Showing papers by "Deborah J. Cook published in 2001"

Deep Vein Thrombosis and Its Prevention in Critically Ill Adults

Abstract: Background Our objective was to systematically review the incidence of deep vein thrombosis (DVT) and the efficacy of thromboprophylaxis in critically ill adults, including patients admitted to intensive care units and following trauma, neurosurgery, or spinal cord injury. Methods Two authors independently searched MEDLINE, EMBASE, abstract databases, and the Cochrane database. Data were extracted independently in triplicate. Results Ten percent to 30% of medical and surgical intensive care unit patients develop DVT within the first week of intensive care unit admission. The use of subcutaneous low-dose heparin reduced the rate by 50% compared with no prophylaxis. Approximately 60% of trauma patients developed DVT within the first 2 weeks of admission. Use of unfractionated heparin appears to decrease the incidence of DVT by only 20%, whereas low-molecular-weight heparin decreases the incidence by a further 30%. The estimated prevalence of DVT in neurosurgical patients not given prophylaxis is 22% to 35%. Mechanical prophylaxis is efficacious, with a pooled odds ratio in 5 randomized trials of 0.28. Use of low-molecular-weight heparin has been investigated as an adjunct to mechanical prophylaxis with a pooled odds ratio of 0.59 compared with graduated compression stockings alone. The incidence of DVT without prophylaxis in acute spinal cord injury patients is likely in excess of 50% to 80%. Studies of prophylaxis in these patients are too sparse to come to any definitive conclusion. Conclusions Critically ill patients commonly develop DVT, with rates that vary from 22% to almost 80%, depending on patient characteristics. Methods of prophylaxis proven in one group do not necessarily generalize to other critically ill patient groups. More potent prophylactic regimens other than unfractionated or low-molecular-weight heparins alone may be needed with higher-risk groups.

The attributable mortality and length of intensive care unit stay of clinically important gastrointestinal bleeding in critically ill patients

Abstract: 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.

Withdrawing and withholding life support in the intensive care unit: a Spanish prospective multi-centre observational study

Abstract: 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.

New strategies for clinical trials in patients with sepsis and septic shock.

Abstract: OBJECTIVE: The difficulty in identifying new treatment modalities that significantly reduce the mortality and morbidity rates associated with sepsis has highlighted the need to reevaluate the approach to clinical trial design. The United Kingdom Medical Research Council convened an International Working Party to address these issues. DATA SOURCES: The subject areas that were to be the focus of discussion were identified by the co-chairs, and group leaders were nominated. Preconference reading material was circulated to group members. STUDY SELECTION AND DATA EXTRACTION: Small-group discussion fed into an iterative process of feedback from plenary sessions, followed by the formulation of recommendations. Finally, each working group prepared a summary of its recommendations and these are reported herein. DATA SYNTHESIS: There were five key recommendations. First, investigators should no longer rely solely on the American College of Chest Physicians/Society of Critical Care Medicine definitions of sepsis or sepsis syndrome as the basis of trial entry. Entry criteria should be based on three principles: a) All patients should have infection; b) there should be evidence of a pathologic process that represents a biologically plausible target for the proposed intervention, for example, an abnormal circulating level of a biological marker pertinent to the study drug; and c) patients should fall into an appropriate category of severity (usually severe sepsis). Second, investigators should use a scoring system for organ dysfunctions that has been validated and that can be incorporated into all sepsis studies; agreement on the use of a single system would simplify comparisons between studies. Third, the primary outcome measure generally should be mortality rates, but under appropriate circumstances major morbidities could be considered as primary end points. Regardless of choice of the duration to primary end point, patients should be followed for > or =90 days. Fourth, sample size needs to be based on a realistic assessment of achievable effect size based on knowledge of the at-risk population. Fifth, subgroups should be few in number and should be defined a priori on the basis of variables present before randomization. CONCLUSIONS: Important changes in several aspects of trial design may improve the quality of clinical studies in sepsis and maximize the chance of identifying effective therapeutic agents.

Multiple organ dysfunction: baseline and serial component scores

Abstract: Objective The multiple organ dysfunction score (MODS) describes and quantifies organ-specific physiology The objective of this study was to examine the relation between six components of MODS (cardiovascular, respiratory, renal, central nervous system, hepatic, and hematologic) measured at admission to the intensive care unit (ICU) and during the ICU stay, with time to death in the ICU Design Prospective observational cohort study Setting Sixteen Canadian ICUs Patients A total of 1,200 patients were mechanically ventilated for >48 hrs Measurements and Main Results The six organ systems comprising MODS were measured at ICU admission (baseline scores) and daily thereafter The change in organ dysfunction each day (serial scores) were calculated as daily component scores minus the corresponding baseline component scores In Cox regression analyses, the independent explanatory variables were the MODS components measured at baseline and serially, and the dependent variable was the time from admission to ICU mortality When each organ system was analyzed individually, both the baseline and serial MODS for the cardiovascular, respiratory, renal, central nervous system, and hematologic components were significantly associated with ICU mortality After adjusting for the serial hepatic score, the baseline hepatic score was unrelated to mortality After adjusting for all baseline and serial MODS components in aggregate, four organ systems were significantly associated with ICU mortality: cardiovascular (baseline relative risk [RR], 15; serial RR, 14); respiratory (baseline RR, 14; serial RR, 14); renal (baseline RR, 13; serial RR, 15); and central nervous system (baseline RR, 16; serial RR, 17) We found that the relative risk of mortality related to organ dysfunction varied significantly over time and among organ systems Baseline respiratory function was not associated with mortality until the second ICU week (week 1: RR, 11 [09–14]; week 2 onward: RR, 19 [15–24]); the same was true for the change in respiratory function as measured by the serial respiratory score (week 1: RR, 12 [10–15]; week 2 onward: RR, 17 [14–21]) The serial hepatic score was not associated with mortality until the fourth ICU week (weeks 1–3: RR, 09 [07–11]; week 4 onward: RR, 14 [10–20]) Conclusions Organ dysfunction scores describe physiology at ICU admission and during ICU stay Although patterns vary by system, daily MODS component scores provide additional prognostic value over baseline MODS

Prevention and diagnosis of venous thromboembolism in critically ill patients: a Canadian survey

Abstract: Background Venous thromboembolism (VTE) confers considerable morbidity and mortality in hospitalized patients, although few studies have focused on the critically ill population. The objective of this study was to understand current approaches to the prevention and diagnosis of deep venous thrombosis (DVT) and pulmonary embolism (PE) among patients in the intensive care unit (ICU).

Colloid use for fluid resuscitation: evidence and spin.

Abstract: In this issue, Wilkes and Navickis present a meta-analysis of albumin versus crystalloids in critically ill patients. This meta-analysis has many strengths, but its weaknesses may limit the inferen...

Agreement between Alternative Classifications of Acute Respiratory Distress Syndrome

Abstract: To examine the agreement between two classifications of acute respiratory distress syndrome (ARDS) that are used interchangeably in clinical practice and clinical research, we classified 118 patients taking part in a randomized trial with respect to the presence of ARDS using the North American–European Consensus Committee (NAECC) and the Lung Injury Severity Score (LISS) criteria. The incidence of ARDS using NAECC criteria was 55.1% (95% confidence interval, 46.1% to 64.1%), and using the LISS criteria 61.9% (95% confidence interval, 53.1% to 70.6%). The p value on the difference between these proportions was 0.07. Raw agreement, chance-corrected agreement (kappa), and chance-independent agreement (phi) on the study occurrence of ARDS using the two classifications were, respectively, 0.73 (95% CI, 0.65 to 0.81), 0.46 (95% CI, 0.32 to 0.61), and 0.63 (95% CI, 0.41 to 0.79). No single component of either index contributed to disagreement to an appreciably greater extent than other components. Baseline char...

Patient autonomy versus parentalism.

Abstract: Several decision-making models have been advanced to characterize the patient-physician relationship. These include the parental model, the informed decision-making model, the interpretive model, and the deliberative model. Although these models are useful to consider in reflecting on the care we gi

Regular Versus As-Needed Short-Acting Inhaled β -Agonist Therapy for Chronic Obstructive Pulmonary Disease

Abstract: Regular short-acting inhaled β -agonist therapy is of uncertain benefit in patients with chronic obstructive pulmonary disease (COPD). We conducted a randomized, concealed, double-blind, placebo-controlled crossover trial in two periods, each of 3-mo duration, involving 53 patients with a smoking history of > 20 pack-years, an FEV1 of < 70% predicted, and an FEV1/VC ratio of < 0.7 after inhalation of 200 μ g albuterol. All patients received regular ipratropium bromide at 20 μ g per puff in 2 puffs four times daily, beclomethasone at 250 μ g per puff or equivalent corticosteroid in 2 puffs twice daily, and open-label inhaled albuterol as needed. Interventional therapy consisted of regular inhaled albuterol (100 μ g per puff, in 2 puffs four times daily) versus placebo. Patients used twice as much active albuterol in the regular use period (mean: 8.07 puffs of coded and 4.68 puffs of open-label medication; total: 12.75 puffs daily) than during the as-needed period (mean: 6.34 puffs of open-label albuterol d...

Guidelines as rationing tools: A qualitative analysis of psychosocial patient selection criteria for cardiac procedures

Abstract: Background: Cardiac procedure guidelines often include psychosocial criteria for selecting patients that potentially introduce social value judgements into clinical decisions and decisions about the rationing of care. The aim of this study was to investigate the terms and justifications for and the meanings of psychosocial patient characteristics used in cardiac procedure guidelines. Methods: We selected English-language guidelines published since 1990 and chapters in textbooks published since 1989. These guidelines amalgamated multiple sources of evidence and expertise and made recommendations regarding patient selection for specific procedures. A multidisciplinary team of physicians and social scientists extracted passages regarding psychosocial criteria and developed categories and conceptual relationships to describe and interpret their content. Results: Sixty-five papers met the criteria for inclusion in the study. Forty-five (69%) mentioned psychosocial criteria as procedure indications or contraindications. The latter fell into several categories, including behavioural and psychological issues, relationships with significant others, financial resources, social roles and environmental circumstances. Interpretation: Psychosocial characteristics are portrayed as having 2 roles in patient selection: as risk factors intrinsic to the candidate or as indicators of need for special intervention. Guidelines typically simply list psychosocial contraindications without clarifying their specific nature or providing any justification for their use. Psychosocial considerations can help in the evaluation of patients for cardiac procedures, but they become ethically controversial when used to restrict access. The use of psychosocial indications and contraindications could be improved by more precise descriptions of the psychosocial problem at issue, explanations regarding why the criterion matters and justification of the characteristic using a biological rationale or research evidence.

Weaning from mechanical ventilation: the evidence from clinical research.

Abstract: Mechanical ventilation incurs substantial morbidity, mortality, and costs. Both premature extubation and delayed extubation can cause harm. Therefore, weaning that is both expeditious and safe is highly desirable. The purpose of this review is to summarize the literature related to weaning modes, spontaneous breathing trials, weaning predictors, weaning with noninvasive positive pressure ventilation, and weaning protocols. We used 5 computerized databases and a duplicate independent review process to select articles for this review. We included randomized clinical trials evaluating any weaning interventions and nonrandomized trials of weaning predictors, with a focus on studies reporting clinically important outcomes. We abstracted quantitative data using several metrics and pooled results across studies only when our assessment of the patients, interventions, and outcomes indicated that pooling was legitimate. The available clinical research evidence suggests that, for progressive weaning of the level of mechanical support, it may be best to choose modes other than synchronized intermittent mandatory ventilation and it is unreasonable to be dogmatic about the use of other modes. There may also be substantial benefits to early extubation with back-up institution of noninvasive positive pressure ventilation, as needed, though this remains an experimental approach. For trials of spontaneous breathing, low levels of pressure support may hasten extubation. We did not uncover any consistently powerful weaning predictors, suggesting that formal use of predictors in patients being considered for reduction or discontinuation of mechanical support is unlikely to improve patient care. The likely explanation is that clinicians already fully consider information from weaning predictors in choosing patients for trials of reduction or discontinuation of mechanical ventilation. Finally, implementation of respiratory therapist- or nurse-driven protocols may be useful for all phases of weaning, and clinicians should adopt daily assessment for a trial of unassisted breathing as a safe method to reduce the duration of mechanical ventilation.

Doctors' perceptions of the effects of interventions tested in prospective, randomised, controlled, clinical trials: results of a survey of ICU physicians.

Abstract: Objectives: To establish a list of therapeutic interventions considered by intensive care unit (ICU) physicians to have been tested by prospective, randomised, controlled clinical trials (RCTs) in critically ill patients, and to survey the perceptions of the same physicians on the therapeutic effect of these interventions as evaluated by RCT. Design and setting: Self- applied questionnaire in an International Symposium of Intensive Care and Emergency Medicine, Brussels, Belgium. Participants: All 3250 registrants at the symposium. Measurements and results: There were 527 questionnaires completed, and 446 were suitable for analysis. Respondents were asked to list the therapeutic interventions used in intensive care medicine which they believed have been shown by RCTs to improve survival. Using a 5-point Likert scale, respondents were then asked to rate their assessment of the effectiveness of each intervention they listed and, using a 3-point scale, to select their level of confidence in those assessments. A total of 512 interventions were identified by the respondents as having been tested by RCT. Analysing the 42 interventions quoted more than 12 times, 31 were believed by the respondents to have been shown to have a beneficial effect, and 11 to have a harmful effect. Many of the interventions noted have not in fact been subjected to RCT. Conclusions: Many interventions that have not been tested by RCT were believed to have been tested; conversely, some interventions actually tested by RCT were not mentioned. Few interventions used in the ICU have actually been shown by RCT to have a positive effect on outcome.

Is the stomach an important source of tracheal contamination and subsequent pneumonia

Abstract: Objective: To determine the role of gastric colonization in the development of tracheal contamination and subsequent pulmonary infection in critically ill patients. Design: Observational cohort study. Setting: Eight tertiary care medical-surgical intensive care units. Participants: ICU patients expected to remain ventilated > 48 hours. We excluded patients with gastrointestinal bleeding, acidaemia, and renal failure. We studied 95 patients receiving continuous enteral nutrition; 38% were female, mean age (SD) was 55.1 (±18.9) years, and mean APACHE II Score was 21.6 (±7.0). Interventions: We prospectively documented microbial growth patterns in the stomach, trachea and enteral feeding reservoir (EFR). At baseline and every Monday, Wednesday and Friday, we sampled the EFR and stomach. Specimens were sent to the microbiology laboratory for culture. Patients were followed for the development of ICU-acquired pneumonia. Measurements and results: Fifty-four patients (56.8%) had a positive tracheal culture du...

Recombinant human activated protein C reduced all-cause mortality in patients with severe sepsis

Abstract: Source Citation Bernard GR, Vincent J-L, Laterre P-F, et al., for the Recombinant Human Activated Protein C Worldwide Evaluation in Severe Sepsis (PROWESS) Study Group. Efficacy and safety of recom...