Midazolam is a widely used medicine that helps people relax or fall asleep before surgery and medical procedures.
It is popular because it works quickly and often prevents patients from remembering the procedure afterward.
Doctors have used it safely for many years, but new research suggests that the time it is given could affect how safe it is.
A research team from the University of Colorado Anschutz Medical Campus examined the medical records of more than 1.7 million patients who received midazolam before surgery.
Most patients recovered without problems, but more than 16,000 showed signs of heart injury after their operations. The findings were published in the journal Frontiers in Cardiovascular Medicine.
When the researchers compared different surgery times, they noticed that heart injuries were more common after operations performed at night. The increased risk was especially noticeable in patients who were otherwise healthy. This unexpected finding led the team to investigate why the time of day might matter.
The answer appears to involve a gene called PER2. This gene is part of the body’s internal clock, known as the circadian rhythm, which helps control sleep, hormone levels, body temperature, and many other daily processes. PER2 also helps protect the heart when it is under stress.
To better understand what was happening, the researchers carried out experiments in mice. They found that midazolam lowered PER2 levels, but only when it was given at night. Because PER2 naturally falls during the night, the extra drop caused by the drug may leave the heart with less protection.
Midazolam works by boosting the activity of GABA, a natural chemical in the brain that helps people feel calm and sleepy. While this effect makes the medicine useful before surgery, the study suggests it may also affect the heart’s natural defense system when given during the body’s nighttime period.
The findings support a growing area of medicine called chronomedicine. This field studies how the timing of treatments changes the way medicines work. Scientists have already found that some blood pressure medicines work better when taken at certain times of the day, and this study suggests that surgery medications may also need to be timed more carefully.
The researchers stress that midazolam remains a safe and effective medicine for most patients. However, the study suggests doctors may need to consider the timing of surgery and medication when planning care. More research is needed to confirm the findings and determine whether changing the timing of treatment could reduce the risk of heart injury.
The study was led by Dr. Tobias Eckle and published in Frontiers in Cardiovascular Medicine. The research highlights how small changes, such as the time a medicine is given, may have an important effect on patient safety and could help improve surgical care in the future.
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