Furosemide vs Placebo for Brain Relaxation

• Sponsor: Northwestern University (Other)
• Overall Status: Terminated
• CT.gov ID: NCT01054404
• Collaborator: (none)
• Enrollment: 23
• Location: 1
• Arms: 2
• Duration (Months): 24.9
• Patients Per Site Per Month: 0.9

Study Details

Study Description

Brief Summary

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 or Disease	Intervention/Treatment	Phase
Brain Swelling; Brain Edema; Dehydration	Drug: Furosemide; Drug: Placebo	N/A

Detailed Description

Rating of brain relaxation will be on a 4-point scale:

0 = brain very relaxed under dura, acceptable

1. = brain adequately relaxed under dura, acceptable

2. = brain slightly tense under dura, acceptable

3. = brain very tense under bulging dura, unacceptable

Study Design

• Study Type: Interventional
• Actual Enrollment: 23 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, 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
• Study Start Date: Feb 1, 2010
• Actual Primary Completion Date: Mar 1, 2012
• Actual Study Completion Date: Mar 1, 2012

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Furosemide Furosemide 0.3 mg/kg	Drug: Furosemide; Furosemide 0.3 mg/kg; Other Names: Lasix
Placebo Comparator: Placebo Up to 5 mL saline	Drug: Placebo; Placebo (up to 5mL); Other Names: Saline

Outcome Measures

Primary Outcome Measures

1. Acceptable vs. Unacceptable Brain Relaxation at Dural Opening [just prior to dural opening for each subject]

   Rating of brain relaxation will be on a 4-point scale: 0 = brain very relaxed under dura, acceptable = brain adequately relaxed under dura, acceptable = brain slightly tense under dura, acceptable = brain very tense under bulging dura, unacceptable

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Locations

	Site	City	State	Country	Postal Code
1	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

Study Documents (Full-Text)

None provided.

More Information

Publications

• 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.
• 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.
• 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.
• 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.

• Responsible Party: John Bebawy, Assistant Professor of Anesthesiology & Neurological Surgery, Northwestern University
• ClinicalTrials.gov Identifier: NCT01054404
• Other Study ID Numbers: STU00016126
• First Posted: Jan 22, 2010
• Last Update Posted: Aug 2, 2013
• Last Verified: Jun 1, 2013

• Keywords provided by John Bebawy, Assistant Professor of Anesthesiology & Neurological Surgery, Northwestern University: Brain Swelling; Brain Edema; Dehydration
• Additional relevant MeSH terms: Brain Edema; Dehydration; Furosemide

Study Results

Participant Flow

Pre-assignment Detail	23 patients enrolled sequentially, no dropouts

Arm/Group Title	Furosemide	Placebo
Arm/Group Description	Furosemide : Furosemide 0.3 mg/kg	Placebo : Placebo (up to 5mL)
Period Title: Overall Study
STARTED	10	13
COMPLETED	10	13
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	Furosemide	Placebo	Total
Arm/Group Description	Furosemide : Furosemide 0.3 mg/kg	Placebo : Placebo (up to 5mL)	Total of all reporting groups
Overall Participants	10	13	23
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	8 80%	10 76.9%	18 78.3%
>=65 years	2 20%	3 23.1%	5 21.7%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	51 (16.6)	52.1 (15.6)	51.6 (15.7)
Sex: Female, Male (Count of Participants)
Female	4 40%	6 46.2%	10 43.5%
Male	6 60%	7 53.8%	13 56.5%
Region of Enrollment (participants) [Number]
United States	10 100%	13 100%	23 100%

Outcome Measures

1. Primary Outcome

Title	Acceptable vs. Unacceptable Brain Relaxation at Dural Opening
Description	Rating of brain relaxation will be on a 4-point scale: 0 = brain very relaxed under dura, acceptable = brain adequately relaxed under dura, acceptable = brain slightly tense under dura, acceptable = brain very tense under bulging dura, unacceptable
Time Frame	just prior to dural opening for each subject

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Furosemide	Placebo
Arm/Group Description	Furosemide : Furosemide 0.3 mg/kg	Placebo : Placebo (up to 5mL)
Measure Participants	10	13
Mean (Standard Error) [units on a scale 0-3]	1.5 (.17)	1.3 (.13)

Adverse Events

Arm/Group Title	Furosemide		Placebo
Arm/Group Description	Furosemide : Furosemide 0.3 mg/kg		Placebo : Placebo (up to 5mL)
All Cause Mortality
	Furosemide		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Furosemide		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/10 (0%)		0/13 (0%)
Other (Not Including Serious) Adverse Events
	Furosemide		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/10 (0%)		0/13 (0%)

Limitations/Caveats

Recruitment was stopped at 23 subjects because of concern that the administration of furosemide was producing such a large diuresis that clinically significant and potentially unsafe hypovolemia and electrolyte abnormalities were developing.

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.