Comparison of effect of equiosmolar doses of Mannitol and mannitol plus glycerol combination on brain relaxation and systemic hemodynamics in elective supratentorial tumor surgeries- A Randomized Controlled Trial

The trial will commence after approval from the Institute ethics committee (IEC) and registration Clinical trials registry of India (CTRI). All participants satisfying the inclusion and exclusion criteria will be enrolled in the study after obtaining written informed consent.Standard pre anaesthetic evaluation of all participants will be performed. Preoperatively, Glasgow coma score (GCS) and imaging parameters including location and size of tumor and midline shift will be noted.

Participants will randomly be allocated into two groups – 20% mannitol (M group), and 10% Glycerol with 10% Mannitol (group G) by a computer-generated randomization table prior to induction of anaesthesia.

In the operating room, peripheral intravenous line will be secured and 0.9% normal saline at 100cc/h will be administered for fluid management. The standard monitors including electrocardiogram (ECG), non-invasive blood pressure (NIBP), and pulse oximeter will be attached. After preoxygenation with 100% O2 for 3 min, general anaesthesia will be induced with 2 mcg/kg fentanyl and 2 mg/kg propofol. Muscle relaxation will be achieved using 0.1 mg/kg vecuronium bromide to facilitate endotracheal intubation. Invasive arterial BP monitoring will be performed in all cases as per protocol. Central venous catheter may be placed depending on surgical requirement. A multiplane Trans esophageal echo probe will be introduced to obtain the mid esophageal long-axis view through which the LVOT diameter (cm) will be recorded. Then the TEE probe will be fixed in the trans-gastric long-axis view and the LVOT-VTI, LV end diastolic area (EDA), end systolic area (ESA), fractional area change, stroke volume (SV), and cardiac output (CO) will be recorded and calculated at baseline.

Intraoperatively, anaesthesia will be maintained using air: oxygen mixture with FiO2 40%, with 0.7–1 minimal alveolar concentration (MAC) of isoflurane. Opioids for analgesia and vecuronium bromide for muscle relaxation will be repeated as per requirement. Ventilatory parameters will be adjusted to maintain normocapnia. HR and invasive arterial blood pressure will be maintained within 20% of the baseline values. Normal saline (0.9%) will be used as maintenance fluid at 2 ml/kg/h with additional replacement for urine output, third space loss, and blood loss. At the time of scalp incision patients will receive 5 ml/kg of either 20% mannitol or 3ml/kg of 10% mannitol with glycerol over a period of 20 minutes. Once the first burr hole is drilled, the operating surgeon will insert a 20G intravenous cannula subdurally for measurement of intracranial pressure. This will be accomplished using a fluid-filled pressure transducer and the value of ICP will be displayed on the monitor. After craniotomy and dural opening, brain relaxation will be assessed by the operating neurosurgeon blinded to the study drug on a four-point scale: Perfectly relaxed – 1, Satisfactorily relaxed – 2, Firm brain – 3, Bulging brain – 4. If surgeon is not satisfied with the degree of brain relaxation on dural opening, an additional bolus dose of 3 ml/kg of Mannitol (Standard drug) will be administered and hyperventilation to a PaCO2 of 30-35 mm Hg will be initiated to provide relaxation for surgical access.

TEE derived parameters- LV end diastolic area (EDA), end systolic area (ESA), fractional area change, stroke volume (SV), left ventricular outflow tract velocity time integral (LVOT-VTI) and cardiac output (CO) are recorded at various time.points- baseline (after induction of anaesthesia), initiation of study drug, completion of study drug infusion, and then 30 minutes for next 2 hours followed by hourly recordings till the end of the procedure.

Details regarding fluid input, blood loss, blood transfused, duration of anaesthesia, extubation will be noted. Blood gas analysis, random blood glucose(RBS), and Serum osmolarity will be performed prior to- and two hours after administration of study drug. At the end of surgery patients will be either extubated or shifted to neurosurgical intensive care unit for elective mechanical ventilation. All data will be recorded on a standard proforma.