The impact of aminophylline on incidence and severity of post-dural puncture headache: A meta-analysis of randomised controlled trials

This meta-analysis aimed at addressing the impact of aminophylline use on risk and severity of post-dural puncture headache (PDPH). Electronic databases (i.e., Medline, Embase, and the Cochrane controlled trials register) were searched from inception to the 12th of January 2021 for randomised controlled trials (RCTs) that assessed the efficacy of aminophylline for treatment (i.e., primary outcome) or prophylaxis (i.e., secondary outcome) against PDPH in various clinical settings. The study is registered with PROSPERO (CRD42020207713). A total of ten RCTs (n = 976) were included for analysis. Five studies (n = 270) revealed a lower pain score in patients with PDPH receiving aminophylline than that in the placebo group (standardised mean differences = −1.34, 95% confidence interval (CI): −1.76 to −0.91). In contrast, five trials (four on Caesarean sections and one on lower extremity surgeries, n = 706) demonstrated no prophylactic effect of aminophylline against PDPH at 24 [risk ratio (RR) = 0.70, 95% CI: 0.30–1.63, n = 637], 48 (RR = 0.48, 95% CI: 0.22–1.05, n = 506), and 72 (RR = 0.89, 95% CI: 0.54–1.48, n = 317) hours. Nevertheless, sensitivity analysis demonstrated significant prophylactic efficacy after removal of one study adopting a relatively low dose of aminophylline (RR = 0.36, 95% CI: 0.19–0.67). Most studies reported no increase in the incidence of adverse events associated with aminophylline use compared with that in the control group. Our results indicated that aminophylline might be a reasonable alternative for treating PDPH. However, its use for prevention was not established in this meta-analysis and further large-scale studies are warranted to support this option.