A Comparison of Intra-op Ketamine vs Placebo in Patients Having Spinal Fusion

Conditions:Post-Surgical Pain
Therapuetic Areas:Musculoskeletal
Age Range:18 - Any
Start Date:August 2014
End Date:December 2018
Contact:Lola Franco, MLS

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A Prospective, Randomized, Single Blinded Comparison of Intraoperative Ketamine Infusion Versus Placebo in Patients Having Spinal Fusion

Postoperative pain is severe after major spine surgery. Opioids such as morphine and
hydromorphone are routinely used for postoperative pain control. These drugs have
significant side effects, most importantly respiratory depression, nausea, constipation and
tolerance. Moreover, many spine surgery patients have used opioid pain medication for back
pain long term, leading to pre-surgical opioid tolerance and increased postoperative pain.
This has led to a search for adjuvant medications to reduce the use of opioids and reduce
opioid mediated side effects and tolerance.

Ketamine is an intravenous anesthetic with analgesic properties in subanesthetic doses.
Ketamine is a noncompetitive antagonist of N-methyl-D-aspartate (NMDA) receptors. NMDA
receptors are involved in central pain sensitization via wind-up phenomenon and altered pain
memory, a process which can be blocked by ketamine. NMDA receptor antagonists may prevent
the development of tolerance to opioids and hyperalgesia. Ketamine has been safely used to
decrease pain in numerous studies. Ketamine can also act as an antidepressant with hours of

Ketamine has rapid brain uptake and subsequent re-distribution with a distribution half-life
of 10-15 minutes and an elimination half-life of 2 hours. Ketamine does not cause
respiratory depression.

This is a prospective, single-blinded, placebo controlled single center trial. One hundred
subjects (50 in each arm) will be enrolled. Subjects undergoing multilevel spinal fusion
will be screened and have the study introduced and discussed with them during the
preadmission visit. Subjects may also contact study personnel or be contacted by study
personnel before admission. Upon admission on the day of surgery, patients will be
re-screened, recruited, have informed consent obtained. After consent is achieved in the
pre-admission clinic prior to surgery, patients will be asked to fill out Beck's depression
inventory, post-operative quality of recovery score(QoR-15) form, visual analog scale (VAS)
for pain and short form McGill pain questionnaire to establish baseline scores. These forms
can be completed at pre-admission testing, at home or on the day of surgery. The three forms
will be on postoperative days (POD) 1, 2 and 3; only the VAS will be given in the PACU.
Eligible subjects will be assigned to either the ketamine or placebo group based on a
computer generated randomization (randomization.com). Baseline demographic data as well as
medical history and medication list will be recorded.

Anesthetic management for this study will be exactly the same management that we are
currently providing for patients undergoing multilevel spinal fusions. The only difference
in care between the placebo group and the treatment group will be the addition of a low dose
ketamine infusion in the treatment group. The placebo group will receive a fentanyl infusion
at 1 mcg/kg/hr during the surgery and a morphine PCA for postoperative pain control. The
placebo group will receive additional fentanyl as needed on the operating room and
additional morphine as needed in the recovery room.

Anesthetic management for both groups will start with IV placement and routine (American
Society of Anesthesiologists - ASA ) monitors. An arterial catheter may be placed at the
discretion of the attending anesthesiologist. After preoxygenation, general anesthesia will
be induced with Propofol 1 to 2 mg/kg, fentanyl 1 to 2 mcg/kg, and rocuronium .6 mg/kg.
Maintenance of anesthesia will be a propofol infusion starting at 150 mcg/kg/min, fentanyl 1
mcg/kg/hr. Additionally, the ketamine group will receive a ketamine infusion at a rate of 10
mcg/kg/min starting after intubation and terminated at the start of skin closure. All
patients will be treated with zofran and ofirmev during surgical closing. Pre-induction
midazolam will be administered at the discretion of the anesthesiologist. No NSAIDS will be
given because of bleeding risk. Sevoflurane may be used for brief periods at the beginning
and end of the procedure to cover times when total intravenous anesthesia (TIVA) is not
practical, i.e. when moving or positioning the patient. Additional fentanyl and rocuronium
boluses can be given as needed. Administration of corticosteroids per surgeon's request will
be recorded. Anesthetics will be titrated to maintain a Bispectral (BIS) index of 40 to 60.
Patients will be awakened, extubated and transferred to the PACU after following simple
commands. Morphine patient controlled anesthesia (PCA) at a setting of 1 mg dose with a 6
minutes lockout will be started immediately on arrival in PACU. While in the PACU, all
subjects who do not have adequate pain control will receive rescue dose of morphine 2 mg. to
4 mg. as indicated by a numeric pain Rating Scale score > 3 or upon subjects' request. All
narcotics and other pain medication given will be recorded. Postoperative nausea will be
treated with droperidol .625 mg IV. If the patient's pain cannot be controlled with PCA
morphine then a pain consult will be obtained. The pain service will be free to administer
any medication deemed necessary to control the patient's pain.

PACU Monitoring: Once in the PACU, all patients will be monitored by PACU nurses per nursing
protocol. The following questionnaires: 1) VAS for pain will be administered in the PACU. On
postoperative day 1, 2 and 3 the McGill short form, VAS, Beck Depression Inventory (BDI) and
QoR15 will be given.

The subjects who enroll in this study will be asked to fill out questionnaires at five
different times. The questionnaires include The Beck depression inventory, McGill's short
form pain questionnaire, Quality of Recovery - 15 form (QoR15) and the visual analog scale
(VAS) for pain. The forms will be filled out at five separate times; preoperatively in
pre-surgical testing or in the pre-surgical holding area of Tisch hospital, in the post
anesthesia care unit of Tisch hospital after the surgery, on postoperative day #1, on
postoperative day #2 and on postoperative day #3. In the PACU on the day of surgery, only
the VAS will be given.

All subjects will be carefully monitored for safety and efficacy. While the ketamine or
placebo is administered in the operating room, an anesthesiologist, Certified Registered
Nurse Anesthetist (CRNA) or anesthesia resident will be present. In the PACU patients will
have 1:1 or 1:2 nursing care. An anesthesiologist is immediately available in the PACU
should a problem arise.

Inclusion Criteria:

1. Adult (>/=18)

2. male or female

3. Undergoing surgery for multilevel (>2 level) spinal fusion from a posterior approach.

4. General anesthesia

5. English speakers such that they can complete the pain score and satisfaction
questionnaires whose scores are a critical outcome variable.

6. If female, subject is non-lactating and is either: a. Post-menopausal or post
hysterectomy; b. Of childbearing potential but is not pregnant at time of baseline as
determined by pre-surgical pregnancy testing.

7. Subject is American Society of Anesthesiologists (ASA) physical status 1, 2, or 3.

Exclusion Criteria:

1. Cognitively impaired (by history)

2. Subject with a history of psychosis

3. Subject known to have significant hepatic disease

4. Subject for whom opioids or ketamine are contraindicated

5. Patients with narrow angle glaucoma

6. Increased intracranial or intraocular pressure

7. If female, is either pregnant or lactating.
We found this trial at
227 East 30th Street
New York City, New York 10016
Phone: 212-263-0531
New York City, NY
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