A Prognostic Enrichment Strategy for Selection of Patients With Acute Respiratory Distress Syndrome in Clinical Trials.

OBJECTIVES: Incomplete or ambiguous evidence for identifying high-risk patients with acute respiratory distress syndrome for enrollment into randomized controlled trials has come at the cost of an unreasonable number of negative trials. We examined a set of selected variables early in acute respiratory distress syndrome to determine accurate prognostic predictors for selecting high-risk patients for randomized controlled trials. DESIGN: A training and testing study using a secondary analysis of data from four prospective, multicenter, observational studies. SETTING: A network of multidisciplinary ICUs. PATIENTS: We studied 1,200 patients with moderate-to-severe acute respiratory distress syndrome managed with lung-protective ventilation. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We evaluated different thresholds for patient's age, PaO2/FIO2, plateau pressure, and number of extrapulmonary organ failures to predict ICU outcome at 24 hours of acute respiratory distress syndrome diagnosis. We generated 1,000 random scenarios as training (n = 900, 75% of population) and testing (n = 300, 25% of population) datasets and averaged the logistic coefficients for each scenario. Thresholds for age (< 50, 50-70, > 70 yr), PaO2/FIO2 (≤ 100, 101-150, > 150 mm Hg), plateau pressure (< 29, 29-30, > 30 cm H2O), and number of extrapulmonary organ failure (< 2, 2, > 2) stratified accurately acute respiratory distress syndrome patients into categories of risk. The model that included all four variables proved best to identify patients with the highest or lowest risk of death (area under the receiver operating characteristic curve, 0.86; 95% CI, 0.84-0.88). Decision tree analyses confirmed the accuracy and robustness of this enrichment model. CONCLUSIONS: Combined thresholds for patient's age, PaO2/FIO2, plateau pressure, and extrapulmonary organ failure provides prognostic enrichment accuracy for stratifying and selecting acute respiratory distress syndrome patients for randomized controlled trials.

A Quantile Analysis of Plateau and Driving Pressures: Effects on Mortality in Patients With Acute Respiratory Distress Syndrome Receiving Lung-Protective Ventilation.

OBJECTIVES: The driving pressure (plateau pressure minus positive end-expiratory pressure) has been suggested as the major determinant for the beneficial effects of lung-protective ventilation. We tested whether driving pressure was superior to the variables that define it in predicting outcome in patients with acute respiratory distress syndrome. DESIGN: A secondary analysis of existing data from previously reported observational studies. SETTING: A network of ICUs. PATIENTS: We studied 778 patients with moderate to severe acute respiratory distress syndrome. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We assessed the risk of hospital death based on quantiles of tidal volume, positive end-expiratory pressure, plateau pressure, and driving pressure evaluated at 24 hours after acute respiratory distress syndrome diagnosis while ventilated with standardized lung-protective ventilation. We derived our model using individual data from 478 acute respiratory distress syndrome patients and assessed its replicability in a separate cohort of 300 acute respiratory distress syndrome patients. Tidal volume and positive end-expiratory pressure had no impact on mortality. We identified a plateau pressure cut-off value of 29 cm H2O, above which an ordinal increment was accompanied by an increment of risk of death. We identified a driving pressure cut-off value of 19 cm H2O where an ordinal increment was accompanied by an increment of risk of death. When we cross tabulated patients with plateau pressure less than 30 and plateau pressure greater than or equal to 30 with those with driving pressure less than 19 and driving pressure greater than or equal to 19, plateau pressure provided a slightly better prediction of outcome than driving pressure in both the derivation and validation cohorts (p < 0.0000001). CONCLUSIONS: Plateau pressure was slightly better than driving pressure in predicting hospital death in patients managed with lung-protective ventilation evaluated on standardized ventilator settings 24 hours after acute respiratory distress syndrome onset.

Effects of PEEP on intracranial pressure in patients with acute brain injury: An observational, prospective and multicenter study.

OBJECTIVE: To analyze the impact of positive end-expiratory pressure (PEEP) changes on intracranial pressure (ICP) dynamics in patients with acute brain injury (ABI). DESIGN: Observational, prospective and multicenter study (PEEP-PIC study). SETTING: Seventeen intensive care units in Spain. PATIENTS: Neurocritically ill patients who underwent invasive neuromonitorization from November 2017 to June 2018. INTERVENTIONS: Baseline ventilatory, hemodynamic and neuromonitoring variables were collected immediately before PEEP changes and during the following 30 min. MAIN VARIABLES OF INTEREST: PEEP and ICP changes. RESULTS: One-hundred and nine patients were included. Mean age was 52.68 (15.34) years, male 71 (65.13%). Traumatic brain injury was the cause of ABI in 54 (49.54%) patients. Length of mechanical ventilation was 16.52 (9.23) days. In-hospital mortality was 21.1%. PEEP increases (mean 6.24-9.10 cmH2O) resulted in ICP increase from 10.4 to 11.39 mmHg, P < .001, without changes in cerebral perfusion pressure (CPP) (P = .548). PEEP decreases (mean 8.96 to 6.53 cmH2O) resulted in ICP decrease from 10.5 to 9.62 mmHg (P = .052), without changes in CPP (P = .762). Significant correlations were established between the increase of ICP and the delta PEEP (R = 0.28, P < .001), delta driving pressure (R = 0.15, P = .038) and delta compliance (R = -0.14, P = .052). ICP increment was higher in patients with lower baseline ICP. CONCLUSIONS: PEEP changes were not associated with clinically relevant modifications in ICP values in ABI patients. The magnitude of the change in ICP after PEEP increase was correlated with the delta of PEEP, the delta driving pressure and the delta compliance.

Medication reconciliation for patients after their discharge from intensive care unit to the hospital ward. / [Artículo traducido] Conciliación de la medicación en el alta desde la unidad de cuidados intensivos a la planta de hospitalización.

OBJECTIVES: The aim of this study was to determine whether the transition of care from the intensive care unit to the ward would pose a high risk for reconciliation errors. The primary outcome of this study was to describe and quantify the discrepancies and reconciliation errors. Secondary outcomes included classification of the reconciliation errors by type of medication error, therapeutic group of the drugs involved and grade of potential severity. METHODS: We conducted a retrospective observational study of reconciliated adult patients discharged from the Intensive Care Unit to the ward. Before a patient was discharged from the intensive care unit, their last intensive care unit's prescriptions were compared with their proposed medication list in the ward. The discrepancies between these were classified as justified discrepancies or reconciliation errors. Reconciliation errors were classified by type of error, potential severity, and therapeutic group. RESULTS: We found that 452 patients were reconciliated. At least one discrepancy was detected in 34.29% (155/452), and 18.14% (82/452) had at least one reconciliation errors. The most found error types were a different dose or administration route (31.79% [48/151]) and omission errors (31.79% [48/151]). High alert medication was involved in 19.20% of reconciliation errors (29/151). CONCLUSIONS: Our study shows that intensive care unit to non-intensive care unit transitions are high-risk processes for reconciliation error. They frequently occur and occasionally involve high alert medication, and their severity could require additional monitoring or cause temporary harm. Medication reconciliation can reduce reconciliation errors.

Medication reconciliation for patients after their discharge from intensive care unit to the hospital ward.

OBJECTIVES: The aim of this study was to determine whether the transition of care from the intensive care unit to the ward would pose a high risk for reconciliation errors. The primary outcome of this study was to describe and quantify the discrepancies and reconciliation errors. Secondary outcomes included classification of the reconciliation errors by type of medication error, therapeutic group of the drugs involved and grade of potential severity. METHODS: We conducted a retrospective observational study of reconciliated adult patients discharged from the Intensive Care Unit to the ward. Before a patient was discharged from the intensive care unit, their last intensive care unit's prescriptions were compared with their proposed medication list in the ward. The discrepancies between these were classified as justified discrepancies or reconciliation errors. Reconciliation errors were classified by type of error, potential severity, and therapeutic group. RESULTS: We found that 452 patients were reconciliated. At least one discrepancy was detected in 34.29% (155/452), and 18.14% (82/452) had at least one reconciliation errors. The most found error types were a different dose or administration route (31.79% (48/151)) and omission errors (31.79% (48/151)). High alert medication was involved in 19.20% of reconciliation errors (29/151). CONCLUSIONS: Our study shows that intensive care unit to non-intensive care unit transitions are high-risk processes for reconciliation error. They frequently occur and occasionally involve high alert medication, and their severity could require additional monitoring or cause temporary harm. Medication reconciliation can reduce reconciliation errors.

Respiratory Subsets in Patients with Moderate to Severe Acute Respiratory Distress Syndrome for Early Prediction of Death.

Introduction: In patients with acute respiratory distress syndrome (ARDS), the PaO2/FiO2 ratio at the time of ARDS diagnosis is weakly associated with mortality. We hypothesized that setting a PaO2/FiO2 threshold in 150 mm Hg at 24 h from moderate/severe ARDS diagnosis would improve predictions of death in the intensive care unit (ICU). Methods: We conducted an ancillary study in 1303 patients with moderate to severe ARDS managed with lung-protective ventilation enrolled consecutively in four prospective multicenter cohorts in a network of ICUs. The first three cohorts were pooled (n = 1000) as a testing cohort; the fourth cohort (n = 303) served as a confirmatory cohort. Based on the thresholds for PaO2/FiO2 (150 mm Hg) and positive end-expiratory pressure (PEEP) (10 cm H2O), the patients were classified into four possible subsets at baseline and at 24 h using a standardized PEEP-FiO2 approach: (I) PaO2/FiO2 ≥ 150 at PEEP < 10, (II) PaO2/FiO2 ≥ 150 at PEEP ≥ 10, (III) PaO2/FiO2 < 150 at PEEP < 10, and (IV) PaO2/FiO2 < 150 at PEEP ≥ 10. Primary outcome was death in the ICU. Results: ICU mortalities were similar in the testing and confirmatory cohorts (375/1000, 37.5% vs. 112/303, 37.0%, respectively). At baseline, most patients from the testing cohort (n = 792/1000, 79.2%) had a PaO2/FiO2 < 150, with similar mortality among the four subsets (p = 0.23). When assessed at 24 h, ICU mortality increased with an advance in the subset: 17.9%, 22.8%, 40.0%, and 49.3% (p < 0.0001). The findings were replicated in the confirmatory cohort (p < 0.0001). However, independent of the PEEP levels, patients with PaO2/FiO2 < 150 at 24 h followed a distinct 30-day ICU survival compared with patients with PaO2/FiO2 ≥ 150 (hazard ratio 2.8, 95% CI 2.2−3.5, p < 0.0001). Conclusions: Subsets based on PaO2/FiO2 thresholds of 150 mm Hg assessed after 24 h of moderate/severe ARDS diagnosis are clinically relevant for establishing prognosis, and are helpful for selecting adjunctive therapies for hypoxemia and for enrolling patients into therapeutic trials.