Use of Analgesic and Sedative Drugs in the NICU: Integrating Clinical Trials and Laboratory Data

Abstract

Recent advances in neonatal intensive care include and are partly attributable to growing attention for comfort and pain control in the term and preterm infant requiring intensive care. Limitation of painful procedures is certainly possible, but most critically ill infants require unavoidable painful or stressful procedures such as intubation, mechanical ventilation, or catheterization. Many analgesics (opioids and nonsteroidal anti-inflammatory drugs) and sedatives (benzodiazepines and other anesthetic agents) are available but their use varies considerably among units. This review summarizes current experimental knowledge on the effects of sedative and analgesic drugs on brain development and reviews clinical evidence that speaks for or against the use of common analgesic and sedative drugs in the NICU but avoids any discussion of anesthesia during surgery. Risk/benefit ratios of intermittent boluses or continuous infusions for the commonly used sedative and analgesic agents are discussed in the light of clinical and experimental studies. The limitations of extrapolating experimental results from animals to humans must be considered while making practical recommendations based on the currently available evidence.

Sedation and analgesia practices in neonatal intensive care units (EUROPAIN): results from a prospective cohort study

“…Discussion about opioid use in ventilated neonates include developmentally regulated pain sensitivity, clinical instability from acute pain or stress, unsynchronised breathing, and suboptimum ventilation, 32 and long-term eff ects on brain development. [33][34][35][36] A Cochrane review concluded that opioids reduce neonatal pain scores, and do not prolong ventilation, alter mortality or subsequent intelligence, motor function, or behaviour, 33 but evidence for the routine treatment of ventilated newborn babies with opioids is insuffi cient. Variations exist in the patterns of opioid use in European countries.…”

Prevention and Management of Procedural Pain in the Neonate: An Update

“…97 Alternative medications, such as methadone, 99 ketamine, propofol, and dexmedetomidine, have been proposed for pain management in neonates; however, few, if any, studies of these agents have been performed in this population, and caution should be exercised when considering them for use because of concerns about unanticipated adverse effects and potential neurotoxic effects. 100 Although the potential benefits of using methadone for the treatment of neonatal pain include satisfactory analgesic effects and enteral bioavailability as well as prolonged duration of action related to its long half-life and lower expense compared with other opiates, safe and effective dosing regimens have yet to be developed. 101 Ketamine is a dissociative anesthetic that, in lower doses, provides good analgesia, amnesia, and sedation.…”

Towards improved animal models of neonatal white matter injury associated with cerebral palsy

“…benzodiazepines) on interneuron populations in humans during critical windows of developmental plasticity (Durrmeyer et al, 2010). Ongoing dialogue between clinicians and basic neuroscientists is necessary to develop advanced models that address the current and complex causes of acquired human newborn neurological injury.…”