Downloaded from https://journals.lww.com/anesthesia-analgesia by BhDMf5ePHKav1zEoum1tQfN4a+kJLhEZgbsIHo4XMi0hCywCX1AWnYQp/IlQrHD3tIQ5gQCIeyzJo54jCNnsT95TC1S31Qivu8lj3l9LHtD5VHdeNO4aHw== on 08/31/2018 Copyright © 2018 International Anesthesia Research Society. Unauthorized reproduction of this article is prohibited. XXX XXX • Volume XXX • Number XXX www.anesthesia-analgesia.org 1 DOI: 10.1213/ANE.0000000000003734 P ostdural puncture headache (PDPH) is a complica- tion 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 fuid (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 epi- dural 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 neostig- mine 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 effcacy of neostigmine and conservative management for the treatment of PDPH. The decision was supported by the well-known pharmacologic profle, safety, and ready availability of neostigmine. METHODS This prospective, randomized, controlled, double-blind trial was performed after approval by the Research and Ethics KEY POINTS • Question: Can neostigmine and atropine improve postdural puncture headache (PDPH) treat- ment when added to conventional management? • Findings: Neostigmine plus atropine improved PDPH after only 2 doses without recurrence of headache or need for an epidural blood patch. • Meaning: Neostigmine plus atropine is a simple pharmacological treatment for PDPH. BACKGROUND: Postdural puncture headache (PDPH) lacks a standard evidence-based treat- ment. A patient treated with neostigmine for severe PDPH prompted this study. METHODS: This randomized, controlled, double-blind study compared neostigmine and atro- pine (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 and 10 μg/kg or an equal volume of saline. RESULTS: Visual analog scale scores were signifcantly 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 pla- cebo 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 neo- stigmine/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 infuence both cerebrospinal fuid 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. (Anesth Analg XXX;XXX:00–00) 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,‡ and Mohamed Abdelhaq, MD‡ 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; and §Faculty of Medicine, Department of Anesthesiology, Fayoum University, Faiyum, Egypt. Accepted for publication July 12, 2018. Funding: Departmental. The authors declare no conficts 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 (www.anesthesia-analgesia.org). Trial registration: The trial was registered at Pan African Clinical Trial Registry (www.pactr.org, 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 carnitin7@yahoo.com. Copyright © 2018 International Anesthesia Research Society