Pediatric Analgesia After Cardiac Surgery; Morphine IV Versus Paracetamol IV After Cardiac Surgery in Neonates and Infants.
Trial Snapshot
- Phase
- Not Applicable
- Status
- Completed
- Sponsor
- Erasmus Medical Center
- Enrollment
- 208
- Primary Endpoint
- The primary outcome measure is weight-adjusted cumulative morphine dose in the first 48 hours post-operatively.
Study Overview
Brief 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.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description
double blind, randomized
Eligibility Criteria
- Ages
- 1 Day to 36 Months (Child)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Informed consent
- •Neonates/infants who are 0-36 months old
- •Cardiac surgery with the use of CPB.
Exclusion Criteria
- •No informed consent
- •Known allergy to or intolerance of paracetamol or morphine
- •Administration of opioids in the 24 h prior to surgery
- •Hepatic dysfunction defined as three times the reference value of alanine aminotransferase/aspartate aminotransferase (ALAT/ASAT)
- •Renal insufficiency at least RIFLE category Risk prior to surgery.
Arms & Interventions
morphine
Standard care, continuous morphine IV.
Intervention: Morphine (Drug)
paracetamol
intervention group, intermittent paracetamol IV
Intervention: paracetamol (Drug)
Outcomes
Primary Outcomes
The primary outcome measure is weight-adjusted cumulative morphine dose in the first 48 hours post-operatively.
Time Frame: 48 hours
dose in micrograms per kilogram
Secondary Outcomes
- The length of PICU stay(immediately after surgery)
- Role of alarmins in the systemic inflammatory response (only at Wilhelmina Children's hospital)(48 hours)
- Analysis of plasma morphine and paracetamo levels in relation to dose after cardia surgery using NONMEM (non-lineair mixed effects modelling).(48 hours)
- Incidence of adverse drug reactions(96 hours)
- Non-inferiority analysis of comparing the proportion of patients with one or more Numaric Rating Scale (NRS) scores of at least 4 between groups(48 hours)
- The role of genetic polymorphisms in morphine metabolism(directly before surgery)
- Concomitant use of sedatives(48 hours)
- mechanical ventilation duration in hours(immediately after surgery)
Investigators
Gerdien (G.A.) Zeilmaker-Roest
clinical investigator
Erasmus Medical Center