Morphine IV vs Paracetamol IV in Neonates and Infants After Cardiac Surgery
Condition: Analgesia; Congenital Heart Disease; Surgery
MeSH terms: Heart Diseases; Heart Defects, Congenital
Study type: Interventional

Summary: 
      The goal of this clinical trial is to compare pain management in neonates and infants under 3
      years of age undergoing cardiac surgery with use of cardiopulmonary bypass. Patients will be
      randomized to either continuous morphine IV (standard) of intermittent paracetamol IV
      (intervention).

      The investigators' hypothesis is that intermittent IV paracetamol is effective as the primary
      analgesic drug in post-cardiac surgery patients up to 3 years of age and that the use of IV
      paracetamol will reduce overall morphine requirements.
    

Detailed description: 
      Congenital heart disease accounts for almost one third of all congenital anomalies. Surgical
      intervention is necessary in 55% within the first year of life and in 67% during the first
      three years of life.

      Morphine is the drug of first choice worldwide for pain relief after major surgery in
      neonates and children. However, morphine can cause unwanted hemodynamic and respiratory
      reactions and therefore patients could potentially benefit from a non-opioid analgesic.

      In a recent randomized controlled trial, intravenous (IV) paracetamol was compared with
      morphine as a primary analgesic drug in non-cardiac post-operative children up to 1 year. IV
      paracetamol was equally effective in pain relief, and no difference in rescue analgesics was
      shown between groups. The IV paracetamol group had a lower cumulative morphine dose the first
      48 h after surgery and less adverse drug reactions.

      Whether these results also apply to neonates and children after cardiac surgery is unclear.
      Pharmacokinetic (PK) parameters are assumed to be different in patients during and after
      cardiac surgery compared with non-cardiac surgery due to use of the cardiopulmonary bypass
      (CPB).

      Hypothesis The investigators' hypothesis is that intermittent IV paracetamol is effective as
      the primary analgesic drug in post-cardiac surgery patients up to 3 years of age and that the
      use of IV paracetamol will reduce overall morphine requirements.

      This hypothesis is currently being tested at three level-4 PICUs in the Netherlands and
      Belgium (Erasmus MC-Sophia Rotterdam, Wilhelmina Children's Hospital University Medical
      Center (UMC) Utrecht, Beatrix Children's Hospital UMC Groningen, University Hospital (UZ)
      Leuven).

      All participants will receive a loading dose of morphine after cardiac surgery. After this,
      participants will be randomized to either standard care (morphine continuous IV) or
      intervention group (intermittent paracetamol IV).

      Validated pain and sedations assessment tools will be used to adjust pain treatment if
      necessary. Rescue morphine as available for both groups.

      A double blind study design is used, with a dummy saline continuous infusion in the
      paracetamol group and a dummy saline intermittent infusion in de continuous morphine group.

      Study medication is stopped 48 hours after surgery and patients are transferred to open label
      morphine and paracetamol when applicable.
    

Intervention name(s): paracetamol; Morphine
Intervention type(s): Drug; Drug
Intervention description(s): paracetamol IV to substitute morphine IV.; standard care
Other intervention name(s): Acetominophen
Intervention MeSH terms: Acetaminophen; Morphine
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: prospective, double blind, randomized controlled trial.
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Treatment
Keywords: morphine; paracetamol; neonates; infants; child; analgesia; congenital heart defect; cardiopulmonary bypass; congenital cardiac surgery; pharmacokinetics