A comparative study of two remifentanil doses for procedural pain in ventilated preterm infants: a randomized, controlled study*.

OBJECTIVES: Remifentanil is an ultrashort-acting synthetic opioid, and the metabolism of which is not influenced by hepatic or renal function. This study aims to compare the efficacy of two remifentanil doses during procedures in ventilated preterm infants.

DESIGN: Prospective, randomized, double-blind, noninferiority trial.

SETTING: Neonatal ICU.

PATIENTS: Preterm infants who were supported by a mechanical ventilator with tracheal tube and requiring central venous access.

INTERVENTIONS: Two remifentanil dosages were administered in mechanically ventilated preterm infants during peripherally inserted central catheter insertion. Fourteen preterm infants were randomly assigned to low-dose (0.1 μg/kg/min) or high-dose (0.25 μg/kg/min) remifentanil infusion. The Premature Infant Pain Profile was used to score pain during the procedure, and changes in the Premature Infant Pain Profile score between needle puncture and baseline were analyzed to investigate the noninferiority of low-dose to high-dose remifentanil. Occurrence of cardiorespiratory complications was also recorded.

MEASUREMENTS AND MAIN RESULTS: The median gestational age (minimum, maximum) was 26 weeks (24, 31), and the median birth weight was 825 g (610, 1,280). Changes in Premature Infant Pain Profile in the high-dose and low-dose groups were 1.43 ± 3.10 and -0.60 ± 5.32, respectively. The difference in changes in the Premature Infant Pain Profile score between the high-dose and low-dose groups was -2.03 ± 4.13. The corresponding lower limit of one-tailed 97.5% CI was -7.24, below the noninferiority margin. Apneic events and bradycardia did not occur in the low-dose group; however, there were three episodes of apnea (42.9%) and one of bradycardia (14.3%) in the high-dose group (p = 0.683 and 0.366, respectively).

CONCLUSION: For mechanically ventilated preterm infants, the use of remifentanil at 0.25 μg/kg/min as an analgesic for short procedures represents a therapeutic option. Our pilot study suggests the need for larger randomized trials.