Drugs are administered at best times for practitioners, not patients

Written by Ilana Landau, Editor

The results of a novel study suggest that medication administration to hospital inpatients is largely determined by staffing schedules rather than ideal dosing times for patients.

It is assumed that important clinical decision making in hospitals occurs continuously throughout the 24 hours a day that they operate. However, a new study, concerning approximately 500,000 drug doses administered to hospital inpatients at a major US children’s hospital between 2010 and 2017, suggests that too many critical clinical decisions in hospitals are made according to what is most practical for healthcare providers, rather than at the ideal dosing times for patients.

In the study, researchers from the Cincinnati Children’s Hospital Medical Center (OH, USA) assessed the daily distribution of roughly 500,000 doses of 12 different drugs to 1546 inpatients at a tertiary pediatric hospital in the USA. Both the order and dosing times of the drugs were monitored.

A key study finding concerns the time-of-day-dependency of drug order times; close to one-third of the total 103,847 drug orders were placed between 8:00 and 10:00 am. Administration of the first drug dose also followed a distinct pattern; the first dose of a requested drug was often given 2 hours after the drug’s request had been made.

Frequently asked questions:

The observed patterns regarding drug requests and first dosing were consistent across a range of drugs, disease indications and inpatient hospital units, and aligned with the rounding times of hospital medical teams more consistently than with patients’ needs.

For example, patient’s clinical responses to hydralazine — an antihypertensive agent —are known to vary throughout the day by a magnitude of up to  4%. In the study, researchers observed that patients were more responsive to hydralazine therapy during nighttime hours, when fewer drug orders were placed and first dosed.

It is important to note that no practice guidelines currently exist specifying time-of-day recommendations for any of the drugs evaluated in this study. Nevertheless, such time-of-day treatment bias is concerning and problematic. Analgesics, for example, should be administered when patients report pain; this does not selectively or predictably occur at any one time of day. 

Lead study co-authors David Smith, Marc Ruben and John Hogenesch (all from Cincinnati Children’s Hospital), commented: “For every drug, order times were time-of-day-dependent, with morning-time surges and overnight lulls. These rhythms corresponded to shift changes and rounding times.”

In the study, the authors conclude: “The prevailing dogma is that hospital treatment is administered as needed regardless of time of day. Our findings challenge this notion and reveal a potential operational barrier to best clinical care.”


Ruben MD, Francey LJ, Guo Y et al. A large-scale study reveals 24-h operational rhythms in hospital treatment. PNAS. doi: 10.1073/pnas.1909557116. (Epud ahead of print) (2019).

What happens during hospital rounds?

During ward rounds, the relevant medical team visit every inpatient and collaboratively develop a treatment plan for each patient. Orders for diagnostics, therapies and referrals to speciality services are commonly placed during rounds, once final consensus is reached among the team.

What is circadian biology?

Circadian biology refers to the natural, internal rhythms that regulate the body’s sleep—wake cycle and repeat every 24 hours. The rhythms are orchestrated by the body’s circadian clocks and can impact ones therapeutic response.