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Pharmacological prevention of sevoflurane- and desflurane-related emergence agitation in children: a meta-analysis of published studies |
Dahmani S, Stany I, Brasher C, Lejeune C, Bruneau B, Wood C, Nivoche Y, Constant I, Murat I |
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CRD summary The review found that prophylactic propofol, ketamine, fentanyl and perioperative analgesia appeared to reduce sevoflurane and desflurane-related emergence agitation in children. The review was well conducted in many respects, but in view of the incomplete retrieval of eligible studies, heterogeneity between the studies and lack of information on some aspects of their quality, some caution in interpretation may be advisable. Authors' objectives To assess the efficacy of pharmacological prophylaxis to reduce the incidence of emergence agitation related to sevoflurane and desflurane anaesthesia in children. Searching PubMed, EMBASE and Cochrane Database of Systematic Reviews were searched to February 2009. Search terms were reported. Reference lists of selected articles, reviews and meta-analyses were checked. The search was limited to articles in English. Study selection Randomised controlled trials (RCTs) of the prevention of emergence agitation among children without neurological disease who were anaesthetised with sevoflurane and/or desflurane using standardised anaesthetic protocols were eligible for inclusion. Studies were required to use a standardised definition of emergence agitation, report agitation, delirium or behavioural disturbances and conduct blinded outcomes assessment. Studies that compared two prophylactic interventions (without a control group) or that explored curative treatments were excluded.
Participants in the review were children aged four months to 11 years (where reported) who underwent a range of procedures (such as hernia repair, ear, nose and throat surgery, dental repair, circumcision and magnetic resonance imaging). All participants received inhalational anaesthesia (halothane, sevoflurane or desflurane) for induction and/or maintenance. Prophylactic interventions included midazolam, propofol, fentanyl, ketamine, a2-adrenoreceptor (a2-AR) agonists, clonidine or dexmedetomidine, perioperative analgesia and 5HT-3 inhibitors. Prophylactic interventions varied in timing, mode and route of administration as well as use of premedications and regional block. Various definitions of emergence agitation were used and only one study used a validated scale.
Two reviewers independently selected the studies. Disagreements were resolved by consensus. Assessment of study quality Study validity was assessed using methods recommended by the Cochrane Collaboration. This appeared to include randomisation, blinding, comparability of anaesthetic protocols and follow-up in the two groups.
Two reviewers independently assessed study validity. Disagreements were resolved by rechecking data. Data extraction Odds ratios (ORs) and 95% confidence intervals (CIs) were extracted or calculated for dichotomous outcomes. Standardised mean differences were calculated for continuous data and transformed to logarithmic odds ratios and standard deviations using the method of Chinn (2000). In studies with more than one intervention group, each group was compared separately with controls. Where there were zero events, one event was added to each group.
Two reviewers independently extracted data. Disagreements resolved by rechecking. Methods of synthesis For outcomes where all primary studies reported dichotomous data, data were combined to calculate pooled odds ratios and 95% CIs using fixed-effect or random-effects models. Inverse variance was used for analyses that included transformed continuous data. Heterogeneity was assessed using Χ2 and I2 tests. Publication bias was assessed with funnel plots and the Begg test (where there were 10 or more studies). The authors stated that where was substantial heterogeneity, a random-effects model was used, differences in study design were considered and the effect of removing studies from the analysis one by one was tested. Subgroup analyses were conducted by the timing and route of intervention, anaesthetic agent, concurrent preoperative analgesia and expected pain (magnetic resonance imaging versus surgical studies). Results of the review Thirty-seven RCTs were included in the review (n=3,172). All were randomised and double-blinded. Anaesthetic and follow-up regimens were similar in intervention and control groups.
The following interventions significantly decreased the incidence of emergence anxiety compared with to controls: propofol (OR 0.21, 95% CI 0.16 to 0.28; 13 RCTs, I2=52%), fentanyl (OR 0.31, 95% CI 0.18 to 0.56; five RCTs, I2=47%), ketamine (OR 0.28, 95% CI 0.13 to 0.60; 10 RCTs, I2=0%), α2-AR agonists (OR 0.23, 95% CI 0.17 to 0.33; four RCTs, I2=24%) and perioperative analgesia (OR 0.15, 95% CI 0.07 to 0.34; three RCTs, I2=8%). Funnel plots were suggestive of possible publication bias for α2-AR agonist analyses, but not for propofol analyses. There was no statistically significant difference between midazolam (four RCTs) and 5HT-antagonists (two RCTs) compared to controls.
Subgroup analyses: Propofol was effective when given continuously or by bolus at the end of surgery, but was ineffective given by bolus at induction. Intranasal fentanyl was effective, but intravenous fentanyl was not. Heterogeneity was substantially lower in these subgroups than in the main analyses. Other subgroup analyses did not change the statistical significance of the results.
Other results were reported in the review. Authors' conclusions Prophylactic propofol, ketamine, fentanyl and perioperative analgesia appeared to reduce sevoflurane and desflurane-related emergence agitation in children. CRD commentary The objective and inclusion criteria of the review were clear. Some relevant sources were searched for studies, although it seemed that no specific attempts were made to retrieve unpublished studies. The search was restricted by language and so the review was at risk of language bias. Two RCTs were excluded due to being unavailable in full text, so some evidence was missing. Appropriate steps were taken to reduce error and bias in review processes and study quality was assessed, although some important aspects were not reported such as adequacy of allocation concealment and loss to follow up. Appropriate statistical methods were used to combine studies, check for heterogeneity and publication bias,and to explore potential sources for heterogeneity where it was detected. It was unclear whether data were extracted on an intention-to-treat basis. The review was well conducted in many respects, but in view of the incomplete retrieval of eligible studies, heterogeneity between studies and lack of information on some aspects of their quality, some caution in interpretation may be advisable. Implications of the review for practice and research The authors did not state any implications for practice.
Research: The authors stated that future studies of prevention of emergence agitation should use a standardised evaluation tool. They also recommended that studies focused on evaluating agents found effective in this review. Bibliographic details Dahmani S, Stany I, Brasher C, Lejeune C, Bruneau B, Wood C, Nivoche Y, Constant I, Murat I. Pharmacological prevention of sevoflurane- and desflurane-related emergence agitation in children: a meta-analysis of published studies. British Journal of Anaesthesia 2010; 104(2): 216-223 Indexing Status Subject indexing assigned by NLM MeSH Akathisia, Drug-Induced /etiology /prevention & Analgesia; Anesthesia Recovery Period; Anesthetics, Inhalation /adverse effects; Anesthetics, Intravenous /therapeutic use; Child; Fentanyl /therapeutic use; Humans; Isoflurane /adverse effects /analogs & Ketamine /therapeutic use; Methyl Ethers /adverse effects; Postoperative Complications /prevention & Propofol /therapeutic use; Receptors, Adrenergic, alpha-2 /therapeutic use; control; control; derivatives AccessionNumber 12010001445 Date bibliographic record published 28/04/2010 Date abstract record published 15/09/2010 Record Status This is a critical abstract of a systematic review that meets the criteria for inclusion on DARE. Each critical abstract contains a brief summary of the review methods, results and conclusions followed by a detailed critical assessment on the reliability of the review and the conclusions drawn. |
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