Objectives: Surges in demand for sedatives for mechanical ventilation during the COVID-19 pandemic caused shortages of sedatives globally. Propranolol, a nonselective beta-adrenergic blocker, has been associated with reduced agitation and sedative needs in observational studies. We aimed to test whether propranolol could reduce the dose of sedatives needed in mechanically ventilated patients.
Design: Open-label randomized controlled trial.
Setting: Three academic hospitals.
Subjects: Any nonparalyzed patient receiving mechanical ventilation and requiring high-dose sedatives.
Interventions: Enteral propranolol 20-60 mg every 6 hours titrated to effect in the intervention group; all participants received protocol-titrated sedation with propofol or midazolam.
Measurements and main results: Mean change in 24 hours dose of sedative from baseline to day 3, proportion of sedation scores within target, and occurrence rate of adverse events. We enrolled a planned 72 patients between January 2021 and October 2022. Sixty-nine percent were male with a mean (sd) age of 54 years (15.91 yr). Most were admitted for COVID or non-COVID pneumonia. Intervention participants received propranolol for a mean of 10 days (mean daily dose, 90 mg). There was a significantly larger decrease in sedative dose from baseline (54% vs. 34%; p = 0.048) and more sedation assessments within target range (48% vs. 35%; p < 0.0001) in the intervention group compared with controls. There were no differences in mortality or adverse events.
Conclusions: Propranolol is an inexpensive drug that effectively lowered the need for sedatives in critically ill patients managed in the COVID-19 pandemic. Propranolol may help preserve limited supplies of sedatives while achieving target sedation.
Objectives: Cardiac surgery is associated with perioperative complications, some of which might be attributable to hypotension. The Hypotension Prediction Index (HPI), a machine-learning-derived early warning tool for hypotension, has only been evaluated in noncardiac surgery. We investigated whether using HPI with diagnostic guidance reduced hypotension during cardiac surgery and in the ICU.
Design: Randomized clinical trial conducted between May 2021 and February 2023.
Setting: Single-center study conducted in an academic hospital in the Netherlands.
Patients: Adults undergoing elective on-pump coronary artery bypass grafting, with or without single heart valve surgery, were enrolled if a mean arterial pressure (MAP) greater than or equal to 65 mm Hg was targeted during the surgical off-pump phases and ICU stay. After eligibility assessment, 142 of 162 patients approached gave informed consent for participation.
Interventions: Patients randomized 1:1 received either diagnostic guidance in addition to standard care if HPI reached greater than or equal to 75 ( n = 72) or standard care alone ( n = 70).
Measurements and main results: The primary outcome was the severity of hypotension, measured as time-weighted average (TWA) of MAP less than 65 mm Hg. Secondary outcomes encompassed hypertension severity and intervention disparities. Of 142 patients randomized, 130 were included in the primary analysis. The HPI group showed 63% reduction in median TWA of hypotension compared with the standard care group, with a median of differences of -0.40 mm Hg (95% CI, -0.65 to -0.27; p < 0.001). In the HPI group, patients spent a median 28 minutes (95% CI, 17-44 min) less in hypotension, with a measurement duration of 322 minutes in the HPI group and 333 minutes in the standard care group. No significant differences were observed in hypertension severity, treatment choice, or fluid, vasopressors, and inotrope amounts.
Conclusions: Using HPI combined with diagnostic guidance on top of standard care significantly decreased hypotension severity in elective cardiac surgery patients compared with standard care.
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