H1-抗组胺药苯海拉明拮抗各种动物中的胆碱酯酶抑制剂中毒。苯海拉明急性解毒作用的一个方面是增加有毒物质的中位致死剂量(LD50)。这项荟萃分析的目的是评估苯海拉明对实验动物胆碱酯酶抑制剂的短期毒性(LD50)的解毒作用。选择的实验研究是根据系统评价和荟萃分析(PRISMA)指南的首选报告项目进行的。它们是在实验动物(小鼠,老鼠,和小鸡)以确定胆碱酯酶抑制剂(有机磷,氨基甲酸酯,和酰亚胺)在苯海拉明与苯海拉明的影响下controls.从对小鼠的12项研究中选择了28条记录(n=242),大鼠(n=27),和小鸡(n=128)。随机两组荟萃分析的森林图评估了效果大小,亚组分析,窗帘预测,异质性,发表偏倚漏斗图以及保护百分比的一组比例荟萃分析。与对照相比,苯海拉明在中毒的实验动物中显著增加组合效应大小(即增加的LD50)(-3.71,标准误差(SE)0.36,95CI-4.46,-2.97)。窗帘图提出了广泛的置信区间。联合效应大小的异质性I2指数高达81.03%(Q=142.3,p<0.0001)。Galbraith回归也表明数据异质性;然而,正常的分位数图没有异常值。亚组分析显示,有机磷(I2=63.72%)和氨基甲酸酯(I2=76.41%)的异质性明显较高,但亚氨基脲含量低(I2=51.48%)。漏斗图和Egger回归检验(t=-13.7,p<0.0001)显示发表偏倚。苯海拉明保护率的中位数为1.655,一组比例荟萃分析的相关森林地块显示出统计学上较高的保护水平(0.594,SE0.083,95CI0.432,0.756),具有高度异质性(I2=99.86)。偏见评估的风险尚不清楚,而每项研究的总分(20分中的16分)偏向低偏倚风险一侧。总之,LD50值的荟萃分析表明,苯海拉明明确保护实验动物免受胆碱酯酶抑制剂的急性毒性.该药物可能是针对胆碱酯酶抑制剂引起的急性中毒的另一种解毒剂,但要注意的是:它不被认为是标准解毒剂硫酸阿托品的替代品。需要进一步的研究来检查苯海拉明对胆碱酯酶抑制剂的不良慢性作用的作用。
The H1-antihistamine diphenhydramine antagonizes cholinesterase inhibitor poisoning in various animal species. One aspect of acute antidotal actions of diphenhydramine is increasing the median lethal doses (LD50) of toxicants. The objective of this meta-analysis was to assess the antidotal action of diphenhydramine against short-term toxicity (LD50) of cholinesterase inhibitors in experimental animals. The experimental studies selected were according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. They were conducted in laboratory animals (mice, rats, and chicks) to determine acute LD50 values of cholinesterase inhibitors (organophosphates, carbamates, and imidocarb) under the influence of diphenhydramine vs. controls. Twenty-eight records were selected from 12 studies on mice (n= 242), rats (n= 27), and young chicks (n= 128). The forest plot of randomized two-group meta-analysis assessed effect size, subgroup analysis, drapery prediction, heterogeneity, publication bias-funnel plot as well as one-group proportions meta-analysis of percent protection. Diphenhydramine significantly increased the combined effect size (i.e. increased LD50) in intoxicated experimental animals in comparison to controls (-3.71, standard error (SE) 0.36, 95%CI -4.46, -2.97). The drapery plot proposed a wide range of confidence intervals. The I2 index of heterogeneity of the combined effect size was high at 81.03% (Q= 142.3, p < 0.0001). Galbraith regression also indicated data heterogeneity; however, the normal quantile plot indicated no outliers. Subgroup analysis indicated significantly high heterogeneity with organophosphates (I2 = 63.72%) and carbamates (I2 = 76.41%), but low with imidocarb (I2 = 51.48%). The funnel plot and Egger regression test (t= -13.7, p < 0.0001) revealed publication bias. The median of the diphenhydramine protection ratio was 1.655, and the related forest plot of one group proportion meta-analysis revealed a statistically high level of protection (0.594, SE 0.083, 95%CI 0.432, 0.756), with high heterogeneity (I2= 99.86). The risk of bias assessment was unclear, while the total score (16 out of 20) of each study leaned towards the side of the low risk of bias. In conclusion, the meta-analysis of LD50 values indicated that diphenhydramine unequivocally protected experimental animals from the acute toxicity of cholinesterase inhibitors. The drug could be an additional
antidote against acute poisoning induced by cholinesterase inhibitors, but a word of caution: it is not to be considered as a replacement for the standard
antidote atropine sulfate. Further studies are needed to examine the action of diphenhydramine on adverse chronic effects of cholinesterase inhibitors.