Brain Relaxation With Mannitol and Furosemide
Condition: Brain Tumors
MeSH terms: Brain Neoplasms
Study type: Interventional

Summary: 
      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.
    

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.
    

Intervention name(s): mannitol; Furosemide; placebo
Intervention type(s): Drug; Drug; Drug
Intervention description(s): This drug is in our routine use of neuroanesthesia, are given in peroperatifyl brain relaxation; This drug is can be used alone or with mannitol for brain relaxation; mannitol alone is compared with placebo
Other intervention name(s): Lasix
Intervention MeSH terms: Furosemide; Mannitol
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary purpose: Treatment
Keywords: Mannitol; Furosemid; Brain Relaxation