Article of the month

Crit Care. 2024 Apr 30;28(1):143. doi: 10.1186/s13054-024-04905-3.

Intermittent intravenous paracetamol versus continuous morphine in infants

undergoing cardiothoracic surgery: a multi-center randomized controlled trial.

Zeilmaker-Roest G(1)(2), de Vries-Rink C(3)(4), van Rosmalen J(5)(6), van Dijk

M(3), de Wildt SN(3)(7), Knibbe CAJ(8)(9), Koomen E(10), Jansen NJG(10)(11),

Kneyber MCJ(12), Maebe S(13), Van den Berghe G(14), Haghedooren R(14),

Vlasselaers D(14), Bogers AJJC(4), Tibboel D(3), Wildschut ED(3).

BACKGROUND: To determine whether intermittent intravenous (IV) paracetamol as

primary analgesic would significantly reduce morphine consumption in children

aged 0-3 years after cardiac surgery with cardiopulmonary bypass.

METHODS: Multi-center, randomized, double-blinded, controlled trial in four

level-3 Pediatric Intensive Care Units (PICU) in the Netherlands and Belgium.

Inclusion period; March 2016-July 2020. Children aged 0-3 years, undergoing

cardiac surgery with cardiopulmonary bypass were eligible. Patients were

randomized to continuous morphine or intermittent IV paracetamol as primary

analgesic after a loading dose of 100 mcg/kg morphine was administered at the

end of surgery. Rescue morphine was given if numeric rating scale (NRS) pain

scores exceeded predetermined cutoff values. Primary outcome was median

weight-adjusted cumulative morphine dose in mcg/kg in the first 48 h

postoperative. For the comparison of the primary outcome between groups, the

nonparametric Van Elteren test with stratification by center was used. For

comparison of the proportion of patients with one or more NRS pain scores of 4

and higher between the two groups, a non-inferiority analysis was performed

using a non-inferiority margin of 20%.

RESULTS: In total, 828 were screened and finally 208 patients were included;

parents of 315 patients did not give consent and 305 were excluded for various

reasons. Fourteen of the enrolled 208 children were withdrawn from the study

before start of study medication leaving 194 patients for final analysis. One

hundred and two patients received intermittent IV paracetamol, 106 received

continuous morphine. The median weight-adjusted cumulative morphine consumption

in the first 48 h postoperative in the IV paracetamol group was 5 times lower

(79%) than that in the morphine group (median, 145.0 (IQR, 115.0-432.5) mcg/kg

vs 692.6 (IQR, 532.7-856.1) mcg/kg; P < 0.001). The rescue morphine consumption

was similar between the groups (p = 0.38). Non-inferiority of IV paracetamol

administration in terms of NRS pain scores was proven; difference in proportion

- 3.1% (95% CI - 16.6-10.3%).

CONCLUSIONS: In children aged 0-3 years undergoing cardiac surgery, use of

intermittent IV paracetamol reduces the median weight-adjusted cumulative

morphine consumption in the first 48 h after surgery by 79% with equal pain

relief showing equipoise for IV paracetamol as primary analgesic. Trial

Registration Clinicaltrials.gov, Identifier: NCT05853263; EudraCT Number:

2015-001835-20.

DOI: 10.1186/s13054-024-04905-3

PMCID: PMC11061924

PMID: 38689310 [Indexed for MEDLINE]

Conflict of interest statement: The authors declare that they have no competing

interests.