Effects of esketamine on postoperative rebound pain in patients undergoing unilateral total knee arthroplasty: a single-center, randomized, double-blind, placebo-controlled trial protocol

Zhu, Youzhuang; Li, Qun; Liu, Guilin; Sheng, Fang; Zhang, Xiaotian; Jiang, Lili; Li, Shaona; He, Jianshuai; Zou, Zhijin; Zhang, Baobo; Wang, Changyao; Jiang, Xin; Zhao, Yao

doi:10.3389/fneur.2023.1179673

Cited by 9 publications

(6 citation statements)

References 29 publications

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“…This single-center, prospective, double-blind, randomized, placebo-controlled, pragmatic study will assess our hypothesis that elderly patients treated with S-ketamine will have a lower risk of POD. We have reason to believe that S-ketamine can significantly reduce postoperative pain scores and opioid consumption, which would be consistent with our previous findings ( Zhu et al, 2023 ). We have reviewed the literature to identify potential preoperative confounding variables, including age, ASA class, education level, comorbidities, electrolyte disturbances, malnutrition, smoking and drinking, history of falls, visual and auditory disorders, depression, dementia, functional status, frailty, and sleep disturbances.…”

Section: Discussionsupporting

confidence: 92%

“…In addition, elderly patients with preoperative dementia, depression, and multiple comorbidities will be included, making the dose of S-ketamine received in the intervention group more conservative. Our previous study found that subjects receiving 0.3 mg/kg/h S-ketamine had hallucinations and dreaminess, although this dose was subanesthetic (Zhu et al, 2023). Therefore, we will use a smaller subanesthetic dose of S-ketamine 0.2 mg/kg infused over 1 h in this trial.…”

Section: Interventionsmentioning

confidence: 99%

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Evaluating the effects of S-ketamine on postoperative delirium in elderly patients following total hip or knee arthroplasty under intraspinal anesthesia: a single-center randomized, double-blind, placebo-controlled, pragmatic study protocol

Zhu,

Feng,

Kong

et al. 2023

Front. Aging Neurosci.

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IntroductionPostoperative delirium (POD) is an acute, transient brain disorder associated with decreased postoperative quality of life, dementia, neurocognitive changes, and mortality. A small number of trials have explored the role of S-ketamine in the treatment of POD due to its neuroprotective effects. Surprisingly, these trials have failed to yield supportive results. However, heterogeneity in delirium assessment methodologies, sample sizes, and outcome settings as well as deficiencies in S-ketamine use methods make the evidence provided by these studies less persuasive. Given the severe impact of POD on the health of elderly patients and the potential for S-ketamine to prevent it, we believe that designing a large sample size, and rigorous randomized controlled trial for further evaluation is necessary.MethodsThis is a single-center, randomized, double-blind, placebo-controlled, pragmatic study. Subjects undergoing total hip or knee arthroplasty will be randomized in a 1:1 ratio to intervention (n = 186) and placebo (n = 186) groups. This trial aims to explore the potential role of S-ketamine in the prevention of POD. Its primary outcome is the incidence of POD within 3 postoperative days. Secondary outcomes include the number of POD episodes, the onset and duration of POD, the severity and subtype of POD, pain scores and opioid consumption, sleep quality, clinical outcomes, and safety outcomes.DiscussionTo our knowledge, this is the first pragmatic study that proposes to use S-ketamine to prevent POD. We reviewed a large body of literature to identify potential preoperative confounding variables that may bias associations between the intervention and primary outcome. We will use advanced statistical methods to correct potential confounding variables, improving the test’s power and external validity of test results. Of note, the patient population included in this trial will undergo intraspinal anesthesia. Although large, multicenter, randomized controlled studies have found no considerable difference in the effects of regional and general anesthesia on POD, patients receiving intraspinal anesthesia have less exposure to at-risk drugs, such as sevoflurane, propofol, and benzodiazepines, than patients receiving general anesthesia. At-risk drugs have been shown to negatively interfere with the neuroprotective effects of S-ketamine, which may be the reason for the failure of a large number of previous studies. There is currently a lack of randomized controlled studies evaluating S-ketamine for POD prevention, and our trial helps to fill a gap in this area.Trial registration: http://www.chictr.org.cn, identifier ChiCTR2300075796.

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Section: Discussionsupporting

confidence: 92%

Section: Interventionsmentioning

confidence: 99%

Evaluating the effects of S-ketamine on postoperative delirium in elderly patients following total hip or knee arthroplasty under intraspinal anesthesia: a single-center randomized, double-blind, placebo-controlled, pragmatic study protocol

Zhu,

Feng,

Kong

et al. 2023

Front. Aging Neurosci.

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“…Local infiltration injections of periarticular medications are also a type of regional block that may lead to postoperative transient rebound pain. The mechanism of rebound pain is unknown, and it may be relatively sudden nociceptive pain due to inadequate analgesia or hyperalgesia caused by regional blockade [ 28 , 29 ]. Other factors may include neurotoxicity of the local anesthetic, withdrawal reactions, potential pain facilitation, and personal or surgical factors.…”

Section: Discussionmentioning

confidence: 99%

Cocktail of Ropivacaine, Morphine, and Diprospan Reduces Pain and Prolongs Analgesic Effects after Total Knee Arthroplasty: A Prospective Randomized Controlled Trial

Luo,

Zeng,

Chen

et al. 2024

International Journal of Clinical Practice

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Background. Local infiltration analgesia (LIA) provides postoperative analgesia for total knee arthroplasty (TKA). The purpose of this study was to evaluate the analgesic effect of a cocktail of ropivacaine, morphine, and Diprospan for TKA. Methods. A total of 100 patients from September 2018 to February 2019 were randomized into 2 groups. Group A (control group, 50 patients) received LIA of ropivacaine alone (80 ml, 0.25% ropivacaine). Group B (LIA group, 50 patients) received an LIA cocktail of ropivacaine, morphine, and Diprospan (80 ml, 0.25% ropivacaine, 0.125 mg/ml morphine, and 62.5 μg/ml compound betamethasone). The primary outcomes were the levels of inflammatory markers C-reactive protein (CRP) and interleukin-6 (IL-6), pain visual analog scale (VAS) scores, opioid consumption, range of motion (ROM), functional tests, and sleeping quality. The secondary outcomes were adverse events, satisfaction rates, HSS scores, and SF-12 scores. The longest follow-up was 2 years. Results. The two groups showed no differences in terms of characteristics (P > 0.05). Group B had lower resting VAS pain scores (1.54 ± 0.60, 95% CI = 1.37 to 1.70 vs. 2.00 ± 0.63, 95% CI = 2.05 to 2.34) and active VAS pain scores (2.64 ± 0.62, 95% CI = 2.46 to 2.81 vs. 3.16 ± 0.75, 95% CI = 2.95 to 3.36) within 48 h postoperatively than Group A (P<0.001), while none of the pain differences exceeded the minimal clinically important difference (MCID). Group B had significantly lower CRP levels (59.49 ± 13.01, 95% CI = 55.88 to 63.09 vs. 65.95 ± 14.41, 95% CI = 61.95 to 69.94) and IL-6 levels (44.11 ± 13.67, 95% CI = 40.32 to 47.89 vs. 60.72 ± 15.49, 95% CI = 56.42 to 65.01), lower opioid consumption (7.60 ± 11.10, 95% CI = 4.52 to 10.67 vs. 13.80 ± 14.68, 95% CI = 9.73 to 17.86), better ROM (110.20 ± 10.46, 95% CI = 107.30 to 113.09 vs. 105.30 ± 10.02, 95% CI = 102.52 to 108.07), better sleep quality (3.40 ± 1.03, 95% CI = 3.11 to 3.68 vs. 4.20 ± 1.06, 95% CI = 3.90 to 4.49), and higher satisfaction rates than Group A within 48 h postoperatively (P < 0.05). Adverse events, HSS scores, and SF-12 scores were not significantly different within 2 years postoperatively. Conclusions. A cocktail of ropivacaine, morphine, and Diprospan prolongs the analgesic effect up to 48 h postoperatively. Although the small statistical benefit may not result in MCID, the LIA cocktail still reduces opioid consumption, results in better sleeping quality and faster rehabilitation, and does not increase adverse events. Therefore, cocktails of ropivacaine, morphine, and Diprospan have good application value for pain control in TKA. This trial is registered with ChiCTR1800018372.

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“… 22 , 23 However, this study found no statistically significant difference in the occurrence of postoperative nausea and vomiting between the two groups, which is consistent with domestic and international studies. 19 , 24 , 25 Furthermore, a meta-analysis on the use of esketamine for postoperative acute pain also indicated that esketamine does not reduce the incidence of postoperative nausea and vomiting. 26 Another consideration when using esketamine during the perioperative period is the occurrence of psychiatric adverse reactions such as hallucinations, nightmares, and delirium.…”

Section: Discussionmentioning

confidence: 99%

Efficacy of Intravenous Administration of Esketamine in Preventing and Treating Rebound Pain After Thoracic Paravertebral Nerve Block: A Prospective Randomized, Double-Blind, Placebo-Controlled Trial

Zeng,

Zhang,

Jiang

et al. 2024

DDDT

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Purpose Investigating the efficacy of intraoperative fractionated intravenous esketamine in the prevention of rebound pain after cessation of thoracic paravertebral nerve blockade. Methods One hundred and twenty patients who underwent elective thoracoscopic lobectomy were selected for the study and were randomly divided into two groups, the esketamine group was given 0.5 mg/kg and 0.3 mg/kg of esketamine at the induction of anaesthesia and 30 minutes before the end of the operation, respectively, and the control group was given an equal amount of saline. The incidence of rebound pain (RP) 7 days after surgery and postoperative recovery were compared between the two groups. Results The NRS pain scores at 24 and 48 hours postoperatively in the esketamine group were significantly lower than those in the control group (P < 0.05). The incidence of postoperative rebound pain was significantly lower in the esketamine group than in the control group (P < 0.05). The consumption of sufentanil was less in the esketamine group in the postoperative 48 hours (P < 0.05). Postoperative recovery was compared between the two groups and the difference was not statistically significant. Conclusion Intravenous esketamine reduces postoperative pain scores, decreases the incidence of rebound pain after cessation of thoracic paravertebral block, and reduces opioid consumption.

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Effects of esketamine on postoperative rebound pain in patients undergoing unilateral total knee arthroplasty: a single-center, randomized, double-blind, placebo-controlled trial protocol

Cited by 9 publications

References 29 publications

Evaluating the effects of S-ketamine on postoperative delirium in elderly patients following total hip or knee arthroplasty under intraspinal anesthesia: a single-center randomized, double-blind, placebo-controlled, pragmatic study protocol

Evaluating the effects of S-ketamine on postoperative delirium in elderly patients following total hip or knee arthroplasty under intraspinal anesthesia: a single-center randomized, double-blind, placebo-controlled, pragmatic study protocol

Cocktail of Ropivacaine, Morphine, and Diprospan Reduces Pain and Prolongs Analgesic Effects after Total Knee Arthroplasty: A Prospective Randomized Controlled Trial

Efficacy of Intravenous Administration of Esketamine in Preventing and Treating Rebound Pain After Thoracic Paravertebral Nerve Block: A Prospective Randomized, Double-Blind, Placebo-Controlled Trial

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