Perioperative Ketamine for Analgesia in Spine Surgery: A Meta-analysis of Randomized Controlled Trials.
ABSTRACT: STUDY DESIGN:A meta-analysis of randomized controlled trials (RCTs). OBJECTIVE:The aim of this study was to evaluate the effectiveness of perioperative supplemental ketamine to reduce postoperative opioid analgesic consumption following spine surgery. SUMMARY OF BACKGROUND DATA:Although low-dose supplemental ketamine has been known to reduce pain after surgery, there is conflicting evidence regarding whether ketamine can be effective to reduce opioid consumption following spine surgery. METHODS:Comprehensive search of PubMed, the Cochrane Central Register of Controlled Trials for prospective RCTs, Web of Science, and Scopus. Patients who received supplemental ketamine were compared with the control group in terms of postoperative morphine equivalent consumption, pain scores, and adverse events. Mean differences (MDs) and 95% confidence intervals (CIs) were used to describe continuous outcomes. Odds ratios (ORs) and 95% CIs were applied to dichotomous outcomes. RESULTS:A total of 14 RCTs comprising 649 patients were selected for inclusion into the meta-analysis. Patients who were administered adjunctive ketamine exhibited less cumulative morphine equivalent consumption at 4, 8, 12, and 24?hours following spine surgery (all Ps??0.05). CONCLUSION:Supplemental perioperative ketamine reduces postoperative opioid consumption up to 24?hours following spine surgery. LEVEL OF EVIDENCE:1.
Project description:<h4>Background and aims</h4>Patient-controlled analgesia (PCA) with morphine is commonly used to provide analgesia following major surgery, but is not sufficient as a monotherapy strategy. This study aimed to compare the adjunctive analgesic effect of ketamine versus tramadol on postoperative analgesia provided via PCA-morphine in patients undergoing major upper abdominal surgeries.<h4>Methods</h4>Forty-two patients undergoing elective major upper abdominal surgery under general anesthesia were allocated to receive either ketamine (load dose of 0.5 mg kg<sup>-1</sup> followed by a continuous infusion of 0.12 mg kg<sup>-1</sup> h<sup>-1</sup> up to 48 postoperative hours; ketamine group, n = 21) or tramadol (load dose of 1 mg kg<sup>-1</sup> followed by a continuous infusion of 0.2 mg kg<sup>-1</sup> h<sup>-1</sup> up to 48 postoperative hours; tramadol group, n = 21) in addition to their standard postoperative analgesia with PCA-morphine. Postoperative data included morphine consumption, visual analog scale (VAS) scores, and side effects during the first 48 postoperative hours after PCA-morphine initiation.<h4>Results</h4>There were no significant differences in patient demographic and intraoperative data between the two groups. Tramadol group had significantly less total morphine consumption during the first 48 postoperative hours (28.905 [16.504] vs 54.524 [20.846] mg [p < 0.001]) and presented significantly lower VAS scores at rest and mobilization (p < 0.05) than the ketamine group. No statistical difference was recorded between the two groups (p > 0.05) regarding postoperative cough, sedation, hallucinations, pruritus, urine retention, and postoperative nausea and vomiting. However, patients in the ketamine group reported dry mouth more frequently than patients in the tramadol group (p = 0.032).<h4>Conclusions</h4>Postoperative administration of tramadol was superior to ketamine due to significantly reduced opioid consumption and better pain scores in patients receiving PCA-morphine after major upper abdominal surgery.
Project description:Ketamine, an N-methyl-D-aspartate (NMDA) receptor antagonist, has been postulated as an adjuvant analgesic for preventing remifentanil-induced hyperalgesia after surgery. This systematic review and meta-analysis aims to assess the effectiveness of ketamine [racemic mixture and S-(+)-ketamine] in reducing morphine consumption and pain intensity scores after remifentanil-based general anesthesia. We performed a literature search of the PubMed, Web of Science, Scopus, Cochrane, and EMBASE databases in June 2017 and selected randomized controlled trials using predefined inclusion and exclusion criteria. To minimize confounding and heterogeneity, studies of NMDA receptor antagonists other than ketamine were excluded and the selected studies were grouped into those assessing minor or major surgery. Methodological quality was evaluated with the PEDro and JADA scales. The data were extracted and meta-analyses were performed where possible. Twelve RCTs involving 156 adults who underwent minor surgery and 413 adults who underwent major surgery were included in the meta-analysis. When used as an adjuvant to morphine, ketamine reduced postoperative morphine consumption in the first 24 h and postoperative pain intensity in the first 2 h in the minor and major surgery groups. It was also associated with significantly reduced pain intensity in the first 24 h in the minor surgery group. Time to the first rescue analgesia was longer in patients who received ketamine and underwent major surgery. No significant differences in the incidence of ketamine-related adverse effects were observed among patients in the intervention group and controls. This systematic review and meta-analysis show that low-dose (?0.5 mg/kg for iv bolus or ?5 ?g/kg/min for iv perfusion) of ketamine reduces postoperative morphine consumption and pain intensity without increasing the incidence of adverse effects.
Project description:BACKGROUND:The analgesic properties of ketamine are associated with its non-competitive antagonism of the N-methyl-D-aspartate receptor; these receptors exhibit an excitatory function on pain transmission and this binding seems to inhibit or reverse the central sensitization of pain. In the literature, the value of this anesthetic for preemptive analgesia in the control of postoperative pain is uncertain. The objective of this study was to ascertain whether preoperative low-dose ketamine reduces postoperative pain and morphine consumption in adults undergoing colon surgery. METHODS:In a double-blind, randomized trial, 48 patients were studied. Patients in the ketamine group received 0.5 mg/kg intravenous ketamine before surgical incision, while the control group received normal saline. The postoperative analgesia was achieved with a continuous infusion of morphine at 0.015 mg?kg-¹?h-¹ with the possibility of 0.02 mg/kg bolus every 10 min. Pain was assessed using the Visual Analog Scale (VAS), morphine consumption, and hemodynamic parameters at 0, 1, 2, 4, 8, 12, 16, and 24 hours postoperatively. We quantified times to rescue analgesic (Paracetamol), adverse effects and patient satisfaction. RESULTS:No significant differences were observed in VAS scores between groups (P>0.05), except at 4 hours postoperatively (P=0.040). There were no differences in cumulative consumption of morphine at any time point (P>0.05). We found no significant differences in incremental postoperative doses of morphine consumption in bolus, except at 12 h (P =0.013) and 24 h (P =0.002). The time to first required rescue analgesia was 70 ± 15.491 min in the ketamine group and 44 ± 19.494 min in the control (P>0.05). There were no differences in hemodynamic parameters or patient satisfaction (P>0.05). CONCLUSIONS:Preoperative low-dose-ketamine did not show a preemptive analgesic effect or efficacy as an adjuvant for decreasing opioid requirements for postoperative pain in patients receiving intravenous analgesia with morphine after colon surgery.
Project description:Background: The days following surgery are a critical period where the use of opioids predicts long-term outcomes in adults. It is currently unknown as to whether opioid consumption throughout the acute postoperative period is associated with long-term outcomes in pediatric patients. The aims of this study were to characterize opioid consumption trajectories in the acute postoperative period, identify predictors of trajectory membership and determine associations between opioid consumption trajectories and long-term patient outcomes. Materials and methods: Medication use, pain and mental health status were assessed at baseline in adolescents with idiopathic scoliosis who were scheduled for spinal fusion surgery. Cumulative 6-hr opioid consumption was recorded for up to 5 days after spinal surgery. At 6 months after surgery, medication use, pain and functional activity were evaluated. Growth mixture modeling was used to identify opioid trajectories. Results: One hundred and six patients were included in the study. Mean cumulative 6-hr opioid consumption in the acute postoperative period was 13.23±5.20 mg/kg. The model with the best fit contained 5 acute postoperative trajectories and a quadratic term (AIC =6703.26, BIC =6767.19). Two types of patient behaviors were identified: high opioid consumers (trajectories 4 and 5) and low opioid consumers (trajectories 1, 2 and 3). Intraoperative intrathecal morphine dose was a predictor of trajectory membership (p=0.0498). Opioid consumption during the acute postoperative period was not significantly associated with pain, functional activity or pain medication use at 6 months after surgery. Conclusion: In pediatric patients, intraoperative intrathecal morphine dose predicts opioid consumption in the acute postoperative period. Importantly, opioid consumption during this period does not affect long-term outcomes in pediatric patients after a spine surgery.
Project description:BACKGROUND:Chronic opioid use is a significant public health concern. Surgery is a risk factor for developing chronic opioid use. Patients undergoing major spine surgery frequently are prescribed opioids preoperatively and may be at risk for chronic opioid use postoperatively. The aim of this study was to investigate the incidence of and perioperative risk factors associated with chronic opioid use after major spine surgery. METHODS:The records of patients who underwent elective major spine surgery at the University of Virginia between March 2011 and February 2016 were retrospectively reviewed. The primary outcome was chronic opioid use through 12 months postoperatively. Demographic data, medical comorbidities, preoperative pain scores, and medication use including daily morphine-equivalent (ME) dose, intraoperative use of lidocaine and ketamine, estimated blood loss, postoperative pain scores and medication use, and postoperative opioid use were collected. Logistic regression models were used to examine factors associated with chronic opioid use. RESULTS:Of 1477 patient records reviewed, 412 patients (27.9%) were opioid naive and 1065 patients (72.3%) used opioids before surgery. Opioid data were available for 1325 patients, while 152 patients were lost to 12-month follow-up and were excluded. Of 958 preoperative opioid users, 498 (52.0%) remained chronic users through 12 months. There was a decrease in opioid dosage (mg ME) from preoperative to 12 months postoperatively with a mean difference of -14.7 mg ME (standard deviation, 1.57; 95% confidence interval [CI], -17.8 to -11.7). Among 367 previously opioid-naive patients, 67 (18.3%) became chronic opioid users. Factors associated with chronic opioid use were examined using logistic regression models. Preoperative opioid users were nearly 4 times more likely to be chronic opioid users through 12 months than were opioid-naive patients (odds ratio, 3.95; 95% CI, 2.51-6.33; P < .001). Mean postoperative pain score (0-10) was associated with increased odds of chronic opioid use (odds ratio for a 1 unit increase in pain score 1.25, 95% CI, 1.13-1.38; P < .001). Use of intravenous ketamine or lidocaine was not associated with chronic opioid use through 12 months. CONCLUSIONS:Greater than 70% of patients presenting for major spine surgery used opioids preoperatively. Preoperative opioid use and higher postoperative pain scores were associated with chronic opioid use through 12 months. Use of ketamine and lidocaine did not decrease the risk for chronic opioid use. Surveillance of patients for these factors may identify those at highest risk for chronic opioid use and target them for intervention and reduction strategies.
Project description:<h4>Introduction</h4>Thoracolumbar interfascial plane (TLIP) block has been discussed widely in spine surgery. The aim of our study is to evaluate analgesic efficacy and safety of TLIP block in spine surgery.<h4>Method</h4>We performed a quantitative systematic review. Randomized controlled trials that compared TLIP block to non-block care or wound infiltration for patients undergoing spine surgery and took the pain or morphine consumption as a primary or secondary outcome were included. The primary outcome was cumulative opioid consumption during 0-24-hour. Secondary outcomes included postoperative pain intensity, rescue analgesia requirement, and adverse events.<h4>Result</h4>9 randomized controlled trials with 539 patients were included for analysis. Compared with non-block care, TLIP block was effective to decrease the opioid consumption (WMD -16.00; 95%CI -19.19, -12.81; p<0.001; I2 = 71.6%) for the first 24 hours after the surgery. TLIP block significantly reduced postoperative pain intensity at rest or movement at various time points compared with non-block care, and reduced rescue analgesia requirement ((RR 0.47; 95%CI 0.30, 0.74; p = 0.001; I2 = 0.0%) and postoperative nausea and vomiting (RR 0.58; 95%CI 0.39, 0.86; p = 0.006; I2 = 25.1%). Besides, TLIP block is superior to wound infiltration in terms of opioid consumption (WMD -17.23, 95%CI -21.62, -12.86; p<0.001; I2 = 63.8%), and the postoperative pain intensity at rest was comparable between TLIP block and wound infiltration.<h4>Conclusion</h4>TLIP block improved analgesic efficacy in spine surgery compared with non-block care. Furthermore, current literature supported the TLIP block was superior to wound infiltration in terms of opioid consumption.
Project description:Purpose:This study aimed to compare the effects of ketamine and ketamine associated with magnesium on opioid consumption and pain scores in patients undergoing abdominoplasty and/or liposuction compared to standard treatment. Patients and Methods:A total of 63 patients were included and randomized as follows: 21 patients in the Control group, 20 patients in the Ketamine group (Ket), and 22 patients in the Ketamine-magnesium group (KetMag). The KetMag group received an IV bolus of 0.3 mg/kg of ketamine and 50 mg/kg magnesium, followed by continuous infusion of ketamine (0.15 mg/kg/h) and magnesium (10 mg/kg/h) until extubation. The Ket group received the same bolus and infusion of ketamine, together with a bolus and continuous infusion of placebo instead of magnesium. The Control group received saline instead of ketamine and magnesium. The groups were compared in morphine consumption during the first 12h, body-postoperative pain and disability scale until the 90th day, the time until the first morphine request on the PCA pump, pain scores, and the adverse effects related to the use of study drugs. Results:The KetMag group had a lower morphine consumption by almost 50% during the first 12h than the Control and the Ket groups. In addition, the KetMag group required the first dose of morphine later than the other two groups. There were no differences in the adverse effects of the proposed treatments. Finally, multiple linear regression and a nonlinear approach analysis indicated that the Control group experienced a higher degree of pain and increased morphine consumption per hour than Ket and KetMag groups. Conclusion:Co-administration of intraoperative ketamine plus magnesium and ketamine alone are an effective and easy regime for reducing pain and opioid consumption in the postoperative period.
Project description:OBJECTIVES:This study aims to evaluate the effects of two different doses of intraarticular ketamine on visual analog scale (VAS) scores at rest and movement, time to first analgesic requirement, and 24-h morphine consumption in patients undergoing arthroscopic meniscectomy as well as to assess the frequency of postoperative nausea&vomiting, respiratory depression, pruritus, urinary retention, and constipation and to compare the time to discharge. PATIENTS AND METHODS:This prospective randomized double-blind study was performed between August 2013 and August 2014 on 75 patients (32 males, 43 females; mean age 46.7±13 years; range, 18 to 75 years) with American Society of Anesthesiologists scores of I-II scheduled for unilateral meniscectomy. Patients were randomized to receive 0.5 mg.kg-1 ketamine (group K1), 1 mg.kg-1 ketamine (group K2) or saline (group S) to a total volume of 20 mL intraarticularly at the end of the surgery. All patients were performed periarticular 10 mL 0.5% bupivacaine infiltration. Visual analog scale at rest and during passive knee movement was used to evaluate pain both preoperatively and at postoperative 0, 30 min, and 1, 2, 4, 6, 12, and 24 h. Time to first analgesic requirement and morphine consumption were recorded. RESULTS:Visual analog scale scores at rest and during movement at postoperative 0 were significantly reduced in group K2 compared with group S (p<0.05). The first analgesic requirement time was significantly longer in group K1 (76.9±25.2 min) and group K2 (93.4±26.1 min) than group S (29.3±7.1 min). Morphine consumption was lower in group K2 compared to group K1 and group S at postoperative 30 min, and 1 and 2 h. However, 24-h morphine consumption was similar in all groups. CONCLUSION:Intraarticular injection of 0.5 mg.kg-1 and 1 mg.kg-1 ketamine for postoperative pain management provided similar analgesic efficacy. However, high dose ketamine more noticeably decreased opioid requirement in the early postoperative period.
Project description:<h4>Background</h4>Gabapentinoid drugs, which include gabapentin and pregabalin, play an established role in the management of neuropathic pain. However, whether preoperative administration of gabapentinoids has a beneficial role in controlling acute pain after spinal surgery is unknown. We performed a systematic review and meta-analysis of randomized controlled trials (RCTs) to determine the efficacy and safety of the preoperative use of gabapentinoids (gabapentin and pregabalin) for the treatment of acute postoperative pain following spinal surgery.<h4>Methods</h4>In March 2017, a systematic computer-based search was conducted in PubMed, EMBASE, Web of Science, Cochrane Library, and Google databases. RCTs comparing gabapentinoids (gabapentin and pregabalin) with placebo in patients undergoing spine surgery were retrieved. The primary endpoint was the visual analogue scale (VAS) score with rest or mobilization at 6, 12, 24, and 48?hours and cumulative morphine consumption at 24 and 48?hours. The secondary outcomes were complications of nausea, vomiting, sedation, dizziness, headache, urine retention, pruritus, and visual disturbances. After tests for publication bias and heterogeneity among studies were performed, data were aggregated for random-effects models when necessary.<h4>Results</h4>Sixteen clinical studies (gabapentin group n?=?8 and pregabalin group n?=?8) were ultimately included in the meta-analysis. Gabapentinoids were associated with reduced pain scores at 6, 12, 24, and 48?hours. Similarly, gabapentinoids were associated with a reduction in cumulative morphine consumption at 24 and 48?hours. Furthermore, gabapentinoids can significantly reduce the occurrence of nausea, vomiting, and pruritus. There were no significant differences in the occurrence of sedation, dizziness, headache, visual disturbances, somnolence, or urine retention.<h4>Conclusions</h4>Preoperative use of gabapentinoids was able to reduce postoperative pain, total morphine consumption, and morphine-related complications following spine surgery. Further studies should determine the optimal dose and whether pregabalin is superior to gabapentin in controlling acute pain after spine surgery.
Project description:BACKGROUND:The primary goal of this study was to determine whether administration of intrathecal morphine reduces postoperative pain. The secondary goal was to determine the effect of intrathecal morphine upon circulating levels of the weakly analgesic endocannabinoids, anandamide (AEA) and 2-arachidonoylglycerol (2-AG), and the related lipids palmitoylethanolamide (PEA) and oleoylethanolamide (OEA). METHODS:Forty two total knee arthroplasty (TKA) patients were enrolled in a prospective, double-blinded, randomized study. The intervention consisted of intrathecal morphine (200 ?g) or placebo administered at the time of the spinal anesthesia. Postoperative pain was measured during the first 4 h after surgery while serum levels of AEA, 2-AG, PEA, OEA, and cortisol were measured at baseline and 4 h after surgery. RESULTS:Administration of intrathecal morphine reduced postoperative pain 4 h after TKA surgery compared to placebo (p?=?0.005) and reduced postoperative systemic opioid consumption (p?=?0.001). At baseline, intrathecal morphine led to a significant reduction in AEA, 2-AG, and OEA levels but did not affect PEA or cortisol levels. In patients administered intrathecal placebo, 2-AG levels were elevated 4 h after surgery; whereas patients receiving intrathecal morphine showed reductions in AEA, PEA, and OEA when compared to placebo. At 4 h after TKA surgery cortisol levels were significantly elevated in the placebo group and reduced in those receiving morphine. CONCLUSIONS:These results indicate that intrathecal morphine reduces postoperative pain in TKA patients. Furthermore, activation of central opioid receptors negatively modulates the endocannabinoid tone, suggesting that potent analgesics may reduce the stimulus for production of peripheral endocannabinoids. This study is the first to document the existence of rapid communication between the central opioid and peripheral endocannabinoid systems in humans. TRIAL REGISTRATION:This trial was registered retrospectively. TRIAL REGISTRY:NCT02620631 . Study to Examine Pain Relief With Supplemental Intrathecal Morphine in TKA Patients, NCT02620631 , 12/03/2015.