Intracranial hemorrhage requiring surgery in neurosurgical patients given ketorolac: A case-control study within a cohort (2001-2010)

BACKGROUND: 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. METHODS:: 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. RESULTS:: 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). CONCLUSION:: 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.