[The effect of deep neuromuscular block combined with low pneumoperitoneum pressure on postoperative pain in patients undergoing laparoscopic radical colorectal surgery].

Objective: To investigate the effect of deep neuromuscular blockade (DNMB) combined with low pneumoperitoneum pressure anesthesia strategy on postoperative pain in patients undergoing laparoscopic colorectal surgery. Methods: This study was a randomized controlled trial. One hundred and twenty patients who underwent laparoscopic colorectal surgery at Cancer Hospital of Chinese Academy of Medical Sciences from December 1, 2022 to May 31, 2023 were selected and randomly divided into two groups by random number table method. Moderate neuromuscular blockade [train of four stimulations count (TOFC)=1-2] was maintained in patients of the control group (group C, n=60) and pneumoperitoneum pressure level was set at 15 mmHg(1 mmHg=0.133 kPa). DNMB [post-tonic stimulation count (PTC)=1-2] was maintained in patients of the DNMB combined with low pneumoperitoneum pressuregroup (group D, n=60) and pneumoperitoneum pressure level was set at 10 mmHg. The primary measurement was incidence of moderate to severe pain at 1 h after surgery. The secondary measurements the included incidence of moderate to severe pain at 1, 2, 3, 5 d and 3 months after surgery, the incidence of rescue analgesic drug use, the doses of sufentanil in analgesic pumps, surgical rating scale (SRS) score, the incidence of postoperative residual neuromuscular block, postoperative recovery [evaluated with length of post anesthesia care unit (PACU) stay, time of first exhaust and defecation after surgery and length of hospital stay] and postoperative inflammation conditions [evaluated with serum concentration of interleukin (IL)-1ß and IL-6 at 1 d and 3 d after surgery]. Results: The incidence of moderate to severe pain in group D 1 h after surgery was 13.3% (8/60), lower than 30.0% (18/60) of group C (P<0.05). The incidence of rescue analgesia in group D at 1 h and 1 d after surgery were 13.3% (8/60) and 4.2% (5/120), respectively, lower than 30.0% (18/60) and 12.5% (15/120) of group C (both P<0.05). The IL-1ß level in group D was (4.1±1.8)ng/L at 1 d after surgery, which was lower than (4.9±2.6) ng/L of group C (P=0.048). The IL-6 level in group D was (2.0±0.7)ng/L at 3 d after surgery, which was lower than (2.4±1.1) ng/L of group C (P=0.018). There was no significant difference in the doses of sufentanil in analgesic pumps, intraoperative SRS score, incidence of neuromuscular block residue, time spent in PACU, time of first exhaust and defecation after surgery, incidence of nausea and vomiting, and length of hospitalization between the two groups (all P>0.05). Conclusion: DNMB combined with low pneumoperitoneum pressure anesthesia strategy alleviates the early-stage pain in patients after laparoscopic colorectal surgery.

Muscular Function Recovery from General Anesthesia in 132 Patients Undergoing Surgery with Acceleromyography, Combined Acceleromyography, and Ultrasonography, and without Monitoring Muscular Function.

BACKGROUND Diaphragmatic thickness fraction (DTF), measured by ultrasound, can predict the occurrence of postoperative residual neuromuscular blockade (RNMB). We hypothesized that the utilization of diaphragmatic ultrasound during the postoperative awakening phase of anesthesia in patients offers a successful means of avoiding RNMB in a notably comfortable manner, as compared to the use of acceleromyograph. MATERIAL AND METHODS Patients who underwent elective thyroid cancer radical surgery were enrolled in this prospective clinical study. Eligible participants were randomly assigned to 1 of 3 groups: 1) combined ultrasonography with acceleromyography group (the US+AMG group), 2) the AMG group, or 3) the usual clinical practice group (the UCP group). The primary outcomes of the study were the incidence of RNMB and hypoxemia after tracheal extubation. RESULTS The study included a total of 127 patients (43 in the US+AMG group, 44 in the AMG group, and 40 in the UCP group). The incidence of RNMB and hypoxemia was higher in the UCP group than in the US+AMG and AMG groups at 15 and 30 min after extubation, respectively. The mean area under the receiver operating characteristic curve, and the decision curve of the recovery rate of DTF (DTF) was greater than that of DTF. CONCLUSIONS The use of diaphragm ultrasound during the postoperative awakening phase of anesthesia can significantly reduce the incidence of RNMB. This method was non-inferior to the use of AMG during the entire perioperative period.

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.

Comparative performance of stimpod electromyography with mechanomyography for quantitative neuromuscular blockade monitoring.

PURPOSE: The purpose of this study was to compare the Stimpod electromyograph neuromuscular blockade monitor to mechanomyography, which is widely considered to be the reference standard. METHODS: The Stimpod electromyograph was used with its designated electrode array on the same hand as the mechanomyograph. Pairs of train-of-four measurements were recorded every 0.5-2 min. When the train-of-four count was zero on the electromyograph monitor, pairs of post tetanic count measurements were recorded every 2.5 min, instead of train-of-four measurements. Measurements were recorded from immediately after induction of anesthesia until just before emergence. Stimulation current was set to 60 mA with a duration of 200 microsec. The mechanomyography recording system recorded each twitch waveform for analysis. High resolution electromyograph waveforms were also recorded using a datalogger accessory provided by the manufacturer, facilitating inspection of individual waveforms. The administration of neuromuscular blocking drugs was left up to the discretion of the anesthesia care team. RESULTS: Twenty-three patients contributed 1,088 data pairs suitable for analysis. Bland-Altman analysis of 415 pairs of train-of-four ratios showed a bias of 0.028 and limits of agreement of -0.18 and 0.24. Two hundred seventy-three train-of-four count data pairs were compared by Cohen's quadratically weighted kappa which was calculated to be 0.44, indicating moderate agreement. Three hundred thirty-eight post tetanic count data pairs were compared by Cohen's quadradically weighted kappa which was calculated to be 0.80, indicating substantial agreement. CONCLUSION: The electromyograph produced results that were comparable to the mechanomyograph.

Low-pressure pneumoperitoneum with deep neuromuscular blockade versus standard pressure pneumoperitoneum in patients undergoing laparoscopic cholecystectomy for gallstone disease: a non-inferiority randomized control trial.

BACKGROUND: Low-pressure pneumoperitoneum (LPP) is an attempt at improving laparoscopic surgery. However, it has the issue of poor working space for which deep neuromuscular blockade (NMB) may be a solution. There is a lack of literature comparing LPP with deep NMB to standard pressure pneumoperitoneum (SPP) with moderate NMB. METHODOLOGY: This was a single institutional prospective non-inferiority RCT, with permuted block randomization of subjects into group A and B [Group A: LPP; 8-10 mmHg with deep NMB [ Train of Four count (TOF): 0, Post Tetanic Count (PTC): 1-2] and Group B: SPP; 12-14 mmHg with moderate NMB]. The level of NMB was monitored with neuromuscular monitor with TOF count and PTC. Cisatracurium infusion was used for continuous deep NMB in group A. Primary outcome measures were the surgeon satisfaction score and the time for completion of the procedure. Secondarily important clinical outcomes were also reported. RESULTS: Of the 222 patients screened, 181 participants were enrolled [F: 138 (76.2%); M: 43 (23.8%); Group A n = 90, Group B n = 91]. Statistically similar surgeon satisfaction scores (26.1 ± 3.7 vs 26.4 ± 3.4; p = 0.52) and time for completion (55.2 ± 23.4 vs 52.5 ± 24.9 min; p = 0.46) were noted respectively in groups A and B. On both intention-to-treat and per-protocol analysis it was found that group A was non-inferior to group B in terms of total surgeon satisfaction score, however, non-inferiority was not proven for time for completion of surgery. Mean pain scores and incidence of shoulder pain were statistically similar up-to 7 days of follow-up in both groups. 4 (4.4%) patients in group B and 2 (2.2%) in group A had bradycardia (p = 0.4). Four (4.4%) cases of group A were converted to group B. One case of group B converted to open surgery. Bile spills and gallbladder perforations were comparable. CONCLUSION: LPP with deep NMB is non-inferior to SPP with moderate NMB in terms of surgeon satisfaction score but not in terms of time required to complete the procedure. Clinical outcomes and safety profile are similar in both groups. However, it could be marginally costlier to use LPP with deep NMB.

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.

Post-operative urinary retention is impacted by neuromuscular block reversal agent choice: A retrospective cohort study in US hospital setting.

STUDY OBJECTIVE: Perioperative neuromuscular blocking agents are pharmacologically reversed to minimize complications associated with residual neuromuscular block. Neuromuscular block reversal with anticholinesterases (e.g., neostigmine) require coadministration of an anticholinergic agent (e.g., glycopyrrolate) to mitigate muscarinic activity; however, sugammadex, devoid of cholinergic activity, does not require anticholinergic coadministration. Single-institution studies have found decreased incidence of post-operative urinary retention associated with sugammadex reversal. This study used a multicenter database to better understand the association between neuromuscular block reversal technique and post-operative urinary retention. DESIGN: Retrospective cohort study utilizing large healthcare database. SETTING: Non-profit, non-governmental and community and teaching hospitals and health systems from rural and urban areas. PATIENTS: 61,898 matched adult inpatients and 95,500 matched adult outpatients. INTERVENTIONS: Neuromuscular block reversal with sugammadex or neostigmine plus glycopyrrolate. MEASUREMENTS: Incidence of post-operative urinary retention by neuromuscular block reversal agent and the independent association of neuromuscular block reversal technique and risk of post-operative urinary retention. MAIN RESULTS: The incidence of post-operative urinary retention was 2-fold greater among neostigmine with glycopyrrolate compared to sugammadex patients (5.0% vs 2.4% inpatients; 0.9% vs 0.4% outpatients; both p < 0.0001). Multivariable logistic regression identified reversal with neostigmine to be independently associated with greater risk of post-operative urinary retention (inpatients: odds ratio, 2.20; 95% confidence interval, 2.00 to 2.41; p < 0.001; outpatients: odds ratio, 2.57; 95% confidence interval, 2.13 to 3.10; p < 0.001). Post-operative urinary retention-related visits within 2 days following discharge were five-fold higher among those reversed with neostigmine than sugammadex among inpatients (0.05% vs. 0.01%, respectively; p = 0.018) and outpatients (0.5% vs. 0.1%; p < 0.0001). CONCLUSION: Though this study suggests that neuromuscular block reversal with neostigmine can increase post-operative urinary retention risk, additional studies are needed to fully understand the association.

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.

Reversal of rocuronium induced neuromuscular block with sugammadex in patients under 2 years of age. A series of 280 cases.

AIM: Neuromuscular muscle relaxants are still indispensable for surgical procedures requiring general anesthesia, and the use of these agents may result in postoperative residual curarization. Sugammadex may offer a distinct advantage to pediatric patients where residual neuromuscular blockade may be poorly tolerated. Sugammadex is approved for use in adults and children over two years. This is the main reason why large-scale studies could not be conducted in the group of patients younger than two years old. This study aimed to evaluate the efficacy and safety of sugammadex for reversing deep rocuronium-induced neuromuscular blockade in children under two years of age. METHODS: Pediatric patients younger than two years of age who underwent neurosurgery under sevoflurane anesthesia were included in the study. Neuromuscular block was achieved by the administration of rocuronium. It was antagonized by the administration of 5 mg/kg sugammadex and evaluated using train-of-four (TOF). Primary outcome measure was the time from sugammadex administration to return of the TOF ratio to 0,9. Postoperative adverse events were also recorded. RESULTS: Two hundred eighty patients (10 day-24 months of age; 3-18 kg) were included in this study. Reversal of deep rocuronium-induced neuromuscular block with sugammadex was rapid in all patients. No residual curarization or recurarization was observed. No adverse events or hypersensitivity reactions were observed after administration of sugammadex. CONCLUSION: Reversal of rocuronium-induced deep neuromuscular block in infants was rapid and safe. Sugammadex provided safe extubation in patients younger than two years of age who had undergone neurosurgery. Research Fund. KEY WORDS: Neuromuscular blockade, Neuromuscular monitoring, Pediatrics, Sugammadex.

Undiagnosed Lambert-Eaton Myasthenic Syndrome in the Era of Sugammadex: A Case Report.

OBJECTIVE: In this case report, we discuss the rare manifestation of prolonged neuromuscular blockade in a patient with history of small cell lung cancer and undiagnosed Lambert-Eaton myasthenic syndrome (LEMS) who had previously received succinylcholine for general anesthesia without incident but subsequently exhibited prolonged neuromuscular blockade during a laparoscopic procedure. We aimed to emphasize the importance of reversal agent safety and precision as well as vigilant perioperative and postoperative care. METHODS: We used the patient's electronic medical record, direct patient care experiences, and comprehensive literature review for this case report. RESULTS: Sugammadex was administered with mild improvement. Suspecting undiagnosed LEMS, neostigmine was administered, yielding satisfactory muscle strength and successful extubation. In retrospect, the patient reported history of weakness when lifting weights that improved upon exertion. CONCLUSIONS: Sugammadex is an efficient and effective agent for reversal of neuromuscular blockade. However, proper monitoring of the depth and recovery of blockade is imperative to when using sugammadex with optimal safety and precision in all patients. Perioperative care teams must remain vigilant with a high index of suspicion for neuromuscular junction pathology to properly plan perioperative care for patients at risk, especially those with small cell lung cancer who may have undiagnosed LEMS.

The arousal effect of sugammadex reversal of neuromuscular blockade differs with anesthetic depth in propofol-remifentanil anesthesia: a randomized controlled trial.

Sugammadex reverses neuromuscular blockade by encapsulating steroidal neuromuscular blockers; therefore, it does not pharmacologically affect sedation levels. However, some clinicians avoid using it because of sudden unwanted acting out or patient arousal. Previous studies suggested sugammadex-induced awakening, but frontal muscle contraction after sugammadex administration compromised reliability of results obtained from EEG-based anesthesia depth monitoring tools like bispectral index (BIS). We hypothesized that sugammadex would affect patients' arousal depending on their baseline levels of sedation. We evaluated arousal signs after sugammadex administration with BIS between 25 - 35 and 45 - 55 under steady-state propofol-remifentanil anesthesia at the end of a surgery (n = 33 in each group). After sugammadex administration, twelve patients with a BIS of 45 - 55 showed clinical signs of awakening but none with a BIS of 25 - 35 (36.4% vs. 0%, P = 0.001). The distribution of the modified observer's assessment of alertness/sedation scale scores was also significantly different between the two groups (P < 0.001). Changes in the BIS were significantly greater in the BIS 45 - 55 than in the 25 - 35 group (median difference, 7; 95% CI 2 - 19, P = 0.002). Arousal after sugammadex was affected by patient sedation levels, and clinical signs of awakening appeared only in those with BIS 45 - 55. Unwanted arousal of the patient should be considered when using sugammadex under shallow anesthesia.Clinical trial registry number: Clinical Trial Registry of Korea ( https://cris.nih.go.kr ; Principal investigator: Jieae Kim; Registration number: KCT0006248; Date of first registration: 11/06/2021).

Effect of neuromuscular block on surgical conditions during laparoscopic surgery in neonates and small infants: A randomised controlled trial.

BACKGROUND: Neuromuscular block (NMB) is routinely used in paediatric and adult anaesthesia to facilitate endotracheal intubation and optimise surgical conditions. However, there are limited data regarding NMB and optimising the conditions for laparoscopic surgery in neonates and small infants. OBJECTIVE: The goal of this study was to determine the effect of NMB on the conditions for laparoscopic surgery in neonates and small infants. DESIGN: A randomised controlled trial. SETTING: Single-centre Children's Hospital, conducted from November 2021 to December 2022. PATIENTS: One hundred and two ASA I-II neonates and small infants aged up to 60 weeks postmenstrual age who were scheduled to undergo an elective laparoscopic Ladd's procedure were included in the study. INTERVENTIONS: Patients were randomised into three groups: no NMB group, shallow NMB group and moderate NMB group. Each group was given different doses of rocuronium to achieve the target depth of NMB. MAIN OUTCOME MEASURES: The primary outcome was the quality of the surgical conditions evaluated with the Leiden-Surgical Rating Scale (L-SRS) by a blinded surgeon. Secondary outcomes included tracheal intubating conditions and adverse events. RESULTS: The percentage of L-SRS scores of 4 or 5 was similar among the three groups at all the assessment times ( P  > 0.05 for each time interval). The distribution of L-SRS scores was also similar among the three groups. There were no significant differences in operating condition scores between the groups at any time interval ( P  > 0.05 for each time interval). The incidence of adverse events during anaesthesia induction was significantly higher in the no NMB group (51.4%) than in the other two groups (13.6% and 14.7%) (adjusted P  = 0.012 and adjusted P  = 0.003). In particular, clinically unacceptable intubation conditions occurred in 12 patients (34.3%) in the no NMB group, significantly more than in the shallow NMB group (6.1%, adjusted P  = 0.012) and moderate NMB group (2.9%, adjusted P  = 0.003). There was no statistically significant difference in the incidence of adverse events in the PACU among the three groups ( P  = 0.103). CONCLUSIONS: The depth of NMB was not associated with superior surgical conditions during laparoscopic surgery, but it was associated with a reduction in adverse events during induction and maintenance of anaesthesia in neonates and small infants. TRIAL REGISTRATION: Registered at www.chictr.org.cn (ChiCTR2100052296).

Influence of the Pringle maneuver during partial hepatectomy on the neuromuscular block induced by intermittent and continuous dosing of rocuronium.

PURPOSE: The Pringle maneuver (PM) is a common procedure in hepatectomy that is known to interrupt drug elimination. The purpose of this study was to examine the influence of PM on the duration of action of rocuronium administered by intermittent bolus dosing, the continuous rocuronium infusion dose required for maintenance of a moderate neuromuscular block, and changes in plasma concentrations of rocuronium. METHODS: Twenty-seven adult patients undergoing partial hepatectomy with PM were enrolled in this study. The duration of action of 0.2 mg/kg rocuronium boluses (DUR), and the continuous rocuronium infusion dose required for maintenance of the height of the first twitch of the train-of-four (T1) at 10-20% of the control value (%T1), respectively, were electromyographically monitored on the adductor digiti minimi muscle. The effects of PM on DUR, %T1, and the plasma concentration of rocuronium were measured. RESULTS: The DUR was significantly prolonged during PM [mean: 42.2 (SD: 8.0) min, P < 0.001] compared to baseline [29.7 (6.3) min]. It was prolonged even after completion of the PM [46.2 (10.5) min, P < 0.001]. The plasma concentration of rocuronium measured at every reappearance of T1 was comparable between before and during PM. %T1 [15.5 (5.6)%] was significantly depressed after the start of PM [6.5 (3.9)%, P < 0.001], with persistence of the depression even after completion of PM. However, there were no significant changes in the plasma concentration of rocuronium. CONCLUSIONS: Rocuronium-induced neuromuscular block is significantly augmented during PM. However, the augmentation is not associated with an increase in plasma rocuronium concentration.

Optimal dose of neostigmine antagonizing cisatracurium-induced shallow neuromuscular block in elderly patients: a randomized control study.

BACKGROUND: Residual neuromuscular block after using neuromuscular blocking agents is a common and potentially harmful complication of general anesthesia. Neostigmine is a widely used antagonist, but its optimal dose for elderly patients is unclear. OBJECTIVES: To compare the optimal dosage and safety of neostigmine for reversing shallow residual block in elderly patients after cisatracurium-induced neuromuscular block. METHODS: A randomized controlled trial was conducted in 196 elderly patients undergoing non-cardiac surgery under general anesthesia with cisatracurium. Patients were assigned to receive either no neostigmine (control group) or neostigmine at 20 µg/kg, 40 µg/kg or 50 µg/kg when train-of-four (TOF) ratio reached 0.2 at the end of surgery. The primary outcome was the time to reach TOF ratio of 0.9 after administration. Secondary outcomes included TOF ratio at 10 min after administration, postoperative nausea and vomiting, postoperative cognitive impairment and post-anesthesia care unit (PACU) stay time. RESULTS: The time to reach TOF ratio of 0.9 in the 20 µg/kg, 40 µg/kg and 50 µg/kg groups was significantly shorter than the control group (H = 104.257, P < 0.01), and the time of 40 µg/kg group and 50 µg/kg group was significantly shorter than the 20 µg/kg group (P < 0.001). There was no significant difference between 40 µg/kg and 50 µg/kg groups (P = 0.249). The TOF ratio at 10 min after administration showed similar results. There were no significant differences among groups in postoperative nausea and vomiting, postoperative cognitive impairment or post-operation hospital stay. CONCLUSIONS: Timely use of neostigmine after general anesthesia in elderly patients can significantly shorten time of TOF value reaching 0.9, among which 40 µg/kg dosage may be a more optimized choice. TRIAL REGISTRATION: this study was registered on chictr.org.cn (ChiCTR2100054685, 24/12/2021).

Postoperative recurarization after sugammadex administration in two patients who received neoadjuvant chemotherapy: case reports and literature review.

BACKGROUND: Preoperative neoadjuvant chemotherapy plays a critical role in multidisciplinary therapy for a variety of malignant tumours. Although oncologists consider myocardial injury to be the most concerning side effect of chemotherapy, unique chemotherapy-mediated skeletal muscular damage has received attention recently. CLINICAL FEATURES: We report two unusual cases of postoperative delayed respiratory failure following administration of the recommended sugammadex dosage for patients undergoing lengthy operations with deep neuromuscular blockade (NMB) after neoadjuvant chemotherapy. Based on clinical outcomes, especially the comparison of muscle imaging results in patients at different treatment time points, we concluded that NMB recurrence had a possible correlation with neoadjuvant chemotherapy-induced muscular damage. CONCLUSION: The early identification of neoadjuvant chemotherapeutic side effects on NMB could be instrumental for clinical safety, especially in cases of major surgery requiring deep NMB. Thus, the timing of NMB antagonism and the recommended dosage of sugammadex warrant special consideration in these patients. In addition to neuromuscular monitoring during the operation, a more extended and closer observation period in the postanesthesia care unit is warranted.

RéSUMé: CONTEXTE: La chimiothérapie néoadjuvante préopératoire joue un rôle crucial dans le traitement multidisciplinaire de diverses tumeurs malignes. Bien que les oncologues considèrent les lésions myocardiques comme l'effet secondaire le plus inquiétant de la chimiothérapie, des lésions musculosquelettiques spécifiques induites par la chimiothérapie ont récemment fait l'objet d'une attention plus précise. CARACTéRISTIQUES CLINIQUES: Nous signalons deux cas inhabituels d'insuffisance respiratoire postopératoire retardée suite à l'administration de la posologie recommandée de sugammadex chez des patient·es bénéficiant d'opérations prolongées avec blocage neuromusculaire (BNM) profond après une chimiothérapie néoadjuvante. Sur la base des résultats cliniques, en particulier de la comparaison des résultats d'imagerie musculaire chez les patient·es à différents moments du traitement, nous avons conclu que la récurrence du BNM avait une corrélation intéressante avec les lésions musculaires induites par la chimiothérapie néoadjuvante. CONCLUSION: L'identification précoce des effets secondaires de la chimiothérapie néoadjuvante sur le BNM pourrait jouer un rôle déterminant dans l'innocuité clinique, en particulier en cas de chirurgie majeure nécessitant un BNM profond. Ainsi, le moment de l'antagonisme du BNM et la posologie recommandée de sugammadex nécessitent une attention particulière chez ces patient·es. En plus du monitorage neuromusculaire pendant l'opération, une période d'observation plus longue et plus étroite en salle de réveil est justifiée.

MRI measurement of the effects of moderate and deep neuromuscular blockade on the abdominal working space during laparoscopic surgery, a clinical study.

BACKGROUND: Conflicting data exist regarding the effects of deep neuromuscular blockade (NMB) on abdominal dimensions during laparoscopic procedures. We performed a clinical study to establish the influence of moderate and deep neuromuscular blockade (NMB) on the abdominal working space, measured by Magnetic Resonance Imaging (MRI), during laparoscopic donor nephrectomy with standard pressure (12 mmHg) pneumoperitoneum under sevoflurane anaesthesia. METHODS: Ten patients were intraoperatively scanned three times in the lateral decubitus position, with pneumoperitoneum maintained by a mobile insufflator. The first scan without NMB (T1) was followed by scans with moderate (T2) and deep NMB (T3). The skin-sacral promontory (S-SP) distance was measured, and 3D pneumoperitoneum volumes were reconstructed. RESULTS: The mean difference in the S-SP distance was -0.32 cm between T2 and T3 (95% CI -1.06 - 0.42 cm; p = 0.344) and + 2.1 cm between T1 and T2 (95% CI 0.81 - 3.39 cm; p = 0.006). The mean differences in pneumoperitoneum volume were 166 mL between T2 and T3 (95% CI, 5 - 327 mL; p = 0.044) and 108 mL between T1 and T2 (95% CI, -273 - 488 mL; p = 0.525). The pneumoperitoneum volume showed high inter-individual variability and no increase in three patients with a high volume at T1. CONCLUSIONS: During laparoscopic surgery in the lateral decubitus position with standard pressure under sevoflurane anaesthesia, deep NMB did not increase the S-SP distance compared to moderate NMB. Moderate NMB increased the S-SP distance by a mean of 2.1 cm (15.2%) compared with no NMB. The mean pneumoperitoneum volume increased slightly from moderate to deep NMB, with high inter-individual variability. TRIAL REGISTRATION: Clinicaltrials.gov ID: NCT03287388.

Good clinical research practice (GCRP) in pharmacodynamic studies of neuromuscular blocking agents III: The 2023 Geneva revision.

The set of guidelines for good clinical research practice in pharmacodynamic studies of neuromuscular blocking agents was developed following an international consensus conference in Copenhagen in 1996 (Viby-Mogensen et al., Acta Anaesthesiol Scand 1996, 40, 59-74); the guidelines were later revised and updated following the second consensus conference in Stockholm in 2005 (Fuchs-Buder et al., Acta Anaesthesiol Scand 2007, 51, 789-808). In view of new devices and further development of monitoring technologies that emerged since then, (e.g., electromyography, three-dimensional acceleromyography, kinemyography) as well as novel compounds (e.g., sugammadex) a review and update of these recommendations became necessary. The intent of these revised guidelines is to continue to help clinical researchers to conduct high-quality work and advance the field by enhancing the standards, consistency, and comparability of clinical studies. There is growing awareness of the importance of consensus-based reporting standards in clinical trials and observational studies. Such global initiatives are necessary in order to minimize heterogeneous and inadequate data reporting and to improve clarity and comparability between different studies and study cohorts. Variations in definitions of endpoints or outcome variables can introduce confusion and difficulties in interpretation of data, but more importantly, it may preclude building of an adequate body of evidence to achieve reliable conclusions and recommendations. Clinical research in neuromuscular pharmacology and physiology is no exception.

Educating anaesthetists on neuromuscular monitoring: the challenges continue.

The need to introduce guidelines on neuromuscular monitoring emphasising the use of quantitative techniques that record the train-of-four ratio is now recognised by an increasing number of national anaesthetic societies in the Western world. But the challenge of convincing individual anaesthetists to adopt and use this practice routinely remains. For >10 yr, it has been recognised that all staff in anaesthetic departments need to have regular training in modern neuromuscular monitoring techniques. We discuss a publication in this journal that describes the challenges of setting up multicentre training in Spain to expand the use of quantitative neuromuscular monitoring and their short-term results.

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.

The impact of electrosurgical devices on electromyography-based neuromuscular monitoring during abdominal laparotomy: a case series.

The present study aimed to evaluate the effect of electrosurgical devices on neuromuscular monitoring using an electromyography (EMG)-based neuromuscular monitor during abdominal laparotomy. Seventeen women (aged 32-64 years) undergoing gynecological laparotomy under total intravenous general anesthesia were enrolled in the study. A TetraGraph™ was placed to stimulate the ulnar nerve and to monitor the abductor digiti minimi muscle. After device calibration, train-of-four (TOF) measurements were repeated at intervals of 20 s. Rocuronium 0.6 to 0.9 mg/kg was administered for induction, and additional doses of 0.1 to 0.2 mg/kg were administered to maintain TOF counts ≤ 2 during the surgery. The primary outcome of the study was the ratio of measurement failure. The secondary outcomes of the study were the total number of measurements, the number of measurement failures, and the most extended consecutive number of measurement failures. The data are expressed as median (range). Of the 3091 (1480-8134) measurements, the number of measurement failures was 94 (60-200), resulting in a failure ratio of 3.5% (1.4-6.5%). The most extended consecutive number of measurement failures was 8 (4-13). All attending anesthesiologists were able to maintain and reverse neuromuscular blocks under EMG guidance. This prospective observational study demonstrated that the use of EMG-based neuromuscular monitoring does not seem to be heavily affected by electrical interference during lower abdominal laparotomic surgery. Trial registration This trial was registered in the University Hospital Medical Information Network under registration number UMIN000048138 (registration date; June 23, 2022).