Search

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.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.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).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.

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. (c) 2021 Elsevier Inc. All rights reserved.

Background E-learning is increasingly used in postgraduate medical education. Its numerous benefits include an enhanced learning experience through learning style individualisation, interactive elements, and assessment through tests and quizzes. Current meta-analyses conclude that the overall effectiveness of e-learning is comparable to traditional teaching modalities. However, studies demonstrating its benefits are heterogeneous and of varying quality. This randomised controlled trial aims to investigate whether contemporary e-learning completed prior to a course in obstetric anaesthesia prepares the course participants better than self-study of written course material. Methods A randomised controlled trial allocated second-year resident anaesthetists to receive either e-learning in postpartum haemorrhage and written course material in preeclampsia or e-learning in preeclampsia and written course material in postpartum haemorrhage, prior to a compulsory course in obstetric anaesthesia. The primary outcome was knowledge after completion of e-learning before the course, assessed by type X multiple-choice questions with a score ranging from zero to 35. The secondary outcomes were anxiety level before course simulations, performance during course simulations, and knowledge four and 12 weeks after the course. Results The per protocol analysis of the primary outcome included 45 participants and demonstrated a mean difference of 1.8 (95% CI 0.7-2.9; p = .002) in knowledge after completion of e-learning before the course, in favour of e-learning compared to written course material. There were no statistically significant differences in the secondary outcomes. Conclusion This blinded parallel group randomised controlled trial found a numerically small but statistically significant difference in knowledge favouring e-learning over written course material.

Background and objectivesCharacteristics of a nerve block depend on the distribution of local anesthetic (LA) close to the nerve. The relationship between longitudinal distribution of LA and nerve block characteristics has not been investigated in vivo, but one in vitro study showed decrements in action potential amplitudes with increasing exposure length. We describe the influence of longitudinal neural exposure to LA on nerve block duration adjusted for other likely influential factors.MethodsWe analyzed data from an ethical board approved prospective consecutive collected dataset of 180 healthy volunteers with a common peroneal nerve block (2.5–20 mL, 5–40 mg of ropivacaine). Data were retrieved from three independent randomized controlled trials. The longitudinal neural exposure to LA in millimeters was evaluated using ultrasound. Interventional covariates and demographics were retrieved. Nerve block duration, the dependent variable in the primary assessment, was defined as time of insensitivity to a cold stimulus and was evaluated blinded to all other covariates. Using a multiple linear mixed-effects model, we explored the association between neural exposure to LA and nerve block duration.ResultsWe found a significant positive association between longitudinal neural exposure to LA and block duration (pConclusionsLongitudinal neural exposure to LA was significantly associated with nerve block duration. LA dose was the strongest determinant for block duration whereas LA volume had no influence.

Background The sensory innervation of the shoulder is complex and there are variations in the branching patterns of the sensory fibres. Articular branches from the axillary nerve to the subacromial bursa are described in more than 50% of investigated shoulders but the isolated contribution of sensory input from the axillary nerve has never been investigated clinically. We hypothesized that a selective block of the axillary nerve would reduce morphine consumption and pain after arthroscopic subacromial decompression. Methods We included 60 patients in a randomized, blinded, placebo-controlled study. Patients were randomized to a preoperative selective ultrasound-guided axillary nerve block with 20 mL ropivacaine (7.5 mg/mL) or 20 mL saline. Primary outcome was intravenous morphine consumption 0–4 h postoperatively. Secondary outcome was postoperative pain evaluated by a visual analogue scale (VAS) score (0–100). Results We analysed data from 50 patients and found no significant difference in 0–4 h postoperative morphine consumption between the two groups (ropivacaine 14 mg, placebo 18 mg (P = 0.12)). There was a reduction in postoperative pain: VAS 0–4 h (area under the curve) (ropivacaine 135, placebo 182 (P = 0.03)), VAS after 8 h (ropivacaine 9, placebo 20 (P = 0.01)) and VAS after 24 h (ropivacaine 7, placebo 18 (P = 0.04)). Eight out of 19 patients with a successful selective axillary nerve block needed an interscalene brachial plexus escape block. Conclusions Selective block of the axillary nerve has some pain relieving effect, but in this setting the effect was unpredictable, variable and far from sufficient in a large proportion of the patients. Trial registration ClinicalTrials.gov (NCT01463865). Registered: November 1, 2011.

The reported variation in nerve block duration is considerable. To individualize nerve block therapy, knowledge of the intra- vs inter-individual variability is essential. We investigated the relative contribution of these 2 parameters to the overall nerve block duration variability.With ethics committee approval, we conducted a randomized cross-over trial where 20 healthy volunteers received 8 common peroneal nerve blockades with lidocaine 0.5% on 4 consecutive days. Allocations were 5 mL to either the right or left side and 10 mL to the opposite side on day 1 and 2 and vice versa on day 3 and 4. With fixed needle entry and nerve target, we repeated local anaesthetic deposition for each blockade. The primary outcome was variation in duration of sensory nerve block defined as insensitivity to a cold stimulus. Data were analysed using linear mixed model regression.The mean sensory block duration of 380 (95% CI = [342; 418]) minutes on day one was 55 [33; 77] minutes longer than on day two (P .001), but there were no differences in mean duration between days 2, 3 and 4. The ratios with 2.5; 97.5 percentiles between inter- and intra-individual variation were 2.4 [0.8; 5.2] for the 5 mL blockades and 3.0 [0.9; 6.7] for the 10 mL blockades. The probabilities of inter- to intra-individual variation-ratios1 were 96% and 97%.The intra-individual variability is a substantially minor contributor to the overall variability in sensory nerve block duration compared with the inter-individual variability.

BACKGROUND Emergency abdominal surgery carries a considerable risk of mortality and post-operative complications, including pulmonary complications. In major elective surgery, epidural analgesia reduces mortality and pulmonary complications. We aimed to evaluate the association between epidural analgesia and mortality in emergency abdominal surgery. METHODS In this population-based cohort study with prospective data collection, we included adults undergoing emergency abdominal laparotomy or laparoscopy between 1 January 2009 and 31 December 2010 at 13 Danish hospitals. Appendectomies were excluded. The primary outcome was 90-day mortality. Secondary outcomes included 30-day mortality and serious adverse events. We used binary logistic regression analyses (odds ratios (ORs) with 95% confidence intervals (CIs)). RESULTS We included 4920 patients, of whom 1134 (23.0%) died within 90 days. Overall, 27.9% of the patients were treated with epidural analgesia perioperatively. This increased to 34.0% among patients undergoing major laparotomy. The crude and adjusted association between epidural analgesia and 90-day mortality was OR 0.99 (95%CI: 0.86-1.15, P = .94) and OR 0.80 (95%CI: 0.67-0.94; P = .01), respectively. For 30-day mortality the corresponding estimates were OR 0.90 (95% CI: 0.76-1.06, P = .21) and OR 0.75 (95% CI: 0.62-0.90, P

Background We performed a randomised blinded pilot study in 16 healthy volunteers to assess whether placing a suture-method catheter in the adductor canal is feasible with two different insertion techniques. Methods Each volunteer had a suture-method catheter placed approximately halfway between the superior anterior iliac spine and base of the patella in both legs. Catheters were placed using a parallel technique in one leg and a perpendicular technique in the other leg, according to randomisation. 15 mL lidocaine 1% was injected in each catheter. Successful placement was defined as loss of cold sensation in the saphenous area 30 min after injection. Volunteers were sent home and returned the following day and another dose of lidocaine (15 mL, 1%) was injected through the catheters. Catheter displacement distance was assessed by ultrasound and cold sensation was assessed. In case of preserved cold sensation, we attempted to reposition the catheter with a subsequent injection of lidocaine and reassessment of cold sensation. Results All primary placements were successful using the perpendicular approach (100%; 95% CI 81%-100%) whereas one placement failed using the parallel approach (94%; 95% CI 72%-99%). Three catheters placed using the perpendicular approach were displaced on day 2, compared to one catheter placed with the parallel approach. Displacement distance was highly variable. All catheters, except one, could be repositioned. Three volunteers reported transient sensory deficits lasting approximately 6-8 weeks. Conclusion The suture-method catheter can be placed in the adductor canal with high success rates for initial placement with both techniques.

IntroductionThe transversus abdominis plane block is widely used in postoperative pain management after abdominal surgery. However, large interindividual variation in the cutaneous distribution area of the block has been demonstrated. The purpose of the present study was to explore the reproducibility of the block by determining the intraindividual variation when repeating the block on two separate days.MethodsUltrasound-guided posterior transversus abdominis plane blocks were performed in 16 healthy volunteers and repeated after at least 2 days. Cutaneous sensory block areas and distributions, thresholds for mechanical stimulation, abdominal muscle thicknesses at rest and during maximal contraction, waist circumferences and block duration times were measured on both days. Outcome measurements from the 2 days were compared using a one-sample t-test and intraclass correlation coefficients were calculated for each parameter. Agreement was evaluated visually using Bland-Altman plots.ResultsNone of the mean values of the outcome measurements differed significantly between the 2 days. Intraclass correlation coefficient was 0.75 (moderate-to-good reliability) for lateral abdominal muscle thickness during maximal contraction, but ranges from −0.07 to 0.67 were found for all other outcome measurements (poor-to-moderate reliability).ConclusionWe found a moderate-to-good reproducibility for lateral abdominal muscle thickness during maximal voluntary contraction, but a moderate-to-poor reproducibility for all other block characteristics. However, the cutaneous distribution of the block was still located primarily inferior to a horizontal line through the umbilicus and lateral relative to a vertical line through the anterior superior iliac spine.

We aimed to examine to what extent a lateral infraclavicular brachial plexus block affected the axillary and the suprascapular nerve. We included patients undergoing hand surgery anaesthetised with a lateral infraclavicular brachial plexus block. Our primary outcome was the relative change in surface electromyography during maximum voluntary isometric contraction of the medial deltoid muscle (axillary nerve) and the infraspinatus muscle (suprascapular nerve) from baseline to 30 min after the block procedure. A reduction in electromyography of 50% defined a successful block. The impact of the block on the shoulder nerves was compared with the surgical target nerves of the arm and hand (musculocutaneous, radial, median and ulnar nerves). Twenty patients were included. The medians of the relative changes in the surface electromyography were significantly reduced (both p 0.001) with 92% for the deltoid muscle and 30% for the infraspinatus muscle, respectively. In total, 18 out of 20 patients had reductions 50% for the deltoid muscle, which was significantly different from the infraspinatus muscle, where the proportion was 5 out of 20 (p 0.001). The medians of the relative reductions in electromyography for the arm and hand muscles were 90-96%, similar to the effect on the deltoid muscle. Our results suggest that a lateral infraclavicular block provides block of the axillary nerve comparable to the block of the surgical target nerves. The suprascapular nerve is blocked to a lesser degree. Combining a lateral infraclavicular brachial plexus block with a selective suprascapular block for shoulder surgery warrants further studies.

BACKGROUND Sciatic nerve blocks are used for many orthopaedic procedures on the knee, lower leg, foot and ankle. However, as nerve block durations vary considerably, the timing of supplemental analgesia is challenging. Therefore, knowledge on the effect of local anaesthetic (LA) dose on block duration is important to outweigh the benefits of increasing LA dose against the risk of LA systemic toxicity. In this randomized, double-blind trial, we aimed to explore the relationship between the volume of ropivacaine 0.2% and sciatic nerve block duration. We hypothesized that increasing LA volume would prolong block duration. METHODS We randomized 60 healthy volunteers to receive one of five volumes of ropivacaine 0.2%: 5, 10, 15, 20, or 30 mL. We used an ultrasound-guided, catheter-based technique targeting the sciatic nerve in the infragluteal region. The primary outcome was sensory block duration defined as the time of insensitivity to a cold stimulus. Intergroup differences were tested using one-way ANOVA. RESULTS Mean (SD) sensory block durations for the tibial nerve (TN) with increasing volume were: 9.3 hours (1.7), 10.4 hours (1.6), 9.7 hours (2.9), 10.7 hours (2.8) and 9.9 hours (2.6). Mean (SD) sensory block durations for the common peroneal nerve (CPN) were: 10.6 hours (2.7), 11.9 hours (1.5), 11.0 hours (3.3), 13.2 hours (3.7), and 13.5 hours (6.1). There were no intergroup differences (P = .67 [TN]; P = .25 [CPN]). CONCLUSION We found no effect of increasing the volume of ropivacaine 0.2% from 5 to 30 mL on sensory sciatic nerve block duration.

Background The emergency surgical airway (ESA) is the final option in difficult airway management. We identified ESA procedures registered in the Danish Anaesthesia Database (DAD) and described the performed airway management. Methods We extracted a cohort of 452 461 adult patients undergoing general anaesthesia and tracheal intubation from the DAD from June 1, 2008 to March 15, 2014. Difficult airway management involving an ESA was retrieved for analysis and compared with hospitals files. Two independent reviewers evaluated airway management according to the ASAs'2003 practice guideline for difficult airway management. Results In the DAD cohort 27 out of 452 461 patients had an ESA representing an incidence of 0.06 events per thousand (95% CI; 0.04 to 0.08). A total of 12 149/452 461 patients underwent Ear-Nose and Throat (ENT) surgery, giving an ESA incidence among ENT patients of 1.6 events per thousand (95% CI; 1.0–2.4). A Supraglottic Airway Device and/or the administration of a neuromuscular blocking agent before ESA were used as a rescue in 6/27 and 13/27 of the patients, respectively. In 19/27 patients ENT surgeons performed the ESA's and anaesthetists attempted 6/27 of the ESAs of which three failed. Reviewers evaluated airway management as satisfactory in 10/27 patients. Conclusions The incidence of ESA in the DAD cohort was 0.06 events per thousand. Among ENT patients, the ESA Incidence was 1.6 events per thousand. Airway management was evaluated as satisfactory for 10/27 of the patients. ESA performed by anaesthetists failed in half of the patients.

Background We performed a randomized, blinded pilot study in 12 volunteers to assess the feasibility to reposition an intentionally displaced suture-method catheter for two different insertion techniques for adductor canal block. Methods Each volunteer had an ultrasound-guided suture-method catheter placed in the adductor canal (AC) in both legs. The catheters were placed using a perpendicular technique in one leg and a parallel technique in the other leg, according to randomization. 15 mL lidocaine 1% (LA) was injected in each catheter. Successful primary placement was defined as combined LA spread within the AC and loss of cold sensation 15 min after injection. All catheters were intentionally displaced, and subsequently repositioned using ultrasound. Another dose of lidocaine (15 mL 1%) was injected through the catheters and assessed for successful repositioning. Results Successful primary placement was achieved in 83% (95% CI 55–95%) of catheters placed perpendicular to the AC, and in 75% (95% CI 47–91%) of catheters placed parallel to the AC. Of those with successful primary placement, 100% (95% CI 72–100%) of catheters placed perpendicular to the AC, and 67% (95% CI 35–88%)) placed parallel to the AC could be repositioned. Conclusions Placement and secondary repositioning after displacement of a suture-method catheter within the adductor canal is achievable. A perpendicular technique seems more reliable. Trial registration NCT03315481 clinicaltrials.gov. The study was submitted on March 1, 2017. Due to clerical error, the study was posted on October 20, 2017. Electronic supplementary material The online version of this article (10.1186/s12871-018-0615-4) contains supplementary material, which is available to authorized users.

Introduction Asymmetric dimethylarginine (ADMA), an endogenous inhibitor of the nitric oxide system, may be associated with an adverse outcome in critically ill patients. The aim of the present review was to clarify if plasma ADMA and the arginine-to-ADMA ratio (arginine/ADMA) are associated with mortality in critically ill patients. Methods We searched PubMed, EMBASE and Web of Science/BIOSIS Previews on 31 July 2017 for studies published after 2000 including critically ill paediatric or adult patients and evaluating any association between all-cause mortality and admission ADMA and/or arginine/ADMA ratio. We pooled data from studies providing sufficient data in random effects meta-analyses. Results We identified 15 studies including a total of 1300 patients. These studies have a medium to high risk of bias and substantial clinical heterogeneity. After contacting authors for homogenous data, six studies including 705 patients could be included in a formal meta-analysis. This analysis revealed a strong association between high plasma ADMA upon admission and mortality (pooled odds ratio 3.13; 95% confidence interval (CI) 1.78-5.51). A significant association between ADMA/arginine ratio and mortality was found in two studies only (54 patients) out of a total of six studies (564 patients). Conclusions A high plasma ADMA level upon admission is strongly associated with mortality in critically ill patients. However, there is no association between the arginine/ADMA ratio and mortality in this group of patients. The pathophysiological role of ADMA in circulatory collapse and its potential as a target for intervention remains to be explored.

Provision of paediatric anaesthesia requires careful consideration of the child's cognitive state, unique body composition and physiology. In an observational cohort study, we describe the population characteristics and conduct of anaesthesia in children aged 2-17 years from 1 January 2005 to 31 December 2015. Children were identified from the Danish Anaesthesia Database. We recorded the following variables: age; sex; comorbidities; indications for anaesthesia; practice of anaesthesia; and complications. Results are presented for two age groups: 2-5 and 6-17 years. In total, 32,840 (61% male) children aged 2-5 years received 50,484 anaesthesia episodes and 91,418 (54% male) children aged 6-17 years received 141,082 anaesthesia episodes. The younger children, compared with the older children, were more frequently anaesthetised at a university hospital (50% vs. 36%) and for non-surgical procedures (24% vs. 8%). For both age groups, general anaesthesia was the primary choice of anaesthesia regardless of the reason for anaesthesia. For surgery, general anaesthesia using inhalational agents in addition to intravenous agents or alone was more frequently used in younger children (49% vs. 15%), whereas older children commonly received total intravenous anaesthesia (50% vs. 83%). Regional anaesthesia was infrequently utilised. Complications occurred in 3.3% of anaesthesia episodes among 2-5 year olds compared with 3.7% of anaesthesia episodes among children aged 6-17 years. In conclusion, we found younger children (aged 2-5), compared with older children (aged 6-17) were more frequently anaesthetised for non-surgical reasons, at a university hospital and using inhalational agents. Complications were rare.

The volume-duration relationship using low concentrations of ropivacaine for peripheral nerve blocks is unknown, even though low concentrations of ropivacaine are increasingly used clinically. We investigated the effect of ropivacaine 0.2% on common peroneal nerve block duration. With ethical committee approval, 60 consenting, healthy volunteers were randomly allocated to receive one of five volumes of ropivacaine 0.2% (2.5, 5.0, 10, 15 or 20 ml) administered by ultrasound-guided, catheter-based injection (at 10 ml.min-1 ) near the common peroneal nerve. Our primary outcome was duration of sensory block, defined by insensitivity to a cold stimulus. Our secondary outcome was duration of motor block. Outcomes were assessed every hour from onset of block to complete remission. Intergroup differences were tested using one-way ANOVA followed by regression analyses using the 20 ml intervention group as reference. Block durations varied significantly (p < 0.0001) between groups. Mean (SD) sensory block durations were 9.2 (3.3), 12.5 (3.0), 15.5 (4.4), 17.3 (3.5) and 17.3 (4.6) h. Mean (SD) motor block durations were 3.3 (2.1), 7.2 (2.5), 9.2 (2.2), 12.7 (2.5) and 12.5 (2.5) h. Regression analysis showed that the effect of volume on block duration was progressively smaller with increasing volume, reaching a threshold volume above which there was no effect on nerve block duration (10 ml for sensory block and 15 ml for motor block). We conclude that there is a ceiling effect of increasing volume of ropivacaine 0.2% on both sensory and motor block duration of the common peroneal nerve.

In patients with perforated peptic ulcer, surgical delay has recently been shown to be a critical determinant of survival. The aim of the present population-based cohort study was to evaluate the association between surgical delay by hour and mortality in high-risk patients undergoing emergency abdominal surgery in general.All in-patients aged ≥ 18 years having emergency abdominal laparotomy or laparoscopy performed within 48 h of admission between 1 January 2009 and 31 December 2010 in 13 Danish hospitals were included. Baseline and clinical data, including surgical delay and 90-day mortality were collected. The crude and adjusted association between surgical delay by hour and 90-day mortality was assessed by binary logistic regression.A total of 2803 patients were included. Median age (interquartile range [IQR]) was 66 (51-78) years, and 515 patients (18.4%) died within 90 days of surgery. Over the first 24 h after hospital admission, each hour of surgical delay beyond hospital admission was associated with a median (IQR) decrease in 90-day survival of 2.2% (1.9-3.3%). No statistically significant association between surgical delay by hour and 90-day mortality was shown; crude and adjusted odds ratio with 95% confidence interval 1.016 (1.004-1.027) and 1.003 (0.989-1.017), respectively. Sensitivity analyses confirmed the primary finding.In the present population-based cohort study of high-risk patients undergoing emergency abdominal surgery, no statistically significant adjusted association between mortality and surgical delay was found. Additional research in diagnosis-specific subgroups of high-risk patients undergoing emergency abdominal surgery is warranted.

Background Emergency upper gastrointestinal bleeding is a common condition with high mortality. Most patients undergo oesophagogastroduodenoscopy (OGD), but no universally agreed approach exists to the type of airway management required during the procedure. We aimed to compare anaesthesia care with tracheal intubation (TI group) and without airway instrumentation (monitored anaesthesia care, MAC group) during emergency OGD. Methods This was a prospective, nationwide, population-based cohort study during 2006–13. Emergency OGDs performed under anaesthesia care were included. End points were 90 day mortality (primary) and length of stay in hospital (secondary). Associations between exposure and outcomes were assessed in logistic and linear regression models, adjusted for the following potential confounders: shock at admission, level of anaesthetic expertise present, ASA score, Charlson comorbidity index score, BMI, age, sex, alcohol use, referral origin (home or in-hospital), Forrest classification, ulcer localization, and postoperative care. Results The study group comprised 3580 patients under anaesthesia care: 2101 (59%) for the TI group and 1479 (41%) for the MAC group. During the first 90 days after OGD, 18.9% in the TI group and 18.4% in the MAC group died, crude odds ratio=1.03 [95% confidence interval (CI)=0.87–1.23, P=0.701], adjusted odds ratio=0.95 (95% CI=0.79–1.15, P=0.590). Patients in the TI group stayed slightly longer in hospital [mean 8.16 (95% CI=7.63–8.60) vs 7.63 days (95%=CI 6.92–8.33), P=0.108 in adjusted analysis]. Conclusions In this large population-based cohort study, anaesthesia care with TI was not different from anaesthesia care without airway instrumentation in patients undergoing emergency OGD in terms of 90 day mortality and length of hospital stay.

BACKGROUND Changes in digit skin temperature may be used to predict and determine upper limb nerve block success. We investigated whether a temperature difference between the blocked and the nonblocked hands, simply registered by touching the skin of the 5th and 2nd digit was valid and reliable as a diagnostic test for predicting a successful lateral infraclavicular block. METHODS Blinded observers investigated temperature difference between the blocked and the nonblocked hands of 40 patients. Sensitivity, specificity, and predictive values of a positive and a negative test were estimated for evaluating the validity of a temperature difference for predicting a successful lateral infraclavicular block defined by sensory and motor block of all 4 major nerves (musculocutaneous, radial, ulnar, and median nerves). κ statistics of interobserver agreement were used for evaluating the reliability of the test. RESULTS As a stand-alone test, a temperature difference between the corresponding 2nd and 5th digits of the blocked and the nonblocked hands predicted a successful block with a sensitivity of 92% (95 % confidence interval (CI), 83%-97%) and with a predictive value of a positive test of 95% (CI, 86%-98%). Fleiss κ for multiple observers was 0.74, (CI, 0.61-0.87) for the 5th digit and 0.87 (CI, 0.73-0.998) for the 2nd digit, respectively. CONCLUSIONS We found that a qualitative difference in skin temperature between the blocked and nonblocked hands, measured distally on the 2nd and 5th digits, was a valid and reliable diagnostic test for predicting successful lateral infraclavicular block.

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, I(2) = 0%, D(2) = 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, I(2) = 70%, D(2) = 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, I(2) = 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, I(2) = 0%, D(2)= 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.

Cohort studies have indicated that avoidance of neuromuscular blocking agents (NMBA) is a risk factor for difficult tracheal intubation. However, the impact of avoiding NMBA on tracheal intubation, possible adverse effects, and postoperative discomfort has not been evaluated in a systematic review of randomised trials. We searched several databases for trials published until January 2017. We included randomised controlled trials comparing the effect of avoiding vs using NMBA. Two independent authors assessed risk of bias and extracted data. The risk of random errors was assessed by trial sequential analysis (TSA). We included 34 trials (3565 participants). In the four trials judged to have low risk of bias, there was an increased risk of difficult tracheal intubation with no use of NMBA [random-effects model, risk ratio (RR) 13.27, 95% confidence interval (CI) 8.19–21.49, P

Increased distal skin temperature can be used to predict the success of lateral infraclavicular (LIC) block. We hypothesized that an “eyeball test” of specific infrared thermographic patterns after LIC block could be used to determine block success. In this observational study, five observers trained in four distinct thermographic patterns independently evaluated thermographic images of the hands of 40 patients at baseline and at one-minute intervals for 30 min after a LIC block. Sensitivity, specificity, and predictive values of a positive and a negative test were estimated to evaluate the validity of specific thermographic patterns for predicting a successful block. Sensory and motor block of the musculocutaneous, radial, ulnar, and median nerves defined block success. Fleiss’ kappa statistics of multiple interobserver agreements were used to evaluate reliability. As a diagnostic test, the defined specific thermographic patterns of the hand predicted a successful block with increasing accuracy over the 30-min observation period. Block success was predicted with a sensitivity of 92.4% (95% confidence interval [CI], 86.8 to 96.2) and with a specificity of 84.0% (95% CI, 70.3 to 92.4) at min 30. The Fleiss’ kappa for the five observers was 0.87 (95% CI, 0.77 to 0.96). We conclude that visual evaluation by an eyeball test of specific thermographic patterns of the blocked hands may be useful as a valid and reliable diagnostic test for predicting a successful LIC block.

Increases in skin temperature may be used as an early predictor of the success of interscalene brachial plexus block (IBPB), but we lack detailed information on the thermographic response.To investigate and characterise the thermographic response after IBPBs.Prospective observational study.University hospital and private hospital.Twenty-nine male and 17 female patients scheduled for ambulatory shoulder surgery. Exclusion criteria were age less than 18 years, body weight more than 120 kg and any coagulation abnormality.Infrared thermographic imaging of the hand before and at 1 min intervals for 30 min after an ultrasound-guided IBPB with 20 ml ropivacaine 7.5 mg ml. Cooling of both hands was performed to standardise measurements.Thermographic changes in skin temperature on the dorsum of the hand.Forty-four blocks were successful and two were failures. Four thermographic patterns were observed after successful blocks: the increase in skin temperature was restricted to the thumb (n = 5); increase in skin temperature of the thumb and the second digit (n = 11); increase in skin temperature of the thumb, the second and fifth digits (n = 4); and an increase in skin temperature in all parts of the hand (n = 24). All successful blocks demonstrated a significant (P 0.0001) increase in median (range) of distal skin temperature of the thumb of 6.6°C (0.7 to 17.2) by 30 min, which was already significant (P 0.0001) by 5 min. By contrast, skin temperature decreased significantly (P 0.0001) in the hand after failed blocks and in the contra-lateral non-blocked hand by -1.5°C (-6.2 to 4.2).Successful IBPB resulted in four thermographic patterns. Skin temperature always increased on the thumb within 30 min and this increase achieved statistical significance at 5 min after the block.

Background Guidelines recommend metformin as the first-line oral treatment for type 2 diabetes. We conducted a systematic review to assess whether the use of second- and third-generation sulfonylurea agents is associated with benefits and harms in terms of patient-important outcomes compared with metformin. Methods We searched several electronic databases and other sources for randomized clinical trials published to August 2011. We included trials that compared sulfonylurea versus metformin monotherapy among patients 18 years or older with type 2 diabetes and that had an intervention period of at least 24 weeks. We assessed risk of bias and extracted data related to interventions and outcomes. The risk of random errors was assessed by trial sequential analysis. Results We included 14 trials (4560 participants). All trials were judged to be at high risk of bias. Data on patient-important outcomes were sparse. Compared with metformin, sulfonylurea did not significantly affect all-cause mortality (relative risk [RR] 0.98, 95% confidence interval [CI] 0.61 to 1.58) or cardiovascular mortality (RR 1.47, 95% CI 0.54 to 4.01). Sulfonylurea significantly decreased the risk of nonfatal macrovascular outcomes (RR 0.67, 95% CI 0.48 to 0.93). However, the definition of this outcome varied among trials, and trial sequential analysis showed that more trials are needed before reliable conclusions can be drawn. No differences between sulfonylurea and metformin were found for change in fasting blood glucose level or glycosylated hemoglobin concentration in the random-effects model. Sulfonylurea resulted in greater weight gain compared with metformin, a finding confirmed in the trial sequential analysis. Significantly more patients in the sulfonylurea arm than in the metformin arm had mild hypoglycemia (RR 2.95, 95% CI 2.13 to 4.07) and severe hypoglycemia (RR 5.64, 95% CI 1.22 to 26.00). Interpretation Some evidence suggests that, compared with metformin, second- and third-generation sulfonylureas may not affect all-cause or cardiovascular mortality but may decrease the risk of nonfatal macrovascular outcomes among patients with type 2 diabetes. They may also increase the risk of hypoglycemia. In general, the available data were too few and inconsistent to provide firm evidence concerning patient-important outcomes in relation to the benefits and harms of sulfonylurea versus metformin monotherapy.

Background Brachial plexus blocks cause changes in hand and digit skin temperature. We investigated thermographic patterns after the lateral infraclavicular brachial plexus block. We hypothesised that a successful lateral infraclavicular block could be predicted by increased skin temperature of the 2nd and 5th digits. Methods We performed an ultrasound-guided lateral infraclavicular block in 45 patients undergoing upper limb surgery. The contralateral hand served as control and we obtained infrared thermographic images of both hands before the block and during the following 30 min. We defined areas of interest on the hands and analysed mean skin temperature of each area. Results Forty patients completed the study. Thirty blocks were successful, six were failures and four were partial failures. Four distinct patterns of skin temperature changes were revealed with highly significant changes in temperature, depending on block success. A simultaneous 1 °C ipsilateral increase in skin temperature of the 2nd and 5th digits predicted a successful block with a positive predictive value of 100%. A 5 °C difference in digit skin temperature compared with the contralateral hand had a positive predictive value of 96%, and a digit skin temperature ≤ 30 °C 30 min after performing the block had a predictive value of 100% for a failed block. Conclusions Four different thermographic patterns were found. Simultaneous increases in skin temperature of both the 2nd and 5th digits predicted lateral infraclavicular block success with a positive predictive value of 100%. Digit skin temperature ≤ 30 °C 30 min after performing the block indicated block failure.

Background Emergency major gastrointestinal (GI) surgery carries a considerable risk of mortality and postoperative complications. Effective management of complications and appropriate organization of postoperative care may improve outcome. The importance of the latter is poorly described in emergency GI surgical patients. We aimed to present mortality data and evaluate the postoperative care pathways used after emergency GI surgery. Methods A population-based cohort study with prospectively collected data from six Capital Region hospitals in Denmark. We included 2904 patients undergoing major GI laparotomy or laparoscopy surgery between January 1, 2009, and December 31, 2010. The primary outcome measure was 30 day mortality. Results A total of 538 patients [18.5%, 95% confidence interval (CI): 17.1–19.9] died within 30 days of surgery. In all, 84.2% of the patients were treated after operation in the standard ward, with a 30 day mortality of 14.3%, and 4.8% were admitted to the intensive care unit (ICU) after a median stay of 2 days (inter-quartile range: 1–6). When compared with ‘admission to standard ward', ‘admission to standard ward before ICU admission' and ‘ICU admission after surgery' were independently associated with 30 day mortality; odds ratio 5.45 (95% CI: 3.48–8.56) and 3.27 (95% CI: 2.45–4.36), respectively. Conclusions Mortality in emergency major GI surgical patients remains high. Failure to allocate patients to the appropriate level of care immediately after surgery may contribute to the high postoperative mortality. Future research should focus on improving risk stratification and evaluating the effect of different postoperative care pathways in emergency GI surgery.

Currently, no standard approach exists to the level of monitoring or presence of staff with anaesthetic expertise required during emergency esophago-gastro-duodenoscopy (EGD) for peptic ulcer bleeding (PUB). We assess the association between anaesthesia care and mortality. We further describe the prevalence and inter-hospital variation of anaesthesia care in Denmark and identify clinical predictors for choosing anaesthesia care.This population-based cohort study included all emergency EGDs for PUB in adults during 2012-2013. About 90-day all-cause mortality after EGD was estimated by crude and adjusted logistic regression. Clinical predictors of anaesthesia care were identified in another logistic regression model.Some 3.056 EGDs performed at 21 hospitals were included; 2074 (68%) received anaesthesia care and 982 (32%) were managed under supervison of the endoscopist. Some 16.7% of the patients undergoing EGD with anaesthesia care died within 90 days after the procedure, compared to 9.8% of the patients who had no anaesthesia care, adjusted OR = 1.51 (95% CI = 1.25-1.83). Comparing the two hospitals with the most frequent (98.6% of al EGDs) and least frequent (6.9%) use of anaesthesia care, mortality was 13.7% and 11.7%, respectively, adjusted OR = 1.22 (95% CI = 0.55-2.71). The prevalence of anaesthesia care varied between the hospitals, median = 78.9% (range 6.9-98.6%). Predictors of choosing anaesthesia care were shock at admission, high ASA score, and no pre-existing comorbidity.Use of anaesthesia care for emergency EGD was associated with increased mortality, most likely because of confounding by indication. The use of anaesthesia care varied greatly between hospitals, but was unrelated to mortality at hospital level.

The specific blocking of the axillary nerve has never been investigated clinically. We present four cases illustrating potential applications of the axillary nerve block in the perioperative setting and discuss possible directions for future research in this area. The axillary nerve blocks were all performed using a newly developed in-plane ultrasound-guided technique. In one patient undergoing arthroscopic shoulder surgery, we used the axillary nerve block as the only analgesic combined with propofol sedation and spontaneous breathing. Chronic shoulder pain was eliminated after the axillary nerve block in two patients. The pain score after arthroscopic shoulder surgery in these two patients remained low until termination of the nerve block. In a fourth patient, severe post-operative pain after osteosynthesis of a displaced proximal humerus fracture was almost eliminated after performing an axillary nerve block. These findings warrant larger clinical trials that investigate the pain-mediating role of the axillary nerve in the perioperative setting.

The modified Mallampati score is used to predict difficult tracheal intubation. We have conducted a meta-analysis of published studies to evaluate the Mallampati score as a prognostic test. A total of 55 studies involving 177 088 patients were included after comprehensive electronic and manual searches. The pooled estimates from the meta-analyses were calculated based on a random-effects model and a summary receiver operating curve. Meta-regression analyses were performed to explore sources of possible heterogeneity between the studies. The summary receiver operating curve demonstrated an area under the curve of 0.75. The pooled odds ratio for a difficult intubation with a modified Mallampati score of III or IV was 5.89 [95% confidence interval (CI), 4.74-7.32]. The pooled estimates of the specificity and sensitivity were 0.91 (CI, 0.91-0.91) and 0.35 (CI, 0.34-0.36), respectively. The pooled positive and negative likelihood ratios were 4.13 (CI, 3.60-4.66) and 0.70 (CI, 0.65-0.75), respectively. The meta-analyses had statistical and clinical heterogeneity ranging from 87.2% to 99.4%. Meta-regression analyses did not identify any significant explanation of the heterogeneity. We conclude that the prognostic value of the modified Mallampati score was worse than that estimated by previous meta-analyses. Our assessment shows that the modified Mallampati score is inadequate as a stand-alone test of a difficult laryngoscopy or tracheal intubation, but it may well be a part of a multivariate model for the prediction of a difficult tracheal intubation.

Background and Objectives The speed of local anesthetic (LA) injections in peripheral regional anesthesia ranges from slow continuous infusions (3–12 mL/h) to rapid manual injections (>7500 mL/h). Optimizing injection speed could augment the spread of LA toward the targeted nerves and influence nerve block characteristics. The objective of this study was to investigate whether injection speed of a single dose of LA affects peripheral nerve block duration. Methods After approval from the Danish Regional Scientific Ethics Committee, we enrolled 60 healthy adult volunteers. We used an ultrasound-guided catheter-based technique to perform a common peroneal nerve block. Participants were randomized to receive 4.0 mL of ropivacaine 0.2% with 1 of 5 injection speeds: 12, 60, 300, 600, or 1800 mL/h. Investigators and participants were blinded to group assignment and intervention. Primary outcome was duration of sensory nerve block defined by insensitivity toward cold. Secondary outcomes were duration of motor nerve block, time to onset of sensory nerve block, and grades of sensory and motor nerve block. Intergroup differences were tested by one-way analysis of variance. Results We found no differences in sensory block duration between the 5 groups. Durations were median [range]: 11 [6–14], 12 [9–14], 10.5 [2–15], 11 [8–17], and 12 [9–18] hours, respectively (P = 0.294). In addition, we found no differences in secondary outcomes. Conclusions Injection speed of LA in the range of 12 to 1800 mL/h did not affect common peroneal nerve block duration. Clinical Trial Registration This study was registered at ClinicalTrials.gov, identifier NCT02801799.

Summary We investigated the diagnostic accuracy of a documented previous difficult tracheal intubation as a stand-alone test for predicting a subsequent difficult intubation. Our assessment included patients from the Danish Anaesthesia Database who were scheduled for tracheal intubation by direct laryngoscopy. We used a four-point scale to grade the tracheal intubation. A previous difficult intubation was defined according to the presence of a record documenting a difficult penultimate tracheal intubation-score for the 15 499 patients anaesthetised more than once. Our assessment demonstrates that a documented history of previous difficult or failed intubation using direct laryngoscopy are strong predictors of a subsequent difficult or failed intubation and may identify 30% of these patients. Although previous investigators have reported predictive values that exceed our findings markedly, a documented previous difficult or failed tracheal intubation appears in everyday anaesthetic practice to be a strong predictor of a subsequent difficult tracheal intubation.

Background Previous studies have failed to detect high body mass index (BMI) as a risk factor for difficult tracheal intubation (DTI). BMI was investigated as a risk factor for DTI in patients planned for direct laryngoscopy. Methods A cohort of 91,332 consecutive patients planned for intubation by direct laryngoscopy was retrieved from the Danish Anesthesia Database. A four-point scale to grade the tracheal intubation was used. Age, sex, American Society of Anesthesiologists physical status classification, priority of surgery, history of previous DTI, modified Mallampati-score, use of neuromuscular blocker, and BMI were retrieved. Logistic regression to assess whether BMI was associated with DTI was performed. Results The frequency of DTI was 5.2% (95% confidence interval [CI] 5.0-5.3). In multivariate analyses adjusted for other significant covariates, BMI of 35 or more was a risk for DTI with an odds ratio of 1.34 (95% CI 1.19-1.51, P < 0.0001). As a stand alone test, BMI of 35 or more predicted DTI with a sensitivity of 7.5% (95% CI 7.3-7.7%) and with a predictive value of a positive test of 6.4% (95% CI 6.3-6.6%). BMI as a continuous covariate was a risk for failed intubation with an odds ratio of 1.031 (95% CI 1.002-1.061, P < 0.04). Conclusions High BMI is a weak but statistically significant predictor of difficult and failed intubation and may be more appropriate than weight in multivariate models of prediction of DTI.

Summary We have developed a peripheral nerve catheter, attached to a needle, which works like an adjustable suture. We used in‐plane ultrasound guidance to place 45 catheters close to the femoral, saphenous, sciatic and distal tibial nerves in cadaver legs. We displaced catheters after their initial placement and then attempted to return them to their original positions. We used ultrasound to evaluate the initial and secondary catheter placements and the spread of injectate around the nerves. In 10 cases, we confirmed catheter position by magnetic resonance imaging. We judged 43/45 initial placements successful and 42/43 secondary placements successful by ultrasound, confirmed in 10/10 cases by magnetic resonance imaging.

Background and Objectives The transversus abdominis plane (TAP) block is a widely used nerve block. However, basic block characteristics are poorly described. The purpose of this study was to assess the cutaneous sensory block area, muscle-relaxing effect, and block duration. Methods Sixteen healthy volunteers were randomized to receive an ultrasound-guided unilateral TAP block with 20 mL 7.5 mg/mL ropivacaine and placebo on the contralateral side. Measurements were performed at baseline and 90 minutes after performing the block. Cutaneous sensory block area was mapped and separated into a medial and lateral part by a vertical line through the anterior superior iliac spine. We measured muscle thickness of the 3 lateral abdominal muscle layers with ultrasound in the relaxed state and during maximal voluntary muscle contraction. The volunteers reported the duration of the sensory block and the abdominal muscle–relaxing effect. Results The lateral part of the cutaneous sensory block area was a median of 266 cm2 (interquartile range, 191–310 cm2) and the medial part 76 cm2 (interquartile range, 54–127 cm2). In all the volunteers, lateral wall muscle thickness decreased significantly by 9.2 mm (6.9–15.7 mm) during a maximal contraction. Sensory block and muscle-relaxing effect duration were 570 minutes (512–716 minutes) and 609 minutes (490–724 minutes), respectively. Conclusions Cutaneous sensory block area of the TAP block is predominantly located lateral to a vertical line through the anterior superior iliac spine. The distribution is nondermatomal and does not cross the midline. The muscle-relaxing effect is significant and consistent. The block duration is approximately 10 hours with large variation.

Summary Both the American Society of Anesthesiologists and the UK NAP4 project recommend that an unspecified pre-operative airway assessment be made. However, the choice of assessment is ultimately at the discretion of the individual anaesthesiologist. We retrieved a cohort of 188 064 cases from the Danish Anaesthesia Database, and investigated the diagnostic accuracy of the anaesthesiologists’ predictions of difficult tracheal intubation and difficult mask ventilation. Of 3391 difficult intubations, 3154 (93%) were unanticipated. When difficult intubation was anticipated, 229 of 929 (25%) had an actual difficult intubation. Likewise, difficult mask ventilation was unanticipated in 808 of 857 (94%) cases, and when anticipated (218 cases), difficult mask ventilation actually occurred in 49 (22%) cases. We present a previously unpublished estimate of the accuracy of anaesthesiologists’ prediction of airway management difficulties in daily routine practice. Prediction of airway difficulties remains a challenging task, and our results underline the importance of being constantly prepared for unexpected difficulties.

Background. In early postpartum haemorrhage (PPH), a low concentration of fibrinogen is associated with excessive subsequent bleeding and blood transfusion. We hypothesized that pre-emptive treatment with fibrinogen concentrate reduces the need for red blood cell (RBC) transfusion in patients with PPH. Methods. In this investigator-initiated, multicentre, double-blinded, parallel randomized controlled trial, we assigned subjects with severe PPH to a single dose of fibrinogen concentrate or placebo (saline). A dose of 2 g or equivalent was given to all subjects independent of body weight and the fibrinogen concentration at inclusion. The primary outcome was RBC transfusion up to 6 weeks postpartum. Secondary outcomes were total blood loss, total amount of blood transfused, occurrence of rebleeding, haemoglobin ,58 g litre 21 , RBC transfusion within 4 h, 24 h, and 7 days, and as a composite outcome of ‘severe PPH’, defined as a decrease in haemoglobin of .40 g litre 21 , transfusion of at least 4 units of RBCs, haemostatic intervention (angiographic embolization, surgical arterial ligation, or hysterectomy), or maternal death. Results. Of the 249 randomized subjects, 123 of 124 in the fibrinogen group and 121 of 125 in the placebo group were included in the intention-to-treat analysis. At inclusion the subjects had severe PPH, with a mean blood loss of 1459 (SD 476) ml and a mean fibrinogen concentration of 4.5 (SD 1.2) g litre 21 . The intervention group received a mean dose of 26 mg kg 21 fibrinogen concentrate, thereby significantly increasing fibrinogen concentration compared with placebo by 0.40 g litre 21 (95% confidence interval, 0.15 –0.65; P¼0.002). Postpartum blood transfusion occurred in 25 (20%) of the fibrinogen group and 26 (22%) of the placebo group (relative risk, 0.95; 95% confidence interval, 0.58 –1.54; P¼0.88). We found no difference in any predefined secondary outcomes, per-protocol analyses, or adjusted analyses. No thromboembolic events were detected. Conclusions. We found no evidence for the use of 2 g fibrinogen concentrate as pre-emptive treatment for severe PPH in patients with normofibrinogenaemia. Clinical trial registration. ClinicalTrials.gov: http://clinicaltrials.gov/show/NCT01359878. Published protocol: http://www.trialsjournal.com/content/pdf/1745-6215-13-110.pdf.

Study objectives To evaluate the effect of perioperative thoracic epidural analgesia followed by postoperative epidural analgesia compared with conventional IV anesthesia on the occurrence of late postoperative hypoxemia in patients undergoing elective coronary bypass graft (CABG) surgery. Design Randomized controlled trial. Setting Cardiac surgery unit at a university hospital. Patients A total of 50 patients undergoing elective CABG surgery. Intervention Patients were randomly assigned to receive either conventional IV anesthesia (CON) or general anesthesia combined with thoracic epidural anesthesia followed by postoperative epidural analgesia (TEA) with bupivacaine. Postoperatively, the patients were monitored in the surgical ward with a pulse oximeter for a total of two postoperative nights (the second and third postoperative nights). Measurements and results The overall incidence of episodic hypoxemia was 56% (28 of 50 patients) on the second postoperative night and 89% (41 of 46 patients) on the third postoperative night. More than 30 episodes of hypoxemia developed on the second night in 22% of patients (11 of 50 patients), and on the third night in 30% of patients (14 of 46 patients). Despite oxygen therapy, 7% of patients (3 of 46 patients) experienced constant hypoxemia on the third night. In general, hypoxemia seemed to be slightly worse on the third postoperative night compared with the second postoperative night. Significantly more patients in the TEA group (25 of 25 patients) experienced episodic hypoxemia on the third postoperative night compared with the CON group (16 of 21 patients; p Conclusions Both episodic and constant hypoxemia were common in the late postoperative period in patients on the ward after CABG surgery with no clinically significant intergroup differences. Thus, perioperative epidural anesthesia/analgesia combined with postoperative epidural anesthesia/analgesia was not protective against hypoxemia, and therapy with opioids did not seem to be of importance for the occurrence of late postoperative hypoxemia on nights 2 and 3 after CABG surgery.

Background A difficult neuraxial block (DNB) may be associated with complications. The aims of this study were to estimate the prevalence of DNB, assess patient-related and organizational factors associated with DNB, and evaluate the diagnostic accuracy of an accumulated risk score for predicting DNB. Methods A consecutive cohort of 73,579 patients was retrieved. A predefined DNB score and information on patient-related and organizational factors were included in the analyses. Logistic regression analysis was performed. We evaluated the diagnostic accuracy of an accumulated weighted point score of the patient-related risk factors of DNB. Results The prevalence of DNB and abandoned neuraxial block was 3.9 (95% confidence interval [95% CI], 3.7–4.0) and 0.2 (95% CI, 0.16–0.22), respectively. Body mass index of 35 or higher and previous DNB were associated with DNB, with 3.23 (95% CI, 2.87–3.65) and 2.00 (95% CI, 1.33–3.00), respectively. However, the remaining patient-related covariates were associated with DNB with substantial lower odds ratios. The diagnostic accuracy of an accumulated sum score demonstrated an area under the curve of 0.62 (95% CI, 0.61–0.64), a positive predictive value of 5%, and a positive likelihood ratio of 1.4. Conclusions Despite of strong statistical association between DNB and the tested risk factors, the low odds ratios and estimates of the diagnostic test indicate that the clinical impact using an accumulated risk sum score is limited.

BACKGROUND: In randomised trials of medical interventions, the most reliable analysis follows the intention-to-treat (ITT) principle. However, the ITT analysis requires that missing outcome data have to be imputed. Different imputation techniques may give different results and some may lead to bias. In anti-obesity drug trials, many data are usually missing, and the most used imputation method is last observation carried forward (LOCF). LOCF is generally considered conservative, but there are more reliable methods such as multiple imputation (MI).OBJECTIVES: To compare four different methods of handling missing data in a 60-week placebo controlled anti-obesity drug trial on topiramate.METHODS: We compared an analysis of complete cases with datasets where missing body weight measurements had been replaced using three different imputation methods: LOCF, baseline carried forward (BOCF) and MI.RESULTS: 561 participants were randomised. Compared to placebo, there was a significantly greater weight loss with topiramate in all analyses: 9.5 kg (SE 1.17) in the complete case analysis (N = 86), 6.8 kg (SE 0.66) using LOCF (N = 561), 6.4 kg (SE 0.90) using MI (N = 561) and 1.5 kg (SE 0.28) using BOCF (N = 561).CONCLUSIONS: The different imputation methods gave very different results. Contrary to widely stated claims, LOCF did not produce a conservative (i.e., lower) efficacy estimate compared to MI. Also, LOCF had a lower SE than MI.

Background We know from previous studies that increasing age, abnormal vital signs and abnormal acid-base status are strongly associated with in-hospital mortality in unselected patients admitted acutely to hospital. A model including this information will make us able to explore associations and predict the risk for future patients. Our aim was to describe a Bayesian model for prediction of adverse outcome in the acute ill adult patient admitted to hospital, based on already existing data from the ‘Acute Admission Database’. Methods The model is as tatic Bayesian network, i.e. as tochastic model where all interdependence is described by conditional probabilities. The net consists of nodes representing variables and pointed arrows of influence. The probabilities connected to the nodes and arrows are conditional probabilities showing how the state of a variable influences the probability distribution for the states of another variable. We based the model on already existing data from the ‘Acute Admission Database’ and imported data from 6279 patients consecutively admitted to Hillerod Hospital through the Emergency Department into the Bayesian net program, Netica “3.7” © Norsys Software Corp. We included the risk factors identified in this cohort in previous studies as nodes, and represented the known associations with directed arrows. Results We tested the use of the model by simulating the path of an acutely ill patient: a male patient, 70 years old and presenting with vomiting blood. By using this evidence in the nodes of relevance, we could assess the most probable distribution of the other nodes, including the outcome of interest. We simulated that more data became available for instance vitals signs and triage categories. This new evidence changed the nodes and finally we entered information about a venous blood gas, which changed the probability distribution of the outcome measures as more evidence was gained. Conclusion By using already existing data, we were able to build a Bayesian network, which can be used to estimate the risk of adverse outcome and serve as a decision support system in assessing future patients admitted acutely to hospital.

Type 2 diabetes mellitus (T2DM) is a growing health problem worldwide. Whether sulphonylureas show better, equal or worse therapeutic effects in comparison with other antidiabetic interventions for patients with T2DM remains controversial.To assess the effects of sulphonylurea monotherapy versus placebo, no intervention or other antidiabetic interventions for patients with T2DM.We searched publications in The Cochrane Library, MEDLINE, EMBASE, Science Citation Index Expanded, LILACS and CINAHL (all until August 2011) to obtain trials fulfilling the inclusion criteria for our review.We included clinical trials that randomised patients 18 years old or more with T2DM to sulphonylurea monotherapy with a duration of 24 weeks or more.Two authors independently assessed the risk of bias. The primary outcomes were all-cause and cardiovascular mortality. Secondary outcomes were other patient-important outcomes and metabolic variables. Where possible, we used risk ratios (RR) with 95% confidence intervals (95% CI) to analyse the treatment effect of dichotomous outcomes. We used mean differences with 95% CI to analyse the treatment effect of continuous outcomes. We evaluated the risk of bias. We conducted trial sequential analyses to assess whether firm evidence could be established for a 10% relative risk reduction (RRR) between intervention groups.We included 72 randomised controlled trials (RCTs) with 22,589 participants; 9707 participants randomised to sulphonylureas versus 12,805 participants randomised to control interventions. The duration of the interventions varied from 24 weeks to 10.7 years. We judged none of the included trials as low risk of bias for all bias domains. Patient-important outcomes were seldom reported.First-generation sulphonylureas (FGS) versus placebo or insulin did not show statistical significance for all-cause mortality (versus placebo: RR 1.46, 95% CI 0.87 to 2.45; P = 0.15; 2 trials; 553 participants; high risk of bias (HRB); versus insulin: RR 1.18, 95% CI 0.88 to 1.59; P = 0.26; 2 trials; 1944 participants; HRB). FGS versus placebo showed statistical significance for cardiovascular mortality in favour of placebo (RR 2.63, 95% CI 1.32 to 5.22; P = 0.006; 2 trials; 553 participants; HRB). FGS versus insulin did not show statistical significance for cardiovascular mortality (RR 1.36, 95% CI 0.68 to 2.71; P = 0.39; 2 trials; 1944 participants; HRB). FGS versus alpha-glucosidase inhibitors showed statistical significance in favour of FGS for adverse events (RR 0.63, 95% CI 0.52 to 0.76; P = 0.01; 2 trials; 246 participants; HRB) and for drop-outs due to adverse events (RR 0.28, 95% CI 0.12 to 0.67; P = 0.004; 2 trials; 246 participants; HRB).Second-generation sulphonylureas (SGS) versus metformin (RR 0.98, 95% CI 0.61 to 1.58; P = 0.68; 6 trials; 3528 participants; HRB), thiazolidinediones (RR 0.92, 95% CI 0.60 to 1.41; P = 0.70; 7 trials; 4955 participants; HRB), insulin (RR 0.96, 95% CI 0.79 to 1.18; P = 0.72; 4 trials; 1642 participants; HRB), meglitinides (RR 1.44, 95% CI 0.47 to 4.42; P = 0.52; 7 trials; 2038 participants; HRB), or incretin-based interventions (RR 1.39, 95% CI 0.52 to 3.68; P = 0.51; 2 trials; 1503 participants; HRB) showed no statistically significant effects regarding all-cause mortality in a random-effects model. SGS versus metformin (RR 1.47; 95% CI 0.54 to 4.01; P = 0.45; 6 trials; 3528 participants; HRB), thiazolidinediones (RR 1.30, 95% CI 0.55 to 3.07; P = 0.55; 7 trials; 4955 participants; HRB), insulin (RR 0.96, 95% CI 0.73 to 1.28; P = 0.80; 4 trials; 1642 participants; HRB) or meglitinide (RR 0.97, 95% CI 0.27 to 3.53; P = 0.97; 7 trials, 2038 participants, HRB) showed no statistically significant effects regarding cardiovascular mortality. Mortality data for the SGS versus placebo were sparse. SGS versus thiazolidinediones and meglitinides did not show statistically significant differences for a composite of non-fatal macrovascular outcomes. SGS versus metformin showed statistical significance in favour of SGS for a composite of non-fatal macrovascular outcomes (RR 0.67, 95% CI 0.48 to 0.93; P = 0.02; 3018 participants; 3 trials; HRB). The definition of non-fatal macrovascular outcomes varied among the trials. SGS versus metformin, thiazolidinediones and meglitinides showed no statistical significance for non-fatal myocardial infarction. No meta-analyses could be performed for microvascular outcomes. SGS versus placebo, metformin, thiazolidinediones, alpha-glucosidase inhibitors or meglitinides showed no statistical significance for adverse events. SGS versus alpha-glucosidase inhibitors showed statistical significance in favour of SGS for drop-outs due to adverse events (RR 0.48, 95% CI 0.24 to 0.96; P = 0.04; 9 trials; 870 participants; HRB). SGS versus meglitinides showed no statistical significance for the risk of severe hypoglycaemia. SGS versus metformin and thiazolidinediones showed statistical significance in favour of metformin (RR 5.64, 95% CI 1.22 to 26.00; P = 0.03; 4 trials; 3637 participants; HRB) and thiazolidinediones (RR 6.11, 95% CI 1.57 to 23.79; P = 0.009; 6 trials; 5660 participants; HRB) for severe hypoglycaemia.Third-generation sulphonylureas (TGS) could not be included in any meta-analysis of all-cause mortality, cardiovascular mortality or non-fatal macro- or microvascular outcomes. TGS versus thiazolidinediones showed statistical significance regarding adverse events in favour of TGS (RR 0.88, 95% CI 0.78 to 0.99; P = 0.03; 3 trials; 510 participants; HRB). TGS versus thiazolidinediones did not show any statistical significance for drop-outs due to adverse events. TGS versus other comparators could not be performed due to lack of data.For the comparison of SGS versus FGS no meta-analyses of all-cause mortality, cardiovascular mortality, non-fatal macro- or microvascular outcomes, or adverse events could be performed.Health-related quality of life and costs of intervention could not be meta-analysed due to lack of data.In trial sequential analysis, none of the analyses of mortality outcomes, vascular outcomes or severe hypoglycaemia met the criteria for firm evidence of a RRR of 10% between interventions.There is insufficient evidence from RCTs to support the decision as to whether to initiate sulphonylurea monotherapy. Data on patient-important outcomes are lacking. Therefore, large-scale and long-term randomised clinical trials with low risk of bias, focusing on patient-important outcomes are required.

Sulphonylureas are widely used for patients with type 2 diabetes mellitus. Sulphonylureas lower blood glucose by stimulating insulin secretion from the pancreas thereby increasing the insulin levels in the blood. Seventy-two trials were included in the systematic review assessing the effects of sulphonylurea as sole therapy versus other comparators in patients with type 2 diabetes mellitus. A total of 22,589 participants were included. The number of participants randomised to a sulphonylurea was 9707 and the number of participants randomised to a comparator was 12,805. The duration of the interventions varied from 24 weeks to 10.7 years. All trials had deficiencies (risk of bias) and for the individual comparisons the number of participants were small, resulting in a high risk of random errors (play of chance). Data on mortality and diabetic complications were sparse and inconclusive. Stopping taking the antidiabetic drug due to adverse events were more common with alpha-glucosidase inhibitors (for example acarbose) compared with second-generation sulphonylureas (for example glibenclamide, glipizide, glibornuride and gliclazide), but the data were sparse. Severe hypoglycaemia was more common with second-generation sulphonylureas compared with metformin and thiazolidinediones (for example pioglitazone), but again the data were sparse. Due to lack of data we could not adequately evaluate health-related quality of life and costs. There is insufficient evidence regarding patient-important outcomes from high-quality randomised controlled trials (RCTs) to support the decision as to whether to initiate sulphonylurea as sole therapy. Large-scale and long-lasting randomised clinical trials with low risk of bias, which focus on mortality, diabetic complications, adverse events and health-related quality of life, are needed.