Morphine Analgesia in Preemies

Effects of morphine analgesia in ventilated preterm neonates: primary outcomes from the NEOPAIN randomized trial. Anand KJ, and the NEOPAIN Trial Investigators Group. Lancet (May 2004);363:1673-82.

BACKGROUND: Opioid analgesia is commonly used during neonatal intensive care. We undertook the Neurologic Outcomes and Pre-emptive Analgesia in Neonates (NEOPAIN) trial to investigate whether pre-emptive morphine analgesia decreases the rate of a composite primary outcome of neonatal death, severe intraventricular haemorrhage (IVH), and periventricular leucomalacia (PVL) in preterm neonates.

METHODS: Ventilated preterm neonates (n=898) from 16 centers were randomly assigned masked placebo (n=449) or morphine (n=449) infusions. After a loading dose (100 microg/kg), morphine infusions (23-26 weeks of gestation 10 microg kg(-1) h(-1); 27-29 weeks 20 microg kg(-1) h(-1); 30-32 weeks 30 microg kg(-1) h(-1)) were continued as long as clinically justified (maximum 14 days). Open-label morphine could be given on clinical judgment (placebo group 242/443 [54.6%], morphine group 202/446 [45.3%]). Analyses were by intention to treat.

FINDINGS: Baseline variables were similar in the randomized groups. The placebo and morphine groups had similar rates of the composite outcome (105/408 [26%] vs. 115/419 [27%]), neonatal death (47/449 [11%] vs. 58/449 [13%]), severe IVH (46/429 [11%] vs. 55/411 [13%]), and PVL (34/367 [9%] vs. 27/367 [7%]). For neonates who were not given open-label morphine, rates of the composite outcome (53/225 [24%] vs. 27/179 [15%], p=0.0338) and severe IVH (19/219 [9%] vs. 6/189 [3%], p=0.0209) were higher in the morphine group than the placebo group. Placebo-group neonates receiving open-label morphine had worse rates of the composite outcome than those not receiving open-label morphine (78/228 [34%] vs. 27/179 [15%], p<0.0001). Morphine-group neonates receiving open-label morphine were more likely to develop severe IVH (36/190 [19%] vs. 19/219 [9%], p=0.0024).

INTERPRETATION: Pre-emptive morphine infusions did not reduce the frequency of severe IVH, PVL, or death in ventilated preterm neonates, but intermittent boluses of open-label morphine were associated with an increased rate of the composite outcome. The morphine doses used in this study decrease clinical signs of pain but can cause significant adverse effects in ventilated preterm neonates.

Comments: Clearly the findings of this study do not support the routine use of Morphine drips for ventilated preterm neonates. I suspect that we would find similar results with fentanyl drips, as the 2 drugs are biochemically similar. It seems that all we can do to minimize discomfort in these infants is to observe minimal touch protocols, and try to limit the number of painful procedures to which they are exposed. ABK

I am aware that this article has already lead to a change in practice in my own unit. I do hope that we continue to manage pain and do consider using morphine infusions for painful disorders such as necrotising enterocolitis.

UserName: Wendy Tyler
Institution: Royal Shrewsnury Hospital
telephone:
email: wendy.tyler@rsh.nhs.uk

Date: 26 Feb 2005
Time: 16:42:03

I hope this study will be an eye opener for everyone working in the NICU about the need for practising evidence based medicine. We should never assume that intervention is better unless supported by objective data.

UserName: Mike sukumar MD
Institution: Shadygrove Adventist Hospital
telephone: 301 279 6392
email: msukumar99@yahoo.com

Date: 26 Feb 2005
Time: 10:00:23

we just have started to switch our medication for elective intubation from midazolam and ketamin to morphine, because we want to reduce midazolam with its described neurotoxic side effects. we had problems with thorax rigidity and no hear of neurotoxic side effects of morphine... minimal handling!

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