Clinical Trials Logo

Clinical Trial Summary

The purpose of this study is to evaluate Neostigmine and Atropine 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.


Clinical Trial Description

Hypothesis: Neostigmine and atropine will reduce the proportion of postpartum women with a PDPH requiring EBP who developed a PDPH after accidental dural puncture with a Tuohy needle. Background: The post dural puncture headache (PDPH) is a well-documented complication of dural puncture. Depending on a number of factors, the overall incidence of PDPH following dural puncture with an epidural Tuohy needle is typically around 50%, but can be as high as 70% for certain populations (1, 2, 3). The headache is characterized as frontal or occipital in nature, with a typical onset of 6-72 hours after dural puncture. It is normally exacerbated by the upright position and improved by the supine position. Associated symptoms may include photophobia, nausea, vomiting, dizziness, tinnitus, neck stiffness, decreased hearing and visual changes (2). These symptoms tend to be extremely debilitating in affected patients, severely limiting their functional capacity until the resolution of the headache (2). The compromise is even greater in postpartum women who also need to care for a newborn, as the time after birth is important for forming attachment and encompasses many new obligations for the new mother. The treatment of the PDPH often begins with conservative treatment including supportive therapies such as hydration, bed rest, acetaminophen, NSAIDs, and oral opioids. In addition, some evidence exists for the use of caffeine (1,2). While these do not hasten recovery, they may improve symptoms. For PDPH of all etiologies, 72% will resolve spontaneously in 7 days and 89% by 14 days (1). For patients with moderate to severe symptoms or long lasting headaches, the gold standard for treatment of headaches that do not resolve is the epidural blood patch (EBP) (1,2,4). This treatment has been shown to be effective in 70-98% of patients (1,2,4). However, it has numerous contraindications including fever, infection, coagulopathy, active neurological disease, patient refusal. In addition, a potential complication is yet another dural puncture. Also, while the EBP is generally very safe, it is an invasive procedure with its own complications; it has been associated with very rare but serious complications including: moderate long-lasting backache, meningitis, epidural abscess formation, epidural hematoma formation, and neurologic deficit development (5-8). The use of neostigmine and atropine in the treatment of PDPH was first described in a randomized placebo-controlled trial in 2018 (9). The addition of neostigmine and atropine to conservative treatment for PDPH resulted in all 41 patients in the treatment group reporting a visual analog scale (NRS) score ≤ 3 after 2 doses, no recurrence of headache, and none receiving EBP. Seven out of 42 (15.9%) patients in the placebo group reported a persistent NRS ≥ 5 and all received EBP. Postulated mechanisms of action of neostigmine and atropine in the treatment of PDPH include increased CSF volume and cerebral vasoconstriction. Patients enrolled in this study developed a PDPH after spinal anesthesia using a 22-gauge Quincke needle. The effects of neostigmine and atropine on PDPH resulting from accidental dural puncture with a larger-bore, 17-gauge epidural Tuohy needle are unknown (9,10). Neostigmine and atropine, when given concomitantly, antagonize each other's adverse effects resulting in a favorable safety profile (12,13). The most common adverse effects reported include blurred vision, dry mouth, abdominal cramps, muscle twitches, and urinary urgency - all of which were transient (9,11). Additionally, simultaneous administration of neostigmine and atropine likely have a net neutral effect on oxytocin release and likely do not affect lactation or breastfeeding for the mother (14). Both neostigmine and atropine are excreted in very small amounts in the breastmilk and are unlikely to affect the breastfed infant more than transiently (15-16). Number of Participants: Enrollment of 36 with goal of 18 evaluable patients Design: Prospective Pilot Study Recruitment: In person contact by OB Anesthesia resident, OB Anesthesia fellow, Anesthesia consultant, or Research Coordinator Recruitment process: Patients will be identified as at risk on the labor and delivery ward after they have experienced a known dural puncture with a Tuohy needle. Patients will be assessed daily while in the hospital for signs and symptoms of a PDPH. If patient meets criteria after dural puncture (a positional headache after known dural puncture, worsened by the upright position, NRS score of ≥ 4), they will be informed of the study procedures, given time to ask questions regarding procedures, and decide if they consent to participation. Patients will also be counseled on the risks and benefits of EBP and can elect to proceed with EBP at any point in the study. Intervention: Parturients with a PDPH after documented accidental dural puncture with a Tuohy needle and a NRS score of ≥ 4 will receive a slow infusion of 20 μg/kg neostigmine and 10 μg/kg atropine IV given over 10 minutes. Patients will be monitored with blood pressure measurements every 3 minutes along with continuous EKG and pulse oximetry during the infusion and for 20 minutes after completion of the infusion. This regimen is repeated every 8 hours for a maximum of 3 doses. Treatments continue until a NRS score ≤ 3 is achieved or the patient elects to proceed with an epidural blood patch. Patients also receive conservative PDPH management which includes encouraging oral hydration, encouraging oral caffeine consumption in patients who regularly consume caffeine, 1 g acetaminophen every 6 hours, and 600 mg ibuprofen every 6 hours. Oxycodone 5-10 mg every 4 hours PRN may be utilized for postoperative pain. Safety Monitoring: Patients receiving the intervention will be monitored during and after the intervention for abdominal or muscle cramps, blurred vision, dry mouth, or urinary urgency by the OB anesthesia provider administering the intervention. They will be instructed to call the research PI if they have any of these complications. Patients will also be monitored with blood pressure measurements every 3 minutes along with continuous EKG and pulse oximetry during the infusion and for 20 minutes after completion of the infusion. Consent process: Consent will be obtained after identification of a PDPH after documented accidental dural puncture with a Tuohy needle and a NRS score of ≥ 4 in the patient's hospital room. Patients will be given sufficient time to ask any questions to the attending/resident anesthesiologist and research personnel related to the procedure and this research study. ;


Study Design


Related Conditions & MeSH terms


NCT number NCT05116930
Study type Interventional
Source Mayo Clinic
Contact
Status Not yet recruiting
Phase Phase 2
Start date November 8, 2021
Completion date December 31, 2023

See also
  Status Clinical Trial Phase
Completed NCT04091321 - Association Between Chronic Headache and Back Pain With Childbirth
Recruiting NCT02813655 - Evaluation of the Effectiveness and Tolerance of Tetracosactide Synacthen® in the Treatment of Post Dural Puncture Headaches (ESYBRECHE) Phase 2
Completed NCT02522013 - Aminophylline for Patients With Post-Dural Puncture Headache Phase 3
Suspended NCT03430531 - Effectiveness of Sphenopalatine Ganglion Block for Post-Dural Puncture Headache Phase 2
Completed NCT04401878 - SGB in Management of Patients With PDPH Using TCD N/A
Completed NCT04327726 - Effectiveness of Nebulized Dexmedetomidine for Treatment of Obstetric Post-Dural Puncture Headache N/A
Completed NCT03475784 - Two Fluid Strategies for Prevention of Post-dural Puncture Headache Phase 3
Not yet recruiting NCT04793490 - Sphenopalatine Ganglion Block for Management of Post- Dural Puncture Headache in Obstetric Patients N/A
Terminated NCT02827058 - The Influence of Needle Diameter on Post Dural Puncture Headache N/A
Completed NCT00370604 - Effect of Small Versus Large Epidural Needles on Postdural Puncture Headache Study N/A
Enrolling by invitation NCT03560349 - RCT of SPG Blocks for Post-dural Headache Phase 2
Not yet recruiting NCT03385772 - The Sphenopalatine Ganglion Block for Post-dural Puncture Headache N/A
Active, not recruiting NCT02362828 - EPiMAP Obstetrics: European Practices in the Management of Accidental Dural Puncture in Obstetrics
Completed NCT02149680 - Long-term Effects of Accidental Dural Puncture in Patients Having Had an Epidural Blood Patch (LEAP) N/A
Completed NCT04844229 - Bilateral Sphenopalatine Ganglion Block With or Without Bilateral Greater Occipital Nerve Block for Treatment of Obstetric Post-Dural Puncture Headache N/A
Completed NCT03997006 - Is Aminophylline More Effective Than Neostigmine/Atropine Mixture in the Treatment of Post-dural Puncture Headache Phase 4
Completed NCT03420352 - Non-Luer Butterfly Needle With One-way Valve for the Epidural Blood Patch: Does it Alter Blood Clotting? N/A
Completed NCT03080610 - The Occurrence of Post Dural Puncture Headache After Epidural Blood Patch N/A
Completed NCT03080779 - Long Term Outcomes After Accidental Dural Puncture ADP Study
Completed NCT02384031 - Post-dural Puncture Headache - Needles and Biomarkers in CSF N/A