Addition of Pyridostigmine to Conventional Management of Postdural Puncture Headache

Postdural puncture headache (PDPH) is a major complication of neuraxial anesthesia that can occur following spinal anesthesia and with inadvertent Dural puncture during epidural anesthesia. The presence of Pyridostigmine in CSF would be expected to increase the level of acetylcholine in CSF and subsequently in the brain through inhibition of cholinesterase. The increased level of acetylcholine would produce cerebral vasoconstriction.

Study Overview

• Status: Completed
• Conditions: Postdural Puncture Headache
• Intervention / Treatment: Drug: Pyridostigmine; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 30
• Phase: Phase 4

Contacts and Locations

Study Locations

• Egypt
  • Suez, Egypt
    • Suez General Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Patients American Society of anesthesiologists' physical status (ASA) II because of pregnancy.
• Patients diagnosed with Postdural puncture headache following intrathecal spinal anesthesia for elective caesarean delivery.

Exclusion Criteria:

1. Patients with PDPH and a visual analog scale (VAS) score <5.
2. Patients with history of chronic headache, cluster headache, migraine, convulsions.
3. Patients with history of cerebrovascular accident, previous neurological diseases.
4. Patients with preeclampsia, eclampsia, coagulopathy.
5. Patients with severe bleeding (>20% of blood volume).
6. Patients undergoing treatment with vasopressors.
7. Patients with bronchial asthma.
8. Patients with arrhythmia, and any type of heart block.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Pyridostigmine; Parturients with postoperative PDPH and a VAS score of ≥5 will receive either 60 mg oral Pyridostigmine every 6 hours.	Drug: Pyridostigmine; Parturients with postoperative Postdural puncture headache and a Visual analogue scale (VAS score) of ≥5 will receive either 60 mg oral Pyridostigmine every 6 hours or Placebo tablets similar in shape to pyridostigmine tablets every 6 hours.
Placebo Comparator: Placebo; Parturients with postoperative PDPH and a VAS score of ≥5 will receive placebo tablets similar in shape to pyridostigmine tablets every 6 hours.	Drug: Placebo; Parturients with postoperative Postdural puncture headache and a Visual analogue scale (VAS score) of ≥5 will receive Placebo tablets similar in shape to pyridostigmine tablets every 6 hours.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The primary outcome is to determine the difference in VAS score between the Pyridostigmine group and the control group.	Participants will be asked to report the severity of their headache after sitting upright for 15 minutes, using a 10-cm VAS( Visual analogue scale) where 10 refers to the worst pain at 0 hours.	15 minutes after sitting upright
The primary outcome is to determine the difference in VAS score between the Pyridostigmine group and the control group.	Participants will be asked to report the severity of their headache after sitting upright for 15 minutes, using a 10-cm VAS( Visual analogue scale) after 6 hours.	6 hours
The primary outcome is to determine the difference in VAS score between the Pyridostigmine group and the control group.	Participants will be asked to report the severity of their headache after sitting upright for 15 minutes, using a 10-cm VAS( Visual analogue scale) after 12 hours.	12 hours
The primary outcome is to determine the difference in VAS score between the Pyridostigmine group and the control group.	Participants will be asked to report the severity of their headache after sitting upright for 15 minutes, using a 10-cm VAS( Visual analogue scale) after 24 hours.	24 hours
The primary outcome is to determine the difference in VAS score between the Pyridostigmine group and the control group.	Participants will be asked to report the severity of their headache after sitting upright for 15 minutes, using a 10-cm VAS( Visual analogue scale) after 36 hours.	36 hours
The primary outcome is to determine the difference in VAS score between the Pyridostigmine group and the control group.	Participants will be asked to report the severity of their headache after sitting upright for 15 minutes, using a 10-cm VAS( Visual analogue scale) after 48 hours.	48 hours
The primary outcome is to determine the difference in VAS score between the Pyridostigmine group and the control group.	Participants will be asked to report the severity of their headache after sitting upright for 15 minutes, using a 10-cm VAS( Visual analogue scale) after 72hours.	72 hours

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The need for an Epidural blood patch in the Pyridostigmine and control groups.	An EBP will be performed during the study if the VAS(Visual analogue scale) will be ≥5 after 72 hours from intervention start following parturient approval and consent, or if requested by the parturient at any time during the study.	72 hours
Appearance of neck stiffness in the Pyridostigmine and control groups.	Appearance of neck stiffness in the Pyridostigmine and control groups and will be recorded after asking the patients by yes or no.	Before giving the Pyridostigmine or the Placebo
Appearance of neck stiffness in the Pyridostigmine and control groups.	Appearance of neck stiffness in the Pyridostigmine and control groups and will be recorded after asking the patients by yes or no.	6 hours after the intervention
Appearance of neck stiffness in the Pyridostigmine and control groups.	Appearance of neck stiffness in the Pyridostigmine and control groups that will be recorded after asking the patients by yes or no.	12 hours after the intervention
Appearance of neck stiffness in the Pyridostigmine and control groups.	Appearance of neck stiffness in the Pyridostigmine and control groups and will be recorded after asking the patients by yes or no.	24 hours after the intervention
Appearance of neck stiffness in the Pyridostigmine and control groups.	Appearance of neck stiffness in the Pyridostigmine and control groups and will be recorded after asking the patients by yes or no.	36 hours after the intervention
Appearance of neck stiffness in the Pyridostigmine and control groups.	Appearance of neck stiffness in the Pyridostigmine and control groups and will be recorded after asking the patients by yes or no.	48 hours after the intervention
Appearance of neck stiffness in the Pyridostigmine and control groups.	Appearance of neck stiffness in the Pyridostigmine and control groups and will be recorded after asking the patients by yes or no.	72 hours after the intervention
Appearance of Nausea and vomiting in the Pyridostigmine and control groups.	Appearance of Nausea and vomiting in the Pyridostigmine and control groups that will be recorded after asking the patients by yes or no.	Before giving the Pyridostigmine or the Placebo
Appearance of Nausea and vomiting in the Pyridostigmine and control groups.	Appearance of Nausea and vomiting in the Pyridostigmine and control groups that will be recorded after asking the patients by yes or no.	6 hours after the intervention
Appearance of Nausea and vomiting in the Pyridostigmine and control groups.	Appearance of Nausea and vomiting in the Pyridostigmine and control groups that will be recorded after asking the patients by yes or no.	12 hours after the intervention
Appearance of Nausea and vomiting in the Pyridostigmine and control groups.	Appearance of Nausea and vomiting in the Pyridostigmine and control groups that will be recorded after asking the patients by yes or no.	24 hours after the intervention
Appearance of Nausea and vomiting in the Pyridostigmine and control groups.	Appearance of Nausea and vomiting in the Pyridostigmine and control groups that will be recorded after asking the patients by yes or no.	36 hours after the intervention
Appearance of Nausea and vomiting in the Pyridostigmine and control groups.	Appearance of Nausea and vomiting in the Pyridostigmine and control groups that will be recorded after asking the patients by yes or no.	48 hours after the intervention
Appearance of Nausea and vomiting in the Pyridostigmine and control groups.	Appearance of Nausea and vomiting in the Pyridostigmine and control groups that will be recorded after asking the patients by yes or no.	72 hours after the intervention

Collaborators and Investigators

• Sponsor: Ain Shams University

Study record dates

Study Major Dates

• Study Start (Actual): July 25, 2023
• Primary Completion (Actual): January 3, 2024
• Study Completion (Actual): January 3, 2024

Study Registration Dates

• First Submitted: June 28, 2023
• First Submitted That Met QC Criteria: July 29, 2023
• First Posted (Actual): August 1, 2023

Study Record Updates

• Last Update Posted (Actual): September 4, 2024
• Last Update Submitted That Met QC Criteria: August 30, 2024
• Last Verified: August 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Pain; Neurologic Manifestations; Headache Disorders; Headache Disorders, Secondary; Headache; Post-Dural Puncture Headache; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Cholinergic Agents; Enzyme Inhibitors; Cholinesterase Inhibitors; Pyridostigmine Bromide
• Other Study ID Numbers: SUEZ Med-IRB 1/2023

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED
• IPD Plan Description: according to the researchers plan
• IPD Sharing Time Frame: 1 year after study publication.
• IPD Sharing Access Criteria: available to all
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No