Dataset Information

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.

ABSTRACT:

Background

Spinal 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.

Methods

We 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.

Results

Of 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 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.

Conclusions

Oxycodone 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.

SUBMITTER: Brinck ECV

PROVIDER: S-EPMC8183989 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Similar Datasets

Project description:Background: Intravenous paracetamol, as an adjunct to multimodal analgesia, has been shown to successfully reduce opioid consumption after joint arthroplasty, abdominal surgery, and caesarean delivery. However, there are limited data on the opioid-sparing effect of intravenous paracetamol on lumbar disc surgery. Objectives: The aim of this study was to investigate the effectiveness and safety of intravenous paracetamol for reducing opioid consumption in lumbar disc surgery. The primary outcome was cumulative opioid consumption within 24 h postoperatively. Method: We followed the PRISMA-P guidelines and used GRADE to assess the quality of evidence. The review was registered in PROSPERO under the registration number CRD42021288168. Two reviewers conducted electronic searches in PubMed, Embase, Cochrane Central Register of Controlled Trials (CENTRAL), Scopus, and Web of Science (Clarivate Analytics). Randomized controlled trials (RCTs) that compared the postoperative opioid consumption of intravenous paracetamol with placebo in lumbar discectomy were included. Results: Five trials comprising a total of 271 patients were included. The overall opioid consumption within 24 h postoperatively was reduced [mean difference (MD), -10.61 (95% CI, -16.00 to -5.22) mg, p = 0.0001, I2 = 90%] in patients with intravenous paracetamol. Intravenous paracetamol significantly reduced the postoperative pain scores at 1 h [MD, -2.37 (95%CI, -3.81 to -0.94), p = 0.001, I2 = 82%], 2 h [MD, -3.17 (95%CI, -3.85 to -2.48), p < 0.00001, I2 = 38%], 6 h [MD, -1.75 (95%CI, -3.10 to -0.40), p = 0.01], 12 h [MD, -0.96 (95%CI, -1.77 to -0.15), p = 0.02], and 24 h [MD, -0.97 (95%CI, -1.67 to -0.27), p = 0.006] compared with the placebo. There were no differences in postoperative adverse effects. Conclusion: Intravenous paracetamol reduced postoperative opioid consumption and decreased postoperative pain scores without increasing adverse effects. The overall GRADE quality of the evidence was rated as low to moderate. Intravenous paracetamol appears to be an applicable option as an important part of multimodal analgesia for postoperative analgesia after lumbar disc surgery. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/, CRD42021288168.

Project description:Backgroundin the United States from 1999 to 2000 through 2017-2018, the prevalence of obesity increased from 30.5 to 42.4%, while the prevalence of severe obesity nearly doubled. In lumbar spine surgery, obesity is associated with increased complications, worse perioperative outcomes, and higher costs. The purpose of this study was to examine the association between body mass index (BMI) and opioid consumption in patients undergoing lumbar spine fusion surgery. We hypothesized that obese patients would require more opioids postoperatively.Methodsretrospective review of 306 patients who underwent one- or two-level posterior lumbar interbody fusion surgery between 2016 and 2020. Patients were stratified by BMI as follows: normal weight (18.5-24.9 kg/m2), overweight (25.0-29.9 kg/m2), obese I (30.0-34.9 kg/m2), and obese II-III (≥ 35.0 kg/m2). Patient demographics and preoperative characteristics were compared across BMI cohorts using one-way ANOVA and chi-square analysis. Patients with prior history of opioid use were excluded. Primary outcome measure was postoperative opioid consumption. Secondary outcomes included operative time, length of stay (LOS), discharge destination, and 30-day re-encounter rates. Outcomes were analyzed using multivariable linear regression adjusted for potential confounders.Resultsof 306 total patients, 17.3% were normal weight, 39.9% were overweight, 25.5% were obese I, and 17.3% were obese II-III. Obesity was associated with longer operative times and length of stay (p < 0.001, p = 0.024). For opioid naïve patients, there was no difference in-house opioid consumption when adjusted for kilograms of body mass and LOS (p = 0.083). Classes II-III patients were prescribed more than twice the number of postoperative opioids (p < 0.001) and were on opioids for a longer time postoperatively (p = 0.019).Conclusionobesity is associated with longer operative times, longer LOS, and increased consumption of postoperative opioids. This should be considered when counseling patients preoperatively prior to lumbar spine fusion procedures.

Project description:BackgroundPoor postoperative pain control is frequently associated with complications and delayed discharge from a hospital. Preemptive analgesia is one of the methods suggested for reducing postoperative pain. Opioids are effective for pain control, but there known addictive properties make physicians cautious about using them. Parecoxib and ketorolac are potent non-opioid NSAIDs that are attractive alternative drugs to opioids to avoid opioid-related side effects. However, there are no good head-to-head comparisons between these two drugs in the aspect of preemptive analgesic effects in lumbar spinal fusion surgery. This study aimed to compare the efficacy in terms of postoperative pain control and safety of parecoxib with ketorolac as preemptive analgesia in posterior lumbar spinal fusion patients.MethodsA prospective, double-blinded randomized controlled trial was carried out in patients undergoing posterior lumbar spinal fusion, who were randomized into 3 groups (n = 32). Parecoxib, ketorolac or a placebo was given to each patient via injection around 30 minutes prior to incision. The efficacy of postoperative pain control was assessed by a verbal numerical rating score (0-10). And various postoperative things were monitored for analysis, such as total opioid consumption, complications, and estimated blood loss.ResultsBoth the ketorolac and parecoxib groups showed significantly better early postoperative pain reduction at the postanesthesia care unit (PACU) than the control group (p < 0.05). There were no differences between the pain scores of ketorolac and parecoxib at any time points. Complications and bleeding were not significantly different between all three groups.ConclusionsPreemptive analgesia using both ketorolac and parecoxib showed a significantly better early postoperative pain control in the PACU than the control group in patients undergoing lumbar spinal fusion.Trial registrationClinicalTrials.gov NCT01859585. Registered 15 May 2013.

Project description:BACKGROUND:This is an updated version of the original Cochrane review published in Issue 4, 2006. Patients may control postoperative pain by self administration of intravenous opioids using devices designed for this purpose (patient controlled analgesia or PCA). A 1992 meta-analysis by Ballantyne et al found a strong patient preference for PCA over non-patient controlled analgesia, but disclosed no differences in analgesic consumption or length of postoperative hospital stay. Although Ballantyne's meta-analysis found that PCA did have a small but statistically significant benefit upon pain intensity, a 2001 review by Walder et al did not find statistically significant differences in pain intensity or pain relief between PCA and groups treated with non-patient controlled analgesia. OBJECTIVES:To evaluate the efficacy and safety of patient controlled intravenous opioid analgesia (termed PCA in this review) versus non-patient controlled opioid analgesia of as-needed opioid analgesia for postoperative pain relief. SEARCH METHODS:We ran the search for the previous review in November 2004. For this update, we searched the Cochrane Central Register of Controlled Trials (CENTRAL 2014, Issue 12), MEDLINE (1966 to 28 January 2015), and EMBASE (1980 to 28 January 2015) for randomized controlled trials (RCTs) in any language, and reference lists of reviews and retrieved articles. SELECTION CRITERIA:We selected RCTs that assessed pain intensity as a primary or secondary outcome. These studies compared PCA without a continuous background infusion with non-patient controlled opioid analgesic regimens. We excluded studies that explicitly stated they involved patients with chronic pain. DATA COLLECTION AND ANALYSIS:Two review authors independently extracted data, which included demographic variables, type of surgery, interventions, efficacy, and adverse events. We graded each included study for methodological quality by assessing risk of bias and employed the GRADE approach to assess the overall quality of the evidence. We performed meta-analysis of outcomes that included pain intensity assessed by a 0 to 100 visual analog scale (VAS), opioid consumption, patient satisfaction, length of stay, and adverse events. MAIN RESULTS:Forty-nine studies with 1725 participants receiving PCA and 1687 participants assigned to a control group met the inclusion criteria. The original review included 55 studies with 2023 patients receiving PCA and 1838 patients assigned to a control group. There were fewer included studies in our updated review due to the revised exclusion criteria. For the primary outcome, participants receiving PCA had lower VAS pain intensity scores versus non-patient controlled analgesia over most time intervals, e.g., scores over 0 to 24 hours were nine points lower (95% confidence interval (CI) -13 to -5, moderate quality evidence) and over 0 to 48 hours were 10 points lower (95% CI -12 to -7, low quality evidence). Among the secondary outcomes, participants were more satisfied with PCA (81% versus 61%, P value = 0.002) and consumed higher amounts of opioids than controls (0 to 24 hours, 7 mg more of intravenous morphine equivalents, 95% CI 1 mg to 13 mg). Those receiving PCA had a higher incidence of pruritus (15% versus 8%, P value = 0.01) but had a similar incidence of other adverse events. There was no difference in the length of hospital stay. AUTHORS' CONCLUSIONS:Since the last version of this review, we have found new studies providing additional information. We reanalyzed the data but the results did not substantially alter any of our previously published conclusions. This review provides moderate to low quality evidence that PCA is an efficacious alternative to non-patient controlled systemic analgesia for postoperative pain control.

Project description:ObjectiveTo confirm the rapid onset anti-suicidal benefits of ketamine in the short term and at six weeks, overall and according to diagnostic group.DesignProspective, double blind, superiority, randomised placebo controlled trial.SettingSeven French teaching hospitals between 13 April 2015 and 12 March 2019.Eligibility criteria for participantsAged 18 or older with current suicidal ideation, admitted to hospital voluntarily. Exclusion criteria included a history of schizophrenia or other psychotic disorders, substance dependence, and contraindications for ketamine.Participants156 participants were recruited and randomised to placebo (n=83) or ketamine (n=73), stratified by centre and diagnosis: bipolar, depressive, or other disorders.InterventionTwo 40 minute intravenous infusions of ketamine (0.5 mg/kg) or placebo (saline) were administered at baseline and 24 hours, in addition to usual treatment.Main outcome measuresThe primary outcome was the rate of patients in full suicidal remission at day 3, according to the scale for suicidal ideation total score ≤3. Analyses were conducted on an intention-to-treat basis.ResultsMore participants receiving ketamine reached full remission of suicidal ideas at day 3 than those receiving placebo: 46 (63.0%) of 83 participants in the ketamine arm and 25 (31.6%) of 73 in the placebo arm (odds ratio 3.7 (95% confidence interval 1.9 to 7.3), P<0.001). This effect differed according to the diagnosis (treatment: P<0.001; interaction: P=0.02): bipolar (odds ratio 14.1 (95% confidence interval 3.0 to 92.2), P<0.001), depressive (1.3 (0.3 to 5.2), P=0.6), or other disorders (3.7 (0.9 to 17.3, P=0.07)). Side effects were limited. No manic or psychotic symptom was seen. Moreover, a mediating effect of mental pain was found. At week 6, remission in the ketamine arm remained high, although non-significantly versus placebo (69.5% v 56.3%; odds ratio 0.8 (95% confidence interval 0.3 to 2.5), P=0.7).ConclusionsThe findings indicate that ketamine is rapid, safe in the short term, and has persistent benefits for acute care in suicidal patients. Comorbid mental disorders appear to be important moderators. An analgesic effect on mental pain might explain the anti-suicidal effects of ketamine.Trial registrationClinicalTrials.gov NCT02299440.

Project description:Numerous placebo-controlled studies have demonstrated the ability of ketamine, an NMDA receptor antagonist, to induce rapid (within hours), transient antidepressant effects when administered intravenously (IV) at subanesthetic doses (0.5 mg/kg over 40 min). However, the optimal antidepressant dose remains unknown. We aimed to compare to active placebo the rapid acting antidepressant properties of a broad range of subanesthetic doses of IV ketamine among outpatients with treatment-resistant depression (TRD). A range of IV ketamine doses were compared to active placebo in the treatment of adult TRD over a 3-day period following a single infusion over 40 min. This was an outpatient study conducted across six US academic sites. Outpatients were 18-70 years old with TRD, defined as failure to achieve a satisfactory response (e.g., less than 50% improvement of depression symptoms) to at least two adequate treatment courses during the current depressive episode. Following a washout period, 99 eligible subjects were randomly assigned to one of the five arms in a 1:1:1:1:1 fashion: a single intravenous dose of ketamine 0.1 mg/kg (n = 18), a single dose of ketamine 0.2 mg/kg (n = 20), a single dose of ketamine 0.5 mg/kg (n = 22), a single dose of ketamine 1.0 mg/kg (n = 20), and a single dose of midazolam 0.045 mg/kg (active placebo) (n = 19). The study assessments (HAM-D-6, MADRS, SDQ, PAS, CGI-S, and CGI-I) were performed at days 0, 1, 3 (endpoint), 5, 7, 14, and 30 to assess the safety and efficacy. The overall group × time interaction effect was significant for the primary outcome measure, the HAM-D-6. In post hoc pairwise comparisons controlling for multiple comparisons, standard dose (0.5 mg/kg) and high dose (1 mg/kg) of intravenous ketamine were superior to active placebo; a low dose (0.1 mg/kg) was significant only prior to adjustment (p = 0.02, p-adj = 0.14, d = -0.82 at day 1). Most of the interaction effect was due to differences at day 1, with no significant adjusted pairwise differences at day 3. This pattern generally held for secondary outcomes. The infusions of ketamine were relatively well tolerated compared to active placebo, except for greater dissociative symptoms and transient blood pressure elevations with the higher doses. Our results suggest that there is evidence for the efficacy of the 0.5 mg/kg and 1.0 mg/kg subanesthetic doses of IV ketamine and no clear or consistent evidence for clinically meaningful efficacy of lower doses of IV ketamine. Trial Registration: NCT01920555.

Project description:ImportanceRacial and ethnic disparities in pain management have been characterized in many hospital-based settings. Painful traumatic injuries are a common reason for 911 activations of the EMS (emergency medical services) system.ObjectiveTo evaluate whether, among patients treated by EMS with traumatic injuries, race and ethnicity are associated with either disparate recording of pain scores or disparate administration of analgesia when a high pain score is recorded.Design, settings, and participantsThis cohort study included interactions from 2019 to 2021 for US patients ages 14 to 99 years who had experienced painful acute traumatic injuries and were treated and transported by an advanced life support unit following the activation of the 911 EMS system. The data were analyzed in January 2023.ExposuresAcute painful traumatic injuries including burns.Main outcomes and measuresOutcomes were the recording of a pain score and the administration of a nonoral opioid or ketamine.ResultsThe study cohort included 4 781 396 EMS activations for acute traumatic injury, with a median (IQR) patient age of 59 (35-78) years (2 497 053 female [52.2%]; 31 266 American Indian or Alaskan Native [0.7%]; 59 713 Asian [1.2%]; 742 931 Black [15.5%], 411 934 Hispanic or Latino [8.6%], 10 747 Native Hawaiian or other Pacific Islander [0.2%]; 2 764 499 White [57.8%]; 16 161 multiple races [0.3%]). The analysis showed that race and ethnicity was associated with the likelihood of having a pain score recorded. Compared with White patients, American Indian and Alaskan Native patients had the lowest adjusted odds ratio (AOR) of having a pain score recorded (AOR, 0.74; 95% CI, 0.71-0.76). Among patients for whom a high pain score was recorded (between 7 and 10 out of 10), Black patients were about half as likely to receive opioid or ketamine analgesia as White patients (AOR, 0.53; 95% CI, 0.52-0.54) despite having a pain score recorded almost as frequently as White patients.Conclusions and relevanceIn this nationwide study of patients treated by EMS for acute traumatic injuries, patients from racial or ethnic minority groups were less likely to have a pain score recorded, with Native American and Alaskan Natives the least likely to have a pain score recorded. Among patients with a high pain score, patients from racial and ethnic minority groups were also significantly less likely to receive opioid or ketamine analgesia treatment, with Black patients having the lowest adjusted odds of receiving these treatments.