Event adjudication and data monitoring in an intensive care unit observational study of thromboprophylaxis.

BACKGROUND: The objective of this report is to describe the roles, responsibilities and recommendations of a 3-member Event Adjudication Committee (EAC) and a 5-member data monitoring committee (DMC) for a prospective multicenter observational study of critically ill patients with renal insufficiency examining the bioaccumulation and bleeding risk associated with dalteparin thromboprophylaxis. METHODS: The EAC reviewed bleeding events to adjudicate whether they were major or minor and whether they were related to dalteparin (uncertain, unlikely, or likely). The DMC reviewed all bleeds deemed by the EAC as uncertain or likely due to dalteparin then recommended either to continue or suspend enrolment pending review by the steering committee, or requested more information. RESULTS: Consensus on bleeding severity was achieved for all cases. At the second planned interim analysis, the EAC recommended to the DMC and steering committee that the EAC should stop adjudicating whether bleeding was related to dalteparin since attribution was challenging in this population with numerous bleeding risk factors; moreover, no bleeding rates were available from prior studies or historical or concurrent controls. CONCLUSIONS: Adjudication of whether an outcome can be attributed to an intervention in an open-label, uncontrolled observational study gives a potentially misleading impression of research oversight without methodological face validity. In this study, the EAC recommended modification of the adjudication process, and the DMC recommended continuing enrolment to achieve the target sample size.

Studies reporting ROC curves of diagnostic and prediction data can be incorporated into meta-analyses using corresponding odds ratios.

OBJECTIVE: To develop an approach by which studies describing the accuracy of diagnostic tests or clinical predictions can be combined in a meta-analysis, even though studies may report their results using different summary measures. STUDY DESIGN: A method is proposed to allow algebraic and numerical conversion of values of the Receiver Operating Characteristic Area Under the Curve (AUC) summary statistic into corresponding odds ratios (OR). A similar conversion is demonstrated for the standard errors (SEs) of these summary statistics. RESULTS: The conversion of the AUC values into OR values was achieved using a logit-threshold model. The delta method was used to convert the associated SEs. An example concerning predictions of mortality in the intensive care unit illustrates the calculations. CONCLUSION: This paper provides an accessible method that permits the meta-analyst to overcome some of the difficulties implied by incomplete and inconsistent reporting of research studies in this area. It allows all studies to be included on the same metric, which in turn more easily permits exploration of issues such as heterogeneity. The method can readily be used for meta-analyses of diagnostic or screening tests, or for prediction data.

Predicting success in weaning from mechanical ventilation.

We identified 65 observational studies of weaning predictors that had been reported in 70 publications. After grouping predictors with similar names but different thresholds, the following predictors met our relevance criteria: heterogeneous populations, 51; COPD patients, 21; and cardiovascular ICU patients, 45. Many variables were of no use in predicting the results of weaning. Moreover, few variables had been studied in > 50 patients or had results presented to generate estimates of predictive power. For stepwise reductions in mechanical support, the most promising predictors were a rapid shallow breathing index (RSBI) < 65 breaths/min/L (measured using the ventilator settings that were in effect at the time that the prediction was made) and a pressure time product < 275 cm H2O/L/s. The pooled likelihood ratios (LRs) were 1.1 (95% confidence interval [CI], 0.95 to 1.28) for a respiratory rate [RR] of < 38 breaths/min and 0.32 (95% CI, 0.06 to 1.71) for an RR of > 38 breaths/min, which indicate that an RR of < 38 breaths/min leaves the probability of successful weaning virtually unchanged but that a value of > 38 breaths/min leads to a small reduction in the probability of success in weaning the level of mechanical support. For trials of unassisted breathing, the most promising weaning predictors include the following: RR; RSBI; a product of RSBI and occlusion pressure < 450 cm H2O breaths/min/L; maximal inspiratory pressure (PImax) < 20 cm H2O; and a knowledge-based system for adjusting pressure support. Pooled results for the power of a positive test result for both RR and RSBI were limited (highest LR, 2.23), while the power of a negative test result was substantial (ie, LR, 0.09 to 0.23). Summary data suggest a similar predictive power for RR and RSBI. In the prediction of successful extubation, an RR of < 38 breaths/min (sensitivity, 88%; specificity, 47%), an RSBI < 100 or 105 breaths/min/L (sensitivity, 65 to 96%; specificity, 0 to 73%), PImax, and APACHE (acute physiology and chronic health evaluation) II scores that are obtained at hospital admission appear to be the most promising. After pooling, two variables appeared to have some value. An RR of > 38 breaths/min and an RSBI of > 100 breaths/min/L appear to reduce the probability of successful extubation, and PImax < 0.3, for which the pooled LR is 2.23 (95% CI, 1.15 to 4.34), appears to marginally increase the likelihood of successful extubation. Judging by areas under the receiver operator curve for all variables, none of these variables demonstrate more than modest accuracy in predicting weaning outcome. Why do most of these tests perform so poorly? The likely explanation is that clinicians have already considered the results when they choose patients for trials of weaning.

Trials comparing alternative weaning modes and discontinuation assessments.

We identified 16 randomized controlled trials (RCTs) of methods for weaning patients from mechanical ventilation, 8 of which were trials of discontinuation assessment strategies, 5 of which were trials of stepwise reduction in mechanical ventilatory support, and 3 of which were trials comparing alternative ventilation modes for weaning periods lasting < 48 h. We found that different thresholds for deciding when a patient is ready for a trial of spontaneous breathing, different criteria for a successful trial, and different thresholds for extubation may overwhelm the impact of alternative ventilation strategies. Nevertheless, the results of these studies suggest the possibility that multiple daily T-piece weaning or pressure support may be superior to synchronized intermittent mandatory ventilation. Other RCTs suggest that early extubation with the back-up institution of noninvasive positive-pressure ventilation as needed may be a useful strategy in selected patients.

Trials of corticosteroids to prevent postextubation airway complications.

We identified three randomized controlled trials (RCTs) that addressed whether preextubation steroid administration reduces postextubation complications in children. The pooled analysis of primary extubation in children demonstrated significantly less stridor (relative risk [RR], 0.57; 95% confidence interval [CI], 0.40 to 0.81) and a trend toward less reintubation (RR, 0.50; 95% CI, 0.02 to 13.87) with corticosteroids. One non-RCT in children who had failed extubation the first time found a significant reduction in duration of prolonged reintubation (> or = 6 days) and in failed reextubations. The four RCTs in adults reported very low reintubation rates, and no conclusions can be drawn. Only one RCT assessed postextubation stridor and found little difference. Overall, we found that corticosteroids decreased the risk of postextubation stridor in children by about 40%. However, the effect of corticosteroids in children and adults to reduce postextubation complications such as reintubation is uncertain.

Noninvasive positive-pressure ventilation: a utilization review of use in a teaching hospital.

BACKGROUND: The use of noninvasive positive-pressure ventilation (NIPPV) for acute respiratory failure (ARF) has become more widespread over the past decade, but its prescription, use and outcomes in the clinical setting remain uncertain. The objective of this study was to review the use of NIPPV for ARF with respect to clinical indications, physician ordering, monitoring strategies and patient outcomes. METHODS: A total of 91 consecutive adult patients admitted between June 1997 and September 1998 to a university-affiliated tertiary care hospital in Hamilton, Ont., who received 95 trials of NIPPV for ARF were included in an observational cohort study. Data abstraction forms were completed in duplicate, then relevant clinical, physiologic, prescribing, monitoring and outcome data were abstracted from the NIPPV registry and hospital records. RESULTS: The most common indications for NIPPV were pulmonary edema (42 of 95 trials [44.2%]) and exacerbation of chronic obstructive pulmonary disease (23 of 95 trials [24.2%]). NIPPV was started primarily in the emergency department (62.1% of trials), however, in terms of total hours of NIPPV the most frequent sites of administration were the intensive care unit (30.9% of total hours) and the clinical teaching unit (20.2% of total hours). NIPPV was stopped in 48.4% of patients because of improvement and in 25.6% because of deterioration necessitating endotracheal intubation. The median time to intubation was 3.0 hours (interquartile range 0.8-12.2 hours). The respirology service was consulted for 28.4% of the patients. Physician orders usually lacked details of NIPPV settings and monitoring methods. We found no significant predictors of the need for endotracheal intubation. The overall death rate was 28.6%. The only independent predictor of death was a decreased level of consciousness (odds ratio 2.9, 95% confidence interval 1.0-8.4). INTERPRETATION: NIPPV was used for ARF of diverse causes in many hospital settings and was started and managed by physicians with various levels of training and experience. The use of this technique outside the critical care setting may be optimized by a multidisciplinary educational practice guideline.

Development, implementation, and evaluation of a ketoconazole practice guideline for ARDS prophylaxis.

PURPOSE: The purpose of this study was to develop, implement, and evaluate a practice guideline using ketoconazole for the prevention of the adult respiratory distress syndrome (ARDS) in critically ill patients. MATERIALS AND METHODS: In hospital A (study hospital), we developed a guideline for ketoconazole prophylaxis in patients at high risk of ARDS using evidence from two randomized trials. We prospectively implemented the guideline using intensive care unit (ICU) teaching sessions, in-services, informational posters, and patient-specific individual audit and feedback. ICU caregivers in hospital B (concurrent control hospital) did not participate in the guideline development or implementation and were unaware of the conduct of the study. RESULTS: Patients at risk of ARDS were similar in hospitals A and B. Implementation of the guideline was associated with a significantly higher use of ketoconazole use for ARDS prevention (P < .0001) and a significantly lower rate of ARDS (P < .05) in hospital A compared with hospital B. Mortality, duration of ventilation, and ICU stay were similar. CONCLUSION: Development and implementation of a prophylactic ketoconazole practice guideline for ICU patients at high risk of ARDS was associated with a higher prescription of ketoconazole and a lower rate of ARDS in the study hospital than in the control hospital.