Drug dosing guidelines poor fit for obese patients

Obesity affects about 12.7 million U.S. children and adolescents – or about 1 in 6 kids across the nation, according to the Centers for Disease Control and Prevention. Despite this, there is a significant dearth of dosing guidelines for practitioners, for example pediatric anesthesiologists, to follow when administering potent anesthetics to pediatric patients who are obese.

Janelle D. Vaughns, M.D., director of bariatric anesthesia within the Division of Anesthesiology, Pain and Perioperative Medicine, says Children’s National Health System sees pediatric and adolescent patients of extreme weight (as much as 450 pounds) presenting for weight-loss surgery. In order to ensure that patients remain anesthetized during their surgical procedures, anesthesiologists use various classes of drugs, including hypnotics, muscle relaxants and pain medications. Dr. Vaughns says providers across the nation face similar challenges when determining accurate and precise dosing of drugs for obese pediatric patients.

“Medical guidelines calibrated for a 13-year-old of typical weight cannot be applied to a 13-year-old who weighs 400 pounds. Because morbid obesity in kids is a relatively new phenomenon in our country and globally, there are no formal guidelines to aid with dosing. In this scenario, most doctors extrapolate from guidelines written for lean patients. Because anesthetic drugs are so strong, it is essential to use the correct dose in all patients,” she says.

A recent brief report that Dr. Vaughns co-authored examines this issue. Researchers at Children’s National and the Washington Hospital Center conducted a retrospective review for 440 adult patients who received rapid sequence endotracheal intubation (RSI) in an urban, tertiary care academic Emergency Department. The patients received succinylcholine (a muscle relaxant) and etomidate (a short-acting anesthetic), whose doses are ideally calculated in milligrams per kilogram of total body weight.

The work, published in the December 2016 issue of American Journal of Emergency Medicine, reinforced the importance of data-driven guidelines for all patients. The research team found that the 129 obese patients included in the study were more likely to receive too little of the studied drugs while the 311 non-obese patients studied were more likely to receive too much medicine.

“Our single-center study demonstrates that obesity is a significant risk factor for underdosing RSI medications, whereas non-obesity is a risk factor for overdosing of these medications,” the research team concludes. This study also was reviewed and featured by the New England Journal of Medicine “Journal Watch” in October 2016.

Broadly, the issue of dosing potent medicines for pediatric obese patients is a national public health concern, Dr. Vaughns says. Research teams across the nation have made a concerted effort to publish papers on topics such as how obesity alters pharmacokinetics – how the body takes up, distributes and disposes of powerful medicines – and the deleterious effect of unhealthy body mass index on treatment outcomes for children with diseases such as acute myeloid leukemia.

Dr. Vaughns is among the clinician researchers working with the Pediatric Trials Network (PTN), sponsored by the Eunice Kennedy Shriver National Institute of Child Health and Human Development, to fill this research gap. Working as a team, she, Evan Nadler, M.D., a bariatric surgeon, and Johannes N. van den Anker, M.D., Ph.D., division chief of Clinical Pharmacology, enroll pediatric patients in ongoing trials with a special focus on surgical patients who are obese.

The network is currently conducting pediatric studies at a number of locations, including Children’s National, leveraging blood samples and other specimens drawn during regular care to better understand how medicines routinely used in pediatric patients actually work in kids and to determine appropriate dosing.

Ultimately, the information PTN researchers discover from their multi-year studies will help the Food and Drug Administration update medicine labels to reflect safer, more accurate and more effective dosing for all pediatric patients.