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

Background: Sugammadex 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.Methods: The 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.Results: In 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).Conclusions: When 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.

Comparison of the TOFscan and the TOF-Watch SX during pediatric neuromuscular function recovery: a prospective observational study

Background TOFscan is a three-dimensional acceleromyography neuromuscular monitoring device that does not require initial calibration before muscle relaxant injection. This study aimed to compare TOFscan with TOF-Watch SX, the currently widely accepted uni-dimensional acceleromyography, for use among the pediatric population. We aimed to assess the agreement between TOFscan with TOF-Watch SX in the pediatric population’s neuromuscular recovery. Methods A total of 35 children aged 6–12 years were enrolled. Prior to any muscle relaxant injection, TOFscan and TOF-Watch SX were applied at each opposite arm and monitoring began concurrently throughout neuromuscular recovery. Calibration was performed for TOF-Watch SX, and train-of-four values were recorded every 15 s. Agreement between the two devices was evaluated with Modified Bland-Altman analysis. Results The bias between TOF-Watch SX and TOFscan were all within the 95% limits of agreement. The bias and standard deviation were smaller and the limit of agreement was narrower in the normalized group than in the non-normalized group [normalized bias −0.002 (95% CI, −0.013 to 0.010), standard deviation (SD) 0.111 vs non-normalized bias 0.010 (95% CI, −0.003 to 0.0236), SD 0.127]. Conclusions TOFscan reliably demonstrated lack of bias and good concordance with TOF-Watch SX throughout the neuromuscular recovery, especially when normalized. Despite technical limitations, the two devices were unbiased along the path of spontaneous and pharmacological reversal in pediatric patients. Trial registration ClinicalTrials.gov NCT03775603. Registered on 13 March 2018

Peri-operative diaphragm ultrasound as a new method of recognizing post-operative residual curarization

Background This study sought to evaluate the diagnostic accuracy of peri-operative diaphragm ultrasound in assessing post-operative residual curarization (PORC). Methods Patients undergoing non-thoracic and non-abdominal surgery under general anaesthesia were enrolled from July 2019 to October 2019 at Peking Union Medical College Hospital. A train-of-four ratio (TOFr) lower than 0.9 was considered as the gold standard for PORC. Diaphragm ultrasound parameters included diaphragmatic excursion (DE) and diaphragm thickening fraction (DTF) during quiet breathing (QB) and deep breathing (DB). The diaphragm excursion fraction (DEF) was calculated as the DE-QB divided by the DE-DB. The diaphragm excursion difference (DED) was defined as DE-DB minus DE-QB. Receiver operating characteristic curve analysis was used to determine the cut-off values of ultrasound parameters for the prediction of PORC. Results In total, 75 patients were included, with a PORC incidence of 54.6%. The DE-DB and DED were positively correlated with the TOFr, while the DEF was negatively correlated with the TOFr. The DE-DB cut-off value for predicting PORC was 3.88 cm, with a sensitivity of 85.4% (95% confidence interval [CI]: 70.1–93.9%), specificity of 64.7% (95% CI: 46.4–79.7%), positive likelihood ratio of 2.42 (95% CI 1.5–3.9), and negative likelihood ratio of 0.23 (95% CI: 0.1–0.5). The DED cut-off value was 1.5 cm, with a specificity of 94.2% (95% CI: 80.3–99.3%), sensitivity of 63.4% (95% CI: 46.9–77.9%), positive likelihood ratio of 10.78 (95% CI: 2.8–42.2), and negative likelihood ratio of 0.39 (95% CI: 0.3–0.6). Conclusions Peri-operative diaphragm ultrasound may be an additional method aiding the recognition of PORC, with DED having high specificity.

Effect of Chronic Exposure to Dexamethasone on Rocuronium-induced Neuromuscular Blockade and Sugammadex Reversal: an in Vivo Study on Rats

Background: Chronic exposure to glucocorticoids is associated with resistance to nondepolarising neuromuscular blocking agents. Therefore, we hypothesised that sugammadex-induced recovery in subjects with chronic exposure to dexamethasone was faster than that in subjects without dexamethasone exposure. Objective: To evaluate the recovery profile of rocuronium-induced neuromuscular blockade after sugammadex administration in rats. Design: An in vivo study on rats.Setting: Asan Institute for Life Sciences, Asan Medical Center, Korea, from April 2017 to October 2017.Animals: Thirty-six male Sprague-Dawley rats.Intervention: Sprague–Dawley rats were allocated to three groups (dexamethasone group, control group, and pair-fed group) for the in vivo study. Dexamethasone group received daily intraperitoneal injections of dexamethasone 500 μg kg-1 or 0.9% saline for 15 days. On the sixteenth day, 3.5 mg kg-1 of rocuronium was administered to achieve complete neuromuscular blockade. Main outcome measures: The recovery time to a train-of-four ratio Results: There were no significant differences in the recovery time to train-of-four ratio to 0.9 among the groups (P = 0.531). The time to second twitch of train-of-four recovery that indicated the duration of rocuronium-induced neuromuscular blockade was significantly shorter in Group D than in Groups C and P (P = 0.001). Conclusion: As previously reported, resistance to rocuronium was observed in rats with chronic exposure to dexamethasone. However, the neuromuscular recovery time after sugammadex administration was not significantly different between groups.

Residual Neuromuscular Block in HIV-Infected Young Patients: A Prospective Observational Study

Objectives: Avoidance of residual neuromuscular blockade (RNMB) is crucial to decrease anesthesia-related pulmonary complications. At present, no data are available for HIV-infected patients about the occurrence of RNMB. In this trial, we aim to investigate the incidence of RNMB in such patients. Methods: Data were prospectively collected on 45 normal and 45 HIV-infected patients (18-65 yr). The train-of-four stimulation (TOF-Watch SX) was used to evaluate the level of neuromuscular block from the induction of anesthesia to back to the postanesthesia care unit (PACU) by an assessor, but blind to the anesthesiologist. Primary endpoint was the presence of RNMB at PACU admission, defined as a train-of-four (TOF) ratio < 0.9. The onset time (from application of cisatracurium to maximum depression of T1), no reaction time (from zero of T1 to non-zero), and clinical duration (from application to 25% recovery of T1) were determined for each patient. Results: The incidence of RNMB was 37.5% in HIV- infected patients and 32.5% in normal patients (difference, 5%; 99% CI, −16% to 26 1%; p=0.815). The onset time was no different between two groups (4.05±0.88 min in HIV-infected group vs. 3.85±1.08 min in normal group (p=0.37)). The no reaction time was also similarly between two groups ( 49.83±3.81min in HIV-infected group vs. 48.98±5.12min in normal group (p=0.40)). The clinical duration was 53.78±3.05 min and 52.40±5.02 min in HIV-infected group and normal group, respectively (p=0.14). Conclusion: The odds of RNMB were not significantly different in HIV-infected young patients compared to normal persons.

A Comparison Between the Adductor Pollicis Muscle and the Abductor Digiti Minimi Muscle Using Electromyography AF-201P in Rocuronium-Induced Neuromuscular Block: A Prospective Comparative Study

Background The AF-201P, a new electromyography (EMG)-based neuromuscular monitor has been developed recently. The aim of this clinical study was to compare two ulnar nerve innervated muscles: the adductor pollicis (AP) muscle and the abductor digiti minimi (ADM) muscle during the recovery from rocuronium-induced neuromuscular block by using EMG AF-201P. Methods Twenty patients undergoing surgery with general anesthesia were enrolled in the study. During total intravenous general anesthesia, train-of-four (TOF) and post-tetanic counts (PTC) responses following 0.9 mg/kg rocuronium administration were concurrently monitored at the AP and the ADM muscles with EMG AF-201P on the opposite arms. At the end of the surgery, sugammadex 2 mg/kg was administered when TOF counts of 2 was observed at both muscles. The primary outcome of the study was time from administration of rocuronium to first appearance of PTC response (first PTC). The secondary outcomes of the study were time from administration of rocuronium to first reappearance of TOF response (first TOF), time from first PTC to first TOF (PTC-TOF time), time to reappearance of TOF counts of 2, and time from administration of sugammadex to TOF ratio ≥ 0.9. Agreement between the two muscles was assessed using the Bland-Altman analysis. Data are expressed as mean ± standard deviation. Results Nineteen patients were included in the analysis. Time for appearance of the first PTC was significantly faster at the ADM muscle than the AP muscle (32.4 ± 13.1min vs 24.4 ± 11.4min, p = 0.006). Interval time between the first PTC and the first TOF was significantly longer with the ADM muscle than the AP muscle (19.4 ± 7.3min vs 12.4 ± 10.6min, p = 0.019). There were no significant differences in time to TOF counts of 2 and sugammadex-facilitated recovery between the two muscles. Bland-Altman analyses showed acceptable ranges of bias and limits of agreement of the two muscles. Conclusions The ADM muscle showed a good agreement with the AP muscle during rocuronium-induced neuromuscular block but faster recovery of PTC response when using EMG. Trial registration : UMIN-CTR (Registration No. UMIN000044904). Registered 19 July 2021 -Retrospectively registered,

Ipsilateral and Simultaneous Comparison of Responses from Acceleromyography- and Electromyography-based Neuromuscular Monitors

Background The paucity of easy-to-use, reliable objective neuromuscular monitors is an obstacle to universal adoption of routine neuromuscular monitoring. Electromyography (EMG) has been proposed as the optimal neuromuscular monitoring technology since it addresses several acceleromyography limitations. This clinical study compared simultaneous neuromuscular responses recorded from induction of neuromuscular block until recovery using the acceleromyography-based TOF-Watch SX and EMG-based TetraGraph. Methods Fifty consenting patients participated. The acceleromyography and EMG devices analyzed simultaneous contractions (acceleromyography) and muscle action potentials (EMG) from the adductor pollicis muscle by synchronization via fiber optic cable link. Bland–Altman analysis described the agreement between devices during distinct phases of neuromuscular block. The primary endpoint was agreement of acceleromyography- and EMG-derived normalized train-of-four ratios greater than or equal to 80%. Secondary endpoints were agreement in the recovery train-of-four ratio range less than 80% and agreement of baseline train-of-four ratios between the devices. Results Acceleromyography showed normalized train-of-four ratio greater than or equal to 80% earlier than EMG. When acceleromyography showed train-of-four ratio greater than or equal to 80% (n = 2,929), the bias was 1.3 toward acceleromyography (limits of agreement, –14.0 to 16.6). When EMG showed train-of-four ratio greater than or equal to 80% (n = 2,284), the bias was –0.5 toward EMG (–14.7 to 13.6). In the acceleromyography range train-of-four ratio less than 80% (n = 2,802), the bias was 2.1 (–16.1 to 20.2), and in the EMG range train-of-four ratio less than 80% (n = 3,447), it was 2.6 (–14.4 to 19.6). Baseline train-of-four ratios were higher and more variable with acceleromyography than with EMG. Conclusions Bias was lower than in previous studies. Limits of agreement were wider than expected because acceleromyography readings varied more than EMG both at baseline and during recovery. The EMG-based monitor had higher precision and greater repeatability than acceleromyography. This difference between monitors was even greater when EMG data were compared to raw (nonnormalized) acceleromyography measurements. The EMG monitor is a better indicator of adequate recovery from neuromuscular block and readiness for safe tracheal extubation than the acceleromyography monitor. Editor’s Perspective What We Already Know about This Topic What This Article Tells Us That Is New

Evaluation of Rocuronium Continuous Infusion in Critically Ill Patients During the COVID-19 Pandemic and Drug Shortages

Background: Limited data exist to support the use of rocuronium continuous infusions in the intensive care unit (ICU). Objective: To evaluate the dosing and monitoring of adult patients who received rocuronium for hypoxemic respiratory failure during the Coronavirus Disease 2019 (COVID-19) pandemic. Methods: This was a retrospective, single-center study from March 1, 2020 to May 31, 2020. We identified all adult patients admitted to any ICU who received rocuronium via continuous infusion. Patients were excluded if they received rocuronium for <6 hours. The main outcome of this study was to determine the median rocuronium maintenance continuous infusion rate in the ICU. Secondary outcomes of this study included the initial continuous infusion rate, duration of therapy, cumulative dose, frequency and median of rocuronium boluses, time to resolution of neuromuscular blockade, and the relationship between the hourly administration rates of rocuronium and train-of-four (TOF) assessments. Results: Seventy-one patients and 97 paralytic infusions were included. Fifty-nine patients (83%) were positive for SARS CoV-2. Of the 97 rocuronium infusions, the median dose at initiation was 3 (3–5) mcg/kg/min and duration of infusion was 45 (23.6–92.5) hours. The median continuous infusion maintenance rate was 4.3 (2.8–7.2) mcg/kg/min. There was a negligible correlation between the dose of rocuronium and the TOF results (r = .04). A total of 1775 TOFs were assessed, of which 46.2% were over-paralyzed, 35.7% well-paralyzed, and 18.1% under-paralyzed. Conclusions: The initial and maintenance infusion doses in our analysis were lower than what have been previously referenced.