Rocuronium-induced Neuromuscular Blockade Research Articles

Rocuronium-specific antibodies drive perioperative anaphylaxis but can also function as reversal agents in preclinical models.

Neuromuscular blocking agents (NMBAs) relax skeletal muscles to facilitate surgeries and ease intubation but can lead to adverse reactions, including complications because of postoperative residual neuromuscular blockade (rNMB) and, in rare cases, anaphylaxis. Both adverse reactions vary between types of NMBAs, with rocuronium, a widely used nondepolarizing NMBA, inducing one of the longest rNMB durations and highest anaphylaxis incidences. rNMB induced by rocuronium can be reversed by the synthetic γ-cyclodextrin sugammadex. However, in rare cases, sugammadex can provoke anaphylaxis. Thus, additional therapeutic options are needed. Rocuronium-induced anaphylaxis is proposed to rely on preexisting rocuronium-binding antibodies. To understand the pathogenesis of rocuronium-induced anaphylaxis and to identify potential therapeutics, we investigated the memory B cell antibody repertoire of patients with suspected hypersensitivity to rocuronium. We identified polyclonal antibody repertoires with a high diversity among V(D)J genes without evidence of clonal groups. When recombinantly expressed, these antibodies demonstrated specificity and low affinity for rocuronium without cross-reactivity for other NMBAs. Moreover, when these antibodies were expressed as human immunoglobulin E (IgE), they triggered human mast cell activation and passive systemic anaphylaxis in transgenic mice, although their affinities were insufficient to serve as reversal agents. Rocuronium-specific, high-affinity antibodies were thus isolated from rocuronium-immunized mice. The highest-affinity antibody was able to reverse rocuronium-induced neuromuscular blockade in nonhuman primates with kinetics comparable to that of sugammadex. Together, these data support the hypothesis that antibodies cause anaphylactic reactions to rocuronium and pave the way for improved diagnostics and neuromuscular blockade reversal agents.

Reversal of Rocuronium-Induced Neuromuscular Blockade by Sugammadex Under Sevoflurane and Desflurane Anesthesia in Children.

In children, neuromuscular blockers may have different effects with various inhalation agents and incomplete reversal of the blockade continues to be a problem. The aim of the study is to observe the effects of sugammadex on reversing the blockade by a single dose of rocuronium, the peak inspiratory pressure, hemodynamic parameters in children under sevoflurane and desflurane anesthesia. One hundred forty-eight children aged 2-10 years old, to be operated under shortterm general anesthesia, were enrolled in this prospective randomized controlled trial. After induction, the patients were intubated at the end of TOF (Train-of-four) ratio of 1.0-0. The time taken until TOF reached 0.25 was recorded, and 2 mg/kg sugammadex was administered to the patients. The period until the TOF was at least 0.9 and in the first 10 minutes after sugammadex injection, peak inspiratory pressure, the systolic-diastolic arterial pressure, and the heart rate were monitored and possible side effects were observed in the recovery room. Following the injection of sugammadex, the time taken for TOF of 0.25 to reach >0.9 was significantly shorter in the 2-4-year-old age group under sevoflurane anesthesia. After sugammadex injection, a small but statistically significant increase in peak inspiratory pressure values was observed in Group D at the 2nd, 5th, and 10th minutes. Rapid and complete recovery was achieved from the block induced by a single dose of 0.6 mg/ kg rocuronium by the use of sugammadex which did not give rise to any side effects.

Sugammadex for reversal of rocuronium-induced neuromuscular blockade during alfaxalone anesthesia in dogs

ObjectiveTo investigate the reversal effect of sugammadex on neuromuscular blockade induced by a single bolus of rocuronium in dogs under alfaxalone anesthesia. Study designRandomized, prospective, crossover experimental study. AnimalsA group of six adult Beagle dogs (three females and three males), weighing 11.3–15.8 kg and aged 6–8 years, were used. MethodsDogs were anesthetized twice with a 1.25 times minimum infusion rate of alfaxalone, with a washout period of at least 14 days between experiments. Neuromuscular function was monitored using acceleromyography with train-of-four (TOF) stimulation of the peroneal nerve. After recording the control TOF ratio (TOFRC), rocuronium (0.5 mg kg–1) was administered intravenously. Subsequently, sugammadex (4 mg kg–1) or an equal volume of saline (control treatment) was administered intravenously when the TOF count returned from 0 to 1 after neuromuscular blockade. Time from rocuronium injection to TOF count = 0 (onset time), time from TOF count = 0 to TOF count = 1 (maximum blockade period), time of first twitch amplitude recovery from 0.25 to 0.75 (recovery index), and time from sugammadex or saline administration to TOF ratio/TOFRC ≥ 0.9 (recovery time) were recorded. ResultsThe onset time and maximum blockade duration did not differ between sugammadex treatment [1.2 (0.7–1.5) minutes and 9.9 (6.3–10.5) minutes, respectively] and control treatment [median (range); 1.0 (0.7–1.1) minutes and 9.9 (8.8–11.5) minutes, respectively] (p = 0.219 and 0.844, respectively). Recovery index was 0.5 (0.3–0.7) minutes in sugammadex treatment, which was shorter than that in control treatment [4.5 (3.7–4.9) minutes] (p = 0.031). Recovery time was 0.8 (0.5–2.8) minutes in sugammadex treatment, which was shorter than that in control treatment [10.5 (6.8–14.3) minutes] (p = 0.031). Conclusions and clinical relevanceRocuronium-induced neuromuscular blockade was effectively reversed by sugammadex in dogs anesthetized with alfaxalone.

Chronic exposure to dexamethasone may not affect sugammadex reversal of rocuronium-induced neuromuscular blockade: an in vivo study on rats.

Chronic glucocorticoid exposure is associated with resistance to nondepolarizing neuromuscular blocking agents. Therefore, we hypothesized that sugammadex-induced recovery would occur more rapidly in subjects exposed to chronic dexamethasone compared to those who were not exposed. This study evaluated the sugammadex-induced recovery profile after neuromuscular blockade (NMB) in rats exposed to chronic dexamethasone. Sprague-Dawley rats were allocated to three groups (dexamethasone, control, and pair-fed group) for the in vivo study. The mice received daily intraperitoneal dexamethasone injections (500 μg/kg) or 0.9% saline for 15 days. To achieve complete NMB, 3.5 mg/kg rocuronium was administered on the sixteenth day. The recovery time to a train-of-four ratio ≥ 0.9 was measured to evaluate the complete recovery following the sugammadex injection. Among the groups, no significant differences were observed in the recovery time to a train-of-four ratio ≥ 0.9 following sugammadex administration (P = 0.531). The time to the second twitch of the train-of-four recovery following rocuronium administration indicated that the duration of NMB was significantly shorter in Group D than that in Groups C and P (P = 0.001). Chronic exposure to dexamethasone did not shorten the recovery time of sugammadex-induced NMB reversal. However, the findings of this study indicated that no adjustments to sugammadex dosage or route of administration is required, even in patients undergoing long-term steroid treatment.

Comparative study between sugammedex and neostigmine as a reversal agent of rocuronium for pediatric patients 2-12 years old going for surgery under general anaesthesia

Aim. The neuromuscular blocker has long been used during surgical procedures. The neuromuscular blockade produced by rocuronium can be reversed with sugammadex and neostigmine as reversal agents. This systematic review aims to determine the impact of sugammadex and neostigmine comparison as a reversal agent of rocuronium for pediatric patients 2-12 years old going for surgery under general anesthesia. Materials and Methods. This review examined recent studies assessing the impact of sugammadex and neostigmine comparison as a reversal agent of rocuronium for pediatric patients 2-12 years old going for surgery under general anesthesia. Data were searched from Google Scholar, PubMed, Hindawi, Anesthesiology, MEDLINE, and CENTRAL using keywords’ General Anesthesia,’ ‘Reversal Agent,’ ‘Rocuronium for Pediatric Patients,’ ‘Neuromuscular Blockers,’ ‘Sugammadex and Neostigmine,’ ‘Role of Analgesics.’ The review followed PRISMA guidelines. Results. The initial search for publications comparing sugammadex and neostigmine as a reversal agent of rocuronium for pediatric patients yielded 9000 papers, from which 600 were selected. The reviews’ articles were further analyzed to ensure they were pertinent to the Comparative Impact of Reversal Agents (Sugammadex And Neostigmine) of Rocuronium for Pediatric Patients. Around 319 references were examined for their potential applicability to the medical field of anesthesia. A total of 15 articles were included, with preference given to those published from 2014 to 2023 during the last ten years. Conclusion. The particular relaxant-binding medication promptly and successfully alleviates rocuronium-induced neuromuscular blockade in pediatric surgery patients. Considering the study’s outcomes, it can be concluded that sugammadex may restore any level of steroidal muscle relaxant-induced neuromuscular block faster than neostigmine.

Conventional reversal of rocuronium-induced neuromuscular blockade by sugammadex in Korean children: pharmacokinetics, efficacy, and safety analyses.

Background: Sugammadex is known to reverse neuromuscular blockade induced by non-depolarizing agents. In children, the recommended dose for reversal of moderate neuromuscular blockade is 2mg/kg. We investigated the pharmacokinetics and pharmacodynamics of sugammadex in Korean children. Methods: Children (2-17years of age) undergoing brain or spine surgery were enrolled and randomly assigned to control (neostigmine) and 2, 4, or 8mg/kg sugammadex groups. Following induction of anesthesia and monitoring of the response to train-of-four stimulation, 1mg/kg rocuronium was intravenously administered. Upon reappearance of the second twitch to train-of-four stimulation, the study drug was administered according to group allocation. The plasma concentrations of rocuronium and sugammadex were serially measured at nine predefined time points following study drug administration. To determine efficacy, we measured the time elapsed from drug administration to recovery of T4/T1 ≥ 0.9. For pharmacokinetics, non-compartmental analysis was performed and we monitored adverse event occurrence from the time of study drug administration until 24h post-surgery. Results: Among the 29 enrolled participants, the sugammadex (2mg/kg) and control groups showed recovery times [median (interquartile range)] of 1.3 (1.0-1.9) and 7.7 (5.3-21.0) min, respectively (p = 0.002). There were no significant differences in recovery time among the participants in sugammadex groups. The pharmacokinetics of sugammadex were comparable to those of literature findings. Although two hypotensive events related to sugammadex were observed, no intervention was necessary. Conclusion: The findings of this pharmacokinetic analysis and efficacy study of sugammadex in Korean children indicated that sugammadex (2mg/kg) may be safely administered for reversing moderate neuromuscular blockade. Some differences in pharmacokinetics of sugammadex were observed according to age. Clinical Trial Registration: http://clinicaltrials.gov (NCT04347486).

Application of neuromuscular blockade using Rocuronium for performing different surgeries and its reversal by Neostigmine-Glycopyrrolate combination in dogs

This study was executed in the clinical setup to investigate the effects of Rocuronium and its reversal by Neostigmine and Glycopyrrolate (Myopyrolate) combination in Propofol-Isoflurane anaesthetized dogs. Rocuronium-induced neuromuscular blockade was applied to 21 clinical cases. Out of which, 19 cases were of orthopaedic surgeries and 2 cases of ovariohysterectomy. After the animal had stabilized on the mixture of isoflurane and oxygen, the relaxation of muscle was induced using Rocuronium @ 0.5 mg/kg b.wt. Immediately IPPV was provided in volume control mode. Neuromuscular blockade was reversed using a single syringe combination drug having both Neostigmine and Glycopyrrolate (Myopyrolate) @ 0.05 mg/kg b.wt and @ 0.01 mg/kg b.wt, respectively. Rocuronium caused the centering of the ocular globe gradually in less than 30 sec. During orthopaedic surgeries, the reduction of fractured ends became easy without much tissue trauma. In ovariohysterectomy surgeries, the appropriate level of abdominal muscle relaxation further helped in the easy exteriorization of the ovarian stump. The onset time for Rocuronium was 17.64±1.10 sec and its duration of action was 27.82±0.72 min. The use of Rocuronium along with IPPV caused minimal alteration of the physiological parameters with no clinical consequences and thus can be considered a complication-free anaesthetic protocol for interventions demanding muscle relaxation.

Sugammadex administration in patients with end-stage renal disease: a narrative review with recommendations.

Due to unknown safety concerns, sugammadex should not be administered to patients withend-stage renal disease (ESRD). However, because the supply of benzylisoquinolinium-typeneuromuscular blocking agents (NMBAs) has been discontinued, rocuronium is the onlynon-depolarizing NMBA that can be used in clinical settings in some countries, includingSouth Korea. The administration of sugammadex cannot be avoided to achieve rapid andcomplete neuromuscular recovery in patients with ESRD or renal transplantation after rocuronium administration. Although there has been a limited number of clinical studies involving the use of sugammadex in patients with ESRD, studies have shown that sugammadexcan effectively and safely reverse rocuronium-induced neuromuscular blockade (NMB) inpatients with ESRD, however recovery of neuromuscular function in patients with ESRD isslower than in patients with normal renal function. Nonetheless, safety-concerns are yet tobe addressed. Considering the small number of clinical studies, high heterogeneity amongstudies, and insufficient safety information, more extensive data on the efficacy and safetyof sugammadex in patients with ESRD are needed. In particular, it is important to securedata on safety, including residual NMB after surgery, recurarization and cardiorespiratorycomplications, anaphylactic reactions, and long-term morbidity and mortality. Furthermore,anesthesiologists should remember that performing proper quantitative neuromuscularmonitoring and neuromuscular management based on the monitoring signs are the mostessential requirements when using sugammadex in patients with ESRD.

Sugammadex in Emergency Situations.

Sugammadex may be required or used in multiple emergency situations. Moderate and high doses of this compound can be used inside and outside the operating room setting. In this communication, recent developments in the use of sugammadex for the immediate reversal of rocuronium-induced neuromuscular blockade were assessed. In emergency surgery and other clinical situations necessitating rapid sequence intubation, the tendency to use rocuronium followed by sugammadex instead of succinylcholine has been increasing. In other emergency situations such as anaphylactic shock caused by rocuronium or if intubation or ventilation is not possible, priority should be given to resuming ventilation maintaining hemodynamic stability, in accordance with the traditional guidelines. If necessary for the purpose of resuming ventilation, reversal of neuromuscular blockade should be done in a timely fashion.

Sugammadex versus neostigmine for neuromuscular blockade reversal in outpatient surgeries: A randomized controlled trial to evaluate efficacy and associated healthcare cost in an academic center.

Neuromuscular blockade is an essential component of the general anesthesia as it allows for a better airway management and optimal surgical conditions. Despite significant reductions in extubation and OR readiness-for-discharge times have been associated with the use of sugammadex, the cost-effectiveness of this drug remains controversial. We aimed to compare the time to reach a train-of-four (TOF) response of ≥0.9 and operating room readiness for discharge in patients who received sugammadex for moderate neuromuscular blockade reversal when compared to neostigmine during outpatient surgeries under general anesthesia. Potential reduction in time for OR discharge readiness as a result of sugammadex use may compensate for the existing cost-gap between sugammadex and neostigmine. We conducted a single-center, randomized, double arm, open-label, prospective clinical trial involving adult patients undergoing outpatient surgeries under general anesthesia. Eligible subjects were randomized (1:1 ratio) into two groups to receive either sugammadex (Groups S), or neostigmine/glycopyrrolate (Group N) at the time of neuromuscular blockade reversal. The primary outcome was the time to reverse moderate rocuronium-induced neuromuscular blockade (TOF ratio ≥0.9) in both groups. In addition, post-anesthesia care unit (PACU)/hospital length of stay (LOS) and perioperative costs were compared among groups as secondary outcomes. Thirty-seven subjects were included in our statistical analysis (Group S= 18 subjects and Group N= 19 subjects). The median time to reach a TOF ratio ≥0.9 was significantly reduced in Group S when compared to Group N (180 versus 540 seconds; p = 0.0052). PACU and hospital LOS were comparable among groups. Postoperative nausea and vomiting was the main adverse effect reported in Group S (22.2% versus 5.3% in Group N; p = 0.18), while urinary retention (10.5%) and shortness of breath (5.3%) were only experienced by some patients in Group N. Moreover, no statistical differences were found between groups regarding OR/anesthesia, PACU, and total admission costs. Sugammadex use was associated with a significantly faster moderate neuromuscular blockade reversal. We found no evidence of increased perioperative costs associated with the use of sugammadex in patients undergoing outpatient surgeries in our academic institution. [https://clinicaltrials.gov/] identifier number [NCT03579589].

Pediatrik olgularda uygulanan rijit bronkoskopi işleminde anestezi derlemesinde sugammadeks ve neostigminin etkinliğininin karşılaştırılması

Aim: To compare the efficacy of sugammadex and neostigmine, which are used to reverse rocuronium- neuromuscular blockade in children who underwent rigid bronchoscopy due to tracheobronchial foreign body aspiration.Materials and Methods: The data of 54 patients who underwent rigid bronchoscopy with the suspicion of foreign body aspiration in children aged 0-18 in our hospital between 2013 and 2018 were retrospectively analyzed.Results: Thirty of the cases were male and 24 were female. Atropine-neostigmine was administered to 23 patients and sugammadex was administered to 31 patients to reverse neuromuscular blockade. While no complications were found in 41 cases, bronchospasm was found in 6 cases, hypoxia in 5 cases, and laryngospasm in 2 cases. Recovery time was shorter in patients who received sugammadex (p<0.001).Conclusion: Recovery time is shorter after sugammadex administration in reversing rocuronium-induced neuromuscular blockade in pediatric rigid bronchoscopy anesthesia.

Effects of hydrocortisone-presensitized sugammadex on recovery from neuromuscular blockade induced by rocuronium: a rodent in vivo study.

BackgroundSugammadex is a specific antagonist of aminosteroidal neuromuscular blocking agents with 1:1 binding to guest molecules. Sugammadex can also bind to other drugs having a steroid component in its chemical structure. In this in vivo experiment, we investigated the differences in the recovery of rocuronium-induced neuromuscular blockade using sugammadex pre-exposed with two different concentrations of hydrocortisone.MethodsThe sciatic nerves and tibialis anterior muscles of 30 adult Sprague–Dawley rats were prepared for the experiment. The sciatic nerves were stimulated using a train-of-four (TOF) pattern with indirect supramaximal stimulation at 20 s intervals. After 15 min of stabilization, a 250 μg loading dose and 125 μg booster doses of rocuronium were serially administered until > 95% depression of the first twitch tension of TOF stimulation (T1) was confirmed. The study drugs were prepared by mixing sugamadex with the same volume of three different stock solutions (0.9% normal saline, 10 mg/ml hydrocortisone, and 100 mg/ml hydrocortisone). The recovery of rats from neuromuscular blockade was monitored by assessing T1 and the TOF ratio (TOFR) simultaneously until T1 was recovered to > 95% and TOFR to > 0.9.ResultsIn the group injected with sugammadex premixed with a high concentration of hydrocortisone, statistically significant intergroup differences were observed in the recovery progression of T1 and TOFR (P < 0.050).ConclusionsWhen sugammadex was pre-exposed to a high dose of hydrocortisone only, recovery from neuromuscular blockade was delayed. Delayed recovery from neuromuscular blockade is not always plausible when sugammadex is pre-exposed to steroidal drugs.

Effects of Rocuronium-induced neuromuscular blockade with sugammadex on diaphragm in rats

Effects of Rocuronium-induced neuromuscular blockade with sugammadex on diaphragm in rats

Perioperative Efficiency of Sugammadex Following Laparoscopic Cholecystectomy in Clinical Practice.

Background: Studies have proposed that the routine use of the modified gamma-cyclodextrin, sugammadex, could provide perioperative time savings. However, these investigations have been limited to small group analyses. The purpose of this study was to test the effectiveness of sugammadex on perioperative times when compared to neostigmine under general clinical practice conditions following rocuronium-induced neuromuscular blockade for laparoscopic cholecystectomy. Methods: Following institutional review board approval, data from 1,611 consecutive surgical records for laparoscopic cholecystectomy were reviewed. Patient characteristics, type of primary neuromuscular blocking reversal agent, operating room (OR) discharge times, and postanesthesia care unit (PACU) recovery times were the measures of interest. Equivalence testing was used to determine the between-group differences of the reversal agents in the two perioperative time periods of interest. Results: OR discharge times averaged 10.9 (95% CI, 10-11.8) minutes for patients administered sugammadex and 8.9 (95% CI, 8.2-9.7) minutes for patients administered neostigmine. PACU recovery times averaged 77.6 (95% CI, 74.1-81.1) minutes for sugammadex and 68.6 (95% CI, 65.9-71.3) minutes for neostigmine. Equivalence testing demonstrated no improvement in the two perioperative times with sugammadex. Conclusion: These results suggest no perioperative time savings with sugammadex when compared to neostigmine following laparoscopic cholecystectomy under general clinical practice conditions.

Efficacy and Safety of Sugammadex for the Reversal of Rocuronium-Induced Neuromuscular Blockade in Patients with End-Stage Renal Disease: A Systematic Review and Meta-Analysis.

Background and Objectives: Sugammadex is widely used in anesthesia to reverse rocuronium-induced neuromuscular blockade (NMB). In patients with compromised kidney function, most drugs show alteration of their pharmacokinetic profile with reduced clearance. The purpose of this article is to examine the efficacy, pharmacokinetics, and safety of sugammadex in end-stage renal disease (ESRD) patients receiving general anesthesia, using a systematic review. Materials and Methods: The databases of PubMed, EMBASE, the Cochrane Library, Web of Science, Scopus, KoreaMed, and ClinicalTrials.gov were searched for studies comparing the efficacy or safety outcomes of sugammadex administration for the reversal of rocuronium-induced NMB, in ESRD patients (group R) or in those with normal renal function (group N) undergoing surgery under general anesthesia. Results: We identified nine studies with 655 patients—six prospective, case-control studies with 179 patients (89 and 90 in groups R and N) and three retrospective observational studies with 476 ESRD patients. In the six prospective studies, the times taken to reach a train-of-four ratio ≥0.9, 0.8, and 0.7 were significantly longer in group R than in group N (weighted mean difference [95% confidence interval] [min]: 1.14 [0.29 to 2.00], 0.9 [0.24 to 1.57], 0.89 [0.20 to 1.57], respectively). The total plasma clearance of sugammadex was significantly lower in group R than in group N. There was no significant difference in the incidence of NMB recurrence and prolonged time to recovery between the groups. In the three retrospective studies, the possibility of sugammadex-related adverse events appears to be insignificant. Conclusions: Sugammadex may effectively and safely reverse rocuronium-induced NMB in patients with ESRD, although the recovery to a TOF ratio of 0.9 may be prolonged compared to patients with normal renal function. Further studies are needed, considering the small number of studies included and the high heterogeneity of some of the results.

Sugammadex versus neostigmine for reversal of rocuronium-induced neuromuscular blockade in infants: A prospective randomized pilot study

BackgroundThis study aimed to compare sugammadex and neostigmine for the antagonism of rocuronium-induced neuromuscular block in pediatric patients with biliary atresia and impaired liver function undergoing Kasai operation. MethodsForty pediatric patients below three months of age underwent the Kasai operation. When the surgery ended and the second response (T2) to train-of-four (TOF) stimulation was detected, patients were randomly assigned to receive either 50 µg/kg neostigmine combined with 20 µg/kg atropine, or 2 mg/kg sugammadex. We recorded the time between receiving the neostigmine or sugammadex and reaching corrected TOF ratios of 0.9 and 1.0.We also noted their length of stay in the post-anesthesia care unit (PACU) and any incidents of postoperative recurrence of neuromuscular blockade or other adverse events during recovery. ResultsThe times taken to reach TOF ratios of 0.9 and 1.0 after sugammadex were shorter than after neostigmine (p<0.001). The mean duration of PACU stay was also shorter with the use of sugammadex compared to neostigmine (22.55±5.76 min vs. 40.50±7.93 min; p<0.001). We did not record any incidents of postoperative recurrence of neuromuscular blockade after administration of either treatment .The total number of patients who suffered from post-operative vomiting were statistically lower in the sugammadex group than in the neostigmine group (2 vs. 9; p = 0.03). One patient (5%) in the sugammadex group versus 13 patients (65%) in the neostigmine group developed tachycardia (p<0.001). ConclusionsSugammadex at a dose of 2.0 mg/kg is a safe, quick, and efficacious reversal agent to rocuronium-induced neuromuscular blockade (NMB) in pediatric patients below three months of age undergoing the Kasai operation, with a lower incidence of post-operative tachycardia, vomiting, and shivering than neostigmine.

Effects of sevoflurane, propofol or alfaxalone on neuromuscular blockade produced by a single intravenous bolus of rocuronium in dogs

ObjectiveTo compare the effects of sevoflurane, propofol and alfaxalone on the neuromuscular blockade induced by a single intravenous bolus of rocuronium in dogs. Study designA randomized, prospective, crossover experimental study. AnimalsA total of eight adult Beagle dogs (four female, four male), weighing 8.9–15.3 kg and aged 5–7 years. MethodsThe dogs were anesthetized three times with 1.25× minimum alveolar concentration of sevoflurane (SEVO treatment) and 1.25× minimum infusion rate of propofol (PROP treatment) or alfaxalone (ALFX treatment) at intervals of ≥14 days. Neuromuscular function was monitored with train-of-four (TOF) stimulation of the peroneal nerve by acceleromyography. After recording the control TOF ratio (TOFRC), a single bolus dose of rocuronium (1 mg kg–1) was administered intravenously. The times from rocuronium administration to achieving TOF count 0 (onset time), from achieving TOF count 0 to the reappearance of TOF count 4 (clinical blockade period), from 25% to 75% of TOFRC (recovery index) and from achieving TOF count 0 to TOF ratio/TOFRC >0.9 (total neuromuscular blockade duration) were recorded. ResultsThe onset time and recovery index did not differ among the treatments. The median clinical blockade period was longer in the SEVO treatment [27.3 (26.0–30.3) minutes] than in PROP [16.6 (15.4–18.0) minutes; p = 0.002] and ALFX [22.4 (18.6–23.1) minutes; p = 0.017] treatments; and longer in the ALFX treatment than in the PROP treatment (p = 0.020). The mean total neuromuscular blockade duration was longer in the SEVO treatment (43.7 ± 9.9 minutes) than in PROP (25.1 ± 2.7 minutes; p < 0.001) and ALFX (32.5 ± 8.4 minutes; p = 0.036) treatments. Conclusions and clinical relevanceCompared with alfaxalone and propofol, sevoflurane prolonged rocuronium-induced neuromuscular blockade by a significantly greater extent in dogs.

Effects of age on sugammadex reversal of neuromuscular blockade induced by rocuronium in Chinese children: a prospective pilot trial

BackgroundSugammadex reverses neuromuscular blockade induced by steroidal relaxants. We compared the recovery for neuromuscular blockade reversal with sugammadex in children aged 1–12 years.MethodsFrom August 2019 to August 2020, patients who received 2.0 mg·kg− 1 sugammadex for neuromuscular blockade reversal after surgery were recruited. The primary outcome was the time for the train-of-four ratio (TOFR) to recover to 0.9; secondary outcomes included the incidence of the TOFR < 0.9, extubation time, length of stay at the post-anesthesia care unit, and adverse events. Hemodynamic parameters before and 5 min after sugammadex administration and vital signs in the recovery room were also recorded.ResultsEighty-six children were recruited (1 to < 3 years, n = 23; 3 to < 5 years, n = 33; 5 to ≤12 years, n = 30). Intergroup differences in the recovery of the TOFR to 0.9 were not statistically significant (F = 0.691, p = 0.504). Recurrence of the TOFR < 0.9 was not observed in any group. Five minutes after sugammadex administration, the heart rates of patients aged 3 to < 5 and 5 to ≤12 years were significantly lower than those at baseline (p < 0.05). Extubation time was similar in patients aged 1 to ≤12 years. Length of stay and end-tidal capnography at the post-anesthesia care unit as well as adverse events did not differ significantly.ConclusionA moderate (TOF count two) rocuronium-induced neuromuscular blockade can be effectively and similarly reversed with sugammadex 2 mg·kg− 1 in Chinese children aged 1–12 years.Trial registrationChinese Clinical Trial Registry: ChiCTR1900023715 (June 8, 2019).

Effects of sevoflurane and adenosine receptor antagonist on the sugammadex-induced recovery from rocuronium-induced neuromuscular blockade in rodent phrenic nerve-hemidiaphragm tissue specimens.

Sevoflurane affects on the A1 receptor in the central nervous system and potentiates the action of neuromuscular blocking agents. In the present study, we investigated whether sevoflurane (SEVO) has the ability to potentiate the neuromuscular blocking effect of rocuronium and if the specific antagonist of adenosine receptor (SLV320) can reverse this effect. In this study, phrenic nerve–hemidiaphragm tissue specimens were obtained from 40 Sprague–Dawley (SD) rats. The specimens were immersed in an organ bath filled with Krebs buffer and stimulated by a train‐of‐four (TOF) pattern using indirect supramaximal stimulation at 20 s intervals. The specimens were randomly allocated to control, 2‐chloroadenosine (CADO), SEVO, or SLV320 + SEVO groups. In the CADO and SLV320 + SEVO groups, CADO and SLV320 were added to the organ bath from the start to a concentration of 10 μM and 10 nM, respectively. We then proceeded with rocuronium‐induced blockade of >95% depression of the first twitch tension of TOF (T1) and TOF ratio (TOFR). In the SEVO and SLV320 + SEVO groups, SEVO was added to the Krebs buffer solution to concentration of 400–500 μM for 10 min. Sugammadex‐induced T1 and TOFR recovery was monitored for 30 min until >95% of T1 and >0.9 of TOFR were confirmed, and the recovery pattern was compared by plotting these data. T1 recovery in the SEVO and CADO groups was significantly delayed compared with the control and SLV320 + SEVO groups (p < .05). In conclusion, sevoflurane affects on the A1 receptor at the neuromuscular junction and delays sugammadex‐induced recovery from neuromuscular blockade.

Recovery Profile of Sugammadex versus Neostigmine in Pediatric Patients Undergoing Cardiac Catheterization: A Randomized Double-Blind Study.

Background:Sugammadex is a selective reversal agent which has the ability to reverse deep neuromuscular blockade. However, there are still controversial results as regard sugammadex effects on the quality of recovery. We hypothesized that Sugammadex may have better recovery profile compared to neostigmine in pediatric patients with congenital heart diseases undergoing cardiac catheterization.Patients and Methods:This prospective randomized double-blind study included 50 pediatric patients aged <2 years who were divided into two groups according to the reversal agent used; Group S (Sugammadex) and Group N (Neostigmine). Both groups received the same anesthetic technique during cardiac catheterization, and basic hemodynamic monitoring was ensured in both groups. After the procedure, reversal was done using 4 mg.kg‒1 sugammadex or 0.04 mg. kg‒1 neostigmine plus 0.02 mg. kg‒1 atropine according to the group allocation. Recovery time and side effects were recorded.Results:The two groups showed comparable findings regarding demographics. Nonetheless, the total time of anesthesia had mean values of 91.06 and 101.25 min in the two groups, respectively (P = 0.003), while recovery time had mean values of 1.61 and 9.23 min in the same groups, respectively (P < 0.001). Hemodynamic profile (heart rate and mean arterial pressure) was better after reversal with sugammadex. Blood sugar levels and side effects showed no significant difference between both groups.Conclusion:Sugammadex can be a more rapid and effective alternative to neostigmine for reversal of rocuronium-induced neuromuscular blockade in pediatric patients undergoing cardiac catheterization.