Poppi

SHORT TITLE: Poppi - Procedural pain in premature infants. FULL TITLE: A blinded randomised controlled trial investigating the efficacy of morphine analgesia for procedural pain in infants

Trial started: 2015  Trial ended: 2018 

Summary

Objectives

To investigate whether a single 100?µg/kg dose of oral morphine sulphate administered before painful clinical procedures provides effective analgesia.

Methods

A single-centre, prospective, randomised controlled trial conducted at the John Radcliffe Hospital, Oxford, UK. Infants aged 34–42 weeks' gestational age requiring a heel lance and retinopathy of prematurity screening on the same test occasion were randomised to receive either 100?µg/kg oral morphine sulphate or placebo 1 hour before the clinically required procedures.

Outcome measures

Co-primary outcomes: Premature Infant Pain Profile-Revised score (a higher score implies more nociceptive processing) during the 30-second period after retinopathy of prematurity screening, and the magnitude of noxious-evoked brain activity (a higher activity implies more nociceptive processing) following the heel lance.

Secondary outcomes: Physiological stability and safety.

Results

Thirty-one infants were randomised (30 studied and one withdrew). The predefined safety stopping boundary was reached after three of the 15 infants who received morphine experienced apnoeas requiring resuscitation with non-invasive positive-pressure ventilation within 24 hours of drug administration, compared with none of the 15 infants who received placebo. The trial was therefore stopped because of profound respiratory adverse effects of morphine without suggestion of analgesic efficacy. There was no significant difference between the treatment groups for either co-primary outcome. The mean PIPP-R score following retinopathy of prematurity screening was 11.1?±?3.2 in the morphine group and 10.5?±?3.4 in the placebo group (mean difference 0.5, 95% confidence interval –2.0 to 3.0; p?=?0.66). Median noxious-evoked brain activity following heel lance was 0.99 (interquartile range 0.40–1.56) in the morphine group and 0.75 (interquartile range 0.33–1.22) in the placebo group (median difference 0.25, 95% confidence interval –0.16 to 0.80; p?=?0.25).

Conclusions

The administration of 100?µg/kg oral morphine to non-ventilated premature infants has the potential for harm without analgesic benefit. Oral morphine is not recommended for retinopathy of prematurity screening, and caution is strongly advised if it is being considered for other acute painful procedures in non-ventilated premature infants.

Adapted from: Monk V, Moultrie F, Hartley C, et al. Oral morphine analgesia for preventing pain during invasive procedures in non-ventilated premature infants in hospital: the Poppi RCT. Efficacy and Mechanism Evaluation. 2019;6(9). https://doi.org/10.3310/eme06090. © Queen's Printer and Controller of HMSO 2019. Adapted for presentation on this website.