Intravenous Paracetamol for Postoperative Pain (IVPARACET)

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

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.

Study Overview

• Status: Completed
• Conditions: Pain, Postoperative; Child; Recovery of Function
• Intervention / Treatment: Drug: Paracetamol; Drug: Ketoprofen; Drug: Tramadol; Drug: Morphine; Drug: Placebo (for paracetamol)

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 54
• Phase: Phase 4

Contacts and Locations

Study Locations

• Lithuania
  • Kaunas, Lithuania, 50009
    • Lithuanian University of Health Sciences Kaunas Clinics

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 year to 18 years (Child, Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: paracetamol and ketoprofen; 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; Other Names: Acetaminophen; Drug: Ketoprofen; Other Names: Ketonal; Drug: Tramadol; 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.; Other Names: Tramal; Drug: Morphine; administered in patients receiving IV PCA with morphine postoperatively. No other opioid is given to these patients.
Placebo Comparator: placebo and ketoprofen; 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: Ketoprofen; Other Names: Ketonal; Drug: Tramadol; 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.; Other Names: Tramal; Drug: Morphine; administered in patients receiving IV PCA with morphine postoperatively. No other opioid is given to these patients.; Drug: Placebo (for paracetamol); Other Names: Normal saline solution; 0.9% sodium cloride solution; Izotonic saline solution

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

Outcome Measure	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

Other Outcome Measures

Outcome Measure	Time Frame
time until the first oral intake after surgery	24 hours postoperatively
time until the first urination after surgery	24 hours postoperatively
time until ambulation after surgery	24 hours postoperatively

Collaborators and Investigators

• Sponsor: Lithuanian University of Health Sciences
• Investigators: Principal Investigator: Danguole C Rugyte, MD. PhD, Lithuanian University of Health Sciences

Publications and helpful links

General Publications

• Ong CK, Seymour RA, Lirk P, Merry AF. Combining paracetamol (acetaminophen) with nonsteroidal antiinflammatory drugs: a qualitative systematic review of analgesic efficacy for acute postoperative pain. Anesth Analg. 2010 Apr 1;110(4):1170-9. doi: 10.1213/ANE.0b013e3181cf9281. Epub 2010 Feb 8.
• Wong I, St John-Green C, Walker SM. Opioid-sparing effects of perioperative paracetamol and nonsteroidal anti-inflammatory drugs (NSAIDs) in children. Paediatr Anaesth. 2013 Jun;23(6):475-95. doi: 10.1111/pan.12163. Epub 2013 Apr 9.
• Hiller A, Silvanto M, Savolainen S, Tarkkila P. Propacetamol and diclofenac alone and in combination for analgesia after elective tonsillectomy. Acta Anaesthesiol Scand. 2004 Oct;48(9):1185-9. doi: 10.1111/j.1399-6576.2004.00473.x.
• Rugyte D, Kokki H. Intravenous ketoprofen as an adjunct to patient-controlled analgesia morphine in adolescents with thoracic surgery: a placebo controlled double-blinded study. Eur J Pain. 2007 Aug;11(6):694-9. doi: 10.1016/j.ejpain.2006.11.001. Epub 2006 Dec 20.

Study record dates

Study Major Dates

• Study Start: November 1, 2012
• Primary Completion (Actual): March 1, 2017
• Study Completion (Actual): March 1, 2017

Study Registration Dates

• First Submitted: September 22, 2014
• First Submitted That Met QC Criteria: September 22, 2014
• First Posted (Estimate): September 25, 2014

Study Record Updates

• Last Update Posted (Actual): March 6, 2017
• Last Update Submitted That Met QC Criteria: March 3, 2017
• Last Verified: March 1, 2017

More Information

Terms related to this study

• Keywords: Adolescent; Child; Anti-Inflammatory Agents, Non-Steroidal; Paracetamol; Pain, Postoperative; Administration, Intravenous
• Additional Relevant MeSH Terms: Pathologic Processes; Postoperative Complications; Pain; Neurologic Manifestations; Pain, Postoperative; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Peripheral Nervous System Agents; Enzyme Inhibitors; Analgesics; Sensory System Agents; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Antirheumatic Agents; Cyclooxygenase Inhibitors; Antipyretics; Analgesics, Opioid; Narcotics; Acetaminophen; Pharmaceutical Solutions; Morphine; Tramadol; Ketoprofen
• Other Study ID Numbers: BEC-MF-10