Objective: Acute respiratory distress syndrome trials powered for mortality require significant resources, limiting the number of evaluable therapies. Validation of intermediate endpoints would enhance the feasibility of testing novel acute respiratory distress syndrome therapies in pilot studies and potentially reduce the frequency of failed large clinical trials. We sought to determine whether a change in the oxygenation index over the first 7 days of acute respiratory distress syndrome could discriminate between therapies likely or unlikely to show benefit in larger clinical trials. Design: A derivation cohort from three acute respiratory distress syndrome studies was used to estimate the 7-day change in oxygenation index. Receiver operating characteristic curves were used to calculate optimal thresholds and predictability of the change in oxygenation index for 28-day mortality and ventilator-free days. The thresholds were then validated in two cohorts. Then, for each individual acute respiratory distress syndrome study, the threshold 7-day oxygenation index change was tested as an outcome measure and compared with mortality and ventilator-free days as reported in the original study. Setting: Medical ICUs. Patients: Acute respiratory distress syndrome patients. Interventions: Various. Measurements and Main Results: Change in oxygenation index, 28-day mortality, and ventilator-free days. In the derivation cohort, the mean 7-day oxygenation index improved by 4.2 (± 11.7) in 28-day survivors compared with an increase of 2.4 (± 11.6) in 28-day nonsurvivors (p < 0.001). The mean 7-day oxygenation index decreased by 5.9 (± 8.4) in patients with more than 14 ventilator-free days, compared with a decrease of 1.9 (± 12.4) among those with less than 14 ventilator-free days (p = 0.001). The optimal 7-day oxygenation index threshold for predicting mortality was an increase of 1.71 and for predicting less than 14 ventilator-free days, a decrease of 2.34. When used as a surrogate endpoint, the optimal 7-day oxygenation index change closely approximated mortality and ventilator-free day outcomes in three Acute Respiratory Distress Syndrome Network studies used for the derivation cohort and a distinct study used for validation. The change in oxygenation index was a poor predictor of individual patient outcome. Conclusions: Failure to meet a threshold improvement in the oxygenation index over the first 7 days of therapy can be used to identify therapies unlikely to succeed in subsequent trials powered for mortality and ventilator-free days. By reducing trial time and costs, use of the 7-day oxygenation index change as an intermediate endpoint could increase the number of clinical trials of promising therapies for acute respiratory distress syndrome and reduce the number of large-scale trials of therapies unlikely to be of benefit.

Objective: To describe the experience of emergency extracorporeal membrane oxygenation in treating life-threatening glyphosate-surfactant intoxication. Design: Case report. Setting: Emergency department and ICU. Patient: A patient with cardiopulmonary failure after glyphosate-surfactant intoxication. Intervention: Extracorporeal membrane oxygenation. Case Report: A 47-year-old man presented with mildly decreased consciousness in our emergency department after ingesting approximately 100?mL of glyphosate-surfactant 1.5 hours previously. Respiratory failure, persistent ventricular tachycardia, profound shock refractory to inotropic agents, and metabolic acidosis developed in the patient within 2 hours. Extracorporeal membrane oxygenation was applied within 4 hours of cardiopulmonary failure. The patient’s condition improved considerably. He was transferred to the general ward on the eighth day with stable hemodynamic status and complete neurological recovery. Conclusions: On the basis of our research, this was the first case in which extracorporeal membrane oxygenation was used to treat severe glyphosate-surfactant intoxication. We recommend early initiation of extracorporeal membrane oxygenation therapy to mitigate cardiopulmonary compromise in patients with glyphosate-surfactant intoxication.

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