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.

Quantitative Neuromuscular Monitoring and Postoperative Outcomes: A Narrative Review.

Over the past five decades, quantitative neuromuscular monitoring devices have been used to examine the incidence of postoperative residual neuromuscular block in international clinical practices, and to determine their role in reducing the risk of residual neuromuscular block and associated adverse clinical outcomes. Several clinical trials and a recent meta-analysis have documented that the intraoperative application of quantitative monitoring significantly reduces the risk of residual neuromuscular blockade in the operating room and postanesthesia care unit. In addition, emerging data show that quantitative monitoring minimizes the risk of adverse clinical events, such as unplanned postoperative reintubations, hypoxemia, and postoperative episodes of airway obstruction associated with incomplete neuromuscular recovery, and may improve postoperative respiratory outcomes. Several international anesthesia societies have recommended that quantitative monitoring be performed whenever a neuromuscular blocking agent is administered. Therefore, a comprehensive review of the literature was performed to determine the potential benefits of quantitative monitoring in the perioperative setting.

Perioperative Methadone and Ketamine for Postoperative Pain Control in Spinal Surgical Patients: A Randomized, Double-blind, Placebo-controlled Trial.

BACKGROUND: Despite application of multimodal pain management strategies, patients undergoing spinal fusion surgery frequently report severe postoperative pain. Methadone and ketamine, which are N-methyl-d-aspartate receptor antagonists, have been documented to facilitate postoperative pain control. This study therefore tested the primary hypothesis that patients recovering from spinal fusion surgery who are given ketamine and methadone use less hydromorphone on the first postoperative day than those give methadone alone. METHODS: In this randomized, double-blind, placebo-controlled trial, 130 spinal surgery patients were randomized to receive either methadone at 0.2 mg/kg (ideal body weight) intraoperatively and a 5% dextrose in water infusion for 48 h postoperatively (methadone group) or 0.2 mg/kg methadone intraoperatively and a ketamine infusion (0.3 mg · kg-1 · h-1 infusion [no bolus] intraoperatively and then 0.1 mg · kg-1 · h-1 for next 48 h [both medications dosed at ideal body weight]; methadone/ketamine group). Anesthetic care was standardized in all patients. Intravenous hydromorphone use on postoperative day 1 was the primary outcome. Pain scores, intravenous and oral opioid requirements, and patient satisfaction with pain management were assessed for the first 3 postoperative days. RESULTS: Median (interquartile range) intravenous hydromorphone requirements were lower in the methadone/ketamine group on postoperative day 1 (2.0 [1.0 to 3.0] vs. 4.6 [3.2 to 6.6] mg in the methadone group, median difference [95% CI] 2.5 [1.8 to 3.3] mg; P < 0.0001) and postoperative day 2. In addition, fewer oral opioid tablets were needed in the methadone/ketamine group on postoperative day 1 (2 [0 to 3] vs. 4 [0 to 8] in the methadone group; P = 0.001) and postoperative day 3. Pain scores at rest, with coughing, and with movement were lower in the methadone/ketamine group at 23 of the 24 assessment times. Patient-reported satisfaction scores were high in both study groups. CONCLUSIONS: Postoperative analgesia was enhanced by the combination of methadone and ketamine, which act on both N-methyl-d-aspartate and µ-opioid receptors. The combination could be considered in patients having spine surgery.

Neuromuscular and Clinical Recovery in Thoracic Surgical Patients Reversed With Neostigmine or Sugammadex.

BACKGROUND: Patients undergoing thoracoscopic procedures may be at high-risk for incomplete neuromuscular recovery and associated complications. The aim of this clinical investigation was to assess the incidence of postoperative residual neuromuscular blockade in adult thoracic surgical patients administered neostigmine or sugammadex when optimal dosing and reversal strategies for these agents were used. The effect of choice of reversal agent on hypoxemic events and signs and symptoms of muscle weakness were also determined. Additionally, operative conditions in each group were graded by surgeons performing the procedures. METHODS: Two hundred patients undergoing thoracoscopic surgical procedures were enrolled in this nonrandomized controlled trial. One hundred consecutive patients maintained at moderate levels of neuromuscular blockade were reversed with neostigmine (neostigmine group) followed by 100 consecutive patients given sugammadex to antagonize deeper levels of neuromuscular blockade (sugammadex group). Anesthetic and neuromuscular management were standardized. Surgeons rated operative conditions at the conclusion of the procedure on a 4-point scale (grade 1 = excellent to grade 4 = poor). Train-of-four ratios were measured immediately before extubation and at PACU admission (primary outcomes). Postoperatively, patients were assessed for adverse respiratory events and 11 signs and 16 symptoms of muscle weakness. RESULTS: The 2 groups were similar in intraoperative management characteristics. The percentage of patients with residual neuromuscular blockade, defined as a normalized train-of-four ratio <0.9, was significantly greater in the neostigmine group than the sugammadex group at both tracheal extubation (80% vs 6%, respectively, P < .0001) and PACU admission (61% vs 1%, respectively, P < .0001). Patients in the neostigmine group had less optimal operative conditions (median score 2 [good] versus 1 [excellent] in the sugammadex group; P < .0001), and more symptoms of muscle weakness were present in these subjects (median number [interquartile range] 4 [1-8] vs 1 [0-2] in the sugammadex group, P < .0001). No differences between groups in adverse airway events were observed. CONCLUSIONS: Despite the application of strategies documented to reduce the risk of residual neuromuscular blockade, a high percentage of thoracoscopic patients whose neuromuscular blockade was reversed with neostigmine were admitted to the PACU with clinical evidence of residual paralysis. In contrast, muscle weakness was rarely observed in patients whose neuromuscular blockade was antagonized with sugammadex.

Postoperative Pain and Analgesic Requirements in the First Year after Intraoperative Methadone for Complex Spine and Cardiac Surgery.

BACKGROUND: Methadone is a long-acting opioid that has been reported to reduce postoperative pain scores and analgesic requirements and may attenuate development of chronic postsurgical pain. The aim of this secondary analysis of two previous trials was to follow up with patients who had received a single intraoperative dose of either methadone or traditional opioids for complex spine or cardiac surgical procedures. METHODS: Preplanned analyses of long-term outcomes were conducted for spinal surgery patients randomized to receive 0.2 mg/kg methadone at the start of surgery or 2 mg hydromorphone at surgical closure, and for cardiac surgery patients randomized to receive 0.3 mg/kg methadone or 12 µg/kg fentanyl intraoperatively. A pain questionnaire assessing the weekly frequency (the primary outcome) and intensity of pain was mailed to subjects 1, 3, 6, and 12 months after surgery. Ordinal data were compared with the Mann-Whitney U test, and nominal data were compared using the chi-square test or Fisher exact probability test. The criterion for rejection of the null hypothesis was P < 0.01. RESULTS: Three months after surgery, patients randomized to receive methadone for spine procedures reported the weekly frequency of chronic pain was less (median score 0 on a 0 to 4 scale [less than once a week] vs. 3 [daily] in the hydromorphone group, P = 0.004). Patients randomized to receive methadone for cardiac surgery reported the frequency of postsurgical pain was less at 1 month (median score 0) than it was in patients randomized to receive fentanyl (median score 2 [twice per week], P = 0.004). CONCLUSIONS: Analgesic benefits of a single dose of intraoperative methadone were observed during the first 3 months after spinal surgery (but not at 6 and 12 months), and during the first month after cardiac surgery, when the intensity and frequency of pain were the greatest.

Awake Volunteer Pain Scores During Neuromuscular Monitoring.

BACKGROUND: There is a need for easy to use, reliable neuromuscular monitors (NMMs). This multicenter, prospective, unblinded study compared the discomfort associated with neurostimulation in unmedicated healthy volunteers when using the new electromyography (EMG)-based TetraGraph and acceleromyography (AMG)-based TOF-Watch NMMs. The secondary aim was to compare the repeatability of the train-of-four (TOF) ratios (TOFRs) obtained with the 2 devices. METHODS: The TOF measurements of 135 volunteers from 3 university hospitals were analyzed (age: 38.3 ± 12 years [mean ± standard deviation [SD]]; male/female ratio = 63:72). The left or right ulnar nerve was stimulated at the wrist in TOF mode with 20, 30, 40, and 50 mA stimulating current intensities with both devices in random order. The TOF-Watch used standard electrocardiography (ECG) electrodes (Red Dot; 3M Health Care) for nerve stimulation. The stimulating surface area of 1 ECG electrode is 113 mm. The piezoelectric probe was attached to the thumb, and a hand adapter was used to ensure consistency of AMG measurements. The TetraGraph uses proprietary surface strip electrodes for nerve stimulation and muscle action potential recording, whose stimulating surface area is roughly twice as big as that of standard ECG electrodes (228.5 mm). The volunteers were asked to rate the discomfort associated with neurostimulation on a 0-10 verbal numerical rating scale (VNRS) score anchored with 0 (no pain) and 10 (worst pain ever experienced). A linear mixed-effects model was used to evaluate the difference in VNRS scores between devices. P <.05 was accepted as the level of significance. RESULTS: In the linear mixed-effects model, there were no differences in VNRS scores between devices at any of the stimulating current intensities, P = .38. The median (range) VNRS scores obtained with TOF-Watch and TetraGraph devices were 2 (0-7) vs 2 (0-8) at 20 mA, 3 (1-9) vs 3 (1-9) at 30 mA, 5 (1-10) vs 5 (1-10) at 40 mA, and 5 (1-10) vs 6 (1-10) at 50 mA stimulating current intensities. The mean of the 1469 TOFRs obtained with TetraGraph was 100.43% ± 7.74% (standard error = 0.2%). Due to technical difficulties, the repeatability of the TOFRs could not be determined. CONCLUSIONS: Despite the different size and design of the stimulating electrodes, the 2 NMMs caused the same level of discomfort in unmedicated healthy volunteers.

Safety of Beach Chair Position Shoulder Surgery: A Review of the Current Literature.

Although uncommon, severe neurological events have been reported in patients undergoing shoulder surgery in the beach chair position. The presumed etiology of central nervous system injury is hypotension and subsequent cerebral hypoperfusion that occurs after alterations in positioning under general anesthesia. Most clinical trials have demonstrated that beach chair positioning results in reductions in regional brain oxygenation, cerebral blood flow, and jugular bulb oxygenation, as well as impairment in cerebral autoregulation and electroencephalographic/processed electroencephalographic variables. Further studies are needed to define the incidence of adverse neurological adverse events in the beach chair position, identify the best intraoperative neurological monitors that are predictive of neurocognitive outcomes, the lowest "safe" acceptable blood pressure during surgery for individual patients, and the optimal interventions to treat intraoperative hypotension.

Comparison of the TOFscan and the TOF-Watch SX during Recovery of Neuromuscular Function.

WHAT WE ALREADY KNOW ABOUT THIS TOPIC: WHAT THIS ARTICLE TELLS US THAT IS NEW: BACKGROUND:: Quantitative neuromuscular monitoring is required to ensure neuromuscular function has recovered completely at the time of tracheal extubation. The TOFscan (Drager Technologies, Canada) is a new three-dimensional acceleromyography device that measures movement of the thumb in multiple planes. The aim of this observational investigation was to assess the agreement between nonnormalized and normalized train-of-four values obtained with the TOF-Watch SX (Organon, Ireland) and those obtained with the TOFscan during recovery from neuromuscular blockade. METHODS: Twenty-five patients were administered rocuronium, and spontaneous recovery of neuromuscular blockade was allowed to occur. The TOFscan and TOF-Watch SX devices were applied to opposite arms. A preload was applied to the TOF-Watch SX, and calibration was performed before rocuronium administration. Both devices were activated, and train-of-four values were obtained every 15 s. Modified Bland-Altman analyses were conducted to compare train-of-four ratios measured with the TOFscan to those measured with the TOF-Watch SX (when train-of-four thresholds of 0.2 to 1.0 were achieved). RESULTS: Bias and 95% limits of agreement between the TOF-Watch SX and the TOFscan at nonnormalized train-of-four ratios between 0.2 and 1.0 were 0.021 and -0.100 to 0.141, respectively. When train-of-four measures with the TOF-Watch SX were normalized, bias and 95% limits of agreement between the TOF-Watch SX and the TOFscan at ratios between 0.2 and 1.0 were 0.015 and -0.097 to 0.126, respectively. CONCLUSIONS: Good agreement between the TOF-Watch SX with calibration and preload application and the uncalibrated TOFscan was observed throughout all stages of neuromuscular recovery.

Neostigmine Administration after Spontaneous Recovery to a Train-of-Four Ratio of 0.9 to 1.0: A Randomized Controlled Trial of the Effect on Neuromuscular and Clinical Recovery.

BACKGROUND: When a muscle relaxant is administered to facilitate intubation, the benefits of anticholinesterase reversal must be balanced with potential risks. The aim of this double-blinded, randomized noninferiority trial was to evaluate the effect of neostigmine administration on neuromuscular function when given to patients after spontaneous recovery to a train-of-four ratio of 0.9 or greater. METHODS: A total of 120 patients presenting for surgery requiring intubation were given a small dose of rocuronium. At the conclusion of surgery, 90 patients achieving a train-of-four ratio of 0.9 or greater were randomized to receive either neostigmine 40 µg/kg or saline (control). Train-of-four ratios were measured from the time of reversal until postanesthesia care unit admission. Patients were monitored for postextubation adverse respiratory events and assessed for muscle strength. RESULTS: Ninety patients achieved a train-of-four ratio of 0.9 or greater at the time of reversal. Mean train-of-four ratios in the control and neostigmine groups before reversal (1.02 vs. 1.03), 5 min postreversal (1.05 vs. 1.07), and at postanesthesia care unit admission (1.06 vs. 1.08) did not differ. The mean difference and corresponding 95% CI of the latter were -0.018 and -0.046 to 0.010. The incidences of postoperative hypoxemic events and episodes of airway obstruction were similar for the groups. The number of patients with postoperative signs and symptoms of muscle weakness did not differ between groups (except for double vision: 13 in the control group and 2 in the neostigmine group; P = 0.001). CONCLUSIONS: Administration of neostigmine at neuromuscular recovery was not associated with clinical evidence of anticholinesterase-induced muscle weakness. VISUAL ABSTRACT: An online visual overview is available for this article.(Figure is included in full-text article.).

Neuromuscular Monitoring in the Perioperative Period.

Neuromuscular monitoring devices were introduced into clinical practice in the 1970s. Qualitative neuromuscular monitors, or peripheral nerve stimulators, provide an electrical stimulus to a motor nerve and the response of corresponding muscle subjectively evaluated. A standard peripheral nerve stimulator provides several patterns of nerve stimulation, including train-of-four (TOF), double-burst, tetanic, and post-tetanic count. Qualitative (and quantitative) monitors are needed to determine onset of neuromuscular blockade, maintain the required depth of muscle relaxation during the surgical procedure, and assess an appropriate dose of reversal agent. However, absence of fade measured with a peripheral nerve stimulator does not exclude residual neuromuscular block; TOF ratios as low as 0.4-0.6 may be present when fade is no longer observed. In addition, the risk of incomplete neuromuscular recovery may be influenced by monitoring site. The adductor pollicis is more sensitive to the effects of neuromuscular blocking agents (compared to the muscles surrounding the eye), and monitoring at this site may more accurately reflect recovery of pharyngeal muscles (the last muscles to recover from the effects of neuromuscular blocking agents, in which dysfunction may persist even at a TOF ratio of 1.0). Quantitative monitors are devices that measure and quantify the degree of muscle weakness and display the results numerically. Several different technologies have been developed, including mechanomyography, electromyography, acceleromyography, kineograph, and phonomyography. Lower doses of anticholinesterases may be used to effectively reverse neuromuscular blockade at TOF ratios of 0.4-0.6; quantitative monitoring is required to determine that this level of neuromuscular recovery has occurred. As clinical tests of muscle strength, peripheral nerve stimulators are unable to determine whether full recovery of neuromuscular function is present at the end of the surgical procedure. The use of quantitative monitors is essential in excluding clinically important muscle weakness (TOF ratios <0.9 to 1.0) at the time of tracheal extubation.

Clinical Effectiveness and Safety of Intraoperative Methadone in Patients Undergoing Posterior Spinal Fusion Surgery: A Randomized, Double-blinded, Controlled Trial.

BACKGROUND: Patients undergoing spinal fusion surgery often experience severe pain during the first three postoperative days. The aim of this parallel-group randomized trial was to assess the effect of the long-duration opioid methadone on postoperative analgesic requirements, pain scores, and patient satisfaction after complex spine surgery. METHODS: One hundred twenty patients were randomized to receive either methadone 0.2 mg/kg at the start of surgery or hydromorphone 2 mg at surgical closure. Anesthetic care was standardized, and clinicians were blinded to group assignment. The primary outcome was intravenous hydromorphone consumption on postoperative day 1. Pain scores and satisfaction with pain management were measured at postanesthesia care unit admission, 1 and 2 h postadmission, and on the mornings and afternoons of postoperative days 1 to 3. RESULTS: One hundred fifteen patients were included in the analysis. Median hydromorphone use was reduced in the methadone group not only on postoperative day 1 (4.56 vs. 9.90 mg) but also on postoperative days 2 (0.60 vs. 3.15 mg) and 3 (0 vs. 0.4 mg; all P< 0.001). Pain scores at rest, with movement, and with coughing were less in the methadone group at 21 of 27 assessments (all P = 0.001 to < 0.0001). Overall satisfaction with pain management was higher in the methadone group than in the hydromorphone group until the morning of postoperative day 3 (all P = 0.001 to < 0.0001). CONCLUSIONS: Intraoperative methadone administration reduced postoperative opioid requirements, decreased pain scores, and improved patient satisfaction with pain management.

Documentation and Treatment of Intraoperative Hypotension: Electronic Anesthesia Records versus Paper Anesthesia Records.

In this study, we examined anesthetic records before and after the implementation of an electronic anesthetic record documentation (AIMS) in a single surgical population. The purpose of this study was to identify any inconsistencies in anesthetic care based on handwritten documentation (paper) or AIMS. We hypothesized that the type of anesthetic record (paper or AIMS) would lead to differences in the documentation and management of hypotension. Consecutive patients who underwent esophageal surgery between 2009 and 2014 by a single surgeon were eligible for the study. Patients were grouped in to 'paper' or 'AIMS' based on the type of anesthetic record identified in the chart. Pertinent patient identifiers were removed and data collated after collection. Predetermined preoperative and intraoperative data variables were reviewed. Consecutive esophageal surgery patients (N = 189) between 2009 and 2014 were evaluated. 92 patients had an anesthetic record documented on paper and 97 using AIMS. The median number of unique blood pressure recordings was lower in the AIMS group (median (Q1,Q3) AIMS 30.0 (24.0, 39.0) vs. Paper 35.0 (28.5, 43.5), p < 0.01). However, the median number of hypotensive events (HTEs) was higher in the AIMS group (median (Q1,Q3) 8.0 (4.0, 18.0) vs. 4.0 (1.0, 10.5), p < 0.001), and the percentage of HTEs per blood pressure recording was higher in the AIMS group (30.4 ((Q1, Q3) (9.5, 60.9)% vs. 12.5 (2.4, 27.5)%), p < 0.01). Multivariable regression analysis identified independent predictors of HTEs. The incidence of HTEs was found to increase with AIMS (IRR = 1.88, p < 0.01). Preoperative systolic blood pressure, increased blood loss, and phenylephrine. A phenylephrine infusion was negatively associated with hypotensive events (IRR = 0.99, p = 0.03). We noted an increased incidence of HTEs associated with the institution of an AIMS. Despite this increase, no change in medical therapy for hypotension was seen. AIMS did not appear to have an effect on the management of intraoperative hypotension in this patient population.

Anesthetic consideration for neuromuscular diseases.

PURPOSE OF REVIEW: The aim of this review is to examine data relating to perioperative management of the patient with neuromuscular disorders RECENT FINDINGS: Patients with pre-existing neuromuscular disorders are at risk for a number of postoperative complications that are related to anesthetic drugs that are administered intraoperatively. Careful preoperative assessment is necessary to reduce morbidity and mortality. In particular, the risk of postoperative respiratory failure and need for long-term ventilation should be reviewed with patients. The use of succinylcholine should be avoided in muscular dystrophies, motor neuron diseases, and intrinsic muscle disease due to a risk of malignant hyperthermia, hyperkalemia, rhabdomyolysis, and cardiac arrest. The use of quantitative neuromuscular monitoring should be strongly considered whenever nondepolarizing neuromuscular blocking agents are administered. A number of case series and reports have been recently published demonstrating that sugammadex can be safely used in patients with neuromuscular disease; the risk of residual neuromuscular is nearly eliminated when this agent is administered intraoperatively. SUMMARY: Careful assessment and management of patients with underlying neuromuscular diseases is required to reduce postoperative complications. This article reviews the anesthetic implications of patients undergoing surgery with neuromuscular disorder.

Consent for Anesthesia Clinical Trials on the Day of Surgery: Patient Attitudes and Perceptions.

BACKGROUND: Opportunities for anesthesia research investigators to obtain consent for clinical trials are often restricted to the day of surgery, which may limit the ability of subjects to freely decide about research participation. The aim of this study was to determine whether subjects providing same-day informed consent for anesthesia research are comfortable doing so. METHODS: A 25-question survey was distributed to 200 subjects providing informed consent for one of two low-risk clinical trials. While consent on the day of surgery was permitted for both studies, a preadmission telephone call was required for one. The questionnaire was provided to each subject at the time of discharge from the hospital. The questions were structured to assess six domains relating to the consent process, and each question was graded on a 5-point Likert scale (1 = strongly disagree to 5 = strongly agree). Overall satisfaction with same-day consent was assessed using an 11-point scale with 0 = extremely dissatisfied and 10 = extremely satisfied. RESULTS: Completed questionnaires were received from 129 subjects. Median scores for satisfaction with the consent process were 9.5 to 10. Most respondents reported that the protocol was well explained and comprehended and that the setting in which consent was obtained was appropriate (median score of 5). Most patients strongly disagreed that they were anxious at the time of consent, felt obligated to participate, or had regrets about participation (median score of 1). Ten percent or less of subjects reported negative responses to any of the questions, and no differences were observed between the study groups. CONCLUSION: More than 96% of subjects who provided same-day informed consent for low-risk research were satisfied with the consent process.

Residual Neuromuscular Block in the Elderly: Incidence and Clinical Implications.

BACKGROUND: Elderly patients are at increased risk for anesthesia-related complications. Postoperative residual neuromuscular block (PRNB) in the elderly, defined as a train-of-four ratio less than 0.9, may exacerbate preexisting muscle weakness and respiratory dysfunction. In this investigation, the incidence of PRNB and associated adverse events were assessed in an elderly (70 to 90 yr) and younger cohort (18 to 50 yr). METHODS: Data were prospectively collected on 150 younger and 150 elderly patients. Train-of-four ratios were measured on arrival to the postanesthesia care unit (PACU). After tracheal extubation, patients were examined for adverse respiratory events during transport to the PACU, for 30 min after PACU admission, and during hospital admission. Postoperative muscle weakness was quantified using a standardized examination, and PACU and hospital lengths of stay were determined. RESULTS: The incidence of PRNB was 57.7% in elderly and 30.0% in younger patients (difference, -27.7%; 99% CI, -41.2 to -13.1%; P < 0.001). Airway obstruction, hypoxemic events, signs and symptoms of muscle weakness, postoperative pulmonary complications, and increased PACU and hospital lengths of stay were observed more frequently in the elderly (all P < 0.01). Within each cohort, most adverse events were observed in patients with PRNB. Younger patients with PRNB received larger total doses of rocuronium than did those without it (60 vs. 50 mg, P < 0.01), but there were no differences in rocuronium dose between elderly patients with PRNB and those without it (both 50 mg). CONCLUSION: The elderly are at increased risk for PRNB and associated adverse outcomes.

Intraoperative Methadone for the Prevention of Postoperative Pain: A Randomized, Double-blinded Clinical Trial in Cardiac Surgical Patients.

BACKGROUND: The intensity of pain after cardiac surgery is often underestimated, and inadequate pain control may be associated with poorer quality of recovery. The aim of this investigation was to examine the effect of intraoperative methadone on postoperative analgesic requirements, pain scores, patient satisfaction, and clinical recovery. METHODS: Patients undergoing cardiac surgery with cardiopulmonary bypass (n = 156) were randomized to receive methadone (0.3 mg/kg) or fentanyl (12 µg/kg) intraoperatively. Postoperative analgesic requirements were recorded. Patients were assessed for pain at rest and with coughing 15 min and 2, 4, 8, 12, 24, 48, and 72 h after tracheal extubation. Patients were also evaluated for level of sedation, nausea, vomiting, itching, hypoventilation, and hypoxia at these times. RESULTS: Postoperative morphine requirements during the first 24 h were reduced from a median of 10 mg in the fentanyl group to 6 mg in the methadone group (median difference [99% CI], -4 [-8 to -2] mg; P < 0.001). Reductions in pain scores with coughing were observed during the first 24 h after extubation; the level of pain with coughing at 12 h was reduced from a median of 6 in the fentanyl group to 4 in the methadone group (-2 [-3 to -1]; P < 0.001). Improvements in patient-perceived quality of pain management were described in the methadone group. The incidence of opioid-related adverse events was not increased in patients administered methadone. CONCLUSIONS: Intraoperative methadone administration resulted in reduced postoperative morphine requirements, improved pain scores, and enhanced patient-perceived quality of pain management.