PURPOSE: To determine whether ketamine added to morphine or hydromorphone patient-controlled analgesia (PCA) provides clinically relevant reductions in postoperative pain, opioid requirements, and adverse events when compared with morphine or hydromorphone PCA in adults undergoing surgery.
SOURCE: We systematically searched six databases up to June 2, 2015 for randomized controlled trials (RCTs) comparing ketamine plus morphine/hydromorphone PCA vs morphine/hydromorphone PCA for postoperative pain in adults.
PRINCIPAL FINDINGS: Thirty-six RCTs including 2,502 patients proved eligible, and 22 of these were at low risk of bias. The addition of ketamine to morphine/hydromorphone PCA decreased postoperative pain intensity at six to 72 hr when measured at rest (weighted mean difference [WMD] on a 10-cm visual analogue scale ranged from -0.4 to -1.3 cm) and during mobilization (WMD ranged from -0.4 to -0.5 cm). Adjunctive ketamine also significantly reduced cumulative morphine consumption at 24-72 hr by approximately 5-20 mg. Predefined subgroup analyses and meta-regression did not detect significant differences across subgroups, including a dose-response relationship. There was no significant difference in patient satisfaction scores at 24 and 48 hr. Nevertheless, the addition of ketamine to morphine/hydromorphone PCA significantly reduced postoperative nausea and vomiting (relative risk, 0.71; 95% confidence interval [CI], 0.60 to 0.85; absolute risk reduction, 8.9%; 95% CI, 4.6 to 12.2). Significant effects on other adverse events (e.g., hallucinations, vivid dreams) were not detected, though only a few studies reported on them.
CONCLUSIONS: Adding ketamine to morphine/hydromorphone PCA provides a small improvement in postoperative analgesia while reducing opioid requirements. Adjunctive ketamine also reduces postoperative nausea and vomiting without a detected increase in other adverse effects; however, adverse events were probably underreported.
Background Intravenous ketamine has been used during general and regional anaesthesia for caesarean section. No systematic review and meta-analysis on the desired effects and adverse effects of ketamine administration during caesarean section have yet been performed. Methods After a systematic literature search a meta-analysis was conducted with the random effects model. Weighted mean difference (WMD) or risk ratio and 95% confidence intervals (CIs) were computed. Results Twelve randomised controlled double-blind trials comprising 953 patients were included: seven studies reported on spinal anaesthesia and five on general anaesthesia. Significant differences in the aforementioned outcome variables were found only in the spinal anaesthesia studies. In the spinal anaesthesia studies the time to the first analgesic request was significantly longer in ketamine-treated women, the WMD was 49.36 min (95% CI 43.31-55.41); visual analogue scale pain scores at rest 2 h after surgery were significantly lower. No differences were observed for maternal nausea, vomiting, pruritus, and psychomimetic effects. Only few data were found for neonatal outcomes. Conclusions We conclude that ketamine enhances post-operative analgesia after caesarean section under spinal anaesthesia. There is a paucity of data for several maternal adverse effects as well as for neonatal well-being. Further studies are needed for general anaesthesia.
BACKGROUND: Perioperative neuropathic pain is under‐recognized and often undertreated. Chronic pain may develop after any routine surgery, but it can have a far greater incidence after amputation, thoracotomy or mastectomy. The peak noxious barrage due to the neural trauma associated with these operations may be reduced in the perioperative period with the potential to reduce the risk of chronic pain. Databases and data treatment: A systematic review of the evidence for perioperative interventions reducing acute and chronic pain associated with amputation, mastectomy or thoracotomy. RESULTS: Thirty‐two randomized controlled trials met the inclusion criteria. Gabapentinoids reduced pain after mastectomy, but a single dose was ineffective for thoracotomy patients who had an epidural. Gabapentinoids were ineffective for vascular amputees with pre‐existing chronic pain. Venlafaxine was associated with less chronic pain after mastectomy. Intravenous and topical lidocaine and perioperative EMLA (eutectic mixture of local anaesthetic) cream reduced the incidence of chronic pain after mastectomy, whereas local anaesthetic infiltration appeared ineffective. The majority of the trials investigating regional analgesia found it to be beneficial for chronic symptoms. Ketamine and intercostal cryoanalgesia offered no reduction in chronic pain. Total intravenous anaesthesia (TIVA) reduced the incidence of post‐thoracotomy pain in one study, whereas high‐dose remifentanil exacerbated chronic pain in another. CONCLUSIONS: Appropriate dose regimes of gabapentinoids, antidepressants, local anaesthetics and regional anaesthesia may potentially reduce the severity of both acute and chronic pain for patients. Ketamine was not effective at reducing chronic pain. Intercostal cryoanalgesia was not effective and has the potential to increase the risk of chronic pain. TIVA may be beneficial but the effects of opioids are unclear. (PsycInfo Database Record (c) 2021 APA, all rights reserved)
OBJECTIVE: As an analgesic and N-methyl-D-aspartate receptor antagonist, ketamine has been increasingly used as an adjunct in the management of acute perioperative pain. Although several meta-analyses have examined low-dose intravenous (IV) ketamine, they do not distinguish between different types of infusions. Additionally, the many clinical trials published on ketamine vary by regimen of administration and surgical site. This review seeks to exclusively examine the evidence supporting the use of low-dose IV infusion of ketamine for the management of perioperative pain.
METHODS: We searched Medline for any clinical trials or meta-analyses that were conducted on low-dose IV infusion of ketamine between 1966 and November 2013. Using six equations, we were left with 695 references. Of those, five meta-analyses and 39 clinical trials met the criteria to be included our review. These clinical trials represent 2,482 patients, 1,403 of whom received ketamine. We then examined the efficacy of low-dose IV ketamine by regimen and site of surgery using pain scores and opioid consumption as endpoints. Finally, we assessed the safety and long-term impact of low-dose ketamine.
RESULTS: Low-dose IV ketamine reduces opioid consumption by 40%. It also lowers pain scores, but these findings are less clear. No major complications have been reported with low-dose IV infusion of ketamine when given up to 48 hours after surgery. While our review lends support to using low-dose IV infusion of ketamine in the management of perioperative pain, its optimal dose and regimen remain to be determined.
CONCLUSIONS: Thirty-nine clinical trials assessed a continuous infusion or a bolus of low-dose ketamine for postoperative analgesia using reduction of pain scores or reduction of the opioid consumption as the primary endpoint. The mean reduction of opioid consumption when using low-dose IV infusion ketamine (infusion rate less than 1.2 mg/kg/h) is 40%. Ketamine also reduces pain scores, but the amplitude of the effect is less clear. No major complications have been reported with low-dose IV infusion of ketamine up to 48 hours following surgery.
While post-operative pain routinely resolves, persistent post-surgical pain (PPSP) is common in certain surgeries; it causes disability, lowers quality of life and has economic consequences. The objectives of this systematic review and meta-analysis were to evaluate the effectiveness of ketamine in reducing the prevalence and severity of PPSP and to assess safety associated with its use. We searched the Cochrane Central Register of Controlled Trials, MEDLINE and EMBASE through December 2012 for articles in any language. We included randomized, controlled trials in adults in which ketamine was administered perioperatively via any route. Seventeen studies, the majority of which administered ketamine intravenously, met all inclusion criteria. The overall risk of developing PPSP was not significantly reduced at any time point in the ketamine group vs. placebo, nor did comparisons of pain severity scores reach statistical significance. Sensitivity analysis of exclusively intravenous ketamine studies included in this meta-analysis demonstrated statistically significant reductions in risk of developing PPSP at 3 and 6 months (P = 0.01 and P = 0.04, respectively). Adverse event rates were similar between ketamine and placebo groups. The study data from our review are heterogeneous and demonstrate efficacy of intravenously administered ketamine only in comparison with placebo. Highly variable timing and dosing of ketamine in these studies suggest that no unifying effective regimen has emerged. Future research should focus on clinically relevant outcomes, should stratify patients with pre-existing pain and possible central sensitization and should enroll sufficiently large numbers to account for loss to follow-up in long-term studies.
PURPOSE: Ketamine is currently the N-methyl-D-aspartate receptor channel blocker in clinical use. Morphine in pain management is usually limited by adverse effect such as nausea and vomiting. Adjuvant treatment with ketamine may be value in giving better analgesia with fewer adverse effects. The purpose of this meta-analysis was to evaluate the differences when patients received morphine with adjuvant ketamine (MK) compared with higher dose of morphine (MO) for acute pain.
METHODS: The PubMed, EMBASE and the Cochrane Library databases were searched (Last search performed on July 1, 2014) by two reviewers independently. Data were extracted independently by the same two individuals who searched the studies.
RESULTS: A total of 7 trials involving 492 patients were included in the current analysis. We found pain scores were lower in the MK group compared to the MO group [MD 2.19, 95% CI (1.24, 3.13) P<0.00001]. And more patients in the MO required diclofenac [OR 1.97, 95% CI (1.06, 3.67) P=0.03]. Furthermore, morphine plus ketamine can reduced post-operative nausea and vomiting (PONV) [OR 3.71, 95% CI (2.37, 5.80) P<0.00001]. Importantly, the wakefulness scores for the MK group were consistently and significantly better than those for the MO group [MD -1.53, 95% CI (-2.67, -0.40) P=0.008].
CONCLUSION: The use of ketamine plus 1/4~2/3 the dose of morphine is better than higher dose of morphine alone in reducing pain scores, and rescuing analgesic requirement. It also improved PONV and wakefulness.
OBJECTIVES: Peri-operative ketamine peritonsillar infiltration in children can reduce the incidence of postoperative nausea and vomiting (PONV), but its postoperative analgesic time is short. A previous meta-analysis in 2011 was inconclusive due to insufficient data. Consequently, we updated the meta-analysis to verify the role of ketamine peritonsillar infiltration for tonsillectomy in pediatric patients.
METHODS: Ten randomized controlled trials with a total of 522 cases were included. Pain intensity was measured by standard modified CHEOPS score.
RESULTS: The pain scores of ketamine group at 30 min and 60 min were significantly lower than placebo group after surgery [weighted mean difference (WMD) -1.20, 95% CI -2.20 to -0.19, P=0.02; WMD -1.71, 95% CI -2.12 to -0.22, P=0.02]. Analgesic requirement in ketamine group were less than placebo group [risk ratio (RR) 0.51, 95% CI 0.26-0.97; P=0.04]. Moreover, the incidence of PONV was lower in ketamine group. (RR 0.73, 95% CI 0.54-0.97; P=0.03). However, there were no differences between these two groups in operation time, anesthesia time, first analgesic time and pain score at 120 min.
CONCLUSIONS: Compared to placebo, ketamine peritonsillar infiltration can relieve postoperative pain within one hour but not at 120 min and reduces analgesic requirement and incidence of PONV. Moreover, there was no difference in the first analgesic time.
BACKGROUND AND OBJECTIVES: The goal of this meta-analysis study was to perform a systematic review of the literature on the effects of ketamine on postoperative pain following tonsillectomy and adverse effects in children.
SUBJECTS AND METHODS: Two authors independently searched three databases (MEDLINE, SCOPUS, Cochrane) from their inception of article collection to February 2014. Studies that compared preoperative ketamine administration (ketamine groups) with no treatment (control group) or opioid administration (opioid group) where the outcomes of interest were postoperative pain intensity, rescue analgesic consumption, or adverse effects (sedation, nausea and vomiting, bad dream, worsening sleep pattern, and hallucination) 0-24 hours after leaving the operation room were included in the analysis.
RESULTS: The pain score reported by the physician during first 4 hours and need for analgesics during 24 hours postoperatively was significantly decreased in the ketamine group versus control group and was similar with the opioid group. In addition, there was no significant difference between ketamine and control groups for adverse effects during 24 hours postoperatively. In the subgroup analyses (systemic and local administration) regarding pain related measurements, peritonsillar infiltration of ketamine was more effective in reducing the postoperative pain severity and need for analgesics.
CONCLUSION: Preoperative administration of ketamine systemically or locally could provide pain relief without side-effects in children undergoing tonsillectomy. However, considering the insufficient evaluation of efficacy of ketamine according to the administration methods and high heterogeneity in some parameters, further clinical trials with robust research methodology should be conducted to confirm the results of this study.
BACKGROUND: Meta-analysis was performed to evaluate the preventive effects of N-methyl-D-aspartate (NMDA) receptor antagonists on remifentanil-induced increase in postoperative pain and analgesic requirement in patients.
METHODS: Pubmed, EMBase, Springer and the Cochrane Controlled Trials Register were searched to identify all randomized controlled trials (RCTs) published to November 2010 which investigated the preventive effects of NMDA receptor antagonists on remifentanil-induced postoperative hyperalgesia and/or tolerance. The studies listed at the end of these articles as reference were also searched. Two authors independently assessed the quality of each study met the inclusion criteria and extracted data. Then Meta-analysis was perfomed using RevMan 5.0 software. The outcomes analyzed were the postoperative analgesic consumption, pain intensity scores, time to first analgesic request, and the incidence of adverse effects.
RESULTS: A total of 623 patients (223 in the ketamine group, 87 in the magnesium group and 313 in the control group) from 14 prospective RCTs were included in the Meta-analysis. Administration of NMDA receptor antagonists reduced the pain scores at 4 hr after operation (P<0.05), and the standardized mean differences (SMD) was -0.21 (95% confidence interval was -0.41 to -0.01). There were no significant differences in postoperative analgesic consumption, pain scores at other time points, time to first analgesic request and the incidence of adverse effects (P>0.05). Further subgroup analyses based on the type of intervention showed that the results were almost the same.
CONCLUSION: These data do not support the use of NMDA receptor antagonists, ketamine and magnesium sulfate to prevent the development of remifentanil-induced postoperative hyperalgesia and tolerance.
To determine whether ketamine added to morphine or hydromorphone patient-controlled analgesia (PCA) provides clinically relevant reductions in postoperative pain, opioid requirements, and adverse events when compared with morphine or hydromorphone PCA in adults undergoing surgery.
SOURCE:
We systematically searched six databases up to June 2, 2015 for randomized controlled trials (RCTs) comparing ketamine plus morphine/hydromorphone PCA vs morphine/hydromorphone PCA for postoperative pain in adults.
PRINCIPAL FINDINGS:
Thirty-six RCTs including 2,502 patients proved eligible, and 22 of these were at low risk of bias. The addition of ketamine to morphine/hydromorphone PCA decreased postoperative pain intensity at six to 72 hr when measured at rest (weighted mean difference [WMD] on a 10-cm visual analogue scale ranged from -0.4 to -1.3 cm) and during mobilization (WMD ranged from -0.4 to -0.5 cm). Adjunctive ketamine also significantly reduced cumulative morphine consumption at 24-72 hr by approximately 5-20 mg. Predefined subgroup analyses and meta-regression did not detect significant differences across subgroups, including a dose-response relationship. There was no significant difference in patient satisfaction scores at 24 and 48 hr. Nevertheless, the addition of ketamine to morphine/hydromorphone PCA significantly reduced postoperative nausea and vomiting (relative risk, 0.71; 95% confidence interval [CI], 0.60 to 0.85; absolute risk reduction, 8.9%; 95% CI, 4.6 to 12.2). Significant effects on other adverse events (e.g., hallucinations, vivid dreams) were not detected, though only a few studies reported on them.
CONCLUSIONS:
Adding ketamine to morphine/hydromorphone PCA provides a small improvement in postoperative analgesia while reducing opioid requirements. Adjunctive ketamine also reduces postoperative nausea and vomiting without a detected increase in other adverse effects; however, adverse events were probably underreported.
Systematic Review Question»Systematic review of interventions
