MedPath

Effect of Parecoxib on Post-craniotomy Pain

Phase 4
Completed
Conditions
Anaesthesia
Interventions
Registration Number
NCT00455117
Lead Sponsor
Melbourne Health
Brief Summary

Aim of this trial:

To investigate whether post-craniotomy analgesia with (i) intravenous (IV) parecoxib plus intravenous paracetamol is superior to (ii) intravenous paracetamol alone.

Study Hypothesis:

Post-operative analgesia with intravenous parecoxib in combination with intravenous paracetamol will be superior to intravenous paracetamol alone.

Detailed Description

Neurosurgical patients undergoing brain procedures (craniotomy patients) are known to suffer moderately severe postoperative pain and high rates of post-operative nausea and vomiting. Post-craniotomy pain is poorly treated with more than 50% of craniotomy patients experiencing postoperative pain of moderate or severe intensity. Fear of drug complications such as sedation, respiratory depression, seizures and intracranial bleeding has inhibited prescribing of effective pain treatment.Non-steroidal anti-inflammatory drugs (NSAIDS) are known to be effective analgesics in the peri-operative period however there use in cranial neurosurgery has been limited due to risk of bleeding. Parecoxib is an injectable form of NSAID that works through inhibiting cyclo-oxygenase type-2 (COX-2). The main benefit of COX-2 inhibitors is that they have minimal inhibition of platelet function and therefore minimal risk of increased bleeding.This project aims to evaluate whether parecoxib is an effective pain reliever (analgesic) after brain surgery. Patients aged 18-65 years presenting for elective craniotomy will be randomly allocated to two different analgesic programs (i) IV parecoxib and IV paracetamol or (ii) IV paracetamol. All patients will receive a standardised anaesthetic. Scalp infiltration, using 20mls of local anesthetic (bupivacaine 0.5% with adrenaline), will occur prior to skin incision. Intermittent morphine administration will used post-operatively to ensure adequate analgesia in each arm of the trial. Immediate post-operative adjunctive analgesia will be provided with nurse administered IV morphine in the post-anaesthetic care unit (PACU) as per protocol (RMH protocol for opioid titration), followed by patient controlled analgesia (PCA) morphine once the verbal rating scale is \< 4 (rating out of ten). A score of less than four is considered to be mild pain. PCA will be continued for the first twenty-four hours then discontinued. Patients will then receive strict oral paracetamol and nurse administered IV morphine as required. The primary study endpoint will be morphine consumption in the first 24 hours. Data will be analysed on an intention to treat basis. Continuous variables will be graphed to determine their distribution. Normally distributed variables will be described using mean and standard deviation and compared using Student's t-tests. Skewed variables will be described using median and range (or interquartile range) and compared using Wilcoxon rank sum tests. A p-value les than 0.05 will be considered statistically significant.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
130
Inclusion Criteria
  • Supratentorial craniotomy, glasgow coma scale 15
Exclusion Criteria
  • Chronic pain,
  • Chronic opioid use.
  • History of significant alcohol or benzodiazepine (BZD) use,
  • Inability to speak English,
  • Pre-operative aphasia or dysphasia,
  • Renal impairment (Creatinine level > 0.1),
  • Asthma (or evidence of reversible airway obstruction,
  • Known ischaemic heart disease or cerebrovascular disease,
  • American Society of Anaesthesiologists (ASA) grade IV or V,
  • Allergy to any study drug (paracetamol, parecoxib, sulphas, morphine, bupivacaine, propofol, remifentanil;
  • Administration of oral paracetamol within previous 8 hours.
  • Pregnancy or breastfeeding

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
1Intravenous Parecoxib ('Dynastat' Pfizer)placebo (2 ml normal saline) administered intravenously at dural closure during craniotomy
2Intravenous Parecoxib ('Dynastat' Pfizer)parecoxib 40 mg in 2 ml normal saline administered intravenously at dural closure during craniotomy
Primary Outcome Measures
NameTimeMethod
Morphine consumption in 24 hour period.24 hours after surgery
Secondary Outcome Measures
NameTimeMethod
Immediate post-operative hypertension (first 2 hours)24 hours after surgery
Pain scores at zero (time of extubation), 1, 2, 4, 12, 24 hours post operatively24 hours after surgery
Analgesic efficacy at 24 hours24 hours after surgery
Incidence of post-operative nausea and vomiting (first 24 hours)24 hours after surgery
Sedation or respiratory depression (first 24 hours)24 hours after surgery
Safety Monitoring (Serious adverse side effects)24 hours after surgery
Post-operative AMI24 hours after surgery
Post-operative renal failure24 hours after surgery
Post-operative thromboembolic stroke24 hours after surgery
Post-operative intracranial haemorrhage24 hours after surgery

Trial Locations

Locations (1)

Royal Melbourne Hospital

🇦🇺

Melbourne, Victoria, Australia

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