Evolution of a laboratory mechanomyograph.

Mechanomyography is currently the accepted laboratory reference standard for quantitative neuromuscular blockade monitoring. Mechanomyographs are not commercially available. Previously, a mechanomyograph was built by our laboratory and used in several clinical studies. It was subsequently redesigned to improve its usability and functionality and to accommodate a wider range of hand sizes and shapes using an iterative design process. Each version of the redesigned device was initially tested for usability and functionality in the lab with the investigators as subjects without electrical stimulation. The redesigned devices were then assessed on patients undergoing elective surgery under general anesthesia without neuromuscular blocking drugs. Since the patients were not paralyzed, the expected train-of-four ratio was 1.0. The device accuracy and precision were represented by the train-of-four ratio mean and standard deviation. If issues with the device's useability or functionality were discovered, changes were made, and the redesign processes repeated. The final mechanomyograph design was used to collect 2,362 train-of-four ratios from 21 patients. The mean and standard deviation of the train-of-four ratios were 0.99 ± 0.030. Additionally, the final mechanomyograph design was easier to use and adjust than the original design and fit a wider range of hand sizes. The final design also reduced the frequency of adjustments and the time needed for adjustments, facilitating data collection during a surgical procedure.

Tolerance to preoperative placement of electrodes for neuromuscular monitoring using the Tetragraph™.

Background: Quantitative train-of-four (TOF) monitoring has recently been shown to be feasible in infants and children using a novel electromyography (EMG)-based monitor with a pediatric-sized self-adhesive sensor. However, placement of the sensor and initiation of TOF monitoring may require additional time in the operating room (OR), delaying workflow and the time to induction of anesthesia. The current study evaluates the feasibility of placing the self-adhesive sensor in the preoperative holding area in pediatric patients before arrival to the OR. Methods: Consented pediatric patients undergoing inpatient surgery requiring the administration of NMBAs were enrolled. The EMG electrode was placed along the ulnar nerve on the volar aspect of the distal forearm to provide neurostimulation. After the induction of anesthesia, monitoring was initiated and TOF recording started before the administration of the NMBA. A Likert score (0-10) was used to assess ease of placement, tolerability of the monitor during the preoperative period, and its ability to generate a recorded response in the OR. Results: The final study cohort included 40 patients with a median age of 3.7 years. Fourteen patients (35%) pulled off the sensor before arrival to the OR and 26 patients (65%) arrived at the OR with the sensor intact and functioning. Older children were more likely to maintain the sensor until arrival to the OR compared to younger patients (median age of 5.24 versus 1 year, P = 0.0521). A median age of 3.7 years correlated with an 80% chance of arriving in the OR with the sensor intact. Application ease and tolerance of the sensor were higher in the group that maintained the sensor until OR arrival. Conclusion: In patients more than 4 years of age, placement of the self-adhesive sensor for EMG-based TOF monitoring may be feasible. However, in younger patients, additional interventions may be required to achieve a similar success rate.

Intraoperative electromyographic monitoring in children using a novel pediatric sensor.

Background: Train-of-four (TOF) monitoring is essential in optimizing perioperative outcomes as a means to assess the depth of neuromuscular blockade and confirm recovery following the administration of neuromuscular blocking agents (NMBAs). Quantitative TOF monitoring has been limited in infants and children primarily due to lack of effective equipment. The current study evaluates a novel electromyography (EMG)-based TOF monitor with a recently developed pediatric-sized self-adhesive sensor in infants and children. Methods: Consented pediatric patients undergoing inpatient surgery requiring the administration of NMBAs were enrolled. The EMG electrode was placed along the ulnar nerve on the volar aspect of the distal forearm. The muscle action potentials from the adductor pollicis muscle were recorded throughout surgery at 20-second intervals. Data from the monitor's built-in memory card were later retrieved and analyzed. Results: The final study cohort included 51 patients who ranged in age from 0.2 to 7.9 years and in weight from 4.2 to 36.0 kilograms. Thirty patients weighed less than 15 kgs. Supramaximal stimulus current intensity (mA) at a pulse width of 200 µsec was 30 mA in 8%; 40 mA in 29%; 50 mA in 16%; and 60 mA in 20% of the patients. Supramaximal stimulus current intensity (mA) at a pulse width of 300 µsec was 50 mA in 4%; 60 mA in 24%. The muscle action potential baseline amplitude was 8.7 ± 3.3 mV and recovered to 7.2 ± 3.7 mV after antagonism of neuromuscular blockade. The average baseline TOF ratio was 100 ± 3% and recovered to 98 ± 7% after antagonism of neuromuscular blockade. No technical issues were noted with application of the sensor or subsequent use of the monitor. Conclusion: Neuromuscular monitoring can be performed intraoperatively in pediatric patients who are less than 8 years of age using a novel commercially available EMG-based monitor with a recently developed pediatric sensor. The novel sensor allows use of an EMG-based monitor in infants and children in whom acceleromyography or subjective (visual) observation of the TOF response may not be feasible. Automatic detection of neuromuscular stimulating parameters (supramaximal current intensity level, baseline amplitude of the muscle action potential) was feasible in pediatric patients of all sizes including those weighing less than 15 kilograms or when there was limited access to the extremity being monitored.

Feasibility of intraoperative quantitative neuromuscular blockade monitoring in children using electromyography.

Background: Quantitative train-of-four (TOF) monitoring remains essential in optimizing anesthetic outcomes by assessing the depth and recovery from neuromuscular blockade. Despite this, residual neuromuscular blockade, defined as a TOF ratio <0.90, remains a concern in both adult and pediatric patients. Quantitative TOF monitoring has seen limited use in infants and children primarily due to a lack of effective equipment. This study evaluates a new electromyography (EMG)-based TOF monitor in pediatric patients undergoing inpatient surgical procedures including laparoscopic (restricted arm access) surgery. Methods: Pediatric patients undergoing inpatient surgery requiring the administration of neuromuscular blocking agents (NMBAs) were enrolled. The EMG electrodes were placed along the ulnar nerve on the volar aspect of the arm to provide neurostimulation. The muscle action potentials from the abductor digiti minimi muscle were recorded. Neuromuscular responses were recorded by the device throughout surgery at 20-s intervals until after tracheal extubation. Data recorded on the monitor's built-in memory card were later retrieved and analyzed. Results: The study cohort included 100 pediatric patients (62% male). The average age was 11 years (IQR: 8, 13) and the average weight was 39.6 kg (30, 48.7). Automatic detection of supramaximal stimulus was obtained in 95% of patients. The muscle action potential mean baseline amplitude (in mV) was 7.5 mV (6, 9.2). The baseline TOF ratio was 100% (100, 104). After administration of a neuromuscular blocking agent, monitoring of the TOF ratio was successful in 93% of the patients. After antagonism of neuromuscular blockade, monitoring was possible in 94% of patients when using an upgraded algorithm. The baseline amplitude recovered to 6.5 mV (5, 7.8), and the TOF ratio recovered to a mean of 90.1% (90,97) before tracheal extubation. Conclusion: Our results indicate that neuromuscular monitoring can be performed intraoperatively in pediatric patients weighing between 20 and 60 kg using the new commercially available EMG-based monitor. Automatic detection of neuromuscular stimulating parameters (supramaximal current intensity level and baseline amplitude of the muscle action potential) by an adult neuromuscular monitor is feasible in pediatric patients receiving nondepolarizing neuromuscular blocking agents.

The Implementation of Protocol-Based Utilization of Neuromuscular Blocking Agent Using Clinical Variables in Acute Respiratory Distress Syndrome Patients.

OBJECTIVES: The recent conflicting data on the mortality benefit of neuromuscular blocking agents in acute respiratory distress syndrome and the potential adverse effects of continuous neuromuscular blocking agent necessitates that these medications should be used judiciously with dose reduction in mind. The aims of the study were to improve the process of care by provider education of neuromuscular blocking agent titration and monitoring and to determine the impact of clinical endpoint based neuromuscular blocking agent titration protocol. DESIGN: We conducted a proof-of-concept historically controlled study of protocol-based intervention standardizing paralytic monitoring and titration using clinical variables. Education of the protocol was provided to ICU staff via bedside teaching and workshops. The primary outcomes were the time to reach goal paralysis and cumulative neuromuscular blocking agent dose. Secondary outcomes included maintenance of deeper sedation (Richmond Agitation and Sedation Scale -5) prior to neuromuscular blocking agent initiation, total time on mechanical ventilation, length of stay, and mortality. SETTING: Medical ICU at a quaternary academic hospital between March 2019 and June 2020. PATIENTS: Adult severe acute respiratory distress syndrome (Pao2/Fio2 <150) patients requiring neuromuscular blocking agent for greater than or equal to 12 hours. Eighty-two patients fulfilled inclusion criteria, 46 in the control group and 36 in the intervention group. INTERVENTIONS: Education and implementation of standardized protocol. MEASUREMENTS AND MAIN RESULTS: Compared with the control group, the time to reach goal paralysis in the intervention group was shorter (8.55 ± 9.4 vs 2.63 ± 5.9 hr; p < 0.0001) on significantly lower dose of cisatracurium (total dose 1,897.96 ± 1,241.0 vs 562.72 ± 546.7 mg; p < 0.0001 and the rate 5.84 ± 2.66 vs 1.99 ± 0.95 µg/kg/min; p < 0.0001). Deeper sedation was achieved at the time of initiation of neuromuscular blocking agent in the intervention arm (mean Richmond Agitation and Sedation Scale -3.3 ± 1.9 vs -4.3 ± 1.7; p = 0.015). There was no significant difference in total time on mechanical ventilation, length of ICU stay, length of hospital stay, and mortality between the two groups. CONCLUSIONS: Implementation of comprehensive education, standardization of sedation prior to neuromuscular blocking agent initiation, integration of clinical variables in determining paralysis achievement, and proper use of peripheral nerve stimulation served as optimal strategies for the titration and monitoring of neuromuscular blocking agent in acute respiratory distress syndrome. This reduced drug utilization while continuing to achieve benefit without causing adverse effects.

Sugammadex: Applications in Pediatric Critical Care.

Sugammadex is a novel pharmacologic agent, which reverses neuromuscular blockade with a mechanism that differs from acetylcholinesterase inhibitors such as neostigmine. There is a growing body of literature demonstrating its efficacy in pediatric patients of all ages. Prospective trials have demonstrated a more rapid and more complete reversal of rocuronium-induced neuromuscular blockade than the acetylcholinesterase inhibitor, neostigmine. Unlike the acetylcholinesterase inhibitors, sugammadex effectively reverses intense or complete neuromuscular blockade. It may also be effective in situations where reversal of neuromuscular blockade is problematic including patients with neuromyopathic conditions or when acetylcholinesterase inhibitors are contraindicated. This article reviews the physiology of neuromuscular transmission as well as the published literature, regarding the use of sugammadex in pediatric population including the pediatric intensive care unit population. Clinical applications are reviewed, adverse effects are discussed, and dosing algorithms are presented.

A retrospective observational study of neuromuscular monitoring practice in 30,430 cases from six Danish hospitals.

Timely application of objective neuromuscular monitoring can avoid residual neuromuscular blockade. We assessed the frequency of objective neuromuscular monitoring with acceleromyography and the last recorded train-of-four ratio in a cohort of Danish patients. We extracted data from all patients receiving general anaesthesia from November 2014 to November 2016 at six hospitals in the Zealand Region of Denmark. Acceleromyography was available in all operating rooms and data were recorded automatically. The primary outcome measure was acceleromyography use in patients receiving neuromuscular blocking agents, divided into non-depolarising agents and succinylcholine only. The dataset included 76,743 cases, of which 30,430 received a neuromuscular blocking drug. Non-depolarising drugs were used in 16,525 (54%) and succinylcholine as the sole drug in 13,905 (46%) cases. Acceleromyography was used in 14,463 (88%) patients who received a non-depolarising neuromuscular blocking drug and in 4224 (30%) receiving succinylcholine alone. Acceleromyography use varied between the departments from 58% to 99% for non-depolarising drugs and from 3% to 79% for succinylcholine alone. The median (IQR [range]) of the last recorded train-of-four ratio before tracheal extubation was 0.97 (0.90-1.06 [0.01-2.20]) when non-depolarising drugs were used, and was less than 0.9 in 22% of cases. The OR for oxygen desaturation was higher with the use of succinylcholine [2.51 (95%CI 2.33-2.70) p < 0.001] and non-depolarising drugs [2.57 (95%CI 2.32-2.84) p < 0.001] as compared with cases where no neuromuscular blockade drug was used. In conclusion, acceleromyography was almost always used in cases where non-depolarising neuromuscular blocking drugs were used, but a train-of-four ratio of 0.9 was not always achieved. Monitoring was used in less than 30% of cases where succinylcholine was the sole drug used.

Incidence, risk factors, and consequences of residual neuromuscular block in the United States: The prospective, observational, multicenter RECITE-US study.

STUDY OBJECTIVE: To determine the incidence burden and associated risk factors of residual neuromuscular block (rNMB) during routine U.S. hospital care. DESIGN: Blinded multicenter cohort study. SETTING: Operating and recovery rooms of ten community and academic U.S. hospitals. PATIENTS: Two-hundred fifty-five adults, ASA PS 1-3, underwent elective abdominal surgery with general anesthesia and ≥1 dose of non-depolarizing neuromuscular blocking agent (NMBA) for endotracheal intubation and/or maintenance of NMB between August 2012 and April 2013. INTERVENTIONS: TOF measurements using acceleromyography were performed on patients already receiving routine anesthetic care for elective open or laparoscopic abdominal surgery. Measurements allowed assessment of the presence of residual neuromuscular block (rNMB), defined as a train-of-four (TOF) ratio <0.9 at tracheal extubation. We recorded patient and procedural characteristics and assessed TOF ratios (T4/T1) at various times throughout the procedure and at tracheal extubation. Differences in patient and clinical characteristics were compared using Fisher's exact test for categorical variables and t-test for continuous variables. Multivariate logistic regression assessed risk factors associated with rNMB at extubation. MAIN RESULTS: Most of the study population, 64.7% (n = 165) had rNMB (TOF ratio < 0.9), among them, 31.0% with TOF ratio <0.6. Among those receiving neostigmine and/or qualitative peripheral nerve stimulation per clinical decision, 65.0% had rNMB. After controlling for confounders, we observed male gender (odds ratio: 2.60, P = 0.008), higher BMI (odds ratio: 1.04/unit, P = 0.043), and surgery at a community hospital (odds ratio: 3.15, P = 0.006) to be independently associated with increased odds of rNMB. CONCLUSIONS: Assessing TOF ratios blinded to the care team, we found that the majority of patients (64.7%) in this study had rNMB at tracheal extubation, despite neostigmine administration and qualitative peripheral nerve stimulation used for routine clinical care. Qualitative neuromuscular monitoring and clinical judgement often fails to detect rNMB after neostigmine reversal with potential severe consequences to the patient. Our data suggests that clinical care could be improved by considering quantitative neuromuscular monitoring for routine care.

Sugammadex Improves Neuromuscular Function in Patients Receiving Perioperative Steroids.

CONTEXT: Sugammadex has steroid-encapsulating effect. AIM: This study was undertaken to assess whether the clinical efficacy of sugammadex was altered by the administration of steroids. SETTING AND DESIGN: Sixty patients between 18 and 60 years of age with the American Society of Anesthesiologists I-IV and undergoing elective direct laryngoscopy/biopsy were included in this study. MATERIALS AND METHODS: Patients were assigned to two groups based on the intraoperative steroid use: those who received steroid (Group S) and who did not (Group C). After standard general anesthesia, patients were monitored with the train of four (TOF) monitoring. The preferred steroid and its dose, timing of steroid administration, and TOF value before and after sugammadex as well as the time to recovery (TOF of 0.9) were recorded. STATISTICAL ANALYSIS USED: SPSS software version 17.0 was used for statistical analysis. RESULTS: There is no statistically significant difference between groups in terms of age, gender, preoperative medication use, and TOF ratio just before administering sugammadex. The reached time to TOF 0.9 after sugammadex administration was significantly shorter in Group S than Group C (P < 0.05). A within-group comparison in Group S showed no difference in TOF ratio immediately before sugammadex as well as the dose of sugammadex in those who received prednisolone; time to TOF 0.9 was higher in prednisolone receivers as compared to dexamethasone receivers (P < 0.05). CONCLUSION: In patients receiving steroids, and particularly dexamethasone, an earlier reversal of neuromuscular block by sugammadex was found, in contrast with what one expect. Further studies are required to determine the cause of this effect which is probably due to a potential interaction between sugammadex and steroids.

Clinical assessment and train-of-four measurements in critically ill patients treated with recommended doses of cisatracurium or atracurium for neuromuscular blockade: a prospective descriptive study.

BACKGROUND: Despite few studies, a monitoring of a neuromuscular blockade with a train of four (TOF) is recommended in intensive care unit (ICU). Our objective was to compare the results of ulnar and facial TOF measurements with an overall clinical assessment for neuromuscular blockade in ICU patients treated with recommended doses of atracurium or cisatracurium, including patients with acute respiratory disease syndrome (ARDS). METHODS: We prospectively included in two ICUs 119 patients, 94 with ARDS, who required a neuromuscular blockade for more than 24 h. Three levels of neuromuscular blockade were defined: "over-paralyzed" (TOF = 0), "well-paralyzed" (TOF = 1-2), and "under-paralyzed" (TOF = 3-4). Physicians blinded for TOF counts were asked to classify patients clinically as "over-paralyzed," "well-paralyzed," or "under-paralyzed". Patients were assessed two times daily. RESULTS: For the whole population 996 ulnar and facial TOF measurements and clinical assessments were obtained (846 with cisatracurium and 150 with atracurium). Proportions of patients classified as over-paralyzed, well-paralyzed, and under-paralyzed based on TOF measurements and clinical assessments differed significantly (p < 0.0001). The number of observed agreements between clinical assessments and facial TOF measurements was of 19.08% (κ = 0.06) and of 17.37% with ulnar TOF measurements (κ = 0.04), while it was of 62.75% between ulnar and facial TOF measurements (κ = 0.45). Results were similar for cisatracurium and atracurium. Repeated facial TOF measurements performed on the first 4 days of mechanical ventilation in ARDS patients showed that the proportion of patients TOF = 1-2 was around 8% and did not vary significantly with time (p = 0.9), proportion of patients TOF = 3-4 increased from 24 to 40% (p = 0.01), proportion of patients TOF = 0 decreased from 71 to 53% (p = 0.005) while objectives for protective ventilation were achieved. Proportions of facial and ulnar TOF = 0 were significantly higher among patients with ICU-acquired weakness (ICU-AW) versus those who did not develop ICU-AW (51 vs. 40%, p = 0.03, and 76 vs. 62%, p = 0.006, respectively). CONCLUSIONS: The study provides data on clinical and TOF monitoring of neuromuscular blockade, which are widely divergent in ICU patients receiving recommended doses of benzylisoquinoliniums.

Current evidence for the use of sugammadex in children.

Sugammadex is a novel pharmacologic agent, which reverses neuromuscular blockade with a mechanism that differs from the commonly used, acetylcholinesterase inhibitors. Although sugammadex has not received approval from the United States Food & Drug administration in children, its use has already been reported to reverse neuromuscular blockade in several clinical scenarios in the pediatric population including the 'cannot intubate-cannot ventilate' scenario. To date, there remains limited data from prospective trials in the pediatric-aged patient. Anecdotal use has been reported for the reversal of neuromuscular blockade in difficult clinical scenarios such as children with neuromuscular diseases including myasthenia gravis, Duchenne muscular dystrophy, and myotonic dystrophy.

Incidence of postoperative residual neuromuscular blockade after general anesthesia: a prospective, multicenter, anesthetist-blind, observational study.

OBJECTIVE: Evidences demonstrate that postoperative residual neuromuscular blockade (rNMB) is a primary and frequent anesthetic risk factor for postoperative complications. This study was designed to mitigate the paucity of data regarding the occurrence and degree of rNMB in a real-life setting. METHODS: This prospective, multicenter, anesthetist-blind, observational study enrolled 1571 Chinese adults undergoing elective open or laparoscopic abdominal surgery lasting ≤4 hours from 32 hospitals across China. The patients received anesthesia in accordance with routine practice at the study site. Neuromuscular blockade (NMB) was monitored using acceleromyography, with rNMB defined as a train-of-four (TOF) ratio <0.9. RESULTS: The patients' mean age was 46 years and 71% were female. The procedures included laparoscopic (67%), open abdominal (31%), and laparoscopic to open abdominal (2%). NMB was reversed with neostigmine in 78% of patients. The overall incidence of rNMB at extubation was 57.8%, and the proportions of participant with TOF ratios <0.6, 0.6-0.7, 0.7-0.8, 0.8-0.9 were 22.9%, 6.9%, 11.1% and 16.9%, respectively, immediately prior to endotracheal extubation. Age <45 years (OR = 0.630, 95% CI = 0.496-0.801, p = 0.002), use of one neuromuscular blocking agent (NMBA) (OR = 0.387, 95% CI = 0.243-0.618, p < 0.0001), time from neostigmine administration to endotracheal extubation ≥10 min (OR = 0.513, 95% CI = 0.400-0.658, p < 0.0001) and time from last NMBA administration to endotracheal extubation ≥60 min (OR = 0.902, 95% CI = 0.801-0.989, p = 0411) were correlated with non-rNMB at the time of extubation. CONCLUSIONS: This observational study demonstrated that the overall incidence of rNMB at the time of endotracheal extubation was high in Chinese patients undergoing abdominal procedures, which necessitates appropriate management in current real-life practice. CLINICAL TRIAL REGISTRY NUMBER: NCT01871064.

Late recurarization in the post-anesthetic care unit after total thyroidectomy: A case report

Residual paralysis, recurarization is defined as a remnant effect of neuromuscular blocking after surgery that can cause postoperative complications. Clinical complications of recurarization include dyspnea, gastric content aspiration, and atelectasis. Therefore, complete recovery of muscle strength at the end of surgery is a significant factor for patient safety. We report a case of a 53-year-old woman who presented with residual paralysis after total thyroidectomy. To improve her condition, we injected sugammadex intravenously in the post-anesthetic care unit. After that, we observed her for 1 hour and her muscle strength gradually recovered. She did not have any symptoms on the next day and was discharged on the 5th post-operative day.

Change in the effect of rocuronium after pneumatic tourniquet release in patients undergoing unilateral total knee arthroplasty

BACKGROUND: A pneumatic tourniquet is commonly used in orthopedic surgery. However, neuromuscular blocking agent can be sequestered in the isolated limb and be reabsorbed into the systemic circulation after tourniquet release, potentially delaying extubation. To investigate the change in the train-of-four (TOF) ratio after tourniquet release and correlate the TOF ratio change with the extubation time. METHODS: Forty patients undergoing unilateral total knee arthroplasty were enrolled. Before and after the pneumatic tourniquet release, 10 measurements of the TOF ratio were averaged and compared. Additionally, we investigated the correlation between the percentage change in the TOF ratio before and after tourniquet release and the extubation time. RESULTS: Among the 40 patient subjects, 30 showed a TOF ratio before tourniquet release and 10 showed only a TOF count. Of the 30 patients with a TOF ratio, 21 showed a TOF ratio increase after tourniquet release and 9 showed a TOF decrease; both increase and decrease were statistically significant (P < 0.001 and P = 0.008, respectively). The extubation time showed a weak negative correlation with the percentage change in the TOF ratio after tourniquet release (P = 0.004). CONCLUSIONS: In orthopedic surgery using a pneumatic tourniquet, neuromuscular function monitoring may be required to monitor the change in the effect of neuromuscular blocking agent before and after tourniquet release, which may help to improve anesthesia safety.