Addition of Neostigmine and Atropine to Conventional Management of Postdural Puncture Headache

A Randomized Controlled Trial

Ahmed Abdelaal Ahmed Mahmoud, MD, FCAI; Amr Zaki Mansour, MD; Hany Mahmoud Yassin, MD; Hazem Abdelwahab Hussein, MD; Ahmed Moustafa Kamal, MD; Mohamed Elayashy, MD, FCAI; Mohamed Farid Elemady, MD; Hany W. Elkady, MD; Hatem Elmoutaz Mahmoud, MD; Barbara Cusack, LRCP&SI, MB MCh, NUI, MCAI; Hisham Hosny, MD; Mohamed Abdelhaq, MD


Anesth Analg. 2018;127(6):1434-1439. 

In This Article

Abstract and Introduction


Background: Postdural puncture headache (PDPH) lacks a standard evidence-based treatment. A patient treated with neostigmine for severe PDPH prompted this study.

Methods: This randomized, controlled, double-blind study compared neostigmine and atropine (n = 41) versus a saline placebo (n = 44) for treating PDPH in addition to conservative management of 85 patients with hydration and analgesics. The primary outcome was a visual analog scale score of ≤3 at 6, 12, 24, 36, 48, and 72 hours after intervention. Secondary outcomes were the need for an epidural blood patch, neck stiffness, nausea, and vomiting. Patients received either neostigmine 20 μg/kg and atropine 10 μg/kg or an equal volume of saline.

Results: Visual analog scale scores were significantly better (P< .001) with neostigmine/atropine than with saline treatment at all time intervals after intervention. No patients in the neostigmine/atropine group needed epidural blood patch compared with 7 (15.9%) in the placebo group (P< .001). Patients required no >2 doses of neostigmine/atropine. There were no between-group differences in neck stiffness, nausea, or vomiting. Complications including abdominal cramps, muscle twitches, and urinary bladder hyperactivity occurred only in the neostigmine/atropine group (P< .001).

Conclusions: Neostigmine/atropine was effective in treating PDPH after only 2 doses. Neostigmine can pass the choroid plexus but not the blood–brain barrier. The central effects of both drugs influence both cerebrospinal fluid secretion and cerebral vascular tone, which are the primary pathophysiological changes in PDPH. The results are consistent with previous studies and clinical reports of neostigmine activity.


Postdural puncture headache (PDPH) is a complication of spinal anesthesia or lumbar puncture and is an unpleasant experience for the patient as well as the anesthetist. It is thought to result from meningeal traction related to low cerebrospinal fluid (CSF) pressure or cerebral vasodilation as an indirect effect of decreased CSF pressure.[1] We encountered a case of PDPH in a patient who had failed conservative management and was scheduled for an epidural blood patch (EBP) procedure. However, the EBP was cancelled following resolution of the PDPH within an hour of receiving neostigmine and atropine for the management of postoperative ileus.[2] The dramatic response to neostigmine in the patient with PDPH and postoperative ileus are in line with the central effects of neostigmine, which can pass through the choroid plexus but not the blood–brain barrier, and atropine on CSF secretion and cerebral vascular tone that are the primary pathophysiological changes associated with PDPH.[3–17] The clinical experience with neostigmine prompted this comparison of the efficacy of neostigmine and conservative management for the treatment of PDPH. The decision was supported by the well-known pharmacologic profile, safety, and ready availability of neostigmine.