Pain Medicine  |   July 2019
Prolonged Perioperative Use of Pregabalin and Ketamine to Prevent Persistent Pain after Cardiac Surgery
Author Notes
  • From the Department of Perioperative Medicine, Barts Heart Centre, London, United Kingdom (S.A.); National Institutes of Health Research Biomedical Research Centre at Barts, London, United Kingdom (S.A., J.C.); and Pain and Anaesthesia Research Centre, St. Bartholomew’s Hospital, London, United Kingdom (S.A., J.R., C.S., R.L.).
  • Supplemental Digital Content is available for this article. Direct URL citations appear in the printed text and are available in both the HTML and PDF versions of this article. Links to the digital files are provided in the HTML text of this article on the Journal’s Web site (www.anesthesiology.org).
    Supplemental Digital Content is available for this article. Direct URL citations appear in the printed text and are available in both the HTML and PDF versions of this article. Links to the digital files are provided in the HTML text of this article on the Journal’s Web site (www.anesthesiology.org).×
  • Submitted for publication October 23, 2018. Accepted for publication March 22, 2019.
    Submitted for publication October 23, 2018. Accepted for publication March 22, 2019.×
  • Address correspondence to Dr. Anwar: Barts Heart Centre, King George V Building. St. Bartholomew’s Hospital. London EC1A 7BE, United Kingdom. s.anwar@qmul.ac.uk. Information on purchasing reprints may be found at www.anesthesiology.org or on the masthead page at the beginning of this issue. Anesthesiology’s articles are made freely accessible to all readers, for personal use only, 6 months from the cover date of the issue.
Article Information
Pain Medicine / Clinical Science / Cardiovascular Anesthesia / Central and Peripheral Nervous Systems / Pain Medicine / Pharmacology
Pain Medicine   |   July 2019
Prolonged Perioperative Use of Pregabalin and Ketamine to Prevent Persistent Pain after Cardiac Surgery
Anesthesiology 7 2019, Vol.131, 119-131. doi:10.1097/ALN.0000000000002751
Anesthesiology 7 2019, Vol.131, 119-131. doi:10.1097/ALN.0000000000002751
Abstract

Editor’s Perspective:

What We Already Know about This Topic:

  • Cardiac surgery is associated with a significant rate of chronic postoperative pain

  • Few proven strategies exist to reduce chronic postoperative pain

What This Article Tells Us That Is New:

  • The administration of pregabalin (14 days) with or without ketamine (2 days) postoperatively reduced the prevalence of pain at 3 and 6 months

  • Side effects from pregabalin and ketamine administration were generally mild

Background: Persistent postsurgical pain is common and affects quality of life. The hypothesis was that use of pregabalin and ketamine would prevent persistent pain after cardiac surgery.

Methods: This randomized, double-blind, placebo-controlled trial was undertaken at two cardiac surgery centers in the United Kingdom. Adults without chronic pain and undergoing any elective cardiac surgery patients via sternotomy were randomly assigned to receive either usual care, pregabalin (150 mg preoperatively and twice daily for 14 postoperative days) alone, or pregabalin in combination with a 48-h postoperative infusion of intravenous ketamine at 0.1 mg · kg−1 · h−1. The primary endpoints were prevalence of clinically significant pain at 3 and 6 months after surgery, defined as a pain score on the numeric rating scale of 4 or higher (out of 10) after a functional assessment of three maximal coughs. The secondary outcomes included acute pain, opioid use, and safety measures, as well as long-term neuropathic pain, analgesic requirement, and quality of life.

Results: In total, 150 patients were randomized, with 17 withdrawals from treatment and 2 losses to follow-up but with data analyzed for all participants on an intention-to-treat basis. The prevalence of pain was lower at 3 postoperative months for pregabalin alone (6% [3 of 50]) and in combination with ketamine (2% [1 of 50]) compared to the control group (34% [17 of 50]; odds ratio = 0.126 [0.022 to 0.5], P = 0.0008; and 0.041 [0.0009 to 0.28], P < 0.0001, respectively) and at 6 months for pregabalin alone (6% [3 of 50]) and in combination with ketamine 0% (0 of 5) compared to the control group (28% [14 of 50]; odds ratio = 0.167 [0.029 to 0.7], P = 0.006; and 0.000 [0 to 0.24], P < 0.0001). Diplopia was more common in both active arms.

Conclusions: Preoperative administration of 150 mg of pregabalin and postoperative continuation twice daily for 14 days significantly lowered the prevalence of persistent pain after cardiac surgery.