Shortened time to neuromuscular recovery with lower doses of rocuronium in elderly patients.

INTRODUCTION: The effect of neuromuscular blocking agents may be reversed by administration of neostigmine, when two twitches are present using train-of-four (TOF) stimulation. However, in elderly patients, limited data are available about when to administer neostigmine. We hypothesised that time to two twitches after TOF (TOF-2) was shorter after rocuronium 0.6 mg/kg than after rocuronium 0.9 mg/kg. Also, we hypothesised that time to TOF-2 would be shorter after rocuronium 0.3 mg/kg than after rocuronium 0.6 mg/kg. METHODS: This was a secondary analysis of 50 elderly patients > 80 years; 16 patients received rocuronium 0.6 mg/kg, another 16 patients received rocuronium 0.9 mg/kg; and, finally, 18 patients received rocuronium 0.3 mg/kg. Patients received total intravenous anaesthesia, and neuromuscular block was monitored with acceleromyography. RESULTS: Time to TOF-2 was shorter after rocuronium 0.6 mg/kg than after rocuronium 0.9 mg/kg: 37 min. versus 59 min. (difference: 22 min. (95% confidence intervals (CI): 10 to 33 min.), p = 0.0007). Time to TOF-2 after rocuronium 0.3 mg/kg was shorter than after rocuronium 0.6 mg/kg: 19 min. versus 37 min. (difference: 18 min. (95% CI: 11 to 25 min.), p = 0.00006). However, only 33% of the patients receiving 0.3 mg/kg obtained full effect i.e. TOF-0. CONCLUSION: Time to TOF-2 was shorter after rocuronium 0.6 mg/kg than after 0.9 mg/kg and shorter after rocuronium 0.3 mg/kg than after 0.6 mg/kg. FUNDING: This work was supported by departmental sources. TRIAL REGISTRATION: This study was a secondary analysis of two clinical trials. CLINICALTRIALS: gov (NCT04512313), (NCT03857750).

Onset time, duration of action, and intubating conditions after mivacurium in elderly and younger patients.

BACKGROUND: The neuromuscular blocking agent mivacurium can be used during anesthesia to facilitate tracheal intubation. Data on onset time, duration of action, and effect on intubating conditions in patients 80 years and older are however limited. We hypothesized that onset time and duration of action of mivacurium would be longer in elderly patients than in younger adults. METHODS: This prospective observational study included 35 elderly (≥80 years) and 35 younger (18-40 years) patients. Induction of anesthesia comprised fentanyl 1-3 µg kg-1 and propofol 1.5-2.5 mg kg-1 and propofol and remifentanil for maintenance. Acceleromyography was used for monitoring neuromuscular blockade. The primary outcome was onset time defined as time from injection of mivacurium 0.2 mg kg-1 to a train-of-four (TOF) count of zero. Other outcomes included duration of action (time to TOF ratio ≥0.9), intubating conditions using the Fuchs-Buder scale and the intubating difficulty scale (IDS), and occurrence of hoarseness and sore throat postoperatively. RESULTS: No difference was found in onset time comparing elderly with younger patients; 219 s (SD 45) versus 203 s (SD 74) (difference: 16 s (95% CI: -45 to 14), p = .30). Duration of action was significantly longer in elderly patients compared with younger patients; 52 min (SD 17) versus 30 min (SD 8) (difference: 22 min [95% CI: 15 to 28], p < .001). No difference was found in the proportion of excellent intubating conditions (Fuchs-Buder); 31/35 (89%) versus 26/35 (74%) (p = .12) or IDS score (p = .13). A larger proportion of younger patients reported sore throat 24 h postoperatively; 34% versus 0%, p = .0002. No difference was found in hoarseness. CONCLUSION: No difference in onset time of mivacurium 0.2 mg kg-1 was found comparing elderly and younger patients. However, elderly patients had significantly longer duration of action. No difference was found in intubating conditions.

Effects of avoidance versus use of neuromuscular blocking agents for facilitation of tracheal intubation in children and infants.

BACKGROUND: The European Society of Anesthesiology and Intensive Care recommends the use of neuromuscular blocking agents (NMBA) in adults, to facilitate tracheal intubation and reduce its associated complications. Children who undergo tracheal intubation may suffer some of the same complications, however, no consensus exists regarding the use of NMBA for tracheal intubation in the pediatric population. We will explore the existing evidence assessing the effects of avoidance versus the use of NMBA for the facilitation of tracheal intubation in children and infants. METHODS: This protocol follows the preferred reporting items for systematic reviews and meta-analyses protocols recommendations. We will include all randomized controlled clinical trials assessing the effects of avoidance versus the use of NMBA for facilitation of tracheal intubation (oral or nasal) using direct laryngoscopy or video laryngoscopy in pediatric participants (<18 years). Our primary outcome is incidence of difficult tracheal intubation. Secondary outcomes include incidence of serious adverse events, failed intubation, events of upper airway discomfort or injury, and difficult laryngoscopy. We will conduct a thorough database search to identify relevant trials, including CENTRAL, MEDLINE, EMBASE, BIOSIS, Web of Science, CINAHL, and trial registries. Two review authors will independently handle the screening of literature and data extraction. Each trial will be evaluated for major sources of bias with the "classic risk of bias tool" used in the Cochrane Collaboration tool from 2011. We will use Review manager (RevMan) or R with the meta package to perform the meta-analysis. We will perform a trial sequential analysis on the meta-analysis of our primary outcome, providing an estimate of statistical reliability. Two review authors will independently assess the quality of the body of evidence using the grading of recommendations assessment, development, and evaluation (GRADE) approach. We will use GRADEpro software to conduct the GRADE assessments and to create "Summary of the findings" tables.

Prolonged duration of action of suxamethonium in pregnant and postpartum patients: A registry study.

BACKGROUND: Suxamethonium is hydrolysed by butyrylcholinesterase (BChE) and a low BChE activity can result in a prolonged duration of action of suxamethonium. The BChE activity is reduced during pregnancy and postpartum period by up to 33%. However, it can also be reduced by mutations in the BChE gene. In this study, we assessed BChE activity and mutations in the BChE gene in pregnant and postpartum patients with prolonged duration of action of suxamethonium. It was hypothesised that at least 30% of patients with a low BChE activity did not have a mutation in the BChE gene. METHODS: In this registry study we focused on pregnant and postpartum patients with a history of prolonged duration of action of suxamethonium referred to the Danish Cholinesterase Research Unit (DCRU) between March 2007 and January 2023. Primary outcome was the proportion of patients without a mutation among patients with a low BChE activity. Secondary outcomes were the proportion of patients with a low BChE activity and the proportion of patients with a mutation out of the total number of patients. RESULTS: A total of 40 patients were included and among patients with a low BChE activity, 6% (95% CI: 1%-21%) did not have a mutation. Out of the total number of included patients referred to the DCRU, 90% (95% CI: 76%-97%) had a mutation and 94% (95% CI: 80%-99%) had a low BChE activity. CONCLUSION: Among pregnant and postpartum patients with a history of prolonged duration of action of suxamethonium and a low BChE activity, 6% did not have a mutation in the BChE gene. Our findings suggest that during pregnancy and postpartum clinically relevant prolonged duration of action of suxamethonium rarely occurs in genotypically normal patients.

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.

Tracheal intubating conditions in elderly patients when train-of-four count is zero after rocuronium 0.6 or 0.9 mg/kg. A secondary analysis.

PURPOSE: The neuromuscular blocking agent rocuronium can be administered to facilitate tracheal intubation. We hypothesized that rocuronium 0.9 mg/kg provided a larger proportion of patients with vocal cords in abducted position compared to rocuronium 0.6 mg/kg at train-of-four (TOF) 0. METHODS: This secondary analysis was based on 52 elderly surgical patients of which 36 patients received rocuronium 0.6 mg/kg and 16 patients received rocuronium 0.9 mg/kg. Neuromuscular block was monitored with acceleromyography with TOF stimulation at the ulnar nerve. The primary outcome was the proportion of patients with vocal cords in abducted position at TOF 0. Secondary outcomes were intubating conditions evaluated by the Fuchs-Buder scale, the Intubating Difficulty Score (IDS), onset time, and duration of action of rocuronium. RESULTS: At TOF 0, a significantly larger proportion of patients had vocal cords in abducted position in the rocuronium 0.9 mg/kg group (81%) compared with the rocuronium 0.6 mg/kg group (53%); difference (%) 28, 95% Cl 3-53, P = 0.05. Excellent intubating conditions (Fuchs-Buder) were more common in the rocuronium 0.9 mg/kg group (62.5%); difference (%) 32.5, 95% Cl 4-61), P = 0.03. No significant difference was found in IDS or onset time of rocuronium (difference 19 s, 95% Cl: -5-43). Duration of action was significantly longer (difference 29 min, 95% Cl: 10-47) in the 0.9 mg/kg group. CONCLUSION: The proportion of patients with vocal cords in abducted position was significantly larger after rocuronium 0.9 mg/kg compared to rocuronium 0.6 mg/kg at TOF 0 monitored at the ulnar nerve.

Collaboration for Evidence-based Practice and Research in Anaesthesia (CEPRA): A consortium initiative for perioperative research.

Evidence in perioperative care is insufficient. There is an urgent need for large perioperative research programmes, including pragmatic randomised trials, testing daily clinical treatments and unanswered question, thereby providing solid evidence for effects of interventions given to a large and growing number of patients undergoing surgery and anaesthesia. This may be achieved through large collaborations. Collaboration for Evidence-based Practice and Research in Anaesthesia (CEPRA) is a novel collaborative research network founded to pursue evidence-based answers to major clinical questions in perioperative medicine. The aims of CEPRA are to (1) improve clinical treatment and outcomes and optimise the use of resources for patients undergoing anaesthesia and perioperative care, and (2) disseminate results and inform caretakers, patients and relatives, and policymakers of evidence-based treatments in anaesthesia and perioperative medicine. CEPRA is inclusive in its concept. We aim to extend our collaboration with all relevant clinical collaborators and patient associations and representatives. Although initiated in Denmark, CEPRA seeks to develop an international network infrastructure, for example, with other Nordic countries. The work of CEPRA will follow the highest methodological standards. The organisation aims to structure and optimise any element of the research collaboration to reduce economic costs and harness benefits from well-functioning research infrastructure. This includes successive continuation of trials, harmonisation of outcomes, and alignment of data management systems. This paper presents the initiation and visions of the CEPRA network. CEPRA aims to be inclusive, patient-focused, methodologically sound, and to optimise all aspects of research logistics. This will translate into faster research conduct, reliable results, and accelerated clinical implementation of results, thereby benefiting millions of patients whilst being cost and labour-saving.

Comparison of onset time, duration of action, and intubating conditions after cisatracurium 0.15 mg/kg in young and elderly patients.

INTRODUCTION: Tracheal intubation during anesthesia can be facilitated by the neuromuscular blocking agent cisatracurium. However, limited data exists about onset time, duration of action and effect on intubating conditions in elderly patients above 80 years of age. We hypothesized that elderly patients would present a longer onset time and duration of action compared to younger adults. METHODS: This prospective observational study included 31 young (18-40 years) and 29 elderly (≥ 80 years) patients. Patients were given fentanyl 2 µg/kg and propofol 1.5-2.5 mg/kg for induction of anesthesia and maintained with remifentanil and propofol. Monitoring of neuromuscular function was performed with acceleromyography. Primary outcome was onset time defined as time from injection of cisatracurium 0.15 mg/kg (based on ideal body weight) to a train-of-four (TOF) count of 0. Other outcomes included duration of action (time to TOF ratio ≥ 0.9), intubation conditions using the Fuchs-Buder scale and the Intubating Difficulty Scale (IDS), and occurrence of hoarseness and sore throat postoperatively. RESULTS: Elderly patients had significantly longer onset time compared with younger patients; 297 seconds (SD 120) vs. 199 seconds (SD 59) (difference: 98 seconds (95% CI: 49-147), P < 0.001)). Duration of action was also significantly longer in elderly patients compared with younger patients; 89 minutes (SD 17) vs. 77 minutes (SD 14) (difference: 12 minutes (95% CI: 2.5-20.5) P = 0.01)). No difference was found in the proportion of excellent intubating conditions (Fuchs-Buder); 19/29 (66%) vs 21/31 (68%) (P = 0.86) or IDS score (P = 0.74). A larger proportion of elderly patients reported hoarseness 24 hours postoperatively; 62% vs 34% P = 0.04. CONCLUSION: In elderly patients cisatracurium 0.15 mg/kg had significantly longer onset time and duration of action compared with younger patients. No difference was found in intubating conditions at a TOF count of 0. TRIAL REGISTRATION: Clinicaltrials.gov (NCT04921735, date of registration 10 June 2021).

Rocuronium 0.3 or 0.9 mg/kg comparing onset time, duration of action, and intubating conditions in patients 80 years and older: A randomized study.

BACKGROUND: Limited data exist about the optimal dose of rocuronium for intubation in elderly patients. We hypothesized that rocuronium 0.9 mg/kg would lead to a shorter onset time than 0.3 mg/kg in patients above 80 years. METHODS: Thirty-four patients were randomized to either rocuronium 0.3 or 0.9 mg/kg. The primary outcome was onset time defined as time to train-of-four (TOF) count of 0. Other outcomes included duration of action (time to TOF ratio >0.9), proportion of excellent intubating conditions using the Fuchs-Buder scale and tracheal intubating conditions using the Intubating Difficulty Scale (IDS). RESULTS: Rocuronium 0.9 mg/kg resulted in shorter onset time compared to rocuronium 0.3 mg/kg; 108 s (SD 40) vs. 228 s (SD 140) (difference: 119 s [95% CI: 41-196], p = .005), respectively. However, in 66% of the patients receiving rocuronium 0.3 mg/kg a TOF count of 0 was not obtained. Duration of action was longer after rocuronium 0.9 mg/kg: 118 min (SD 43) vs. 46 min (SD 13) (difference: 72 min [95% CI: 49-95] p < .0001), and a greater proportion of excellent intubating conditions (Fuchs-Buder) was obtained; 11/16 (69%) vs 4/18 (22%) (p = .006). No difference was found regarding IDS score. CONCLUSION: Rocuronium 0.9 mg/kg resulted in a shorter onset time compared to rocuronium 0.3 mg/kg in patients above 80 years of age. In 66% of the patients receiving rocuronium 0.3 mg/kg a TOF count of 0 was not obtained.

A blinded randomized study comparing intubating conditions after either rocuronium 0.6 mg·kg-1 or remifentanil 2 µg·kg-1 in elderly patients.

BACKGROUND: To facilitate tracheal intubation, either a neuromuscular blocking agent or a bolus dose of remifentanil can be administered. We hypothesized that rocuronium 0.6 mg·kg-1 provided a larger proportion of excellent intubating conditions compared to remifentanil 2 µg·kg-1 in patients above 80 years. METHODS: A total of 78 patients were randomized to either rocuronium 0.6 mg·kg-1 or remifentanil 2 µg·kg-1 . General anaesthesia was initiated with fentanyl and propofol. Two minutes after the administration of either rocuronium or remifentanil, tracheal intubating conditions were evaluated using the Fuchs-Buder scale by a blinded investigator, and our primary outcome was the proportion of patients presenting intubating conditions deemed as excellent. Further outcomes included the Intubating Difficulty Scale (IDS), hoarseness or sore throat 24 h postoperatively, and intervention against hypotension. RESULTS: No difference in the occurrence of excellent intubating conditions was found comparing the rocuronium group with the remifentanil group; 10 (28%) versus 15 (39%) (p = .29), respectively, relative risk = 0.72. Interventions against hypotension were used in 24 (67%) versus 28 (74%) (p = .51), respectively. Hoarseness and sore throat 24 h postoperatively were found in 37% versus 35% p = .86, and 14% versus 5% p = .20, respectively. The IDS score was 2 versus 2 p = .48. CONCLUSION: No difference in intubating conditions was found 2 min after the administration of either rocuronium 0.6 mg·kg-1 or remifentanil 2 µg·kg-1 in patients aged above 80 years. Intubation conditions were less than optimal in a large proportion of this patient population. CLINICAL TRIALS REGISTRATION: NCT04287426.

Onset time and duration of action of rocuronium 0.6 mg/kg in patients above 80 years of age: A comparison with young adults.

BACKGROUND: The number of elderly is increasing, and a large proportion of these people will require surgery and anaesthesia. However, little data exist regarding rocuronium in patients above 80 years of age. The aim of this study was to determine the onset time and duration of action for rocuronium 0.6 mg/kg in patients above 80 years compared with young adults. METHODS: This prospective observational study included 16 young (18-40 years) and 16 elderly (>80 years) patients scheduled for total intravenous anaesthesia. Neuromuscular block following rocuronium 0.6 mg/kg was monitored with acceleromyography using train-of-four (TOF) stimulation. The primary outcome was onset time (from administration of rocuronium until TOF count = 0). Secondary outcomes were duration of action (from administration to TOF ratio >0.9) and intubating conditions according to Intubation Difficulty Score. RESULTS: Elderly patients, median age of 84 years, had significantly prolonged onset time compared to younger patients; median 135 seconds (135-158) vs 90 seconds (90-105), respectively, a mean difference of 82 seconds (40-124) and Wilcoxon Mann-Whitney odds (WMW) of 19.48 (7.48-X). Duration of action in elderly patients was significantly longer, with a median time of 81 minute (71-97) vs 53 minute (42-73), respectively, a mean difference of 31 minute (14-48), and WMW odds of 6.35 (2.59-X). There was no significant difference in intubating conditions. CONCLUSIONS: Patients above 80 years had significantly prolonged onset time and duration of action after rocuronium 0.6 mg/kg compared with patients aged 18-40 years.

Incidence of residual neuromuscular blockade in children below 3 years after a single bolus of cisatracurium 0.1 mg/kg: A quality assurance study.

BACKGROUND: The aim of this quality assurance study was to determine the proportion of patients with residual block (train-of-four (TOF) ratio <0.9) upon conclusion of surgery after a bolus of cisatracurium 0.1 mg/kg. It was considered good quality if less than 10% of the study population had residual block upon conclusion of surgery. METHODS: A total of 40 patients ≤3 years of age scheduled for cleft lip and palate repair were consecutively enrolled. They received general anaesthesia with either sevoflurane and fentanyl (n = 20) or propofol and remifentanil (n = 20). TOF stimulation using acceleromyography was applied on the tibial nerve. Cisatracurium 0.1 mg/kg was administered to facilitate tracheal intubation. RESULTS: Three patients (8%; 95% CI: 1.7-21) had a TOF ratio <0.9 at conclusion of surgery, all three receiving sevoflurane. In the sevoflurane group, this corresponded to 16% (95% CI: 3.3-40) of the patients. Mean duration of action of cisatracurium 0.1 mg/kg was 119 minutes (SD 40) with sevoflurane and 73 minutes (SD 29) during total intravenous anaesthesia (P < .001). Onset time of cisatracurium 0.1 mg/kg was 166 seconds (SD 37) with sevoflurane and 199 seconds (SD 60) during total intravenous anaesthesia. CONCLUSION: We found that 8% of the children had residual neuromuscular blockade (TOF ratio <0.9) after administration of a single bolus of cisatracurium 0.1 mg/kg but we cannot exclude that the true proportion is around 20%.