Early sedation with dexmedetomidine in ventilated critically ill patients and heterogeneity of treatment effect in the SPICE III randomised controlled trial.

PURPOSE: To quantify potential heterogeneity of treatment effect (HTE), of early sedation with dexmedetomidine (DEX) compared with usual care, and identify patients who have a high probability of lower or higher 90-day mortality according to age, and other identified clusters. METHODS: Bayesian analysis of 3904 critically ill adult patients expected to receive invasive ventilation > 24 h and enrolled in a multinational randomized controlled trial comparing early DEX with usual care sedation. RESULTS: HTE was assessed according to age and clusters (based on 12 baseline characteristics) using a Bayesian hierarchical models. DEX was associated with lower 90-day mortality compared to usual care in patients > 65 years (odds ratio [OR], 0.83 [95% credible interval [CrI] 0.68-1.00], with 97.7% probability of reduced mortality across broad categories of illness severity. Conversely, the probability of increased mortality in patients ≤ 65 years was 98.5% (OR 1.26 [95% CrI 1.02-1.56]. Two clusters were identified: cluster 1 (976 patients) mostly operative, and cluster 2 (2346 patients), predominantly non-operative. There was a greater probability of benefit with DEX in cluster 1 (OR 0.86 [95% CrI 0.65-1.14]) across broad categories of age, with 86.4% probability that DEX is more beneficial in cluster 1 than cluster 2. CONCLUSION: In critically ill mechanically ventilated patients, early sedation with dexmedetomidine exhibited a high probability of reduced 90-day mortality in older patients regardless of operative or non-operative cluster status. Conversely, a high probability of increased 90-day mortality was observed in younger patients of non-operative status. Further studies are needed to confirm these findings.

Modified rapid shallow breathing index adjusted with anthropometric parameters increases predictive power for extubation failure compared with the unmodified index in postcardiac surgery patients.

OBJECTIVE: The aim of this study was to determine the best predictors of successful extubation after cardiac surgery, by modifying the rapid shallow breathing index (RSBI) based on patients' anthropometric parameters. DESIGN: Single-center prospective observational study. SETTING: Two general intensive care units at a single research institute. PARTICIPANTS: Patients who had undergone uncomplicated cardiac surgery. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The following parameters were investigated in conjunction with modification of the RSBI: Actual body weight (ABW), predicted body weight, ideal body weight, body mass index (BMI), and body surface area. Using the first set of patient data, RSBI threshold and modified RSBI for extubation failure were determined (threshold value; RSBI: 77 breaths/min (bpm)/L, RSBI adjusted with ABW: 5.0 bpm×kg/mL, RSBI adjusted with BMI: 2.0 bpm×BMI/mL). These threshold values for RSBI and RSBI adjusted with ABW or BMI were validated using the second set of patient data. Sensitivity values for RSBI, RSBI modified with ABW, and RSBI modified with BMI were 91%, 100%, and 100%, respectively. The corresponding specificity values were 89%, 92%, and 93%, and the corresponding receiver operator characteristic values were 0.951, 0.977, and 0.980, respectively. CONCLUSIONS: Modified RSBI adjusted based on ABW or BMI has greater predictive power than conventional RSBI.