Meeta Prasad Kerlin

The Preventability of Ventilator-Associated Events: The CDC Prevention Epicenters’ Wake Up and Breathe Collaborative

RATIONALE The CDC introduced ventilator-associated event (VAE) definitions in January 2013. Little is known about VAE prevention. We hypothesized that daily, coordinated spontaneous awakening trials (SATs) and spontaneous breathing trials (SBTs) might prevent VAEs. OBJECTIVES To assess the preventability of VAEs. METHODS We nested a multicenter quality improvement collaborative within a prospective study of VAE surveillance among 20 intensive care units between November 2011 and May 2013. Twelve units joined the collaborative and implemented an opt-out protocol for nurses and respiratory therapists to perform paired daily SATs and SBTs. The remaining eight units conducted surveillance alone. We measured temporal trends in VAEs using generalized mixed effects regression models adjusted for patient-level unit, age, sex, reason for intubation, Sequential Organ Failure Assessment score, and comorbidity index. MEASUREMENTS AND MAIN RESULTS We tracked 5,164 consecutive episodes of mechanical ventilation: 3,425 in collaborative units and 1,739 in surveillance-only units. Within collaborative units, significant increases in SATs, SBTs, and percentage of SBTs performed without sedation were mirrored by significant decreases in duration of mechanical ventilation and hospital length-of-stay. There was no change in VAE risk per ventilator day but significant decreases in VAE risk per episode of mechanical ventilation (odds ratio [OR], 0.63; 95% confidence interval [CI], 0.42-0.97) and infection-related ventilator-associated complications (OR, 0.35; 95% CI, 0.17-0.71) but not pneumonias (OR, 0.51; 95% CI, 0.19-1.3). Within surveillance-only units, there were no significant changes in SAT, SBT, or VAE rates. CONCLUSIONS Enhanced performance of paired, daily SATs and SBTs is associated with lower VAE rates. Clinical trial registered with www.clinicaltrials.gov (NCT 01583413).

Use of therapeutic hypothermia after in-hospital cardiac arrest.

Objectives:Formal guidelines recommend that therapeutic hypothermia be considered after in-hospital cardiac arrest. The rate of therapeutic hypothermia use after in-hospital cardiac arrest and details about its implementation are unknown. We aimed to determine the use of therapeutic hypothermia for adult in-hospital cardiac arrest, whether use has increased over time, and to identify factors associated with its use. Design:Multicenter, prospective cohort study. Setting:A total of 538 hospitals participating in the Get With the Guidelines-Resuscitation database (2003–2009). Patients:A total of 67,498 patients who had return of spontaneous circulation after in-hospital cardiac arrest. Interventions:None. Measurements and Main Results:The primary outcome was the initiation of therapeutic hypothermia. We measured the proportion of therapeutic hypothermia patients who achieved target temperature (32–34°C) and were overcooled. Of 67,498 patients, therapeutic hypothermia was initiated in 1,367 patients (2.0%). The target temperature (32–34°C) was not achieved in 44.3% of therapeutic hypothermia patients within 24 hours and 17.6% were overcooled. The use of therapeutic hypothermia increased from 0.7% in 2003 to 3.3% in 2009 (p < 0.001). We found that younger age (p < 0.001) and occurrence in a non-ICU location (p < 0.001), on a weekday (p = 0.005), and in a teaching hospital (p = 0.001) were associated with an increased likelihood of therapeutic hypothermia being initiated. Conclusions:After in-hospital cardiac arrest, therapeutic hypothermia was used rarely. Once initiated, the target temperature was commonly not achieved. The frequency of use increased over time but remained low. Factors associated with therapeutic hypothermia use included patient age, time and location of occurrence, and type of hospital.

Outcomes and statistical power in adult critical care randomized trials.

RATIONALE Intensive care unit (ICU)-based randomized clinical trials (RCTs) among adult critically ill patients commonly fail to detect treatment benefits. OBJECTIVES Appraise the rates of success, outcomes used, statistical power, and design characteristics of published trials. METHODS One hundred forty-six ICU-based RCTs of diagnostic, therapeutic, or process/systems interventions published from January 2007 to May 2013 in 16 high-impact general or critical care journals were studied. MEASUREMENT AND MAIN RESULTS Of 146 RCTs, 54 (37%) were positive (i.e., the a priori hypothesis was found to be statistically significant). The most common primary outcomes were mortality (n = 40 trials), infection-related outcomes (n = 33), and ventilation-related outcomes (n = 30), with positive results found in 10, 58, and 43%, respectively. Statistical power was discussed in 135 RCTs (92%); 92 cited a rationale for their power parameters. Twenty trials failed to achieve at least 95% of their reported target sample size, including 11 that were stopped early due to insufficient accrual/logistical issues. Of 34 superiority RCTs comparing mortality between treatment arms, 13 (38%) accrued a sample size large enough to find an absolute mortality reduction of 10% or less. In 22 of these trials the observed control-arm mortality rate differed from the predicted rate by at least 7.5%. CONCLUSIONS ICU-based RCTs are commonly negative and powered to identify what appear to be unrealistic treatment effects, particularly when using mortality as the primary outcome. Additional concerns include a lack of standardized methods for assessing common outcomes, unclear justifications for statistical power calculations, insufficient patient accrual, and incorrect predictions of baseline event rates.

Post-Acute Care Use and Hospital Readmission after Sepsis.

RATIONALE The epidemiology of post-acute care use and hospital readmission after sepsis remains largely unknown. OBJECTIVES To examine the rate of post-acute care use and hospital readmission after sepsis and to examine risk factors and outcomes for hospital readmissions after sepsis. METHODS In an observational cohort study conducted in an academic health care system (2010-2012), we compared post-acute care use at discharge and hospital readmission after 3,620 sepsis hospitalizations with 108,958 nonsepsis hospitalizations. We used three validated, claims-based approaches to identify sepsis and severe sepsis. MEASUREMENTS AND MAIN RESULTS Post-acute care use at discharge was more likely after sepsis, driven by skilled care facility placement (35.4% after sepsis vs. 15.8%; P < 0.001), with the highest rate observed after severe sepsis. Readmission rates at 7, 30, and 90 days were higher postsepsis (P < 0.001). Compared with nonsepsis hospitalizations (15.6% readmitted within 30 d), the increased readmission risk was present regardless of sepsis severity (27.3% after sepsis and 26.0-26.2% after severe sepsis). After controlling for presepsis characteristics, the readmission risk was found to be 1.51 times greater (95% CI, 1.38-1.66) than nonsepsis hospitalizations. Readmissions after sepsis were more likely to result in death or transition to hospice care (6.1% vs. 13.3% after sepsis; P < 0.001). Independent risk factors associated with 30-day readmissions after sepsis hospitalizations included age, malignancy diagnosis, hospitalizations in the year prior to the index hospitalization, nonelective index admission type, one or more procedures during the index hospitalization, and low hemoglobin and high red cell distribution width at discharge. CONCLUSIONS Post-acute care use and hospital readmissions were common after sepsis. The increased readmission risk after sepsis was observed regardless of sepsis severity and was associated with adverse readmission outcomes.

Nighttime intensivist staffing, mortality, and limits on life support: a retrospective cohort study.

BACKGROUND Evidence regarding nighttime physician staffing of ICUs is suboptimal. We aimed to determine how nighttime physician staffing models influence patient outcomes. METHODS We performed a multicenter retrospective cohort study in a multicenter registry of US ICUs. The exposure variable was the ICUs nighttime physician staffing model. The primary outcome was hospital mortality. Secondary outcomes included new limitations on life support, ICU length of stay, hospital length of stay, and duration of mechanical ventilation. Daytime physician staffing was studied as a potential effect modifier. RESULTS The study included 270,742 patients in 143 ICUs. Compared with nighttime staffing with an attending intensivist, nighttime staffing without an attending intensivist was not associated with hospital mortality (OR, 1.03; 95% CI, 0.92-1.15; P = .65). This relationship was not modified by daytime physician staffing (interaction P = .19). When nighttime staffing was subcategorized, neither attending nonintensivist nor physician trainee staffing was associated with hospital mortality compared with attending intensivist staffing. However, nighttime staffing without any physician was associated with reduced odds of hospital mortality (OR, 0.79; 95% CI, 0.68-0.91; P = .002) and new limitations on life support (OR, 0.83; 95% CI, 0.75-0.93; P = .001). Nighttime staffing was not associated with ICU or hospital length of stay. Nighttime staffing with an attending nonintensivist was associated with a slightly longer duration of mechanical ventilation (hazard ratio, 1.05; 95% CI, 1.02-1.09; P < .001). CONCLUSIONS We found little evidence that nighttime physician staffing models affect patient outcomes. ICUs without physicians at night may exhibit reduced hospital mortality that is possibly attributable to differences in end-of-life care practices.

Original Research: Critical Care Medicine FeaturedNighttime Intensivist Staffing, Mortality, and Limits on Life Support: A Retrospective Cohort Study

BACKGROUND Evidence regarding nighttime physician staffing of ICUs is suboptimal. We aimed to determine how nighttime physician staffing models influence patient outcomes. METHODS We performed a multicenter retrospective cohort study in a multicenter registry of US ICUs. The exposure variable was the ICUs nighttime physician staffing model. The primary outcome was hospital mortality. Secondary outcomes included new limitations on life support, ICU length of stay, hospital length of stay, and duration of mechanical ventilation. Daytime physician staffing was studied as a potential effect modifier. RESULTS The study included 270,742 patients in 143 ICUs. Compared with nighttime staffing with an attending intensivist, nighttime staffing without an attending intensivist was not associated with hospital mortality (OR, 1.03; 95% CI, 0.92-1.15; P = .65). This relationship was not modified by daytime physician staffing (interaction P = .19). When nighttime staffing was subcategorized, neither attending nonintensivist nor physician trainee staffing was associated with hospital mortality compared with attending intensivist staffing. However, nighttime staffing without any physician was associated with reduced odds of hospital mortality (OR, 0.79; 95% CI, 0.68-0.91; P = .002) and new limitations on life support (OR, 0.83; 95% CI, 0.75-0.93; P = .001). Nighttime staffing was not associated with ICU or hospital length of stay. Nighttime staffing with an attending nonintensivist was associated with a slightly longer duration of mechanical ventilation (hazard ratio, 1.05; 95% CI, 1.02-1.09; P < .001). CONCLUSIONS We found little evidence that nighttime physician staffing models affect patient outcomes. ICUs without physicians at night may exhibit reduced hospital mortality that is possibly attributable to differences in end-of-life care practices.

Twenty-four-Hour Intensivist Staffing in Teaching Hospitals: Tensions Between Safety Today and Safety Tomorrow

There is an inherent tension between the training needs of inexperienced clinicians and the safety of the patients for whom they are responsible. Our society has accepted this tension as a necessary trade-off to maintain a competent workforce of physicians year after year. However, recent trends in medical education have diminished resident autonomy in favor of the safety of current patients. One dramatic example is the rapid increase in the number of academic ICUs that provide coverage by attending physicians at all hours. The potential benefits of this staffing model have strong face validity: improved quality and efficiency from the constant involvement of experienced intensivists, increased family and staff satisfaction from the immediate availability of attending physicians, and reduced burn-out among intensivists from reduced on-call responsibilities. Thus, many hospitals have moved toward 24-h coverage by attending intensivist physicians without evidence that these benefits actually accrue and perhaps without full consideration of possible unintended consequences. In this article, we discuss the potential benefits and risks of nocturnal intensivist staffing, considering the needs of current and future patients. Furthermore, we suggest that there remains sufficient uncertainty about these benefits and risks that it is both necessary and ethical to study the effects in earnest.

An Official American Thoracic Society Systematic Review: The Effect of Nighttime Intensivist Staffing on Mortality and Length of Stay among Intensive Care Unit Patients

Background: Studies of nighttime intensivist staffing have yielded mixed results. Goals: To review the association of nighttime intensivist staffing with outcomes of intensive care unit (ICU) patients. Methods: We searched five databases (2000‐2016) for studies comparing in‐hospital nighttime intensivist staffing with other nighttime staffing models in adult ICUs and reporting mortality or length of stay. We abstracted data on staffing models, outcomes, and study characteristics and assessed study quality, using standardized tools. Meta‐analyses used random effects models. Results: Eighteen studies met inclusion criteria: one randomized controlled trial and 17 observational studies. Overall methodologic quality was high. Studies included academic hospitals (n = 10), community hospitals (n = 2), or both (n = 6). Baseline clinician staffing included residents (n = 9), fellows (n = 4), and nurse practitioners or physician assistants (n = 2). Studies included both general and specialty ICUs and were geographically diverse. Meta‐analysis (one randomized controlled trial; three nonrandomized studies with exposure limited to nighttime intensivist staffing with adjusted estimates of effect) demonstrated no association with mortality (odds ratio, 0.99; 95% confidence interval, 0.75‐1.29). Secondary analyses including studies without risk adjustment, with a composite exposure of organizational factors, stratified by intensity of daytime staffing and by ICU type, yielded similar results. Minimal or no differences were observed in ICU and hospital length of stay and several other secondary outcomes. Conclusions: Notwithstanding limitations of the predominantly observational evidence, our systematic review and meta‐analysis suggests nighttime intensivist staffing is not associated with reduced ICU patient mortality. Other outcomes and alternative staffing models should be evaluated to further guide staffing decisions.

A "placement of death" approach for studies of treatment effects on ICU length of stay.

Length of stay in the intensive care unit (ICU) is a common outcome measure in randomized trials of ICU interventions. Because many patients die in the ICU, it is difficult to disentangle treatment effects on length of stay from effects on mortality; conventional analyses depend on assumptions that are often unstated and hard to interpret or check. We adapt a proposal from Rosenbaum that addresses concerns about selection bias and makes its assumptions explicit. A composite outcome is constructed that equals ICU length of stay if the patient was discharged alive and indicates death otherwise. Given any preference ordering that compares death with possible lengths of stay, we can estimate the intervention’s effects on the composite outcome distribution. Sensitivity analyses can show results for different preference orderings. We discuss methods for constructing approximate confidence intervals for treatment effects on quantiles of the outcome distribution or on proportions of patients with outcomes preferable to various cutoffs. Strengths and weaknesses of possible primary significance tests (including the Wilcoxon–Mann–Whitney rank sum test and a heteroskedasticity-robust variant due to Brunner and Munzel) are reviewed. An illustrative example reanalyzes a randomized trial of an ICU staffing intervention.

Acute Gastrointestinal Bleeding

Acid-base balance has been studied in 21 patients with acute upper gastrointestinal bleeding. A low plasma bicarbonate concentration was found in nine patients, accompanied in each case by a base deficit of more than 3 mEq/litre, indicating a metabolic acidosis. Three patients had a low blood pH. Hyperlactataemia appeared to be a major cause of the acidosis. This was not accompanied by a raised blood pyruvate concentration. The hyperlactataemia could not be accounted for on the basis of hyperventilation, intravenous infusion of dextrose, or arterial hypoxaemia. Before blood transfusion it was most pronounced in patients who were clinically shocked, suggesting that it may have resulted from poor tissue perfusion and anaerobic glycolysis. Blood transfusion resulted in a rise in lactate concentration in seven patients who were not clinically shocked, and failed to reverse a severe uncompensated acidosis in a patient who was clinically shocked. These effects of blood transfusion are probably due to the fact that red blood cells in stored bank blood, with added acid-citratedextrose solution, metabolize the dextrose anaerobically to lactic acid. Monitoring of acid-base balance is recommended in patients with acute gastrointestinal bleeding who are clinically shocked. A metabolic acidosis can then be corrected with intravenous sodium bicarbonate. one a probable Mallory-Weiss lesion, one a small-bowel reticulosis, and one had thrombocytopenia. In four patients the cause of bleeding was not identified. Arterial blood samples were taken within 36 hours of hospital admission, with the patients breathing air. No patient received any drugs known to cause a lactic acidosis. Though patients were supine at rest when the blood samples were taken, conditions were iiOt truly basal, as some of them were anxious and not all were fasting. In 14 patients an arterial blood sample was taken before blood transfusion, and in seven the first sample was taken during blood transfusion. The blood samples were analysed immediately for pH, carbon dioxide tension (Pco.), and oxygen tension (Poe) with a Radiometer electrode system at 37°C. Plasma bicarbonate concentration and base deficit were derived from pH and Pco2 by use of Siggaard-Andersens (1963) nomogram. An aliquot of the blood sample was deproteinized at the bedside with icecold perchloric acid. Blood lactate and pyruvate concentrations were measured by means of a lactate dehydrogenase enzyme assay, the reagent kits supplied by Biochemica Test Combination being used as specified by the manufacturers (Boehringer und Soehne, 1967). For the purpose of this study arterial hypoxaemia has been defined as an arterial oxygen tension of less than 80 mm Hg, and clinical shock as the presence of cold, sweaty extremities in combination with a systolic blood pressure of less than 100 mm Hg.