Convalescent Plasma for Covid-19-Induced ARDS in Mechanically Ventilated Patients.

BACKGROUND: Passive immunization with plasma collected from convalescent patients has been regularly used to treat coronavirus disease 2019 (Covid-19). Minimal data are available regarding the use of convalescent plasma in patients with Covid-19-induced acute respiratory distress syndrome (ARDS). METHODS: In this open-label trial, we randomly assigned adult patients with Covid-19-induced ARDS who had been receiving invasive mechanical ventilation for less than 5 days in a 1:1 ratio to receive either convalescent plasma with a neutralizing antibody titer of at least 1:320 or standard care alone. Randomization was stratified according to the time from tracheal intubation to inclusion. The primary outcome was death by day 28. RESULTS: A total of 475 patients underwent randomization from September 2020 through March 2022. Overall, 237 patients were assigned to receive convalescent plasma and 238 to receive standard care. Owing to a shortage of convalescent plasma, a neutralizing antibody titer of 1:160 was administered to 17.7% of the patients in the convalescent-plasma group. Glucocorticoids were administered to 466 patients (98.1%). At day 28, mortality was 35.4% in the convalescent-plasma group and 45.0% in the standard-care group (P = 0.03). In a prespecified analysis, this effect was observed mainly in patients who underwent randomization 48 hours or less after the initiation of invasive mechanical ventilation. Serious adverse events did not differ substantially between the two groups. CONCLUSIONS: The administration of plasma collected from convalescent donors with a neutralizing antibody titer of at least 1:160 to patients with Covid-19-induced ARDS within 5 days after the initiation of invasive mechanical ventilation significantly reduced mortality at day 28. This effect was mainly observed in patients who underwent randomization 48 hours or less after ventilation initiation. (Funded by the Belgian Health Care Knowledge Center; ClinicalTrials.gov number, NCT04558476.).

Intraoperative ketorolac in high-risk breast cancer patients. A prospective, randomized, placebo-controlled clinical trial.

BACKGROUND: Ketorolac has been associated with a lower risk of recurrence in retrospective studies, especially in patients with positive inflammatory markers. It is still unknown whether a single dose of pre-incisional ketorolac can prolong recurrence-free survival. METHODS: The KBC trial is a multicenter, placebo-controlled, randomized phase III trial in high-risk breast cancer patients powered for 33% reduction in recurrence rate (from 60 to 40%). Patients received one dose of ketorolac tromethamine or a placebo before surgery. Eligible patients were breast cancer patients, planned for curative surgery, and with a Neutrophil-to-Lymphocyte Ratio≥4, node-positive disease or a triple-negative phenotype. The primary endpoint was Disease-Free Survival (DFS) at two years. Secondary endpoints included safety, pain assessment and overall survival. FINDINGS: Between February 2013 and July 2015, 203 patients were assigned to ketorolac (n = 96) or placebo (n = 107). Baseline characteristics were similar between arms. Patients had a mean age of 55.7 (SD14) years. At two years, 83.1% of the patients were alive and disease free in the ketorolac vs. 89.7% in the placebo arm (HR: 1.23; 95%CI: 0.65-2.31) and, respectively, 96.8% vs. 98.1% were alive (HR: 1.09; 95%CI: 0.34-3.51). CONCLUSIONS: A single administration of 30 mg of ketorolac tromethamine before surgery does not increase disease-free survival in high risk breast cancer patients. Overall survival difference between ketorolac tromethamine group and placebo group was not statistically significant. The study was however underpowered because of lower recurrence rates than initially anticipated. No safety concerns were observed. TRIAL REGISTRATION: ClinicalTrials.gov NCT01806259.

Cuff pressure of endotracheal tubes after changes in body position in critically ill patients treated with mechanical ventilation.

BACKGROUND: In order to avoid microaspiration and tracheal injury, the target for endotracheal tube cuff pressure is 20 to 30 cm H2O. OBJECTIVE: To assess the effect of changes in body position on cuff pressure in adult patients. METHODS: Twelve orally intubated and sedated patients received neuromuscular blockers and were positioned in a neutral starting position (backrest, head-of-bed elevation 30º, head in neutral position) with cuff pressure at 25 cm H2O. Then, 16 changes in position were performed: anteflexion head, hyperextension head, left and right lateral flexion of head, left and right rotation of the head, semirecumbent position (head-of-bed elevation 45°), recumbent position (head-of-bed elevation 10°), horizontal backrest, Trendelenburg position (10°), and left and right lateral positioning over 30°, 45°, and 90°. Once a patient was correctly positioned, cuff pressure was recorded during an end-expiratory ventilatory hold. The pressure observed was compared with the cuff pressure at the starting position. Values outside the target range (20-30 cm H2O) were considered clinically relevant. RESULTS: A total of 192 measurements were performed (12 subjects × 16 positions). A significant deviation in cuff pressure occurred with all 16 changes (P < .05). No pressures were less than the lower limit (20 cm H2O). Pressures were greater than the upper limit (30 cm H2O) in 40.6% of the measurements. In each position, the upper target limit was exceeded at least once. Within-patient variability was substantial (P = .02). CONCLUSION: Simple changes in patients' positioning can result in potentially harmful cuff pressures.