'Nociceptive brain activity as a measure of analgesic efficacy in infants', an article by Caroline Hartley and the team validating the measure of infant nociceptive brain activity used in the Poppi trial.
The aim of the Poppi Trial (Procedural Pain in Premature Infants) is to test whether morphine can provide effective pain relief in babies during invasive medical procedures. While morphine is frequently given to adults when they experience pain, it is not clear whether morphine provides effective pain relief in babies. This means morphine is usually not prescribed to babies when clinical staff perform clinically-essential medical procedures.
An example of a painful procedure that is frequently and regularly performed on premature babies is an eye exam that tests for Retinopathy of Prematurity – this is a disease which if untreated can lead to permanent blindness. Although the eye exam is considered to be painful, and stressful for both infants and parents, and can result in unstable breathing and heartbeat for up to 24 hours after the exam, the pain relief currently provided during this procedure, which includes sucrose, breast milk and topical eye drops, has been shown to be ineffective.
The Poppi trial will use clinical pain assessment tools to measure pain in babies during the eye exam and during a clinically-required blood test. We will test whether babies who are given morphine experience less pain, and whether this improves the stability of the babies breathing and heartbeat after the procedure. We will also use some recently developed brain-imaging techniques to observe how morphine can affect pain-related brain activity. Given that babies cannot tell us when they are in pain, this is an important new approach which will help us understand how the infant brain processes pain and will tell us whether pain-relieving drugs are effectively reducing patterns of pain-related brain activity.
Clinical Trials Unit:
National Perinatal Epidemiology Unit CTU
University of Oxford
NIHR Efficacy and Mechanism Evaluation (EME) Programme and The Wellcome Trust and
156 babies (33 month recruitment period)
Duration of Study:
September 2015 - November 2018
Babies will be randomly allocated to receive either morphine sulphate or placebo (inactive solution) prior to ROP screening. Neither parents nor staff caring for a baby will know which treatment has been allocated- a blinded randomised controlled trial.
During the ROP screening and after the drug has been administered, the babies will be attached to the EEG, EMG and video monitoring equipment. A clinical heel lance and heel lance-control stimuli (where the lancet is rotated such that on release the blade does not touch the foot) will be performed. During each procedure pain-related (nociceptive-specific) brain activity will be recorded.
To test whether administration of morphine reduces clinical pain scores (Premature infant pain profile -PIPP) during the 30 second period after ROP screening compared with a placebo (inactive solution).
To test whether administration of morphine reduces nociceptive-specific brain activity following a clinically-essential heel lance compared with a placebo (inactive solution).
To test whether administration of morphine improves clinical stability after ROP screening in the 6-hour and 24-hour period following the exam.
To test whether administration of morphine reduces clinical pain scores (PIPP) and reflex withdrawal activity following a clinically-essential heel lance compared with a placebo (inactive solution).
To test whether administration of morphine is safe by determining whether it results in episodes of respiratory depression or hypotension that require intervention compared with a placebo.