Millions of people receive medicines before surgery to help them relax and reduce anxiety. One of the most common is midazolam, a sedative that helps patients stay calm and may also make them forget parts of the procedure.
Although doctors have used it for many years, new research suggests the time of day it is given could affect how safe it is.
Researchers at the University of Colorado Anschutz Medical Campus wanted to find out whether the body’s internal clock changes the way people respond to midazolam.
Every person has a natural daily rhythm, called the circadian rhythm, that controls sleeping, waking, hormones, and many other body functions. Scientists now know this internal clock can also influence how medicines work.
The team studied the medical records of more than 1.7 million patients who received midazolam before surgery. More than 16,000 of these patients experienced heart problems after their operations. When the researchers looked more closely at the data, they noticed that heart injuries were more common after surgeries performed at night.
The increased risk was seen even in patients who were generally healthy. This surprising pattern suggested that something about nighttime treatment was making the heart more vulnerable. The scientists then searched for a biological explanation.
They focused on a gene called PER2, which helps control the body’s circadian rhythm. Earlier research has shown that PER2 also helps protect the heart during times of stress. If the activity of this gene falls, the heart may be less able to protect itself.
To better understand the process, the researchers carried out laboratory experiments in mice. They found that midazolam increased the activity of GABA, a brain chemical that produces calming effects. At the same time, the drug reduced the activity of the PER2 gene, especially during the night.
This reduction in PER2 activity may weaken the heart’s natural defenses, making it more likely to be injured during surgery. The findings suggest that the same medicine can have different effects depending on when it is given. However, the researchers say more studies are needed before changing medical practice.
The study adds to growing evidence that treatment timing matters. Some medicines, including certain blood pressure drugs, are already known to work better or cause fewer side effects when taken at specific times of day. Scientists believe this approach, known as chronomedicine, could help improve many types of medical care.
The researchers are not advising patients to avoid midazolam when it is needed. Instead, they hope doctors will continue studying whether choosing the best time to give certain medicines can improve safety, especially for people with a higher risk of heart disease.
The study was led by Tobias Eckle and colleagues at the University of Colorado Anschutz Medical Campus and published in Frontiers in Cardiovascular Medicine.
The findings suggest that the body’s natural clock may play an important role in how patients respond to medicines used during surgery. If confirmed in future research, paying attention to treatment timing could become another way to make operations safer and improve recovery.
If you care about heart disease, please read studies that herbal supplements could harm your heart rhythm, and how eating eggs can help reduce heart disease risk.
For more health information, please see recent studies that apple juice could benefit your heart health, and results showing yogurt may help lower the death risks in heart disease.
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