Ketamine in Patients Undergoing Anterior Cervical Discectomy and Fusion
Status:
Withdrawn
Trial end date:
2015-04-01
Target enrollment:
Participant gender:
Summary
Ketamine is an IV anesthetic with non-opioid analgesic properties that has been shown to
reduce pain while also decreasing intraoperative and postoperative opioid requirements when
used in subanesthetic doses after a variety of surgical procedures.1 It is a non-competitive
antagonist of N-methyl-D-aspartate (NMDA) receptors, and by this mechanism ketamine is
believed to block the development of central sensitization and wind-up phenomenon,2,3 which
may be helpful in preventing acute and chronic pain after repetitive insults. In a systematic
review of ketamine as an adjuvant to opioid analgesia, low-dose ketamine was found to be a
useful addition to standard postoperative pain management practice with opioids in 54% of
studies.1 The studies that did not show a significant effect were in patient populations with
low opioid requirements. Therefore, it has been suggested that future clinical trials be
focused on patient populations with significant post-operative pain, such as spine surgery
and major orthopedic surgery not amenable to regional analgesia, and postoperative pain in
patients on chronic preoperative opioid therapy.1
There are few studies examining outcomes after ketamine in the perioperative period after
spine surgery. Loftus et al randomized patients with a history of chronic preoperative opioid
use (i.e., daily opiate use for at least 6 weeks) to intraoperative ketamine versus placebo
and found a 30% reduction in morphine consumption at 48 hours and an approximately 25%
reduction in visual analog scale (VAS) pain score in the post anesthesia care unit and at 6
weeks.4 Although this study provided evidence that there may be reduction in long-term
postoperative pain, additional studies are needed to provide evidence that this effect is
sustained beyond the 6-week period.
We are interested in examining ketamine more closely in spine surgery because this patient
population experiences significant postoperative pain that may be difficult to control due to
preoperative opioid use (i.e., opioid tolerance). The investigators chose to study ACDF
patients specifically because it is a common spine procedure throughout the United States and
the patients have significant opioid requirements postoperatively. In a study examining the
effects of the low dose ketamine for postoperative IV PCA fentanyl after cervical and lumbar
surgery, patients in the placebo group (and thus only receiving fentanyl PCA) reported mean
VAS scores of 4-5 with movement while receiving opioids.5
Further, while previous studies have shown an opioid-sparing effect of ketamine as measured
by opioid consumption and a decrease in pain as measured by VAS scores, no study to our
knowledge has examined quality of recovery after intraoperative ketamine infusion. The
Quality of recovery (QoR-40) score was developed by Myles et al to assess quality of recovery
after anesthesia based on forty questions in five dimensions,6 and this score has been shown
to be a reliable and valid outcome for patients undergoing both spine and cranial surgery.7
QoR-40 is also of interest because it should be able to provide a global assessment of the
possible benefit or harm of using ketamine in patients by simultaneously characterizing the
detrimental side effects as well as the positive benefits of ketamine when used as an
infusion at subanesthetic levels (studies thus far have shown that there are minimal side
effects such as hallucinations).1,4
Significance:
Previous studies have shown an opioid-sparing effect of ketamine, however further research is
warranted in patients whose pain may be difficult to control and whether this effect is
sustained. ACDF patients experience significant pain post-operatively, and ketamine may
improve their quality of recovery due to its opioid-sparing effects and prevention of chronic
pain. Further, patient centered outcomes as measured by the QoR-40 have not been reported in
the literature when ketamine, or other opioid sparing anesthetics, have been administered.
This study will not only determine if the "moderate" dose of ketamine is beneficial or
detrimental to the recovery of patients but also whether it can improve long term patient
function, presumably by decreasing central pain sensitization. In addition, this study will
set the stage for further RCT's examining other analgesic strategies in cervical spine
surgery patients (i.e., intraoperative lidocaine infusions, volatile anesthetic vs. propofol
as the primary hypnotic, COX-2 inhibitors, pregabalin, etc.). The overall goal would be to
develop a multi-faceted regimen that decreases the postoperative inpatient opioid
requirements of these patients and may facilitate long term recovery.
The research questions:Does ketamine improve the quality of recovery at 24 hours after
anterior cervical discectomy and fusion (ACDF)? The hypothesis: the investigators hypothesize
that ketamine will improve the quality of recovery after ACDF surgery