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Clinically effective implementation of intravenous paracetamol as primary analgesia after major surgery in neonates and young infants
  1. Manuel A Baarslag1,
  2. Erwin Ista1,
  3. Tom de Leeuw2,
  4. Joost van Rosmalen3,
  5. Dick Tibboel1,
  6. Monique van Dijk1,
  7. Saskia N de Wildt1,4
  1. 1 Intensive Care and Pediatric Surgery, Erasmus Medical Center-Sophia Children’s Hospital, Rotterdam, The Netherlands
  2. 2 Department of Anesthesiology, Erasmus Medical Center, Rotterdam, The Netherlands
  3. 3 Department of Biostatistics, Erasmus Medical Center, Rotterdam, The Netherlands
  4. 4 Department of Pharmacology and Toxicology, Radboud University, Nijmegen, The Netherlands
  1. Correspondence to Dr Manuel A Baarslag, Intensive Care and Pediatric Surgery, Erasmus Medical Center-Sophia Children’s Hospital, Rotterdam 3000 CB, The Netherlands; m.baarslag{at}

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We previously showed that intravenous paracetamol as primary analgesic after major non-cardiac (laparotomy or thoracotomy) surgery in infants <1 year of age reduces postoperative morphine consumption by 66% when compared with continuous intravenous morphine.1 Implementation of trial results is often challenging due to barriers such as low acceptance by healthcare professionals, lack of motivation and lack of awareness.2 Given the morphine-sparing effects of intravenous paracetamol we implemented intravenous paracetamol into our hospital’s clinical practice. We now present the real-life efficacy of intravenous paracetamol for this indication and adherence to the new postoperative pain protocol.

The setting for this observational study was a tertiary care paediatric intensive care unit (PICU). In our new postoperative pain protocol, starting from January 2014, intravenous paracetamol is the primary analgesic (figure 1) for postoperative infants. Before implementation, clinical staff was educated in a 30 min training and we provided bedside flow charts, pocket cards and screensavers on all the desktops in the PICU. Pain was assessed by the COMFORT-B scale and numeric rating scale every 2 hours or clinically indicated, like in the trial. The primary clinical endpoint was total morphine consumption in the 48 hours after surgery including loading and rescue doses. The primary implementation endpoint was the number of patients receiving intravenous paracetamol. Clinical data were retrospectively collected from our electronic patient data management system. Patients having received morphine <24 hours before surgery or with locoregional or epidural anaesthesia were excluded from analysis. If patients received another opioid for intraoperative loading dose, morphine equivalents were calculated. The efficacy outcomes were compared with data of the paracetamol group of our previous randomised controlled trial (RCT), using a Mann-Whitney U test. Categorical data were tested with Fisher’s exact test. The Erasmus MC research ethics board provided a waiver for ethics approval and informed consent according to the Dutch law on research in humans as only data from patient charts were collected.

Figure 1

Bedside pain protocol flow chart. NRS, numeric rating scale; PICU, paediatric intensive care unit.

From February 2014 to January 2016, of all postoperative patients (n=149), data of 75 patients were included. Main efficacy outcome: The median cumulative morphine dose was 121.1 (IQR 92.6–319.9) mcg/kg per 48 hours, similar to the RCT paracetamol group: 121 (IQR 99–264) mcg/kg per 48 hours, p=0.724 (table 1). Main adherence outcome: Intravenous paracetamol was given to 74 of 75 patients (98.7%). Secondary outcomes: 67 of 75 patients (89.3%) received a postoperative opioid loading dose according to protocol. Thirty-five (46.7%) patients needed additional morphine rescue boluses of which only 27 patients (36%) needed continuous morphine infusion. Pain scores were significantly lower in our patient cohort than in the paracetamol RCT group.

Table 1

Outcome measures of implementation cohort versus original RCT in major non-cardiac surgery infants

We demonstrated a similar opioid-sparing effect of intravenous paracetamol after implementation in clinical practice compared with our RCT results, as overall morphine consumptions were similar in the paracetamol RCT group and our clinical implementation cohort. Adherence to the new protocol was high as intravenous paracetamol was started in all patients but one. This implementation study shows that use of intravenous paracetamol in infants after major non-cardiac surgery is feasible and effective, resulting in low additional morphine need in a clinical setting.



  • Contributors MAB: data collection and writing of the first draft of manuscript. EI: study design, statistical analysis and writing of the first draft of manuscript. TdL: data verification and contribution to the final manuscript. JvR: statistical analysis and contribution to the final manuscript. DT and MvD: study design and contribution to the final manuscript. SNdW: study design, coordination and contribution to the final manuscript.

  • Competing interests None declared.

  • Patient consent Not required.

  • Ethics approval METC Erasmus MC.

  • Provenance and peer review Not commissioned; internally peer reviewed.

  • Data sharing statement Data are provided on request.