Department of Anesthesia and Intensive Care, Policlinico Umberto 1, University of Rome, La Sapienza, Rome, Italy.
Anesth Analg. 2013 Feb;116(2):443-7. doi: 10.1213/ANE.0b013e3182746eda. Epub 2013 Jan 9.
Ketorolac tromethamine (ketorolac) is a nonsedating drug with potent analgesic and moderate anti-inflammatory activity, which does not increase the sedation level. The safety of ketorolac with respect to risk of bleeding has been demonstrated in large numbers of patients undergoing general surgery, yet comparable safety data for neurosurgical patients are lacking. We studied the risk of symptomatic bleeding requiring surgery in patients undergoing elective neurosurgical procedures who received ketorolac as analgesic therapy.
We established a cohort of patients who had elective intracranial procedures from January 2001 to August 2010 (excluding patients with urgent surgery, coagulopathy, history of anticoagulant or nonsteroidal, anti-inflammatory drug therapy) and verified the occurrence of postcraniotomy intracranial hemorrhage (ICH; detected by computed tomography and requiring surgery) in patients who received or did not receive ketorolac. Then, to control for potential confounders, we conducted a "nested" case-control study within the cohort: cases were defined as patients with ICH; controls were patients without ICH matched in a 2:1 ratio.
The cohort included 4086 craniotomy patients (mean age, 52.4±14.3 years, 2124 male, 52%). Of the 1571 patients who received ketorolac (mean dosage, 50±15 mg/d), 8 (0.5%) suffered ICH; of the 2515 patients who did not receive ketorolac, 35 (1.3%) had ICH (relative risk, 0.37; 95% confidence interval, 0.17-0.79; P=0.007). In the nested case-control study, the adjusted odds ratio for ketorolac administration between the 2 groups was 1.09 (95% confidence interval, 0.35-3.44; P=0.88).
Although the adjusted estimate for risk of symptomatic bleeding requiring surgery and ketorolac use is very close to the null effect, it may be not reproducible, and the width of the confidence interval is not conclusive evidence of the safety of ketorolac after elective neurosurgical procedures.
酮咯酸氨丁三醇（酮咯酸）是一种非镇静药物，具有强效的镇痛作用和中度的抗炎活性，不会增加镇静水平。大量接受普通外科手术的患者的研究表明，酮咯酸在出血风险方面是安全的，但缺乏针对神经外科患者的可比安全性数据。我们研究了接受择期神经外科手术的患者在接受酮咯酸作为镇痛治疗时发生需要手术的症状性出血的风险。
我们建立了一个从 2001 年 1 月至 2010 年 8 月接受择期颅内手术的患者队列（不包括紧急手术、凝血功能障碍、抗凝或非甾体抗炎药治疗史的患者），并验证了接受或未接受酮咯酸的患者中手术后颅内出血（ICH；通过计算机断层扫描检测并需要手术）的发生情况。然后，为了控制潜在的混杂因素，我们在队列中进行了一项“嵌套”病例对照研究：病例定义为 ICH 患者；对照组为未发生 ICH 的患者，按 2:1 比例匹配。
该队列包括 4086 例开颅手术患者（平均年龄 52.4±14.3 岁，2124 例男性，52%）。在接受酮咯酸治疗的 1571 例患者中（平均剂量为 50±15mg/d），有 8 例（0.5%）发生 ICH；在未接受酮咯酸治疗的 2515 例患者中，有 35 例（1.3%）发生 ICH（相对风险，0.37；95%置信区间，0.17-0.79；P=0.007）。在嵌套病例对照研究中，两组之间使用酮咯酸的调整后比值比为 1.09（95%置信区间，0.35-3.44；P=0.88）。
尽管症状性出血需要手术和酮咯酸使用的风险调整估计值非常接近零效应，但可能无法重现，置信区间的宽度并不能为择期神经外科手术后酮咯酸的安全性提供确凿证据。
