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.
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: To evaluate the preemptive analgesia effects of ketamine for postoperative pain. METHODS: PubMed, EMBASE and Cochrane Library were searched to identify randomized controlled trials (RCTs) involved in ketamine for preemptive analgesic up to March 2013. The relative risk (RR) or mean difference (MD) as well as the confounding 95% confidence interval (CI) were calculated by the Revman 5.0 software. RESULTS: A total of five studies including 266 patients were included in this meta-analysis. Overall, ketamine could reduce the postoperative morphine consumption and significantly prolong the time to first analgesic (p < 0.00001, MD = 0.91, 95% CI: 0.56 to 1.26). However, there was no significant difference in indicators of nausea and vomiting (p = 0.87, RR = 1.04, 95% CI: 0.67 to 1.60), surgical time (p = 0.41, MD = -2.13, 95% CI: -7.21 to 2.95) and anesthetic time (p = 0.53, MD = -1.54, 95% CI: -6.34 to -3.26) between ketamine and control group. CONCLUSIONS: Ketamine was able to accomplish some preemptive analgesic effects of reducing postoperative morphine consumption and prolonging the time to first analgesic. Meanwhile, ketamine was as safe as physiological saline in side effects of nausea and vomiting. .
PURPOSE: Perioperative intravenous ketamine may be a useful addition in pain management regimens. Previous systematic reviews have included all methods of ketamine administration, and heterogeneity between studies has been substantial. This study addresses this issue by narrowing the inclusion criteria, using a random effects model, and performing subgroup analysis to determine the specific types of patients, surgery, and clinical indications which may benefit from perioperative ketamine administration.
SOURCE: We included published studies from 1966 to 2010 which were randomized, double-blinded, and placebo-controlled using intravenous ketamine (bolus or infusion) to decrease postoperative pain. Studies using any form of regional anesthesia were excluded. No limitation was placed on the ketamine dose, patient age, or language of publication.
PRINCIPAL FINDINGS: Ninety-one comparisons in seventy studies involving 4,701 patients met the inclusion criteria (2,652 in ketamine groups and 2,049 in placebo groups). Forty-seven of these studies were appropriate for evaluation in the core meta-analysis, and the remaining 23 studies were used to corroborate the results. A reduction in total opioid consumption and an increase in the time to first analgesic were observed across all studies (P < 0.001). The greatest efficacy was found for thoracic, upper abdominal, and major orthopedic surgical subgroups. Despite using less opioid, 25 out of 32 treatment groups (78%) experienced less pain than the placebo groups at some point postoperatively when ketamine was efficacious. This finding implies an improved quality of pain control in addition to decreased opioid consumption. Hallucinations and nightmares were more common with ketamine but sedation was not. When ketamine was efficacious for pain, postoperative nausea and vomiting was less frequent in the ketamine group. The dose-dependent role of ketamine analgesia could not be determined.
CONCLUSION: Intravenous ketamine is an effective adjunct for postoperative analgesia. Particular benefit was observed in painful procedures, including upper abdominal, thoracic, and major orthopedic surgeries. The analgesic effect of ketamine was independent of the type of intraoperative opioid administered, timing of ketamine administration, and ketamine dose.
Ketamine, an N-methyl-D-aspartate receptor antagonist, is known to be analgesic and to induce psychomimetic effects. Benefits and risks of ketamine for the control of postoperative pain are not well understood. We systematically searched for randomised comparisons of ketamine with inactive controls in surgical patients, reporting on pain outcomes, opioid sparing, and adverse effects. Data were combined using a fixed effect model. Fifty-three trials (2839 patients) from 25 countries reported on a large variety of different ketamine regimens and surgical settings. Sixteen studies tested prophylactic intravenous ketamine (median dose 0.4 mg/kg, range (0.1-1.6)) in 850 adults. Weighted mean difference (WMD) for postoperative pain intensity (0-10 cm visual analogue scale) was -0.89 cm at 6 h, -0.42 at 12 h, -0.35 at 24 h and -0.27 at 48 h. Cumulative morphine consumption at 24 h was significantly decreased with ketamine (WMD -15.7 mg). There was no difference in morphine-related adverse effects. The other 37 trials tested in adults or children, prophylactic or therapeutic ketamine orally, intramuscularly, subcutaneously, intra-articulary, caudally, epidurally, transdermally, peripherally or added to a PCA device; meta-analyses were deemed inappropriate. The highest risk of hallucinations was in awake or sedated patients receiving ketamine without benzodiazepine; compared with controls, the odds ratio (OR) was 2.32 (95%CI, 1.09-4.92), number-needed-to-harm (NNH) 21. In patients undergoing general anaesthesia, the incidence of hallucinations was low and independent of benzodiazepine premedication; OR 1.49 (95%CI 0.18-12.6), NNH 286. Despite many published randomised trials, the role of ketamine, as a component of perioperative analgesia, remains unclear.
Ketamine hydrochloride is a well known general anesthetic and short acting analgesic in use for almost 3 decades. The role of the NMDA receptor in the processing of nociceptive input has led naturally to renewed clinical interest in N-methyl-D-aspartate (NMDA) receptor antagonists such as ketamine. This paper reviews the use and efficacy of low-dose ketamine in the management of acute postoperative pain. The literature was obtained from a computer search of the MEDLINE database from 1966 through December 1998. Studies were included for review if they were randomized, prospective, controlled, double-blind and reported pain scores. We evaluate the clinical literature and discuss the efficacy of low-dose ketamine in the management of acute postoperative pain when administered alone or in conjunction with other agents via the oral, intramuscular, subcutaneous, intravenous and intraspinal routes. Low-dose ketamine is defined as a bolus dose of less than 2 mg/g when given intramuscularly or less than 1 mg/kg when administered via the intravenous or epidural route. For continuous i.v. administration low-dose ketamine is defined as a rate of < or =20 microg/kg per min. We conclude that ketamine may provide clinicians with a tool to improve postoperative pain management and to reduce opioid related adverse effects. The evidence suggests that low-dose ketamine may play an important role in postoperative pain management when used as an adjunct to local anesthetics, opioids, or other analgesic agents. Further research is required in the following areas: (a) dose-finding studies for ketamine as an adjunct to opioids and local anesthetics (b) efficacy and optimal route of administration (c) the role of S(+)-ketamine; (d) the influence of ketamine on long-term outcome such as chronic pain (e) long-term physical and chemical stability of mixtures containing ketamine (f) spinal toxicity of ketamine and (g) effects of low-dose ketamine on cognitive and memory functioning after surgery.
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.
