Claudio M. Martin

A multicenter, randomized, controlled clinical trial of transfusion requirements in critical care. Transfusion Requirements in Critical Care Investigators, Canadian Critical Care Trials Group.

BACKGROUND To determine whether a restrictive strategy of red-cell transfusion and a liberal strategy produced equivalent results in critically ill patients, we compared the rates of death from all causes at 30 days and the severity of organ dysfunction. METHODS We enrolled 838 critically ill patients with euvolemia after initial treatment who had hemoglobin concentrations of less than 9.0 g per deciliter within 72 hours after admission to the intensive care unit and randomly assigned 418 patients to a restrictive strategy of transfusion, in which red cells were transfused if the hemoglobin concentration dropped below 7.0 g per deciliter and hemoglobin concentrations were maintained at 7.0 to 9.0 g per deciliter, and 420 patients to a liberal strategy, in which transfusions were given when the hemoglobin concentration fell below 10.0 g per deciliter and hemoglobin concentrations were maintained at 10.0 to 12.0 g per deciliter. RESULTS Overall, 30-day mortality was similar in the two groups (18.7 percent vs. 23.3 percent, P= 0.11). However, the rates were significantly lower with the restrictive transfusion strategy among patients who were less acutely ill -- those with an Acute Physiology and Chronic Health Evaluation II score of < or =20 (8.7 percent in the restrictive-strategy group and 16.1 percent in the liberal-strategy group; P=0.03) -- and among patients who were less than 55 years of age (5.7 percent and 13.0 percent, respectively; P=0.02), but not among patients with clinically significant cardiac disease (20.5 percent and 22.9 percent, respectively; P=0.69). The mortality rate during hospitalization was significantly lower in the restrictive-strategy group (22.3 percent vs. 28.1 percent, P=0.05). CONCLUSIONS A restrictive strategy of red-cell transfusion is at least as effective as and possibly superior to a liberal transfusion strategy in critically ill patients, with the possible exception of patients with acute myocardial infarction and unstable angina.

Is a low transfusion threshold safe in critically ill patients with cardiovascular diseases

ObjectiveTo compare a restrictive red blood cell transfusion strategy with a more liberal strategy in volume-resuscitated critically ill patients with cardiovascular disease. SettingTwenty-two academic and three community critical care units across Canada. Study Design Randomized controlled clinical trial. Study PopulationThree hundred fifty-seven critically ill patients with cardiovascular diseases from the Transfusion Requirements in Critical Care trial who had a hemoglobin concentration of <90 g/L within 72 hrs of admission to the intensive care unit. InterventionsPatients were randomized to a restrictive strategy to receive allogeneic red blood cell transfusions at a hemoglobin concentration of 70 g/L (and maintained between 70 and 90 g/L) or a liberal strategy to receive red blood cells at 100 g/L (and maintained between 100 and 120 g/L). ResultsBaseline characteristics in the restrictive (n = 160) and the liberal group (n = 197) were comparable, except for the use of cardiac and anesthetic drugs (p < .02). Average hemoglobin concentrations (85 ± 6.2 vs. 103 ± 6.7 g/L;p < .01) and red blood cell units transfused (2.4 ± 4.1 vs. 5.2 ± 5.0 red blood cell units;p < .01) were significantly lower in the restrictive compared with the liberal group. Overall, all mortality rates were similar in both study groups, including 30-day (23% vs. 23%;p = 1.00), 60-day, hospital, and intensive care unit rates. Changes in multiple organ dysfunction from baseline scores were significantly less in the restrictive transfusion group overall (0.2 ± 4.2 vs. 1.3 ± 4.4;p = .02). In the 257 patients with severe ischemic heart disease, there were no statistically significant differences in all survival measures, but this is the only subgroup where the restrictive group had lower but nonsignificant absolute survival rates compared with the patients in the liberal group. ConclusionA restrictive red blood cell transfusion strategy generally appears to be safe in most critically ill patients with cardiovascular disease, with the possible exception of patients with acute myocardial infarcts and unstable angina.

Effect of noninvasive positive pressure ventilation on mortality in patients admitted with acute respiratory failure : A meta-analysis

OBJECTIVE To critically appraise and summarize the trials examining the addition of noninvasive positive pressure ventilation to standard therapy on hospital mortality and need for endotracheal intubation in patients admitted with acute respiratory failure. DATA SOURCES We searched MEDLINE (1966 to September 1995) and key references were searched forward using the Scientific Citation Index (SCISEARCH). Bibliographies of all selected articles and review articles were examined. Authors of all selected and review articles were contacted by letter to identify unpublished work. STUDY SELECTION a) POPULATION patients with acute respiratory failure; b) intervention: noninvasive positive pressure ventilation; c) outcome: mortality and/or endotracheal intubation; and d) design: randomized, controlled study. Two of us independently selected the articles for inclusion; disagreements were settled by consensus. Seven (three unpublished) of 212 initially identified studies were selected. DATA EXTRACTION Two authors independently extracted data and evaluated methodologic quality of the studies. DATA SYNTHESIS Noninvasive positive pressure ventilation was associated with decreased mortality (odds ratio = 0.29; 95% confidence interval 0.15 to 0.59) and a decreased need for endotracheal intubation (odds ratio = 0.20; 95% confidence interval 0.11 to 0.36). Sensitivity analysis suggested a greater benefit of noninvasive positive pressure ventilation in patients with chronic obstructive pulmonary disease (COPD). The inclusion/exclusion of unpublished trials did not influence these results. CONCLUSIONS The addition of noninvasive positive pressure ventilation to standard therapy in patients with acute respiratory failure improves survival and decreases the need for endotracheal intubation. However, this effect is restricted to patients whose cause of acute respiratory failure is an exacerbation of COPD. Further research is warranted to determine whether noninvasive positive pressure ventilation confers benefit in patients without COPD who have acute respiratory failure.

A Canadian survey of transfusion practices in critically ill patients

OBJECTIVES To characterize the contemporary red cell transfusion practice in the critically ill and to define clinical factors that influence these practices. DESIGN Scenario-based national survey. STUDY POPULATION Canadian critical care practitioners. MEASUREMENTS AND MAIN RESULTS We evaluated transfusion thresholds before transfusion and the number of red cell units ordered, under the given conditions. Of 254 Canadian critical care physicians, 193 (76%) responded to the survey. The primary specialty of most respondents was internal medicine (56%). Internal medicine respondents were in practice for an average of 8.4 +/- 5.7 (SD) yrs, and worked most often in combined medical/surgical intensive care units. Baseline hemoglobin transfusion thresholds averaged from 8.3 +/- 1.0 g/dL in a scenario involving a young stable trauma victim to 9.5 +/- 1.0 g/dL for an older patient after gastrointestinal bleeding. Transfusion thresholds differed significantly (p< .0001) between all four separate scenarios. With the exception of congestive heart failure (p> .05), all clinical factors (including age, Acute Physiology and Chronic Health Evaluation II score, preoperative status, hypoxemia, shock, lactic acidosis, coronary ischemia, and chronic anemia) significantly (p< .0001) modified the transfusion thresholds. A statistically significant (p< .01) difference in baseline transfusion thresholds was noted across four major regions (with a maximum of five academic centers per region) of the country. Low physician numbers in two of the regions did not allow for further investigation of regional variations. CONCLUSIONS There is significant variation in critical care transfusion practice, with many intensivists adhering to a 10.0-g/dL threshold, while other physicians described a much more restrictive approach to red cell transfusion. Also, many physicians opted to administer multiple units, despite published guidelines to the contrary. Additionally, the administration of red cells was strongly influenced by a number of clinical factors, many unique to intensive care unit patients. There is a need for prospective studies to define optimal practice in the critically ill.

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

Background: Previous studies have suggested that a patients 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 ≥ 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.

Patients readmitted to the intensive care unit during the same hospitalization: Clinical features and outcomes

OBJECTIVE To determine the clinical features and outcomes of patients readmitted to the intensive care unit (ICU) during the same hospital stay and the causes for these readmissions. DESIGN Multicenter, cohort study. SETTING Three ICUs from two teaching hospitals and four ICUs from four community hospitals. PATIENTS All ICU admissions were collected prospectively for a registry database in the seven ICUs. We retrospectively analyzed ICU admissions between January 1, 1995 and February 29, 1996. INTERVENTIONS None. MEASUREMENTS AND MAIN RESULTS During the study period, 236 (4.6%) of the patients discharged alive from the ICU were readmitted to the unit. Patients with gastrointestinal (GI) and neurologic diagnoses had the highest readmission rate. Of the readmissions, 45% had recurrence of the initial disease, 39% experienced new complications, and 14% required further planned operation. Among patients readmitted for the same illness, cardiovascular and respiratory problems were the most frequent diagnoses. Of patients readmitted with a new diagnosis, 30% initially had GI diseases, while respiratory diseases accounted for 58% of the new complications. Readmissions within 24 hrs occurred in 27% of all readmissions. Patients requiring readmission had a higher hospital mortality rate (31.4%) compared with those not requiring readmission (4.3%, p < .001), even after adjustment for disease severity score (odds ratio = 5.93, p < .001). CONCLUSIONS Patients with GI and neurologic diseases are at greatest risk of requiring ICU readmission. Respiratory diseases are the major reason for readmission due to new complications. Readmitted patients have a high risk of hospital death that may be underestimated by the usual physiologic indicators on either initial admission or readmission. Further studies are required to determine if patients at risk for readmission can be identified early to improve the outcome.

A prospective, observational registry of patients with severe sepsis: The Canadian Sepsis Treatment and Response Registry*

Objective:To determine the location of acquisition, timing, and outcomes associated with severe sepsis in community and teaching hospital critical care units. Design:Prospective, observational study. Setting:Twelve Canadian community and teaching hospital critical care units. Patients:All patients admitted between March 17, 2003, and November 30, 2004 to the study critical care units with at least a 24-hr length of stay or severe sepsis identified during the first 24 hrs. Interventions:Daily monitoring for severe sepsis. Measurements and Main Results:We recorded data describing characteristics of patients, infections, systemic responses, and organ dysfunction. Severe sepsis occurred in 1238 patients (overall rate, 19.0%; range, 8.2%–35.3%). Hospital mortality was 38.1% (95% confidence interval [CI]: 35.4–40.8). Median intensive care unit length of stay was 10.3 days (interquartile range: 5.5, 17.9). Variables associated with mortality in multivariable analysis included age (odds ratio [OR] by decade 1.50; 95% CI: 1.36–1.65), acquisition location of severe sepsis (with community as the reference—hospital [OR: 1.69; CI: 1.16–2.46], early intensive care unit [OR: 2.15; CI: 1.42–3.25], late intensive care unit [OR: 2.65; CI: 1.82–3.87]), late intensive care unit (OR: 2.65; CI: 1.82–3.87), any comorbidity (OR: 1.42; CI: 1.04–1.93), chronic renal failure (OR: 2.03; CI: 1.10–3.76), oliguria (OR: 1.34; CI: 1.02–1.76), thrombocytopenia (OR: 2.12; CI: 1.43–3.13), metabolic acidosis (OR: 1.54; CI: 1.13–2.10), Multiple Organ Dysfunction Score (OR: 1.15; CI: 1.09–1.21) and Acute Physiology and Chronic Health Evaluation II predicted risk (OR: 3.75; CI: 2.08–6.76). Conclusion:These data confirm that sepsis is common and has high mortality in general intensive care unit populations. Our results can inform healthcare system planning and clinical study designs. Modifiable variables associated with worse outcomes, such as nosocomial infection (hospital acquisition), and metabolic acidosis indicate potential targets for quality improvement initiatives that could decrease mortality and morbidity.

Effect of prone positioning in patients with acute respiratory distress syndrome: A meta-analysis

Objective: To review the effectiveness of prone position as compared with supine position, with respect to mortality, improvement in oxygenation, number of days on mechanical ventilation, and ventilator-associated pneumonia. Data Source: PubMed, EMBASE, Cochrane database, and a manual review of article bibliographies. Study Selection: Randomized controlled trials comparing ≥6 hrs of prone position with supine position in adult patients with adult respiratory distress syndrome. Data Extraction: Two reviewers independently performed assessment of abstracts and study quality. Data were combined in a meta-analysis using random-effect models. Main Findings: Five studies were identified. We did not find any significant differences in intensive care unit mortality (three studies, 466 patients; odds ratio, 0.79; 95% confidence interval [CI], 0.45–1.39), 28- to 30-day mortality (three studies, 1,231 patients; odds ratio, 0.95; 95% CI, 0.71–1.28), and 90-day mortality (four studies, 1,271 patients; odds ratio, 0.99; 95% CI, 0.77–1.27). However, prone position showed significant reduction in mortality in patients with higher illness severity (two studies, 113 patients; odds ratio, 0.29; 95% CI, 0.12–0.70). Prone positioning also showed significant and persistent improvement in the Pao2/Fio2 ratio in early (12 hrs to 2 days) (four studies, 866 patients; weighted mean difference, 51.5; 95% CI, 6.95–96.05), intermediate (4 days) (three studies, 754 patients; weighted mean difference, 43.87; 95% CI, 13.86–73.88), and late (10 days) period (four studies, 833 patients; weighted mean difference, 24.89; 95% CI, 15.3–34.48). There were no significant differences in number of days on mechanical ventilation (two studies, 831 patients; weighted mean difference, −0.42 days; 95% CI, −1.56 to 0.72) or incidence of ventilator-associated pneumonia (three studies, 967 patients; weighted mean difference, 0.78%; 95% CI, 0.40–1.51). Conclusion: Based on the results of this meta-analysis, prone position improves oxygenation in patients with adult respiratory distress syndrome, and in patients with higher illness severity, it also may reduce mortality.

The impact of ventilator-associated pneumonia on the Canadian health care system

INTRODUCTION Ventilator-associated pneumonia (VAP) is a cause of morbidity and mortality in critically ill patients. It is associated with increased health care costs and duration of mechanical ventilation. Using published data and information from public health care providers, we sought to determine the impact of VAP on the Canadian health care system. METHODS Ventilator-associated pneumonia incidence, attributable mortality, and intensive care unit (ICU) utilization/resource data were obtained through Canadian published and institutional data. Ontario case cost methodology was used for the cost of a critical care bed which is CAN dollars 2396 per day, excluding treatment costs. Antibiotic acquisition costs for Ontario were used. Physician reimbursement rates were obtained from the provincial ministries of health. Ventilator-associated pneumonia data, ICU resource data, and costs were combined to determine the impact of VAP. RESULTS For the Canadian health care system; ICU utilization is 217 episodes per 100000 population and 1150 days of mechanical ventilation per 100000. The incidence of VAP is 10.6 cases per 1000 ventilator days (95% CI, 5.1-16.1). Ventilator-associated pneumonia increases ICU length of stay 4.3 days (95% CI, 1.5-7.0 days) per episode. The attributable mortality of VAP is 5.8% (95% CI, -2.4 to 14). The number of cases of VAP is estimated to be approximately 4000 cases per year (95% CI, 1900-6100). This results in 230 deaths per year with the lower and upper confidence intervals ranging from 0 to 580. Ventilator-associated pneumonia accounts for approximately 17000 ICU days per year or around 2% of all ICU days in Canada. The cost to the health care system is CAN dollars 46 million (possible range, dollars 10 million to 82 million) per year. CONCLUSION The impact of VAP on the Canadian health care system is considerable. Eradication of this preventable nosocomial infection would save lives and conserve scarce health care resources.

Interobserver variability in data collection of the Apache Ii score in teaching and community hospitals

OBJECTIVES To examine interobserver reliability of the Acute Physiologic and Chronic Health Evaluation (APACHE) II score and identify major causes of variability in data collection. DESIGN Descriptive, comparative analysis. SETTING Nine intensive care units in two teaching and six community hospitals SUBJECTS A random sample of 342 patient records selected from a network database. INTERVENTION None. MEASUREMENTS AND MAIN RESULTS Data were reabstracted and compared with the original records. Individual physiologic points derived from the APACHE II scoring system (instead of the actual physiologic values) were compared using the kappa statistic. Paired measurements of the continuous variables were compared using the interclass correlation coefficient and Bland-Altman plots. Excellent agreement was found in most demographic, admission, and discharge data. The system failure requiring intensive care unit admission was consistently identified by both data collectors in 88% of cases, but only 66% agreed on the exact admitting diagnosis. For APACHE II score components, the kappa statistic ranged from 0.315 for the Glasgow Coma Scale point to 0.976 for the age point. Significant disagreement regarding the probability of death derived from the APACHE II model was evident in some patient records. Overall agreement among groups of patients regarding the APACHE II score was good, however, with no significant difference in the mean score (20.2 vs. 20.1; p = .758). The predicted mortality from the reabstracted data was 30%, similar to the 27% predicted mortality from the original data (p = .380). CONCLUSION Reliability of data collection varied widely in different components of the APACHE II probability-of-death model. Significant discrepancies in some components suggested a lack of explicit definitions and timing for consistent data collection between institutions or between data collectors. Nonetheless, variability resulting from data collection appears to be randomly distributed, so that comparisons of group means are valid.