Critically ill patients require sedation for mechanical ventilation, with dexmedetomidine and propofol being the first-line options. However, the COVID-19 pandemic led to global shortages of propofol, while dexmedetomidine is costly and not ideal for deep sedation. Benzodiazepines, another alternative, are linked to higher mortality in sepsis, increased delirium, and longer ICU stays.
Agitation and delirium in critically ill patients are driven by excessive sympathetic nervous system activity, primarily mediated by norepinephrine from the locus ceruleus (LC). Propranolol, a nonselective beta-blocker that crosses the blood-brain barrier, can suppress LC activity and has been associated with reduced agitation, shorter ICU stays, and lower mortality in traumatic brain injury and severe burns. A previously published study suggested propranolol significantly reduced sedative requirements while maintaining adequate sedation.
Given the risk of sedative shortages during pandemic-related surges in mechanical ventilation, a prospective randomised study was conducted to evaluate whether propranolol could effectively reduce sedative use and improve patient outcomes, including delirium rates, ICU/hospital length of stay, mortality, and drug costs.
The intervention group received enteral propranolol (20–60 mg every 6 hours, titrated to effect), while all participants received sedation with propofol or midazolam, adjusted per protocol.
The study measured changes in sedative doses over 3 days, the proportion of sedation scores within the target, and adverse events. A total of 72 patients were enrolled between January 2021 and October 2022, with 69% male and an average age of 54 years. Most were admitted for COVID or non-COVID pneumonia. The intervention group received propranolol for an average of 10 days (mean daily dose: 90 mg). This group showed a greater reduction in sedative use (54% vs. 34%) and more sedation assessments within the target range (48% vs. 35%) compared to controls. There were no significant differences in mortality or adverse events.
This study found that propranolol significantly reduced sedative use and improved adherence to sedation targets in mechanically ventilated ICU patients without increasing adverse events. This suggests propranolol may be a safe, cost-effective sedative-sparing strategy, particularly useful during sedative shortages or in low-resource settings.
Propranolol has shown benefits in traumatic brain injury and burn patients, and previous retrospective studies suggested it could reduce sedative needs in ICU patients. While concerns exist about beta-blocker use in critical illness, adverse events in this study were similar between groups. Propranolol's effects resemble those of dexmedetomidine but at a lower cost and without the need for specialised equipment.
The study was designed to assess sedative-sparing effects rather than patient outcomes like mortality. Though not powered for these endpoints, secondary outcomes showed a trend toward benefit.
Propranolol significantly reduced sedative requirements in mechanically ventilated patients, making it a potential strategy to preserve sedative supplies during future surges, such as those seen during the COVID-19 pandemic. This approach could also benefit ICUs with limited resources by reducing reliance on costly sedatives. Future blinded studies with larger sample sizes are needed to confirm these findings and assess patient-centred outcomes, including mortality and PTSD risk.
Source: Critical Care Medicine
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