title: Subanaesthetic ketamine spares postoperative morphine and controls pain better than standard morphine does alone in orthopaedic-oncological patients.
abstract: BACKGROUND
  Postoperative pain in patients with bone and soft tissue cancer is different from that of other surgical patients due to the severity of the pain generated during surgery and because many of them have already been in pain preoperatively. The search for optimal intravenous pharmacologic management for this population is an ongoing one. We conducted a 10-month prospective, randomised, double blind study to compare the effects of a standard morphine dose to a 35%-lower dose plus a subanaesthetic dose of ketamine for postoperative pain control in patients undergoing bone and soft tissue cancer surgery under standardised general anaesthesia.
  
  
  METHODS
  After extubation, when objectively awake (>or=5/10 on a 0-10 visual analogue scale (VAS)) and complaining of pain (>or=5/10 VAS), patients were connected to an intravenous patient-controlled analgesia (IV-PCA) device that delivered 1.5 mg morphine/bolus (MO group) or 1 mg morphine+5mg ketamine/bolus (MK group), with a 7 min lockout time. Rescue intramuscular diclofenac 75 mg was available Q4/day. Follow-up lasted 96 h.
  
  
  RESULTS
  Fifty-seven patients (24 males, aged 18-74 years) completed the study. Pain scores were lower in the MK group compared to the MO patients, although MO patients (n=29) used 32.9+/-24.9 mg/patient morphine during the first 24 postoperative h compared to 14.6+/-11.4 mg/patient (P<0.05) for the MK patients (n=28). At that time point, 11 MO versus 4 MK patients still required IV-PCA (P<0.05). Diclofenac was also used more in the MO group. All vital signs were similar between the groups. The physiotherapy score was 35% higher for the MK patients (P<0.05). No patient had hallucinations. Postoperative nausea and vomiting rates were higher in the MO group.
  
  
  CONCLUSIONS
  The use of subanaesthetic ketamine plus 2/3 the standard dose of morphine following bone and tissue resections results in 1) lower and more stable pain score, 2) approximately 60% morphine sparing effect, 3) a shorter period of postoperative IV-PCA dependence. Such therapy is also associated with better early physical performance.
authors.affiliation: Department of Orthopaedic Oncology, Tel Aviv Sourasky Medical Centre and the Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
authors.forename: Yehuda
authors.initials: Y
authors.lastname: Kollender
authors.forename: Jacob
authors.initials: J
authors.lastname: Bickels
authors.forename: Daniel
authors.initials: D
authors.lastname: Stocki
authors.forename: Nissim
authors.initials: N
authors.lastname: Maruoani
authors.forename: Shoshana
authors.initials: S
authors.lastname: Chazan
authors.forename: Alexander
authors.initials: A
authors.lastname: Nirkin
authors.forename: Isaac
authors.initials: I
authors.lastname: Meller
authors.forename: Avi A
authors.initials: AA
authors.lastname: Weinbroum
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000700:Analgesics / Q000008:administration & dosage*; D000704:Analysis of Variance; D001859:Bone Neoplasms / Q000601:surgery*; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D007649:Ketamine / Q000008:administration & dosage* / Q000009:adverse effects; D008297:Male; D008875:Middle Aged; D009020:Morphine / Q000008:administration & dosage* / Q000009:adverse effects; D010147:Pain Measurement; D010149:Postoperative Pain / Q000517:prevention & control*; D026741:Physical Therapy Modalities; D020250:Postoperative Nausea and Vomiting / Q000139:chemically induced; D011446:Prospective Studies; D012983:Soft Tissue Neoplasms / Q000601:surgery*
chemical_list: D000700:Analgesics; D007649:Ketamine; D009020:Morphine