Analgesic trials in children: safety, efficacy and innovation

Abstract

A premature newborn infant is being treated in a neonatal intensive care unit, quite ill and subject to an array of invasive procedures. We wish to do all we can to minimize that individual’s suffering. Which analgesics may be effective? Are they safe? Are they metabolized by the youngest of human beings in a predictable way? Clearly, to answer these questions it is necessary to conduct clinical trials on children within this population. But is it ethical? Is it feasible? That is the tension experienced by pediatric practitioners who wish to invoke evidence to ease children’s pain in a safe and effective manner. The magnitude of the problem may be appreciated when one examines the epidemiology of pain in children. A prospective study conducted in neonatal intensive care settings showed that over the first 14 days of admission, each premature infant experienced a median of 75 (range: 3–364) painful procedures and ten (range: 0–51) painful procedures per day of hospitalization. Among the total of 42,413 painful procedures observed, newborns were provided with pharmacologic therapy specifically targeting the procedural pain only 2.1% of the time [1]. This study, and others in the field, tells us little about other, more ongoing pain in neonates, such as disease-related and postoperative pain. Of course, beyond the neonatal period, infants and children commonly experience acute pain due to surgery or injuries. In addition to acute pain, 5–23% of school-age children experience significant recurrent pain, such as headache, chest pain, abdominal pain and limb pain [2–4]. Children also endure chronic daily pain from headache disorders, neurodegenerative diseases, inflammatory and autoimmune disease, post-traumatic neuropathic pain conditions including complex regional pain syndrome, small fiber neuropathies and pain due to malignancies and other life-limiting diseases.