Why Ketamine and Propofol Should Be Primary Sedation Agents and Opioids and Benzodiazepines Should be avoided?

Opioids and benzodiazepines should be avoided for sedation due to the dangerous synergistic effects they can have on respiratory depression. When benzodiazepines are combined with opioids, they can potentiate the respiratory depressant effects of opioids (Sun et al., 2017). This combination can lead to increased sedation risks, especially when used after surgery, potentially leading to higher opioid use and associated risks (Santosa et al., 2022). While moderate sedation with a benzodiazepine/opioid combination has been associated with high satisfaction levels and low adverse events, the risks of respiratory depression and sedation-related adverse events remain alarmingly significant (Müller & Wehrmann, 2011).

Furthermore, the concomitant use of opioids and benzodiazepines has been associated with increased sedation drug dose requirements, highlighting the potential for higher sedation risks with their combined use (Sanampudi et al., 2021). While sedation is commonly achieved using opioids and benzodiazepines, propofol is increasingly being favored due to its faster onset of action, shorter half-life, deeper sedation levels, and quicker recovery compared to benzodiazepines and opioids (Sáenz-López et al., 2006). While the American Society for Gastrointestinal Endoscopy (ASGE) recommends a combination of an opiate and benzodiazepine for minimal-to-moderate sedation during certain procedures, this regimen may not be suitable for the majority of patients, especially those with risk factors for sedation-related adverse events (Nishizawa et al., 2021).

Studies have shown that the use of propofol as an adjunct to traditional sedatives like benzodiazepines and opioids can provide a safer sedation option with lower complication risks, improved patient cooperation, satisfaction, and quicker recovery post-procedure (Delgado et al., 2019). 

While propofol has a place in procedural sedation and mechanical ventilation sedation, Ketamine is a valuable agent for sedation due to its unique pharmacological properties. It has been shown to provide hemodynamic benefits during rapid sequence intubation (RSI) and is effective for post-intubation analgesia and sedation (Merelman et al., 2019). Unlike other sedatives and analgesics, ketamine acts as a bronchodilator, positively affects hemodynamics, and possesses both analgesic and sedative properties, making it an appealing choice for critically ill patients (Patanwala et al., 2015). Additionally, ketamine can be used as an adjunct to other sedatives to reduce their dose and duration, making it a potential alternative in specific cases such as in COVID-19 patients (Karamchandani et al., 2021).

Studies have demonstrated promising results when using ketamine for sedation in traumatic brain injuries, showing its efficacy in induction, maintenance, and sedation in these patients (Chang et al., 2013). Ketamine has also been utilized for continuous sedation in hypotensive patients requiring mechanical ventilation, highlighting its versatility in different clinical scenarios (Umunna et al., 2015). In cases where traditional agents have been ineffective, ketamine has been clinically used for pain and sedation management, showcasing its role in refractory situations (Pruskowski et al., 2017).

Ketamine's pharmacological profile as an N-methyl-D-aspartate antagonist allows it to provide both analgesia and sedation, making it an attractive option for sedation in various settings (Shurtleff et al., 2018). Furthermore, ketamine has been found to maintain passive upper-airway collapsibility and induce compensatory respiratory responses, which can be advantageous in sedation procedures (Mishima et al., 2020). Its use as an adjunct sedative in acute respiratory distress syndrome due to COVID-19 pneumonia has shown potential in reducing the need for other sedatives and vasopressors (Garner et al., 2021).

In conclusion, the avoidance of opioids and benzodiazepines for sedation is crucial to mitigate the risks of respiratory depression, sedation-related adverse events, and the need for higher sedative doses. Ketamine and Propofol, as alternatives to traditional sedatives, offer a safer and more effective option for sedation during various medical procedures. Ketamine's unique properties make it a favorable agent for sedation in various clinical contexts, ranging from traumatic brain injuries to critically ill patients, including those with COVID-19. Its hemodynamic benefits, bronchodilator effects, and dual analgesic-sedative properties position ketamine as a versatile and effective option for sedation in diverse medical scenarios. Healthcare providers should carefully consider the risks and benefits of different sedation regimens to ensure patient safety and optimal outcomes.


  • Chang, L., Raty, S., Ortiz, J., Bailard, N., & Mathew, S. (2013). The emerging use of ketamine for anesthesia and sedation in traumatic brain injuries. CNS Neuroscience & Therapeutics, 19(6), 390-395.
  • Delgado, A., Ribeiro, I., Bazarbashi, A., Santos, M., Bernardo, W., & Moura, E. (2019). Propofol vs traditional sedatives for sedation in endoscopy: a systematic review and meta-analysis. World Journal of Gastrointestinal Endoscopy, 11(11), 573-588.
  • Garner, O., Patterson, J., Mejia, J., Anand, V., Deleija, J., Nemeh, C., … & Morgan, C. (2021). Impact of ketamine as an adjunct sedative in acute respiratory distress syndrome due to covid-19 pneumonia. Respiratory Medicine, 189, 106667.
  • Karamchandani, K., Dalal, R., Patel, J., Modgil, P., & Quintili, A. (2021). Challenges in sedation management in critically ill patients with covid-19: a brief review. Current Anesthesiology Reports, 11(2), 107-115.
  • Merelman, A., Perlmutter, M., & Strayer, R. (2019). Alternatives to rapid sequence intubation: contemporary airway management with ketamine. Western Journal of Emergency Medicine, 20(3), 466-471.
  • Mishima, G., Sanuki, T., Sato, S., Kobayashi, M., Kurata, S., & Ayuse, T. (2020). Upper‐airway collapsibility and compensatory responses under moderate sedation with ketamine, dexmedetomidine, and propofol in healthy volunteers. Physiological Reports, 8(10).
  • Müller, M. and Wehrmann, T. (2011). How best to approach endoscopic sedation?. Nature Reviews Gastroenterology & Hepatology, 8(9), 481-490.
  • Nishizawa, T., Yoshida, S., Toyoshima, O., Matsuno, T., Irokawa, M., Arano, T., … & Koike, K. (2021). Risk factors for prolonged hospital stay after endoscopy. Clinical Endoscopy, 54(6), 851-856.
  • Patanwala, A., Martin, J., & Erstad, B. (2015). Ketamine for analgosedation in the intensive care unit: a systematic review. Journal of Intensive Care Medicine, 32(6), 387-395.
  • Pruskowski, K., Harbourt, K., Pajoumand, M., Chui, S., & Reynolds, H. (2017). Impact of ketamine use on adjunctive analgesic and sedative medications in critically ill trauma patients. Pharmacotherapy the Journal of Human Pharmacology and Drug Therapy, 37(12), 1537-1544.
  • Sanampudi, S., Jayavarapu, R., & Raissi, D. (2021). Opioid and/or psychotropic use increases intraprocedural sedation drug requirements. Journal of Clinical Interventional Radiology Isvir, 6(01), 23-27.
  • Santosa, K., Wang, C., Hu, H., Mullen, C., Brummett, C., Englesbe, M., … & Waljee, J. (2022). Opioid coprescribing with sedatives after implant-based breast reconstruction. Plastic & Reconstructive Surgery, 150(6), 1224e-1235e.
  • Shurtleff, V., Radosevich, J., & Patanwala, A. (2018). Comparison of ketamine- versus nonketamine-based sedation on delirium and coma in the intensive care unit. Journal of Intensive Care Medicine, 35(6), 536-541.
  • Sun, E., Dixit, A., Humphreys, K., Darnall, B., Baker, L., & Mackey, S. (2017). Association between concurrent use of prescription opioids and benzodiazepines and overdose: retrospective analysis. BMJ, j760.
  • Sáenz-López, S., Muñoz, S., Rodríguez-Alcalde, D., Franco, A., Marin, J., Cruz, J., … & Herruzo, J. (2006). Endoscopist controlled administration of propofol: an effective and safe method of sedation in endoscopic procedures. Revista Española De Enfermedades Digestivas, 98(1).
  • Umunna, B., Tekwani, K., Barounis, D., Kettaneh, N., & Kulstad, E. (2015). Ketamine for continuous sedation of mechanically ventilated patients. Journal of Emergencies Trauma and Shock, 8(1), 11.

Recent blogs: