SGEM #397: Give a Little Bit…of Oseltamivir to Pediatric Patients Admitted with Influenza

Date: February 27, 2023 Reference: Walsh PS, Schnadower D, Zhang Y, Ramgopal S, Shah SS, Wilson PM. Association of early oseltamivir with improved outcomes in hospitalized children with influenza, 2007-2020. JAMA Pediatr. 2022. Guest Skeptic: Dr. Marisu Rueda-Altez is a pediatric infectious disease fellow at Children’s National Hospital in Washington, DC. She is also the President of the Junior Section of the Society for Pediatric Research. Dr. Marisu Rueda-Altez Case: A 5-year-old child presents to the emergency department in the midst of flu season with three days of fever, upper respiratory symptoms, and malaise. His parents also report that he has lost his appetite and refusing to drink liquids. Nasopharyngeal PCR testing is positive for Influenza A. On physical exam, he is tired appearing and showing signs of respiratory distress with tachypnea and accessory muscle use. His lips look dry and cracked. His oxygen saturation is hovering around 88-90%. His chest radiograph does not demonstrate any focal opacities. After a discussion with his parents, you all agree that it is best for him to be admitted to the for IV hydration and close monitoring. His parents ask you, “A few years ago when we had the flu, we took a medication that helped reduce the length of our symptoms. Would he benefit from that too?” Background: Oseltamivir is recommended by the American Academy of Pediatrics, Infectious Diseases Society of America and Center for Disease Control and Prevention for the treatment of influenza in both adults and children. [1-3] Possible benefits include reduction in duration of symptoms and improvement of outcomes in hospitalized patients. Most of these recommendations are based on data from adult studies during the H1N1 pandemic with limited pediatric data. The SGEM has covered the use of oseltamivir for influenza on SGEM #98 and SGEM #312. Despite the recommendations from these various organizations, there remains some controversy (and skepticism) about the use of oseltamivir due to unpublished trial data, lack of access to the research data by the authors, and ghost-written papers. The BMJ was involved in a long legal battle with the manufacturer that you can read about here. Suffice it to say, that there were more harms than originally reported (including nausea and vomiting, neuropsychiatric events, headaches), and it is possible that the potential benefits were exaggerated.[4] Clinical Question: Will early administration of oseltamivir reduce length of hospitalization and complications of influenza infection? Reference: Walsh PS, Schnadower D, Zhang Y, Ramgopal S, Shah SS, Wilson PM. Association of early oseltamivir with improved outcomes in hospitalized children with influenza, 2007-2020. JAMA Pediatr. 2022. Population: Children <18 year from Pediatric Health Information System (PHIS) database hospitalized with Influenza from 2007-2020. Excluded: Transfers to other hospitals, repeated encounters (if >7 days between encounters, picked one at random; if <7 days, picked the first one), death/ECMO on day 0 or 1 to avoid immortal time bias. Exposure: Early administration of oseltamivir (HD 0 or 1) Comparison: Late administration of oseltamivir (HD 2 or later) or none. Outcome: Primary Outcome: Hospital length of stay (LOS) Secondary Outcomes: 7-day hospital readmission, late ICU transfer (on or after hospital day 2 after being admitted to general ward), composite outcome of in-hospital death or ECMO use. Authors’ Conclusions: "Early use of oseltamivir is associated with shorter hospital stay and lower odds of 7-day readmission, ICU transfer, ECMO use and death." Quality Checklist for Observational Study: Did the study address a clearly focused issue? Yes Did the authors use an appropriate method to answer their question? Unsure. Was the cohort recruited in an acceptable way? Unsure Was the exposure accurately measured to minimize bias...