Abstract by Marlene Walden, PhD, RNC, NNP
Preterm neonates in the Neonatal Intensive Care Unit (NICU) frequently encounter multiple stressful and/or painful diagnostic and therapeutic procedures that are a necessary part of their medical and nursing care. Despite scientific evidence that preterm neonates have the anatomic and functional capacity to perceive pain coupled with the ongoing fears that prolonged analgesia may be associated with tolerance, withdrawal, and other adverse consequences, many health care providers fail to provide adequate analgesia for diagnostic and therapeutic procedures in the NICU. Existing scientific evidence suggests that chronic or repeated stress and pain in preterm neonates leads to clinical instability and may contribute to adverse developmental outcomes. Little is known, however, about the short- and long-term effects of sedatives or prolonged analgesia in preterm neonates, particularly at a time when the preterm neonate is experiencing rapid brain growth and development.
A multicenter pilot clinical trial (Neonatal Outcome and Prolonged Analgesia in Neonates or NOPAIN trial) was conducted to test the hypothesis that preemptive analgesia may reduce the incidence of poor neurologic outcomes in preterm neonates who require ventilatory support. Of particular concern were the potential contributions of pain and stress in the development of early intraventricular hemorrhage (IVH) and/or ischemic lesions leading to periventricular leukomalacia (PVL). Anand and colleagues (1999) hypothesized that the use of preemptive analgesia in preterm neonates requiring ventilatory support would lead to fewer neonatal deaths and may reduce the incidence of severe IVH (grade III or grade IV) and PVL, two primary factors which contribute to poor neurologic outcomes.
In a blinded, pilot clinical trial, 67 preterm neonates from 9 participating medical centers in the NOPAIN trial were randomly assigned to receive either continuous infusions of morphine sulfate, midazolam hydrochloride, or a 10% dextrose placebo. Physicians, nurses, and all NICU staff were blinded to the identity of the study drug that the infants were receiving. Preterm neonates born between 24 and 32 weeks' gestation and who had been intubated and required ventilatory support for less than 8 hours were eligible to participate in the study if they were enrolled within 72 hours of birth. Neonates with major congenital anomalies, severe intrapartum asphyxia (defined as a 5-minute Apgar score < 3), or who were participating in other research studies which interfered with the NOPAIN study procedures or outcomes were excluded from participating in the study.
With the exception of increased frequency of fetal distress in the morphine group, demographic, clinical, and socioeconomic variables for neonates and mothers were similar among the 3 groups. Severity of medical illness at birth was assessed using the Clinical Risk Index for Babies and was similar among the 3 randomized groups. However, significant differences were noted in severity of illness at time of hospital discharge. These differences were hypothesized by the researchers to be attributable to neonatal complications of therapy received during the course of the infant's hospital stay.
Loading and maintenance doses of morphine and midazolam were based on data from recent clinical and pharmacokinetic studies in preterm neonates. The continuous drug infusions of morphine, midazolam, or the placebo dextrose infusion were continued for as long as determined clinically necessary by the infant's physician. When the drugs were no longer needed for sedation or analgesia, the drugs were weaned and stopped using predetermined study criteria. No differences were noted in the amount of additional analgesia prescribed during the study or in the duration of continuous drug therapy between the 3 groups. Adequacy of analgesia and sedation were measured before, during, and 12 hours after discontinuation of drug infusions. COMFORT scores measured levels of sedation, while responses to pain were measured using the Premature Infant Pain Profile (PIPP). Within group comparisons demonstrated significantly reduced PIPP scores during drug infusions from baseline levels for only the morphine group, suggesting morphine provides superior relief of discomfort associated with the procedure. PIPP scores were also significantly reduced during endotracheal suctioning in the morphine and midazolam groups compared with the dextrose placebo group, supporting sedative and/or analgesic effectiveness experienced by the midazolam and morphine groups. Significantly decreased sedation was also noted in the morphine group at 12 hours after stopping the drug infusion, possibly indicating agitation associated with mild withdrawal from opioids in this group of neonates.
Poor neurologic outcomes were defined as neonatal death or the presence of severe IVH or PVL as measured by cranial ultrasound examinations. Overall, neonates who received morphine had significantly better neurologic outcomes than did the neonates in the other 2 groups. Specifically, only 4% of neonates in the morphine group had poor neurologic outcomes as compared with 32% of neonates in the midazolam group and 24% of neonates in the placebo dextrose group. While no neonatal deaths occurred in the morphine group, 1 neonate in the midazolam group and 2 neonates in the placebo dextrose group died.
The study also examined several secondary outcomes including number of days required for mechanical ventilation, continuous positive airway pressure (CPAP) or oxygen therapy, duration of NICU or hospital stay, and tolerance of enteral feeds. Although no significant differences occurred among the three groups in any of the secondary outcomes, trends for reduced duration of ventilation, CPAP, oxygen therapy and hospital stay as well as reduced requirements for additional analgesia were noted in the morphine group. Neurobehavioral outcomes at 36 weeks postconceptional age were similar among the 3 randomized groups.
Although these results are preliminary, this study supports the short-term benefits of analgesia and sedation in preterm neonates who require ventilatory support. Prophylactic administration of morphine analgesia appears to be superior in improving the neurologic outcomes identified in this study. The small sample size, however, limits the generalizability of the results and supports the need for a large multicenter randomized trial to confirm the safety and effectiveness of these drugs before widespread changes in clinical practice can be recommended.
In summary, it is evident from this study that nurses must play an important role in facilitating caregiving practices which prevent and/or minimize the occurrence of repetitive stress and pain in preterm neonates in the NICU. Nurses are in an optimal position to observe infant responses to caregiving practices and to effectively advocate for the use of sedation and/or analgesia when deemed clinically necessary.
Anand, KJS, McIntosh, M., Lagercrantz, H., Pelausa, R., Young, T., & Rohitkumar, V.: Analgesia and sedation in preterm neonates who require ventilatory support: Results from the NOPOAIN Trial. Arch Pediatr Adolesc Med, 153(4):331-338, 1999.
See Chapter 9 in Essentials of Pediatric Nursing, 5th edition.
See Chapter 10 in Nursing Care of Infants and Children, 6th edition.
March 15, 2002
~ Other Papers
Home ~
~ Wong on Web Home ~