Effect of Mannitol 20% Versus Hypertonic Saline 7.5% in Brain Metabolism and Oxygenation
Condition: Brain Edema; Metabolic Disturbance; Electrolyte and Fluid Balance Conditions
MeSH terms: Brain Edema
Study type: Interventional
Phase: Phase 4

Summary: 
      Usage of osmotic agents is a standard practice in neuroanesthesia since cerebral edema is a
      very common situation for patients with pathology in the brain. Cerebral edema is defined as
      the accumulation of fluid in the intracellular or extracellular compartments of the brain.
      Among other situations that have nothing to do with the brain, a supratentorial pathology
      such as a tumor, traumatic injury or an aneurysm, will lead to disruption of blood-brain
      barrier, and energy crisis of the cells that will cause mainly vasogenic and cytotoxic
      cerebral edema. The most common monitoring method for "measuring" cerebral edema is ICP
      (intracranial pressure) in which normal values are (with differences in the bibliography)
      10-15 mmHg.

      The osmotic agents used most in neuroanesthesia are mannitol 20% and hypertonic NaCl 7.5% or
      3%. Their brain relaxation effectiveness is supposed to be quite the same between the two
      different agents. Their main difference is that mannitol induces diuresis. Also, electrolyte
      disorders are another possibility after mannitol infusion. On the other hand, NaCl 7.5%
      causes vasodilation, does not induce diuresis and hemodynamically, even though it reduces
      SBP, it raises CO because of its excessive vasodilation. But both reduce cerebral edema due
      to the change of osmotic pressure in the vessels, that leads to extracting water from brain
      cells.

      A supratentorial craniotomy is de facto worsening the oxygenation and metabolism condition of
      the surgical site, adding to the problem the intracranial pathology causes in the first
      place. So if oxygen provided is low and the metabolic rate is high, the rate of anaerobic
      metabolism will raise. Measuring the oxygen in the jugular bulb is the most reliable
      monitoring method of cerebral oxygenation and metabolism.

      It becomes evident that optimization of cerebral oxygenation during a craniotomy will
      possibly affect the outcome of a patient, by improving it. So, if any superiority of one
      osmotic agent over the other could be demonstrated this will be very helpful in the decision
      making in routine clinical practice.
    

Detailed description: 
      Each participant will receive standard monitoring (ECG, SpO2, SBP, BIS, urine output,
      temperature). More detailed hemodynamic monitoring will be obtained by Edwards Lifesciences
      ClearSight system (CO, CI, SV, SVI, SVV, SVR, SVRI).

      TCI Propofol and Remifentanil will be the agents of choice for induction and maintenance in
      anesthesia and cisatracurium will be used for neuromuscular blockade for intubation.

      Protective mechanical ventilation will be chosen (7ml/kg IBW) with a Respiratory rate to
      obtain a PaCO2 of 35-40 mmHg. PEEP will be changed for the best PaO2/FiO2 ratio and FiO2 of
      choice will be 0.5.

      The radial artery catheterization will be applied for direct blood pressure measurement and
      arterial blood gas sampling ( pH, PaO2, PaCO2, HCO3, BE, Osmolality, Lactic acid, Hb,
      Glucose, Na, K will be measured).

      The jugular bulb ipsilateral to the craniotomy site will be catheterized for receiving blood
      samples for blood gas analysis. The following oxygenation and metabolic parameters /
      derivates will be measured or calculated: SjvO2, pH, PjvO2, PjvCO2, HCO3, BE, Osmolality,
      Lactic acid jv, Hb, Glucose, Na, K, AjvDO2, AjvCO2, O2ERbr, eRQbr, AjvDL, and LOI.

      The osmotic agent will be administered 20 minutes before dura matter incision. Before the
      dura mater opening the subdural space pressure will be measured and relevant CPP will be
      calculated. Brain Relaxation Score will be assessed by the neurosurgeon.

      Phases

        -  T0: 5 minutes before administration of the osmotic agent

        -  T15: 15 minutes after administration of the osmotic agent

        -  T30: 30 minutes after administration of the osmotic agent

        -  T60: 60 minutes after administration of the osmotic agent

        -  T90: 90 minutes after administration of the osmotic agent

        -  T120: 120 minutes after administration of the osmotic agent

        -  T180: 180 minutes after administration of the osmotic agent

        -  T240: 240 minutes after administration of the osmotic agent Blood samples for measuring
           S-100b will be collected at phases T0, T240 and 12 hours after osmotic agent
           administration.

      Postoperative complications, length of ICU stay, GOS-E (Glasgow Outcome Scale) and other
      neurological deficits will be recorded.
    

Intervention name(s): Mannitol; NaCl 7.5%
Intervention type(s): Drug; Drug
Intervention description(s): 4.6 ml/kg will be administered before dura opening; 2 ml/kg will be administered before dura opening
Intervention MeSH terms: Mannitol
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Outcomes Assessor)
Primary purpose: Treatment
Keywords: mannitol; hypertonic saline; brain metabolism; brain oxygenation