PAIN MEDICINE Anesthesiology 2010; 113:639–46 Copyright © 2010, the American Society of Anesthesiologists, Inc. Lippincott Williams & Wilkins Intraoperative Ketamine Reduces Perioperative Opiate Consumption in Opiate-dependent Patients with Chronic Back Pain Undergoing Back Surgery Randy W. Loftus, M.D.,* Mark P. Yeager, M.D.,† Jeffrey A. Clark, M.D.,* Jeremiah R. Brown, M.S., Ph.D.,‡ William A. Abdu, M.S., M.D.,§ Dilip K. Sengupta, M.D., Ph.D.,࿣ Michael L. Beach, M.D., Ph.D.† Downloaded from http://pubs.asahq.org/anesthesiology/article-pdf/113/3/639/452546/0000542-201009000-00025.pdf by guest on 02 October 2021 ABSTRACT weeks. The average reported pain intensity was significantly Background: Ketamine is an N-methyl-D-aspartate receptor reduced in the postanesthesia care unit and at 6 weeks. The antagonist that has been shown to be useful in the reduction groups had no differences in known ketamine- or opiate- of acute postoperative pain and analgesic consumption in a related side effects. variety of surgical interventions with variable routes of ad- Conclusions: Intraoperative ketamine reduces opiate con- ministration. Little is known regarding its efficacy in opiate- sumption in the 48-h postoperative period in opiate-depen- dependent patients with a history of chronic pain. We hy- dent patients with chronic pain. Ketamine may also reduce pothesized that ketamine would reduce postoperative opiate opioid consumption and pain intensity throughout the post- consumption in this patient population. operative period in this patient population. This benefit is Methods: This was a randomized, prospective, double- without an increase in side effects. blinded, and placebo-controlled trial involving opiate-depen- dent patients undergoing major lumbar spine surgery. Fifty-two patients in the treatment group were administered 0.5 mg/kg What We Already Know about This Topic intravenous ketamine on induction of anesthesia, and a contin- ❖ Ϫ Ϫ Acute pain management of patients with chronic pain who are uous infusion at 10 ␮gkg 1min 1 was begun on induction and opioid-tolerant is often difficult. terminated at wound closure. Fifty patients in the placebo group ❖ Few interventions have reduced postoperative opioid require- received saline of equivalent volume. Patients were observed for ments or pain scores in this patient population. 48 h postoperatively and followed up at 6 weeks. The primary What This Article Tells Us That Is New outcome was 48-h morphine consumption. ❖ In a randomized controlled trial, intraoperative administration Results: Total morphine consumption (morphine equiva- of ketamine reduced opioid consumption after spine surgery lents) was significantly reduced in the treatment group 48 h in these patients with chronic pain who are opioid-tolerant. after the procedure. It was also reduced at 24 h and at 6 ETAMINE is an N-methyl-D-aspartate (NMDA) re- * Assistant Professor, † Professor, Department of Anesthesiol- ceptor antagonist that has been shown to be useful in ogy, § Professor, ࿣ Assistant Professor, Department of Orthopae- K dic Surgery, Dartmouth-Hitchcock Medical Center, Lebanon, the reduction of acute postoperative pain and analgesic New Hampshire. ‡ Instructor, The Dartmouth Institute for Health consumption in a variety of surgical interventions with Policy and Clinical Practice, Dartmouth College, Section of Car- 1 diology, Dartmouth-Hitchcock Medical Center. variable routes of administration. It has multiple mech- Received from the Department of Anesthesiology, Dartmouth- anisms of action, including but not limited to decreasing Hitchcock Medical Center, Lebanon, New Hampshire. Submitted for central excitability, decreasing acute postoperative opiate publication January 12, 2010. Accepted for publication April 15, tolerance, and a possible modulation of opiate receptors. 2010. Support was provided solely from institutional and/or depart- mental sources. Presented in part at the Annual Meeting of the Amer- Furthermore, it has been shown to be effective in the ican Society of Anesthesiologists, San Francisco, California, October 13, 2007. Presented at the 57th Annual Meeting of the Association of University Anesthesiologists, Denver, Colorado, April 8, 2010. ᭛ This article is featured in “This Month in Anesthesiology.” Address correspondence to Dr. Loftus: Department of Anesthesiol- Please see this issue of ANESTHESIOLOGY, page 9A. ogy, Dartmouth-Hitchcock Medical Center, 1 Medical Center Dr, Leb- ᭜ This article is accompanied by an Editorial View: Please see: anon, New Hampshire 03756. [email protected]. Information on purchasing reprints may be found at www.anesthesiology.org or on Angst MS, Clark JD: Ketamine for managing perioperative the masthead page at the beginning of this issue. ANESTHESIOLOGY’s pain in opioid-dependent patients with chronic pain: A unique articles are made freely accessible to all readers, for personal use only, indication? ANESTHESIOLOGY 2010;113:514–5. 6 months from the cover date of the issue. Anesthesiology, V 113 • No 3 • September 2010 639 PAIN MEDICINE presence and absence of opiates, nonsteroidal antiinflam- ing area and obtained informed consent. Duration of daily matory medications, and acetaminophen.2,3 opiate consumption was confirmed, and in accordance with Intraoperative use of preventative ketamine has been clinical practice, baseline morphine equivalents were deter- shown to generate a modest reduction in acute postoperative mined based on the preceding 24-h opiate requirements per opioid consumption (median 33%) and pain intensity (20– patient report. The opiate class was tracked and recorded, 25%) up to 48 h after the surgical insult.4,5 The clinical and standard opiate conversions were used.10 Patients taking benefit, however, remains unclear, because (1) opiate-naive only tramadol were not considered eligible for enrollment. patients were largely enrolled; (2) patients typically con- Patients taking tramadol in addition to other opiate medica- sumed small amounts of opioid medications and were rea- tions were included, but use of tramadol was tracked and sonably comfortable in the postoperative period, making it recorded as an adjunctive agent for later comparisons. Pa- difficult to assess the impact of the reduction in analgesic tients were also identified by the primary anesthesia team, consumption on opiate-related side effects; and (3) the side- received a standard preoperative evaluation, and provided Downloaded from http://pubs.asahq.org/anesthesiology/article-pdf/113/3/639/452546/0000542-201009000-00025.pdf by guest on 02 October 2021 effect profile of low-dose ketamine was not well character- consent for general anesthesia. ized. Thus, the last 15 yr has yielded little insight into the utility of preventative NMDA receptor antagonism in pa- Study Protocol tients with a history of chronic pain who use opiate medica- After consent, a computer-generated block randomization tions preoperatively. This has been suggested as a primary scheme was used to randomize patients in groups of eight to target for research, because patients with chronic pain are one of two treatment regimens: racemic ketamine (JHP thought to be at increased risk of suboptimal postoperative Pharmaceuticals, Parsippany, NJ) or placebo (saline). Prin- pain management and consequently at increased risk of car- cipal investigators, patients, nursing staff, and anesthesia pro- diopulmonary complications and chronic postsurgical viders were blinded to the treatment assignments during the pain.6–9 The primary hypothesis of the current study was entire hospital stay, through the first surgical follow-up visit, that intraoperative preventative ketamine would reduce and during data analysis. All participants were asked to use a acute postoperative analgesic requirements in opiate-depen- visual analog scale to rate their average daily pain preopera- dent patients with a history of chronic back pain who are tively, postoperatively, and at the first follow-up visit. undergoing painful surgery. A standardized anesthesia induction and maintenance protocol was followed. This protocol included 2 mg mida- Materials and Methods zolam before leaving the preoperative holding area, 2–3 ␮g/kg fentanyl before induction, 2–2.5 mg/kg propofol on General Description induction, and isoflurane for maintenance of anesthesia. Un- This was a randomized, prospective, double-blinded, and less contraindicated (fusion procedure), all anesthesia pro- placebo-controlled trial investigating the efficacy of preven- viders were asked to administer 15 mg ketorolac to patients tative ketamine infusions in patients with chronic pain who before emergence. Nitrous oxide was not allowed because of were undergoing elective back surgery. The study was con- its NMDA antagonistic properties. All additional adjunctive ducted over a 2-yr period (February 2007 to April 2009) at agents administered intraoperatively were tracked and Dartmouth-Hitchcock Medical Center (Lebanon, New recorded. Hampshire). Approval was obtained from the Committee for Patients were allowed to receive morphine while anesthe- Protection of Human Subjects. Informed patient consent tized up to their daily opiate dose, plus an additional 0.1 was obtained from all patients. mg/kg morphine at or before emergence. Additional opiates Adult patients with a history of daily opiate use for at least could be used by the anesthesia team if clinically indicated. 6 weeks and chronic back pain for at least 3 months who were All patients were to have patient-controlled analgesia