Neurosurgical Considerations: Pharmacological Aspects

Example: Supratentorial Intracranial Tumors

• Supratentorial Intracranial Tumors

  • Meningiomas

  • Gliomas

  • metastatic lesions

•  Compensatory mechanisms to accommodate tumor growth:

  •  CSF compartment compression

  •  Cerebral vein compression

• Initially minimal clinical presentations despite elevated ICP, brain structural shifts, and significant mass effect

•  Factors causing significant increases in ICP:

  •  Development of a hemorrhagic, necrotic, central volume-- which may increase in volume rapidly

  •  Increased cerebral edema surrounding lesion

  •  In the absence of remaining compensatory mechanisms to accommodate increasing mass effect, small increases in arterial pressure can cause large increases in CBF (increases in intracranial volume & ICP)

•  Primary goal: reduction of intracranial volume

  • Pharmacological agents:

    •  Corticosteroids; diuretics; anesthetic agents

  • Non-pharmacological interventions:

    •  Hyperventilation; BP control; fluid restriction; body position; hypothermia

• Management of intracranial hypertension

  •  ICP reduction--rapid-brain dehydration

    • Mannitol (Osmitrol) --Osmotic diuretic

      • IV infusion; 0.25-1.0 g/kg; duration of action = two hours; action begins in about 10-15 minutes

      • Larger doses -- longer duration of action; may induce metabolic abnormalities;

      • Mechanism of action: Mannitol (Osmitrol) increases blood osmolality relative to the brain -- pulling water from the brain to restore osmolar balance.

        • Mannitol (Osmitrol) may cause vascular smooth muscle dilation:

        •  Vasodilation of intracranial & extracranial vessels transiently increase ICP (systemic blood-pressure will decrease during this time)

      •  To avoid/minimize initial ICP increase due to mannitol (Osmitrol):

        • Infuse slowly (> 10 minutes infusion time)

        • Administer mannitol (Osmitrol) concurrently with other interventions that decrease ICP, e.g. hyperventilation, steroids

      •  Cautious Use -- mannitol (Osmitrol):

        • Patients with cardiovascular disease

          •  Rationale: increase in intravascular volume due to mannitol (Osmitrol) may cause left ventricular failure

          • In this patient subgroup, with reduced left ventricular capacity: furosemide (Lasix) may be more appropriate for lowering ICP

        •  Prolonged use: -- mannitol (Osmitrol)

          •  Dehydration

          •  Hyperosmolality

          •  Reduced kidney function

          •  Dehydration

    • Furosemide (Lasix)-- loop diuretic

      • Mechanisms of action responsible for ICP reduction:

        1. Systemic diuresis

        2. Decreased CSF production

        3. Reducing cerebral edema by enhancing water transport

      • Furosemide (Lasix) reduces ICP without increasing cerebral blood volume or blood osmolality

      • Not as effective in reducing ICP compared to mannitol (Osmitrol)

      • Administration:

        •  Monotherapy: (0.5-1 mg/kg)

        •  In combination with mannitol (Osmitrol) -- furosemide (Lasix) (lower dose: 0.15-0.3 mg/kg)

        •  Combination treatment (furosemide (Lasix) + mannitol (Osmitrol)):

          •  More effective than mannitol (Osmitrol) alone in reducing intracranial pressure

          •  More severe electrolyte imbalance and dehydration

            •   Combination treatment-- intraoperative implications:

              •  Monitor electrolytes carefully

              •  Replace potassium when required.

  •  ICP Reduction: Corticosteroids

    •  Hours to days required for clear ICP effect

    •  Preoperative steroid administration may cause neurologic improvement before ICP reduction

    •  Several suggested mechanisms of action for reduced cerebral edema including:

      •  Brain dehydration

      •  Blood-brain barrier repair

      •  Enhancement of water & electrolyte excretion

• ICP Reduction-- Mainstay Therapeutic Intervention is Hyperventilation to a PaCO₂ of 25-30 mm Hg

  •  Effective for both acute and subacute management

  •  Mechanism of action:

    •  Decreases CBF by cerebral vasoconstriction

  • Duration of effectiveness: as short as four-six hours (depending on CSF pH)

  • Effectiveness of hyperventilation for lowering ICP:

    • Requires normal cerebrovascular CO₂ reactivity

    • Factors which may impair cerebrovascular CO₂ responsiveness include:

      •  Vasoparalysis secondary to significant intracranial disease (ischemia, trauma, infection, tumor)

  • Therapeutic concerns:

    •  PaCO₂ < 20 mm Hg (< 25 mm Hg in some cases) may lead to ischemia secondary to extreme cerebral vasoconstriction

      • Therapeutic effectiveness/safety assessment: monitor jugular venous oxygen saturation (SjO₂) as an indication of cerebral global oxygenation)

    • With enflurane (Ethrane), hyperventilation increases the risk of seizure activity (which may increase cerebral metabolic rate and CO₂ production)

      •  These changes can increase CBF, further increasing ICP.

•  Therapeutic Goals: Management of blood pressure and ICP:

  •  Maintain/control cerebral perfusion pressure and intracranial vascular dynamics to avoid:

    •  Cerebral ischemia

    •  Hemorrhage

    •  Edema

    •  Herniation

  • Management of severe hypotension which may cause cerebral ischemia

    •  Volume replacement, positive isotropic drugs, vasopressors

  •  Severe hypertension:

    • Worsened cerebral edema

    • Intracranial hemorrhage

    • Herniation

    • Agents which reduce systemic blood pressure in patients with elevated ICP with limited/no effect on CBF or ICP:

      • Propranolol (Inderal)

      • Esmolol (Brevibloc)

      • Labetalol (Trandate, Normodyne) (combined alpha-& beta-adrenergic blockade)

Muscle Relaxants and Intracranial Pressure (ICP)

•  Succinylcholine (Anectine):

  •  Increases ICP in some patients with compromised intracranial compliance

    •  Probably secondary to increased muscle afferent activity causing increased CNS stimulation

  •  Succinylcholine (Anectine)-mediated increase blocked by:

    • a full, paralyzing vecuronium (Norcuron) dose or

    • by pretreatment (defasciculating dose) of metocurine (Metubine Iodide)-- probably a reducing afferent input following succinylcholine (Anectine)

    • Succinylcholine (Anectine): Not recommended for elective neurosurgery

    • Succinylcholine (Anectine): Best agent for rapid sequence tracheal intubation to achieve total paralysis

      • Use recommended in ER/ICU setting -- with aspiration risk present or immediate neurological assessment is required

      • Anesthetic depth should be established which minimizes ICP-increases associated with laryngoscopy, intubation, and tracheal suctioning.

    •  Avoid succinylcholine (Anectine) in hemiplegic/paraplegic patients due to hyperkalemia risk

      •  Succinylcholine (Anectine)-induced hyperkalemia also seen in non-paraplegic patients who have:

        • Closed head injury

        • Ruptured cerebral aneurysm

• Nondepolarizing muscle relaxants:

  • Appropriate except for those agents which promotes histamine release (histamine: decreases BP, increases ICP (lowering cerebral perfusion pressure))

  • Agents which release histamine (which may increase ICP): d-tubocurarine> metocurine (Metubine Iodide) > atracurium (Tracrium) > mivacurium (Mivacron)

  • Doxacurium (Nuromax): minimal/no histamine release

  • Atracurium (Tracrium): at intubating doses: no significant ICP, BP, or CPP effect in neurosurgical patients

• Preferred agents: -- Steroidal compounds

  • Pancuronium (Pavulon), pipecuronium (Arduan), vecuronium (Norcuron), rocuronium (Zemuron): no direct effects on ICP

    •  In patients with abnormal autoregulation, vagolytic effects associated with pancuronium (Pavulon) may produce an ICP increase.

• Induction Sequence: with elevated ICP

  • IV thiopental (Pentothal) (3-5 mg/kg) then an opioid (fentanyl (Sublimaze) 3-5 ug/kg and muscle relaxant

    •  Vecuronium (Norcuron) (0.1 mg/kg) with concurrent controlled hyperventilation with 100 percent O₂.

    •  Deepen anesthesia:

      • Fentanyl (Sublimaze) -- 50 ug increments: total dose-- 10 ug/kg (noting blood-pressure response)

    •  Lidocaine (Xylocaine) (1.5 mg/kg) administered IV 90 seconds prior to intubation (laryngeal reflex suppression)

      •  Following disappearance of peripheral muscle twitch: additional 2-3 mg/kg thiopental (Pentothal) bolus.

    •  Esmolol (Brevibloc) may be required to reduce heart rate/BP associated with laryngoscopy and intubation

• Anesthesia Maintenance in patients with supratentorial tumors

  • Nitrous oxide-opioid mixture; nitrous oxide-volatile agent

    • Most common opioid used: fentanyl (Sublimaze)

    • Most common volatile agent used: isoflurane (Forane)

  • Nitrous oxide -- 50%-70% in oxygen reduces total IV agent dose or volatile agent concentration required

    •  Note that nitrous oxide may increase ICP and CBF more than isoflurane (Forane)

  • In patients with high ICP or low intracranial compliance: nitrous oxide or high isoflurane (Forane) concentrations (> 1%) may be avoided using:

    •  an opioid-thiopental (Pentothal) or propofol (Diprivan) technique with midazolam (Versed) or low-dose isoflurane (Forane) added for amnestic effect

  • With severe intracranial hypertension despite (a) steroids (b) hyperventilation and (c) diuretic administration--totally IV technique recommended, e.g.:

    • thiopental (Pentothal) infusion + fentanyl (Sublimaze) boluses/infusion and/or lidocaine (Xylocaine) infusion