Brain Relaxation With Mannitol and Furosemide

March 14, 2016 updated by: Eren Fatma Akcil, Istanbul University

Comparison of Mannitol Alone Versus Different Doses of Mannitol in Combination With Furosemide on Brain Relaxation in Supratentorial Mass Resection Surgery

Although mannitol is used for brain relaxation during neurosurgery and in the treatment of raised intracranial pressure; there is not a consensus on its safe and effective dose, the duration of its administration and its use in combination with loop diuretics. This study aimed to compare the effects of the mannitol alone and in combination with furosemide in different doses, on the brain relaxation, electrolyte, lactate levels of the blood, peroperative fluid balance and the volume of the urine in supratentorial mass resection surgeries.

This prospective, randomized, double blind, placebo controlled study included fifty one patients (ASA I-III) scheduled for elective supratentorial mass resection surgery. The patients were randomized into three groups for investigation of the effects of mannitol alone and in combination with furosemide in different doses. Blood sodium, potassium, chlorine, lactate, urine and osmolarity levels were recorded. The brain relaxation score (BRS) was evaluated twice by the surgeon using a 4 point scale (1=very good, 2=good, 3=bad, 4=very bad); at dura opening, and 30 minutes after the administration of the study drug.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

After obtaining approval from the ethics committee and informed consent, a total of 51 patients aged 20-70 years, conscious and American Society of Anesthesiologists (ASA) class I-III, who had intracranial shift and who were scheduled for supratentorial mass resection under elective conditions, were included in the present prospective, randomized, double-blind and placebo-controlled study. Patients with decompensated heart failure, kidney insufficiency, diabetes insipidus, electrolyte imbalance and who are unconscious were excluded from the study.

Drug doses were determined based on the ideal body weight (IBW) or adjusted body weight (ABW) if the real body weight was 30 percent higher than the calculated ideal weight.

After premedication with midazolam (0.03 mg.kg-1) (Dormicum®, Roche, Basel, Switzerland), the patients were moved to the operating room and placed under continuous monitoring with electrocardiography (ECG), non-invasive blood pressure measurement and peripheral oxygen saturation. Intravenous (IV) bolus doses of propofol (2 mg.kg-1) (Propofol®, Fresenius Kabi, Homburg, Germany) rocuronium (0.6 mg.kg-1) (Curon®, Mustafa Nevzat, Istanbul, Turkey), remifentanil infusion (0.15 µg.kg-1) (Ultiva®, Glaxo Smith Kline, London, UK) and 0.7 FiO2 oxygen-air were used in the induction of anesthesia, while remifentanil (0.15 µg.kg-1) (Ultiva®, Glaxo Smith Kline, London, UK), rocuronium (0.03 mg.kg-1) (Curon®, Mustafa Nevzat, Istanbul, Turkey) infusions, and 0.5-1 MAC sevoflurane (Sevorane®, Abbvie, North Chicago, USA) in a mixture of 0.4 FiO2 oxygen-air were used in the maintenance. A nasogastric tube was inserted into each patient after intubation, and invasive blood pressure monitoring was continued with arterial cannulation, while urine output was monitored by inserting a foley urinary catheter. The body temperature was measured by urinary catheter. In the IV fluid management; balanced fluids were administered (Isolayte-S® , Eczacıbaşı Baxter, Istanbul, Turkey) for maintenance and replacement, colloids and blood products were also administered in the case of bleeding. At the time of wound closure tramadol 100 mg (Contramal®, Abdi İbrahim, Istanbul, Turkey) and ondansetron 8 mg IV (Zofer®, Glaxo Smith Kline, London, UK) were administered. At the end of the operation, decurarization was carried out through the administration of atropine (0.01 mg.kg-1) (Atropine sülfat®, Galen, Istanbul, Turkey) and neostigmine (0.02 mg.kg-1) (Neostigmine®, Adeka, Samsun, Turkey).

The patients were randomized into 3 groups using a closed envelope method, group 1; mannitol 0.5 g.kg-1 and furosemide 0.5 mg.kg-1 (G1), group 2; mannitol 1 g.kg-1 and furosemide 0.5 mg.kg-1 (G2) and group 3; mannitol 0.5 g.kg-1 and placebo (G3). All medications were prepared by a single nurse in 100 mL of a 0.9 percent isotonic saline solution. After head fixation, all patients were administered with mannitol (over 20 minutes) and the study drug. Arterial blood gas (ABG) analysis (Cobas b 221 blood gas analyzer, Roche®, Basel, Switzerland) was made at 30 minute intervals in the first 2 hour and then again in the 6th, 12th and 24th hours after study drug administration. Blood sodium, potassium, chlorine, lactate levels and urine output were recorded in each intervals. Blood osmolarity measured levels were recorded before the study drug administration and 2nd hours. The brain relaxation score (BRS) was evaluated twice by the surgical team using a 4 point scale (1= very good, 2= good, 3= bad, 4= very bad); first, at the time of dura opening, and second, 30 minutes after the administration of the study drug.

All patients were extubated at the end of the surgery and followed in the neurosurgical-intensive care unit (NICU) for 24 hours postoperatively.

The surgery type was recorded. The volume of peroperative blood loss, transfused blood products, the volume of the given peroperative IV fluids and fluid balance were also recorded.

Statistical analysis:

On the basis of previous study (10) and the assumption that a difference of 1 unit on BRS from 1 to 4 in brain relaxation is clinically relevant, setting α equal to 0.05 and β equal to 0.9, we calculated a sample size of 15 patients per group. To compensate for dropouts, the study included 51 patients.

Statistical analysis was performed using SPSS (Statistical Package for Social Sciences) for Windows 21.0. Differences between the groups were analysed by using one-way analysis of variance (ANOVA) with the post-hoc Tukey analysis. The differences in ASA, gender and BRS between groups were analyzed by using Pearson chi-square test. Differences within groups in electrolyte and lactate levels, osmolarity and BRS were analyzed by repeated measures of ANOVA with the post-hoc Bonferroni correction test. Values of p ≤ 0.05 were considered statistically significant.

Study Type

Interventional

Enrollment (Actual)

47

Phase

  • Not Applicable

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

20 years to 70 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Intracranial shift
  • Scheduled for supratentorial mass resection under elective conditions

Exclusion Criteria:

  • Decompensated heart failure
  • kidney insufficiency
  • Diabetes insipidus,
  • Electrolyte imbalance and
  • Who are unconscious

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Mannitol,furosemide
Mannitol 0.5mg/kg and furosemide 0.5mg/kg IV is compared with mannitol 1mg/kg and furosemide 0.5mg/kg
Drug: mannitol
This drug is in our routine use of neuroanesthesia, are given in peroperatifyl brain relaxation
Drug: Furosemide
This drug is can be used alone or with mannitol for brain relaxation
Other Names:
  • Lasix
Placebo Comparator: Mannitol, placebo
Mannitol 0.5mg/kg and placebo is compared with mannitol+forosemide
Drug: mannitol
This drug is in our routine use of neuroanesthesia, are given in peroperatifyl brain relaxation
Drug: placebo
mannitol alone is compared with placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
brain relaxation score
Time Frame: Change in brain relaxation in 30 minutes after drug administration
evaluated by surgical team using 4 point scale (1= very good, 2= good, 3= bad, 4= very bad)
Change in brain relaxation in 30 minutes after drug administration

Secondary Outcome Measures

Outcome Measure
Time Frame
Blood sodium levels (mEq/L)
Time Frame: change in 30 minute intervals in the first 2 hour and then again in the 6th, 12th and 24th hours after study drug administration
change in 30 minute intervals in the first 2 hour and then again in the 6th, 12th and 24th hours after study drug administration
Blood potassium levels (mEq/L)
Time Frame: change in 30 minute intervals in the first 2 hour and then again in the 6th, 12th and 24th hours after study drug administration
change in 30 minute intervals in the first 2 hour and then again in the 6th, 12th and 24th hours after study drug administration
Blood chlorine levels (mEq/L)
Time Frame: change in 30 minute intervals in the first 2 hour and then again in the 6th, 12th and 24th hours after study drug administration
change in 30 minute intervals in the first 2 hour and then again in the 6th, 12th and 24th hours after study drug administration
Blood lactate levels (mmol/L)
Time Frame: change in 30 minute intervals in the first 2 hour and then again in the 6th, 12th and 24th hours after study drug administration
change in 30 minute intervals in the first 2 hour and then again in the 6th, 12th and 24th hours after study drug administration
24 hours diuresis (mL)
Time Frame: change in 24th hours after study drug administration
change in 24th hours after study drug administration
Fluid balance during operation (mL)
Time Frame: Change in balance during operation time
Change in balance during operation time

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Istanbul University

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

July 1, 2013

Primary Completion (Actual)

May 1, 2015

Study Completion (Actual)

November 1, 2015

Study Registration Dates

First Submitted

March 1, 2016

First Submitted That Met QC Criteria

March 14, 2016

First Posted (Estimate)

March 18, 2016

Study Record Updates

Last Update Posted (Estimate)

March 18, 2016

Last Update Submitted That Met QC Criteria

March 14, 2016

Last Verified

March 1, 2016

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • Cerrahpasa Neuroanesthesia

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

Undecided

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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