Anesthesia Pharmacology:  General Anesthesia

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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 and ICP)

Management of intracranial volume

  •  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 by means of 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 and 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 and electrolyte excretion

 Continual perioperative steroid administration may result in these complications



GI bleeding


Electrolyte abnormalities

  • 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 α-and β-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

Stoelting, R.K., "Inhaled Anesthetics", in Pharmacology and Physiology in Anesthetic Practice, Lippincott-Raven Publishers, 1999, pp 36-76

Bendo, A.A., Kass, I.S., Hartung, J and Cottrell, J. E., "Anesthesia for Neurosurgery", in Clincial Anesthesia, 3rd Edition, ( Barash, P.G, Cullen, B. F. and Stoelting, R. K., eds) Lippincott-Raven Publishers, 1997, pp 717-720.

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