The research team, led by the pediatric otolaryngologist David Smith and the circadian biologist John Hogenesch, analyzed approximately 500,000 doses of a dozen drugs—including painkillers, antibiotics, and corticosteroids—given to inpatients at the Cincinnati Children’s Hospital Medical Center from 2010 to 2017. The researchers found that the times at which drugs were ordered and administered weren’t uniformly distributed—instead, there were “distinct morning-time surges and overnight lulls.” (The researchers, who are based at the Cincinnati hospital, declined an interview request.) Roughly a third of all orders were submitted in the four-hour period from 8 a.m. to noon. And most of those were concentrated between 8 and 10:30 a.m., when clinicians were conducting their morning rounds.
The finding makes sense, says Garret FitzGerald, who directs the Institute for Translational Medicine and Therapeutics at the University of Pennsylvania, and was not involved in the research. “Any of us that are physicians know that a lot of hospital behavior is driven by rounding times, and those rounding times are chosen for all sorts of reasons that don’t necessarily have any particular scientific basis,” he told me.
That doesn’t make the synchrony between rounding and prescribing medically sound, however. Patients should get drugs when they need them, not just when it’s convenient for clinicians, and there’s no evidence to suggest that, say, infections or inflammation or pain are confined to the morning. (In fact, patient pain tends to worsen at night.) “A lot of the times the schedules that are in place have nothing to do with the biological requirements of the patient that may be driven by circadian rhythms,” says Michael Smolensky, a medical chronobiologist at the University of Texas at Austin. The flood of morning orders also seemed to create an operational bottleneck; the delay between when drugs were prescribed and when they were administered was longest for medications ordered in that 8-to-noon window, the researchers found. It’s not clear whether these delays affected patient outcomes, but it’s certainly conceivable that they could have.
In addition to these potential problems, there’s the fact that our bodies are not stable systems. Our own internal rhythms mean that time of day can influence how well a given drug works or how severe its side effects are. Many ailments wax and wane in predictable ways over the course of the day—cold and allergy symptoms tend to be worst in the morning, while heartburn often strikes overnight—as do blood flow, liver function, and other physiological processes that can affect drug metabolism. A compound that’s quickly eliminated from the body during the day can linger at night. “We know that giving drugs at different times of the day can often result in different blood levels of those drugs or different adverse effects,” FitzGerald said. Our responses to various drugs, he added, are “conditioned by the clock.”