Effects of Perioperative Pregabalin for Post-Craniotomy Pain
Effects of Perioperative Pregabalin for Post-Craniotomy Pain
Objective: To compare the incidence of chronic pain at 3 months among adults undergoing
 craniotomy between those received two different doses of pregabalin and those receiving
 placebo.
Hypothesis: Perioperative pregabalin will reduce the incidence of chronic post-operative
 pain, and will reduce the opioid consumption, opioid-related side effects, and hospital
 length of stay compared with placebo in patients undergoing elective craniotomy.

 Methods: 316 adults (18-65y), ASA I-III, undergoing elective craniotomy will be randomized to
 receive: 100mg or 150mg pregabalin or placebo once pre-operatively and 50mg or 75mg or
 placebo twice daily for 14 post-operative days. NRS pain scores, opioid consumption and side
 effects will be assessed up to 48h, and long-term pain at days 7, 14, 30, and 90. The primary
 analysis will involve the comparison between the 2 treatment groups together vs. placebo. A
 stepwise method will be used to evaluate the pairwise comparisons.

 Outcomes: The primary outcome will be the incidence of chronic post-craniotomy pain at 3 mos.
 Important secondary outcomes are: neuropathic component of pain at 3 mos., total opioid
 consumption in the first 24h, and incidence and severity of opioid-related side effects at
 days 1, 2 and 7.
Inclusion Criteria:

 -  Adults, 18 to 65 years (limited to 65 years to lower the risk of over-sedation for
 elderly patients)

 -  Undergoing elective craniotomy (supratentorial or infratentorial) under general
 anaesthesia for: biopsy or resection of a tumour, clipping of an unruptured aneurysm,
 or excision of an arteriovenous malformation

 -  ASA physical status I-III

 Exclusion Criteria:

 -  predicted need for prolonged post-operative ventilation (> 12 hours)

 -  chronic pain secondary to previous craniotomy

 -  known adverse reaction to drugs used (gabapentin, pregabalin, hydromorphone, and/or
 acetaminophen)

 -  prior use of pregabalin or gabapentin (within 2 weeks before surgery)

 -  current history of moderate to severe headaches (NRS ≥ 4) related to intracranial
 pathology (tumour pain) since it may be difficult to discriminate between ongoing
 tumour pain and surgery-related post-operative pain

 -  current history of migraines

 -  pre-existing chronic pain requiring chronic opioid use (30mg morphine equivalent
 within 4 weeks of surgery)

 -  currently taking any drug that could interact with pregabalin

 -  current history of alcohol or recreational drug abuse

 -  known or suspected addiction to narcotic substances or chronic narcotic use in the
 last 2 weeks

 -  history of malignant hyperthermia (contraindicates the anaesthesia protocol of this
 study)

 -  history of angioedema

 -  Body Mass Index ≤ 18.4 or ≥ 35

 -  history of untreated obstructive sleep apnea

 -  any condition that would contraindicate the use of patient-controlled analgesia (PCA)

 -  lacks fluency in English

 -  pre-existing renal impairment (for pregabalin elimination)

 -  pregnancy