Can Versed (midazolam) cause bradycardia?

From the Guidelines

Versed (midazolam) can cause bradycardia, although it is a rare side effect. Midazolam is a benzodiazepine medication commonly used for sedation, anxiety relief, and as part of anesthesia. According to the study by the AGA Institute review of endoscopic sedation 1, midazolam's major side effects include respiratory depression, and while cardiac dysrhythmia has been reported rarely, it does not specifically mention bradycardia as a common side effect. However, considering the pharmacological properties of midazolam and its potential to affect the cardiovascular system, particularly in vulnerable populations such as the elderly or those with pre-existing cardiac conditions, the possibility of bradycardia cannot be entirely ruled out.

Key points to consider:

• Midazolam enhances the inhibitory effect of gamma-aminobutyric acid (GABA) in the central nervous system, which can affect the cardiovascular control centers in the brain and potentially reduce sympathetic tone, leading to decreased heart rate.
• The risk of bradycardia may be increased when midazolam is administered rapidly intravenously or at higher doses, especially in combination with other sedatives or opioids.
• Healthcare providers should monitor vital signs, including heart rate, when administering midazolam, especially in high-risk patients.
• If significant bradycardia develops, dose reduction, slower administration, or in severe cases, administration of a reversal agent like flumazenil may be necessary, as suggested by the general principles of managing benzodiazepine-induced side effects 1.

From the FDA Drug Label

Fluctuations in vital signs were the most frequently seen findings following parenteral administration of midazolam in adults and included decreased tidal volume and/or respiratory rate decrease ... and apnea ... as well as variations in blood pressure and pulse rate. Slow heart rates (less than 65/minute), particularly in patients taking propranolol for angina, tended to rise slightly; faster heart rates (e.g., 85/minute) tended to slow slightly.

Bradycardia can be a concern when using Versed (midazolam), as it may cause variations in pulse rate. Although the label does not explicitly state that midazolam causes bradycardia, it does mention that slow heart rates tended to rise slightly, implying that midazolam may have some effect on heart rate. However, the label also notes that faster heart rates tended to slow slightly, suggesting a possible association with bradycardia. 2 2

From the Research

Versed (Midazolam) and Bradycardia

• Versed, also known as midazolam, is a benzodiazepine used for sedation, anesthesia, and treatment of seizures and status epilepticus 3.
• The effects of midazolam on heart rate have been studied in various contexts, including its use in electrophysiologic studies and procedural sedation.
• One study found that midazolam did not significantly alter the inducibility of arrhythmias, including reentrant tachycardia, in patients undergoing electrophysiologic studies 4.
• Another study investigated the use of midazolam for sedation during electrical cardioversion and found that it was effective and well-tolerated, with no serious adverse events reported 5.
• However, a study comparing midazolam to propofol for procedural sedation during direct current cardioversion found that 26.1% of patients experienced peri-procedural adverse events, including bradycardia, although these events were similar between the two groups and were successfully managed by the cardiologist 6.
• It is worth noting that midazolam has been associated with respiratory depression and cardiac arrest when used in combination with an opioid, particularly in the elderly, although all ages are at risk for respiratory depression 3.
• In terms of its direct effect on heart rate, one study found that midazolam caused a minor decrease in sinus cycle length, but this effect was not significant in terms of inducing bradycardia 4.
• Overall, while midazolam may be associated with some cardiovascular effects, including bradycardia, in certain contexts, the evidence suggests that it is generally safe and well-tolerated when used for procedural sedation and other indications 7, 5, 6, 4.