Sedation and analgesia from prolonged pain and stress during mechanical ventilation in preterm infants: is dexmedetomidine an alternative to current practice?

Abstract

Mechanical ventilation is an uncomfortable and potentially painful intervention. Opioids, such as morphine and fentanyl, are used for analgesia and sedation but there is uncertainty whether they reduce pain in mechanically ventilated infants. Moreover, there may be short-term and long-term adverse consequences such as respiratory depression leading to prolonged mechanical ventilation and detrimental long-term neurodevelopmental effects. Despite this, opioids are widely used, possibly due to a lack of alternatives.Dexmedetomidine, a highly selective alpha-2-adrenergic agonist with analgesic and sedative effects, currently approved for adults, has come into use in newborn infants. It provides analgesia and simulates natural sleep with maintenance of spontaneous breathing and upper airway tone. Although data on pharmacokinetics–pharmacodynamics in preterm infants are scant, observational studies report that using dexmedetomidine in conjunction with opioids/benzodiazepines or on its own can reduce the cumulative exposure to opioids/benzodiazepines. As it does not cause respiratory depression, dexmedetomidine could enable quicker weaning and extubation. Dexmedetomidine has also been suggested as an adjunct to therapeutic hypothermia in hypoxic ischaemic encephalopathy and others have used it during painful procedures and surgery. Dexmedetomidine infusion can cause bradycardia and hypotension although most report clinically insignificant effects.The increasing number of publications of observational studies and clinical use demonstrates that dexmedetomidine is being used in newborn infants but data on safety and efficacy are scant and not of high quality. Importantly, there are no data on long-term neurodevelopmental impact on preterm or term-born infants. The acceptance of dexmedetomidine in routine clinical practice must be preceded by clinical evidence. We need adequately powered and well-designed randomised controlled trials investigating whether dexmedetomidine alone or with opioids/benzodiazepines in infants on mechanical ventilation reduces the need for opioids/benzodiazepine and improves neurodevelopment at 24 months and later as compared with the use of opioids/benzodiazepines alone.

RETRACTED ARTICLE: The Neonatal Withdrawal Assessment Tool (NWAT): pilot inter-rater reliability and content validity

“…In addition, assessing the use of the NWAT tool specifically in a cohort of infants with in-utero opioid exposure who are born preterm is warranted in future studies, with or without comparison to the FNAST or ESC NOWS assessment method. Outcomes to be evaluated include length of sedation medication weans, length of hospitalizations, central line days, adverse events and complications, long-term outcomes, and further assessments of content validity from a larger NICU provider base including providers with more varying years of clinical experience 14,15,29,30 .…”

Use of Dexmedetomidine and Opioids in Hospitalized Preterm Infants

“…In a retrospective observational study, infants who received dexmedetomidine compared with infants who received opioids had lower comfort scores, which represented improved patient comfort . Currently available studies address dexmedetomidine adverse effects as difficult to interpret due to the small sample size or use of several concomitant agents that can cause bradycardia and hypotension . Additionally, these studies were limited by an older subset of patients .…”

“… 9 Currently available studies address dexmedetomidine adverse effects as difficult to interpret due to the small sample size or use of several concomitant agents that can cause bradycardia and hypotension. 7 , 10 , 19 Additionally, these studies were limited by an older subset of patients. 10 As more data have become available on dexmedetomidine’s safety and effectiveness, clinicians appear to be using it in the NICU despite it not being indicated in this population.…”

Dexmedetomidine: An Alternative to Pain Treatment in Neonatology

“…More specifically in the field of neonatology, its use has recently been described by Ojha S et al and Tauzin et al in two patient-focused reviews on invasive and non invasive mechanical ventilation [ 63 , 64 ]. It has been shown to be safe and as effective as fentanyl in premature infants when administered as continuous intravenous infusion.…”