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Addition of Neostigmine and Atropine to Conventional Management of Postdural Puncture Headache: A Randomized Controlled Trial

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

doi: 10.1213/ANE.0000000000003734
Regional Anesthesia and Acute Pain Medicine: Original Clinical Research Report

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.

From the *Faculty of Medicine, Department of Anesthesiology, Beni-Suef University, Beni Suef, Egypt

Department of Anaesthesia, Tallaght University Hospital, Dublin, Ireland

Faculty of Medicine, Department of Anesthesiology, Cairo University, Giza, Egypt

§Faculty of Medicine, Department of Anesthesiology, Fayoum University, Faiyum, Egypt.

Published ahead of print 12 July 2018.

Accepted for publication July 12, 2018.

Funding: Departmental.

The authors declare no conflicts of interest.

Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal’s website.

Trial registration: The trial was registered at Pan African Clinical Trial Registry (, PACTR201510001299332). On October 9, 2015. The principal investigator was A.A.A.M.

Reprints will not be available from the authors.

Address correspondence to Ahmed Abdelaal Ahmed Mahmoud, MD, FCAI, Department of Anaesthesia, Tallaght University Hospital, Tallaght, Dublin 24, D24 NR0A, Ireland. Address e-mail to

Copyright © 2018 International Anesthesia Research Society
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