Furosemide vs Placebo for Brain Relaxation - Full Text View

Purpose

Increased brain bulk may be problematic during brain surgery for tumors because it may limit surgical exposure and access to the surgical site. Mannitol, an osmotic diuretic, is commonly given to alleviate brain bulk, and sometimes furosemide in a small dose is added if mannitol alone is insufficient. It is unclear if adding this furosemide truly helps to diminish brain bulk, and it is possible that furosemide may cause too much diuresis, leading to dehydration and its side effects (e.g., low blood pressure). Our purpose is to investigate what the effects of furosemide are in the setting of brain surgery for tumors, specifically with regards to decreasing brain bulk and/or causing dehydration.

Study Hypothesis: The addition of furosemide to mannitol will result in improved brain relaxation in human subjects undergoing craniotomy for brain tumor resection than that seen with mannitol alone. However, the combination of mannitol and furosemide will also lead to more significant intravascular volume depletion than that seen with mannitol alone.

Condition	Intervention
Brain Swelling Brain Edema Dehydration	Drug: Furosemide Drug: Placebo

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Efficacy Study Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor) Primary Purpose: Treatment
Official Title:	The Effect of Furosemide Versus Placebo on Brain Relaxation and Incidence of Significant Intravascular Volume Depletion in Human Subjects Receiving Mannitol

Resource links provided by NLM:

MedlinePlus related topics: Dehydration Edema

Drug Information available for: Furosemide

U.S. FDA Resources

Further study details as provided by Northwestern University:

Primary Outcome Measures:

acceptable vs. unacceptable brain relaxation at dural opening [ Time Frame: 134 patients enrolled, 266 patients enrolled, 400 patients enrolled ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

intravascular volume status [ Time Frame: 134 patients enrolled, 266 patients enrolled, 400 patients enrolled ] [ Designated as safety issue: Yes ]

Enrollment:	23
Study Start Date:	February 2010
Study Completion Date:	March 2012
Primary Completion Date:	March 2012 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Active Comparator: Furosemide	Drug: Furosemide Furosemide 0.3 mg/kg
Placebo Comparator: Placebo	Drug: Placebo Placebo (up to 5mL)

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Inclusion criteria include:
- ASA PS I-III
- Age 18 or older
- Presenting for elective resection of primary or metastatic supratentorial brain tumor(s)

Exclusion Criteria:

• ASA PS IV or V
- Age less than 18
- Emergency surgery due to severely elevated ICP/impending brainstem herniation
- Concurrent use of diuretics for any indication
- Infratentorial/posterior fossa/cerebellar tumor resection
- Moderate/severe cardiac disease with limitation in contractility as measured by preoperative echocardiogram (EF < 30%)
- Severe pulmonary hypertension as measured and/or observed by preoperative studies
- Preoperative use of steroids (within 6 months, including those on standing doses)
- Pregnancy

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT01054404

Locations

United States, Illinois
Northwestern University
Chicago, Illinois, United States, 60611

Sponsors and Collaborators

Northwestern University

Investigators

Principal Investigator:	John F Bebawy, MD	Northwestern University
Study Director:	Dhanesh K Gupta, MD	Northwestern University

More Information

Publications:

Thenuwara K, Todd MM, Brian JE Jr. Effect of mannitol and furosemide on plasma osmolality and brain water. Anesthesiology. 2002 Feb;96(2):416-21.

Todd MM, Cutkomp J, Brian JE. Influence of mannitol and furosemide, alone and in combination, on brain water content after fluid percussion injury. Anesthesiology. 2006 Dec;105(6):1176-81.

Rudehill A, Lagerkranser M, Lindquist C, Gordon E. Effects of mannitol on blood volume and central hemodynamics in patients undergoing cerebral aneurysm surgery. Anesth Analg. 1983 Oct;62(10):875-80.

Todd MM, Warner DS, Sokoll MD, Maktabi MA, Hindman BJ, Scamman FL, Kirschner J. A prospective, comparative trial of three anesthetics for elective supratentorial craniotomy. Propofol/fentanyl, isoflurane/nitrous oxide, and fentanyl/nitrous oxide. Anesthesiology. 1993 Jun;78(6):1005-20.

Rozet I, Tontisirin N, Muangman S, Vavilala MS, Souter MJ, Lee LA, Kincaid MS, Britz GW, Lam AM. Effect of equiosmolar solutions of mannitol versus hypertonic saline on intraoperative brain relaxation and electrolyte balance. Anesthesiology. 2007 Nov;107(5):697-704.

Responsible Party:	John Bebawy, Assistant Professor of Anesthesiology & Neurological Surgery, Northwestern University
ClinicalTrials.gov Identifier:	NCT01054404 History of Changes
Other Study ID Numbers:	STU00016126
Study First Received:	January 20, 2010
Last Updated:	April 2, 2013
Health Authority:	United States: Institutional Review Board

Keywords provided by Northwestern University:

Brain Swelling
Brain Edema
Dehydration

Additional relevant MeSH terms:

Brain Edema
Dehydration
Edema
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Water-Electrolyte Imbalance
Metabolic Diseases
Pathologic Processes
Signs and Symptoms

Furosemide
Sodium Potassium Chloride Symporter Inhibitors
Membrane Transport Modulators
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Diuretics
Natriuretic Agents
Physiological Effects of Drugs
Cardiovascular Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on May 23, 2013