Morphine vs. intravenous Acetaminophen after surgery in patients under the age of 1 year.

SUMMARY Morphine intravenous vs. Acetaminophen intravenous in neonates and young infants undergoing major non-cardiac surgery



Rationale: Hypotheses:

Patients after non-cardiac thoracic or abdominal major surgery receive morphine as pain relief medication whereas this is associated with morphine related side effects. In these patients a non-opioid drug could be appropriate for postoperative pain relief. Intermittent administration of intravenous acetaminophen, to young infants up to 48 hours after major surgery e.g. thoracic and abdominal, will lead to a clinically significant (>30%) morphine sparing effect.



Objective:
The aim of this study is to test the hypothesis that intravenous acetaminophen will reduce morphine requirements in postoperative infants significantly (>30%).



Study design:
Single centre prospective, randomized double blind study.



Study population:
Infants less than one year of age, who are admitted to the ICU after major thoracic (non-cardiac) or abdominal surgery.



Intervention:
Patients will be randomized to receive either intermittent intravenous acetaminophen or continuous morphine IV infusion up to 48 hrs after surgery, with additional morphine boluses as escape medication in both groups.



Main study parameters/endpoints:
Body weight corrected morphine dose needed in the first 48 hrs post surgery. Mean morphine dose needed will be 30% less in the infants receiving acetaminophen IV as compared to the patients who received only morphine



Nature and extent of the burden and risks associated with participation, benefit and group relatedness:

Possible burden and risk of study participation is the risk of insufficient analgesia after surgery with acetaminophen IV. This risk is minimized by the provision in the protocol for the administration of additional morphine in case of insufficient analgesia.

Acetaminophen has been widely studied in children over all age ranges and is deemed safe in the population to be studied when administered in therapeutic doses.

Benefits of participation can be better observation of the patient in relation to his/her analgesia and more prompt response with additional morphine if necessary. Hence, we expect patients in the study to be more pain free than patients not participating in a pain trial.

Also, if acetaminophen indeed reduces the total morphine dose required, a reduction in adverse effects of morphine can be expected (less post operative vomiting, less respiratory depression).

The study can only be carried out in this population as results from adults or healthy children cannot be extrapolated to this group of patients (critically ill children), due to differences in age and the underlying disease, which are mainly life threatening congenital anomalies, resulting in differences in pharmacokinetics and pharmacodynamics of both drugs.

Patients after non-cardiac thoracic or abdominal major surgery receive morphine as pain relief medication whereas this is associated with morphine related side effects. In these patients a non-opioid drug could be appropriate for postoperative pain relief. Intermittent administration of intravenous acetaminophen, to young infants up to 48 hours after major surgery e.g. thoracic and abdominal, will lead to a clinically significant (>30%) morphine sparing effect.

Patients are followed 48 hours post operatively or is ended after an earlier discharge.

After surgery patients will be randomised for treatment with Morphine or Acetaminophen intravenoously.

In case of post operative pain (COMFORT score>=17 and/or VAS>= 4) additional morphine in both groups is administrated following our post-operative pain protocol.

For PK-PD relationship for acetaminophen IV and morphine in this population three blood samples are taken from an indwelling arterial line and saliva cortisol is obtained.