| OBJECTIVE1. Use meta–analysis to assess the propofol pharmacokinetics in elderly patients, to get medical evidence for propofol administration in elderly.2. Evaluate the propofol pharmacokinetics in children, to improve safety medication of propofol in children.METHODS1. Trials were located through electronic searches of the Medline, Ovid,Springer Link, CNKI, VIP, WANFANG database, CBM, supplemented by manual retrieval ,to collect all published literatures of propofol pharmacokinetics.2. Collect all clinical controlled trials of propofol pharmacokinetics in elderly. Using Cochrane systematic review methods to evaluate the methodological quality of included studies and to extract valid data.Meta-analysis were performed with the Cochrane Collaboration's Revman 4.2 software.3. Select all literatures of propol pharmacokinetics in children.Spearman's rank correlation coefficients as a distribution-free measure of association were determined from individual data to examine the influence of patients age,body weight on the pharmacokinetics of propofol. Using meta-analysis to evaluate the propofol pharmacokinetics in children.RESULTS1. 877 documents of propofol pharmacokinetics were retrieved, 211 relevant literatures were initially included, excluding those which does not match the study, finally 5 non-randomized clinical controlled trials were included. Meta-analysis showed:①the central volume distribution and clearance of propofol in the elderly were significantly less than the youth (WMD = -0.17, 95% CI -0.25 to -0.09,P<0.0001; WMD=-3.89,95%CI -6.05 to -1.73,P=0.004).②There was no difference in half lives of propofol .Compared with young people,the elderly could significantly increase the rate constants K10 and K12 (WMD = 0.07,95%CI 0.01 to 0.13,P=0.01; WMD=0.05,95%CI 0.02 to 0.08 ,P=0.0002).But there were no diffenrence in K21 and K13.③One literature showed there was no difference in the volume of distribution at steady state (Vdss) , while another three articles showed the area under the curve (AUC) was significantly larger than the young people (WMD =24.56, 95% CI 19.57 to 29.55 ,P<0.00001).2. 877 literatures of propofol pharmacokinetics were retrieved.,finally 17 literatures of propofol pharmacokinetics in children were included (exclude the unrelated and repetitive literatures).①At the asserted 0.05 level, the children's age (0.03yr~7.9yr) and body weight (2.51kg ~ 25.8kg) were not correlated with propofol pharmacokinetic parameters (Vc, Vdss, Cl1, t1/2α, t1/2β, t1/2γ, K10), P values were> 0.05.②The meta-analyzed Vc was 1.087±0.062 L ? kg-1. The combined effects of Vdss was 6.37±2.92 L ? kg-1, with a 0.95-confidence interval [0, 13.50]. The pooled average Cl1 was 38.56±13.6 mL ? kg-1 ? min-1, with a 0.95-confidence interval [10.83,61.69], while the mean values ranged from 15 mL·kg-1·min-1 to 74.5 mL·kg-1·min-1. The estimated half-lives were 2.99±0.86 min(t1/2α), 23.65±0.18min(t1/2β), 148.26±113.17min (t1/2γ). The elimination rate constant K10 was 0.083±0.0004 min-1.CONCLUSIONS1. Meta-analysis of non-randomized controlled trials is feasible .2.The pharmacokinetics of propofol in the elderly were different from the youth.Limited current evidence showed the Vc and Cl of propofol in the elderly were lower than young adults , while the AUC was higher ,suggesting the dose of propofol for induction and maintenance of anaesthesia should be lower in the elderly.3. The children's age and body weight were not correlated with propofol pharmacokinetic parameters. 4. The combined effect size of propofol pharmacokinetics Vdss, t1/2β, K10 in children had larger standard error . The slow distribution half life t1/2γhad a larger coefficient variation. |
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