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.

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.

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