• Eur J Pain · May 2019

    Randomized Controlled Trial

    Ketamine infusion for 96 hr after thoracotomy: Effects on acute and persistent pain.

    Why is this significant?

    This is the first randomised controlled trial looking at the impact of perioperative ketamine on persistent post-surgical (PPS) pain 1 year after thoracic surgery. Thoracotomy is associated with both severe and a high incidence (up to 50% at 6 months) chronic pain.

    Ketamine has important analgesic properties through NMDA blockade, and has been long thought (hoped) that via this it may modify chronic post-surgical pain. Nonetheless, many studies have been unable to show a benefit for ketamine in reducing PPS pain.

    What did they show?

    Chumbley et al. ran ketamine infusions at 0.1 mg/kg/hour for 96 hours in patients undergoing thoracotomy, starting with a 0.1 mg/kg bolus 10 minutes before surgery. Patients also received either an epidural or paravertebral infusion for post-operative analgesia.

    Although there were small differences in acute pain (notably the ketamine group used less PCA morphine) there was no difference in persistent post-surgical pain at 12 months.

    Bottom-line

    The evidence continues to mount against perioperative ketamine, suggesting it does not reduce persistent post-surgical pain, not-withstanding its acute analgesia benefits. Await results of the ROCKet trial (Reduction Of Chronic Post-surgical Pain with Ketamine) to provide greater clarity...

    An afterthought

    Notably, the researchers did demonstrate a dramatically lower incidence of PPS pain than for similar studies (27%, 18%, 13% at 3, 6, 12 months) across both the ketamine and placebo group. This suggests that either the study participants were not representative of the typical thoracotomy patient (unlikely), or other care associated with the study had a beneficial effect on reducing PPS – perhaps even via a Hawthorne-like effect.

    summary
    • Gillian M Chumbley, Lindsey Thompson, Joanna E Swatman, and Catherine Urch.
    • Imperial College Healthcare NHS Trust, London, UK.
    • Eur J Pain. 2019 May 1; 23 (5): 985-993.

    IntroductionPain which persists after thoracotomy is well recognized, and activation of the N-methyl-d-aspartate (NMDA) receptor could be a contributing factor. This study sought to establish whether ketamine given peri-operatively could reduce persistent post-surgical pain.Trial DesignDouble-blind, randomized, placebo-controlled trial comparing low-dose intravenous ketamine and saline placebo.MethodsSeventy patients undergoing thoracotomy were randomized to receive either intravenous ketamine (0.1 mg kg-1  hr-1 ) or saline placebo for 96 hr, starting 10 min prior to surgery. A bolus dose of 0.1 mg/kg of ketamine/placebo was given prior to starting the infusion. Post-operative analgesia consisted of either an epidural infusion or patient-controlled analgesia (PCA), +/- a paravertebral infusion of local anaesthetic. Pain scores and opioid consumption were collected at 24 and 48 hr after surgery. Patients completed numeric pain scores (NPS), modified Brief Pain Inventory (BPI), the short form Leeds Assessment of Neuropathic Symptoms and Signs (S-Lanss) at baseline, 6 weeks, 3, 6 and 12 months after surgery.ResultsThere were no significant differences in post-operative pain, except the ketamine group reported less pain at rest 48 hr after surgery (p = 0.03). The ketamine group requested significantly less morphine via PCA in the first 24 hr (p = 0.03). There were no differences in pain measures or opioid consumption at 6 weeks, 3, 6 or 12 months. Patients in the ketamine group were more lightheaded (p = 0.02) and experienced more vivid dreams (p = 0.001).ConclusionsKetamine reduced opioid consumption compared to placebo after surgery, but we were unable to detect any differences in persistent post-surgical pain between the groups.SignificanceThis study adds to the growing body of evidence advocating the use of ketamine to reduce opioid consumption. No previous studies of peri-operative ketamine have followed patients for a year after thoracotomy. This study found no reduction in persistent post-surgical pain.© 2019 European Pain Federation - EFIC®.

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    This article appears in the collection: Does ketamine reduce persistent post-surgical pain?.

    Notes

    summary
    1

    Why is this significant?

    This is the first randomised controlled trial looking at the impact of perioperative ketamine on persistent post-surgical (PPS) pain 1 year after thoracic surgery. Thoracotomy is associated with both severe and a high incidence (up to 50% at 6 months) chronic pain.

    Ketamine has important analgesic properties through NMDA blockade, and has been long thought (hoped) that via this it may modify chronic post-surgical pain. Nonetheless, many studies have been unable to show a benefit for ketamine in reducing PPS pain.

    What did they show?

    Chumbley et al. ran ketamine infusions at 0.1 mg/kg/hour for 96 hours in patients undergoing thoracotomy, starting with a 0.1 mg/kg bolus 10 minutes before surgery. Patients also received either an epidural or paravertebral infusion for post-operative analgesia.

    Although there were small differences in acute pain (notably the ketamine group used less PCA morphine) there was no difference in persistent post-surgical pain at 12 months.

    Bottom-line

    The evidence continues to mount against perioperative ketamine, suggesting it does not reduce persistent post-surgical pain, not-withstanding its acute analgesia benefits. Await results of the ROCKet trial (Reduction Of Chronic Post-surgical Pain with Ketamine) to provide greater clarity...

    An afterthought

    Notably, the researchers did demonstrate a dramatically lower incidence of PPS pain than for similar studies (27%, 18%, 13% at 3, 6, 12 months) across both the ketamine and placebo group. This suggests that either the study participants were not representative of the typical thoracotomy patient (unlikely), or other care associated with the study had a beneficial effect on reducing PPS – perhaps even via a Hawthorne-like effect.

    Daniel Jolley  Daniel Jolley
     
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