From the Guidelines
Ketamine and midazolam can be effectively combined for procedural sedation, particularly in emergency settings, with a recommended regimen of ketamine 1-2 mg/kg IV (or 4-5 mg/kg IM) with midazolam 0.02-0.05 mg/kg IV for adults, and ketamine 1-1.5 mg/kg IV (or 4 mg/kg IM) with midazolam 0.05-0.1 mg/kg IV for pediatric patients, as supported by the study by Wathen et al 1. This combination is beneficial as it leverages ketamine's dissociative anesthesia and analgesia while midazolam reduces emergence reactions and provides anxiolysis. When administering this combination, it is crucial to ensure proper monitoring of vital signs, have resuscitation equipment available, and maintain a patent airway as both medications can cause respiratory depression. The onset of action is typically 1-2 minutes for IV administration, with a duration of 15-30 minutes, as noted in the study by McCarty et al 1. Patients should be monitored until fully recovered from sedation, typically 1-2 hours. This combination is contraindicated in patients with severe hypertension, increased intracranial pressure, or psychosis. The synergistic effect allows for lower doses of each medication, potentially reducing side effects while maintaining efficacy for painful procedures, as seen in the study by Godambe et al 1. Some key points to consider when using this combination include:
- Monitoring for respiratory depression and having reversal agents available, as discussed in the study by Bailey et al 1.
- Being aware of the potential for increased recovery agitation in patients over 10 years old when midazolam is added to ketamine, as noted in the study by Wathen et al 1.
- Considering the use of alternative sedation regimens, such as propofol and fentanyl, which may have different efficacy and safety profiles, as seen in the study by Godambe et al 1. Overall, the combination of ketamine and midazolam can be a safe and effective option for procedural sedation in emergency settings when used appropriately and with careful monitoring, as supported by the highest quality study by Wathen et al 1.
From the FDA Drug Label
The FDA drug label does not answer the question.
From the Research
Ketamine Plus Midazolam for Procedural Sedation and Analgesia
- The combination of midazolam and ketamine has been studied for procedural sedation and analgesia in adult emergency department patients 2.
- A prospective, observational trial conducted in an urban level II trauma center found that this combination provides effective procedural sedation and analgesia, with a low incidence of adverse effects 2.
- The study found that the mean time to achieve discharge criteria was 64 +/- 24 minutes, and only one patient indicated that she was not satisfied with the sedation regimen 2.
Comparison with Other Sedation Regimens
- A study comparing propofol/fentanyl with ketamine/midazolam for brief orthopedic procedural sedation in a pediatric emergency department found that propofol/fentanyl had a shorter recovery time, but both regimens were effective in reducing procedural distress 3.
- Another study found that small-dose ketamine in combination with midazolam provided satisfactory intraoperative sedation, analgesia, and amnesia in healthy plastic-surgery patients, with fewer side effects associated with ketamine in the smaller-dose group 4.
Prevention of Recovery Agitation
- A randomized double-blind clinical trial found that premedication with midazolam or haloperidol significantly reduced ketamine-induced recovery agitation in adult patients undergoing procedural sedation, but delayed recovery 5.
- The study found that midazolam and haloperidol significantly reduced the maximum observed Pittsburgh Agitation Scale score and Richmond Agitation-Sedation Scale scores at 5,15, and 30 minutes after ketamine administration 5.
Pharmacology of Sedation Agents
- A review of the pharmacology of sedation agents and reversal agents found that midazolam is the benzodiazepine of choice for sedation due to its shorter duration of action and better pharmacokinetic profile 6.
- The review also noted that ketamine is not a popular agent for sedation in modern endoscopic practice, but can be used in combination with other agents for procedural sedation and analgesia 6.