Does midazolam cause hypotension?

From the Guidelines

Midazolam can cause hypotension as a side effect, particularly when administered intravenously or at higher doses, as evidenced by its inclusion in the list of adverse effects in the clinical practice guidelines for the management of pain, agitation, and delirium in adult patients in the intensive care unit 1.

Key Points to Consider

• The hypotensive effect of midazolam is dose-dependent and occurs more frequently with rapid IV administration.
• Typical IV doses range from 1-2.5 mg for adults, while oral doses are generally 7.5-15 mg.
• The mechanism behind midazolam-induced hypotension involves vasodilation and decreased peripheral vascular resistance, as well as mild myocardial depression.
• Patients with hypovolemia, cardiovascular disease, or the elderly are at higher risk for significant blood pressure drops.
• When administering midazolam, healthcare providers should monitor vital signs closely, administer the medication slowly when given IV, have resuscitation equipment available, and consider using lower initial doses in high-risk patients.

Important Considerations for Administration

• Midazolam is metabolized by the liver, and its clearance is reduced in patients with hepatic dysfunction, elderly patients, and when administered with other medications that inhibit cytochrome P450 enzyme systems and/or glucuronide conjugation in the liver 1.
• The active metabolites of midazolam may accumulate with prolonged administration, especially in patients with renal dysfunction 1.
• Delayed emergence from sedation with midazolam can result from prolonged administration, advanced age, hepatic dysfunction, or renal insufficiency 1.

From the FDA Drug Label

Hypotension may be observed in patients who are critically ill, particularly those receiving opioids and/or when midazolam is rapidly administered. When initiating an infusion with midazolam in hemodynamically compromised patients, the usual loading dose of midazolam should be titrated in small increments and the patient monitored for hemodynamic instability, e.g., hypotension. Hypotension may be observed in patients who are critically ill and in preterm and term infants, particularly those receiving fentanyl and/or when midazolam is administered rapidly Midazolam administered rapidly as an intravenous injection (less than 2 minutes) has been associated with severe hypotension in neonates, particularly when the patient has also received fentanyl.

Midazolam can cause hypotension, especially in critically ill patients, those receiving opioids, and when administered rapidly. Patients who are hemodynamically compromised should be monitored for hypotension when initiating an infusion with midazolam 2, 2, 2.

From the Research

Midazolam and Hypotension

• Midazolam can cause hypotension, as shown in a study comparing midazolam and etomidate for emergency department rapid sequence intubation, where 19.5% of patients had hypotension after being given midazolam 3.
• Another study found that during induction, two patients in the midazolam group had hypotension, although no hemodynamic or biochemical changes were detected in any of the treatment groups 4.
• A study on procedural sedation in the emergency department found that hypotension was a sedation event, but it was less common in patients sedated with midazolam (6 events) compared to other sedation events such as transient apnea 5.
• The evidence suggests that midazolam can cause hypotension, but the frequency and severity of this effect may vary depending on the context and population being studied 3, 4, 5.

Comparison with Other Sedatives

• A study comparing midazolam with propofol for procedural sedation found that propofol was more effective and at least as safe as midazolam, with fewer instances of hypotension 5.
• Another study found that etomidate was less likely to cause hypotension than midazolam when used as an induction agent for rapid sequence intubation 3.
• The comparison of midazolam with other sedatives suggests that the risk of hypotension may vary depending on the specific sedative used and the context in which it is administered 3, 5.

Population-Specific Effects

• A study on the use of midazolam for sedation before procedures in adults and children found that the effect of midazolam on hypotension was not consistently reported across different studies and populations 6, 7.
• The evidence suggests that the risk of hypotension associated with midazolam may vary depending on the population being studied, with some studies suggesting a higher risk in certain groups such as older adults 3.