Monaz: Hello, I'm Monaz Mehta, editor in the Cochrane Editorial and Methods department. The Cochrane Neonatal Group has produced more than 400 Cochrane Reviews over the last two decades, updating these periodically as new evidence becomes available. In March 2021, they published the update of their review of opioids for newborn babies requiring mechanical ventilation and we asked two co-authors of the review, Olga Romantsik and Matteo Bruschettini from Skåne University Hospital in Lund, Sweden, to tell us about the latest findings.

Matteo: Hello Olga. Let’s begin with a few words on why some newborn babies need to receive drugs such as opioids.

Olga: Thanks Matteo. Yes, the starting point is that a baby admitted to a neonatal intensive care unit may need help with their breathing, leading to the use of mechanical ventilation. Intubation, which means the insertion of the tube into the airways to allow this to happen and the mechanical ventilation itself cause discomfort and pain, and newborn babies are very sensitive to pain. Even more, pain may have negative effects on their neurodevelopment so it’s important to reduce this pain as much as possible, sometimes with help of the drugs such as morphine and fentanyl. I know that this is an area your group have done a lot of work on, in order to help understand and judge pain in newborns, so perhaps you could say something about this.

Matteo: Thanks. People who work in neonatal intensive care units receive special training to read the signs of discomfort and distress in newborn babies, even in those born very prematurely and several scales focus on the baby's appearance and behavior, and on other objective parameters such as heart rate. Long-lasting pain is very stressful for anyone, but especially for newborn infants and so by using drugs such as morphine and fentanyl, which are called opioids, that reduce pain might improve the long-term development of newborns babies needing mechanical ventilation. This review is a good opportunity to investigate if this is the case.

Olga: Indeed. We found 23 studies enrolling approximately 2000 babies. Most of the studies were done in preterm infants, but five also included infants born after a full 9 months of pregnancy. In 15 studies, either morphine or fentanyl was compared to either a placebo or no intervention. The other 8 studies compared morphine or fentanyl either to each other or to other painkillers and so we analyzed them separately. Matteo, perhaps you could summarize the main results.

Matteo: We found that the use of morphine or fentanyl has little to no effect in reducing the duration of mechanical ventilation and neonatal mortality and are actually uncertain whether opioids have an effect on pain in these infants because too few of the included studies reported this outcome or there were limitations in study design or discordant findings. Only one of the studies reported on neurodevelopmental outcome at 18-24 months of age, but this included only 78 babies, which is probably too few to determine if there is any difference between the infants given an opioid or the placebo.

Olga: That suggests that more research is needed. What should new studies investigate?

Matteo: Future studies should enroll only newborns who are showing indicators of pain based on validated pain scores when they are on mechanical ventilation and we particularly need data for very preterm infants. We also need studies that look at the long-term neurodevelopmental outcome as the babies become children and possibly even into their adolescence. 

Olga: Thanks. If someone would like to learn more about this topic how can they get hold of the review?

Matteo: The review is published online and is available at Cochrane Library dot com. If people go to the website and search for 'opioids for newborn infants receiving mechanical ventilation’' they'll see the link to it.