Intravenous Paracetamol for Postoperative Pain

Study Overview
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Brief Summary
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The purpose of this study is to define if intravenous paracetamol may improve analgesia and outcome in pediatric surgical patients treated with non-steroidal anti-inflammatory drugs (NSAIDs) postoperatively. Hypothesis: intravenous paracetamol in a dose 60 mg/kg/24 h IV, given in addition to IV ketoprofen (4,5 mg/kg/24h), improves analgesia and physical recovery in children and adolescents following surgery.

Detailed Description
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Patients aged 1-18 years undergoing general, plastic or orthopedic surgery with expected moderate to severe pain at least for 24 hours postoperatively, who meet inclusion criteria and does not meet exclusion criteria, are enrolled. At the end of surgical procedure, at skin closure, all patients are given 1,5 mg/kg intravenous ketoprofen and repeated every 8 hours up till 4,5 mg/kg/24 h. Patients in paracetamol group are additionally given the first dose of IV paracetamol 20 mg/kg and repeated 6 and 20 hours postoperatively up till 60 mg/kg/24 h. Patients in the placebo group are given 0.9% sodium chloride 2 ml/kg IV and repeated 6 and 20 hours postoperatively. After surgery optional rescue analgesia is given on patient request: either tramadol in a dose of 2 mg/kg (up till 4 mg/kg/24h), either patient-controlled analgesia (PCA) with morphine, as indicated according to the standard of care. Patients are evaluated up till 24 hours postoperatively. After that patients are followed up as long as indicated per standard of care.

Official Title
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The Effect of Intravenous Paracetamol in Combination With NSAIDs for Postoperative Pain in Children

Conditions
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Pain, Postoperative, Recovery of Function, Child

Intervention / Treatment
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* Drug: Paracetamol
* Drug: Placebo (for paracetamol)
* Drug: Ketoprofen
* Drug: Tramadol
* Drug: Morphine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients 1-18 years of age, undergoing general, plastic or orthopedic surgery with expected median to severe pain postoperatively. physical status of the patient corresponding to American Society of Anesthesiologists (ASA) class 1 or 2 Signed written informed consent by parents/official caregivers. Exclusion Criteria: Allergy to paracetamol, ketoprofen, tramadol, morphine or any NSAID oncologic disease central nervous system disease renal dysfunction hepatic dysfunction bronchial asthma ulcer(s) in gastrointestinal system hemorrhagic diathesis chronic use of NSAIDs chronic use of opioids chronic use of anticoagulants female patient is known to be pregnant

Ages Eligible for Study
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Minimum Age: 1 Year
Maximum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: paracetamol and ketoprofen<br>paracetamol 20 mg/kg (1% 2 ml/kg) IV at the end of surgery 6 and 20 hours thereafter. ketoprofen 1.5 mg/kg IV at the end of surgery 8 and 16 hours thereafter. tramadol 2 mg/kg IV on patient request up til 4 mg/kg or PCA morphine during 24 hours postoperatively. | Drug: Paracetamol<br> <br> * Other names: Acetaminophen;Drug: Ketoprofen<br> <br> * Other names: Ketonal;Drug: Tramadol<br>* Administered on request as rescue medication in a dose 2 mg/kg IV up till 2 doses. No other opioid is given to these patients.<br>* Other names: Tramal;Drug: Morphine<br>* administered in patients receiving IV PCA with morphine postoperatively. No other opioid is given to these patients.<br>|
| Placebo Comparator: placebo and ketoprofen<br>0.9% sodium chloride (2 ml/kg) IV at the end of surgery 6 and 20 hours thereafter. ketoprofen 1.5 mg/kg IV at the end of surgery 8 and 16 hours thereafter. tramadol 2 mg/kg IV on patient request up til 4 mg/kg or PCA morphine during 24 hours postoperatively. | Drug: Placebo (for paracetamol)<br> <br> * Other names: Izotonic saline solution;Drug: Ketoprofen<br> <br> * Other names: Ketonal;Drug: Tramadol<br>* Administered on request as rescue medication in a dose 2 mg/kg IV up till 2 doses. No other opioid is given to these patients.<br>* Other names: Tramal;Drug: Morphine<br>* administered in patients receiving IV PCA with morphine postoperatively. No other opioid is given to these patients.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| change in postoperative intravenous opioid dose |  | 24 hours postoperatively | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| change in pain level (analgesia) assessed by 10 point pain scales |  | 1 hour postoperatively | 
| change in pain level (analgesia) assessed by 10 point pain scales |  | 24 hours postoperatively | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Pain, Postoperative, Paracetamol, Administration, Intravenous, Anti-Inflammatory Agents, Non-Steroidal, Child, Adolescent