Waleed Alhazzani

Endovascular Thrombectomy for Acute Ischemic Stroke: A Meta-analysis

IMPORTANCE Endovascular intervention for acute ischemic stroke improves revascularization. But trials examining endovascular therapy yielded variable functional outcomes, and the effect of endovascular intervention among subgroups needs better definition. OBJECTIVE To examine the association between endovascular mechanical thrombectomy and clinical outcomes among patients with acute ischemic stroke. DATA SOURCES We systematically searched MEDLINE, EMBASE, CINAHL, Google Scholar, and the Cochrane Library without language restriction through August 2015. STUDY SELECTION Eligible studies were randomized clinical trials of endovascular therapy with mechanical thrombectomy vs standard medical care, which includes the use of intravenous tissue plasminogen activator (tPA). DATA EXTRACTION AND SYNTHESIS Independent reviewers evaluated the quality of studies and abstracted the data. We calculated odds ratios (ORs) and 95% CIs for all outcomes using random-effects meta-analyses and performed subgroup and sensitivity analyses to examine whether certain imaging, patient, treatment, or study characteristics were associated with improved functional outcome. The strength of the evidence was examined for all outcomes using the GRADE method. MAIN OUTCOMES AND MEASURES Ordinal improvement across modified Rankin scale (mRS) scores at 90 days, functional independence (mRS score, 0-2), angiographic revascularization at 24 hours, symptomatic intracranial hemorrhage within 90 days, and all-cause mortality at 90 days. RESULTS Data were included from 8 trials involving 2423 patients (mean [SD] age, 67.4 [14.4] years; 1131 [46.7%] women), including 1313 who underwent endovascular thrombectomy and 1110 who received standard medical care with tPA. In a meta-analysis of these trials, endovascular therapy was associated with a significant proportional treatment benefit across mRS scores (OR, 1.56; 95% CI, 1.14-2.13; P = .005). Functional independence at 90 days (mRS score, 0-2) occurred among 557 of 1293 patients (44.6%; 95% CI, 36.6%-52.8%) in the endovascular therapy group vs 351 of 1094 patients (31.8%; 95% CI, 24.6%-40.0%) in the standard medical care group (risk difference, 12%; 95% CI, 3.8%-20.3%; OR, 1.71; 95% CI, 1.18-2.49; P = .005). Compared with standard medical care, endovascular thrombectomy was associated with significantly higher rates of angiographic revascularization at 24 hours (75.8% vs 34.1%; OR, 6.49; 95% CI, 4.79-8.79; P < .001) but no significant difference in rates of symptomatic intracranial hemorrhage within 90 days (70 events [5.7%] vs 53 events [5.1%]; OR, 1.12; 95% CI, 0.77-1.63; P = .56) or all-cause mortality at 90 days (218 deaths [15.8%] vs 201 deaths [17.8%]; OR, 0.87; 95% CI, 0.68-1.12; P = .27). CONCLUSIONS AND RELEVANCE Among patients with acute ischemic stroke, endovascular therapy with mechanical thrombectomy vs standard medical care with tPA was associated with improved functional outcomes and higher rates of angiographic revascularization, but no significant difference in symptomatic intracranial hemorrhage or all-cause mortality at 90 days.

Proton pump inhibitors versus histamine 2 receptor antagonists for stress ulcer prophylaxis in critically ill patients: a systematic review and meta-analysis

Background:Critically ill patients may develop bleeding caused by stress ulceration. Acid suppression is commonly prescribed for patients at risk of stress ulcer bleeding. Whether proton pump inhibitors are more effective than histamine 2 receptor antagonists is unclear. Objectives:To determine the efficacy and safety of proton pump inhibitors vs. histamine 2 receptor antagonists for the prevention of upper gastrointestinal bleeding in the ICU. Search Methods:We searched Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE, ACPJC, CINHAL, online trials registries (clinicaltrials.gov, ISRCTN Register, WHO ICTRP), conference proceedings databases, and reference lists of relevant articles. Selection CriteriaRandomized controlled parallel group trials comparing proton pump inhibitors to histamine 2 receptor antagonists for the prevention of upper gastrointestinal bleeding in critically ill patients, published before March 2012. Data Collection and Analysis:Two reviewers independently applied eligibility criteria, assessed quality, and extracted data. The primary outcomes were clinically important upper gastrointestinal bleeding and overt upper gastrointestinal bleeding; secondary outcomes were nosocomial pneumonia, ICU mortality, ICU length of stay, and Clostridium difficile infection. Trial authors were contacted for additional or clarifying information. Results:Fourteen trials enrolling a total of 1,720 patients were included. Proton pump inhibitors were more effective than histamine 2 receptor antagonists at reducing clinically important upper gastrointestinal bleeding (relative risk 0.36; 95% confidence interval 0.19–0.68; p = 0.002; I2 = 0%) and overt upper gastrointestinal bleeding (relative risk 0.35; 95% confidence interval 0.21–0.59; p < 0.0001; I2 = 15%). There were no differences between proton pump inhibitors and histamine 2 receptor antagonists in the risk of nosocomial pneumonia (relative risk 1.06; 95% confidence interval 0.73–1.52; p = 0.76; I2 = 0%), ICU mortality (relative risk 1.01; 95% confidence interval 0.83–1.24; p = 0.91; I2 = 0%), or ICU length of stay (mean difference −0.54 days; 95% confidence interval −2.20 to 1.13; p = 0.53; I 2 = 39%). No trials reported on C. difficile infection. Conclusions:In critically ill patients, proton pump inhibitors seem to be more effective than histamine 2 receptor antagonists in preventing clinically important and overt upper gastrointestinal bleeding. The robustness of this conclusion is limited by the trial methodology, differences between lower and higher quality trials, sparse data, and possible publication bias. We observed no differences between drugs in the risk of pneumonia, death, or ICU length of stay.

Benzodiazepine versus nonbenzodiazepine-based sedation for mechanically ventilated, critically ill adults: a systematic review and meta-analysis of randomized trials.

Background:Use of dexmedetomidine or propofol rather than a benzodiazepine sedation strategy may improve ICU outcomes. We reviewed randomized trials comparing a benzodiazepine and nonbenzodiazepine regimen in mechanically ventilated adult ICU patients to determine if differences exist between these sedation strategies with respect to ICU length of stay, time on the ventilator, delirium prevalence, and short-term mortality. Methods:We searched CINAHL, MEDLINE, the Cochrane databases, and the American College of Critical Care Medicine’s Pain, Agitation, Delirium Management Guidelines’ literature database from 1996 to 2013. Citations were screened for randomized trials that enrolled critically ill, mechanically ventilated adults comparing an IV benzodiazepine-based to a nonbenzodiazepine-based sedative regimen and reported duration of ICU length of stay, duration of mechanical ventilation, delirium prevalence, and/or short-term mortality. Trial characteristics and results were abstracted in duplicate and independently, and the Cochrane risk of bias tool was used for quality assessment. We performed random effects model meta-analyses where possible. Results:We included six trials enrolling 1,235 patients: midazolam versus dexmedetomidine (n = 3), lorazepam versus dexmedetomidine (n = 1), midazolam versus propofol (n = 1), and lorazepam versus propofol (n = 1). Compared to a benzodiazepine sedative strategy, a nonbenzodiazepine sedative strategy was associated with a shorter ICU length of stay (n = 6 studies; difference = 1.62 d; 95% CI, 0.68–2.55; I2 = 0%; p = 0.0007) and duration of mechanical ventilation (n = 4 studies; difference = 1.9 d; 95% CI, 1.70–2.09; I2 = 0%; p < 0.00001) but a similar prevalence of delirium (n = 2; risk ratio = 0.83; 95% CI, 0.61–1.11; I2 = 84%; p = 0.19) and short-term mortality rate (n = 4; risk ratio = 0.98; 95% CI, 0.76–1.27; I2 = 30%; p = 0.88). Conclusions:Current controlled data suggest that use of a dexmedetomidine- or propofol-based sedation regimen rather than a benzodiazepine-based sedation regimen in critically ill adults may reduce ICU length of stay and duration of mechanical ventilation. Larger controlled studies are needed to further define the impact of nonbenzodiazepine sedative regimens on delirium and short-term mortality.

Fluid Resuscitation in Sepsis: A Systematic Review and Network Meta-analysis

Resuscitation with crystalloids compared with colloids for critically ill patients has been evaluated in large randomized, controlled trials (16) and meta-analyses (713). One meta-analysis(10) including 74 trials reported no difference in mortality between critically ill patients resuscitated with crystalloids and albumin (relative risk [RR], 1.01 [95% CI, 0.93 to 1.10]), hydroxyethyl starch (HES) (RR, 1.10 [CI, 0.91 to 1.32]), gelatin (RR, 0.91 [CI, 0.49 to 1.72]), or dextran (RR, 1.24 [CI, 0.94 to 1.65]). Another meta-analysis (8) reported that resuscitation with an albumin-containing solution in patients with sepsis may decrease mortality compared with solutions containing no albumin (RR, 0.82 [CI, 0.67 to 1.00]). Recent evidence suggests that starches, compared with other fluids and regardless of molecular weight, may be associated with acute kidney injury in the general population of critically ill patients and in those with sepsis (5, 11, 1315). A recent large pragmatic trial comparing colloids (mostly starches) with crystalloids (mostly 0.9% sodium chloride) suggested a 90-day mortality benefit with colloids (RR, 0.92 [CI, 0.86 to 0.99]) (16). Crystalloids can be characterized on the basis of tonicity and electrolyte content. The presence of an organic anion (for example, lactate, acetate, or gluconate) and correspondingly lower chloride content that more closely resembles the composition of plasma suggest that a crystalloid is balanced (for example, Ringer lactate and acetate solutions) (17). The most commonly used crystalloid, normal saline (0.9% sodium chloride), is far from normal, with a pH much less than 7.0 and a supraphysiologic chloride content of 154 mmol/L (18, 19). Compared with a balanced crystalloid solution, normal saline predisposes patients to hyperchloremic metabolic acidosis, decreased renal blood flow to the glomerulus, and impaired smooth-muscle contractility (20). Investigators have not done randomized, controlled trials (RCTs) comparing balanced and unbalanced crystalloids. However, 1 large beforeafter study of critically ill patients showed that balanced versus unbalanced fluid solution was associated with a lower incidence of acute kidney injury (8.4% vs. 14%; P< 0.01) and renal replacement therapy (6.3% vs. 10%; P= 0.05) but no differences in hospital mortality (18). Colloids include natural compounds, such as albumin, and synthetic compounds of HES, gelatin, or dextran. Expansion of plasma volume increases in proportion to the osmotic or oncotic potential, and colloids theoretically require less volume than crystalloids to achieve equivalent hemodynamic effect (19). Limitations of colloids include development of acute kidney injury and coagulation disorders with starches (14) and albumin creates risk for exposure to blood products (19). Another important consideration is the biochemical properties of the crystalloid solution in which the colloid is dissolved. For example, the chloride concentrations in HES may vary between 154 mmol/L (Voluven, Fresenius Kabi) and 118 mmol/L (Tetraspan, B. Braun Medical) (21). Whether any of these fluid properties translate into a survival advantage remains unclear, particularly regarding the optimal fluid for resuscitation in patients with sepsis. Fluid resuscitation, in addition to antibiotics and source control, is a cornerstone of initial management of sepsis (22). However, fluid management in patients with sepsis varies widely in practice (16, 23, 24). Meta-analyses of fluid resuscitation have been limited by not focusing on patients with sepsis (7, 9, 10), not considering electrolyte composition (5, 8, 10, 11), considering only 2 or 3 categories of fluid (25), not including direct and indirect comparisons in the same model, and omission of recent large RCTs(35, 16). Therefore, we did a network meta-analysis (NMA) considering direct and indirect comparisons of all types of fluid resuscitation tested in RCTs in patients with severe sepsis and septic shock, focusing on the effect of these interventions on mortality. Methods Data Sources and Searches This review was done using a predefined protocol. Initially, we searched MEDLINE (1948 to December 2012), EMBASE (1980 to December 2012), ACP Journal Club (1991 to December 2012), the Cochrane Central Register of Controlled Trials, HealthSTAR, the Allied and Complementary Medicine Database, and CINAHL. We updated the MEDLINE and EMBASE searches in August 2013 and March 2014. We screened previously published meta-analyses for relevant citations. Supplement 1 presents the search terms used. Supplement 1. WinBUGS Code for NMA Six reviewers working in 3 pairs screened the titles and abstracts to determine potential eligibility, and entries identified by any reviewer proceeded to the full-text eligibility review. Pretested eligibility forms were used for full-text review, which was also done in duplicate. A third adjudicator helped to resolve disagreements through consensus. Study Selection We selected parallel-group RCTs, including factorial designs, but excluded quasi-randomized and crossover trials. We excluded all studies published by Dr. Joachim Boldt because of suspected lack of integrity (26, 27). We did not apply restrictions on language or publication date. We included studies that involved adult (aged 16 years) critically ill patients with severe sepsis or septic shock as defined by the investigators and who required fluid resuscitation (defined as the administration of a bolus of intravenous fluid exceeding the amount required for maintenance or replacement fluids). We included studies with mixed critically ill populations whenever separate data for patients with sepsis were available. We excluded studies in which most patients had the systemic inflammatory response syndrome secondary to other causes (such as burn, pancreatitis, and trauma) without a clear sepsis subgroup and those focusing on patients after elective surgery. Interventions studied included any fluid or fluid strategy used for resuscitation compared with another fluid or fluid strategy. We excluded studies in which the primary goal was to assess short-term hemodynamic response. Our outcome was 90-day mortality or, if not available, 30-day, intensive care unit, or hospital mortality, whichever was longest. Data Extraction Pairs from the same 6 reviewers abstracted data in duplicate. Another clinician reviewed disagreements, and consensus was reached by discussion. We contacted authors of primary publications for missing or unclear information. Risk of Bias Independently and in duplicate, reviewers assessed risk of bias using a modified version of the Cochrane Collaboration assessment tool (28, 29). We judged each included study as having low, probably low, probably high, or high risk of bias for randomization-sequence generation, randomization concealment, blinding, incomplete data, selective reporting, and free of other bias (including intention-to-treat analysis). The overall rating of risk of bias for each study was the lowest rating for any of the criteria (Appendix Table). Appendix Table. Risk of Bias, by Study Data Synthesis and Analysis Our analysis classified fluids as crystalloids (divided into balanced and unbalanced solutions) and colloids (divided into albumin, gelatin, and low- and high-molecular-weight HES [threshold molecular weight, 150000 kDa]). We considered fluid balanced if it contained an anion of a weak acid (buffer) and its chloride content was correspondingly less than in 0.9% sodium chloride (21). The relevant analyses were a 4-node NMA (crystalloids vs. albumin vs. HES vs. gelatin), a 6-node NMA (crystalloids vs. albumin vs. HES vs. gelatin, with crystalloids divided into balanced or unbalanced and HES divided into low or high molecular weight), and a conventional direct frequentist fixed-effects meta-analytic comparison of crystalloids versus colloids. To calculate direct estimates of treatment effect for each pair of treatments in the 4- and 6-node networks, we did a frequentist fixed-effects meta-analysis. We reported the results as odds ratios (ORs) and corresponding 95% CIs. We evaluated heterogeneity by estimating the variance between studies (chi-square test and I 2 statistic) (30, 31). Using a Bayesian framework, we did 4- and 6-node fixed-effects NMAs for each treatment. We reported the results as ORs and corresponding 95% credibility intervals (CrIs), which are the Bayesian analogue of 95% CIs(32). The ORs reported are relative effects of compared fluids. The models are based on 80000 iterations with a burn-in of 40000 and a thin of 10. We used a random seed and vague priors. We assessed nonconvergence on the basis of BrooksGelmanRubin plots (33). We used the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach to assess confidence in estimates of effect (quality of evidence) associated with specific comparisons, including estimates from direct, indirect, and final NMAs (Supplement 2) (34). Our confidence assessment addressed risk of bias, incoherence, imprecision, inconsistency, indirectness, and publication bias. Supplement 2. GRADE Confidence Explanations for All Point Estimates The starting point for confidence in direct and indirect estimates was high. However, indirect estimates were potentially rated down for intransitivity (that is, differences in patients, co-interventions, or settings that could lead to effect modification and thus a misleading comparison of fluid management strategies). We inferred confidence in indirect estimates by examining the connecting loops associated with the particular comparison. The confidence rating chosen was the lowest of the direct estimates contributing to the indirect comparison. For example, consider a comparison of A versus B that is informed by comparisons of A versus C and B versus C. If A versus C was rated as high confidence and B versus C as moderate confidence, the overall indirect confidence rating was ini

Neuromuscular blocking agents in acute respiratory distress syndrome: a systematic review and meta-analysis of randomized controlled trials

IntroductionRandomized trials investigating neuromuscular blocking agents in adult acute respiratory distress syndrome (ARDS) have been inconclusive about effects on mortality, which is very high in this population. Uncertainty also exists about the associated risk of ICU-acquired weakness.MethodsWe conducted a systematic review and meta-analysis. We searched the Cochrane (Central) database, MEDLINE, EMBASE, ACP Journal Club, and clinical trial registries for randomized trials investigating survival effects of neuromuscular blocking agents in adults with ARDS. Two independent reviewers abstracted data and assessed methodologic quality. Primary study investigators provided additional unpublished data.ResultsThree trials (431 patients; 20 centers; all from the same research group in France) met inclusion criteria for this review. All trials assessed 48-hour infusions of cisatracurium besylate. Short-term infusion of cisatracurium besylate was associated with lower hospital mortality (RR, 0.72; 95% CI, 0.58 to 0.91; P = 0.005; I2 = 0). This finding was robust on sensitivity analyses. Neuromuscular blockade was also associated with lower risk of barotrauma (RR, 0.43; 95% CI, 0.20 to 0.90; P = 0.02; I2 = 0), but had no effect on the duration of mechanical ventilation among survivors (MD, 0.25 days; 95% CI, 5.48 to 5.99; P = 0.93; I2 = 49%), or the risk of ICU-acquired weakness (RR, 1.08; 95% CI, 0.83 to 1.41; P = 0.57; I2 = 0). Primary studies lacked protracted measurements of weakness.ConclusionsShort-term infusion of cisatracurium besylate reduces hospital mortality and barotrauma and does not appear to increase ICU-acquired weakness for critically ill adults with ARDS.

Chronic Subdural Hematoma Management: A Systematic Review and Meta-analysis of 34829 Patients

Objective:To compare the efficacy and safety of multiple treatment modalities for the management of chronic subdural hematoma (CSDH) patients. Background:Current management strategies of CSDHs remain widely controversial. Treatment options vary from medical therapy and bedside procedures to major operative techniques. Methods:We searched MEDLINE (PubMed and Ovid), EMBASE, CINAHL, Google scholar, and the Cochrane library from January 1970 through February 2013 for randomized and observational studies reporting one or more outcome following the management of symptomatic patients with CSDH. Independent reviewers evaluated the quality of studies and abstracted the data on the safety and efficacy of percutaneous bedside twist-drill drainage, single or multiple operating room burr holes, craniotomy, corticosteroids as a main or adjuvant therapy, use of drains, irrigation of the hematoma cavity, bed rest, and treatment of recurrences following CSDH management. Mortality, morbidity, cure, and recurrence rates were examined for each management option. Randomized, prospective, retrospective, and overall observational studies were analyzed separately. Pooled estimates, confidence intervals (CIs), and relative risks (RRs) were calculated for all outcomes using a random-effects model. Results:A total of 34,829 patients from 250 studies met our eligibility criteria. Sixteen trials were randomized, and the remaining 234 were observational. We included our unpublished single center series of 834 patients. When comparing percutaneous bedside drainage to operating room burr hole evacuation, there was no significant difference in mortality (RR, 0.69; 95% CI, 0.46–1.05; P = 0.09), morbidity (RR, 0.45; 95% CI, 0.2–1.01; P = 0.05), cure (RR, 1.05; 95% CI, 0.98–1.11; P = 0.15), and recurrence rates (RR, 1; 95% CI, 0.66–1.52; P = 0.99). Higher morbidity was associated with the adjuvant use of corticosteroids (RR, 1.97; 95% CI, 1.54–2.45; P = 0.005), with no significant improvement in recurrence and cure rates. The use of drains following CSDH drainage resulted in a significant decrease in recurrences (RR, 0.46; 95% CI, 0.27–0.76; P = 0.002). Craniotomy was associated with higher complication rates if considered initially (RR, 1.39; 95% CI, 1.04–1.74; P = 0.01); however, craniotomy was superior to minimally invasive procedures in the management of recurrences (RR, 0.22; 95% CI, 0.05–0.85; P = 0.003). Conclusions:Percutaneous bedside twist-drill drainage is a relatively safe and effective first-line management option. These findings may result in potential health cost savings and eliminate perioperative risks related to general anesthetic.

The effect of selenium therapy on mortality in patients with sepsis syndrome: a systematic review and meta-analysis of randomized controlled trials.

Background:Patients with sepsis syndrome commonly have low serum selenium levels. Several randomized controlled trials have examined the efficacy of selenium supplementation on mortality in patients with sepsis. Objective:To determine the efficacy and safety of high-dose selenium supplementation compared to placebo for the reduction of mortality in patients with sepsis. Sources of Data:We searched Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE, SciFinder, and Clinicaltrials.gov. Selection Criteria:Randomized controlled parallel group trials comparing selenium supplementation in doses greater than daily requirement to placebo on the outcome of mortality in patients with sepsis syndrome. Data Collection and Analysis:Two reviewers independently applied eligibility criteria, assessed quality, and extracted data. The primary outcome was mortality; secondary outcomes were ICU length of stay, nosocomial pneumonia, and adverse events. Trial authors were contacted for additional or clarifying information. Results:Nine trials enrolling a total of 792 patients were included. Selenium supplementation in comparison to placebo was associated with lower mortality (odds ratio, 0.73; 95% CI, 0.54, 0.98; p = 0.03; I2 = 0%). Among patients receiving and not receiving selenium, there was no difference in ICU length of stay (mean difference, 2.03; 95% CI, –0.51, 4.56; p = 0.12; I2 = 0%) or nosocomial pneumonia (odds ratio, 0.83; 95% CI, 0.28, 2.49; p = 0.74; I2 = 56%). Significant heterogeneity among trials in adverse event reporting precluded pooling of results. Conclusions:In patients with sepsis, selenium supplementation at doses higher than daily requirement may reduce mortality. We observed no impact of selenium on ICU length of stay or risk of nosocomial pneumonia.

Toothbrushing for Critically Ill Mechanically Ventilated Patients: A Systematic Review and Meta-analysis of Randomized Trials Evaluating Ventilator-associated Pneumonia*

Background:Oral care may decrease ventilator-associated pneumonia in the ICU. The objective of this review was to summarize and critically appraise randomized trials in mechanically ventilated patients in the ICU testing the effect of oral care strategies involving toothbrushing on ventilator-associated pneumonia. Search Methods:We searched EMBASE, MEDLINE, and the Cochrane Controlled Trials Register and Database of Systematic Reviews from 1980 until March 2012, independently and in duplicate, as well as personal files and reference lists. In duplicate, articles were selected if they were randomized trials, enrolled adult critically ill patients, compared any kind of oral care involving toothbrushing with any other kind of oral care or control with or without toothbrushing, and examined ventilator-associated pneumonia. In duplicate, we abstracted trial characteristics and quality using the Cochrane risk of bias tool. The results were combined using a random effects model. Results:We included six trials enrolling 1,408 patients, five of which compared toothbrushing to usual oral care and one of which compared electric with manual toothbrushing. In four trials, there was a trend toward lower ventilator-associated pneumonia rates (risk ratio, 0.77; 95% confidence interval, 0.50–1.21; p = 0.26). This trend was also observed in one trial reporting fewer cases of ventilator-associated pneumonia per 1,000 ventilator days (20.68 vs. 25.89; p = 0.53) in patients receiving toothbrushing vs. no toothbrushing. The only trial with low risk of bias suggested that toothbrushing significantly reduced ventilator-associated pneumonia (risk ratio, 0.26; 95% confidence interval, 0.10–0.67; p = 0.006). Use of chlorhexidine antisepsis seems to attenuate the effect of toothbrushing on ventilator-associated pneumonia (p for the interaction = 0.02). One trial comparing electric vs. manual toothbrushing showed no difference in ventilator-associated pneumonia rates (risk ratio, 0.96; 95% confidence interval, 0.47–1.96; p = 0.91). Toothbrushing did not impact on length of ICU stay, or ICU or hospital mortality. Conclusions:In intubated, mechanically ventilated critically ill patients, toothbrushing did not significantly reduce the risk of ventilator-associated pneumonia overall. Toothbrushing has no effect on mortality or length of stay. Electric and manual toothbrushing seem to have similar effects. More research is needed on this aspect of oral care to evaluate its potential to decrease ventilator-associated pneumonia.

Heparin thromboprophylaxis in medical-surgical critically ill patients: a systematic review and meta-analysis of randomized trials.

Objective:Venous thromboembolism prevention during critical illness is a widely used quality metric. The objective of this systematic review was to systematically review the efficacy and safety of heparin thromboprophylaxis in medical-surgical patients in the ICU. Data Sources:We searched EMBASE, MEDLINE, the Cochrane Controlled Trials Register, Clinicaltrials.gov, and personal files through May 2012. Study Selection:Randomized trials in adult medical-surgical ICU patients comparing any heparin (unfractionated heparin or low-molecular-weight heparin) with each other or no anticoagulant prophylaxis, evaluating deep vein thrombosis, pulmonary embolism, major bleeding, or mortality. Data Extraction:Independently, in duplicate, we abstracted trial characteristics, outcomes, and risk of bias. Data Synthesis:Seven trials involved 7,226 patients. Any heparin thromboprophylaxis compared with placebo reduced rates of deep vein thrombosis (pooled risk ratio, 0.51 [95% CI, 0.41, 0.63]; p < 0.0001; I2 = 77%) and pulmonary embolism (risk ratio, 0.52 [95% CI, 0.28, 0.97]; p = 0.04; I2 = 0%) but not symptomatic deep vein thrombosis (risk ratio, 0.86 [95% CI, 0.59, 1.25]; p = 0.43). Major bleeding (risk ratio, 0.82 [95% CI, 0.56, 1.21]; p = 0.32; I2 = 50%) and mortality (risk ratio, 0.89 [95% CI, 0.78, 1.02]; p = 0.09; I2 = 0%) rates were similar. Compared with unfractionated heparin, low-molecular-weight heparin reduced rates of pulmonary embolism (risk ratio, 0.62 [95% CI, 0.39, 1.00]; p = 0.05; I2 = 53%) and symptomatic pulmonary embolism (risk ratio, 0.58 [95% CI, 0.34, 0.97]; p = 0.04) but not deep vein thrombosis (risk ratio, 0.90 [95% CI, 0.74, 1.08]; p = 0.26; I2 = 0%), symptomatic deep vein thrombosis (risk ratio, 0.87 [95% CI, 0.60, 1.25]; p = 0.44; I2 = 0%), major bleeding (risk ratio, 0.97 [95% CI, 0.75, 1.26]; p = 0.83; I2 = 0%), or mortality (risk ratio, 0.93 [95% CI, 0.82, 1.04]; p = 0.20; I2 = 31%). Conclusions:Trial evidence to date suggests that any type of heparin thromboprophylaxis decreases deep vein thrombosis and pulmonary embolism in medical-surgical critically ill patients, and low-molecular-weight heparin compared with bid unfractionated heparin decreases pulmonary embolism and symptomatic pulmonary embolism. Major bleeding and mortality rates do not appear to be significantly influenced by heparin thromboprophylaxis in the ICU setting. Trial methodology, indirectness, and the heterogeneity and imprecision of some results temper inferences from this literature.

Liberation From Mechanical Ventilation in Critically Ill Adults: An Official American College of Chest Physicians/American Thoracic Society Clinical Practice Guideline: Inspiratory Pressure Augmentation During Spontaneous Breathing Trials, Protocols Minimizing Sedation, and Noninvasive Ventilation Immediately After Extubation.

Background An update of evidence‐based guidelines concerning liberation from mechanical ventilation is needed as new evidence has become available. The American College of Chest Physicians (CHEST) and the American Thoracic Society (ATS) have collaborated to provide recommendations to clinicians concerning liberation from the ventilator. Methods Comprehensive evidence syntheses, including meta‐analyses, were performed to summarize all available evidence relevant to the guideline panel’s questions. The evidence was appraised using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) approach, and the results were summarized in evidence profiles. The evidence syntheses were discussed and recommendations developed and approved by a multidisciplinary committee of experts in mechanical ventilation. Results Recommendations for three population, intervention, comparator, outcome (PICO) questions concerning ventilator liberation are presented in this document. The guideline panel considered the balance of desirable (benefits) and undesirable (burdens, adverse effects, costs) consequences, quality of evidence, feasibility, and acceptability of various interventions with respect to the selected questions. Conditional (weak) recommendations were made to use inspiratory pressure augmentation in the initial spontaneous breathing trial (SBT) and to use protocols to minimize sedation for patients ventilated for more than 24 h. A strong recommendation was made to use preventive noninvasive ventilation (NIV) for high‐risk patients ventilated for more than 24 h immediately after extubation to improve selected outcomes. The recommendations were limited by the quality of the available evidence. Conclusions The guideline panel provided recommendations for inspiratory pressure augmentation during an initial SBT, protocols minimizing sedation, and preventative NIV, in relation to ventilator liberation.