Sepsis-induced myocardial depression is associated with transcriptional changes in energy metabolism and contractile related genes: a physiological and gene expression-based approach.

BACKGROUND: Increased nitric oxide production and altered mitochondrial function have been implicated in sepsis-induced cardiac dysfunction. The molecular mechanisms underlying myocardial depression in sepsis and the contribution of nitric oxide in this process however, are incompletely understood. OBJECTIVES: To assess the transcriptional profile associated with sepsis-induced myocardial depression in a clinically relevant mouse model, and specifically test the hypothesis that critical transcriptional changes are inducible nitric oxide synthase-dependent. DESIGN: Laboratory investigation. SETTING: University affiliated research laboratory. SUBJECTS: C57/BL6 wild type and congenic B6 129P2-Nos2tm1Lau/J (iNOS) mice. INTERVENTIONS: Assessment of myocardial function after 48 hrs of induction of polymicrobial sepsis by caecal ligation and perforation. MEASUREMENTS AND RESULTS: We compared the myocardial transcriptional profile in C57/BL6 wild type mice and congenic B6 129P2-Nos2tm1Lau/J litter mates after 48 hrs of polymicrobial sepsis induced by caecal ligation and perforation. Profiling of 22,690 expressed sequence tags by gene set enrichment analysis demonstrated that inducible nitric oxide synthase -/- failed to down regulate critical bioenergy and metabolism related genes including the gene for peroxisome proliferator-activated receptor gamma coactivator 1. Bioinformatics analysis identified a striking concordance in down regulation of transcriptional activity of proliferator-activated receptor gamma coactivator 1-related transcription factors resulting in sepsis associated myocardial remodeling as shown by isoform switching in the expression of contractile protein myosin heavy chain. In inducible nitric oxide synthase -/- deficient mice, contractile depression was minimal, and the transcriptional switch was absent. CONCLUSIONS: Metabolic and myosin isoform gene expression switch in sepsis-induced myocardial depression is inducible nitric oxide synthase-dependent. Furthermore, we suggest that the molecular switch favoring the expression of fetal isoforms of contraction related proteins is associated with regulation of proliferator-activated receptor gamma coactivator 1 and related transcription factors in an inducible nitric oxide synthase-dependent manner.

The intensive care unit work environment: current challenges and recommendations for the future.

UNLABELLED: The need for critical care services has grown substantially in the last decade in most of the G8 nations. This increasing demand has accentuated an already existing shortage of trained critical care professionals. Recent studies argue that difficulty in recruiting an appropriate workforce relates to a shortage of graduating professionals and unhealthy work environments in which critical care professionals must work. OBJECTIVE: This narrative review summarizes existing literature and experiences about the key work environment challenges reported within the critical care context and suggests best practices-implemented in hospitals or suggested by professional associations-which can be an initial step in enhancing patient care and professional recruitment and retention in our intensive care units, with particular emphasis on the recruitment and retention of an appropriately trained and satisfied workforce. The experiences are categorized for the physical, emotional, and professional environments. A case study is appended to enhance understanding of the magnitude and some of the proposed remedies of these experiences.

Critical care services in Ontario: a survey-based assessment of current and future resource needs.

PURPOSE: In response to the challenges of an aging population and decreasing workforce, the provision of critical care services has been a target for quality and efficiency improvement efforts. Reliable data on available critical care resources is a necessary first step in informing these efforts. We sought to describe the availability of critical care resources, forecast the future requirement for the highest-level critical care beds and to determine the physician management models in critical care units in Ontario, Canada. METHODS: In June 2006, self-administered questionnaires were mailed to the Chief Executive Officers of all acute care hospitals, identified through the Ontario government's hospital database. The questionnaire solicited information on the number and type of critical care units, number of beds, technological resources and management of each unit. RESULTS: Responses were obtained from 174 (100%) hospitals, with 126 (73%) reporting one or more critical care units. We identified 213 critical care units in the province, representing 1789 critical care beds. Over half (59%) of these beds provided mechanical ventilation on a regular basis, representing a capacity of 14.9 critical care and 8.7 mechanically ventilated beds per 100,000 population. Sixty-three percent of units with capacity for mechanical ventilation involved an intensivist in admission and coordination of care. Based on current utilization, the demand for mechanically ventilated beds by 2026 is forecast to increase by 57% over levels available in 2006. Assuming 80% bed utilization, it is estimated that an additional 810 ventilated beds will be needed by 2026. CONCLUSION: Current utilization suggests a substantial increase in the need for the highest-level critical care beds over the next two decades. Our findings also indicate that non-intensivists direct care decisions in a large number of responding units. Unless major investments are made, significant improvements in efficiency will be required to maintain future access to these services.

Intensive care outcomes in bone marrow transplant recipients: a population-based cohort analysis.

INTRODUCTION: Intensive care unit (ICU) admission for bone marrow transplant recipients immediately following transplantation is an ominous event, yet the survival of these patients with subsequent ICU admissions is unknown. Our objective was to determine the long-term outcome of bone marrow transplant recipients admitted to an ICU during subsequent hospitalizations. METHODS: We conducted a population-based cohort analysis of all adult bone marrow transplant recipients who received subsequent ICU care in Ontario, Canada from 1 January 1992 to 31 March 2002. The primary endpoint was mortality at 1 year. RESULTS: A total of 2,653 patients received bone marrow transplantation; 504 of which received ICU care during a subsequent hospitalization. Patients receiving any major procedure during their ICU stay had higher 1-year mortality than those patients who received no ICU procedure (87% versus 44%, P < 0.0001). Death rates at 1 year were highest for those receiving mechanical ventilation (87%), pulmonary artery catheterization (91%), or hemodialysis (94%). In combination, the strongest independent predictors of death at 1 year were mechanical ventilation (odds ratio, 7.4; 95% confidence interval, 4.8 to 11.4) and hemodialysis (odds ratio, 8.7; 95% confidence interval, 2.1 to 36.7), yet no combination of procedures uniformly predicted 100% mortality. CONCLUSION: The prognosis of bone marrow transplant recipients receiving ICU care during subsequent hospitalizations is very poor but should not be considered futile.

Legislative barriers to outpatient e-prescribing in a randomized trial.

Newer outpatient electronic prescribing software programs produce typewritten paper prescriptions with electronically created signatures. Current Canadian federal legislation forbids static (unchanging) signature images on prescriptions. We conducted a randomized trial of electronic prescribing in outpatients at a university-affiliated hospital. The application was a wireless Palm-based system that creates a prescription that is either printed and given to the patient or faxed to a pharmacy. Using the software, the physician creates a unique signature image for each prescription. We successfully overcame challenges related to wireless network reliability, local printer availability and physician training. However, to comply with federal legislation and provincial regulations, we were required to design workarounds to create acceptable prescribing processes. Our experience suggests that the legality of the electronic signature must be clearly defined to realize the full potential of standalone outpatient electronic prescribing systems and fully integrated hospital-wide electronic medical records.

Sex-and age-based differences in the delivery and outcomes of critical care.

BACKGROUND: Previous studies have suggested that a patient's sex may influence the provision and outcomes of critical care. Our objective was to determine whether sex and age are associated with differences in admission practices, processes of care and clinical outcomes for critically ill patients. METHODS: We used a retrospective cohort of 466,792 patients, including 24,778 critically ill patients, admitted consecutively to adult hospitals in Ontario between Jan. 1, 2001, and Dec. 31, 2002. We measured associations between sex and age and admission to the intensive care unit (ICU); use of mechanical ventilation, dialysis or pulmonary artery catheterization; length of stay in the ICU and hospital; and death in the ICU, hospital and 1 year after admission. RESULTS: Of the 466,792 patients admitted to hospital, more were women than men (57.0% v. 43.0% for all admissions, p < 0.001; 50.1% v. 49.9% for nonobstetric admissions, p < 0.001). However, fewer women than men were admitted to ICUs (39.9% v. 60.1%, p < 0.001); this difference was most pronounced among older patients (age > or = 50 years). After adjustment for admission diagnoses and comorbidities, older women were less likely than older men to receive care in an ICU setting (odds ratio [OR] 0.68, 95% confidence interval [CI] 0.66-0.71). After adjustment for illness severity, older women were also less likely than older men to receive mechanical ventilation (OR 0.91, 95% CI 0.81-0.97) or pulmonary artery catheterization (OR 0.80, 95% CI 0.73-0.88). Despite older men and women having similar severity of illness on ICU admission, women received ICU care for a slightly shorter duration yet had a longer length of stay in hospital (mean 18.3 v. 16.9 days; p = 0.006). After adjustment for differences in comorbidities, source of admission, ICU admission diagnosis and illness severity, older women had a slightly greater risk of death in the ICU (hazard ratio 1.20, 95% CI 1.10-1.31) and in hospital (hazard ratio 1.08, 95% CI 1.00-1.16) than did older men. INTERPRETATION: Among patients 50 years or older, women appear less likely than men to be admitted to an ICU and to receive selected life-supporting treatments and more likely than men to die after critical illness. Differences in presentation of critical illness, decision-making or unmeasured confounding factors may contribute to these findings.

Knowledge translation in critical care: factors associated with prescription of commonly recommended best practices for critically ill patients.

OBJECTIVE: To describe prescription rates of commonly recommended best practices (clinical interventions with a strong base of evidence supporting their implementation) for critically ill patients and determine factors associated with increased rates of prescription. DESIGN: A retrospective observational study. SETTING: A university-affiliated medical-surgical-trauma intensive care unit over a 1-yr period. PATIENTS: One hundred randomly selected critically ill patients. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Among the best practices studied, there was great variability in the proportion of patients eligible (median 36.5%, range 10% to 100%) and the proportion without contraindication (32.5%, range 10% to 86%) for each practice. The median rate of prescription of best practices for eligible patients was 56.5%, with a range from 8% to 95%. There was greater prescription of best practices when standard admission orders included an option to prescribe them (p = .048). Among those practices with standard admission orders, there was greatest prescription for practices additionally having a specialty consultation service (p = .004). There was an inverse association between severity of illness and prescription of best practices (p = .001): Sicker patients were less likely to be prescribed best practices. CONCLUSIONS: There may be substantial variability in the acceptance and prescription of commonly recommended best practices for critically ill patients. Standard order sets and focused specialty consultation may improve knowledge translation and prescription of best practice.

Risk factors associated with resistance to ciprofloxacin in clinical bacterial isolates from intensive care unit patients.

OBJECTIVE: To determine risk factors and outcomes associated with ciprofloxacin resistance in clinical bacterial isolates from intensive care unit (ICU) patients. DESIGN: Prospective cohort study. SETTING: Twenty-bed medical-surgical ICU in a Canadian tertiary care teaching hospital. PATIENTS: All patients admitted to the ICU with a stay of at least 72 hours between January 1 and December 31, 2003. METHODS: Prospective surveillance to determine patient comorbidities, use of medical devices, nosocomial infections, use of antimicrobials, and outcomes. Characteristics of patients with a ciprofloxacin-resistant gram-negative bacterial organism were compared with characteristics of patients without these pathogens. RESULTS: Ciprofloxacin-resistant organisms were recovered from 20 (6%) of 338 ICU patients, representing 38 (21%) of 178 nonduplicate isolates of gram-negative bacilli. Forty-nine percent of Pseudomonas aeruginosa isolates and 29% of Escherichia coli isolates were resistant to ciprofloxacin. In a multivariate analysis, independent risk factors associated with the recovery of a ciprofloxacin-resistant organism included duration of prior treatment with ciprofloxacin (relative risk [RR], 1.15 per day [95% confidence interval {CI}, 1.08-1.23]; P<.001), duration of prior treatment with levofloxacin (RR, 1.39 per day [95% CI, 1.01-1.91]; P=.04), and length of hospital stay prior to ICU admission (RR, 1.02 per day [95% CI, 1.01-1.03]; P=.005). Neither ICU mortality (15% of patients with a ciprofloxacin-resistant isolate vs 23% of patients with a ciprofloxacin-susceptible isolate; P=.58) nor in-hospital mortality (30% vs 34%; P=.81) were statistically significantly associated with ciprofloxacin resistance. CONCLUSIONS: ICU patients are at risk of developing infections due to ciprofloxacin-resistant organisms. Variables associated with ciprofloxacin resistance include prior use of fluoroquinolones and duration of hospitalization prior to ICU admission. Recognition of these risk factors may influence antibiotic treatment decisions.

Hospital volume and mortality for mechanical ventilation of medical and surgical patients: a population-based analysis using administrative data.

OBJECTIVE: In an effort to improve efficiency and quality of care, regionalization of adult critical care services, similar to trauma and neonatal intensive care, has been suggested. However, there is little research to understand if hospitals with higher patient volumes have better outcomes. Our objective is to determine whether hospital volume is associated with improved survival for medical or surgical patients receiving mechanical ventilation. DESIGN: Population-based retrospective cohort study. SETTING: Province of Ontario, Canada. PATIENTS: A total of 13,846 medical and 6,373 surgical patients receiving mechanical ventilation for greater than two consecutive days between 1998 and 2000. INTERVENTIONS: None. MEASUREMENTS: Odds ratio for death within 30 days of initiation of mechanical ventilation was calculated in relation to hospital volume of ventilation. Estimates were adjusted for patient demographics, diagnoses, and urgency status; hospital region and rural location; and accounted for clustering within hospitals. MAIN RESULTS: There was no effect of volume on mortality for surgical patients. After adjustment for clustering, among medical patients, the lowest-volume category (<100 episodes/yr) had a nonsignificant increase in mortality, with an odds ratio (95% confidence interval) of 1.13 (0.87-1.47) compared with the highest-volume category (> or =700 episodes/yr). A post hoc analysis revealed that within the lowest-volume category, the proportion of patients transferred to larger hospitals was 81% for hospitals with <20 episodes/yr and only 32% for hospitals with 20-99 episodes/yr, with odds ratios (95% confidence interval) for mortality of 0.74 (0.49-1.12) and 1.18 (0.90-1.54), respectively, compared with the highest-volume category. CONCLUSIONS: For surgical patients requiring mechanical ventilation for >2 days, hospital volume had no effect on mortality. For medical patients, higher mortality may occur in a subgroup of low-volume hospitals that do not routinely transfer their patients to larger-volume facilities. This finding needs further investigation in a larger-sized study.

Intensive care and emergency medicine: progress over the past 25 years.

Over the last quarter of a century, intensive care medicine has developed into an established hospital specialty with its own unique identity and characteristics. Significant advances have occurred, mostly in a succession of small steps rather than any dramatic leap, with many being linked to advances in health care across other disciplines. In addition, many changes have resulted from the scientific identification of the detrimental effects of certain traditional practices once thought to be therapeutic. Here, in an attempt to learn from the past and offer guidance for future progress, we detail some of the key changes in various aspects of intensive care medicine including respiratory, cardiovascular, metabolic, and nutritional care, as well as sepsis, polytrauma, organization, and management.

Differential inducible nitric oxide synthase activity in circulating neutrophils vs. mononuclears of septic shock patients.

OBJECTIVE: To compare nitric oxide synthase (NOS) activity in circulating neutrophils and mononuclear cells of patients with septic shock to healthy subjects. DESIGN AND SETTING: Prospective study in the general intensive care unit (30 beds) of a university affiliated-hospital and the A.C. Burton Vascular Biology Research Laboratory. PATIENTS: Six septic patients and seven healthy volunteers. MEASUREMENTS AND RESULTS: We measured NOS in circulating neutrophils and mononuclears. Constitutive (cNOS) and inducible (iNOS) activities were analyzed by the [3H]L-arginine-L-citrulline assay. Plasma NOx- was determined by chemiluminescence. NOx- was higher in septic vs. controls (median 110, IQR 39-250 vs. 23, 14-46 microM; p<0.05). cNOS in septic cells was unmeasurable. iNOS in septic neutrophils was higher (median 34.9, IQR 10.4-95.8 vs. controls 2.5, 0-2.7 U; p<0.05) while iNOS in septic mononuclears was unaltered (median 16.4, IQR 9.1-52.6 vs. controls 8.9, 5.9-20.3 U; p=0.240). CONCLUSIONS: Increased iNOS activity was found in circulating neutrophils of septic shock patients compared to healthy volunteers. Moreover, differential iNOS activity was evident in circulating neutrophils vs. mononuclears of patients with septic shock. Further investigations are warranted to confirm this differential iNOS activity and to explore its significance.

Projected incidence of mechanical ventilation in Ontario to 2026: Preparing for the aging baby boomers.

OBJECTIVE: The aging baby boomers are expected to have a significant impact on the healthcare system. Mechanical ventilation is an age-dependent, costly, and relatively nondiscretionary medical service that may be particularly affected by the aging population. We forecast the future incidence of mechanical ventilation to the year 2026 to understand the impact of aging baby boomers on critical care resources. DESIGN: Population-based, sex-specific, and age-specific mechanical ventilation incidences for adults for the year 2000 were directly standardized to population projections to estimate the incidence of mechanical ventilation, in 5-yr intervals, from 2006 to 2026. Sensitivity analyses were performed by varying population projections and mechanical ventilation incidence for the elderly. SETTING: Province of Ontario, Canada. PATIENTS: Noncardiac surgery, mechanically ventilated adults. INTERVENTIONS: None. MAIN RESULTS: The projected number of ventilated patients in 2026 was 34,478, representing an 80% increase from 2000. The crude incidence increased 31%, from 222 to 291 per 100,000 adults. The annually compounded projected growth rate during this 26-yr period was 2.3%, similar to the actual growth rate experienced in the 1990s. The projected incidence was relatively insensitive to changes in assumptions, with estimates for 2026 ranging from 31,473 to 36,313 ventilated adults. CONCLUSIONS: The incidence of mechanical ventilation projected to the year 2026 will steadily increase and outpace population growth as occurred in the 1990s. In the current environment in which intensive care unit resources are limited and ventilated patients already use a significant proportion of acute care resources, planning for this continued growth is necessary. Existing evidence-based strategies that improve both the efficiency and efficacy of critical care services should be carefully evaluated for widespread implementation.

Shockingly complex: the difficult road to introducing new ideas to critical care.

Resuscitation of critically ill patients with trauma or sepsis continues to challenge clinicians. Early imperatives include diagnostic judgment as to the presenting problem - sepsis or trauma. Subsequently, the clinician decides on the phase of resuscitation required for support - 'ebb' versus 'flow'. Finally, the clinician needs to determine what therapeutic strategies to employ and then judge when resuscitation is complete. Shortcomings of current approaches to determining the adequacy of circulatory resuscitation have prompted the evaluation of new technologies purported to directly assess microcirculatory flow as a clinical endpoint for the adequacy of resuscitation. While early studies are intriguing, this technology requires much more study before it can be considered for widespread adoption by the clinician.

Mechanical ventilation in Ontario, 1992-2000: incidence, survival, and hospital bed utilization of noncardiac surgery adult patients.

OBJECTIVE: Mechanical ventilation is a common therapy used in caring for critically ill patients, but its epidemiology is poorly understood. We describe population-based, temporal trends in the incidence, survival, and hospital bed utilization of mechanically ventilated, noncardiac surgery adult patients. DESIGN: Retrospective, observational cohort study using linked administrative databases. SETTING: Province of Ontario, Canada. PATIENTS: Subjects were 150,755 unique patients who received mechanical ventilation between 1992 and 2000. INTERVENTIONS: None. MEASUREMENTS: Annual measures of mechanical ventilation incidence, 30-day patient mortality rate, and number of mechanical ventilation days and inpatient days for mechanically ventilated patients as a proportion of total adult inpatient bed days. MAIN RESULTS: From 1992 to 2000, the crude and age- and gender-adjusted incidence of mechanical ventilation increased 9% (p <.001) and 2% (p <.027), respectively, to 217 per 100,000 adults. Crude mortality rate 30 days after initiation of mechanical ventilation increased from 27% to 32% (p <.001). Significant predictors of 30-day mortality rate (adjusted hazard ratio, 95% confidence interval) were calendar year (1.03, 1.02-1.03), age >80 yrs (2.3, 2.2-2.3), Charlson score 3+ (2.0, 2.0-2.1), and specific diagnosis. From 1992 to 2000, the number of mechanical ventilation days and inpatient days for mechanically ventilated patients, as a proportion of total adult inpatient bed days, increased 69% and 30% (both p <.001), respectively, to 1.8% and 6.2%. CONCLUSIONS: There was a small, but important, increase in mechanical ventilation incidence and a substantial increase in the proportion of inpatient bed days used by mechanically ventilated patients in Ontario during the 1990s. These trends are important in planning for expansion of health care resources to meet the needs of the aging population. The increase, over time, in risk-adjusted mortality rate of mechanically ventilated patients is concerning and requires further investigation.

Pseudomonas pneumonia-mediated sepsis induces expression of pancreatitis-associated protein-I in rat pancreas.

Severe impairment of exocrine pancreatic secretion has recently been demonstrated in a clinical study in sepsis and septic shock patients. The purpose of this study was to further evaluate involvement of the pancreas in the acute phase reaction in sepsis. Using a normotensive rat model of Pseudomonas pneumonia-induced sepsis, we assessed the expression of PAP-I, amylase and trypsinogen mRNA, PAPI protein levels, and cytokine expression in the pancreas by Northern and Western blot analysis and RT-M PCR, respectively. Presence of several well-established features of pancreatitis in sepsis-induced animals were examined by biochemical and histopathological methods as well as by a determination of both water and myeloperoxidase content. Sepsis resulted in an up-regulation of PAP-I gene expression and increase in its protein level in pancreas while the mRNA levels of amylase and trypsinogen were down-regulated. Differences in the pancreatic cytokine expression, serum amylase and serum lipase levels, the occurrence of pancreatic edema as well as the severity of inflammatory infiltration and necrosis were not significantly different between sham and pneumonia groups. Acinar cells showed increased vacuolization in pneumonia animals 24 hours after the treatment. These findings demonstrate that the pancreas is actively involved in the acute phase reaction in sepsis of remote origin. This involvement occurs without concomitant biochemical and histopathologic alterations observed in pancreatitis. Taken all together, these features are indicative of a sepsis-specific dysfunction of the pancreas.

Tissue oxygen delivery and the microcirculation.

In health, acute anemia is accompanied by changes in the distribution of blood flows at all of the central, regional, and microcirculatory levels. This redistribution in blood flows provides the capacity to maintain tissue oxygenation with hematocrit as low as 21%. What is not known with certainty is whether the capacity to maintain tissue oxygenation in the presence of acute anemia can be influenced significantly by concurrent disease such as sepsis and cardiac disease. The single clinical trial found an apparent survival benefit by not exposing patients with sepsis to blood transfusions until the hemoglobin concentration was less than 70 g/L. The question remains as to whether this observation was the consequence of a protective effect anemia or an injurious effect of transfusing old stored blood.

Transmission of severe acute respiratory syndrome during intubation and mechanical ventilation.

Nosocomial transmission of severe acute respiratory syndrome from critically ill patients to healthcare workers has been a prominent and worrisome feature of existing outbreaks. We have observed a greater risk of developing severe acute respiratory syndrome for physicians and nurses performing endotracheal intubation (relative risk [RR], 13.29; 95% confidence interval [CI], 2.99 to 59.04; p = 0.003). Nurses caring for patients receiving noninvasive positive-pressure ventilation may be at an increased risk (RR, 2.33; 95% CI, 0.25 to 21.76; p = 0.5), whereas nurses caring for patients receiving high-frequency oscillatory ventilation do not appear at an increased risk (RR, 0.74; 95% CI, 0.11 to 4.92; p = 0.6) compared with their respective reference cohorts. Specific infection control recommendations concerning the care of critically ill patients may help limit further nosocomial transmission.

Multicentre, cluster-randomized clinical trial of algorithms for critical-care enteral and parenteral therapy (ACCEPT).

BACKGROUND: The provision of nutritional support for patients in intensive care units (ICUs) varies widely both within and between institutions. We tested the hypothesis that evidence-based algorithms to improve nutritional support in the ICU would improve patient outcomes. METHODS: A cluster-randomized controlled trial was performed in the ICUs of 11 community and 3 teaching hospitals between October 1997 and September 1998. Hospital ICUs were stratified by hospital type and randomized to the intervention or control arm. Patients at least 16 years of age with an expected ICU stay of at least 48 hours were enrolled in the study (n = 499). Evidence-based recommendations were introduced in the 7 intervention hospitals by means of in-service education sessions, reminders (local dietitian, posters) and academic detailing that stressed early institution of nutritional support, preferably enteral. RESULTS: Two hospitals crossed over and were excluded from the primary analysis. Compared with the patients in the control hospitals (n = 214), the patients in the intervention hospitals (n = 248) received significantly more days of enteral nutrition (6.7 v. 5.4 per 10 patient-days; p = 0.042), had a significantly shorter mean stay in hospital (25 v. 35 days; p = 0.003) and showed a trend toward reduced mortality (27% v. 37%; p = 0.058). The mean stay in the ICU did not differ between the control and intervention groups (10.9 v. 11.8 days; p = 0.7). INTERPRETATION: Implementation of evidence-based recommendations improved the provision of nutritional support and was associated with improved clinical outcomes.