Joe Pagliarello

Risk factors for clinically important upper gastrointestinal bleeding in patients requiring mechanical ventilation

OBJECTIVE To evaluate the incidence and risk factors for clinically important upper gastrointestinal bleeding in critically ill patients requiring mechanical ventilation. DESIGN In duplicate, blinded adjudicators determined the presence of clinically important gastrointestinal bleeding using a priori criteria, evaluating relevant clinical, laboratory, and diagnostic data. Cox proportional hazards regression analyses were used to examine baseline and time-dependent risk factors for bleeding. SETTING Sixteen university-affiliated intensive care units (ICUs) in Canada. PATIENTS A total of 1,077 critically ill ICU patients ventilated for at least 48 hrs. INTERVENTIONS Patients were randomized to stress ulcer prophylaxis with intravenous ranitidine or nasogastric sucralfate; otherwise, management was at the discretion of the ICU team. MEASUREMENTS AND MAIN RESULTS Demographic data included patient characteristics, Acute Physiology and Chronic Health Evaluation II score, and multiple organ dysfunction (MOD) score. Each day in the ICU, physiologic measurements including MOD score, feeding, and other treatment variables were recorded. The significant risk factors for upper gastrointestinal bleeding in the univariable analyses were low platelet count, maximum serum creatinine, maximum MOD score, maximum pulmonary component of the MOD score, maximum hepatic component of the MOD score, maximum renal component of the MOD score, enteral nutrition, and stress ulcer prophylaxis with ranitidine. The only independent predictors of bleeding in the multivariable analysis were maximum serum creatinine (relative risk = 1.16 [95% confidence interval = 1.02-1.32]), enteral nutrition (relative risk = 0.30 [95% confidence interval = 0.13-0.67]), and ranitidine administration (relative risk = 0.39 [95% confidence interval = 0.17-0.83]). CONCLUSIONS In critically ill ventilated patients, renal failure was independently associated with an increased risk of clinically important gastrointestinal bleeding, whereas enteral nutrition and stress ulcer prophylaxis with ranitidine conferred significantly lower bleeding rates.

Organ donor management in Canada: recommendations of the forum on Medical Management to Optimize Donor Organ Potential

In collaboration with the Canadian Critical Care Society, the Canadian Association of Transplantation and the Canadian Society of Transplantation, the Canadian Council for Donation and Transplantation (CCDT) sponsored a forum entitled „Medical Management to Optimize Donor Organ Potential,” 23–

The PRECISE RCT: Evolution of an Early Septic Shock Fluid Resuscitation Trial

Severe sepsis and septic shock are the most common reasons for admission to an intensive care unit; and the risk of death is substantial, estimated at approximately 40%. Evidence suggests that early resuscitation strategies that include the use of resuscitation fluids, antibiotics, blood, and inotropes reduce death. Although fluid resuscitation is an immediate life-saving intervention, a fundamental question that remains unanswered is whether the type of resuscitation fluid impacts survival when it is initiated very early in the course of septic shock. A randomized controlled trial published in 2008 confirmed that hydroxyethyl starch fluids cause acute renal failure defined by the requirement for renal replacement therapy. In contrast, a subgroup analysis from a randomized controlled trial suggests that 4% albumin fluid may reduce death from severe sepsis; however, these findings require confirmation in a large randomized trial. Our team is planning a pragmatic early septic shock fluid resuscitation trial that will compare the effectiveness of 5% albumin vs normal saline on 90-day mortality (PRECISE). In this article, we summarize the scientific rationale and inherent challenges associated with the conduct of PRECISE, the background work and planning elements that have been undertaken, and the PRECISE RCT protocol with rationale and justifications provided for the chosen population, the interventions, and the outcome measures.

Fluid Resuscitation with 5% albumin versus Normal Saline in Early Septic Shock: a pilot randomized, controlled trial.

PURPOSE Randomized, controlled trials of fluid resuscitation in early septic shock face many logistic challenges. We describe the Fluid Resuscitation with 5% albumin versus Normal Saline in Early Septic Shock (PRECISE) pilot trial study design and report feasibility of patient recruitment. MATERIALS AND METHODS Six Canadian academic centers enrolled adult patients with early suspected septic shock from the emergency department and intensive care unit department. Consent was deferred. Using concealed allocation, participants were randomized to either 5% albumin or 0.9% sodium chloride. Blinded fluid resuscitation started immediately and continued for 7 days in the intensive care unit. Target recruitment was established a priori at 2 patients per site per month. RESULTS Fifty-one patients were enrolled; 50 patients received study fluid. We recruited a median of 2.5 patients (interquartile range [IQR], 1.5-3.0) per site per month into the trial. Median age and Acute Physiology and Chronic Health Evaluation II scores were 64.5 (IQR, 55.0-78.0) and 25.0 (IQR, 20.0-29.0), respectively. Most patients (n = 37 [74.0%]) were enrolled from the emergency department for a median of 1.6 hours (IQR, 0.8-3.5 hours) from their first hypotensive event and received a median of 2.4 L (IQR, 1.5-3.0 L) of resuscitation fluid before inclusion. Consent was deferred for 44 patients (89.8%). CONCLUSIONS Patient recruitment into the PRECISE pilot trial met our prespecified feasibility targets, and the PRECISE team is planning the larger trial.