Midazolam is a medicine that helps people feel calm or sleepy before surgery. It works so well that most patients don’t remember anything about the operation afterward. But a new study shows that when midazolam is given at night, it might have an unexpected and serious side effect—possible harm to the heart.
Scientists at the University of Colorado Anschutz Medical Campus discovered this by studying more than 1.7 million patient records. These patients had all been given midazolam before surgery. Among them, over 16,000 showed signs of heart injury afterward.
But when the scientists looked more closely, they noticed a pattern: the risk of heart injury was higher when surgeries were done at night, especially in patients who were otherwise healthy.
This strange finding led the researchers to investigate why time of day could make such a difference. Their search brought them to a special gene called PER2.
This gene helps protect the heart and is part of our body’s internal clock—also known as the circadian rhythm. The circadian rhythm controls how our body responds to day and night and is heavily influenced by light.
In experiments with mice, the scientists found that midazolam may lower the levels of the PER2 gene during the night. This is a problem because the PER2 gene is especially important in protecting the heart. So if PER2 levels are reduced right when the heart needs its protection, the chance of injury goes up.
Midazolam works by boosting a calming chemical in the brain called GABA. This makes people feel relaxed, which is why it’s used before surgery. But the study showed that this same calming effect might also affect the heart’s natural protection system—especially at night, when PER2 levels are already lower than during the day.
This discovery is important because it reminds us that the timing of medication can matter just as much as the medicine itself. Our bodies respond differently to drugs depending on what time it is. This field of research, called chronomedicine, looks at how timing affects drug safety and effectiveness.
Some medicines, like those for high blood pressure, are already known to work better when taken at night. Now, this study suggests that we should pay more attention to the timing of sedatives like midazolam too—especially if the patient is otherwise healthy and the surgery is scheduled at night.
The study was led by Dr. Tobias Eckle and published in Frontiers in Cardiovascular Medicine. It shows how medical researchers are always finding new ways to make treatments safer and more effective. Even though midazolam is a common and useful medicine, knowing when to use it could help prevent heart problems in some patients.
This research is a powerful example of how tiny details—like the time of day—can make a big difference in our health and safety.
If you care about heart health, please read studies about how eating eggs can help reduce heart disease risk, and Vitamin K2 could help reduce heart disease risk.
For more information about health, please see recent studies that olive oil may help you live longer, and Vitamin C linked to lower risk of heart failure.
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