Midazolam is a common medicine used before and during medical procedures. It helps patients feel calm and sleepy, reduces anxiety, and can make it difficult to remember what happened during a procedure.
The drug has been used safely for many years, but new research suggests that timing may matter. Researchers at the University of Colorado Anschutz Medical Campus found that giving midazolam at night may be linked to a greater risk of heart injury during surgery.
Our bodies do not work exactly the same way throughout the day. They follow a roughly 24-hour internal clock, known as the circadian rhythm, which helps control sleep, hormones, body temperature, blood pressure, and many other functions.
The heart also follows this daily rhythm. Changes in the body’s internal clock can affect how the heart responds to stress, including the physical stress caused by surgery.
To investigate midazolam, the researchers examined more than 1.7 million medical records from patients who received the drug during surgery. More than 16,000 of these patients experienced some form of heart injury.
The researchers found that heart injuries were more common when surgery took place at night. The connection was particularly noticeable among patients who were otherwise considered healthy.
The team then turned to laboratory experiments to understand why this pattern might occur. They focused on a gene called PER2, which is an important part of the body’s internal clock and also appears to help protect the heart from damage.
Midazolam works partly by increasing the effects of GABA, a chemical messenger that reduces activity in the brain and helps produce a calming effect. Experiments in mice suggested that when midazolam was given at night, this process also reduced the activity of PER2.
That change could matter because lower PER2 activity may weaken some of the heart’s natural protection during periods of stress. The researchers believe this may help explain why nighttime use of midazolam was associated with more heart injuries in their analysis.
The findings do not mean that midazolam is unsafe or that patients should avoid needed nighttime surgery. Medical decisions depend on many factors, and urgent operations often cannot be moved to a different time.
Instead, the research adds to growing evidence that the same medicine can affect the body differently depending on when it is given. Scientists are increasingly studying whether treatment schedules can be adjusted to work with the body’s natural daily rhythms.
This approach could eventually become another part of personalized medicine. Doctors may one day consider not only which medicine is best for a patient and what dose to use, but also the safest or most effective time to give it.
The study was led by Dr. Tobias Eckle and researchers at the University of Colorado Anschutz Medical Campus and was published in the journal Frontiers in Cardiovascular Medicine. The findings show why understanding the link between medicines and the body’s internal clock could help make medical care safer.
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