Nursing Pharmacology Chapter 14:  General Anesthesia Comparative Pharmacology and Physiology

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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 & 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--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 and electrolyte excretion

 Continual perioperative steroid administration -- 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:


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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