Department of Anesthesiology, Yale University School of Medicine, New Haven, CT, USA.
Pain Pract. 2012 Jun;12(5):357-65. doi: 10.1111/j.1533-2500.2011.00514.x. Epub 2011 Oct 19.
From the time that Sinatra et al. (Anesthesiology. 2005;102:822) was published to FDA apaproval of intravenous (IV) acetaminophen, an expanded analysis of the original raw study data became necessary for the regulatory submission. The following analyses were conducted: (1) sum of pain intensity differences over 24 hours (SPID24) using currently accepted imputation methods to account for both missing data and the effects of rescue; (2) efficacy results after the first 6 hours; (3) effects of gender, race/ethnicity, age, weight, surgical site, ASA Class, and serotonin antagonists; and (4) a stepwise regression analysis of why adverse events of nausea and vomiting were numerically (although not statistically) higher in the IV acetaminophen group compared with placebo.
Sum of pain intensity differences over 24 hours using a 0- to 100-mm visual analog scale was statistically significantly (P < 0.001) in favor of IV acetaminophen (n = 49) compared with placebo (n = 52). Time to rescue was found to be 3.9 and 2.1 hours, respectively, for total hip and knee arthroplasty compared with 0.8 hours for the placebo group. Rescue medication consumption, requests, and actual administration were all significantly lower in the IV acetaminophen group compared with placebo for each dosing interval, except in the 6- to 12-hours interval where a numerical trend was observed. Analysis of various subset variables demonstrated similar efficacy for each variable. A stepwise regression analysis demonstrated that AE reports of nausea and vomiting were most likely due to prerandomization events, particularly opioid consumption and presence of nausea prior to randomization.
Repeated-dose 24-hours end points were found to be as robust as previously published results. IV acetaminophen efficacy and safety appeared to be unaffected by specific subset variables.▪
自 Sinatra 等人发表《麻醉学》（2005；102：822）以来，为了获得 FDA 的批准，静脉注射（IV）对乙酰氨基酚需要对原始研究数据进行扩展分析，以提交监管部门。进行了以下分析：（1）24 小时内疼痛强度差总和（SPID24），使用目前接受的插补方法来同时考虑缺失数据和救援的影响；（2）前 6 小时的疗效结果；（3）性别、种族/民族、年龄、体重、手术部位、ASA 分级和 5-羟色胺拮抗剂的影响；（4）对为什么与安慰剂相比，IV 对乙酰氨基酚组的恶心和呕吐不良事件的数值（尽管不是统计学上）更高的原因进行逐步回归分析。
使用 0-100mm 视觉模拟量表的 24 小时疼痛强度差异总和在统计学上明显（P < 0.001）有利于 IV 对乙酰氨基酚（n = 49）与安慰剂（n = 52）相比。全髋关节和膝关节置换术的解救时间分别为 3.9 和 2.1 小时，而安慰剂组为 0.8 小时。与每个剂量间隔的安慰剂组相比，IV 对乙酰氨基酚组的解救药物消耗、请求和实际给药均明显较低，除了在 6-12 小时间隔观察到数值趋势。对各种亚变量的分析表明，每个变量的疗效相似。逐步回归分析表明，AE 报告的恶心和呕吐最有可能是由于随机分组前的事件，特别是阿片类药物的消耗和随机分组前恶心的存在。
重复剂量 24 小时终点与之前发表的结果一样可靠。IV 对乙酰氨基酚的疗效和安全性似乎不受特定亚变量的影响。
