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Background: Resuscitation directives should be a sign of patient's preference. Our objective was to ascertain prevalence, predictors, and procurement pattern of cardiopulmonary resuscitation directives within 24 h of admission to the intensive-care unit (ICU)., Methods: We enrolled 2916 patients aged 18 years and older from 15 ICUs in four countries, and recorded whether, when, and by whom their cardiopulmonary resuscitation directives were established. By polychotomous logistic regression we identified factors associated with a resuscitate or do-not-resuscitate directive., Findings: Of 2916 patients, 318 (11%; 95% CI 9.8-12.1) had an explicit resuscitation directive. In 159 (50%; 44.4-55.6) patients, the directive was do-not-resuscitate. Directives were established by residents for 145 (46%; 40.0-51.3) patients. Age strongly predicted do-not-resuscitate directives: for 50-64, 65-74, and 75 years and older, odds ratios were 3.4 (95% CI 1.6-7.3), 4.4 (2.2-9.2), and 8.8 (4.4-17.8), respectively. APACHE II scores greater than 20 predicted resuscitate and do-not-resuscitate directives in a similar way. An explicit directive was likely for patients admitted at night (odds ratio 1.4 [1.0-1.9] and 1.6 [1.2-2.3] for resuscitate and do-not-resuscitate, respectively) and during weekends (1.9 [1.3-2.7] and 2.2 [1.5-3.2], respectively). Inability to make a decision raised the likelihood of a do-not-resuscitate (3.7 [2.6-5.4]) than a resuscitate (1.7 [1.2-2.3]) directive (p=0.0005). Within Canada and the USA, cities differed strikingly, as did centres within cities., Interpretation: Cardiopulmonary resuscitation directives established within 24 h of admission to ICU are uncommon. As well as clinical factors, timing and location of admission might determine rate and nature of resuscitation directives.

Objective: To estimate the mortality and length of stay in the intensive care unit (ICU) attributable to clinically important gastrointestinal bleeding in mechanically ventilated critically ill patients., Design: Three strategies were used to estimate the mortality attributable to bleeding in two multicentre databases. The first method matched patients who bled with those who did not (matched cohort), using duration of ICU stay prior to the bleed, each of six domains of the Multiple Organ Dysfunction Score (MODS) measured 3 days prior to the bleed, APACHE II score, age, admitting diagnosis, and duration of mechanical ventilation. The second approach employed Cox proportional hazards regression to match bleeding and non-bleeding patients (model-based matched cohort). The third method, instead of matching, derived estimates based on regression modelling using the entire population (regression method). Three parallel analyses were conducted for the length of ICU stay attributable to clinically important bleeding., Setting: Sixteen Canadian university-affiliated ICUs., Patients: A total of 1666 critically ill patients receiving mechanical ventilation for at least 48 hours., Measurements: We prospectively collected data on patient demographics, APACHE II score, admitting diagnosis, daily MODS, clinically important bleeding, length of ICU stay, and mortality. Independent adjudicators determined the occurrence of clinically important gastrointestinal bleeding, defined as overt bleeding in association with haemodynamic compromise or blood transfusion., Results: Of 1666 patients, 59 developed clinically important gastrointestinal bleeding. The mean APACHE II score was 22.9 +/- 8.6 among bleeding patients and 23.3 +/- 7.7 among non-bleeding patients. The risk of death was increased in patients with bleeding using all three analytic approaches (matched cohort method: relative risk [RR]= 2.9, 95% confidence interval (CI)= 1.6-5.5; model-based matched cohort method: RR = 1.8, 95% CI = 1.1-2.9; and the regression method: RR = 4.1, 95% CI = 2.6-6.5). However, this was not significant for the adjusted regression method (RR = 1.0, 95% CI = 0.6-1.7). The median length of ICU stay attributable to clinically important bleeding for these three methods, respectively, was 3.8 days (95% CI = -0.01 to 7.6 days), 6.7 days (95% CI = 2.7-10.7 days), and 7.9 days (95% CI = 1.4-14.4 days)., Conclusions: Clinically important upper gastrointestinal bleeding has an important attributable morbidity and mortality, associated with a RR of death of 1-4 and an excess length of ICU stay of approximately 4-8 days.

Objective: To determine how frequently life support is withheld or withdrawn from adult critically ill patients, and how physicians and patients families agree on the decision regarding the limitation of life support., Design: Prospective multi-centre cohort study., Setting: Six adult medical-surgical Spanish intensive care units (ICUs)., Patients and Participants: Three thousand four hundred ninety-eight consecutive patients admitted to six ICUs were enrolled., Measurements and Results: Data collected included age, sex, SAPS II score on admission and within 24 h of the decision to limit treatment, length of ICU stay, outcome at ICU discharge, cause and mode of death, time to death after the decision to withhold or withdraw life support, consultation and agreement with patient's family regarding withholding or withdrawal, and the modalities of therapies withdrawn or withheld. Two hundred twenty-six (6.6%) of 3,498 patients had therapy withheld or withdrawn and 221 of them died in the ICU. Age, SAPS II and length of ICU stay were significantly higher in patients dying patients who had therapy withheld or withdrawn than in patients dying despite active treatment. The proposal to withhold or withdraw life support was initiated by physicians in 210 (92.9%) of 226 patients and by the family in the remaining cases. The patient's family was not involved in the decision to withhold or withdraw life support therapy in 64 (28.3%) of 226 cases. Only 21 (9%) patients had expressed their wish to decline life-prolonging therapy prior to ICU admission., Conclusions: The withholding and withdrawing of treatment was frequent in critically ill patients and was initiated primarily by physicians.

Background: Understanding the risk factors for ventilator-associated pneumonia can help to assess prognosis and devise and test preventive strategies., Objective: To examine the baseline and time-dependent risk factors for ventilator-associated pneumonia and to determine the conditional probability and cumulative risk over the duration of stay in the intensive care unit., Design: Prospective cohort study., Setting: 16 intensive care units in Canada., Patients: 1014 mechanically ventilated patients., Measurements: Demographic and time-dependent variables reflecting illness severity, ventilation, nutrition, and drug exposure. Pneumonia was classified by using five methods: adjudication committee, bedside clinician's diagnosis, Centers for Disease Control and Prevention definition, Clinical Pulmonary Infection score, and positive culture from bronchoalveolar lavage or protected specimen brush., Results: 177 of 1014 patients (17.5%) developed ventilator-associated pneumonia 9.0 +/- 5.9 days (median, 7 days [interquartile range, 5 to 10 days]) after admission to the intensive care unit. Although the cumulative risk increased over time, the daily hazard rate decreased after day 5 (3.3% at day 5, 2.3% at day 10, and 1.3% at day 15). Independent predictors of ventilator-associated pneumonia in multivariable analysis were a primary admitting diagnosis of burns (risk ratio, 5.09 [95% CI, 1.52 to 17.03]), trauma (risk ratio, 5.00 [CI, 1.91 to 13.11]), central nervous system disease (risk ratio, 3.40 [CI, 1.31 to 8.81]), respiratory disease (risk ratio, 2.79 [CI, 1.04 to 7.51]), cardiac disease (risk ratio, 2.72 [CI, 1.05 to 7.01]), mechanical ventilation in the previous 24 hours (risk ratio, 2.28 [CI, 1.11 to 4.68]), witnessed aspiration (risk ratio, 3.25 [CI, 1.62 to 6.50]), and paralytic agents (risk ratio, 1.57 [CI, 1.03 to 2.39]). Exposure to antibiotics conferred protection (risk ratio, 0.37 [CI, 0.27 to 0.51]). Independent risk factors were the same regardless of the pneumonia definition used., Conclusions: The daily risk for pneumonia decreases with increasing duration of stay in the intensive care unit. Witnessed aspiration and exposure to paralytic agents are potentially modifiable independent risk factors. Exposure to antibiotics was associated with low rates of early ventilator-associated pneumonia, but this effect attenuates over time.

We conducted a randomized, double-blind, placebo-controlled trial in mechanically ventilated intensive care unit (ICU) patients to evaluate the effect of cisapride on gastric emptying using an acetaminophen absorption model. We enrolled 72 patients expected to remain in the ICU for more than 48 h; 39% were female; the average age was 54.0 +/- 19.1 yr; 47% were postoperative, 83% were receiving narcotics, and the mean simplified acute physiology score (SAPS) was 9.5 +/- 3.0. Within 72 h of admission to ICU, 1.6 g of acetaminophen suspension was administered via a nasogastric tube into the stomach (Day 1). Blood samples were drawn at baseline, 30, 60, 90, 120, and 180 min for measurement of plasma acetaminophen levels. The following morning (Day 2), patients were randomized to receive 20 mg of cisapride or placebo and gastric emptying was again assessed. The difference (Day 2-Day 1) in the maximal plasma concentration was 49.1 mumol/L in the cisapride groups compared with 12.3 mumol/L in the placebo group (p = 0.005) and the time to reach maximal concentration was significantly shorter in the cisapride group (-40.8 min versus -4.2 min, p = 0.02). The difference in area under the time-acetaminophen concentration curve was also greater in the patients receiving cisapride (5,534 versus 2,832, p = 0.09). We conclude that cisapride enhances gastric emptying in critically ill patients. Studies to examine the effect of cisapride on tolerance to enteral nutrition, infectious morbidity, and other clinically important outcomes are warranted.

Objective: To systemically review the effect of interventions designed to achieve supraphysiologic values of cardiac index, oxygen delivery (DO2), and oxygen consumption (VO2) in critically ill patients., Data Sources: Computerized bibliographic search of published research, citation review of relevant articles, and contact with primary investigators., Study Selection: We included all randomized clinical trials of adult intensive care unit (ICU) patients that evaluated interventions (fluids, inotropes, and vasoactive drugs) designed to achieve supraphysiologic values of cardiac index, DO2, and/or VO2. Independent review of 64 articles identified seven relevant studies of 1,016 patients., Data Extraction: We abstracted data on the population, interventions, outcomes, and methodologic quality of the studies by duplicate independent review. Agreement was high (weighed kappa 0.73); differences were resolved by consensus., Data Synthesis: Targeting therapy to achieve supraphysiologic end points in critically ill patients is associated with a nonstatistically significant trend toward decreased mortality rates (relative risk 0.86, 95% confidence intervals 0.62 to 1.20). For the two studies in which supraphysiologic goals were initiated preoperatively, the relative risk was 0.20 (95% confidence intervals 0.07 to 0.55). This value differed significantly from the combined estimate of the remaining studies, in which the intervention was started after ICU admission (relative risk 0.98, 95% confidence intervals 0.79 to 1.22; p<.01). However, there are several methodologic problems with the primary studies. In no trials were caregivers or outcome assessors blinded to treatment allocation. Only three of seven trials analyzed patients according to the group to which they were allocated. None adequately controlled for cointerventions, and there was considerable crossover between groups (patients in the control group achieved the goals of the intervention group and vice versa)., Conclusions: Interventions designed to achieve supraphysiologic goals of cardiac index, DO2, and VO2 did not significantly reduce mortality rates in all critically ill patients. However, there may be a benefit in those patients in which the therapy is initiated preoperatively. Methodologic limitations weaken the inferences that can be drawn from these studies and preclude any evidence-based clinical recommendations.

Purpose: To resolve discrepancies in previous systematic overviews and provide estimates of the effect of stress ulcer prophylaxis on gastrointestinal bleeding, pneumonia, and mortality in critically ill patients., Data Identification: Computerized search of published and unpublished research, bibliographies, pharmaceutical and personal files, and conference abstract reports., Study Selection: Independent review of 269 articles identified 63 relevant randomized trials for inclusion., Data Abstraction: We made independent, duplicate assessment of the methodologic quality, population, intervention, and outcomes of each trial., Results: The source of discrepancies between prior meta-analyses included incomplete identification of relevant studies, differential inclusion of non-English language and nonrandomized trials, different definitions of bleeding, provision of additional information through direct correspondence with authors, and different statistical methods. The current overview demonstrates that prophylaxis with histamine2-receptor antagonists decreases the incidence of overt gastrointestinal bleeding (odds ratio [OR], 0.58; 95% confidence interval [CI], 0.42 to 0.79) and clinically important bleeding (OR, 0.44; 95% CI, 0.22 to 0.88). There is a trend toward decreased overt bleeding when antacids are compared with no therapy (OR, 0.66; 95% CI, 0.37 to 1.17). Histamine2-receptor antagonists and antacids are associated with a trend toward lower clinically important bleeding rates than sucralfate is. There is a trend toward an increased risk of pneumonia associated with histamine2-receptor antagonists as compared with no prophylaxis (OR, 1.25; 95% CI, 0.78 to 2.00). Sucralfate is associated with a lower incidence of nosocomial pneumonia when compared with antacids (OR, 0.80; 95% CI, 0.56 to 1.15) and histamine2-receptor antagonists (OR, 0.77; 95% CI, 0.60 to 1.01). Sucralfate is also associated with a reduced mortality rate (OR, 0.73; 95% CI, 0.54 to 0.97) relative to antacids and to histamine2-receptor antagonists (OR, 0.83; 95% CI, 0.63 to 1.09)., Conclusions: Our results emphasize the need for registries to include all randomized trials and demonstrate the importance of explicit methodology for systematic reviews. There is strong evidence of reduced clinically important gastrointestinal bleeding with histamine2-receptor antagonists. Sucralfate may be as effective in reducing bleeding as gastric pH-altering drugs and is associated with lower rates of pneumonia and mortality. However, the data are insufficient to determine the net effect of sucralfate compared with no prophylaxis.

Objectives: To describe current enteral nutrition-prescribing practices for critically ill patients, and to identify factors associated with initiation of, and tolerance to, enteral nutrition., Design: A prospective, cohort study., Setting: Two tertiary care medical-surgical intensive care units (ICU) in Ontario, Canada., Patients: We enrolled 99 consecutive patients who were expected to stay in the ICU for > 3 days and who were unable to tolerate oral nutrition. We followed patients for 21 days or until they tolerated enteral nutrition, tolerated oral nutrition, were discharged from the ICU, or died., Measurements and Main Results: We recorded time elapsed from ICU admission to initiation and tolerance of enteral feedings, and examined factors associated with these events. We defined tolerance as receiving 90% of estimated daily energy requirements for > 48 hrs without gastrointestinal dysfunction (i.e., high gastric residuals, vomiting, diarrhea, abdominal distention). Seventy-three (74%) of 99 patients were started on enteral feedings an average 3.1 days (range 1 to 18) after ICU admission. Of 26 patients never started on enteral nutrition, three (12.5%) patients eventually tolerated oral nutrition, 14 (54.0%) patients were discharged from the ICU, and seven (27.0%) patients died. Reasons for not initiating enteral nutrition included absence of bowel sounds (27.0%), high nasogastric drainage (16.9%), contraindication to enteral nutrition (16.7%), tolerance of oral nutrition (6.8%), and no apparent reason (5.1%). Abdominal surgery, use of vasoactive drugs, and admission to one hospital made initiation of enteral nutrition less likely, whereas presence of bowel sounds and admission to the other hospital made initiation of enteral nutrition more likely. Thirty-five (42.9%) of 73 patients started on enteral nutrition achieved tolerance of the regimen. The average time from ICU admission to tolerance of feedings was 5.8 days (range 1 to 14). Once started on enteral nutrition, the most common reasons for decreasing or discontinuing feedings included high gastric residuals (51.0%), mechanical feeding tube problems (15.4%), medical or surgical procedures (5.4%), and vomiting (5.1%). Use of paralytic agents and the presence of high gastric residuals were associated with intolerance. Of 38 patients who did not achieve tolerance, 20 (52.6%) patients were discharged from the ICU, eight (21.0%) patients died, and eight (21.0%) patients eventually tolerated oral nutrition., Conclusions: Enteral nutrition is not started in all eligible ICU patients. Approximately half of those patients receiving enteral nutrition achieved tolerance of the regimen. Gastrointestinal dysfunction causing intolerance to enteral nutrition is a common reason for not starting, or discontinuing, feedings.

Objective: To examine the attitudes of health care workers regarding the withdrawal of life support., Design: Cross-sectional survey., Participants: Attending staff, house staff, and intensive care unit (ICU) nurses in 37 Canadian university-affiliated hospitals., Main Outcome Measures: Health care workers' ratings of the importance of 17 factors considered in the decision to withdraw life support, and their ratings of five levels of care ranging from comfort measures to intensive care in two of 12 different clinical scenarios., Results: We surveyed 1361 respondents (149 of 167 potentially eligible ICU attending staff, 142 of 173 ICU house staff, and 1070 of 1455 ICU nurses, with response rates of 89%, 82% and 74%, respectively). The most important factors were likelihood of surviving the current episode, likelihood of long-term survival, premorbid cognitive function, and age of the patient. In choosing the level of care for the patient scenarios, the same option was chosen by more than 50% of respondents in only one of 12 scenarios; opposite extremes of care were chosen by more than 10% of the respondents in eight of 12 scenarios. Respondent characteristics affecting choices included the number of years since graduation, the city and province in which they worked, the number of beds in their ICU, and their assessment of the likelihood that they would withdraw life support in comparison with their colleagues (P < .001 for all comparisons)., Conclusions: While ICU health care workers consistently identify a number of patient factors as important in decisions to withdraw care, there is extreme variability, which may be explained in part by the values of individual health care providers.

Objective: To examine the relationship between the formulation of enteral nutrition and nosocomial infection in critical illness., Data Sources: Computerized search of published research and reference list review., Study Selection: Review of 151 citations. Included are 31 primary studies in which the authors described the formulation of enteral nutrition and its effect on infectious morbidity and mortality rates in critically ill humans or animals., Data Extraction: Abstraction of the methods of primary studies and the impact of the composition of enteral nutrition on infectious morbidity and mortality rates., Data Synthesis: There is no evidence that the addition of branch-chain amino acids or nucleotides to enteral nutrition reduces infectious morbidity in animals or humans. Supplementation with fish oil, arginine, or glutamine has a variable impact on survival in animal models; there are no clinical trials in critically ill patients that demonstrate reduced infectious morbidity or mortality rates. Some animal studies suggest that intestinal overgrowth and bacterial translocation may be related to the type of fiber used, or elemental or polymeric formulas. Preliminary evidence suggests that Modular Tube Feeds (an enteral formula developed at the Shriner's Burn Institute, Cincinnati, OH), and a commercially available enteral formula (enhanced with omega-3-fatty acids, arginine, and yeast RNA; Impact, Sandoz Nutrition, Minneapolis, MN) may result in decreased infections in burn and postoperative cancer patients, respectively, but not in critically ill patients. Acidification of enteral feeding results in decreased bacterial colonization of the stomach in critically ill patients., Conclusions: Insufficient experimental data exist to permit conclusions that enteral nutrition formulations or supplements reduce infectious morbidity and mortality rates, but results are promising enough to warrant further research.

We performed a meta-analysis to evaluate whether stress ulcer prophylaxis with histamine-2-receptor antagonists or antacids reduces mortality in critically ill patients. It appears that sucralfate results in a lower incidence of nosocomial pneumonia than either antacids or histamine-2-receptor antagonists. With respect to mortality, strong trends favored sucralfate over both antacids and histamine-receptor antagonists.

Background: The efficacy of prophylaxis against stress ulcers in preventing gastrointestinal bleeding in critically ill patients has led to its widespread use. The side effects and cost of prophylaxis, however, necessitate targeting preventive therapy to those patients most likely to benefit., Methods: We conducted a prospective multicenter cohort study in which we evaluated potential risk factors for stress ulceration in patients admitted to intensive care units and documented the occurrence of clinically important gastrointestinal bleeding (defined as overt bleeding in association with hemodynamic compromise or the need for blood transfusion)., Results: Of 2252 patients, 33 (1.5 percent; 95 percent confidence interval, 1.0 to 2.1 percent) had clinically important bleeding. Two strong independent risk factors for bleeding were identified: respiratory failure (odds ratio, 15.6) and coagulopathy (odds ratio, 4.3). Of 847 patients who had one or both of these risk factors, 31 (3.7 percent; 95 percent confidence interval, 2.5 to 5.2 percent) had clinically important bleeding. Of 1405 patients without these risk factors, 2 (0.1 percent; 95 percent confidence interval, 0.02 to 0.5 percent) had clinically important bleeding. The mortality rate was 48.5 percent in the group with bleeding and 9.1 percent in the group without bleeding (P < 0.001)., Conclusions: Few critically ill patients have clinically important gastrointestinal bleeding, and therefore prophylaxis against stress ulcers can be safely withheld from critically ill patients unless they have coagulopathy or require mechanical ventilation.

Objective: To examine the relationship between enteral nutrition (EN) and infection in the critically ill., Setting: Computerized search of published research and review of relevant reference lists., Study Selection: 151 citations were reviewed and 39 articles met selection criteria. Primary studies were included if they evaluated EN in critically ill humans and its effect on infectious morbidity and mortality., Measurements and Results: Relevant data were abstracted on the timing and impact of EN on morbidity, the optimal route of administration, composition and pH of EN, and bacterial contamination of EN. The evidence from human studies that EN, particularly early EN, results in reduced septic morbidity as compared to parenteral nutrition is limited to small, unblinded studies with non-rigorous definitions of pneumonia. There is no evidence to support a preference of feeding into the stomach versus the small bowel. The addition of fish oil, arginine, glutamine and fiber to enteral feeds has a variable impact on survival in animal models; there are no trials in critically ill patients that demonstrate a reduction in infectious morbidity and mortality. Acidification of enteral nutrition results in decreased bacterial colonization of the stomach in critically ill patients. Bacterial contamination of enteral nutrition is an important source of infection., Conclusions: Evidence from experimental data in critically ill patients suggests that enteral nutrition may have a favourable impact on gastrointestinal immunological function and infectious morbidity.