Addition of Pyridostigmine to Conventional Management of Postdural Puncture Headache

Study Overview
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Brief Summary
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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.

Official Title
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Addition of Pyridostigmine to Conventional Management of Postdural Puncture Headache

Conditions
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Postdural Puncture Headache

Intervention / Treatment
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* Drug: Pyridostigmine
* Drug: Placebo


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

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 40 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Pyridostigmine<br>Parturients with postoperative PDPH and a VAS score of ≥5 will receive either 60 mg oral Pyridostigmine every 6 hours. | Drug: Pyridostigmine<br>* 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.<br>|
| Placebo Comparator: Placebo<br>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<br>* 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.<br>|

What is the study measuring?
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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 |