BACKGROUND: According to current recommendations a multimodal approach is believed to be the gold standard for postoperative pain treatment in children. However, several surveys in the last few years demonstrated that postoperative pain in children is still a serious problem, mainly because opioids are avoided. One of the reasons for this is the fear of severe adverse events following opioid administration. Tramadol is a weak mu-opioid agonist and inhibits reuptake of noradrenaline and serotonin (5HT). Because of a relatively wide therapeutic window and a ceiling effect with a lower risk for severe adverse events (for example respiratory depression) tramadol is a widely used opioid in children. However, the exact efficacy and occurrence of adverse events following tramadol (in comparison with placebo or other opioids) for postoperative pain treatment in children and adolescents are currently not clear.
OBJECTIVES: To assess the effectiveness and side effect profile of tramadol for postoperative pain relief in children and adolescents undergoing different surgical procedures.
SEARCH METHODS: We searched the following electronic databases: the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2014, Issue 6), MEDLINE via PubMed (January 1966 to July 2014) and EMBASE via Ovid (January 1947 to July 2014). There were no restrictions regarding language or date of publication. The reference lists of all included trials were checked for additional studies.
SELECTION CRITERIA: All randomised controlled clinical trials investigating the perioperative administration of tramadol compared to placebo or other opioids for postoperative pain treatment in children and adolescents were included.
DATA COLLECTION AND ANALYSIS: Three review authors independently assessed the study eligibility, performed the data extraction and assessed the risk of bias of included trials.
MAIN RESULTS: Twenty randomised controlled trials involving 1170 patients were included in this systematic review. The overall risk of bias in included trials was assessed as unclear, because concealment of allocation processes and blinding of outcome assessors were poorly described. Due to inconsistent outcome reporting, data from 17 included trials could be pooled for some endpoints only. Eight trials compared tramadol administration with placebo and five trials found that the need for rescue analgesia in the postoperative care unit (PACU) was reduced in children receiving tramadol (RR 0.40; 95% CI 0.20 to 0.78; low quality evidence). Only one trial investigated the number of patients with moderate to severe pain, but a non-validated pain scale was used (very low quality evidence). Four trials compared morphine with tramadol administration. There was no clear evidence of difference in the need for rescue analgesia in the PACU (RR 1.25; 95% CI 0.83 to 1.89; low quality evidence) with tramadol compared with morphine. No trials could be pooled for the outcome 'number of patients with moderate to severe pain'. Three trials were included for the comparison of tramadol with nalbuphine. There was no clear evidence for the need for rescue analgesia in the PACU (RR 0,63; 95% CI 0.16 to 2.45; low quality evidence). Only one trial reported the number of patients with moderate to severe pain, but used a non-validated pain scale (very low quality evidence). Two out of six included trials, which compared pethidine with tramadol, reported the number of children with a need for rescue analgesia within the PACU and showed no clear evidence (RR 0.93; 95% CI 0.43 to 2.02; very low quality evidence). Two trials reported the number of patients with moderate to severe pain and showed a lower RR in patients treated with tramadol (RR 0.64; 95% CI 0.36 to 1.16; low quality evidence). Only one trial was included, which compared tramadol with fentanyl, reporting the number of patients with the need for rescue analgesia (very low quality evidence). Generally, adverse events were poorly reported. Most data could be pooled for the comparison with placebo focusing on the RR for postoperative nausea and vomiting (PONV) in the postoperative care unit and 24 h postoperation. Children treated with tramadol, compared to placebo, did not show clear evidence of benefit for PONV in the postoperative care unit (RR 0.84; 95% CI 0.28 to 2.52; moderate quality evidence) and 24 h postoperation (RR 0.78; 95% CI 0.54 to 1.12; moderate quality evidence).
AUTHORS' CONCLUSIONS: The overall evidence regarding tramadol for postoperative pain in children is currently low or very low and should be interpreted with caution due to small studies and methodological problems (different validated and non-validated pain scales with different pain triggers, missing sample size calculations and missing intention-to-treat analysis). Nevertheless, we demonstrated that tramadol administration might provide appropriate analgesia when compared to placebo; this is based on results showing reduced rescue analgesia in children treated with tramadol compared to placebo. In contrast, the evidence regarding the comparison with other opioids (for example morphine) was uncertain. Adverse events were only poorly reported, so an accurate risk-benefit analysis was not possible.
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.
BACKGROUND: The aim of this quantitative systematic review was to assess the efficacy and adverse effects of ketamine added to caudal local anaesthetics in comparison with local anaesthetics alone in children undergoing urological, lower abdominal, or lower limb surgery.
METHODS: The systematic search, data extraction, critical appraisal, and pooled data analysis were performed according to the PRISMA statement. All randomized controlled trials (RCTs) were included in this meta-analysis and relative risk (RR), mean difference (MD), and the corresponding 95% confidence intervals (CIs) were calculated using the Revman(®) statistical software for dichotomous and continuous outcomes.
RESULTS: Thirteen RCTs (published between 1991 and 2008) including 584 patients met the inclusion criteria. There was a significant longer time to first analgesic requirements in patients receiving ketamine in addition to a local anaesthetic compared with a local anaesthetic alone (MD: 5.60 h; 95% CI: 5.45-5.76; P<0.00001). There was a lower RR for the need of rescue analgesia in children receiving a caudal regional anaesthesia with ketamine in addition to local anaesthetics (RR: 0.71; 95% CI: 0.44-1.15; P=0.16).
CONCLUSIONS: Caudally administered ketamine, in addition to a local anaesthetic, provides prolonged postoperative analgesia with few adverse effects compared with local anaesthetics alone. There is a clear benefit of caudal ketamine, but the uncertainties about neurotoxicity relating to the dose of ketamine, single vs repeated doses and the child's age, still need to be clarified for use in clinical practice.
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.
INTRODUCTION: Balanced analgesia, using both opioid and nonopioids agents, has become the standard care for postoperative pain management. Ketamine, a compound with analgesic and antihyperalgesic properties, has been shown to decrease postoperative pain and opioid requirements in adults. The goal of the present meta-analysis was to investigate postoperative analgesic properties of ketamine in pediatric patients.
MATERIAL AND METHODS: A comprehensive literature search was conducted to identify clinical trials that used ketamine as a perioperative analgesic compound in children and infants. Outcomes measured were postoperative analgesic consumption, pain intensity and duration of sensory block (when ketamine was used by caudal route) during the postoperative care unit (PACU) stay and the early postoperative period (6-24 h after leaving the operative room). The data from each trial were combined to calculate the pooled odds ratios or standard mean differences and their 95% confidence intervals.
RESULTS: Thirty-five randomized, blinded controlled studies were retrieved from the literature. Systemic ketamine was effective in decreasing PACU pain intensity and analgesic requirement but failed to influence early (6-24 h) pain intensity and analgesic requirement. Ketamine administered locally during tonsillectomy, decreased PACU and early (6-24 h) pain intensity and PACU analgesic requirements. Used as an adjuvant for caudal analgesia, ketamine increased the duration of sensory block and PACU analgesic requirement without impacting PACU pain intensity. Ketamine failed to exhibit a postoperative opioid-sparing effect.
CONCLUSIONS: This meta-analysis found that administration of ketamine was associated with decreased PACU postoperative pain intensity and nonopioid analgesic requirement. However, ketamine failed to exhibit a postoperative opioid-sparing effect.
Background. Emergence agitation (EA) in children is increased after sevoflurane anaesthesia. The efficacy of prophylactic treatment is controversial. The aim of this study was to provide a meta-analysis of the studies of the pharmacological prevention of EA in children.MethodsA comprehensive literature search was conducted to identify clinical trials that focused on the prevention of EA in children anaesthetized with sevoflurane, desflurane, or both. The data from each trial were combined using the Mantel-Haenszel model to calculate the pooled odds ratio (OR) and 95 confidence interval. I2 statistics were used to assess statistics heterogeneity and the funnel plot and the Begg-Mazumdar test to assess bias.ResultsThirty- seven articles were found which included a total of 1695 patients in the intervention groups and 1477 in the control ones. Midazolam and 5HT3 inhibitors were not found to have a protective effect against EA [OR=0.88 (0.44, 1.76); OR=0.39 (0.12, 1.31), respectively], whereas propofol [OR=0.21 (0.16, 0.28)], ketamine [OR=0.28 (0.13, 0.60)], 2-adrenoceptors [OR=0.23 (0.17, 0.33)], fentanyl [OR=0.31 (0.18, 0.56)], and peroperative analgesia [OR=0.15 (0.07, 0.34)] were all found to have a preventive effect. Subgroup analysis according to the peroperative analgesia given does not affect the results.ConclusionsThis meta-analysis found that propofol, ketamine, fentanyl, and preoperative analgesia had a prophylactic effect in preventing EA. The analgesic properties of these drugs do not seem to have a role in this effect.
According to current recommendations a multimodal approach is believed to be the gold standard for postoperative pain treatment in children. However, several surveys in the last few years demonstrated that postoperative pain in children is still a serious problem, mainly because opioids are avoided. One of the reasons for this is the fear of severe adverse events following opioid administration. Tramadol is a weak mu-opioid agonist and inhibits reuptake of noradrenaline and serotonin (5HT). Because of a relatively wide therapeutic window and a ceiling effect with a lower risk for severe adverse events (for example respiratory depression) tramadol is a widely used opioid in children. However, the exact efficacy and occurrence of adverse events following tramadol (in comparison with placebo or other opioids) for postoperative pain treatment in children and adolescents are currently not clear.
OBJECTIVES:
To assess the effectiveness and side effect profile of tramadol for postoperative pain relief in children and adolescents undergoing different surgical procedures.
SEARCH METHODS:
We searched the following electronic databases: the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2014, Issue 6), MEDLINE via PubMed (January 1966 to July 2014) and EMBASE via Ovid (January 1947 to July 2014). There were no restrictions regarding language or date of publication. The reference lists of all included trials were checked for additional studies.
SELECTION CRITERIA:
All randomised controlled clinical trials investigating the perioperative administration of tramadol compared to placebo or other opioids for postoperative pain treatment in children and adolescents were included.
DATA COLLECTION AND ANALYSIS:
Three review authors independently assessed the study eligibility, performed the data extraction and assessed the risk of bias of included trials.
MAIN RESULTS:
Twenty randomised controlled trials involving 1170 patients were included in this systematic review. The overall risk of bias in included trials was assessed as unclear, because concealment of allocation processes and blinding of outcome assessors were poorly described. Due to inconsistent outcome reporting, data from 17 included trials could be pooled for some endpoints only. Eight trials compared tramadol administration with placebo and five trials found that the need for rescue analgesia in the postoperative care unit (PACU) was reduced in children receiving tramadol (RR 0.40; 95% CI 0.20 to 0.78; low quality evidence). Only one trial investigated the number of patients with moderate to severe pain, but a non-validated pain scale was used (very low quality evidence). Four trials compared morphine with tramadol administration. There was no clear evidence of difference in the need for rescue analgesia in the PACU (RR 1.25; 95% CI 0.83 to 1.89; low quality evidence) with tramadol compared with morphine. No trials could be pooled for the outcome 'number of patients with moderate to severe pain'. Three trials were included for the comparison of tramadol with nalbuphine. There was no clear evidence for the need for rescue analgesia in the PACU (RR 0,63; 95% CI 0.16 to 2.45; low quality evidence). Only one trial reported the number of patients with moderate to severe pain, but used a non-validated pain scale (very low quality evidence). Two out of six included trials, which compared pethidine with tramadol, reported the number of children with a need for rescue analgesia within the PACU and showed no clear evidence (RR 0.93; 95% CI 0.43 to 2.02; very low quality evidence). Two trials reported the number of patients with moderate to severe pain and showed a lower RR in patients treated with tramadol (RR 0.64; 95% CI 0.36 to 1.16; low quality evidence). Only one trial was included, which compared tramadol with fentanyl, reporting the number of patients with the need for rescue analgesia (very low quality evidence). Generally, adverse events were poorly reported. Most data could be pooled for the comparison with placebo focusing on the RR for postoperative nausea and vomiting (PONV) in the postoperative care unit and 24 h postoperation. Children treated with tramadol, compared to placebo, did not show clear evidence of benefit for PONV in the postoperative care unit (RR 0.84; 95% CI 0.28 to 2.52; moderate quality evidence) and 24 h postoperation (RR 0.78; 95% CI 0.54 to 1.12; moderate quality evidence).
AUTHORS' CONCLUSIONS:
The overall evidence regarding tramadol for postoperative pain in children is currently low or very low and should be interpreted with caution due to small studies and methodological problems (different validated and non-validated pain scales with different pain triggers, missing sample size calculations and missing intention-to-treat analysis). Nevertheless, we demonstrated that tramadol administration might provide appropriate analgesia when compared to placebo; this is based on results showing reduced rescue analgesia in children treated with tramadol compared to placebo. In contrast, the evidence regarding the comparison with other opioids (for example morphine) was uncertain. Adverse events were only poorly reported, so an accurate risk-benefit analysis was not possible.
Systematic Review Question»Systematic review of interventions
