Combined Dexamethasone and Dexmedetomidine as Adjuncts to Popliteal and Saphenous Nerve Blocks in Patients Undergoing Surgery of the Foot or Ankle: A Randomized, Blinded, Placebo-controlled Clinical Trial.

BACKGROUND: Both dexamethasone and dexmedetomidine increase the duration of analgesia of peripheral nerve blocks. The authors hypothesized that combined intravenous dexamethasone and intravenous dexmedetomidine would result in a greater duration of analgesia when compared with intravenous dexamethasone alone and placebo. METHODS: The authors randomly allocated participants undergoing surgery of the foot or ankle under general anesthesia and with a combined popliteal (sciatic) and saphenous nerve block to a combination of 12 mg dexamethasone and 1 µg/kg dexmedetomidine, 12 mg dexamethasone, or placebo (saline). The primary outcome was the duration of analgesia measured as the time from block performance until the first sensation of pain in the surgical area as reported by the participant. The authors predefined a 33% difference in the duration of analgesia as clinically relevant. RESULTS: A total of 120 participants from two centers were randomized and 119 analyzed for the primary outcome. The median [interquartile range] duration of analgesia was 1,572 min [1,259 to 1,715] with combined dexamethasone and dexmedetomidine, 1,400 min [1,133 to 1,750] with dexamethasone alone, and 870 min [748 to 1,138] with placebo. Compared with placebo, the duration was greater with combined dexamethasone and dexmedetomidine (difference, 564 min; 98.33% CI, 301 to 794; P < 0.001) and with dexamethasone (difference, 489 min; 98.33% CI, 265 to 706; P < 0.001). The prolongations exceeded the authors' predefined clinically relevant difference. The duration was similar when combined dexamethasone and dexmedetomidine was compared with dexamethasone alone (difference, 61 min; 98.33% CI, -222 to 331; P = 0.614). CONCLUSIONS: Dexamethasone with or without dexmedetomidine increased the duration of analgesia in patients undergoing surgery of the foot or ankle with a popliteal (sciatic) and saphenous nerve block. Combined dexamethasone and dexmedetomidine did not increase the duration of analgesia when compared with dexamethasone.

Mixing short- and long-acting local anaesthetics in peripheral nerve blocks: Protocol for a systematic review and meta-analysis.

INTRODUCTION: This protocol describes a systematic review and meta-analysis to evaluate the clinical effects of mixing short- and long-acting local anaesthetics in peripheral nerve blocks. Clinicians often combine short- and long-acting local anaesthetics to achieve a briefer onset time. However, this may come with a prize, namely a shorter total duration of the block, which is of clinical importance. OBJECTIVE: This systematic review aims to strengthen the knowledge of the clinical effects associated with this practice. The primary outcome is the duration of block analgesia. Secondary outcomes are block onset time, sensory and motor block duration. Exploratory outcomes are postoperative pain scores, cumulative 24-h opioid consumption and the prevalence of serious adverse events. METHODS: We will conduct a meta-analysis of the extracted data, and the risk of bias for each study will be evaluated. We will perform a Trial Sequential Analysis, subgroup, and sensitivity analyses and assess the overall risk of publication bias. Finally, we will evaluate the review using the GRADE principles.

Peripheral nerve blocks for closed reduction of distal radius fractures-A protocol for a systematic review.

BACKGROUND: Current methods of anaesthesia used for closed reduction of distal radial fractures may be insufficient for pain relief and muscle relaxation, potentially compromising reduction quality and patient satisfaction. Peripheral nerve blocks have already been implemented for surgery of wrist fractures and may provide optimal conditions for closed reduction due to complete motor and sensory blockade of the involved nerves. However, existing literature on peripheral nerve blocks for closed reduction is sparse, and no updated systematic review or meta-analysis exists. AIMS: This protocol is developed according to the PRISMA-P statement. The systematic review and meta-analysis aim to consolidate the literature regarding the effect and harm of peripheral nerve blocks compared with other anaesthesia modalities for closed reduction of distal radius fractures in adults. METHODS: The two primary outcomes are the proportion of participants needing surgery after closed reduction and pain during closed reduction. We will only include randomised clinical trials. Two review authors will each independently screen literature, extract data, and assess risk of bias with Risk of Bias 2 Tool. Meta-analysis will be carried out with Rstudio. We will also perform a Trial Sequential Analysis. The certainty of evidence will be judged using GRADE guidelines. DISCUSSION: We will use up-to-date methodology when conducting the systematic review outlined in this protocol. The results may guide clinicians in their decision-making regarding the use of anaesthesia for closed reduction of distal radius fractures in adults.

Pain treatment after total hip arthroplasty: Detailed statistical analysis plan for the RECIPE randomised clinical trial.

BACKGROUND: The RECIPE trial systematically investigates the effects of different combinations of paracetamol, ibuprofen and dexamethasone for pain treatment after total hip arthroplasty. To preserve transparency, minimise risk of bias and to prevent data-driven analysis, we present this detailed statistical analysis plan. METHODS: The RECIPE trial is a randomised, blinded, parallel four-group multicenter clinical trial for patients undergoing planned primary total hip arthroplasty. Interventions are initiated preoperatively and continued for 24 h postoperatively. Primary outcome is total opioid consumption 0-24 h after end of surgery. Primary analysis will be performed in the modified intention to treat population of all patients undergoing total hip arthroplasty, and all analyses will be stratified for site. We will perform pairwise comparisons between each of the four groups. The primary outcome will be analysed using the van Elteren test and we will present Hodges-Lehmann median differences and confidence intervals. Binary outcomes will be analysed using logistic regression. To preserve a family-wise error rate of <0.05, we will use a Bonferroni-adjusted alfa of 0.05/6 = 0.0083 for all six pairwise comparisons between groups when analysing the primary outcome. We will systematically assess the underlying statistical assumptions for each analysis. Data will be analysed by two blinded independent statisticians, and we will write abstracts covering all possible combinations of conclusions, before breaking the blind. DISCUSSION: The RECIPE trial will provide important information on benefit and harm of combinations of the most frequently used non-opioid analgesics for pain after primary hip arthroplasty.

Implementation of video laryngoscopes and the development in airway management strategy and prevalence of difficult tracheal intubation: A national cohort study.

BACKGROUND: We aimed to determine the development in the use of video laryngoscopy over a 9-year period, and its possible impact on airway planning and management. METHODS: We retrieved 822,259 records of tracheal intubations recorded from 2008 to 2016 in the Danish Anaesthesia Database. The circumstances regarding pre-operative airway assessment, the scheduled airway management plan and the actual airway management concerning video laryngoscopy were reported for each year of observation. Further, the association between year of observation and various airway management related outcomes was evaluated by multivariate logistic regression. RESULTS: There was a significant increase in airway management with 'advanced technique successfully used within two attempts' from 2.7% in 2008 to 15.5% in 2016 (p < .0001). This predominantly reflects use of video laryngoscopy. The prevalence of tracheal intubations 'scheduled for video laryngoscopy' increased from 3.5% in 2008 to 10.6% in 2016 (p < .0001). We found a significant increase in the prevalence of anticipated difficulties with intubations by direct laryngoscopy from 1.8% in 2008 to 5.2% in 2016 (p < .0001). The prevalence of failed tracheal intubations decreased from 0.14% in 2008 to 0.05% in 2016 (p < .0001). CONCLUSION: From 2008 to 2016, a period of massive implementation of video laryngoscopes, a significant change in airway management behaviour was recorded. Increasingly, video laryngoscopy is becoming a first-choice device for both acute and routine airway management. Most importantly, the data showed a noticeable reduction in failed intubation over the time of observation.

A new tool to assess Clinical Diversity In Meta-analyses (CDIM) of interventions.

OBJECTIVE: To develop and validate Clinical Diversity In Meta-analyses (CDIM), a new tool for assessing clinical diversity between trials in meta-analyses of interventions. STUDY DESIGN AND SETTING: The development of CDIM was based on consensus work informed by empirical literature and expertise. We drafted the CDIM tool, refined it, and validated CDIM for interrater scale reliability and agreement in three groups. RESULTS: CDIM measures clinical diversity on a scale that includes four domains with 11 items overall: setting (time of conduct/country development status/units type); population (age, sex, patient inclusion criteria/baseline disease severity, comorbidities); interventions (intervention intensity/strength/duration of intervention, timing, control intervention, cointerventions); and outcome (definition of outcome, timing of outcome assessment). The CDIM is completed in two steps: first two authors independently assess clinical diversity in the four domains. Second, after agreeing upon scores of individual items a consensus score is achieved. Interrater scale reliability and agreement ranged from moderate to almost perfect depending on the type of raters. CONCLUSION: CDIM is the first tool developed for assessing clinical diversity in meta-analyses of interventions. We found CDIM to be a reliable tool for assessing clinical diversity among trials in meta-analysis.

Reporting of methodological studies in health research: a protocol for the development of the MethodologIcal STudy reportIng Checklist (MISTIC).

INTRODUCTION: Methodological studies (ie, studies that evaluate the design, conduct, analysis or reporting of other studies in health research) address various facets of health research including, for instance, data collection techniques, differences in approaches to analyses, reporting quality, adherence to guidelines or publication bias. As a result, methodological studies can help to identify knowledge gaps in the methodology of health research and strategies for improvement in research practices. Differences in methodological study names and a lack of reporting guidance contribute to lack of comparability across studies and difficulties in identifying relevant previous methodological studies. This paper outlines the methods we will use to develop an evidence-based tool-the MethodologIcal STudy reportIng Checklist-to harmonise naming conventions and improve the reporting of methodological studies. METHODS AND ANALYSIS: We will search for methodological studies in the Cumulative Index to Nursing and Allied Health Literature, Cochrane Library, Embase, MEDLINE, Web of Science, check reference lists and contact experts in the field. We will extract and summarise data on the study names, design and reporting features of the included methodological studies. Consensus on study terms and recommended reporting items will be achieved via video conference meetings with a panel of experts including researchers who have published methodological studies. ETHICS AND DISSEMINATION: The consensus study has been exempt from ethics review by the Hamilton Integrated Research Ethics Board. The results of the review and the reporting guideline will be disseminated in stakeholder meetings, conferences, peer-reviewed publications, in requests to journal editors (to endorse or make the guideline a requirement for authors), and on the Enhancing the QUAlity and Transparency Of health Research (EQUATOR) Network and reporting guideline websites. REGISTRATION: We have registered the development of the reporting guideline with the EQUATOR Network and publicly posted this project on the Open Science Framework (www.osf.io/9hgbq).

Avoidance versus use of neuromuscular blocking agents for improving conditions during tracheal intubation or direct laryngoscopy in adults and adolescents.

BACKGROUND: Tracheal intubation during induction of general anaesthesia is a vital procedure performed to secure a patient's airway. Several studies have identified difficult tracheal intubation (DTI) or failed tracheal intubation as one of the major contributors to anaesthesia-related mortality and morbidity. Use of neuromuscular blocking agents (NMBA) to facilitate tracheal intubation is a widely accepted practice. However, because of adverse effects, NMBA may be undesirable. Cohort studies have indicated that avoiding NMBA is an independent risk factor for difficult and failed tracheal intubation. However, no systematic review of randomized trials has evaluated conditions for tracheal intubation, possible adverse effects, and postoperative discomfort. OBJECTIVES: To evaluate the effects of avoiding neuromuscular blocking agents (NMBA) versus using NMBA on difficult tracheal intubation (DTI) for adults and adolescents allocated to tracheal intubation with direct laryngoscopy. To look at various outcomes, conduct subgroup and sensitivity analyses, examine the role of bias, and apply trial sequential analysis (TSA) to examine the level of available evidence for this intervention. SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, BIOSIS, International Web of Science, LILACS, advanced Google, CINAHL, and the following trial registries: Current Controlled Trials; ClinicalTrials.gov; and www.centerwatch.com, up to January 2017. We checked the reference lists of included trials and reviews to look for unidentified trials. SELECTION CRITERIA: We included randomized controlled trials (RCTs) that compared the effects of avoiding versus using NMBA in participants 14 years of age or older. DATA COLLECTION AND ANALYSIS: Two review authors extracted data independently. We conducted random-effects and fixed-effect meta-analyses and calculated risk ratios (RRs) and their 95% confidence intervals (CIs). We used published data and data obtained by contacting trial authors. To minimize the risk of systematic error, we assessed the risk of bias of included trials. To reduce the risk of random errors caused by sparse data and repetitive updating of cumulative meta-analyses, we applied TSA. MAIN RESULTS: We identified 34 RCTs with 3565 participants that met our inclusion criteria. All trials reported on conditions for tracheal intubation; seven trials with 846 participants described 'events of upper airway discomfort or injury', and 13 trials with 1308 participants reported on direct laryngoscopy. All trials used a parallel design. We identified 18 dose-finding studies that included more interventions or control groups or both. All trials except three included only American Society of Anesthesiologists (ASA) class I and II participants, 25 trials excluded participants with anticipated DTI, and obesity or overweight was an excluding factor in 13 studies. Eighteen trials used suxamethonium, and 18 trials used non-depolarizing NMBA.Trials with an overall low risk of bias reported significantly increased risk of DTI with no use of NMBA (random-effects model) (RR 13.27, 95% CI 8.19 to 21.49; P < 0.00001; 508 participants; four trials; number needed to treat for an additional harmful outcome (NNTH) = 1.9, I2 = 0%, D2 = 0%, GRADE = moderate). The TSA-adjusted CI for the RR was 1.85 to 95.04. Inclusion of all trials resulted in confirmation of results and of significantly increased risk of DTI when an NMBA was avoided (random-effects model) (RR 5.00, 95% CI 3.49 to 7.15; P < 0.00001; 3565 participants; 34 trials; NNTH = 6.3, I2 = 70%, D2 = 82%, GRADE = low). Again the cumulative z-curve crossed the TSA monitoring boundary, demonstrating harmful effects of avoiding NMBA on the proportion of DTI with minimal risk of random error. We categorized only one trial reporting on upper airway discomfort or injury as having overall low risk of bias. Inclusion of all trials revealed significant risk of upper airway discomfort or injury when an NMBA was avoided (random-effects model) (RR 1.37, 95% CI 1.09 to 1.74; P = 0.008; 846 participants; seven trials; NNTH = 9.1, I2 = 13%, GRADE = moderate). The TSA-adjusted CI for the RR was 1.00 to 1.85. None of these trials reported mortality. In terms of our secondary outcome 'difficult laryngoscopy', we categorized only one trial as having overall low risk of bias. All trials avoiding NMBA were significantly associated with difficult laryngoscopy (random-effects model) (RR 2.54, 95% CI 1.53 to 4.21; P = 0.0003; 1308 participants; 13 trials; NNTH = 25.6, I2 = 0%, D2= 0%, GRADE = low); however, TSA showed that only 6% of the information size required to detect or reject a 20% relative risk reduction (RRR) was accrued, and the trial sequential monitoring boundary was not crossed. AUTHORS' CONCLUSIONS: This review supports that use of an NMBA may create the best conditions for tracheal intubation and may reduce the risk of upper airway discomfort or injury following tracheal intubation. Study results were characterized by indirectness, heterogeneity, and high or uncertain risk of bias concerning our primary outcome describing difficult tracheal intubation. Therefore, we categorized the GRADE classification of quality of evidence as moderate to low. In light of defined outcomes of individual included trials, our primary outcomes may not reflect a situation that many clinicians consider to be an actual difficult tracheal intubation by which the patient's life or health may be threatened.

Lack of national consensus in preoperative airway assessment.

INTRODUCTION: Difficult airway management is associated with an increased risk of morbidity and mortality. Several preoperative risk factors associated with airway management difficulties have been proposed; however, no clear guideline for airway assessments exists. We therefore hypothesised that Danish airway assessment was lacking uniformity. We aimed to examine whether multivariable risk assessment tools and predictors for difficult intubation and mask ventilation were used systematically. METHODS: Heads of anaesthesia departments were sent a six-question survey at the beginning of 2012. We asked if systematic risk assessment tools, particularly the Simplified Airway Risk Index (SARI), and predictors for difficult intubation and mask ventilation were used. Additionally, we asked if any risk factors were pre-printed on the anaesthesia record. RESULTS: In all, 29 of 31 (94%) departments responded. The SARI was implemented in 8 of 29 (28%, 95% confidence interval (CI): 15-46%) departments with major regional differences. There was no significant association between using the SARI and a reduced number of unanticipated difficult intubation (p = 0.06). Mallampati classification (95.2%, 95% CI: 77.3-99.2%), history of airway management difficulties (85.7%, 95% CI: 65.4-95.0%), ability to prognath (81.0%, 95% CI: 60.0-92.3%) and neck mobility (81.0%, 95% CI: 60.0-92.3%) were the main predictors registered. CONCLUSION: We found considerable inter-departmental variance in the standards employed for airway assessment and no uniform pattern in the registration of risk factors for airway management difficulties. Better prediction of difficult intubation could not be detected in departments that used the SARI. FUNDING: none. TRIAL REGISTRATION: not relevant.