Effectiveness of Nebulized Dexmedetomidine for Treatment of Obstetric Post-Dural Puncture Headache

Study Overview
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Brief Summary
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Postdural puncture headache (PDPH) is a common complication, following neuraxial techniques. The obstetric population is particularly prone to PDPH. Therefore, treatment of PDPH is a key issue in obstetric anesthesia. Dexmedetomidine is a highly selective, centrally acting α2-adrenergic agonist with analgesic and anxiolytic effects. Moreover, it decreases cerebral blood flow (CBF) in humans and animals secondary to cerebrovascular vasoconstriction. It has been used via the intranasal and inhalational routes for many purposes including premedication, sedation and postoperative analgesia. Because of its desirable properties, we hypothesized that dexmedetomidine nebulization could be effective in the treatment of patients suffering from PDPH after caesarean section.

Detailed Description
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Post-Dural puncture headache (PDPH) is a well-known common devastating complication of subarachnoid block. Despite the decreasing incidences of PDPH over the last years due to the advancement in the design and smaller size of spinal needles, PDPH remains to be a common complication in post-partum patients. Female gender, typically pregnant females, young age, low body mass index, dilutional anemia, and the preference of neuraxial anesthesia for Cesarean Section renders obstetric patients to be more exposed to PDPH. Consequently, treating this complication is of paramount importance in obstetric anesthesia. The cause of PDPH is not entirely known but there is a considerable evidence support the explanation of the low cerebrospinal fluid (CSF) pressure resulting from continuous CSF leak through the tear in meninges that exceeds the CSF production rate as a main cause of PDPH. As little as 10% CSF volume loss could induce PDPH from the traction on the pain sensitive intracranial structures in the upright position combined with reflex vasodilatation. Several treatment options have been proposed which are usually consisting of bed rest in supine position, fluid therapy, analgesics, sumatriptan and caffeine. Epidural blood patch remained the gold standard therapy but it is an invasive technique. Dexmedetomidine (Dex) is a highly selective centrally acting α2-adrenoreceptor agonist that produces cooperative sedation, anxiolysis, and analgesia with minimal respiratory depression. Moreover it was found to attenuate the stress and inflammatory response to anesthetic and surgical procedures. Stimulation of α2-receptors in substantia gelatinosa of the dorsal horn leads to suppression of nociceptive neurons firing and inhibition of substance-P release also, its stimulation in the locus coeruleus area which is known to be a significant nociceptive transmission modulator terminates pain signals transmission resulting in analgesia. Additionally, an existing literature supports that Dex decreases cerebral blood flow (CBF) in humans and animals secondary to cerebrovascular vasoconstriction. Thus, the use of Dex might be a useful adjunct in certain situations that require cerebral vasoconstriction together with analgesia such as PDPH. The present study will be undertaken to test this hypothesis.

Official Title
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Effectiveness of Nebulized Dexmedetomidine for Treatment of Post-Dural Puncture Headache in Parturients Undergoing Elective Cesarean Section Under Spinal Anesthesia: Randomized Controlled Study

Conditions
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Post-Dural Puncture Headache

Intervention / Treatment
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* Drug: Dexmedetomidine Nebulization
* Other: 0.9% Saline Nebulization


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Post-partum females diagnosed with PDPH after elective caesarean section under spinal anesthesia and with visual analogue score (VAS) ≥ 4 and Lybecker et al. classification score ≥2. Age 21- 40 years old. ASA I and ASA II. Accepted mental state of the patient. Exclusion Criteria: Patient refusal. ASA Grade III and IV. Emergent caesarean section. Inadequate temporal window. Hypertensive disorders of the pregnancy. Atrial fibrillation. History of allergy to local anesthetics. History of chronic headache, migraine, convulsions, and cerebrovascular accident. Contraindication to spinal anesthesia: coagulopathy, infection at site of injection

Ages Eligible for Study
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Minimum Age: 21 Years
Maximum Age: 40 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

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: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Control group<br>received ultrasonic nebulization of 4mL 0.9% saline twice daily for 3 days | Other: 0.9% Saline Nebulization<br>* nebulization of 4mL 0.9% saline<br>|
| Active Comparator: Dexmedetomidine group<br>received ultrasonic nebulization of 1 µg/kg dexmedetomidine diluted in 4mL 0.9% saline twice daily for 3 days. The intervention will be continued until achieving a VAS score ≤3 and Lybecker et al. classification score <2 and or for a maximum of 72 hours. Patients in this group who achieved the target scores before 72 hours will be given 4ml of saline 0.9% nebulization to maintain blinding. | Drug: Dexmedetomidine Nebulization<br>* ultrasonic nebulization of 1 µg/kg dexmedetomidine for PDPH treatment<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| visual analogue score (VAS) | using the 10-cm visual analogue score (VAS) where score 0 is no headache and 10 is the worst imaginable headache with 1-3 classified as mild, 4-6 moderate, and 7-10 severe our aim to get VAS </= 3 at 24 hour from starting treatment | 24 hour | 
| Lybecker headache classification score | our aim to get Lybecker score < 2 at 24hour following treatment Lybecker et al. classification of PDPH score 1: Mild PDPH where daily activities slightly restricted. Patient is not bedridden. No associated symptoms*. Score 2:Moderate: Daily activities significantly restricted and most of the day patient is bedridden with or without associated symptoms. Score 3:Severe Daily activities completely restricted, patient is bedridden all the day and always with associated symptoms Associated symptoms include: Nausea, vomiting, vertigo, dizziness, tinnitus Photophobia, diplopia, and neck stiffness. | 24 hour | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| the effects of nebulized dexmedetomidine on cerebral blood flow by using Trans-Cranial Doppler (TCD) | TCD measurements (mean flow velocity, pulsatility index) will be performed at 0, 24, 48, 72hours | 72 hours | 
| adverse effects related to nebulized Dexmedetomidine | occurrence of any adverse effects (Hypotension, bradycardia, sedation) related to nebulized Dexmedetomidine | 72 hours |