Variation in diurnal sedation in mechanically ventilated patients who are managed with a sedation protocol alone or a sedation protocol and daily interruption.

BACKGROUND: Mechanically ventilated patients may receive more sedation during the night than during the day, potentially delaying extubation. We compared nighttime and daytime benzodiazepine and opioid administration in adult patients enrolled in a multicenter sedation trial comparing protocolized sedation alone or protocolized sedation combined with daily sedation interruption; and we evaluated whether nighttime and daytime doses were associated with liberation from mechanical ventilation. METHODS: This is a secondary analysis of a randomized trial which was conducted in 16 North American medical-surgical ICUs. In all 423 patients, nurses applied a validated sedation scale hourly to titrate benzodiazepine and opioid infusions to achieve a light level of sedation. Using fentanyl equivalents and midazolam equivalents, we compared dosages administered during night (19:00 to 07:00) and day (07:00 to 19:00) shifts. Using multivariable logistic regression we evaluated the association between nighttime and daytime opioid and sedative doses, and spontaneous breathing trial (SBT) conduct, SBT success, and extubation. RESULTS: Nighttime benzodiazepine and opioid doses were significantly higher than daytime doses (mean difference midazolam equivalents 23.3 mg, 95 % CI 12.9, 33.8, p < 0.0001; mean difference fentanyl equivalents 356 mcg, 95 % CI 130, 582, p = 0.0021). Mean Sedation Agitation Scale score was similar between night and day, and was at target (3.2 vs 3.3, 95 % CI -0.05, 0.02, p = 0.35). Self-reported nurse workload was similar during the night and day. Patients were more often restrained during day shifts (76.3 % vs 73.7 %, p < 0.0001), and there were more unintentional device removals during the day compared with night (15.9 % vs 9.1 %, p < 0.0001). Increases in nighttime drug doses were independently associated with failure to meet SBT screening criteria, SBT failure, and the decision not to extubate the patient despite successful SBT. CONCLUSION: Patients received higher doses of opioids and benzodiazepines at night. Higher nighttime doses were associated with SBT failure and delayed extubation. TRIAL REGISTRATION: ClinicalTrials.gov NCT00675363 . Registered 7 May 2008.

Extracorporeal carbon dioxide removal in patients with chronic obstructive pulmonary disease: a systematic review.

INTRODUCTION: Extracorporeal carbon dioxide removal (ECCO2R) has been proposed for hypercapnic respiratory failure in chronic obstructive pulmonary disease (COPD) exacerbations, to avoid intubation or reduce length of invasive ventilation. Balance of risks, efficacy, and benefits of ECCO2R in patients with COPD is unclear. METHODS: We systematically searched MEDLINE and EMBASE to identify all publications reporting use of ECCO2R in COPD. We looked at physiological and clinical efficacy. A favorable outcome was defined as prevention of intubation or successful extubation. Major and minor complications were compiled. RESULTS: We identified 3123 citations. Ten studies (87 patients), primarily case series, met inclusion criteria. ECCO2R prevented intubation in 65/70 (93%) patients and assisted in the successful extubation of 9/17 (53%) mechanically ventilated subjects. One case-control study matching to noninvasively ventilated controls reported lower intubation rates and hospital mortality with ECCO2R that trended toward significance. Physiological data comparing pre- to post-ECCO2R changes suggest improvements for pH (0.07-0.15 higher), PaCO2 (25 mmHg lower), and respiratory rate (7 breaths/min lower), but not PaO2/FiO2. Studies reported 11 major (eight bleeds requiring blood transfusion of 2 units, and three line-related complications, including one death related to retroperitoneal bleeding) and 30 minor complications (13 bleeds, five related to anticoagulation, and nine clotting-related device malfunctions resulting in two emergent intubations). CONCLUSION: The technique is still experimental and no randomized trial is available. Recognizing selection bias associated with case series, there still appears to be potential for benefit of ECCO2R in patients with COPD exacerbations. However, it is associated with frequent and potentially severe complications. Higher-quality studies are required to better elucidate this risk-benefit balance.

Pressure-Controlled vs Volume-Controlled Ventilation in Acute Respiratory Failure: A Physiology-Based Narrative and Systematic Review.

BACKGROUND: Mechanical ventilation is a cornerstone in the management of acute respiratory failure. Both volume-targeted and pressure-targeted ventilations are used, the latter modes being increasingly used. We provide a narrative review of the physiologic principles of these two types of breath delivery, performed a literature search, and analyzed published comparisons between modes. METHODS: We performed a systematic review and meta-analysis to determine whether pressure control-continuous mandatory ventilation (PC-CMV) or pressure control-inverse ratio ventilation (PC-IRV) has demonstrated advantages over volume control-continuous mandatory ventilation (VC-CMV). The Cochrane tool for risk of bias was used for methodologic quality. We also introduced physiologic criteria as quality indicators for selecting the studies. Outcomes included compliance, gas exchange, hemodynamics, work of breathing, and clinical outcomes. Analyses were completed with RevMan5 using random effects models. RESULTS: Thirty-four studies met inclusion criteria, many being at high risk of bias. Comparisons of PC-CMV/PC-IRV and VC-CMV did not show any difference for compliance or gas exchange, even when looking at PC-IRV. Calculating the oxygenation index suggested a poorer effect for PC-IRV. There was no difference between modes in terms of hemodynamics, work of breathing, or clinical outcomes. CONCLUSIONS: The two modes have different working principles but clinical available data do not suggest any difference in the outcomes. We included all identified trials, enhancing generalizability, and attempted to include only sufficient quality physiologic studies. However, included trials were small and varied considerably in quality. These data should help to open the choice of ventilation of patients with acute respiratory failure.

Prediction scores do not correlate with clinically adjudicated categories of pulmonary embolism in critically ill patients.

BACKGROUND: Prediction scores for pretest probability of pulmonary embolism (PE) validated in outpatient settings are occasionally used in the intensive care unit (ICU). OBJECTIVE: To evaluate the correlation of Geneva and Wells scores with adjudicated categories of PE in ICU patients. METHODS: In a randomized trial of thromboprophylaxis, patients with suspected PE were adjudicated as possible, probable or definite PE. Data were then retrospectively abstracted for the Geneva Diagnostic PE score, Wells, Modified Wells and Simplified Wells Diagnostic scores. The chance-corrected agreement between adjudicated categories and each score was calculated. ANOVA was used to compare values across the three adjudicated PE categories. RESULTS: Among 70 patients with suspected PE, agreement was poor between adjudicated categories and Geneva pretest probabilities (kappa=0.01 [95% CI -0.0643 to 0.0941]) or Wells pretest probabilities (kappa=-0.03 [95% CI -0.1462 to 0.0914]). Among four possible, 16 probable and 50 definite PEs, there were no significant differences in Geneva scores (possible = 4.0, probable = 4.7, definite = 4.5; P=0.90), Wells scores (possible = 2.8, probable = 4.9, definite = 4.1; P=0.37), Modified Wells (possible = 2.0, probable = 3.4, definite = 2.9; P=0.34) or Simplified Wells (possible = 1.8, probable = 2.8, definite = 2.4; P=0.30). CONCLUSIONS: Pretest probability scores developed outside the ICU do not correlate with adjudicated PE categories in critically ill patients. Research is needed to develop prediction scores for this population.

Intra-abdominal hypertension in the critically ill: interrater reliability of bladder pressure measurement.

PURPOSE: Intra-abdominal hypertension is frequently underdiagnosed and defined by intra-abdominal pressure (IAP) 12 mm Hg or higher. Increasing IAP may compromise organ viability and culminate in abdominal compartment syndrome. Bladder pressure measurement is a surrogate for IAP, but measurement properties are unknown in the intensive care unit. Our primary objective was to assess the agreement of bladder pressure measurements in critically ill patients. METHODS: We conducted an observational study examining the correlation of measurement variability of bladder pressure. Four raters (2 nurses and 2 physicians) measured IAP. Patient's age, Acute Physiology and Chronic Health Evaluation II, body mass index, mechanical ventilation parameters, and demographics were collected. RESULTS: Fifty-one patients had bladder pressures measured in quadruplicate, producing 204 measurements. Among 51 patients, the mean age was 61.9 years, Acute Physiology and Chronic Health Evaluation II was 23.8, and body mass index was 27.8 kg/m2. The average bladder pressure was 12.4 (SD, ±6.2) mm Hg. The interrater agreement by intraclass correlation coefficient was 0.745 (95% confidence interval [CI], 0.637-0.825), 0.804 (95% CI, 0.684-0.882), and 0.626 (95% CI, 0.428-0.767) among all raters, physicians, and nurses, respectively. CONCLUSIONS: Agreement on bladder pressure was high among 4 clinicians and were not significantly different between physicians and nurses. Given that medical/surgical treatments are considered on bladder pressure values, understanding their reliability is essential to monitor critically ill patients.

An antimicrobial stewardship program improves antimicrobial treatment by culture site and the quality of antimicrobial prescribing in critically ill patients.

INTRODUCTION: Increasing antimicrobial costs, reduced development of novel antimicrobials, and growing antimicrobial resistance necessitate judicious use of available agents. Antimicrobial stewardship programs (ASPs) may improve antimicrobial use in intensive care units (ICUs). Our objective was to determine whether the introduction of an ASP in an ICU altered the decision to treat cultures from sterile sites compared with nonsterile sites (which may represent colonization or contamination). We also sought to determine whether ASP education improved documentation of antimicrobial use, including an explicit statement of antimicrobial regimen, indication, duration, and de-escalation. METHODS: We retrospectively analyzed consecutive patients with positive bacterial cultures admitted to a 16-bed medical-surgical ICU over 2-month periods before and after ASP introduction (April through May 2008 and 2009, respectively). We evaluated the antimicrobial treatment of positive sterile- versus nonsterile-site cultures, specified a priori. We reviewed patient charts for clinician documentation of three specific details regarding antimicrobials: an explicit statement of antimicrobial regimen/indication, duration, and de-escalation. We also analyzed cost and defined daily doses (DDDs) (a World Health Organization (WHO) standardized metric of use) before and after ASP. RESULTS: Patient demographic data between the pre-ASP (n = 139) and post-ASP (n = 130) periods were similar. No difference was found in the percentage of positive cultures from sterile sites between the pre-ASP period and post-ASP period (44.9% versus 40.2%; P = 0.401). A significant increase was noted in the treatment of sterile-site cultures after ASP (64% versus 83%; P = 0.01) and a reduction in the treatment of nonsterile-site cultures (71% versus 46%; P = 0.0002). These differences were statistically significant when treatment decisions were analyzed both at an individual patient level and at an individual culture level. Increased explicit antimicrobial regimen documentation was observed after ASP (26% versus 71%; P < 0.0001). Also observed were increases in formally documented stop dates (53% versus 71%; P < 0.0001), regimen de-escalation (15% versus 23%; P = 0.026), and an overall reduction in cost and mean DDDs after ASP implementation. CONCLUSIONS: Introduction of an ASP in the ICU was associated with improved microbiologically targeted therapy based on sterile or nonsterile cultures and improved documentation of antimicrobial use in the medical record.

Potential impact on estimated treatment effects of information lost to follow-up in randomised controlled trials (LOST-IT): systematic review.

OBJECTIVE: To assess the reporting, extent, and handling of loss to follow-up and its potential impact on the estimates of the effect of treatment in randomised controlled trials. DESIGN: Systematic review. We calculated the percentage of trials for which the relative risk would no longer be significant under a number of assumptions about the outcomes of participants lost to follow-up. DATA SOURCES: Medline search of five top general medical journals, 2005-07. ELIGIBILITY CRITERIA: Randomised controlled trials that reported a significant binary primary patient important outcome. RESULTS: Of the 235 eligible reports identified, 31 (13%) did not report whether or not loss to follow-up occurred. In reports that did give the relevant information, the median percentage of participants lost to follow-up was 6% (interquartile range 2-14%). The method by which loss to follow-up was handled was unclear in 37 studies (19%); the most commonly used method was survival analysis (66, 35%). When we varied assumptions about loss to follow-up, results of 19% of trials were no longer significant if we assumed no participants lost to follow-up had the event of interest, 17% if we assumed that all participants lost to follow-up had the event, and 58% if we assumed a worst case scenario (all participants lost to follow-up in the treatment group and none of those in the control group had the event). Under more plausible assumptions, in which the incidence of events in those lost to follow-up relative to those followed-up is higher in the intervention than control group, results of 0% to 33% trials were no longer significant. CONCLUSION: Plausible assumptions regarding outcomes of patients lost to follow-up could change the interpretation of results of randomised controlled trials published in top medical journals.

Specific instructions for estimating unclearly reported blinding status in randomized trials were reliable and valid.

OBJECTIVE: To test the reliability and validity of specific instructions to classify blinding, when unclearly reported in randomized trials, as "probably done" or "probably not done." STUDY DESIGN AND SETTING: We assessed blinding of patients, health care providers, data collectors, outcome adjudicators, and data analysts in 233 randomized trials in duplicate and independently using detailed instructions. The response options were "definitely yes," "probably yes," "probably no," and "definitely no." We contacted authors for data verification (46% response). For each of the five questions, we assessed reliability by calculating the agreement between the two reviewers and validity by calculating the agreement between reviewers' consensus and verified data. RESULTS: The percentage with unclear blinding status varied between 48.5% (patients) and 84.1% (data analysts). Reliability was moderate for blinding of outcome adjudicators (κ=0.52) and data analysts (κ=0.42) and substantial for blinding of patients (κ=0.71), providers (κ=0.68), and data collectors (κ=0.65). The raw agreement between the consensus record and the author-verified record varied from 84.1% (blinding of data analysts) to 100% (blinding of health care providers). CONCLUSION: With the possible exception of blinding of data analysts, use of "probably yes" and "probably no" instead of "unclear" may enhance the assessment of blinding in trials.

Red blood cell transfusion and increased length of storage are not associated with deep vein thrombosis in medical and surgical critically ill patients: a prospective observational cohort study.

INTRODUCTION: With prolonged storage times, cell membranes of red blood cells (RBCs) undergo morphologic and biochemical changes, termed 'RBC storage lesions'. Storage lesions may promote inflammation and thrombophilia when transfused. In trauma patients, RBC transfusion was an independent risk factor for deep vein thrombosis (DVT), specifically when RBC units were stored > 21 days or when 5 or more units were transfused. The objective of this study was to determine if RBC transfusions or RBC storage age predicts incident DVT in medical or surgical intensive care unit (ICU) patients. METHODS: Using a database which prospectively enrolled 261 patients over the course of 1 year with an ICU stay of at least 3 days, we analyzed DVT and RBC transfusions using Cox proportional hazards regression. Transfusions were analyzed with 4 thresholds, and storage age using 3 thresholds. DVTs were identified by twice-weekly proximal leg ultrasounds. Multivariable analyses were adjusted for 4 significant DVT predictors in this population (venous thrombosis history, chronic dialysis, platelet transfusion and inotropes). RESULTS: Of 261 patients, 126 (48.3%) had at least 1 RBC transfusion; 46.8% of those transfused had ≥ 5 units in ICU. Patients receiving RBCs were older (68.8 vs 64.1 years), more likely to be female (47.0 vs 30.7), sicker (APACHEII 26.8 vs 24.4), and more likely to be surgical (21.4 vs 8.9) (P < 0.05). The total number of RBCs per patient was 1-64, mean was 6.3 (SD 7.5), median was 4 (IQR 2,8). In univariate analyses, there was no association between DVT and RBC exposure (1 day earlier, 3 days earlier, 7 days earlier, or ever) or RBC storage (≤ 7 or > 7 days, ≤ 14 or > 14 days, ≤ 21 or > 21 days). Among patients transfused, no multivariable analyses showed that RBC transfusion or storage age predicted DVT. Trends were counter to the hypothesis (e.g., RBC storage for ≤ 7 days suggested a higher DVT risk compared to > 7 days (HR 5.3; 95% CI 1.3-22.1). CONCLUSIONS: We were unable to detect any association between RBC transfusions or prolonged red cell storage and increased risk of DVT in medical or surgical ICU patients. Alternate explanations include a lack of sufficient events or patients' interaction, between patient groups, a mixing of red cell storage times creating differential effects on DVT risk, and unmeasured confounders.