Low-dose ketamine infusion reduces postoperative hydromorphone requirements in opioid-tolerant patients following spinal fusion

Boenigk, Kirsten; Echevarría, Ghislaine C.; Nisimov, Emmanuel; Granell, Annelise E von Bergen; Cuff, Germaine; Wang, Jing; Atchabahian, Arthur

doi:10.1097/eja.0000000000000877

Cited by 46 publications

(34 citation statements)

References 27 publications

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“…Ketamine, which is a NMDA receptor antagonist, might have been effective in the Loftus and Nielsen studies as their patients had NMDA-receptor-activation due to chronic opioid use (pointing towards opioid-induced hyperalgesia). A recently published trial confirms this hypothesis (Boenigk et al, 2019). In our study, the proportion of preoperative chronic users of strong opioids was low, which could explain the lack of efficacy of ketamine.…”

Section: Discussionsupporting

confidence: 83%

Perioperative intravenous low‐dose ketamine for neuropathic pain after major lower back surgery: A randomized, placebo‐controlled study

Czarnetzki

Desmeules

Tessitore

et al. 2019

European Journal of Pain

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Background Chronic pain after major lower back surgery is frequent. We investigated in adults the effect of perioperative low‐dose ketamine on neuropathic lower back pain, assessed by the DN4 questionnaire, 6 and 12 months after major lower back surgery. Methods In this single‐centre randomized trial, 80 patients received intravenous ketamine 0.25 mg/kg preoperatively, followed by 0.25 mg kg−1 hr−1 intraoperatively, and 0.1 mg kg−1 hr−1 from 1 hr before the end of surgery until the end of recovery room stay; 80 controls received placebo. Results Preoperatively, 47.4% of patients in the ketamine group and 46.3% in the placebo group had neuropathic pain; 10% and 3.8%, respectively, were using strong opioids. At the end of the infusion, the median cumulative dose of ketamine was 84.8 mg (IQR 67.4–106.7) and the median plasma level was 97 ng/ml (IQR 77.9–128.0). At 6 months, 28.8% of patients in the ketamine group and 23.5% in the placebo group had neuropathic pain (absolute difference, 5.2%; 95% CI −10.7 to 21.1; p = .607). At 12 months, 26.4% of patients in the ketamine group and 17.9% in the placebo group had neuropathic pain (absolute difference 8.5%; 95% CI −6.7 to 23.6; p = .319). Conclusions In this patient population with a high prevalence of neuropathic lower back pain undergoing major lower back surgery, a perioperative intravenous low‐dose ketamine infusion did not have an effect on the prevalence of neuropathic lower back pain at 6 or 12 months postoperatively. Significance We were unable to show any analgesic benefit of a short‐term perioperative ketamine infusion as an adjuvant to multimodal analgesia in patients with a high prevalence of neuropathic lower back pain undergoing major back surgery. Based on these data, the widespread opinion that ketamine is universally analgesic across different pain conditions must be challenged. Prior presentations Abstract presentation at the annual congress of the Swiss Society of Anaesthesiology, 2016, Basel, Switzerland. Clinical trial number and registry URL Registered by Dr Christoph Czarnetzki as principal investigator on February 20, 2008 at clinicaltrials.gov (NCT00618423).

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Section: Discussionsupporting

confidence: 83%

Perioperative intravenous low‐dose ketamine for neuropathic pain after major lower back surgery: A randomized, placebo‐controlled study

Czarnetzki

Desmeules

Tessitore

et al. 2019

European Journal of Pain

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“…Data indicating low incidence of ketamine-related adverse events (PONV and CNS adverse events) has been consistent in previous studies. 11,12,33 Likewise, our study showed that adjunct S-ketamine in oxycodone IV-PCA was well tolerated. There are several reports of ketamine’s beneficial effect on analgesia, opioid-sparing, and PONV in the postoperative period, without increasing the risk for hallucinations.…”

Section: Discussionsupporting

confidence: 55%

“…32 Another recent study further confirmed that postoperative low-dose ketamine infusion reduced hydromorphone requirements for the first 24 h after spinal fusion surgery in opioid-tolerant patients, but not in opioid-naïve patients. 33 However, it is recognized that previous opioid use alters pain processing, and these patients typically require higher opioid doses postoperatively. Thus, results of these studies cannot be directly applied to all patients.…”

Section: Discussionmentioning

confidence: 99%

S-ketamine in patient-controlled analgesia reduces opioid consumption in a dose-dependent manner after major lumbar fusion surgery: a randomized, double-blind, placebo-controlled clinical trial

Brinck

Virtanen

Mäkelä

et al. 2021

Preprint

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BACKGROUNDSpinal fusion surgery causes severe pain. Strong opioids, commonly used as postoperative analgesics, may have unwanted side effects. S-ketamine may be an effective analgesic adjuvant in opioid patient-controlled analgesia (PCA). However, the optimal adjunct S-ketamine dose to reduce postoperative opioid consumption is still unknown.METHODSWe randomized 107 patients at two tertiary hospitals in a double-blinded, placebo-controlled clinical trial of adults undergoing major lumbar spinal fusion surgery. Patients were randomly allocated to four groups in order to compare the effects of three different doses of adjunct S-ketamine (0.25, 0.5, and 0.75 mg ml-1) or placebo on postoperative analgesia in oxycodone PCA. Study drugs were administered for 24 hours postoperative after which oxycodone-PCA was continued for further 48 hours. Our primary outcome was cumulative oxycodone consumption at 24 hours after surgery.RESULTSOf the 100 patients analyzed, patients receiving 0.75 mg ml-1 S-ketamine in oxycodone PCA needed 25% less oxycodone at 24 h postoperatively (61.2 mg) compared with patients receiving 0.5 mg ml-1 (74.7 mg) or 0.25 mg ml-1 (74.1 mg) S-ketamine in oxycodone or oxycodone alone (81.9 mg) (mean difference: -20.6 mg; 95% confidence interval [CI]: -41 to - 0.20; P = 0.048). A significant beneficial effect in mean change of pain intensity at rest was seen in the group receiving 0.75 mg ml-1 S-ketamine in oxycodone PCA compared with patients receiving lower ketamine doses or oxycodone alone (standardized effect size: 0.17, 95% CI: 0.013–0.32, P = 0.033). The occurrence of adverse events was similar among the groups.CONCLUSIONSOxycodone PCA containing S-ketamine as an adjunct at a ratio of 1: 0.75 decreased cumulative oxycodone consumption at 24 h after major lumbar spinal fusion surgery without additional adverse effects.

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“…Moreover, all patients were administered perioperative pregabalin, which would further reduce postoperative pain (18), masking the benefit of ketamine on APSP. Second, several studies showed that ketamine reduced postoperative opioid requirements only in opioidtolerant patients, not in opioid-naïve patients (19,20).…”

Section: Effect Of Ketamine On Persistent Postsurgical Pain Discussionmentioning

confidence: 99%

Effects of Intraoperative Low-Dose Ketamine on Persistent Postsurgical Pain after Breast Cancer Surgery: A Prospective, Randomized, Controlled, Double-Blind Study

et al. 2020

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Background: Compared to acute postsurgical pain, studies regarding the role of ketamine in persistent postsurgical pain (PPSP) are limited. Objectives: The aim of this clinical trial was to test if intraoperative low-dose ketamine without postoperative infusion would reduce PPSP development after breast cancer surgery. Study design: We used a randomized, double-blinded, placebo study design. Setting: This study was conducted at Pusan National University Hospital, Republic of Korea, between December 2013 and August 2016. Methods: A total of 184 patients scheduled for breast cancer surgery were randomly assigned to either the control or ketamine group. Before skin incision, a bolus (0.5 mg/kg of ketamine or placebo), followed by a continuous infusion (0.12 mg/kg/h of ketamine or placebo), was administered until the end of the surgery. The patients were interviewed via telephone 1, 3, and 6 months after surgery. The first question was whether the patient had surgery-related pain. If answered affirmatively, questions from the Numeric Rating Scale for pain at rest (NRSr) and for coughing (NRSd) were also asked. Our primary outcome was the incidence of PPSP at 3 months after surgery. Results: For PPSP analysis, 168 patients were included. The number of patients who experienced pain was significantly lower in the ketamine group at 3 months (86.9% in the control group vs 69.0% in the ketamine group, P = .005) postoperatively. However, the NRSr and NRSd did not differ between the groups throughout the follow-up. Limitations: There were no postoperative low-dose ketamine infusion groups to compare due to hospital regulations. Dosage of ketamine was too low to reduce the severity of PPSP. And by using propofol and remifentanil for anesthesia, different results can be deduced with volatile anesthetics. Data from written questionnaires would have been more specific than telephone interviews for long-term assessment. Conclusions: Though intraoperative low-dose ketamine without postoperative infusion significantly reduced the incidence of PPSP up to 3 months after breast cancer surgery, it failed to reduce clinically significant PPSP and improve patients’ quality of life. Key words: Analgesia, breast cancer, chronic pain, ketamine, mastectomy, morphine, pain, postoperative, propofol

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Low-dose ketamine infusion reduces postoperative hydromorphone requirements in opioid-tolerant patients following spinal fusion

Abstract: NCT03274453 with clinicaltrials.gov.

Cited by 46 publications

References 27 publications

Perioperative intravenous low‐dose ketamine for neuropathic pain after major lower back surgery: A randomized, placebo‐controlled study

Perioperative intravenous low‐dose ketamine for neuropathic pain after major lower back surgery: A randomized, placebo‐controlled study

S-ketamine in patient-controlled analgesia reduces opioid consumption in a dose-dependent manner after major lumbar fusion surgery: a randomized, double-blind, placebo-controlled clinical trial

Effects of Intraoperative Low-Dose Ketamine on Persistent Postsurgical Pain after Breast Cancer Surgery: A Prospective, Randomized, Controlled, Double-Blind Study

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