The cuff leak test in critically ill patients: An international survey of intensivists.

BACKGROUND: The cuff leak test (CLT) is used to assess laryngeal edema prior to extubation. There is limited evidence for its diagnostic accuracy and conflicting guidelines surrounding its use in critically ill patients who do not have risk factors for laryngeal edema. The primary study aim was to describe intensivists' beliefs, attitudes, and practice regarding the use of the CLT. METHODS: A 13-item survey was developed, pilot-tested, and subjected to clinical sensibility testing. The survey was distributed electronically through MetaClinician®. Descriptive statistics and multivariable regression analysis were performed to examine associations between participant demographics and survey responses. RESULTS: 1184 practicing intensivists from 17 countries in North and South America, Europe, Oceania, and Asia participated. The majority (59%) of respondents reported rarely or never perform the CLT prior to extubating patients not at high risk of laryngeal edema, which correlated with 54% of respondents reporting they believed a failed CLT did not predict reintubation. Intensivists from the Middle East were 2.4 times more likely to request a CLT compared to those from North America. Intensivists with base training in medicine or emergency medicine were more likely to request a CLT prior to extubation compared to those with base training in anesthesiology. CONCLUSION: Use of the CLT prior to extubating patients not at high risk of laryngeal edema in the intensive care unit is highly variable. Practice appears to be influenced by country of practice and base specialty training.

Scale-up and sustainability of a personalized end-of-life care intervention: a longitudinal mixed-methods study.

BACKGROUND: Scaling-up and sustaining healthcare interventions can be challenging. Our objective was to describe how the 3 Wishes Project (3WP), a personalized end-of-life intervention, was scaled-up and sustained in an intensive care unit (ICU). METHODS: In a longitudinal mixed-methods study from January 12,013 - December 31, 2018, dying patients and families were invited to participate if the probability of patient death was > 95% or after a decision to withdraw life support. A research team member or bedside clinician learned more about each of the patients and their family, then elicited and implemented at least 3 personalized wishes for patients and/or family members. We used a qualitative descriptive approach to analyze interviews and focus groups conducted with 25 clinicians who cared for the enrolled patients. We used descriptive statistics to summarize patient, wish, and clinician characteristics, and analyzed outcome data in quarters using Statistical Process Control charts. The primary outcome was enrollment of terminally ill patients and respective families; the secondary outcome was the number of wishes per patient; tertiary outcomes included wish features and stakeholder involvement. RESULTS: Both qualitative and quantitative analyses suggested a three-phase approach to the scale-up of this intervention during which 369 dying patients were enrolled, having 2039 terminal wishes implemented. From a research project to clinical program to an approach to practice, we documented a three-fold increase in enrolment with a five-fold increase in total wishes implemented, without a change in cost. Beginning as a study, the protocol provided structure; starting gradually enabled frontline staff to experience and recognize the value of acts of compassion for patients, families, and clinicians. The transition to a clinical program was marked by handover from the research staff to bedside staff, whereby project catalysts mentored project champions to create staff partnerships, and family engagement became more intentional. The final transition involved empowering staff to integrate the program as an approach to care, expanding it within and beyond the organization. CONCLUSIONS: The 3WP is an end-of-life intervention which was implemented as a study, scaled-up into a clinical program, and sustained by becoming integrated into practice as an approach to care.

Mortality and morbidity in acutely ill adults treated with liberal versus conservative oxygen therapy (IOTA): a systematic review and meta-analysis.

BACKGROUND: Supplemental oxygen is often administered liberally to acutely ill adults, but the credibility of the evidence for this practice is unclear. We systematically reviewed the efficacy and safety of liberal versus conservative oxygen therapy in acutely ill adults. METHODS: In the Improving Oxygen Therapy in Acute-illness (IOTA) systematic review and meta-analysis, we searched the Cochrane Central Register of Controlled Trials, MEDLINE, Embase, HealthSTAR, LILACS, PapersFirst, and the WHO International Clinical Trials Registry from inception to Oct 25, 2017, for randomised controlled trials comparing liberal and conservative oxygen therapy in acutely ill adults (aged ≥18 years). Studies limited to patients with chronic respiratory diseases or psychiatric disease, patients on extracorporeal life support, or patients treated with hyperbaric oxygen therapy or elective surgery were excluded. We screened studies and extracted summary estimates independently and in duplicate. We also extracted individual patient-level data from survival curves. The main outcomes were mortality (in-hospital, at 30 days, and at longest follow-up) and morbidity (disability at longest follow-up, risk of hospital-acquired pneumonia, any hospital-acquired infection, and length of hospital stay) assessed by random-effects meta-analyses. We assessed quality of evidence using the grading of recommendations assessment, development, and evaluation approach. This study is registered with PROSPERO, number CRD42017065697. FINDINGS: 25 randomised controlled trials enrolled 16 037 patients with sepsis, critical illness, stroke, trauma, myocardial infarction, or cardiac arrest, and patients who had emergency surgery. Compared with a conservative oxygen strategy, a liberal oxygen strategy (median baseline saturation of peripheral oxygen [SpO2] across trials, 96% [range 94-99%, IQR 96-98]) increased mortality in-hospital (relative risk [RR] 1·21, 95% CI 1·03-1·43, I2=0%, high quality), at 30 days (RR 1·14, 95% CI 1·01-1·29, I2=0%, high quality), and at longest follow-up (RR 1·10, 95% CI 1·00-1·20, I2=0%, high quality). Morbidity outcomes were similar between groups. Findings were robust to trial sequential, subgroup, and sensitivity analyses. INTERPRETATION: In acutely ill adults, high-quality evidence shows that liberal oxygen therapy increases mortality without improving other patient-important outcomes. Supplemental oxygen might become unfavourable above an SpO2 range of 94-96%. These results support the conservative administration of oxygen therapy. FUNDING: None.

Atraumatic versus conventional lumbar puncture needles: a systematic review and meta-analysis.

BACKGROUND: Atraumatic needles have been proposed to lower complication rates after lumbar puncture. However, several surveys indicate that clinical adoption of these needles remains poor. We did a systematic review and meta-analysis to compare patient outcomes after lumbar puncture with atraumatic needles and conventional needles. METHODS: In this systematic review and meta-analysis, we independently searched 13 databases with no language restrictions from inception to Aug 15, 2017, for randomised controlled trials comparing the use of atraumatic needles and conventional needles for any lumbar puncture indication. Randomised trials comparing atraumatic and conventional needles in which no dural puncture was done (epidural injections) or without a conventional needle control group were excluded. We screened studies and extracted data from published reports independently. The primary outcome of postdural-puncture headache incidence and additional safety and efficacy outcomes were assessed by random-effects and fixed-effects meta-analysis. This study is registered with the International Prospective Register of Systematic Reviews, number CRD42016047546. FINDINGS: We identified 20 241 reports; after exclusions, 110 trials done between 1989 and 2017 from 29 countries, including a total of 31 412 participants, were eligible for analysis. The incidence of postdural-puncture headache was significantly reduced from 11·0% (95% CI 9·1-13·3) in the conventional needle group to 4·2% (3·3-5·2) in the atraumatic group (relative risk 0·40, 95% CI 0·34-0·47, p<0·0001; I2=45·4%). Atraumatic needles were also associated with significant reductions in the need for intravenous fluid or controlled analgesia (0·44, 95% CI 0·29-0·64; p<0·0001), need for epidural blood patch (0·50, 0·33-0·75; p=0·001), any headache (0·50, 0·43-0·57; p<0·0001), mild headache (0·52, 0·38-0·70; p<0·0001), severe headache (0·41, 0·28-0·59; p<0·0001), nerve root irritation (0·71, 0·54-0·92; p=0·011), and hearing disturbance (0·25, 0·11-0·60; p=0·002). Success of lumbar puncture on first attempt, failure rate, mean number of attempts, and the incidence of traumatic tap and backache did not differ significantly between the two needle groups. Prespecified subgroup analyses of postdural-puncture headache revealed no interactions between needle type and patient age, sex, use of prophylactic intravenous fluid, needle gauge, patient position, indication for lumbar puncture, bed rest after puncture, or clinician specialty. These results were rated high-quality evidence as examined using the grading of recommendations assessment, development, and evaluation. INTERPRETATION: Among patients who had lumbar puncture, atraumatic needles were associated with a decrease in the incidence of postdural-puncture headache and in the need for patients to return to hospital for additional therapy, and had similar efficacy to conventional needles. These findings offer clinicians and stakeholders a comprehensive assessment and high-quality evidence for the safety and efficacy of atraumatic needles as a superior option for patients who require lumbar puncture. FUNDING: None.

Chloride and Other Electrolyte Concentrations in Commonly Available 5% Albumin Products.

OBJECTIVE: Use of hyperchloremic IV fluids for resuscitation in sepsis may be associated with increased mortality and use of renal replacement therapy. After crystalloids, 5% human albumin represents the second most common resuscitation fluid in the ICU. Its chloride concentration is rarely considered in the clinical setting. This study quantifies previously undocumented chloride concentrations of three 5% albumin solutions using biochemical analysis. DESIGN: We performed blinded analysis of the electrolyte concentration of albumin samples obtained directly from the national blood supplier (Canadian Blood Services). Two-tailed independent t tests were performed for all possible comparative analyses. Analysis of variance testing was performed for relevant three-way comparisons. Significance threshold was set at p less than 0.05. SETTING: All samples were analyzed in the core laboratory at an academic hospital associated with McMaster University in Hamilton, Ontario, Canada. SUBJECTS: We analyzed 65 albumin samples from three available brands obtained through Canadian Blood Services. They include Plasbumin (n = 21), Alburex (n = 24), Octalbin (n = 20). INTERVENTION: Laboratory technologists blinded to product identification measured the concentration of electrolytes, extended electrolytes, lactate, and albumin of each sample using the Abbott ARCHITECT c8000 chemistry analyzer. MEASUREMENTS AND MAIN RESULTS: The mean chloride concentration of Plasbumin, Alburex, and Octalbin, respectively, were 109.4 mmol/L (SD, 1.3), 123.6 mmol/L (SD, 1.3), and 136.8 mmol/L (SD, 0.4). The mean sodium concentration of Plasbumin, Alburex, and Octalbin, respectively, were 139.6 mmol/L (SD, 1.6), 137.3 mmol/L (SD, 2.2), and 149.4 mmol/L (SD, 0.5). The chloride and sodium concentration differed significantly for all two-way comparisons (p < 0.0001) and multiple comparison testing (p < 0.0001). CONCLUSION: This study is the first to identify and document a statistically significant variability in the chloride concentration of available 5% albumin products. This study has also informed a pilot randomized controlled trial examining the effect of administering high chloride versus low chloride fluids in critically ill patients with sepsis.

Fluid resuscitation in sepsis: a systematic review and network meta-analysis.

BACKGROUND: Fluid resuscitation is the cornerstone of sepsis treatment. However, whether balanced or unbalanced crystalloids or natural or synthetic colloids confer a survival advantage is unclear. PURPOSE: To examine the effect of different resuscitative fluids on mortality in patients with sepsis. DATA SOURCES: MEDLINE, EMBASE, ACP Journal Club, CINAHL, HealthSTAR, the Allied and Complementary Medicine Database, and the Cochrane Central Register of Controlled Trials through March 2014. STUDY SELECTION: Randomized trials that evaluated different resuscitative fluids in adult patients with sepsis or septic shock and death. No language restrictions were applied. DATA EXTRACTION: Two reviewers extracted data on study characteristics, methods, and outcomes. Risk of bias for individual studies and quality of evidence were assessed. DATA SYNTHESIS: 14 studies (18916 patients) were included with 15 direct comparisons. Network meta-analysis at the 4-node level showed higher mortality with starches than with crystalloids (high confidence) and lower mortality with albumin than with crystalloids (moderate confidence) or starches (moderate confidence). Network meta-analysis at the 6-node level showed lower mortality with albumin than with saline (moderate confidence) and low-molecular-weight starch (low confidence) and with balanced crystalloids than with saline (low confidence) and low- and high-molecular-weight starches (moderate confidence). LIMITATIONS: These trials were heterogeneous in case mix, fluids evaluated, duration of fluid exposure, and risk of bias. Imprecise estimates for several comparisons in this network meta-analysis contribute to low confidence in most estimates of effect. CONCLUSION: Among patients with sepsis, resuscitation with balanced crystalloids or albumin compared with other fluids seems to be associated with reduced mortality. PRIMARY FUNDING SOURCE: The Hamilton Chapter of the Canadian Intensive Care Foundation and the Critical Care Medicine Residency Program and Critical Care Division Alternate Funding Plan at McMaster University.

Digitalis for treatment of heart failure in patients in sinus rhythm.

BACKGROUND: Digitalis glycosides have been in clinical use for the treatment of heart failure (HF) for longer than 200 years. In recent years, several trials have been conducted to address concerns about their efficacy and toxicity. OBJECTIVES: To examine the effectiveness of digitalis glycosides in treating HF in patients with normal sinus rhythm. To examine the effects of digitalis in patients taking diuretics and angiotensin-converting enzyme inhibitors; in patients with varying severity and duration of disease; in patients with prior exposure to digitalis versus no prior exposure; and in patients with "HF due to systolic dysfunction" versus "HF with preserved ejection fraction." SEARCH METHODS: Searches on the following databases were updated in May 2013: The Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, and Dissertation Abstracts. Annual meeting abstracts of the American Heart Association, the American College of Cardiology, and the European Society of Cardiology were searched from 1996 to March 2013. In addition, reference lists provided by the pharmaceutical industry (GlaxoSmithKline and Covis Pharma) were searched. SELECTION CRITERIA: Included were randomized placebo-controlled trials of 20 or more adult participants of either sex with symptomatic HF who were studied for seven weeks or longer. Excluded were trials in which the prevalence of atrial fibrillation was 2% or greater, or in which any arrhythmia that might compromise cardiac function or any potentially reversible cause of HF such as acute ischemic heart disease or myocarditis was present. DATA COLLECTION AND ANALYSIS: Articles selected from the searches described above were evaluated in a joint effort of the review authors. The staff of the Cochrane Heart Group ran searches on the Cochrane Central Register of Controlled Trials, MEDLINE, and EMBASE. MAIN RESULTS: No new studies were identified in the updated searches. Thirteen studies (7896 participants) are included, and major endpoints of mortality, hospitalization, and clinical status, based respectively on 8, 4, and 12 of these selected studies, were recorded and analyzed. The data show no evidence of a difference in mortality between treatment and control groups, whereas digitalis therapy is associated with lower rates of both hospitalization and clinical deterioration. The largest study, in which most participants were taking angiotensin-converting enzyme inhibitors, showed a significant rise in "other cardiac" deaths, possibly due to arrhythmias. However collectively, these findings were based on studies done before beta-blockers, as well as angiotensin receptor blockers and aldosterone antagonists, became widely used to treat HF. AUTHORS' CONCLUSIONS: The literature indicates that digitalis may have a useful role in the treatment of patients with HF who are in normal sinus rhythm. New trials are needed to elucidate the importance of the dosage of digitalis and its usefulness in the era of beta-blockers and other agents shown to be effective in treating HF.

How to read a systematic review and meta-analysis and apply the results to patient care: users' guides to the medical literature.

Clinical decisions should be based on the totality of the best evidence and not the results of individual studies. When clinicians apply the results of a systematic review or meta-analysis to patient care, they should start by evaluating the credibility of the methods of the systematic review, ie, the extent to which these methods have likely protected against misleading results. Credibility depends on whether the review addressed a sensible clinical question; included an exhaustive literature search; demonstrated reproducibility of the selection and assessment of studies; and presented results in a useful manner. For reviews that are sufficiently credible, clinicians must decide on the degree of confidence in the estimates that the evidence warrants (quality of evidence). Confidence depends on the risk of bias in the body of evidence; the precision and consistency of the results; whether the results directly apply to the patient of interest; and the likelihood of reporting bias. Shared decision making requires understanding of the estimates of magnitude of beneficial and harmful effects, and confidence in those estimates.

Methods proposed for monitoring the implementation of evidence-based research: a cross-sectional study.

OBJECTIVES: Evidence-based research (EBR) is the systematic and transparent use of prior research to inform a new study so that it answers questions that matter in a valid, efficient, and accessible manner. This study surveyed experts about existing (e.g., citation analysis) and new methods for monitoring EBR and collected ideas about implementing these methods. STUDY DESIGN AND SETTING: We conducted a cross-sectional study via an online survey between November 2022 and March 2023. Participants were experts from the fields of evidence synthesis and research methodology in health research. Open-ended questions were coded by recurring themes; descriptive statistics were used for quantitative questions. RESULTS: Twenty-eight expert participants suggested that citation analysis should be supplemented with content evaluation (not just what is cited but also in which context), content expert involvement, and assessment of the quality of cited systematic reviews. They also suggested that citation analysis could be facilitated with automation tools. They emphasized that EBR monitoring should be conducted by ethics committees and funding bodies before the research starts. Challenges identified for EBR implementation monitoring were resource constraints and clarity on responsibility for EBR monitoring. CONCLUSION: Ideas proposed in this study for monitoring the implementation of EBR can be used to refine methods and define responsibility but should be further explored in terms of feasibility and acceptability. Different methods may be needed to determine if the use of EBR is improving over time.

The methodological approach used to develop the 2013 Pain, Agitation, and Delirium Clinical Practice Guidelines for adult ICU patients.

OBJECTIVE: In 2006, the American College of Critical Care Medicine assembled a 20-member task force to revise the 2002 guidelines for sedation and analgesia in critically ill adults. This article describes the methodological approach used to develop the American College of Critical Care Medicine's 2013 ICU Pain, Agitation, and Delirium Clinical Practice Guidelines. DESIGN: Review article. SETTING: Multispecialty critical care units. PATIENTS: Adult ICU patients. INTERVENTIONS: The task force was divided into four subcommittees, focusing on pain, sedation, delirium, and related outcomes. Unique aspects of this approach included the use of: 1) the Grading of Recommendations Assessment, Development and Evaluation method to evaluate the literature; 2) a librarian to conduct literature searches and to create and maintain the pain, agitation, and delirium database; 3) creation of a single web-based database; 4) rigorous psychometric analyses of pain, sedation, and delirium assessment tools; 5) the use of anonymous electronic polling; and 6) creation of an ICU pain, agitation, and delirium care bundle. RESULTS: The pain, agitation, and delirium database includes over 19,000 references. With the help of psychometric experts, members developed a scoring system and analyzed the psychometric properties of 6 behavioral pain scales, 10 sedation/agitation scales, and 5 delirium monitoring tools. A meta-analysis was performed to assess the overall impact of benzodiazepine versus nonbenzodiazepine sedation on ICU outcomes. The pain, agitation, and delirium guidelines include 54 evidence-based statements and recommendations. The quality of evidence and strength for each statement and recommendation was ranked. In the absence of sufficient evidence or group consensus, no recommendations were made. An ICU pain, agitation, and delirium care bundle was created to facilitate adoption of the pain, agitation, and delirium guidelines. It focuses on taking an integrated approach to assessing, treating, and preventing pain, agitation/sedation, and delirium in critically ill patients, and it links pain, agitation, and delirium management to spontaneous awakening trials, spontaneous breathing trials, and ICU early mobility and sleep hygiene programs in order to achieve synergistic benefits to ICU patient outcomes. CONCLUSIONS: The 2013 ICU pain, agitation, and delirium guidelines provide critical care providers with an evidence-based, integrated, and interdisciplinary approach to managing pain, agitation/sedation, and delirium. The methodological approach used to develop the guidelines ensures that they are rigorous, evidence-based, and transparent. Implementation of the ICU pain, agitation, and delirium care bundle is expected to have a significant beneficial impact on ICU outcomes and costs.

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 CRITERIA: Randomized 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; I = 0%) and overt upper gastrointestinal bleeding (relative risk 0.35; 95% confidence interval 0.21-0.59; p < 0.0001; I = 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; I = 0%), ICU mortality (relative risk 1.01; 95% confidence interval 0.83-1.24; p = 0.91; I = 0%), or ICU length of stay (mean difference -0.54 days; 95% confidence interval -2.20 to 1.13; p = 0.53; I = 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.

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; I=77%) and pulmonary embolism (risk ratio, 0.52 [95% CI, 0.28, 0.97]; p=0.04; I=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; I=50%) and mortality (risk ratio, 0.89 [95% CI, 0.78, 1.02]; p=0.09; I=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; I=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; I=0%), symptomatic deep vein thrombosis (risk ratio, 0.87 [95% CI, 0.60, 1.25]; p=0.44; I=0%), major bleeding (risk ratio, 0.97 [95% CI, 0.75, 1.26]; p=0.83; I=0%), or mortality (risk ratio, 0.93 [95% CI, 0.82, 1.04]; p=0.20; I=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.

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; I = 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; I = 0%) or nosocomial pneumonia (odds ratio, 0.83; 95% CI, 0.28, 2.49; p = 0.74; I = 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.

Clinical practice guidelines for the management of pain, agitation, and delirium in adult patients in the intensive care unit.

OBJECTIVE: To revise the "Clinical Practice Guidelines for the Sustained Use of Sedatives and Analgesics in the Critically Ill Adult" published in Critical Care Medicine in 2002. METHODS: The American College of Critical Care Medicine assembled a 20-person, multidisciplinary, multi-institutional task force with expertise in guideline development, pain, agitation and sedation, delirium management, and associated outcomes in adult critically ill patients. The task force, divided into four subcommittees, collaborated over 6 yr in person, via teleconferences, and via electronic communication. Subcommittees were responsible for developing relevant clinical questions, using the Grading of Recommendations Assessment, Development and Evaluation method (http://www.gradeworkinggroup.org) to review, evaluate, and summarize the literature, and to develop clinical statements (descriptive) and recommendations (actionable). With the help of a professional librarian and Refworks database software, they developed a Web-based electronic database of over 19,000 references extracted from eight clinical search engines, related to pain and analgesia, agitation and sedation, delirium, and related clinical outcomes in adult ICU patients. The group also used psychometric analyses to evaluate and compare pain, agitation/sedation, and delirium assessment tools. All task force members were allowed to review the literature supporting each statement and recommendation and provided feedback to the subcommittees. Group consensus was achieved for all statements and recommendations using the nominal group technique and the modified Delphi method, with anonymous voting by all task force members using E-Survey (http://www.esurvey.com). All voting was completed in December 2010. Relevant studies published after this date and prior to publication of these guidelines were referenced in the text. The quality of evidence for each statement and recommendation was ranked as high (A), moderate (B), or low/very low (C). The strength of recommendations was ranked as strong (1) or weak (2), and either in favor of (+) or against (-) an intervention. A strong recommendation (either for or against) indicated that the intervention's desirable effects either clearly outweighed its undesirable effects (risks, burdens, and costs) or it did not. For all strong recommendations, the phrase "We recommend …" is used throughout. A weak recommendation, either for or against an intervention, indicated that the trade-off between desirable and undesirable effects was less clear. For all weak recommendations, the phrase "We suggest …" is used throughout. In the absence of sufficient evidence, or when group consensus could not be achieved, no recommendation (0) was made. Consensus based on expert opinion was not used as a substitute for a lack of evidence. A consistent method for addressing potential conflict of interest was followed if task force members were coauthors of related research. The development of this guideline was independent of any industry funding. CONCLUSION: These guidelines provide a roadmap for developing integrated, evidence-based, and patient-centered protocols for preventing and treating pain, agitation, and delirium in critically ill patients.

Surviving sepsis campaign: international guidelines for management of severe sepsis and septic shock: 2012.

OBJECTIVE: To provide an update to the "Surviving Sepsis Campaign Guidelines for Management of Severe Sepsis and Septic Shock," last published in 2008. DESIGN: A consensus committee of 68 international experts representing 30 international organizations was convened. Nominal groups were assembled at key international meetings (for those committee members attending the conference). A formal conflict of interest policy was developed at the onset of the process and enforced throughout. The entire guidelines process was conducted independent of any industry funding. A stand-alone meeting was held for all subgroup heads, co- and vice-chairs, and selected individuals. Teleconferences and electronic-based discussion among subgroups and among the entire committee served as an integral part of the development. METHODS: The authors were advised to follow the principles of the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system to guide assessment of quality of evidence from high (A) to very low (D) and to determine the strength of recommendations as strong (1) or weak (2). The potential drawbacks of making strong recommendations in the presence of low-quality evidence were emphasized. Some recommendations were ungraded (UG). Recommendations were classified into three groups: 1) those directly targeting severe sepsis; 2) those targeting general care of the critically ill patient and considered high priority in severe sepsis; and 3) pediatric considerations. RESULTS: Key recommendations and suggestions, listed by category, include: early quantitative resuscitation of the septic patient during the first 6 hrs after recognition (1C); blood cultures before antibiotic therapy (1C); imaging studies performed promptly to confirm a potential source of infection (UG); administration of broad-spectrum antimicrobials therapy within 1 hr of recognition of septic shock (1B) and severe sepsis without septic shock (1C) as the goal of therapy; reassessment of antimicrobial therapy daily for de-escalation, when appropriate (1B); infection source control with attention to the balance of risks and benefits of the chosen method within 12 hrs of diagnosis (1C); initial fluid resuscitation with crystalloid (1B) and consideration of the addition of albumin in patients who continue to require substantial amounts of crystalloid to maintain adequate mean arterial pressure (2C) and the avoidance of hetastarch formulations (1C); initial fluid challenge in patients with sepsis-induced tissue hypoperfusion and suspicion of hypovolemia to achieve a minimum of 30 mL/kg of crystalloids (more rapid administration and greater amounts of fluid may be needed in some patients) (1C); fluid challenge technique continued as long as hemodynamic improvement, as based on either dynamic or static variables (UG); norepinephrine as the first-choice vasopressor to maintain mean arterial pressure ≥ 65 mm Hg (1B); epinephrine when an additional agent is needed to maintain adequate blood pressure (2B); vasopressin (0.03 U/min) can be added to norepinephrine to either raise mean arterial pressure to target or to decrease norepinephrine dose but should not be used as the initial vasopressor (UG); dopamine is not recommended except in highly selected circumstances (2C); dobutamine infusion administered or added to vasopressor in the presence of a) myocardial dysfunction as suggested by elevated cardiac filling pressures and low cardiac output, or b) ongoing signs of hypoperfusion despite achieving adequate intravascular volume and adequate mean arterial pressure (1C); avoiding use of intravenous hydrocortisone in adult septic shock patients if adequate fluid resuscitation and vasopressor therapy are able to restore hemodynamic stability (2C); hemoglobin target of 7-9 g/dL in the absence of tissue hypoperfusion, ischemic coronary artery disease, or acute hemorrhage (1B); low tidal volume (1A) and limitation of inspiratory plateau pressure (1B) for acute respiratory distress syndrome (ARDS); application of at least a minimal amount of positive end-expiratory pressure (PEEP) in ARDS (1B); higher rather than lower level of PEEP for patients with sepsis-induced moderate or severe ARDS (2C); recruitment maneuvers in sepsis patients with severe refractory hypoxemia due to ARDS (2C); prone positioning in sepsis-induced ARDS patients with a PaO2/FIO2 ratio of ≤ 100 mm Hg in facilities that have experience with such practices (2C); head-of-bed elevation in mechanically ventilated patients unless contraindicated (1B); a conservative fluid strategy for patients with established ARDS who do not have evidence of tissue hypoperfusion (1C); protocols for weaning and sedation (1A); minimizing use of either intermittent bolus sedation or continuous infusion sedation targeting specific titration endpoints (1B); avoidance of neuromuscular blockers if possible in the septic patient without ARDS (1C); a short course of neuromuscular blocker (no longer than 48 hrs) for patients with early ARDS and a Pao2/Fio2 < 150 mm Hg (2C); a protocolized approach to blood glucose management commencing insulin dosing when two consecutive blood glucose levels are > 180 mg/dL, targeting an upper blood glucose ≤ 180 mg/dL (1A); equivalency of continuous veno-venous hemofiltration or intermittent hemodialysis (2B); prophylaxis for deep vein thrombosis (1B); use of stress ulcer prophylaxis to prevent upper gastrointestinal bleeding in patients with bleeding risk factors (1B); oral or enteral (if necessary) feedings, as tolerated, rather than either complete fasting or provision of only intravenous glucose within the first 48 hrs after a diagnosis of severe sepsis/septic shock (2C); and addressing goals of care, including treatment plans and end-of-life planning (as appropriate) (1B), as early as feasible, but within 72 hrs of intensive care unit admission (2C). Recommendations specific to pediatric severe sepsis include: therapy with face mask oxygen, high flow nasal cannula oxygen, or nasopharyngeal continuous PEEP in the presence of respiratory distress and hypoxemia (2C), use of physical examination therapeutic endpoints such as capillary refill (2C); for septic shock associated with hypovolemia, the use of crystalloids or albumin to deliver a bolus of 20 mL/kg of crystalloids (or albumin equivalent) over 5 to 10 mins (2C); more common use of inotropes and vasodilators for low cardiac output septic shock associated with elevated systemic vascular resistance (2C); and use of hydrocortisone only in children with suspected or proven "absolute"' adrenal insufficiency (2C). CONCLUSIONS: Strong agreement existed among a large cohort of international experts regarding many level 1 recommendations for the best care of patients with severe sepsis. Although a significant number of aspects of care have relatively weak support, evidence-based recommendations regarding the acute management of sepsis and septic shock are the foundation of improved outcomes for this important group of critically ill patients.

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

INTRODUCTION: Randomized 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. METHODS: We 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. RESULTS: Three 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. CONCLUSIONS: Short-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.

Small bowel feeding and risk of pneumonia in adult critically ill patients: a systematic review and meta-analysis of randomized trials.

INTRODUCTION: This systematic review and meta-analysis aimed to evaluate the effect of small bowel feeding compared with gastric feeding on the frequency of pneumonia and other patient-important outcomes in critically ill patients. METHODS: We searched EMBASE, MEDLINE, clinicaltrials.gov and personal files from 1980 to Dec 2012, and conferences and proceedings from 1993 to Dec 2012 for randomized trials of adult critically ill patients in the intensive care unit (ICU) comparing small bowel feeding to gastric feeding, and evaluating risk of pneumonia, mortality, length of ICU stay, achievement of caloric requirements, duration of mechanical ventilation, vomiting, and aspiration. Independently, in duplicate, we abstracted trial characteristics, outcomes and risk of bias. RESULTS: We included 19 trials with 1394 patients. Small bowel feeding compared to gastric feeding was associated with reduced risk of pneumonia (risk ratio [RR] 0.70; 95% CI, 0.55, 0.90; P = 0.004; I2 = 0%) and ventilator-associated pneumonia (RR 0.68; 95% CI 0.53, 0.89; P = 0.005; I2 = 0%), with no difference in mortality (RR 1.08; 95% CI 0.90, 1.29; P = 0.43; I2 = 0%), length of ICU stay (WMD -0.57; 95%CI -1.79, 0.66; P = 0.37; I2 = 0%), duration of mechanical ventilation (WMD -1.01; 95%CI -3.37, 1.35; P = 0.40; I2 = 17%), gastrointestinal bleeding (RR 0.89; 95% CI 0.56, 1.42; P = 0.64; I2 = 0%), aspiration (RR 0.92; 95% CI 0.52, 1.65; P = 0.79; I2 = 0%), and vomiting (RR 0.91; 95% CI 0.53, 1.54; P = 0.72; I2 = 57%). The overall quality of evidence was low for pneumonia outcome. CONCLUSIONS: Small bowel feeding, in comparison with gastric feeding, reduces the risk of pneumonia in critically ill patients without affecting mortality, length of ICU stay or duration of mechanical ventilation. These observations are limited by variation in pneumonia definition, imprecision, risk of bias and small sample size of individual trials.