Effect of Intraoperative Midazolam on Postoperative Distraction in Elderly Surgical Cases – A Prospective Study
What is Midazolam?
Midazolam, a benzodiazepine, serves primarily as a sedative, anxiolytic, and muscle relaxant, often administered to alleviate anxiety or induce sleepiness before surgeries or medical procedures. Its fast-acting nature, especially when delivered intravenously, makes it suitable for procedural sedation, seizure management (like in acute seizure episodes and status epilepticus), and as an adjunct to anesthesia.
Mechanism of Action
Midazolam works by enhancing GABA receptor activity in the central nervous system, which slows brain function, providing sedative, anxiolytic, and muscle-relaxant effects. It also induces amnesia, helping patients avoid recalling procedural discomfort.

Indications
Midazolam is utilized in a range of settings:
- Anesthesia: It can induce general anesthesia or supplement local and regional anesthesia.
- Seizure Control: Effective in managing acute seizures and status epilepticus, with intranasal and buccal routes favored in pediatric cases.
- Critical Care Sedation: Administered in intensive care to sedate ventilated patients.
Administration and Dosage
Midazolam can be given via various routes: intravenous (IV), intramuscular (IM), oral, intranasal, and buccal. Dosages differ based on use case, patient age, and health status. IV midazolam is usually titrated at 0.05-0.15 mg/kg for sedation, while IM dosages are often 0.07-0.1 mg/kg for premedication.
Side Effects
Common side effects include drowsiness, amnesia, dizziness, nausea, and injection-site reactions. Serious reactions like respiratory depression, hypotension, confusion, and agitation can also occur, especially in elderly patients or when combined with other CNS depressants.
Special Considerations
Careful dosing is critical in the elderly and those with liver or kidney issues due to slower drug clearance. Midazolam should be avoided in those with narrow-angle glaucoma and used cautiously in patients with respiratory conditions (e.g., COPD), as it can exacerbate respiratory depression.
Drug Interactions
Midazolam may interact with a range of medications, including certain antivirals, opioids, and CNS depressants, increasing the risk of severe side effects. Food interactions include grapefruit juice, which inhibits its metabolism and can heighten its effects.
Toxicity and Overdose Management
In cases of overdose, symptoms may include hypotension, respiratory depression, and coma. The antidote, flumazenil, is typically used with caution, particularly when other CNS depressants are involved, due to potential risks of seizures.
Study Summary:
This study investigates how intraoperative midazolam affects postoperative delirium (POD) in older patients. Midazolam is a short-acting benzodiazepine that provides sedation, reduces anxiety, and causes amnesia. While it’s useful for sedation during surgery, it requires caution in older adults due to their increased sensitivity, risk of respiratory depression, and potential for prolonged sedation and cognitive impairment.
Study Details:
- Study Location & Duration:
The study took place in multiple hospitals across China from April 2020 to April 2022. - Study Participants:
The study included patients aged 65 and older who received general anesthesia.
- Assessment Method:
POD was checked within 7 days after surgery using a quick test called the 3-minute Diagnostic Interview for Confusion Assessment Method (3D-CAM).
- Statistical Analysis:
Researchers used logistic regression models to analyze the link between midazolam use and POD, adjusting for hospital random effects. Kaplan-Meier curves were also used to compare the timing of POD onset in patients who received midazolam versus those who did not.
Results:
- Study Population:
Out of 5,663 patients, 723 (12.8%) developed POD. - Logistic Regression Results:
The logistic regression results showed no significant link between midazolam use and POD:- Unadjusted Risk Ratio (RR) = 0.96, 95% Confidence Interval (CI): 0.90–1.30, P=0.38
- Adjusted Risk Ratio (RR) = 1.09, 95% CI: 0.91–1.33, P=0.35
- Kaplan-Meier Analysis:
This analysis showed no difference in the timing of POD onset between groups:- Hazard Ratio (HR) = 1.02, 95% CI: 0.88–1.18, P=0.82
- Subgroup Analyses:
Subgroup analyses confirmed that midazolam use did not affect POD in specific patient subgroups.
Conclusion:
Intraoperative midazolam administration did not increase the risk of postoperative delirium (POD) in older adults undergoing non-cardiac surgery.
Midazolam Overview:
Midazolam is a short-acting benzodiazepine used for various purposes, including:
- Preoperative Sedation: Helps relax patients and reduce anxiety before surgery.
- Procedural Sedation: Keeps patients relaxed and comfortable during minor surgeries or procedures.
- Induction of Anesthesia: Used in some cases to induce general anesthesia.
- ICU Sedation: Sedates patients on ventilators or in intensive care.
- Anticonvulsant: Used in emergencies to stop prolonged seizures.
Midazolam works by enhancing the activity of GABA (gamma-aminobutyric acid), a neurotransmitter that calms brain activity. It is typically administered by injection, but oral and nasal forms are also available. Due to its sedative properties, midazolam can cause side effects such as respiratory depression and is closely monitored during use.
Midazolam in Older Patients:
Older adults require extra care when using midazolam due to their increased sensitivity to the drug and associated risks.
- Increased Sensitivity: Older adults often need lower doses, as they are more sensitive to midazolam’s effects.
- Cognitive Impairment: Midazolam can cause confusion or delirium, which may worsen existing cognitive issues in older adults.
- Risk of Respiratory Depression: Elderly patients with respiratory problems are more at risk for breathing difficulties when using midazolam.
- Prolonged Sedation: Older adults metabolize midazolam more slowly, which may lead to longer-lasting sedation and delayed recovery.
- Falls and Balance Issues: Even short-term use can affect balance and coordination, increasing the risk of falls and injuries.
- Alternative Options: Due to these risks, clinicians may choose non-benzodiazepine alternatives or reduce the dose and duration of midazolam use.
Methods for Administering Midazolam to Older Patients:
For older patients, it’s crucial to adjust the dose and method of administration carefully. Below are key practices for the safe use of midazolam:
- Dose Adjustment:
Start with a lower dose than for younger patients and gradually increase it as needed. - Slow Titration:
Administer midazolam slowly to reduce the risk of oversedation, especially when given intravenously. - Individualized Dosing:
Customize the dose based on the patient’s weight, liver and kidney function, and any other health conditions. - Preferred Routes of Administration:
- Intravenous (IV): Allows precise control and quick cessation if necessary.
- Oral: Used for minor sedation but requires careful dosing and monitoring.
- Intranasal or Buccal: Less common in older patients due to variable absorption.
- Avoid Continuous Infusions:
Intermittent boluses are preferred over continuous infusions to avoid drug accumulation and prolonged sedation. - Use of Alternatives:
Consider using adjunctive agents or non-benzodiazepine sedatives to reduce the need for midazolam. - Close Monitoring:
Monitor vital signs (especially breathing) and cognitive status continuously, particularly when using IV midazolam. - Short Duration of Use:
Limit the duration of midazolam use to reduce the risks of prolonged sedation, cognitive effects, and dependency.
Final Conclusion:
This study demonstrates that intraoperative midazolam use does not increase the risk of postoperative delirium in older adults undergoing non-cardiac surgeries. Proper dosing and monitoring are key to ensuring its safe use in this patient population.
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