Ketamine in Patients Undergoing Anterior Cervical Discectomy and Fusion

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