LITTLE ROCK -- Routine doses of morphine for pain and stress in premature babies could harm rather than help the infants, according to a study led by researchers at the University of Arkansas for Medical Sciences (UAMS) and Arkansas Children’s Hospital Research Institute (ACHRI) and published today in The Lancet, a leading medical journal.

UAMS and Arkansas Children’s Hospital were the leading sites that participated in the NEOPAIN trial, which was supported by the National Institutes of Health and a consortium of other funding agencies. Twelve centers in the United States participated in the study, including two in Sweden, one in Scotland and one in France.

Dr. K.S. “Sunny” Anand, UAMS Professor of Pediatrics, Anesthesiology, Pharmacology and Neurobiology, served as the study chairman. Dr. Anand is also the Morris and Hettie Oakley Chair in Critical Care Medicine in the UAMS College of Medicine.  NIH funding for the study was provided to the Arkansas Children’s Hospital Research Institute.

“Some physicians across the country are using a lot of morphine in preterm babies,” Anand said. “This certainly cautions them that its use can lead to side effects and that morphine is not the panacea it initially seemed to be.”

Premature babies are exposed to many procedures required for their medical care that cause repetitive pain and stress while their brains are immature and vulnerable to early brain injury.  These babies have an increased sensitivity to pain and respond intensely with rapid changes in heart rate, blood pressure, oxygen level and other behaviors. Morphine is one of the drugs used most commonly to relieve pain in these infants.

The NEOPAIN Trial -- the largest study ever done using pain-relieving medications in infants -- investigated the short-term outcomes following routine morphine treatment in extremely premature babies who require a ventilator to support their breathing after birth. NEOPAIN is an acronym that stands for “NEurologic Outcomes & Pre-emptive Analgesia In Neonates.”

Smaller studies have suggested that routine morphine therapy could prevent early brain damage or death in premature babies, Anand said. The NEOPAIN study shows that contrary to investigators’ expectation, there was no difference in the rates of early brain damage or death between the groups of infants who did or did not receive routine morphine.

Anand said the main side effect of routine morphine use was lowered blood pressure. “This occurred in the sickest and most premature babies and may possibly decrease blood flow to the brain, thus possibly promoting the very type of injury the morphine use was designed to prevent,” he said.

Anand said the study should cause physicians and nurses to be more guarded in using morphine and realize it is a “double-edged sword.”

“What this study shows is while repetitive pain by itself is bad if untreated, giving pain relief in absence of pain is also bad,” Anand said. “This is where the art of medicine comes in to balance the amount of pain relief with the degree of pain that is occurring.”

Anand said two colleagues – Dr. R. Whit Hall, medical director of the UAMS Neonatal Intensive Care Nursery and Dr. Joanna Siebert, UAMS professor of Pediatrics and Radiology – played major roles locally in the clinical trial.

The study involved 898 babies from 23 to 32 weeks of gestation. The doctors and nurses did not know which babies received intravenous morphine and which babies received intravenous sugar-water solution (the placebo treatment).  However, the study allowed the doctors and nurses to give additional morphine doses to babies who appeared to be in pain, regardless of their treatment group. 

ACH is a clinical, teaching and research affiliate of UAMS, the state’s only academic health sciences center. The Arkansas Children's Hospital Research Institute (ACHRI) is a not-for-profit corporation owned by Arkansas Children's Hospital (ACH). Essentially all of the physicians and surgeons on the ACH campus are UAMS College of Medicine faculty. Research is a major component of the missions of UAMS and ACH. ACHRI was created to provide a research environment on the ACH campus to meet the research needs of UAMS faculty.