Sugammadex and neuromuscular disease: a systematic review with assessment of reporting quality and content validity.

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).

Microsynt: Exploring the syntax of EEG microstates.

Microstates represent electroencephalographic (EEG) activity as a sequence of switching, transient, metastable states. Growing evidence suggests the useful information on brain states is to be found in the higher-order temporal structure of these sequences. Instead of focusing on transition probabilities, here we propose "Microsynt", a method designed to highlight higher-order interactions that form a preliminary step towards understanding the syntax of microstate sequences of any length and complexity. Microsynt extracts an optimal vocabulary of "words" based on the length and complexity of the full sequence of microstates. Words are then sorted into classes of entropy and their representativeness within each class is statistically compared with surrogate and theoretical vocabularies. We applied the method on EEG data previously collected from healthy subjects undergoing propofol anesthesia, and compared their "fully awake" (BASE) and "fully unconscious" (DEEP) conditions. Results show that microstate sequences, even at rest, are not random but tend to behave in a more predictable way, favoring simpler sub-sequences, or "words". Contrary to high-entropy words, lowest-entropy binary microstate loops are prominent and favored on average 10 times more than what is theoretically expected. Progressing from BASE to DEEP, the representation of low-entropy words increases while that of high-entropy words decreases. During the awake state, sequences of microstates tend to be attracted towards "A - B - C" microstate hubs, and most prominently A - B binary loops. Conversely, with full unconsciousness, sequences of microstates are attracted towards "C - D - E" hubs, and most prominently C - E binary loops, confirming the putative relation of microstates A and B to externally-oriented cognitive processes and microstate C and E to internally-generated mental activity. Microsynt can form a syntactic signature of microstate sequences that can be used to reliably differentiate two or more conditions.

Reviewing next of kin regrets in surgical decision-making: cross-sectional analysis of systematically searched literature.

BACKGROUND: Decision-making concerning relatives undergoing surgery is challenging. It remains unclear to what extent implicated next of kin eventually regret their decisions and how this regret is assessed. Our aim was to systematically review the literature on decisional regret of next of kin and to describe the assessment tools used and the surgical populations studied. METHODS: We included interventional or observational, quantitative or qualitative studies reporting the measurement of decisional regret of next of kin concerning relatives undergoing surgery. We searched a variety of databases without restriction on publication year. We assessed the quality of reporting of quantitative studies using the NIH Quality Assessment Tool for Observational Cohort and Cross-Sectional Studies and of qualitative studies using the Critical Appraisal Skills Program Checklist. RESULTS: Thirteen cross-sectional, five prospective cohorts and five qualitative studies matched our inclusion criteria. In 18 studies (78%), patients were children, in five (22%), young or middle-aged adults. No study included elderly or frail patients. Thirteen studies (57%) used the original Decision Regret Scale which was validated for patients, but not for next of kin. Only 3 of the 18 (17%) quantitative studies and only one of the 4 (25%) qualitative studies were rated as "good" in the quality assessment. CONCLUSION: None of the retrieved studies used validated tools to assess the decisional regret of next of kin and none of them examined this issue in elderly or frail surgical patients.

EEG microstate dynamics indicate a U-shaped path to propofol-induced loss of consciousness.

Evidence suggests that the stream of consciousness is parsed into transient brain states manifesting themselves as discrete spatiotemporal patterns of global neuronal activity. Electroencephalographical (EEG) microstates are proposed as the neurophysiological correlates of these transiently stable brain states that last for fractions of seconds. To further understand the link between EEG microstate dynamics and consciousness, we continuously recorded high-density EEG in 23 surgical patients from their awake state to unconsciousness, induced by step-wise increasing concentrations of the intravenous anesthetic propofol. Besides the conventional parameters of microstate dynamics, we introduce a new implementation of a method to estimate the complexity of microstate sequences. The brain activity under the surgical anesthesia showed a decreased sequence complexity of the stereotypical microstates, which became sparser and longer-lasting. However, we observed an initial increase in microstates' temporal dynamics and complexity with increasing depth of sedation leading to a distinctive "U-shape" that may be linked to the paradoxical excitation induced by moderate levels of propofol. Our results support the idea that the brain is in a metastable state under normal conditions, balancing between order and chaos in order to flexibly switch from one state to another. The temporal dynamics of EEG microstates indicate changes of this critical balance between stability and transition that lead to altered states of consciousness.

Dexamethasone for the treatment of established postoperative nausea and vomiting: A randomised dose finding trial.

BACKGROUND: Dexamethasone is widely used for the prevention of postoperative nausea and vomiting (PONV) but little is known about its efficacy for the treatment of established PONV. OBJECTIVE: To test the antiemetic efficacy of intravenous dexamethasone for the treatment of established PONV in adults undergoing surgery under general anaesthesia and to determine whether there is dose-responsiveness. DESIGN: The DexPonv trial is a multicentre, placebo-controlled, randomised, double-blind, dose-finding study. Inclusion of patients was between September 2012 and November 2017. Follow-up for PONV symptoms was for 24 h. Thirty days postoperatively, patients were contacted by study nurses for any information on postoperative bleeding and infection. SETTING: Four public hospitals in Switzerland. PATIENTS: A total of 803 adults scheduled for elective surgery without any antiemetic prophylaxis signed the consent form; 714 were included. Among those, 319 had PONV and 281 patients were eventually randomised (intention to treat population and safety set). The per protocol set consisted of 260 patients. INTERVENTIONS: Patients with PONV symptoms (including retching) were randomised to a single intravenous dose of dexamethasone 3, 6 or 12 mg or matching placebo. MAIN OUTCOME MEASURES: The primary endpoint was the absence of further nausea or vomiting (including retching), within 24 h after administration of the study drug. RESULTS: Dexamethasone was ineffective during the first 24 h, whatever the dosage, compared to placebo, even when the model was adjusted for known risk factors (P = 0.170). There were no differences in the time to treatment failure or the quality of sleep during the first night. There was a positive correlation between the dose of dexamethasone and blood glucose concentrations (P < 0.001), but not with bleeding risk, wound infections or other adverse effects. CONCLUSION: This randomised trial failed to show anti-emetic efficacy of any of the tested intravenous regimens of dexamethasone for the treatment of established PONV in adults undergoing surgery under general anaesthesia. TRIAL REGISTRATION: clinicaltrials.gov (NCT01975727).

Rapid Sequence Induction With a Standard Intubation Dose of Rocuronium After Magnesium Pretreatment Compared With Succinylcholine: A Randomized Clinical Trial.

BACKGROUND: Succinylcholine remains the muscle relaxant of choice for rapid sequence induction (RSI) but has many adverse effects. High-dose rocuronium bromide may be an alternative to succinylcholine for RSI but recovery times are nearly doubled compared with a standard intubating dose of rocuronium. Magnesium sulfate significantly shortens the onset time of a standard intubating dose of rocuronium. We set out to investigate whether intravenous (IV) pretreatment with MgSO4 followed by a standard intubating dose of rocuronium achieved superior intubation conditions compared with succinylcholine. METHODS: Adults were randomized to receive a 15-minute IV infusion of MgSO4 (60 mg·kg-1) immediately before RSI with propofol 2 mg·kg-1, sufentanil 0.2 µg·kg-1 and rocuronium 0.6 mg·kg-1, or a matching 15-minute IV infusion of saline immediately before an identical RSI, but with succinylcholine 1 mg·kg-1. Primary end point was the rate of excellent intubating conditions 60 seconds after administration of the neuromuscular blocking agent and compared between groups using multivariable log-binomial regression model. Secondary end points were blood pressure and heart rate before induction, before and after intubation, and adverse events up to 24 hours postoperatively. RESULTS: Among 280 randomized patients, intubating conditions could be analyzed in 259 (133 MgSO4-rocuronium and 126 saline-succinylcholine). The rate of excellent intubating conditions was 46% with MgSO4-rocuronium and 45% with saline-succinylcholine. The analysis adjusted for gender and center showed no superiority of MgSO4-rocuronium compared with saline-succinylcholine (relative risk [RR] 1.06, 95% confidence interval [CI], 0.81-1.39, P = .659). The rate of excellent intubating conditions was higher in women (54% [70 of 130]) compared with men (37% [48 of 129]; adjusted RR 1.42, 95% CI, 1.07-1.91, P = .017). No significant difference between groups was observed for systolic and diastolic blood pressures. Mean heart rate was significantly higher in the MgSO4-rocuronium group. The percentage of patients with at least 1 adverse event was lower with MgSO4-rocuronium (11%) compared with saline-succinylcholine (28%) (RR 0.38, 95% CI, 0.22-0.66, P < .001). With saline-succinylcholine, adverse events consisted mainly of postoperative muscle pain (n = 26 [19%]) and signs of histamine release (n = 13 [9%]). With MgSO4-rocuronium, few patients had pain on injection, nausea and vomiting, or skin rash during the MgSO4-infusion (n = 5 [4%]). CONCLUSIONS: IV pretreatment with MgSO4 followed by a standard intubating dose of rocuronium did not provide superior intubation conditions to succinylcholine but had fewer adverse effects.

Genetic Susceptibility Toward Nausea and Vomiting in Surgical Patients.

Postoperative nausea and vomiting (PONV) are frequently occurring adverse effects following surgical procedures. Despite predictive risk scores and a pallet of prophylactic antiemetic treatments, it is still estimated to affect around 30% of the patients, reducing their well-being and increasing the burden of post-operative care. The aim of the current study was to characterize selected genetic risk factors of PONV to improve the identification of at risk patients. We genotyped 601 patients followed during the first 24 h after surgery for PONV symptoms in the absence of any antiemetic prophylaxis. These patients were recruited in the frame of a randomized, placebo controlled clinical study aiming to test the efficacy of dexamethasone as a treatment of established PONV. We examined the impact of selected single nucleotide polymorphisms (SNPs) located around 13 different genes and the predicted activity of 6 liver drug metabolizing enzymes from the cytochromes P450 family (CYP) on the occurrence and recurrence of PONV. Our genetic study confirms the importance of genetic variations in the type 3B serotonin receptor in the occurrence of PONV. Our modelling shows that integration of rs3782025 genotype in preoperative risk assessments may help improve the targeting of antiemetic prophylaxis towards patients at risk of PONV.

Preparedness and Reorganization of Care for Coronavirus Disease 2019 Patients in a Swiss ICU: Characteristics and Outcomes of 129 Patients.

OBJECTIVES: In many countries, large numbers of critically ill patients with coronavirus disease 2019 are admitted to the ICUs within a short period of time, overwhelming usual care capacities. Preparedness and reorganization ahead of the wave to increase ICU surge capacity may be associated with favorable outcome. The purpose of this study was to report our experience in terms of ICU organization and anticipation, as well as reporting patient characteristics, treatment, and outcomes. DESIGN: A prospective observational study. SETTING: The division of intensive care at the Geneva University Hospitals (Geneva, Switzerland). PATIENTS: All consecutive adult patients with acute respiratory failure due to coronavirus disease 2019 admitted in the ICU between March 9, 2020, and May 19, 2020, were enrolled. Patients' demographic data, comorbidities, laboratory values, treatments, and clinical outcomes were collected. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The ICU was reorganized into cells of six to eight patients under the care of three physicians and five nurses. Its capacity increased from 30 to 110 beds, fully equipped and staffed, transforming the surgical intermediate care unit, the postoperative care facility, and operating theaters into ICUs. Surge capacity has always exceeded the number of patients hospitalized. Among 129 critically ill patients with severe acute hypoxemic respiratory failure, 96% required invasive mechanical ventilation. A total of 105 patients (81%) were discharged alive and 24 died, corresponding to a mortality of 19%. Patients who died were significantly older, with higher severity scores at admission, had higher levels of d-dimers, plasma creatinine, high-sensitive troponin T, C-reactive protein, and procalcitonin, and required more frequent prone sessions. CONCLUSIONS: A rapid increase in ICU bed capacity, including adequate equipment and staffing, allowed for a large number of critically ill coronavirus disease 2019 patients to be taken care of within a short period of time. Anticipation and preparedness ahead of the wave may account for the low mortality observed in our center. These results highlight the importance of resources management strategy in the context of the ongoing coronavirus disease 2019 pandemic.

The optimal dose of succinylcholine for rapid sequence induction: a systematic review and meta-analysis of randomized trials.

BACKGROUND: The evidence base for the widely accepted standard regimen of succinylcholine for rapid sequence induction (1.0 mg kg- 1) remains unclear. METHODS: We performed a systematic review and meta-analysis of randomized trials comparing any succinylcholine regimen with the standard regimen (1.0 mg kg- 1) and reporting on intubating conditions and/or apnoea times. Results were expressed as absolute risk differences (ARD) for dichotomous data and mean differences (MD) for continuous data. RESULTS: We retrieved six trials with relevant data of 864 patients (ASA 1 or 2, aged 18-65 years, body mass index < 30 kg m- 2). Four regimens (0.3, 0.4, 0.5, 0.6 mg kg- 1) were compared with 1.0 mg kg- 1 in at least three trials each, and three (0.8, 1.5, 2 mg kg- 1) in one each. With 0.3 to 0.5 mg kg- 1, the likelihood of excellent intubating conditions was significantly decreased (ARD - 22% to - 67%). With 0.3 and 0.4 mg kg- 1, but not with 0.5, 0.6, 0.8, 1.5 and 2.0 mg kg- 1, the likelihood of unacceptable intubating conditions was significantly increased (ARD + 22% and + 32%, respectively). With 2.0 mg kg- 1, but not with 0.8 or 1.5 mg kg- 1, the likelihood of excellent intubating conditions was significantly increased (ARD + 23%). Apnoea times were significantly shorter with regimens ≤0.8 mg kg- 1 (MD - 1.0 to - 3.4 min) but were not reported with 1.5 or 2.0 mg kg- 1. CONCLUSIONS: With succinylcholine regimens ≤0.5 mg kg- 1, excellent intubating conditions are less likely and apnoea times are shorter, compared with 1 mg kg- 1. With 0.3 and 0.4 mg kg- 1, unacceptable intubating conditions are more common. Succinylcholine 1.5 mg kg- 1 does not produce more often excellent conditions compared with 1 mg kg- 1, while 2.0 mg kg- 1 does, but the database with these regimens is weak and apnoea times remain unknown. Limited information size and strong statistical heterogeneity decrease the certainty of the evidence.

Assessment of spontaneous neuromuscular recovery: A comparison of the TOF-Cuff® with the TOF Watch SX®.

BACKGROUND: TOF-Cuff® is a modified blood pressure cuff used to monitor neuromuscular block. We compared the assessment of spontaneous neuromuscular recovery between TOF-Cuff® (test device) and TOF Watch SX® (reference device). METHODS: Forty patients aged 18-65 years undergoing elective surgery were enrolled. TOF-Cuff® was installed on an upper arm and the TOF Watch SX® on the thumb of the opposite side. Anaesthesia was induced and maintained with intravenous propofol and sufentanil. After induction, the devices were calibrated and continuous train-of-four (TOF) stimulation was started. A single intravenous dose of rocuronium (0.6 mg kg-1 ) was administered for intubation. The primary outcome was total recovery time (time in minutes from the injection of rocuronium to a normalized TOF ratio of 90%). Agreement between the two devices was calculated using mean difference and limits of agreement. RESULTS: The primary outcome could be analysed in 27 patients because of 13 exclusions due to neuromuscular block reversal for shorter procedure surgical time, necessity of reinjection of rocuronium or technical failures of one of the two devices. Median total recovery time with the test device was 45 minutes (interquartile range [IQR] 38.5-61.5) and 63 minutes (IQR 51.1-74.5) with the reference device. Total recovery time with the test device was on average 16.4 minutes shorter (limits of agreement, -6.1 to 39); increasing total recovery time was associated with increasing difference. The TOF ratio of the reference device was on average 0.59 (SD 0.23) when the test device indicated complete recovery. The TOF ratio of the test device was on average 0.98 (SD 0.03) when the reference device indicated complete recovery. CONCLUSION: When compared with the TOF Watch SX® , TOF-Cuff® overestimates spontaneous recovery of a rocuronium-induced neuromuscular block.

Reporting of conflicts of interest and of sponsorship of guidelines in anaesthesiology. A cross-sectional study.

Guideline recommendations may be biased due to conflicts of interest (COI) of panel members and sponsorship of the guideline. Potential impact of COI, and their management, should be transparently reported. We analysed 110 guidelines published in ten anaesthesia journals from 2007 to June 2018. We report on the number (%) that 1) published COI disclosures; 2) in a distinct paragraph; 3) described and explained the COI of panel members, and 4) of the Chairperson; 5) reported and described the presence or absence and potential impact of a sponsor of the guideline on the recommendations; and 6) reported how COI were managed. COI were published in 70/110 (64%) guidelines; in a distinct paragraph in 25/70 (36%). Panel members reported having no COI in 27/70 (39%) guidelines, disclosed COI without describing their potential impact in 41/70 (59%), and described their potential impact in 2/70 (3%). Chairpersons were identified in 50 guidelines, 32 of which published COI disclosures; 16/32 (50%) reported having no COI, 14/32 (44%) disclosed COI without describing their potential impact, 1/32 (3%) described their impact and 1/32 (3%) made no statement regarding COI. Presence or absence of a sponsor of the guideline was reported in 40 guidelines; 12/40 (30%) declared none, 24/40 (60%) reported sponsoring without explanation of the potential impact, and 4/40 (10%) described the potential influence of the sponsor on the guideline recommendations. Seventy-five guidelines reported COI of panel members and/or sponsorship of the guideline but only seven described how the COI had been managed. Disclosures of COI of panel members and of sponsors of guidelines have increased over the 12 year period, but remain insufficiently described and their potential influence on the guidelines' recommendations is poorly documented.

Intravenous Lidocaine for the Prevention of Cough: Systematic Review and Meta-analysis of Randomized Controlled Trials.

BACKGROUND: It remains unclear to what extent intravenous lidocaine prevents cough and whether there is dose-responsiveness and risk of harm. METHODS: We searched electronic databases to January 1, 2017 for randomized trials comparing intravenous lidocaine with placebo for the prevention of cough in surgical patients. Primary outcome was the incidence of cough. Data were analyzed using a random-effects model and were expressed as risk ratio (RR) and number needed to treat (NNT) with 95% confidence interval. RESULTS: In 20 trials in adults (n = 3062) and 5 trials in children (n = 445), intravenous lidocaine 0.5-2 mg·kg was tested for the prevention of intubation-, extubation-, or opioid-induced cough. Twenty-two trials included only American Society of Anesthesiologists I or II patients; 3 trials (n = 99) also included American Society of Anesthesiologists III patients. Lidocaine was associated with a lower incidence of cough compared to placebo in adults and children, irrespective of dosage and cough etiology. Data from adults suggested dose-responsiveness; with 0.5 mg·kg, RR was 0.66 (0.50-0.88) and NNT was 8 (5.4-14.3); with 1 mg·kg, RR was 0.58 (0.49-0.69) and NNT was 7 (4.6-8.9); with 1.5 mg·kg, RR was 0.44 (0.33-0.58) and NNT was 5 (3.3-5.2); and with 2 mg·kg, RR was 0.39 (0.24-0.62) and NNT was 3 (2.0-3.4). Adverse effect reporting was sparse. CONCLUSIONS: Within a range of 0.5-2 mg·kg, intravenous lidocaine dose dependently prevents intubation-, extubation-, and opioid-induced cough in adults and children with NNTs ranging from 8 to 3. The risk of harm in high-risk patients remains unknown.

Transcranial Doppler in the Diagnosis of Cerebral Vasospasm: An Updated Meta-Analysis.

OBJECTIVES: To evaluate the performance of transcranial Doppler and transcranial color-coded duplex Doppler in patients with cerebral vasospasm due to aneurysm rupture. Angiography was considered as the gold standard comparator. DATA SOURCES: Search in MEDLINE, Embase, and Central from January 2001 to October 2017, without language restriction. Bibliographies of retrieved articles were screened for additional studies. STUDY SELECTION: Randomized studies comparing transcranial Doppler or transcranial color-coded duplex Doppler with angiography in adults. DATA EXTRACTION: Data were extracted independently by several investigators. Sensitivity and specificity were combined across studies using a bivariate model. Preferred Reporting Items for Systematic Reviews and Meta-Analyses was used for reporting and Quality Assessment of Diagnostic Accuracy Studies-2 for quality assessment. DATA SYNTHESIS: We included 18 studies. Fifteen tested transcranial Doppler. For the middle cerebral artery (10 studies, 1,408 tests), the pooled sensitivity was 66.7% (95% CI, 55.9-75.9) and specificity was 89.5% (80.3-94.7). Three studies (278 tests) tested transcranial color-coded duplex Doppler for the middle cerebral artery. The pooled sensitivity was 81.5% (66.0-90.0), and specificity was 96.6% (93.0-98.0). For an arbitrarily chosen prevalence of vasospasm of 70%, positive and negative predictive values were 93.7% (88.9-96.6) and 53.4% (46.7-60.9) for transcranial Doppler and 98.2% (96.4-99.1) and 69.1% (56.1-80.9) for transcranial color-coded duplex Doppler. CONCLUSIONS: Assuming a high prevalence of vasospasm of the middle cerebral artery, both transcranial Doppler and transcranial color-coded duplex Doppler are likely to detect it, but neither is useful to exclude it. There is no convincing evidence that the accuracy of transcranial color-coded duplex Doppler is any better than that of transcranial Doppler. For arteries other than middle cerebral artery, there is a lack of evidence of the usefulness of transcranial Doppler.

Identification of ethics committees based on authors' disclosures: cross-sectional study of articles published in the European Journal of Anaesthesiology and a survey of ethics committees.

BACKGROUND: Since 2010, the European Journal of Anaesthesiology has required the reporting of five items concerning ethical approval in articles describing human research: ethics committee's name and address, chairperson's name, study's protocol number and approval date. We aimed to assess whether this requirement has helped to identify and to contact the referenced ethics committees. METHODS: In this cross-sectional study, we analysed articles requiring ethical approval, according to the Swiss federal law for human research and published in the European Journal of Anaesthesiology in 2011. Ethics committees were searched through our institutional Internet access based on information provided in the articles. The last search was performed in November 2015. Numbers (%) of items reported, of ethics committees identified, and of those that confirmed having provided ethical approval are reported. RESULTS: Of 76 articles requiring ethical approval, 74 (97%) declared it. Ethics committees' names and addresses were mentioned in 63/74 (85%), protocol numbers in 51/74 (69%), approval dates in 48/74 (65%), and chairpersons' names in 45/74 (61%). We could identify 44/74 (59%) committees; 36/74 (49%) answered our inquiry and 24/74 (32%) confirmed their role. Thirty-four of 74 articles (46%) reported all five items; in 25/34 (74%), we were able to identify an ethics committee, 18/34 (53%) answered our inquiry, and 15/34 (44%) confirmed their role. Forty of 74 articles (54%) reported ≤4 items; in 19/40 (48%), we were able to identify an ethics committee, 18/40 (45%) answered our inquiry, and 9/40 (23%) confirmed their role. Reporting five items significantly increased identification of ethics committees (p = 0.023) and their confirmation of ethical approval (p = 0.048). Twelve of 74 ethics committees (16%) were unable to confirm their role in approving the study. CONCLUSIONS: Even when details concerning ethical approval were reported in these studies of human research, we were unable to identify almost half of the ethics committees concerned. The reporting of five items, compared with reporting ≤4, was associated with facilitated identification of ethics committees, and increased the likelihood that they would be able to confirm the study's approval. Future research should identify which information facilitates identification of, and contact with, ethics committees.

Benefit and Harm of Adding Epinephrine to a Local Anesthetic for Neuraxial and Locoregional Anesthesia: A Meta-analysis of Randomized Controlled Trials With Trial Sequential Analyses.

BACKGROUND: This systematic review examines the benefit and harm of adding epinephrine to local anesthetics for epidural, intrathecal, or locoregional anesthesia. METHODS: We searched electronic databases to October 2017 for randomized trials comparing any local anesthetic regimen combined with epinephrine, with the same local anesthetic regimen without epinephrine, reporting on duration of analgesia, time to 2 segments regression, or any adverse effects. Trial quality was assessed using the Cochrane risk of bias tool and a random-effects model was used. Trial sequential analyses (TSA) were applied to identify the information size (IS; number of patients needed to reach a definite conclusion) and were set to detect an increase or decrease of effect of 30%-50%, depending on the end point considered. Alpha levels were adjusted (1%) for multiple outcome testing. RESULTS: We identified 70 trials (3644 patients, 17 countries, from 1970 to 2017). Median number of patients per trial was 44 (range, 9-174). Thirty-seven trials (1781 patients) tested epinephrine for epidural, 27 (1660) for intrathecal, and 6 (203) for locoregional anesthesia (sciatic, femoral, popliteal, axillary blocks). TSA enabled us to conclude that adding epinephrine to epidural local anesthetics could not decrease postoperative pain intensity by 30%, and did not impact the risk of intraoperative arterial hypotension. IS was insufficient to conclude on the impact of epinephrine on the risk of motor block (IS, 4%), arterial hypotension (20%), urinary retention (23%), or pain intensity at rest (27%) during labor. TSA confirmed that adding epinephrine to intrathecal local anesthetics increased the duration of motor block (weighted mean difference [WMD] 64 minutes; 99% CI, 37-91), analgesia (WMD 34 minutes; 99% CI, 6-62), and the time to 2 segments regression (WMD 20 minutes; 99% CI, 11-28). IS was insufficient to conclude on its impact on arterial hypotension (IS, 15%), or when administrated in a combined spinal-epidural, on motor block (IS, 11%) or arterial hypotension (IS, 11%). Adding epinephrine to local anesthetics for a locoregional block increased the duration of analgesia (WMD 66 minutes; 98% CI, 32-100]). CONCLUSIONS: Adding epinephrine to intrathecal or locoregional local anesthetics prolongs analgesia and motor block by no more than 60 minutes. The impact of adding epinephrine to epidural local anesthetics or to a combined spinal-epidural remains uncertain.

Patient-Controlled Versus Clinician-Controlled Sedation With Propofol: Systematic Review and Meta-analysis With Trial Sequential Analyses.

BACKGROUND: Sedation with propofol is frequently used to facilitate diagnostic and therapeutic procedures. Propofol can be administrated by the patient (patient-controlled sedation [PCS]) or by a clinician (clinician-controlled sedation [CCS]). We aimed to compare these 2 techniques. METHODS: PubMed, Embase, CENTRAL, and trial registries were searched up to October 2017 for randomized controlled trials comparing PCS with CCS with propofol. The primary end points were the risks of presenting at least 1 episode of oxygen desaturation, arterial hypotension, and bradycardia, and the risk of requiring a rescue intervention (pharmacologic therapies or physical maneuvers) for sedation-related adverse events. Secondary end points were the dose of propofol administrated, operator and patient satisfaction, and the risk of oversedation. A random-effects model and an α level of .02 to adjust for multiple analyses were used throughout. Trial sequential analyses were performed for primary outcomes. Quality of evidence was assessed according to the Grades of Recommendation, Assessment, Development, and Evaluation system. RESULTS: Thirteen trials (1103 patients; median age, 47 years; American Society of Anesthesiologists physical status I-III) describing various diagnostic and therapeutic procedures with propofol sedation were included. PCS had no impact on the risk of oxygen desaturation (11 trials, 31/448 patients [6.9%] with PCS versus 46/481 [9.6%] with CCS; risk ratio, 0.74 [98% confidence interval, 0.35-1.56]) but decreased the risk of requiring a rescue intervention for adverse events (11 trials, 29/449 patients [6.5%] with PCS versus 74/482 [15.4%] with CCS; risk ratio, 0.45 [98% confidence interval, 0.25-0.81]). For both outcomes, Trial sequential analyses suggested that further trials were unlikely to change the results, although the quality of evidence was graded very low for all primary outcomes. For the risk of arterial hypotension and bradycardia, the required sample size for a definitive conclusion had not been reached. Analysis of secondary outcomes suggested that PCS decreased the risk of oversedation and had no impact on propofol dose administrated, or on operator or patient satisfaction. CONCLUSIONS: PCS with propofol, compared with CCS with propofol, had no impact on the risk of oxygen desaturation, but significantly decreased the risk of rescue interventions for sedation-related adverse events. Further high-quality trials are required to assess the risks and benefits of PCS.

Contraction response to muscle percussion: A reappraisal of the mechanism of this bedside test.

OBJECTIVE: To study whether the contraction evoked by muscle percussion stems from the excitation of the muscle or of the nerve and to discuss the changes of this response in neuromuscular disorders. METHODS: In 30 neurologically healthy patients undergoing surgery (for ear, nose, or throat problems unrelated to the study) under general anesthesia with propofol and sufentanil we measured with an electrogoniometer the maximal dorsiflexion of the ankle evoked by reflex hammer percussion of the tibialis anterior muscle before and under neuromuscular junction blockade with rocuronium bromide. In 3 additional healthy volunteers we searched for F-waves to disclose whether percussion excites axons within the muscle. RESULTS: Responses from 28 neurologically healthy patients (15 women) were analyzed after exclusion of 2 due to technical problems. Mean age (SD) was 28 (9) years. Maximal dorsiflexion of the ankle was not significantly modified by neuromuscular junction blockade (mean difference 0.01 mV [95%CI, -0.07 to 0.08], p=0.879). Muscle percussion evoked F-waves in the 3 healthy volunteers tested. CONCLUSIONS: Maximal contraction response to muscle percussion has a muscular rather than a neural origin. However, percussion also excites axons within the muscle. SIGNIFICANCE: These findings may provide clues to understand the changes observed in neuromuscular disorders.