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Background: Efficacy and safety of sugammadex for the reversal of neuromuscular blocking agents (NMBAs) in patients with neuromuscular diseases remains unclear. We summarised the available evidence and evaluated the quality of data reporting and the validity of published reports., Methods: We searched for reports (any design) on the usage of sugammadex (any regimen) for the reversal of an NMBA in patients (any age) with any neuromuscular disease. We used a modified CARE checklist (maximum score 23) to assess the quality of data reporting and an original specific validity checklist (maximum score 41) that was developed through a Delphi process., Results: We retrieved 126 observational reports (386 patients). Most dealt with myasthenia gravis patients receiving rocuronium. The train-of-four ratio returned to ≥0.9 in 258 of 265 (97.4%) patients in whom neuromonitoring was used. Adverse events occurred in 14 of 332 (4.2%) patients in whom adverse events were reported as present or absent. In 90 case reports, the median score of the 23-point CARE checklist was 13.5 (inter-quartile range [IQR] 11-16). In all 126 reports, the median score of the 41-point validity checklist was 23 (IQR 20-27). Scores were positively correlated., Conclusions: These uncontrolled observations (of mainly low to moderate quality and validity) do not allow confident assessment of the efficacy and safety of sugammadex for the reversal of NMBAs in patients with neuromuscular diseases. Reporting of observational data should follow established guidelines, include specific information to ensure validity, and emphasise what the new data add to current knowledge., Systematic Review Protocol: PROSPERO 2019 (CRD42019119924)., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: Maximising patient comfort during and after surgery is a primary concern of anaesthetists and other perioperative clinicians, but objective measures of what constitutes patient comfort in the perioperative period remain poorly defined. The Standardised Endpoints in Perioperative Medicine initiative was established to derive a set of standardised endpoints for use in perioperative clinical trials., Methods: We undertook a systematic review to identify measures of patient comfort used in the anaesthetic, surgical, and other perioperative literature. A multi-round Delphi consensus process that included up to 89 clinician researchers was then used to refine a recommended list of outcome measures., Results: We identified 122 studies in a literature search, which were the basis for a preliminary list of 24 outcome measures and their definitions. The response rates for Delphi Rounds 1, 2, and 3 were 100% (n=22), 90% (n=79), and 100% (n=13), respectively. A final list of six defined endpoints was identified: pain intensity (at rest and during movement) at 24 h postoperatively, nausea and vomiting (0-6 h, 6-24 h, and overall), one of two quality-of-recovery (QoR) scales (QoR score or QoR-15), time to gastrointestinal recovery, time to mobilisation, and sleep quality., Conclusions: As standardised outcomes will support benchmarking and pooling (meta-analysis) of trials, one or more of these recommended endpoints should be considered for inclusion in clinical trials assessing patient comfort and pain after surgery., (Copyright © 2018 British Journal of Anaesthesia. All rights reserved.)

Background: Immobilization of the cervical spine worsens tracheal intubation conditions. Various intubation devices have been tested in this setting. Their relative usefulness remains unclear., Methods: We searched MEDLINE, EMBASE, and the Cochrane Library for randomized controlled trials comparing any intubation device with the Macintosh laryngoscope in human subjects with cervical spine immobilization. The primary outcome was the risk of tracheal intubation failure at the first attempt. Secondary outcomes were quality of glottis visualization, time until successful intubation, and risk of oropharyngeal complications., Results: Twenty-four trials (1866 patients) met inclusion criteria. With alternative intubation devices, the risk of intubation failure was lower compared with Macintosh laryngoscopy [risk ratio (RR) 0.53; 95% confidence interval (CI) 0.35-0.80]. Meta-analyses could be performed for five intubation devices (Airtraq, Airwayscope, C-Mac, Glidescope, and McGrath). The Airtraq was associated with a statistically significant reduction of the risk of intubation failure at the first attempt (RR 0.14; 95% CI 0.06-0.33), a higher rate of Cormack-Lehane grade 1 (RR 2.98; 95% CI 1.94-4.56), a reduction of time until successful intubation (weighted mean difference -10.1 s; 95% CI -3.2 to -17.0), and a reduction of oropharyngeal complications (RR 0.24; 95% CI 0.06-0.93). Other devices were associated with improved glottis visualization but no statistically significant differences in intubation failure or time to intubation compared with conventional laryngoscopy., Conclusions: In situations where the spine is immobilized, the Airtraq device reduces the risk of intubation failure. There is a lack of evidence for the usefulness of other intubation devices., (© The Author 2015. Published by Oxford University Press on behalf of the British Journal of Anaesthesia.)

Background: Pathophysiological changes due to obesity may complicate mechanical ventilation during general anaesthesia. The ideal ventilation strategy is expected to optimize gas exchange and pulmonary mechanics and to reduce the risk of respiratory complications., Methods: Systematic search (databases, bibliographies, to March 2012, all languages) was performed for randomized trials testing intraoperative ventilation strategies in obese patients (BMI ≥ 30 kg m(-2)), and reporting on gas exchange, pulmonary mechanics, or pulmonary complications. Meta-analyses were performed when data from at least three studies or 100 patients could be combined., Results: Thirteen studies (505 obese surgical patients) reported on a variety of ventilation strategies: pressure- or volume-controlled ventilation (PCV, VCV), various tidal volumes, and different PEEP or recruitment manoeuvres (RM), and combinations thereof. Definitions and reporting of endpoints were inconsistent. In five trials (182 patients), RM added to PEEP compared with PEEP alone improved intraoperative PaO2/FIO2 ratio [weighted mean difference (WMD), 16.2 kPa; 95% confidence interval (CI), 8.0-24.4] and increased respiratory system compliance (WMD, 14 ml cm H(2)O(-1); 95% CI, 8-20). Arterial pressure remained unchanged. In four trials (100 patients) comparing PCV with VCV, there was no difference in PaO2/FIO2 ratio, tidal volume, or arterial pressure. Comparison of further ventilation strategies or combination of other outcomes was not feasible. Data on postoperative complications were seldom reported., Conclusions: The ideal intraoperative ventilation strategy in obese patients remains obscure. There is some evidence that RM added to PEEP compared with PEEP alone improves intraoperative oxygenation and compliance without adverse effects. There is no evidence of any difference between PCV and VCV.

Background: Bispectral (BIS) and state/response entropy (SE/RE) indices have been widely used to estimate depth of anaesthesia and sedation. In adults, independent of age, adequate and safe depth of anaesthesia for surgery is usually assumed when these indices are between 40 and 60. Since the EEG is changing with increasing age, we investigated the impact of advanced age on BIS, SE, and RE indices during induction., Methods: BIS and SE/RE indices were recorded continuously in elderly (> or =65 yr) and young (< or =40 yr) surgical patients who received propofol until loss of consciousness (LOC) using stepwise increasing effect-site concentrations. LOC was defined as an observer assessment of alertness/sedation score <2, corresponding to the absence of response to mild prodding or shaking., Results: We analysed 35 elderly [average age, 78 yr (range, 67-96)] and 34 young [35 (19-40)] patients. At LOC, all indices were significantly higher in elderly compared with young patients: BIS(LOC), median 70 (range, 58-91) vs 58 (40-70); SE(LOC), 71 (31-88) vs 55.5 (23-79); and RE(LOC), 79 (35-96) vs 59 (25-80) (P<0.001 for all comparisons). With all three monitors, only a minority of elderly patients lost consciousness within a 40-60 index range: two (5.7%) with BIS and RE each, and seven (20%) with SE. In young patients, the respective numbers were 20 (58.8%) for BIS, 13 (38.2%) for SE, and nine (26.5%) for RE., Conclusions: In adults undergoing propofol induction, BIS, SE, and RE indices at LOC are significantly affected by age.

Intrathecal morphine without local anaesthetic is often added to a general anaesthetic to prevent pain after major surgery. Quantification of benefit and harm and assessment of dose-response are needed. We performed a meta-analysis of randomized trials testing intrathecal morphine alone (without local anaesthetic) in adults undergoing major surgery under general anaesthesia. Twenty-seven studies (15 cardiac-thoracic, nine abdominal, and three spine surgery) were included; 645 patients received intrathecal morphine (dose-range, 100-4000 microg). Pain intensity at rest was decreased by 2 cm on the 10 cm visual analogue scale up to 4 h after operation and by about 1 cm at 12 and 24 h. Pain intensity on movement was decreased by 2 cm at 12 and 24 h. Opioid requirement was decreased intraoperatively, and up to 48 h after operation. Morphine-sparing at 24 h was significantly greater after abdominal surgery {weighted mean difference, -24.2 mg [95% confidence interval (CI) -29.5 to -19.0]}, compared with cardiac-thoracic surgery [-9.7 mg (95% CI -17.6 to -1.80)]. The incidence of respiratory depression was increased with intrathecal morphine [odds ratio (OR) 7.86 (95% CI 1.54-40.3)], as was the incidence of pruritus [OR 3.85 (95% CI 2.40-6.15)]. There was no evidence of linear dose-responsiveness for any of the beneficial or harmful outcomes. In conclusion, intrathecal morphine decreases pain intensity at rest and on movement up to 24 h after major surgery. Morphine-sparing is more pronounced after abdominal than after cardiac-thoracic surgery. Respiratory depression remains a major safety concern.

Nefopam, a centrally acting analgesic, has been used in the surgical setting in many countries since the mid-1970s. However, clinical trials provide contflicting results for its analgesic potency. We performed a systematic search (multiple databases, bibliographies, any language, to January 2008) for randomized, placebo-controlled trials of nefopam for the prevention of postoperative pain. Data were combined using classic methods of meta-analyses and were expressed as weighted mean difference (WMD), relative risk (RR), and number needed to treat/harm (NNT/H) with 95% confidence interval (CI). Nine trials (847 adult patients, 359 received nefopam) were included. Nefopam (cumulative doses, 20-160 mg) was given orally or i.v., as single or multiple doses, or as a continuous infusion. Compared with placebo, cumulative 24 h morphine consumption was decreased with nefopam: WMD -13 mg (95% CI -17.9 to -8.15). Pain intensity at 24 h was also decreased: on a 100 mm visual analogue scale, WMD -11.5 mm (95% CI -15.1 to -7.85). The incidence of tachycardia was increased with nefopam (RR 3.12, 95% CI 1.11-8.79; NNH 7), as was the incidence of sweating (RR 4.92, 95% CI 2.0-12.1; NNH 13). There is limited evidence from the published literature that nefopam may be a useful non-opioid analgesic in surgical patients. The analgesic potency seems to be similar to non-steroidal anti-inflammatory drugs. However, dose responsiveness and adverse effect profile remain unclear, and the role of nefopam as part of multimodal analgesia needs to be established. Data in children are lacking.

Metoclopramide has been used for almost 40 yr to prevent postoperative nausea and vomiting (PONV). We have reviewed the efficacy and safety of metoclopramide for the prevention of PONV. A systematic search (MEDLINE, EMBASE, manufacturers' databases, hand searching, bibliographies, all languages, up to June 1998) was performed for full reports of randomized comparisons of metoclopramide with placebo in surgical patients. Relevant end-points were prevention of early PONV (within 6 h after operation), late PONV (48 h) and adverse effects. Combined data were analysed using relative benefit/risk and number-needed-to-treat/harm. In 66 studies, 3260 patients received 18 different regimens of metoclopramide, and 3006 controls received placebo or no treatment. There was no evidence of dose-responsiveness with oral, i.m., intranasal or i.v. metoclopramide in children and adults. In adults, the best documented regimen was 10 mg i.v. There was no significant anti-nausea effect. The numbers-needed-to-treat to prevent early and late vomiting were 9.1 (95% confidence intervals 5.5-27) and 10 (6-41), respectively. In children, the best documented regimen was 0.25 mg kg-1 i.v. The number-needed-to-treat to prevent early vomiting was 5.8 (3.9-11). There was no significant late anti-vomiting effect. Minor drug-related adverse effects (sedation, dizziness, drowsiness) were not significantly associated with metoclopramide. There was one adult who experienced extrapyramidal symptoms with metoclopramide.

We have estimated the effect of omitting antagonism of neuromuscular block on postoperative nausea and vomiting. A systematic search (MEDLINE, EMBASE, Biological Abstracts, Cochrane library, reference lists and hand searching; no language restriction, up to March 1998) was performed for relevant randomized controlled trials. In eight studies (1134 patients), antagonism with neostigmine or edrophonium was compared with spontaneous recovery after general anesthesia with pancuronium, vecuronium, mivacurium or tubocurarine. On combining neostigmine data, there was no evidence of an antiemetic effect when it was omitted. However, the highest incidence of emesis with neostigmine 1.5 mg was lower than the lowest incidence of emesis with 2.5 mg. Numbers-needed-to-treat to prevent emesis by omitting neostigmine compared with using it were consistently negative with 1.5 mg, and consistently positive (3-6) with 2.5 mg. There was a lack of evidence for edrophonium. In two studies, three patients with spontaneous recovery after mivacurium or vecuronium needed rescue anticholinesterase drugs because of clinically relevant muscle weakness (number-needed-to-harm, 30). Omitting neostigmine may have a clinically relevant antiemetic effect when high doses are used. Omitting antagonism, however, introduces a non-negligent risk of residual paralysis even with short-acting neuromuscular blocking agents.

As part of the development of a model for the study of adverse events, we have investigated the risk of bradycardia with propofol. A systematic search for any type of report, published and unpublished, was made to review the evidence that propofol increases the risk of bradycardia, asystole and death from bradycardic events. Quantitative and qualitative analyses of data with different strengths of evidence were performed. Sixty-five published and 187 spontaneous reports to drug monitoring centres described with different strength of evidence a biological basis for propofol-induced bradycardia, 1444 bradycardias, 86 asystoles and 24 deaths. In controlled clinical trials, propofol significantly increased the risk of bradycardia compared with other anaesthetics (number-needed-to-harm 11.3 (95% confidence interval 7.7-21)). In paediatric strabismus surgery the number-needed-to-harm was 4.1 (3-6.7). One of 660 patients undergoing propofol anaesthesia had an asystole. The risk of bradycardia-related death during propofol anaesthesia was estimated to be 1.4 in 100,000. Data from the phase IV study of propofol did not agree with data from controlled studies. Propofol carries a finite risk for brady-cardia with potential for major harm. Study of adverse events should be made with systematically searched data and, in contrast with study of efficacy, not restricted to randomized, controlled trials.