Perioperative Ketamine in Opioid-Tolerant Patients Undergoing Lumbar Spine Surgery
Perioperative Ketamine in Opioid-Tolerant Patients Undergoing Lumbar Spine Surgery
The goal of this study is to determine whether comprehensive perioperative administration of
 the N-methyl-D-aspartate (NMDA) receptor antagonist ketamine can increase postoperative pain
 tolerance and reduce opiate consumption in chronic back pain patients undergoing spinal
 laminectomy/fusion when compared to placebo

 Opioid dependence will be defined as daily opioid use (2 or more doses per day) for a period
 of two-months or longer. Intraoperatively, patients will receive a 1 mg/kg dose of
 intravenous ketamine or saline with 15 minutes after induction of general anesthesia.
 Thereafter, a continuous infusion of 0.20 mg/kg/hr ketamine with a maximum dose of 20 mg/hr
 or saline will be run to conclude at 24 hours after the end of the surgery (fascial closure).
 The primary outcome measure will be hydromorphone PCA usage during the first 72 hours
 postoperatively. Secondary outcome measures will be VAS pain scores at rest and with movement
 in PACU, 24 hr, 48 hr, 72 hr, 2 week (post-op visit), 6 week follow-up visit, as well as,
 McGill Pain Questionnaire, Pain Catastrophizing Scale, and emotional distress surveys
 assessing depression and anxiety at preop/screening, postop and 6 week follow-up (PROMIS
 Emotional Distress-Anxiety Short Form, PROMIS Emotional Distress-Depression Short Form), as
 well as a Neuro-QOL Short Form v1.1 - Satisfaction with Social Roles and Activities .
Patients will be recruited from the University of Pittsburgh Medical Center (UPMC)
 Neurosurgery Clinic and Operating Room Schedule. The primary surgeon will identify patients
 who would be eligible for inclusion, ask them if they would be interested in participating,
 and if so, the enrollment and consent process would be initiated. The participating
 neurosurgeons include Dr. Moossy,Dr. Kanter, Dr. Okonkwo, and Dr. Hamilton, all who have
 agreed to allow us access to their patients. Informed consent will be performed by Dr.
 Moossy, or the PI. Enrollment will be performed by the study coordinator and/or trained
 representative from the Acute Interventional Perioperative Pain Service (AIPPS). Enrollment
 will include review of eligibility, and detailed explanation of the study.

 Screening Visit:

 After patients are enrolled into the study at the preoperative neurosurgery clinic, a number
 of forms will be filled out by the participants: McGill Pain questionaire-Short form, pain
 medication review form, and the Pain Catastrophizing Scale (PCS) (Sullivan, 1995). PROMIS
 Emotional Distress-Anxiety Short Form and PROMIS Emotional Distress-Depression Short Form,
 Brief Psychiatric Rating Scale and Neuro-QoL Short Form v1.1 - Satisfaction with Social Roles
 and Activities will also be completed.

 Pre-Operative Visit:

 The participant will be asked to come into the Aiken Medical Building, Suite 407 on a date
 after the clinic visit but before their day of surgery for a Pre-Operative Visit.
 Investigators will work with the participant to determine their opioid dose regimen, and the
 participant will be asked to come into the Aiken Medical Building thirty minutes before their
 opioid dose is due and will be asked to bring with them their upcoming dose of pain
 medication. Prior to taking their pain medication, the participant will then be administered
 a cold-pressor pain sensitivity test. Heart rate and blood pressure will be recorded before
 and after the cold-pressor test. Once the cold pressor test is completed, the McGill Pain
 Questionnaire will be administered. After this questionnaire is complete, the participant
 will take the dose of opioid medication they have brought from home and are scheduled to
 receive and will wait in the clinic for 30 minutes for the pain medication to take effect.
 Once the 30 minutes is complete, the cold-pressor test will be repeated, heart rate and blood
 pressure collected before and after, and McGill Pain Questionnaire will be administered
 again.

 Surgical Visit:

 At the day of surgery, participants will be seen by team members of the Acute Interventional
 Perioperative Pain Service preoperatively. Patients will be randomized into the Ketamine
 Group or the Placebo Group.

 A standardized general anesthesia protocol will be used by the hands-on provider. All drugs
 used intraoperatively, including total hydromorphone dose, will be collected from the
 electronic chart.

 The amount of narcotics and non-narcotic analgesics administered in the operative and
 postoperative period will be collected from the electronic chart from day of surgery until
 discharge. Visual Analogue Scale (VAS) pain scores will be collected.

 Post-Op Visit:

 Patients will follow-up at Neurosurgery clinic at 10-14 days postoperatively. At this time
 daily opioid usage will be assessed and converted to morphine equivalents/24 hr. At this
 visit: pain medication review form, and the Pain Catastrophizing Scale (PCS) (Sullivan,
 1995). PROMIS Emotional Distress-Anxiety Short Form and PROMIS Emotional Distress-Depression
 Short Form, Brief Psychiatric Rating Scale and Neuro-QoL Short Form v1.1 - Satisfaction with
 Social Roles and Activities will also be completed by the participant.

 6-Week Follow-Up Visit:

 The participant will be asked to come to the Aiken Medical Building, Suite 407 approximately
 6 weeks after their surgery. Investigators will work with the participant to determine their
 post-operative opioid dose regimen. Prior to taking their pain medication, the participant
 will then be administered a cold-pressor pain sensitivity test, in a manner identical to that
 use during the pre-operative assessment.In addition to the McGill Pain Questionnaire-Short
 form, a pain medication review form, the Pain Catastrophizing Scale (PCS) (Sullivan, 1995),
 the PROMIS Emotional Distress-Anxiety Short Form, the PROMIS Emotional Distress-Depression
 Short Form, Brief Psychiatric Rating Scale and Neuro-QoL Short Form v1.1 - Satisfaction with
 Social Roles and Activities will also be completed.
Inclusion Criteria

 -  Patients undergoing lumbar, thoracic or cervical spine surgery of at least one level,
 and no more than 6 levels.

 -  Patients with chronic back pain (>3 months)

 -  Anaesthetic risk assessment (ASA) 1-3

 -  Opiate-dependent with daily opiate use for at least 2 months and regimented daily
 narcotic dose twice a day/bis in die (BID) or greater

 Exclusion Criteria

 -  Intolerance or known allergy to ketamine

 -  History of increased intraocular pressure (> 22mmHg)

 -  Uncontrolled hypertension (systolic blood pressure greater than or equal to 180,
 diastolic blood pressure greater than equal to 100)

 -  Increased intracranial pressure

 -  History of psychosis

 -  Pregnancy

 -  Patients with significant liver disease {signs and symptoms of liver injury, such as
 discolored skin and eyes that appear yellowish, abdominal pain and swelling, Itchy
 skin that doesn't seem to go away, dark urine color, pale stool color, bloody or
 tar-colored stool, chronic fatigue, nausea, loss of appetite, with or without elevated
 Liver Function Tests (LFTs): aspartate aminotransferase (AST) > 120 IU/ml, alkaline
 phosphatase (AP) >130 IU/ml, and alanine aminotransferase (ALT) >40 IU/ml}

 -  Patients with exposure to Cytochrome P450, family 3, subfamily A (CYP3A) and / or
 Cytochrome P450 Family 2 Subfamily B Member 6 (CYP2B6) inhibitors, including the herbs
 and the over-the-counter compounds (list of drugs can be found at
 http://www.fda.gov/drugs/developmentapprovalprocess/developmentresources/druginteracti
 onslabeling/ucm093664.htm)