However, with the widespread availability of sugammadex, rocuronium is able to be reversed in a timely manner. SUMMARY: In patients with traumatic brain injury necessitating intubation, rocuronium appears to be safer than succinylcholine.

Quantitative Neuromuscular Monitoring in Clinical Practice: A Professional Practice Change Initiative.

BACKGROUND: Residual neuromuscular blockade can be avoided with quantitative neuromuscular monitoring. The authors embarked on a professional practice initiative to attain documented train-of-four ratios greater than or equal to 0.90 in all patients for improved patient outcomes through reducing residual paralysis. METHODS: The authors utilized equipment trials, educational videos, quantitative monitors in all anesthetizing locations, and electronic clinical decision support with real-time alerts, and initiated an ongoing professional practice metric. This was a retrospective assessment (2016 to 2020) of train-of-four ratios greater than or equal to 0.9 that were documented before extubation. Anesthesia records were manually reviewed for neuromuscular blockade management details. Medical charts of surgical patients who received a neuromuscular blocking drug were electronically searched for patient characteristics and outcomes. RESULTS: From pre- to postimplementation, more patients were assigned American Society of Anesthesiologists Physical Status III to V, fewer were inpatients, the rocuronium average dose was higher, and more patients had a prereversal train-of-four count less than 4. Manually reviewed anesthesia records (n = 2,807) had 2 of 172 (1%) cases with documentation of train-of-four ratios greater than or equal to 0.90 in November 2016, which was fewer than the cases in December 2020 (250 of 269 [93%]). Postimplementation (February 1, 2020, to December 31, 2020), sugammadex (650 of 935 [70%]), neostigmine (195 of 935 [21%]), and no reversal (90 of 935 [10%]) were used to attain train-of-four ratios greater than or equal to 0.90 in 856 of 935 (92%) of patients. In the electronically searched medical charts (n = 20,181), postimplementation inpatients had shorter postanesthesia care unit lengths of stay (7% difference; median [in min] [25th, 75th interquartile range], 73 [55, 102] to 68 [49, 95]; P < 0.001), pulmonary complications were less (43% difference; 94 of 4,138 [2.3%] to 23 of 1,817 [1.3%]; P = 0.010; -1.0% difference [95% CI, -1.7 to -0.3%]), and hospital length of stay was shorter (median [in days] [25th, 75th], 3 [2, 5] to 2 [1, 4]; P < 0.001). CONCLUSIONS: In this professional practice initiative, documentation of train-of-four ratios greater than or equal to 0.90 occurred for 93% of patients in a busy clinical practice. Return-of-strength documentation is an intermediate outcome, and only one of many factors contributing to patient outcomes.

Adamgammadex in patients to reverse a moderate rocuronium-induced neuromuscular block.

AIMS: The aim of this study was to investigate the effectiveness, safety and pharmacokinetics of adamgammadex in surgical patients. METHODS: Forty-eight patients aged 18-64 years old were randomized to receive adamgammadex (2, 4, 6, and 8 mg.kg-1 ) or placebo at a ratio of 10:2 for reversal of 0.6 mg.kg-1 rocuronium-induced neuromuscular block. Neuromuscular function was monitored by TOF-Watch® SX. When the T2 of train-of-four (TOF) reappeared at the end of surgery, patients received an intravenous administration of adamgammadex or placebo. RESULTS: The recovery time of the TOF ratio to 0.9 decreased significantly from 39.3 [29.5, 50.2] minutes in the group that received placebo to 3.0 [2.3, 3.9] minutes, P < .0001; 2.1 [1.5, 3.0] minutes, P < .0001; 2.1 [1.8, 3.3] minutes, P < .0001; and 1.8 [1.5, 2.2] minutes, P < .0001 in the 2, 4, 6 and 8 mg.kg-1 adamgammadex groups, respectively. Then, adamgammadex also showed a shortened recovery time for the TOF ratio recovered to 0.8 and 0.7. Adamgammadex was well tolerated, and no cases of anaphylactic reactions, post-operative bleeding, recurarization, abnormal basic vital signs and prolonged QT intervals were observed. The pharmacokinetics of adamgammadex in plasma increased in dose-dependent manner. The 24-hour cumulative fraction of adamgammadex in urine was 65-83%, and that of rocuronium was increased after using adamgammadex from 15% to about 25-30%. CONCLUSION: Adamgammadex was found to be effective for reversal of rocuronium-induced neuromuscular block, and it was safe and well tolerated in patients.

Pro-Con Debate: Do We Need Quantitative Neuromuscular Monitoring in the Era of Sugammadex?

In this Pro-Con article, we debate the merits of using quantitative neuromuscular blockade monitoring. Consensus guidelines recommend their use to guide the administration of nondepolarizing neuromuscular blockade and reversal agents. A major impediment to this guideline is that until recently, reliable quantitative neuromuscular blockade monitors have not been widely available. Without them, anesthesia providers have been trained with and are adept at using a variety of qualitative neuromuscular blockade monitors otherwise known as peripheral nerve stimulators. Although perhaps less accurate, anesthesia providers find them reliable and easy to use. They have a long track record of using them with the perception that their use leads to effective neuromuscular blockade reversal and minimizes clinically significant adverse events from residual neuromuscular blockade. In the recent past, 2 disruptive developments have called upon anesthesia care providers to reconsider their practice in neuromuscular blockade administration, reversal, and monitoring. These include: (1) commercialization of more reliable quantitative neuromuscular monitors and (2) widespread use of sugammadex, a versatile reversal agent of neuromuscular blockade. Sugammadex appears to be so effective at rapidly and effectively reversing even the deepest of neuromuscular blockades, and it has left anesthesia providers wondering whether quantitative monitoring is indeed necessary or whether conventional, familiar, and less expensive qualitative monitoring will suffice? This Pro-Con debate will contrast anesthesia provider perceptions with evidence surrounding the use of quantitative neuromuscular blockade monitors to explore whether quantitative neuromuscular monitoring (NMM) is just another technology solution looking for a problem or a significant advance in NMM that will improve patient safety and outcomes.

Characterizing the Heart Rate Effects From Administration of Sugammadex to Reverse Neuromuscular Blockade: An Observational Study in Patients.

BACKGROUND: Reversal of neuromuscular blockade (NMB) with sugammadex can cause marked bradycardia and asystole. Administration of sugammadex typically occurs in a dynamic period when anesthetic adjuvants and gas concentrations are being titrated to achieve emergence. This evaluation examined the heart rate (HR) responses to sugammadex to reverse moderate to deep NMB during a steady-state period and sought mechanisms for HR changes. METHODS: Patients with normal sinus rhythm, who were undergoing elective surgery that included rocuronium for NMB, were evaluated. After surgery, while at steady-state surgical depth anesthesia with sevoflurane and mechanical ventilation, patients received either placebo or 2 or 4 mg/kg of sugammadex to reverse moderate to deep NMB. Study personnel involved in data analysis were blinded to treatment. Continuous electrocardiogram (ECG) was recorded from the 5 minutes before and 5 minutes after sugammadex/placebo administration. R-R intervals were converted to HR and averaged in 1-minute increments. The maximum prolongation of an R-R interval after sugammadex was converted to an instantaneous HR. RESULTS: A total of 63 patients were evaluated: 8 received placebo, and 38 and 17 received 2 and 4 mg/kg sugammadex. Age, body mass index, and patient factors were similar in groups. Placebo did not elicit HR changes, whereas sugammadex caused maximum instantaneous HR slowing (calculated from the longest R-R interval), ranging from 2 to 19 beats/min. There were 7 patients with maximum HR slowing >10 beats/min. The average HR change and 95% confidence interval (CI) during the 5 minutes after 2 mg/kg sugammadex were 3.1 (CI, 2.3-4.1) beats/min, and this was not different from the 4 mg/kg sugammadex group (4.1 beats/min [CI, 2.5-5.6]). HR variability derived from the standard deviation of consecutive R-R intervals increased after sugammadex. CONCLUSIONS: Sugammadex to reverse moderate and deep NMB resulted in a fast onset and variable magnitude of HR slowing in patients. A difference in HR slowing as a function of dose did not achieve statistical significance. The observational nature of the investigation prevented a full understanding of the mechanism(s) of the HR slowing.

Residual neuromuscular blockade in the ICU: a prospective observational study and national survey.

Residual neuromuscular blockade is associated with significant morbidity. It has been widely studied in anaesthesia; however, the incidence of residual neuromuscular blockade in patients managed in the ICU is unknown. We conducted a prospective observational study in a tertiary ICU to determine the incidence of residual neuromuscular blockade using quantitative accelerographic monitoring. We tested for residual neuromuscular blockade (defined as a train-of-four ratio < 0.9) before cessation of sedation in anticipation of tracheal extubation. We also surveyed 16 other ICUs in New Zealand to determine their use of neuromuscular monitoring. A total of 191 patients were included in the final analysis. The incidence (95%CI) of residual neuromuscular blockade was 43% (36-50%), with a similar incidence observed in non-postoperative and postoperative patients. There was a lower risk of residual neuromuscular blockade with atracurium than rocuronium (risk ratio (95%CI) of 0.39 (0.12-0.78)) and a higher risk with pancuronium than rocuronium (1.59 (1.06-2.49)). Our survey shows that, in New Zealand ICUs, monitoring of neuromuscular function is rarely carried out before tracheal extubation. When neuromuscular monitoring is undertaken, it is based on individual clinician suspicion and performed using qualitative measurements. No ICU reported using a quantitative monitor or a clinical guideline. The results demonstrate a high incidence of residual neuromuscular blockade in our ICU patients and identify the type of neuromuscular blocking drug as a possible risk factor. Monitoring neuromuscular function before tracheal extubation is not currently the standard of care in New Zealand ICUs. These data suggest that residual neuromuscular blockade may be an under-recognised problem in ICU practice.

Time interval between alfentanil and rocuronium administration necessary to prevent rocuronium-induced withdrawal movement.

BACKGROUND: We aimed to determine the time interval between alfentanil and rocuronium administration, at a 50% probability of preventing pain-induced withdrawal movement from rocuronium injection (TimeAR50). METHODS: A total of 64 patients scheduled for general anesthesia were enrolled in this study (33 men and 31 women). Anesthesia was induced with target-controlled infusion of propofol, at an effect-site target concentration of 3 µg/mL. Then, alfentanil 15 µg/kg was injected for 30 s. After 60 s, rocuronium 0.6 mg/kg was administered to the first patient. The Dixon's up-and-down method was used to determine the time interval for each subsequent patient (interval of 5 s). Mean arterial pressure (MAP) and heart rate (HR) were recorded at three time points: T0, pre-induction; T1, before rocuronium injection; and T2, 1 min after rocuronium injection. RESULTS: The TimeAR50 ± standard deviation (SD) was 5.6 ± 3.7 s and 21.9 ± 5.6 s in the male and female patients, respectively. Based on the probit regression, the TimeAR50 was 4.7 s (95% confidence interval [CI], 1.2-7.6 s) and 20.3 s (95% CI, 7.7-26.1 s) in the male and female patients, respectively. The TimeAR95 was 10.6 s (95% CI, 7.7-25.3 s) and 35.0 s (95% CI, 28.1-95.5 s) in the male and female patients, respectively, with significantly higher values in females than in males (P < 0.001). Compared with the T0, MAP and HR decreased significantly at T1 and T2 in both groups. CONCLUSION: The TimeAR50 required for preventing rocuronium-induced withdrawal movement were 4.7 s and 20.3 s in male and female patients, respectively. TRIAL REGISTRATION: This study was registered with the Chinese Clinical Trials Registry on April 7, 2021 (URL: http://www.chictr.org.cn . Registry number: ChiCTR2100045137 ) .

Efficacy and safety of sugammadex for neuromuscular blockade reversal in pediatric patients: an updated meta-analysis of randomized controlled trials with trial sequential analysis.

BACKGROUND: A recent survey revealed that extensive off-label use of sugammadex in pediatric anesthesia deserved particular attention. The present study with trial sequential analysis (TSA) aimed to evaluate the effects of sugammadex for antagonizing neuromuscular blockade (NMB) in pediatric patients, and to investigate whether the findings achieved the required information size to draw conclusions. METHODS: PubMed, Embase, Cochrane Library and China National Knowledge Infrastructure (CNKI) were searched from inception to April 2021. All randomized controlled trials used sugammadex as reversal agent in pediatric patients were enrolled. Time from NMB reversal to recovery of the train-of-four ratio (TOFr) to 0.9 and extubation time were considered as co-primary outcomes, and incidences of adverse events were considered as secondary outcomes. Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system was used to rate the quality of evidences. RESULTS: Data from 18 studies involving 1,065 pediatric patients were acquired. The results revealed that use of sugammadex was associated with shorter duration from administration of reversal agents to TOFr > 0.9 (MD = -14.42, with 95% CI [-17.08, -11.75]) and shorter interval from reversal from NMB to extubation (MD = -13.98, with 95% CI [-16.70, -11.26]) compared to control groups. TSA also indicated that the current sample sizes were sufficient with unnecessary further trials. Analysis of secondary outcomes indicated that administration of sugammadex was associated with less incidence of postoperative nausea and vomiting (PONV), bradycardia, and dry mouth compared to control groups. CONCLUSION: Considering of satisfactory and rapid neuromuscular blockade reversal with low incidences of adverse events, sugammadex might be considered as the preferred option for children in clinical anesthesia practice compared to acetylcholinesterase inhibitors. However, overall low-quality evidences in present study rated by GRADE system indicated that superiority of sugammadex employed in pediatric patients needs to be confirmed by more studies with high quality and large sample size in future.

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

BACKGROUND: Few randomized studies have assessed recovery from rocuronium- or vecuronium-induced moderate or deep neuromuscular blockade with sugammadex in pediatric participants. AIM: To assess sugammadex for reversal of neuromuscular blockade in pediatric participants. METHODS: This was a randomized, phase IV, active comparator-controlled, double-blind study. Participants aged 2 to <17 years, under moderate or deep neuromuscular blockade, were administered sugammadex (2 or 4 mg/kg) or neostigmine (50 µg/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 2 mg/kg versus neostigmine for reversal of moderate neuromuscular blockade, analyzed by analysis of variance adjusted for neuromuscular blocking agent and age. RESULTS: 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 2 mg/kg, sugammadex 4 mg/kg, and neostigmine groups, respectively. No hypersensitivity or anaphylaxis events were observed. Recovery to a train-of-four ratio of ≥0.9 with sugammadex 2 mg/kg was faster than neostigmine (1.6 min, 95% CI 1.3 to 2.0 vs. 7.5 min, 95% CI 5.6 to 10.0; p < .0001) and was comparable to sugammadex 4 mg/kg (2.0 min, 95% CI 1.8 to 2.3). CONCLUSIONS: Pediatric participants recovered from rocuronium- or vecuronium-induced moderate neuromuscular blockade significantly faster with sugammadex 2 mg/kg than with neostigmine. Time to reversal of deep neuromuscular blockade with sugammadex 4 mg/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 <17 years. CLINICAL TRIAL REGISTRATION: NCT03351608/EudraCT 2017-000692-92.