The Effect of Intravenous Fluid Therapy in Acute Migraine Attacks

The Utility of Adding 1 L Intravenous Normal Saline to Standard 75 mg Intramuscular Diclofenac Potassium Injection in Patients Presented to the Emergency Department With an Acute Migraine Attack

The study is a single-center, double-blind, randomized protocol comparison. The study will be conducted in Marmara University School of Medicine Pendik Training and Research Hospital, Department of Emergency Medicine between April 2020 and October 2020.

The population consists of non-pregnant, adult patients (age of 18 or more) who will be confirmed as migraine according to The International Classification of Headache Disorders 3rd edition (ICHD-3) in the emergency department (ED). After the patient was found suitable for the standard treatment protocol, they will be randomized to receive a 1000 ml bolus of normal saline for 1 hour or normal saline at 10 cc/h for 1 hour. The pain level, functional status, and side effects will be assessed before the beginning, at the 1st hour, 2nd hour and at the 24th hour.

The objective of this study is to determine the effect of an intravenous (IV) fluid bolus on migraine headache among patients treated in the ED.

Study Overview

• Status: Unknown
• Conditions: Migraine Disorders; Headache; Acute Pain
• Intervention / Treatment: Other: Bolus fluid administration

Detailed Description

Introduction Headache is a common complaint that is seen in 70-80% of the population and is a common health problem in emergency services. When evaluating the patient with headache, the first step is to determine whether the headache is primary or secondary (1, 2). Primary headaches are classified according to their symptoms and clinical features. Tension-type headache, migraine, and cluster headache are the most common types of primary headaches (3). Secondary headaches can be classified as headaches due to the head and neck trauma, headaches secondary to neurovascular diseases, and headaches due to withdrawal syndromes secondary to drug abuse (4). Migraine is a primary type of headache characterized by recurrent throbbing (usually unilateral) and associated with photophobia, phonophobia, nausea, and other symptoms. Patients with migraine are usually not pleased with the treatment options due to headaches refractory to treatment (5).

The current approach to the treatment of migraine headaches consists of two components: treatment of the acute migraine attacks, and prophylactic treatment.

According to the World Health Organization (WHO), migraine attacks are the eighth cause of loss of work and performance in the attack period among all lifelong diseases (12). Therefore, effective treatment of migraine attacks is important for the patient and socioeconomic wellbeing of the community. More than 90% of the migraine patients experience acute migraine attacks despite prophylactic treatment and need pain medications (6). Common treatment options used in the ED are phenothiazines (7), serotonin receptor agonists (8), and corticosteroids (9). Headache guideline of the American Academy of Neurology published in 2000 also recommends diclofenac as an effective alternative for the treatment of acute migraine attacks (10, 11). Effective attack therapy has the potential to significantly reduce inefficiency caused by migraine attacks by shortening the duration and reducing the severity of attacks.

Although clinical evidence is uncertain, approximately 40% of patients presenting to the ED with a headache are treated with IV fluids (13). Studies with healthy volunteers showed that mild dehydration reduces the pain threshold and increases central pain-related activity in the anterior cingulate cortex, insula, and thalamus (14). Therefore, it is logical to think that dehydration may trigger acute migraine attacks (15). This led to the common approach to use IV fluids besides pain medications in the ED as a routine procedure. A clear benefit would obviously increase the satisfaction of the patient from the ED services, by increasing the pain threshold, decreasing length of stay, and need for rescue treatment. However, on the contrary, IV fluid therapy without an obvious benefit to the patient has a cost burden on the system, uses labor and time of the ED staff, and may increase the duration of the length of stay in the ED.

Therefore, the aim of this study is to evaluate the efficacy and side effects related to the addition of 1000 cc bolus NS to the standard treatment of migraine in the ED.

• Study Type: Interventional
• Enrollment (Anticipated): 120
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Yusuf Turan, MD; Phone Number: 8807 00902166254545; Email: dryusufturan@gmail.com

Study Locations

• Turkey
  • Istanbul, Turkey
    • Recruiting
    • Marmara University Pendik Education and Research Hospital
    • Contact: Yusuf Turan, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion criteria:

• age 18 years or older
• migraine with or without aura according to International Classification of Headache Disorders-3 (ICHD-3) diagnostic criteria confirmed by one-to-one physical exam in the ED
• no declaration and sign of pregnancy, or pregnancy not diagnosed during the ED evaluation before randomization,
• did not receive any IV fluid of 100 cc or more at any facility in the last 12 hours,
• intramuscular diclofenac potassium 75 mg, the standard treatment protocol, is ordered by the physician (no history of known allergic reaction to diclofenac potassium),
• severe dehydration not present as determined by the researcher (hypotension, dry mouth, tongue and eyeballs, decreased urine output)
• no other indication for fluid infusion,
• no contraindication to fluid administration (heart failure patients with diuretic use, renal failure patients with fluid restriction, hemodynamic instability),
• do not have accompanying symptoms and signs related to headaches secondary to other obvious pathologies rather than migraine,
• consent to be included in the study.

Exclusion criteria: no patients will be excluded from the study after randomization. All patients will be evaluated for the primary outcome with an intent-to-treat approach.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: SUPPORTIVE_CARE
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: TRIPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Saline; 1000 ml of 0.9% normal saline bolus over one hour.	Other: Bolus fluid administration; 1000 ml of 0.9% normal saline bolus over one hour
NO_INTERVENTION: No Saline; 10 ml of 0.9% normal saline over one hour.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
VAS(headache)	The patient will be asked to place a mark between the 0 and 10 cm points indicated on a 10 cm line, the distance of the marked point to 0 will be taken as the VAS(headache) score in mm.	at the 2nd hour

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
VAS(headache)	The patient will be asked to place a mark between the 0 and 10 cm points indicated on a 10 cm line, the distance of the marked point to 0 will be taken as the VAS(headache) score in mm.	at the 1st hour
VAS(nausea)	The patient will be asked to place a mark between the 0 and 10 cm points indicated on a 10 cm line, the distance of the marked point to 0 will be taken as the VASnausea score in mm.	at the 1st hour
VAS(nausea)	The patient will be asked to place a mark between the 0 and 10 cm points indicated on a 10 cm line, the distance of the marked point to 0 will be taken as the VASnausea score in mm.	at the 2nd hour
Level of Functional Disability	Categorized as none, mild (makes it difficult to do daily tasks), moderate (not able to do daily tasks), severe (requires bed rest).	at the 1st hour
Level of Functional Disability	Categorized as none, mild (makes it difficult to do daily tasks), moderate (not able to do daily tasks), severe (requires bed rest).	at the 2nd hour
Level of Functional Disability	Categorized as none, mild (makes it difficult to do daily tasks), moderate (not able to do daily tasks), severe (requires bed rest).	at the 24th hour
Adverse Events	The proportion of patients with the following adverse events in each group will be actively pursued during the administration of treatment at the ED: hypernatremia, fluid retention, high blood pressure, injection site reactions	at the 1st hour
Adverse Events	The proportion of patients with the following adverse events in each group will be actively pursued during the administration of treatment at the ED: hypernatremia, fluid retention, high blood pressure, injection site reactions	at the 2nd hour
Adverse Events	The proportion of patients with the following adverse events in each group will be actively pursued during the administration of treatment at the ED: hypernatremia, fluid retention, high blood pressure, injection site reactions	at the 24th hour
Successful Treatment	The proportion of patients will successful and failed treatments will be compared between study groups. Successful treatment is defined if VAS(headache) is decreased at least 50% from the highest VAS(headache) reported by the patient at any time-point without the need of additional analgesics and/or antiemetics. Failed treatment is defined if VAS(headache) is decreased not more than 10% from the highest VAS(headache) or patient's declaration that the headache is the same at the 2nd hour. All patients defined as failed treatment will be offered the rescue treatment (analgesic and/or antiemetic).	at the 2nd hour
Time-to-discharge	Duration between the time of admission to the emergency department and discharge up to 24 hours.	0 to 24 hours
The presence of headache	The patients will be asked to answer if their headache is still present or not, and will be requested to answer as "yes" or "no".	at the 24th hour
The recurrence of headache	The patients will be asked to answer if their headache has recurred (may still be present or not) or not, and will be requested to answer as "yes" or "no".	at the 24th hour
Ability to tolerate oral intake	If the patient could eat a regular meal without vomiting in the 30 minutes after intake, they will be considered as "able to eat". All other conditions will be considered a "no".	at the 24th hour

Collaborators and Investigators

• Sponsor: Marmara University
• Investigators: Study Director: Haldun Akoglu, MD., Prof., Marmara University

Publications and helpful links

General Publications

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Study record dates

Study Major Dates

• Study Start (ACTUAL): April 1, 2020
• Primary Completion (ANTICIPATED): October 1, 2021
• Study Completion (ANTICIPATED): November 1, 2021

Study Registration Dates

• First Submitted: December 5, 2019
• First Submitted That Met QC Criteria: February 25, 2020
• First Posted (ACTUAL): February 27, 2020

Study Record Updates

• Last Update Posted (ACTUAL): December 29, 2020
• Last Update Submitted That Met QC Criteria: December 28, 2020
• Last Verified: December 1, 2020

More Information

Terms related to this study

• Keywords: pain; adult; emergency department; migraine; diclofenac; normal saline; acute attack
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Pain; Neurologic Manifestations; Headache Disorders, Primary; Headache Disorders; Migraine Disorders; Headache; Acute Pain
• Other Study ID Numbers: 09.2019.497

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No