Midazolam, a short-acting benzodiazepine, is commonly used as a sedative and anxiolytic in medical procedures. Its efficacy in inducing sedation and reducing anxiety is well documented, particularly in preoperative and procedural settings. However, as more and more emphasis is placed on faster recovery and discharge after anesthesia, the recovery time associated with midazolam must also be considered. The effect of midazolam on recovery time, particularly in comparison to other sedatives, is a topic of considerable interest in anesthesiology, due to potential implications for patient outcomes.
The pharmacokinetic profile of midazolam suggests a relatively short duration of action, with a half-life of approximately 1.5 to 2.5 hours in healthy adults. However, recovery time from sedation is influenced by factors beyond its pharmacokinetics, including patient-specific variables such as age, weight, underlying medical conditions, and concomitant use of other medications. Recovery time can be defined as the time required for a patient to regain full cognitive and motor function after sedation. In the case of midazolam, this period may extend beyond its immediate half-life due to its prolonged sedative effects on the CNS. This is particularly important in elderly patients and those with impaired liver function, in whom benzodiazepines tend to accumulate and are metabolized more slowly (1).
Studies comparing midazolam with other sedatives, such as propofol, have shown a clear difference in recovery time. Propofol, another widely used sedative-hypnotic, has a faster recovery profile due to its ultra-short half-life and rapid metabolism. In a randomized trial comparing the recovery profiles of patients sedated with midazolam and propofol for flexible bronchoscopy, patients in the propofol group had faster recovery from sedation than those who received midazolam (2). In clinical practice, this means that patients receiving midazolam may require prolonged recovery monitoring to ensure that they are alert, oriented, and able to be safely discharged from medical supervision.
In addition to slowing recovery time, midazolam has been associated with postoperative cognitive dysfunction (POCD), particularly in elderly patients. POCD is a common problem following surgery and sedation, with symptoms ranging from temporary memory impairment to longer-term problems with executive function. Midazolam’s effects on memory and cognition may contribute to delayed cognitive recovery, particularly in elderly patients or those with pre-existing cognitive impairment (3). This prolonged cognitive recovery not only affects the patient’s ability to return to daily activities, but also increases the burden on healthcare resources as these patients may require prolonged observation and care following their procedures.
Despite these concerns, midazolam continues to be preferred for many procedures because of its excellent anxiolytic properties and its ability to induce anterograde amnesia, which prevents patients from recalling potentially unpleasant procedures, an important part of procedural sedation. In addition, when used in combination with opioids such as fentanyl, midazolam can provide adequate sedation at reduced doses, potentially mitigating some of the problems associated with one or both of the drugs. A study evaluating the combination of midazolam and fentanyl found that while recovery times were slightly prolonged, the combination provided
effective sedation at lower doses, which may reduce the overall impact on recovery compared to the use of midazolam alone (4).
References
1. Lee SY, Kim KJ, Lee HJ, et al. Effect of midazolam premedication on postanesthetic recovery and discharge-readiness after brief outpatient surgery. Korean J Anesthesiol. 2008;55(2):205-210. Available at: https://ekja.org/journal/view.php?number=3498.
2. Clark G, Licker M, Younossian AB, et al. Titrated sedation with propofol or midazolam for flexible bronchoscopy: A randomized trial. Eur Respir J. 2009;34(6):1277-1283. doi:10.1183/09031936.00142108.
3. Newman S, Stygall J, Hirani S, Shaefi S, Maze M, Warltier DC. Postoperative Cognitive Dysfunction after Noncardiac Surgery: A Systematic Review. Anesthesiology. 2007;106(3):572-590. doi: 10.1097/00000542-200703000-00023
4. Padmanabhan U, Leslie K, Eer AS, Maruff P, Silbert BS. Early Cognitive Impairment After Sedation for Colonoscopy: The Effect of Adding Midazolam and/or Fentanyl to Propofol. Anesth Analg. 2009;109(5):1448-1455. doi: 10.1213/ane.0b013e3181a6ad31