Factors Associated With Mortality Among Patients Managed for Large Volume Hemorrhage in a Medical Intensive Care Unit.

PURPOSE: Our goal was to describe resuscitation practices in critically ill medical patients with active hemorrhage requiring large volume resuscitation and identify factors associated with poor outcomes. PATIENTS AND METHODS: This was a single center retrospective observational cohort study. Patients admitted to the medical intensive care unit from 2011 to 2017 who received ≥5 units of packed red blood cells (pRBCs) within 24 h were included. Data including volume of blood products and crystalloid administered, baseline sequential organ failure assessment (SOFA) scores, and outcomes were abstracted. Univariate and multivariate analyses were performed to determine clinical factors associated with hospital mortality. RESULTS: Two hundred forty-six patients were identified. Mean volumes of 2,448 mL of pRBCs and 3.9L of crystalloid were transfused over 24 h. Inpatient mortality for the entire cohort was 48%. Multivariable analysis identified factors associated with hospital mortality; higher BMI (OR 1.047, 95% CI 1.013-1.083), higher ratio of fresh frozen plasma (FFP) to pRBCs (OR 2.744, 95% CI 1.1-6.844), and higher baseline SOFA scores (OR 1.3, 95% CI 1.175-1.437). CONCLUSION: In a cohort of critically ill medical patients undergoing resuscitation for hemorrhage, higher BMI, increased ratio of FFP to pRBCs, and higher SOFA scores were associated with increased mortality. Further studies are needed to clarify resuscitation practices associated with outcomes in this population.

Effect of Ganciclovir on IL-6 Levels Among Cytomegalovirus-Seropositive Adults With Critical Illness: A Randomized Clinical Trial.

Importance: The role of cytomegalovirus (CMV) reactivation in mediating adverse clinical outcomes in nonimmunosuppressed adults with critical illness is unknown. Objective: To determine whether ganciclovir prophylaxis reduces plasma interleukin 6 (IL-6) levels in CMV-seropositive adults who are critically ill. Design, Setting, and Participants: Double-blind, placebo-controlled, randomized clinical trial (conducted March 10, 2011-April 29, 2016) with a follow-up of 180 days (November 10, 2016) that included 160 CMV-seropositive adults with either sepsis or trauma and respiratory failure at 14 university intensive care units (ICUs) across the United States. Interventions: Patients were randomized (1:1) to receive either intravenous ganciclovir (5 mg/kg twice daily for 5 days), followed by either intravenous ganciclovir or oral valganciclovir once daily until hospital discharge (n = 84) or to receive matching placebo (n = 76). Main Outcomes and Measures: The primary outcome was change in IL-6 level from day 1 to 14. Secondary outcomes were incidence of CMV reactivation in plasma, mechanical ventilation days, incidence of secondary bacteremia or fungemia, ICU length of stay, mortality, and ventilator-free days (VFDs) at 28 days. Results: Among 160 randomized patients (mean age, 57 years; women, 43%), 156 patients received 1or more dose(s) of study medication, and 132 patients (85%) completed the study. The mean change in plasma IL-6 levels between groups was -0.79 log10 units (-2.06 to 0.48) in the ganciclovir group and -0.79 log10 units (-2.14 to 0.56) in the placebo group (point estimate of difference, 0 [95% CI, -0.3 to 0.3]; P > .99). Among secondary outcomes, CMV reactivation in plasma was significantly lower in the ganciclovir group (12% [10 of 84 patients] vs 39% [28 of 72 patients]); absolute risk difference, -27 (95% CI, -40 to -14), P < .001. The ganciclovir group had more median VFDs in both the intention-to-treat (ITT) group and in the prespecified sepsis subgroup (ITT group: 23 days in ganciclovir group vs 20 days in the placebo group, P = .05; sepsis subgroup, 23 days in the ganciclovir group vs 20 days in the placebo group, P = .03). There were no significant differences between the ganciclovir and placebo groups in duration of mechanical ventilation (5 days for the ganciclovir group vs 6 days for the placebo group, P = .16), incidence of secondary bacteremia or fungemia (15% for the ganciclovir group vs 15% for the placebo group, P = .67), ICU length of stay (8 days for the ganciclovir group vs 8 days for the placebo group, P = .76), or mortality (12% for the ganciclovir group vs 15% for the placebo group, P = .54). Conclusions and Relevance: Among CMV-seropositive adults with critical illness due to sepsis or trauma, ganciclovir did not reduce IL-6 levels and the current study does not support routine clinical use of ganciclovir as a prophylactic agent in patients with sepsis. Additional research is necessary to determine the clinical efficacy and safety of CMV suppression in this setting. Trial Registration: clinicaltrials.gov Identifier: NCT01335932.

The evolution of eProtocols that enable reproducible clinical research and care methods.

Unnecessary variation in clinical care and clinical research reduces our ability to determine what healthcare interventions are effective. Reducing this unnecessary variation could lead to further healthcare quality improvement and more effective clinical research. We have developed and used electronic decision support tools (eProtocols) to reduce unnecessary variation. Our eProtocols have progressed from a locally developed mainframe computer application in one clinical site (LDS Hospital) to web-based applications available in multiple languages and used internationally. We use eProtocol-insulin as an example to illustrate this evolution. We initially developed eProtocol-insulin as a local quality improvement effort to manage stress hyperglycemia in the adult intensive care unit (ICU). We extended eProtocol-insulin use to translate our quality improvement results into usual clinical care at Intermountain Healthcare ICUs. We exported eProtocol-insulin to support research in other US and international institutions, and extended our work to the pediatric ICU. We iteratively refined eProtocol-insulin throughout these transitions, and incorporated new knowledge about managing stress hyperglycemia in the ICU. Based on our experience in the development and clinical use of eProtocols, we outline remaining challenges to eProtocol development, widespread distribution and use, and suggest a process for eProtocol development. Technical and regulatory issues, as well as standardization of protocol development, validation and maintenance, need to be addressed. Resolution of these issues should facilitate general use of eProtocols to improve patient care.

Randomized, placebo-controlled clinical trial of an aerosolized ß2-agonist for treatment of acute lung injury.

RATIONALE: ß2-Adrenergic receptor agonists accelerate resolution of pulmonary edema in experimental and clinical studies. OBJECTIVES: This clinical trial was designed to test the hypothesis that an aerosolized ß2-agonist, albuterol, would improve clinical outcomes in patients with acute lung injury (ALI). METHODS: We conducted a multicenter, randomized, placebo-controlled clinical trial in which 282 patients with ALI receiving mechanical ventilation were randomized to receive aerosolized albuterol (5 mg) or saline placebo every 4 hours for up to 10 days. The primary outcome variable for the trial was ventilator-free days. MEASUREMENTS AND MAIN RESULTS: Ventilator-free days were not significantly different between the albuterol and placebo groups (means of 14.4 and 16.6 d, respectively; 95% confidence interval for the difference, -4.7 to 0.3 d; P = 0.087). Rates of death before hospital discharge were not significantly different between the albuterol and placebo groups (23.0 and 17.7%, respectively; 95%confidence interval for the difference,-4.0 to 14.7%;P = 0.30). In the subset of patients with shock before randomization, the number of ventilator-free days was lower with albuterol, although mortality was not different. Overall, heart rates were significantly higher in the albuterol group by approximately 4 beats/minute in the first 2 days after randomization, but rates of new atrial fibrillation (10% in both groups) and other cardiac dysrhythmias were not significantly different. CONCLUSIONS: These results suggest that aerosolized albuterol does not improve clinical outcomes in patients with ALI. Routine use of ß2-agonist therapy in mechanically ventilated patients with ALI cannot be recommended. Clinical trial registered with www.clinicaltrials.gov (NCT 00434993).