Spontaneous intracranial hypotension (SIH) is a rare clinical condition that may occur due to cerebrospinal fluid leakage. The purpose of this study was to compare the safety and efficacy of single catheter multisite epidural blood patch(CA-EBP) with standard procedures, including blinded and targeted epidural blood patch (EBP) for the treatment of SIH, and to investigate the effectiveness of dexamethasone as an adjuvant. Clinical data of 68 patients with postoperative SIH who underwent EBP between March 2022 and May 2024. In this prospective cohort trial, 68 patients were allocated to four groups: blind EBP, targeted EBP, CA-EBP, and CA-EBP + dexamethasone, based on the procedure received. Patients were assessed for pain using the visual analog scale (VAS), anxiety and depression using the Hospital Anxiety and Depression Scale (HADS), and quality of life using the Headache lmpact Test (HIT-6). Adverse events were documented to evaluate the safety of the procedure. A total of 68 patients were recruited for the study, comprising 41 females and 27 males, with a mean age of 40.76 years. The participants were distributed as follows: 9 in the blind EBP group, 17 in the targeted EBP group, 20 in the CA-EBP group, and 22 in the CA-EBP + dexamethasone group. After a single treatment, the severity of headaches significantly decreased in 5 (55.56%) patients in the blinded EBP group, 13 (76.47%) patients in the targeted EBP group, 19 (95.00%) patients in the CA-EBP group, and 20 (90.91%) patients in the CA-EBP + dexamethasone group. The most frequent complications in both groups were transient intracranial hypertension
however, no serious complications were reported. CA-EBP stands out as a safe and effective therapy for SIH. It notably alleviates pain, enhances quality of life, and surpasses standard EBP procedures. Moreover, dexamethasone, when used as an adjunct, proves effective in mitigating postoperative complications.