Jury Still Out on Premedicating Kawasaki Disease Patients Before IVIG Therapy

Premedicating children with Kawasaki disease (KD) using hydration and agents such as acetaminophen, antihistamines, histamine 2 receptor antagonists or corticosteroids to prevent infusion-related reactions associated with IV immune globulin (IVIG) may not necessarily be helpful, according to a recent study by pharmacists from Jersey Shore University Medical Center, in Neptune, N.J.

The researchers reviewed records for 66 children with KD who were given a total of 81 IVIG administrations between January 2014 and June 30, 2019. This included 42 boys and 24 girls, ages 4 months to 15 years. Sixty-four patients (97%) were premedicated prior to infusion. However, 17 in 66 patients (26%) experienced IVIG-related adverse events, most commonly chills, vomiting and spiking fever. Despite appropriate medication management, five patients (7.6%) developed coronary abnormalities (Pediatr Allergy Immunol 2021;32[4]:750-755).

There were strong patterns in premedication, said lead study author Elaine Liu, PharmD, a PGY-2 infectious diseases pharmacy resident at Hartford Hospital, in Connecticut. She was a pharmacy student at the Ernest Mario School of Pharmacy at Rutgers, the State University of New Jersey, at the time of the study, and continued her PGY-1 training at the N.J. medical center. The most common premedication regimen seen in the study was a combination of acetaminophen and diphenhydramine, which accounted for 65% of regimens used and was given prior to 63% of IVIG infusions.

Other commonly used regimens were diphenhydramine alone, and a triple combination of acetaminophen, diphenhydramine and famotidine. Of the 25 documented adverse events, 16 were immediate, occurring within six hours of starting IVIG, and nine were delayed, occurring after six hours.

Overall, she said, patients demonstrated appropriate clinical outcomes, with an average fever duration of eight days and average hospital stay of about four days, similar to national data.

Although premedication was not shown to adversely affect patient outcomes, Dr. Liu said, “we didn’t really observe much of a benefit when looking at a reduction in adverse events, at least compared with historically reported incidences of adverse event profiles with IVIG” of about 20%.

More Studies Needed

Due to a lack of formal guidelines or recommendations on premedication regimens prior to IVIG therapy, more studies are needed, said senior study author Anita Siu, PharmD, BCPS, the neonatal and pediatric pharmacy clinician at K. Hovnanian Children’s Hospital at Jersey Shore, in Neptune, and a clinical professor of pharmacy practice and administration at the Ernest Mario School of Pharmacy, in Piscataway.

Published studies on the use of premedication agents have been conflicting, Dr. Siu said. Ultimately, the efficacy of premedication continues to pose a clinical question, she added.

Secondary consequences of premedication, such as unnecessary drug exposure, IVIG treatment delays and increased costs, are issues to be considered in the face of what could be a questionably beneficial yet widely used practice, she said. “We really hope that more larger randomized controlled trials will come out of this.”

Dr. Liu added, “This encourages us to reevaluate our practices and supports the need to have further large, potentially prospective studies, given that the literature available right now is so mixed. Ours was a single-center study, but there are many other patient demographics and a lot of other institutions. We would love to see more data arise to get a bigger picture of overall practice and really discern if there is a benefit in this strategy at all.”

In the pediatric population, Drs. Liu and Siu said, adverse events from IVIG occur in an estimated 1% to 40% of patients (Eur Ann Allergy Clin Immunol 2017;49[1]:11-14). Other than premedication, common mitigation strategies include slowing the infusion rate, switching from IV to subcutaneous immune globulin, changing to another IG product or discontinuing infusion. ■

The authors reported no relevant financial disclosures.