Neostigmine and Glycopyrrolate for the Treatment of Headache After Dural Puncture

NCT05116930 | Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: 21-009530
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to evaluate Neostigmine and Glycopyrrolate to treat post-dural puncture headache (PDPH) to reduce the proportion of postpartum women with a PDPH requiring epidural blood patch (EBP) who developed a PDPH after accidental dural puncture.

Conditions

Post-Dural Puncture Headache

Outcome Measures

Primary Outcomes (1)

• Number of postpartum women requiring epidural blood patch

  Total number of postpartum women with a post dural puncture headache (PDPH) requiring epidural blood patch (EBP)

  2 weeks

Secondary Outcomes (2)

• Change in pain scores

  Baseline, 1 hour, 8 hours, 16 hours, 24 hours, 48 hours, 1 week, and 2 weeks after intervention

• Adverse Events

  2 weeks

Study Arms (1)

Postpartum dural puncture headache following dural puncture from Tuohy needle

EXPERIMENTAL

Subjects identified as experienced a post dural puncture headache after a confirmed dural puncture from a Tuohy needle will receive an IV administration of the study medications neostigmine and glycopyrrolate.

Drug: Neostigmine; Drug: Glycopyrrolate

Interventions

Neostigmine DRUG

IV infusion 20 μg/kg over 10 minutes repeated every 8 hours for a maximum of 3 doses

Postpartum dural puncture headache following dural puncture from Tuohy needle

Glycopyrrolate DRUG

IV infusion 4 μg/kg over 10 minutes repeated every 8 hours for a maximum of 3 doses

Postpartum dural puncture headache following dural puncture from Tuohy needle

Eligibility Criteria

• Age: 18 Years - 54 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Post-dural puncture headache (PDPH) after documented dural puncture with Tuohy needle during placement of epidural analgesia for labor and no other explanation for headache (HA).
• Onset of HA within 72 hours of delivery.

You may not qualify if:

• Patient refusal.
• Visual analog scale (NRS) score \< 4.
• History of migraine headaches.
• Asthma.
• Arrhythmia.
• Heart block.
• Myasthenia gravis.
• Inability to understand pain scores and other questionnaires.
• Inability to speak English.
• Contraindication to acetaminophen or NSAIDs.
• Temperature \> 38.5 C.
• Prior EBP done for this HA.

Sponsors & Collaborators

• Mayo Clinic: lead

Study Sites (1)

Mayo Clinic in Rochester

Rochester, Minnesota, 55905, United States

RECRUITING

Related Publications (14)

• Turnbull DK, Shepherd DB. Post-dural puncture headache: pathogenesis, prevention and treatment. Br J Anaesth. 2003 Nov;91(5):718-29. doi: 10.1093/bja/aeg231.

  PMID: 14570796 BACKGROUND

• Amorim JA, Gomes de Barros MV, Valenca MM. Post-dural (post-lumbar) puncture headache: risk factors and clinical features. Cephalalgia. 2012 Sep;32(12):916-23. doi: 10.1177/0333102412453951. Epub 2012 Jul 27.

  PMID: 22843225 BACKGROUND

• Flaatten H, Rodt S, Rosland J, Vamnes J. Postoperative headache in young patients after spinal anaesthesia. Anaesthesia. 1987 Feb;42(2):202-5. doi: 10.1111/j.1365-2044.1987.tb03001.x.

  PMID: 3826597 BACKGROUND

• Abouleish E, Vega S, Blendinger I, Tio TO. Long-term follow-up of epidural blood patch. Anesth Analg. 1975 Jul-Aug;54(4):459-63. doi: 10.1213/00000539-197554040-00012.

  PMID: 125053 BACKGROUND

• Cornwall RD, Dolan WM. Radicular back pain following lumbar epidural blood patch. Anesthesiology. 1975 Dec;43(6):692-3. doi: 10.1097/00000542-197512000-00023. No abstract available.

  PMID: 127535 BACKGROUND

• Mehta SP, Keogh BP, Lam AM. An epidural blood patch causing acute neurologic dysfunction necessitating a decompressive laminectomy. Reg Anesth Pain Med. 2014 Jan-Feb;39(1):78-80. doi: 10.1097/AAP.0000000000000025.

  PMID: 24310044 BACKGROUND

• Reynolds AF Jr, Hameroff SR, Blitt CD, Roberts WL. Spinal subdural epiarachnoid hematoma: a complication of a novel epidural blood patch technique. Anesth Analg. 1980 Sep;59(9):702-3. No abstract available.

  PMID: 7191232 BACKGROUND

• Sperry RJ, Gartrell A, Johnson JO. Epidural blood patch can cause acute neurologic deterioration. Anesthesiology. 1995 Jan;82(1):303-5. doi: 10.1097/00000542-199501000-00038. No abstract available.

  PMID: 7832316 BACKGROUND

• Abdelaal Ahmed Mahmoud A, Mansour AZ, Yassin HM, Hussein HA, Kamal AM, Elayashy M, Elemady MF, Elkady HW, Mahmoud HE, Cusack B, Hosny H, Abdelhaq M. Addition of Neostigmine and Atropine to Conventional Management of Postdural Puncture Headache: A Randomized Controlled Trial. Anesth Analg. 2018 Dec;127(6):1434-1439. doi: 10.1213/ANE.0000000000003734.

  PMID: 30169405 BACKGROUND

• Nair AS. Questions Regarding the Use of Neostigmine-Atropine to Treat Postdural Puncture Headache. Anesth Analg. 2019 Jun;128(6):e126-e127. doi: 10.1213/ANE.0000000000004156. No abstract available.

  PMID: 31094821 BACKGROUND

• Daoud M, Asfour M, Mubashirulhassan S. Missed Neostigmine-Atropine Side Effects: Uncommonly Noticed Postanesthesia but Commonly Noticed in Other Situations. Anesth Analg. 2019 Jun;128(6):e128. doi: 10.1213/ANE.0000000000004158. No abstract available.

  PMID: 31094823 BACKGROUND

• Abrishami A, Ho J, Wong J, Yin L, Chung F. Sugammadex, a selective reversal medication for preventing postoperative residual neuromuscular blockade. Cochrane Database Syst Rev. 2009 Oct 7;(4):CD007362. doi: 10.1002/14651858.CD007362.pub2.

  PMID: 19821409 BACKGROUND

• Luo J, Chen S, Min S, Peng L. Reevaluation and update on efficacy and safety of neostigmine for reversal of neuromuscular blockade. Ther Clin Risk Manag. 2018 Dec 10;14:2397-2406. doi: 10.2147/TCRM.S179420. eCollection 2018.

  BACKGROUND

• Salem MG, Richardson JC, Meadows GA, Lamplugh G, Lai KM. Comparison between glycopyrrolate and atropine in a mixture with neostigmine for reversal of neuromuscular blockade. Studies in patients following open heart surgery. Br J Anaesth. 1985 Feb;57(2):184-7. doi: 10.1093/bja/57.2.184.

  PMID: 2857570 BACKGROUND

Related Links

• Mayo Clinic Clinical Trials
• Statement on Sugammadex during pregnancy and lactation. Soap.org.
• Drugs and Lactation Database (LactMed)
• Statement on Resuming Breastfeeding after Anesthesia. Asahq.org.

MeSH Terms

Conditions

Post-Dural Puncture Headache

Interventions

Neostigmine; Glycopyrrolate

Condition Hierarchy (Ancestors)

Headache Disorders, Secondary; Headache Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

Intervention Hierarchy (Ancestors)

Phenylammonium Compounds; Quaternary Ammonium Compounds; Amines; Organic Chemicals; Onium Compounds; Pyrrolidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Mark Rollins, MD, PhD

  Mayo Clinic

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: November 2, 2021
• First Posted: November 11, 2021
• Study Start: November 19, 2021
• Primary Completion (Estimated): December 1, 2027
• Study Completion (Estimated): December 1, 2027
• Last Updated: March 23, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)