Brain Relaxation With Mannitol and Furosemide

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.

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.

Eligibility Criteria:
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