Abstract: We included 10 RCTs (1611 participants) in this review with a majority of women (72%), mostly parturients (women in labour) (913), after a lumbar puncture for regional anaesthesia. Drugs assessed were epidural and spinal morphine, spinal fentanyl, oral caffeine, rectal indomethacin, intravenous cosyntropin, intravenous aminophylline and intravenous dexamethasone. All the included RCTs reported data on the primary outcome, i.e. the number of participants affected by PDPH of any severity after a lumbar puncture. Epidural morphine and intravenous cosyntropin reduced the number of participants affected by PDPH of any severity after a lumbar puncture when compared to placebo. Also, intravenous aminophylline reduced the number of participants affected by PDPH of any severity after a lumbar puncture when compared to no intervention, while intravenous dexamethasone increased it. Spinal morphine increased the number of participants affected by pruritus when compared to placebo, and epidural morphine increased the number of participants affected by nausea and vomiting when compared to placebo. Oral caffeine increased the number of participants affected by insomnia when compared to placebo. The remainder of the interventions analysed did not show any relevant effect for any of the outcomes. None of the included RCTs reported the number of days that patients stayed in hospital. Morphine and cosyntropin have shown effectiveness for reducing the number of participants affected by PDPH of any severity after a lumbar puncture, when compared to placebo, especially in patients with high risk of PDPH, such as obstetric patients who have had an inadvertent dural puncture. Aminophylline also reduced the number of participants affected by PDPH of any severity after a lumbar puncture when compared to no intervention in patients undergoing elective caesarean section. Dexamethasone increased the risk of PDPH, after spinal anaesthesia for caesarean section, when compared to placebo. Morphine also increased the number of participants affected by adverse events (pruritus and nausea and vomiting) There is a lack of conclusive evidence for the other drugs assessed (fentanyl, caffeine, indomethacin and dexamethasone). These conclusions should be interpreted with caution, owing to the lack of information, to allow correct appraisal of risk of bias and the small sample sizes of studies.

Plain-language summary: We included 10 randomised clinical trials (RCTs), with a total of 1611 participants, that assessed seven medications (epidural and spinal morphine, spinal fentanyl, oral caffeine, rectal indomethacin, intravenous cosyntropin, intravenous aminophylline and intravenous dexamethasone). Epidural morphine and intravenous cosyntropin proved to be effective at reducing the number of participants affected by PDPH of any severity after lumbar puncture compared to placebo. Aminophylline also reduced the number of participants affected by PDPH of any severity after a lumbar puncture compared to no intervention. Dexamethasone increased the risk of PDPH when compared to placebo after spinal anaesthesia for caesarean section. Morphine also increased the number of participants affected by adverse events such as itching, nausea and vomiting. The other interventions (fentanyl, caffeine, indomethacin and dexamethasone) did not show conclusive evidence of effectiveness. Combining data was possible only for subgroups of one study comparing different dosages of caffeine to placebo, because the other RCTs appraised diverse drugs, outcomes or populations. A meta-analysis (combining of data) was not possible because all the included RCTs assessed different drugs, different doses, different outcomes or different baseline participants' characteristics. These conclusions should be interpreted carefully, given the lack of information to evaluate the risk of bias properly, and the small number of participants in the included studies.