Intrathecal Neostigmine for Prevention of PDPH

NCT03587441 | Completed Phase 4

• 1 other identifier: M335
• Study Type: interventional
• Target: 240
• Locations: 1 country
• Sites: 1

Brief Summary

Neuraxial blocks continue to be the cornerstone of anesthesia and postoperative analgesia for normal vaginal delivery and elective caesarean section due to its approved safety and efficiency for decades. Post-dural puncture headache (PDPH) is still one of the most common complications of neuraxial anesthetic techniques. The headache could be severe and limit the activities of the new mother to care for her baby, prolong hospital stay. PDPH is defined as a headache that develops within five days of dural puncture and can't be attributed to any other types of headache and mostly is postural in character. Neostigmine methylsulfate is a synthetic carbamic acid ester which reversibly inhibits the enzyme Acetylcholine esterase (AChE) that makes more Acetylcholine molecules available at cholinergic receptors. Neostigmine is used in anesthesia mainly as a reversal for non-depolarizing neuromuscular agents. Intrathecal (IT) neostigmine was tried as an adjuvant to local anesthetics in IT block for elective cesarean sections to decrease local anesthetic consumption and to prolong postoperative analgesia. Side effects of IT neostigmine are dose-dependent with doses more than 25 µg especially nausea and vomiting and could be decreased by increasing the baricities of the local anesthetic solutions and by early head up position after IT injection. However, its effect on PDPH was not investigated before in literature. Parturients will be randomly assigned into one of two groups: the intervention group will receive 20 µg with IT Bupivacaine and the control group will receive an equivalent volume of dextrose 5% with the IT Bupivacaine. The objective of the current study is to evaluate the efficacy and safety of IT neostigmine as an adjuvant to bupivacaine in reducing the incidence and severity of post-dural puncture headache in parturients scheduled for an elective cesarean section.

Conditions

Post-Dural Puncture Headache

Keywords

postural headache; intrathecal neostigmine for prevention of PDPH

Outcome Measures

Primary Outcomes (1)

• incidence of post-dural puncture headache

  any headache that develops within five days of dural puncture and can't be attributed to any other types of headache and mostly is postural in character

  At day 5 from intrathecal block

Secondary Outcomes (26)

• Visual analog score of post-dural puncture headache (PDPH) at presentation

  At 24 hours after headache onset

• Visual analog score of post-dural puncture headache (PDPH) after medical treatment

  At 48 hours after starting medical treatment

• highest Visual analog score of post-dural puncture headache

  At 48 hours after starting medical treatment

• Percent of participants with neck stiffness

  At 48 hours after headache onset

• Percent of participants in need for epidural blood patch

  After 48 hours from onset of headache

Study Arms (2)

The Intervention Group (N)

ACTIVE COMPARATOR

Neostigmine Methylsulfate intervention : A one milliliter syringe will contain 20 µg of Neostigmine methyl sulfate. 0.5 mg ampule (1 ml) will be diluted in 4 ml dextrose 5% to make a solution of 100 µg/ml, 0.2 ml of this solution will be added to 2.5 ml of hyperbaric bupivacaine 0.5 % used for intrathecal injection.

Drug: Neostigmine Methylsulfate; Drug: Dextrose 5% in water

The Control Group (P)

PLACEBO COMPARATOR

Dextrose 5% in water intervention : an equal volume (0.2 ml) of dextrose 5% will be added to 2.5 ml of hyperbaric bupivacaine 0.5 % used for intrathecal injection.

Drug: Dextrose 5% in water

Interventions

Neostigmine Methylsulfate DRUG

20 µg Neostigmine Methylsulfate intrathecal in 0.2 ml of Dextrose 5% solution

Also known as: Neostigmine (0.5 mg)

The Intervention Group (N)

Dextrose 5% in water DRUG

intrathecal

Also known as: Dextrose 5% in Water (D5W)

The Control Group (P); The Intervention Group (N)

Eligibility Criteria

• Age: 20 Years - 40 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• American society association (ASA) physical status II parturients who will be scheduled for an elective caesarean section by IT anesthesia

You may not qualify if:

• significant renal, hepatic, and cardiovascular diseases
• pre-eclampsia
• any contraindication to regional anesthesia such as local infection or bleeding disorders
• allergy to neostigmine
• long-term opioid use
• a history of chronic pain, migraine, cluster headache
• digestive problems with nausea or vomiting
• cognitive or memory disorders
• history of urinary retention; bronchial asthma
• perioperative blood transfusion

Sponsors & Collaborators

• Fayoum University Hospital: lead

Study Sites (1)

Fayoum University hospital

El Fayoum Qesm, Faiyum Governorate, 63514, Egypt

Location

Related Publications (5)

• Headache Classification Committee of the International Headache Society (IHS). The International Classification of Headache Disorders, 3rd edition (beta version). Cephalalgia. 2013 Jul;33(9):629-808. doi: 10.1177/0333102413485658. No abstract available.

  PMID: 23771276 BACKGROUND

• Arevalo-Rodriguez I, Munoz L, Godoy-Casasbuenas N, Ciapponi A, Arevalo JJ, Boogaard S, Roque I Figuls M. Needle gauge and tip designs for preventing post-dural puncture headache (PDPH). Cochrane Database Syst Rev. 2017 Apr 7;4(4):CD010807. doi: 10.1002/14651858.CD010807.pub2.

  PMID: 28388808 BACKGROUND

• Nath S, Koziarz A, Badhiwala JH, Alhazzani W, Jaeschke R, Sharma S, Banfield L, Shoamanesh A, Singh S, Nassiri F, Oczkowski W, Belley-Cote E, Truant R, Reddy K, Meade MO, Farrokhyar F, Bala MM, Alshamsi F, Krag M, Etxeandia-Ikobaltzeta I, Kunz R, Nishida O, Matouk C, Selim M, Rhodes A, Hawryluk G, Almenawer SA. Atraumatic versus conventional lumbar puncture needles: a systematic review and meta-analysis. Lancet. 2018 Mar 24;391(10126):1197-1204. doi: 10.1016/S0140-6736(17)32451-0. Epub 2017 Dec 7.

  PMID: 29223694 BACKGROUND

• Fattahi Z, Hadavi SM, Sahmeddini MA. Effect of ondansetron on post-dural puncture headache (PDPH) in parturients undergoing cesarean section: a double-blind randomized placebo-controlled study. J Anesth. 2015 Oct;29(5):702-7. doi: 10.1007/s00540-015-2000-5. Epub 2015 Mar 27.

  PMID: 25812804 BACKGROUND

• Cossu AP, De Giudici LM, Piras D, Mura P, Scanu M, Cossu M, Saba M, Finco G, Brazzi L. A systematic review of the effects of adding neostigmine to local anesthetics for neuraxial administration in obstetric anesthesia and analgesia. Int J Obstet Anesth. 2015 Aug;24(3):237-46. doi: 10.1016/j.ijoa.2015.05.002. Epub 2015 May 19.

  PMID: 26119258 BACKGROUND

MeSH Terms

Conditions

Post-Dural Puncture Headache

Interventions

Neostigmine; Glucose; Water

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; Hexoses; Monosaccharides; Sugars; Carbohydrates; Hydroxides; Alkalies; Inorganic Chemicals; Anions; Ions; Electrolytes; Oxides; Oxygen Compounds

Study Officials

• Hany M Yassin, MD

  Faculty of medicine, Fayoum university

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor of Anesthesiology

Study Record Dates

• First Submitted: June 13, 2018
• First Posted: July 16, 2018
• Study Start: August 4, 2018
• Primary Completion: February 5, 2019
• Study Completion: February 10, 2019
• Last Updated: July 15, 2019

Record last verified: 2019-07

Data Sharing

• IPD Sharing: Will not share

Locations

EG (1)