Midazolam: Nothing for night owls – DocCheck

The sedative midazolam should not be administered at night – this is shown by a current study that deals with so-called chronotherapy. The authors complain: We know too little about this topic.

A common drug that makes patients drowsy and less anxious before surgery is linked to an increased risk of heart damage when operations are performed at night, according to a study. This was the conclusion reached by researchers from the University of Colorado Anschutz Medical Campus. It’s further evidence that the time of day the drug is administered can affect its effectiveness.

“We analyzed a large data set and showed that the administration of midazolam is associated with an increased risk of myocardial damage in non-cardiac surgery when operations are performed at night and in healthier patients,” says Dr. Tobias Eckle, professor of anesthesiology at the University of Colorado School of Medicine and lead author of the study. “This is very important because these results could have a huge impact on patient mortality.” The study was published in the journal Frontiers of Cardiovascular Medicine released

Nocturnal risk of heart damage

Eckle is one of the few experts in the field of chronotherapy, which administers drugs at specific times of the day to better match circadian rhythms. In this study, researchers used the large Multicenter Perioperative Outcomes Group to analyze 1,773,118 cases in which 951,345 people were given the sedative midazolam. Of these, 16,404 met criteria for myocardial injury or MINS. Although there was no association between the medication and the risk of heart damage in the study population as a whole, the researchers found that the timing of the medication was important. “We found a strong association between the administration of midazolam and the risk of MINS when the surgery was performed at night or in healthier patients,” Eckle said.

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The reasons for this are unclear, but could lie in the PER2 gene, a light-regulated protein that Eckle says helps protect the heart from injury. In mouse studies, researchers found a link between midazolam, circadian protein expression, and cardiac ischemia. “This suggests that midazolam disrupts the circadian system in humans,” Eckle said. The drug increases the neurotransmitter GABA, which inhibits certain brain signals, giving it a calming effect. This in turn may reduce the expression of higher nocturnal levels of PER2. As levels fall, the heart may become more susceptible to damage when midazolam is given at night.

Underrated chronotherapy

According to Eckle, the whole field of chronotherapy is still under-researched and could provide clues for more effective use of routine therapies. He believes that new drugs should be tested to see what time of day is best to use them. Blood pressure medication, for example, works best at night. “Medications are often given in the most effective way,” he said. “But what is most effective can also cause harm.

This article is based on a Press Release from the University of Colorado. We have a study for you here and referenced in the text.

Image source: At Nugroho, Unsplash

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