In order to reduce pain, decrease anxiety, and avoid complications, sedating mechanically ventilated patients is common practice. While mechanical ventilators have recently undergone technical advances to improve comfort, medical professionals continue to administer light sedation during ventilation to ease discomfort caused by the endotracheal tube and avoid complications caused by the ventilator’s inability to synchronize with the patient’s natural breathing patterns [1]. To achieve this goal of light sedation — a state of reduced physical activity with a conserved ability to react to verbal commands — the ideal medication would be inexpensive, have minimal respiratory depression and accumulation, a short context-sensitive half-life allowing for a rapid recovery, and a lack of active metabolites [2]. However, no medication developed so far exhibits all of these qualities. Instead, critical care medical professionals must weigh the costs and benefits of benzodiazepines, propofol, and dexmedetomidine, the three most common sedatives for mechanically ventilated patients [1, 2, 3].
Benzodiazepines, a class of psychoactive depressants, cause sedation by enhancing the effect of GABA, the neurotransmitter responsible for reducing neuronal excitability throughout the central nervous system. While the administration of benzodiazepines — most commonly lorazepam (Ativan) or midazolam (Versed) — used to be the standard of care for mechanically ventilated patients, recent studies suggest that the use of these drugs worsens patient outcomes [1, 3]. Oversedation, delirium, delay in extubation, increased length of hospitalization, and increased risk of mortality have been shown to be associated with benzodiazepines, especially when compared to the sedative dexmedetomidine [4] and the anesthetic propofol [5]. While benzodiazepines remain a popular and inexpensive choice for light sedation during mechanical ventilation and treating conditions such as delirium tremens and status epilepticus, a growing body of literature supports a shift away from benzodiazepines in favor of propofol or dexmedetomidine to improve patient outcomes [2].
Propofol, like benzodiazepines, enhances the effect of GABA, but also functions as a diisopropylphenol anesthetic. Although the anesthetic maintains a rapid onset of action and a predictable dose response, it may accumulate in peripheral tissues, causing a delayed recovery [6]. Additionally, propofol can cause hypotension, irregular heart rhythms, and respiratory depression or cessation, leading many medical professionals away from this drug [6]. Studies comparing propofol with benzodiazepines have shown that propofol is associated with fewer days on mechanical ventilation compared to lorazepam, and faster recovery, fewer days on mechanical ventilation, less cost and more or equally effective sedation compared to midazolam [3]. While critical care medical professionals must anticipate adverse effects by monitoring the patient’s serum levels of pH, creatine, and triglycerides, as well as their electrocardiograms, propofol is considered a better option for sedating mechanically ventilated patients compared to benzodiazepines [2].
Another alternative is dexmedetomidine, an alpha-2 receptor agonist and sedative. Like propofol, dexmedetomidine has a rapid onset and may accumulate in peripheral tissues, but a shorter recovery compared to benzodiazepines [7]. Adverse effects of dexmedetomidine include bradycardia, hypotension, and nausea; additionally, hypertension can occur, particularly when the medication is administered through bolus dosing, causing some medical professionals to avoid this drug [7]. However, studies have shown that dexmedetomidine is associated with fewer days of delirium and coma, fewer days on mechanical ventilation, and lower cost compared to the benzodiazepines lorazepam and midazolam [3]. Moreover, while some studies have indicated that dexmedetomidine may be associated with a lower cost than propofol [3], both medications have been shown to provide equally effective sedation without affecting mortality [8].
In summary, benzodiazepines, propofol, and dexmedetomidine can each reduce the anxiety, pain, and discomfort experienced by mechanically ventilated patients. Although benzodiazepines remain inexpensive, recent studies recommend opting for propofol or dexmedetomidine instead to improve patient outcomes; however, choosing which sedative to utilize depends on the needs of the particular patient and the sedation protocol.
References
1: Moreira, F. and Neto, A. (2016). Sedation in mechanically ventilated patients — time to stay awake? Annals of Translational Medicine, vol. 4. DOI: 10.21037/atm.2016.09.37.
2: Hughes, C., McGrane, S., and Pandharipande, P. (2012). Sedation in the intensive care setting. Clinical Pharmacology, vol. 4. DOI: 10.2147/CPAA.S26582.
3: Patel, S. and Kress, P. (2011). Sedation and analgesia in the mechanically ventilated patient. American Journal of Respiratory and Critical Care Medicine, vol. 185. DOI: 10.1164/rccm.201102-0273CI.
4: Pandharipande, P., Pun, B., Herr, D., Maze, M., Girard, T., Millar, R., Shintani, A., Thompson, J., Jackson, J., Deppen, S., Stiles, R., Dittus, R., Bernard, G., and Ely, E. (2007). Effect of sedation with dexmedetomidine vs. lorazepam on acute brain dysfunction in mechanically ventilated patients. JAMA, vol. 298. DOI: 10.1001/jama.298.22.2644.
5: Lonardo, N., Mone, M., Nirula, R., Kimball, E., Ludwig, K., Zhou, X., Sauer, B., Nechodom, K., Teng, C., and Barton, R. (2013). Propofol is associated with favorable outcomes compared with benzodiazepines in ventilated intensive care unit patients. American Journal of Respiratory and Critical Care Medicine, vol. 189. DOI: 10.1164/rccm.201312-2291OC.
6: Folino, T., Muco, E., Safadi, A., and Parks, L. (2020). Propofol. StatPearls. Online article. URL: https://www.ncbi.nlm.nih.gov/books/NBK430884/.
7: Gertler, R., Brown, C., Mitchell, D., and Silvius, E. (2001). Dexmedetomidine: a novel sedative-analgesic agent. Baylor University Medical Center Proceedings, vol. 14. DOI: 10.1080/08998280.2001.11927725.
8: Hughes, C., Mailloux, P., Devlin, J., Swan, J., Sanders, R., Anzueto, A., Jackson, J., Hoskins, A., Pun, B., Orun, O., Raman, R., Stollings, J., et al. (2021). Dexmedetomidine or propofol for sedation in mechanically ventilated adults with sepsis. New England Journal of Medicine, vol. 384. DOI: 10.1056/NEJMoa2024922.