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In this study, patients with severe sepsis were assigned to fluid resuscitation with starch (HES 130/0.4) or Ringer's acetate. The starch group had an increased risk of death at day 90 and increased use of renal-replacement therapy, as compared with the Ringer's acetate group. Intravenous fluids are the mainstay of treatment for patients with hypovolemia due to severe sepsis. Colloid solutions are used to obtain rapid and lasting circulatory stabilization, but there are limited data to support this practice. 1 The Surviving Sepsis Campaign guidelines recommend the use of either colloids or crystalloids, 2 but high-molecular-weight hydroxyethyl starch (HES) may cause acute kidney failure in patients with severe sepsis, as observed in two randomized trials. 3 , 4 Those trials had substantial limitations, and participants received HES solutions with a molecular weight of 200 kD and a substitution ratio (the number of hydroxyethyl groups per glucose molecule) of . . .

Hydroxyethyl starch (HES) [corrected] is widely used for fluid resuscitation in intensive care units (ICUs), but its safety and efficacy have not been established in patients with severe sepsis. In this multicenter, parallel-group, blinded trial, we randomly assigned patients with severe sepsis to fluid resuscitation in the ICU with either 6% HES 130/0.42 (Tetraspan) or Ringer's acetate at a dose of up to 33 ml per kilogram of ideal body weight per day. The primary outcome measure was either death or end-stage kidney failure (dependence on dialysis) at 90 days after randomization. Of the 804 patients who underwent randomization, 798 were included in the modified intention-to-treat population. The two intervention groups had similar baseline characteristics. At 90 days after randomization, 201 of 398 patients (51%) assigned to HES 130/0.42 had died, as compared with 172 of 400 patients (43%) assigned to Ringer's acetate (relative risk, 1.17; 95% confidence interval [CI], 1.01 to 1.36; P=0.03); 1 patient in each group had end-stage kidney failure. In the 90-day period, 87 patients (22%) assigned to HES 130/0.42 were treated with renal-replacement therapy versus 65 patients (16%) assigned to Ringer's acetate (relative risk, 1.35; 95% CI, 1.01 to 1.80; P=0.04), and 38 patients (10%) and 25 patients (6%), respectively, had severe bleeding (relative risk, 1.52; 95% CI, 0.94 to 2.48; P=0.09). The results were supported by multivariate analyses, with adjustment for known risk factors for death or acute kidney injury at baseline. Patients with severe sepsis assigned to fluid resuscitation with HES 130/0.42 had an increased risk of death at day 90 and were more likely to require renal-replacement therapy, as compared with those receiving Ringer's acetate. (Funded by the Danish Research Council and others; 6S ClinicalTrials.gov number, NCT00962156.).

Background It has been argued that postoperative pain treatment should be “procedure-specific”, since different analgesics may have specific effects dependent on the surgical procedure. The aim of the present subgroup analysis was to compare the beneficial and harmful effects of perioperative gabapentin treatment in different surgical procedures. Methods Relevant databases were searched for randomized clinical trials (RCTs) comparing gabapentin versus placebo. Two authors independently screened titles and abstracts, extracted data and assessed risk of bias. The primary outcomes were differences in 24-h morphine consumption, and serious adverse events (SAE) between surgical procedures. These subgroup analyses were predefined in a PRISMA compliant systematic review registered at PROSPERO (ID: CRD42013006538). It was predefined that conclusions should primarily be based on trials classified as overall low risk of bias. Results Seventy-four RCTs with 5645 patients were included, assessing benefit and harm in cholecystectomy, hysterectomy, mastectomy, and arthroplasty surgery, spinal surgery, and thoracic surgery. Only eight of 74 trials were classified as overall low risk of bias limiting our ability to conclude on the estimates in most meta-analyses. The differences between surgical procedures in these trials were not statistically significant when tested for subgroup differences. Fifteen trials with 1377 patients reported a total of 59 SAEs, most of which were observed in the thoracic surgery group. Conclusion Both beneficial and harmful effects in these subgroup analyses were influenced by bias and insufficient data, limiting conclusions. With these limitations, we could not adequately test for differences in beneficial or harmful outcomes between six surgical subgroups undergoing perioperative gabapentin treatment.

To develop and validate Clinical Diversity In Meta-analyses (CDIM), a new tool for assessing clinical diversity between trials in meta-analyses of interventions. 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. 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. 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.

Background and ObjectivesAdductor canal block (ACB) is predominantly a sensory nerve block, but excess volume may spread to the femoral triangle and reduce quadriceps strength. We hypothesized that reducing the local anesthetic volume from 30 to 10 mL may lead to fewer subjects with quadriceps weakness.MethodsWe performed a paired, blinded, randomized trial including healthy men. All subjects received bilateral ACBs with ropivacaine 0.1%; 10 mL in 1 leg and 30 mL in the other leg. The primary outcome was the difference in number of subjects with quadriceps strength reduced by more than 25% from baseline in 2 consecutive assessments. Secondary outcomes were quadriceps strength as a percentage of baseline at predefined time points, functional outcome assessed by the 30-Second Chair Stand Test (1 leg at a time), and sensory block. Clinicaltrials.gov Identifier: NCT01981746.ResultsWe included and analyzed 26 subjects. For either volume, 2 subjects had a reduction in quadriceps strength by more than 25% from baseline (difference, 0%; 95% confidence interval, −13 to 13; P > 0.999). Similarly, we found no significant differences between volumes in quadriceps strength at any of the predefined time points or in sensory block. The only statistically significant difference between volumes was found in the 30-Second Chair Stand Test at 2 hours (P = 0.02), but this difference had disappeared at 4 hours (P = 0.06).ConclusionsVarying the volume of ropivacaine 0.1% used for ACB between 10 and 30 mL did not have a statistically significant or clinically relevant impact on quadriceps strength.

During the last 15 years, gabapentin has become an established component of postoperative pain treatment. Gabapentin has been employed in a wide range of doses, but little is known about the optimal dose, providing the best balance between benefit and harm. This systematic review with meta-analyses aimed to explore the beneficial and harmful effects of various doses of gabapentin administered to surgical patients. Data in this paper were derived from an original review, and the subgroup analyses were predefined in an International Prospective Register of Systematic Reviews published protocol: PROSPERO (ID: CRD42013006538). The methods followed Cochrane guidelines. The Cochrane Library's CENTRAL, PubMed, EMBASE, Science Citation Index Expanded, Google Scholar, and FDA database were searched for relevant trials. Randomized clinical trials comparing gabapentin versus placebo were included. Four different dose intervals were investigated: 0-350, 351-700, 701-1050, and >1050 mg. Primary co-outcomes were 24-hour morphine consumption and serious adverse events (SAEs), with emphasis put on trials with low risk of bias. One hundred and twenty-two randomized clinical trials, with 8466 patients, were included. Sixteen were overall low risk of bias. No consistent increase in morphine-sparing effect was observed with increasing doses of gabapentin from the trials with low risk of bias. Analyzing all trials, the smallest and the highest dose subgroups demonstrated numerically the most prominent reduction in morphine consumption. Twenty-seven trials reported 72 SAEs, of which 83% were reported in the >1050 mg subgroup. No systematic increase in SAEs was observed with increasing doses of gabapentin. Data were sparse, and the small number of trials with low risk of bias is a major limitation for firm conclusions. Taking these limitations into account, we were not able to demonstrate a clear relationship between the dosage of gabapentin and opioid-sparing or harmful effects. These subgroup analyses are exploratory and hypothesis-generating for future trialists.