The effects of analgesia in the vulnerable infant during the perinatal period

Several recent studies have changed our understanding of pain [1], pain assessment [2], and analgesia in newborn neonates and infants [3-6]. As a result, many newborns are now given drugs such as morphine, fentanyl, or acetaminophen from the very first hours of life. Although our knowledge of pain and its management in the perinatal period has increased [7], little is known about the first hours and days of life when major physiologic transition events occur. Transition from the intrauterine to the extrauterine environment in both preterm and term-born neonates is a complicated process. Adaptation to extrauterine life takes place in various organs during the first 24 to 49 hours. This process is already complicated in a term baby born after an uneventful pregnancy and delivery but is especially troublesome in critically ill newborns with disturbed liver and kidney function and resulting aberrations in drug metabolism. In critically ill term-born neonates and in preterm newborn neonates, circulatory and pulmonary problems of prematurity and underlying pathology add to this complexity. For example, prenatal and postnatal events that promote inflammation and infection may blunt the effects of resuscitation efforts, as increasing levels of circulating cytokines can result in persistent respiratory problems, hypovolemia, and hypotension [8]. The effects of drugs in this period have hardly been investigated. There is limited knowledge about the metabolism for 80% of commonly used drugs [9] such as antibiotics and analgesics, and great harm is possible even with the best intent. Adverse drug reactions during pregnancy, eventually contributing to the development of congenital anomalies, have made perinatologists and neonatologists extremely careful in their use of drugs that have not been attentively studied in neonates. Rational drug therapy in newborns is often confounded by a combination of unpredictable and often poorly investigated pharmacokinetic and pharmacodynamic interactions [10]. The studies focusing on analgesic drug use during this period are often limited to one dose or to the first 24 or 48 hours of life [3,4]. Clinicians, however, seek information about effects during the neonatal intensive care stay, a period that extends from 1 to 2 weeks in selected babies.