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. 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 are randomly assign; 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.
Use of pregabalin and ketamine
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. In total; 150 patients are randomize; 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. Persistent postsurgical pain is common and has long-term effects on quality of life.
Postsurgical pain is common
Defined as a new pain developing postoperatively in and around the incision site and persisting for at least 3 months after surgery; it is difficult to treat once established. Prevention of this phenomenon therefore seems attractive given the considerable impact on quality of life. Up to half of all patients undergoing any type of surgery to the chest may be at risk; and over half of these cases will demonstrate features of neuropathic pain. Postoperative pain can persist for many years for at least 5 yr after breast surgery, for example with effects on quality of life.
Long-term data for pain after cardiac surgery are limit; but level 1 clinical trial data reveal a prevalence of 27 to 41% at 3 postoperative months Surgical incision is believed to cause hyperalgesia and sensitize the central nervous system. The gabapentinoids are effective in neuromodulating these processes during the treatment of establish neuropathic pain. They have also been shows to suppress central sensitization in other centrally drive processes, such as chronic cough; leading to reduce symptoms as well as improve quality of life.