Medication Summary
The goals of treatment in patients with subarachnoid hemorrhage (SAH) are as follows:
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Blood pressure control
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Prevention of seizures
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Treatment of nausea
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Management of intracranial pressure
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Prevention of vasospasm
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Control of pain
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Maintenance of cerebral perfusion
Medications used for these purposes include analgesics, calcium channel blockers, antiepileptic drugs, stool softeners, antihypertensive agents, antiemetics, osmotic agents, diuretics, and general anesthetics. The use of aminocaproic acid for hemostasis is controversial.
Opioid Analgesics
Class Summary
Pain control is essential to quality patient care. It ensures patient comfort and promotes pulmonary toilet. Most analgesics have sedating properties that benefit patients who experience pain.
Fentanyl citrate (Actiq, Abstral, Onsolis, Fentora, Duragesic)
Fentanyl is a synthetic opioid that is 75-200 times more potent than morphine sulfate and has a much shorter half-life. It has less of a hypotensive effect and is safer in patients with hyperactive airway disease than morphine because of minimal to no associated histamine release. By itself, fentanyl causes little cardiovascular compromise, although the addition of benzodiazepines or other sedatives may result in decreased cardiac output and blood pressure.
Consider giving fentanyl by continuous infusion because of its short half-life. The parenteral form is the drug of choice for conscious sedation analgesia. It is ideal for analgesic action of short duration during anesthesia and the immediate postoperative period. It is also an excellent choice for pain management and sedation, with its short duration (30-60 min) and easy titration. After the initial parenteral dose, subsequent parenteral doses should not be titrated more frequently than every 3 or 6 hours.
The transdermal form of fentanyl is used only for chronic pain conditions in opioid-tolerant patients. When using the transdermal dosage form, most patients are controlled with 72-hour dosing intervals; however, some patients require dosing intervals of 48 hours.
The effects of fentanyl are easily and quickly reversed by naloxone. Fentanyl is highly lipophilic and protein bound. Prolonged exposure leads to accumulation in fat and delays the weaning process.
Calcium Channel Blockers
Class Summary
In specialized conducting and automatic cells in the heart, calcium is involved in the generation of the action potential. The calcium channel blockers inhibit movement of calcium ions across the cell membrane, depressing both impulse formation (automaticity) and conduction velocity. These agents may attenuate deleterious effects of calcium influx in patients with acute neurotrauma.
Nimodipine (Nymalize)
Nimodipine is indicated to reduce poor outcome related to aneurysmal subarachnoid hemorrhage. [32] While studies have shown benefit regarding severity of neurologic deficits caused by cerebral vasospasm following SAH, no evidence exists that nimodipine either prevents or relieves spasms of cerebral arteries. Thus, the actual mechanism of action is unknown.
Begin therapy within 96 hours of SAH. Nimodipine is given orally. If the patient cannot swallow the gel capsule because he or she is undergoing surgery or is unconscious, administer the oral solution (Nymalize, 60 mg/20 mL) via nasogastric or gastric tube and flush tubing before and after with normal saline. If the oral solution is not available, make holes at both ends of the gel capsule with an 18-gauge needle and extract the contents into a syringe, empty the contents into the patient's in situ nasogastric tube, and flush the tube with 30 mL of isotonic saline.
Anticonvulsants, Other
Class Summary
These agents prevent seizure recurrence and terminate clinical and electrical seizure activity. The use of antiepileptic drugs in patients with SAH who have not had seizures is controversial and depends on the individual preference of the neurosurgeon; they usually are used only in patients who have had seizures. Conventional loading doses may be used.
Phenytoin (Dilantin, Phenytek)
Phenytoin may act in the motor cortex, where it may inhibit spread of seizure activity. The activity of brainstem centers responsible for the tonic phase of grand mal seizures also may be inhibited. The dose should be individualized. If the daily dose cannot be divided equally, administer the larger portion at bedtime.
Phenobarbital
Phenobarbital elevates the seizure threshold and limits the spread of seizure activity; it also has sedative properties.
Fosphenytoin (Cerebyx)
Fosphenytoin is a diphosphate ester salt of phenytoin that acts as a water-soluble prodrug of phenytoin; plasma esterases convert fosphenytoin to phosphate, formaldehyde, and phenytoin; phenytoin, in turn, stabilizes neuronal membranes and decreases seizure activity.
The dose of fosphenytoin is expressed as phenytoin equivalents (PE), to avoid the need to perform molecular weight–based adjustments when converting between fosphenytoin and phenytoin sodium doses.
Fosphenytoin is intended for parenteral administration. Intravenous use is the route of choice and should be used in emergency situations.
Stool Softeners
Class Summary
These agents prevent elevation of intracranial pressure from the Valsalva maneuver.
Docusate sodium (Colace, Correctol, Dok)
Docusate is an anionic surfactant used for patients who should avoid straining during defecation. This agent allows incorporation of water and fat into stool, causing stool to soften. It has minimal laxative effect.
Senna (Senokot, Ex-Lax, Senexon, SennaGen)
Senna is an anthraquinone stimulant hydrolyzed by colonic bacteria into an active compound. It is more potent than cascara sagrada and produces considerably more abdominal pain. Senna usually produces action 8-12 hours after administration.
Beta-Blockers, Alpha Activity
Class Summary
In patients who have suffered SAH from a ruptured aneurysm, these agents are used to maintain blood pressure in a range that allows for sufficient cerebral perfusion yet limits the risk of rebleeding from elevated ICP.
Labetalol (Trandate)
Labetalol blocks alpha-, beta1-, and beta2-adrenergic receptor sites, decreasing blood pressure.
Antiemetic Agents
Class Summary
These agents are used for the treatment of nausea or vomiting.
Promethazine (Phenergan, Phenadoz, Promethegan)
Promethazine is an antidopaminergic agent effective in the treatment of emesis. It blocks postsynaptic mesolimbic dopaminergic receptors in the brain and reduces stimuli to the brainstem reticular system.
Diuretics, Osmotic Agents
Class Summary
These agents are used in an attempt to lower ICP and cerebral edema by creating an osmotic gradient across an intact blood-brain barrier; as water diffuses from the brain into the intravascular compartment, ICP decreases.
Mannitol (Osmitrol, Aridol)
Mannitol may reduce pressure within the subarachnoid space by creating an osmotic gradient between the CSF in the arachnoid space and the plasma. This agent is not for long-term use.
Diuretics, Loop
Class Summary
These agents are used to decrease plasma volume and edema by causing diuresis.
Furosemide (Lasix)
Furosemide is used in the acute setting for reduction of increased ICP. Doses must be individualized. The proposed mechanisms in lowering ICP include the following:
• Suppression of cerebral sodium uptake
• Inhibition of carbonic anhydrase, resulting in decreased CSF production
• Inhibition of the cellular membrane cation-chloride pump, thereby affecting transport of water into astroglial cells
Hemostatics
Class Summary
These agents are potent inhibitors of fibrinolysis and can reverse states that are associated with excessive fibrinolysis. Their use is controversial; consultation with admitting physicians is urged prior to use.
Aminocaproic acid (Amicar)
Aminocaproic acid inhibits fibrinolysis via inhibition of plasminogen activator substances and, to a lesser degree, through antiplasmin activity. The main problems with its use are that thrombi that form during treatment are not lysed and its effectiveness is uncertain. This agent has been used to prevent recurrence of SAH.
General Anesthetics, Systemic
Class Summary
These agents provide sedation when neuromuscular blocking agents are used for intubation.
Thiopental
Thiopental is a short-acting barbiturate sedative-hypnotic with rapid onset and a duration of action of 5-20 minutes. Like methohexital, it is most commonly used as an induction agent for intubation.
Thiopental depresses consciousness and diminishes or terminates seizure effects; it facilitates transmission or impulses from the thalamus to the cortex of the brain, resulting in an imbalance in central inhibitory and facilitating mechanisms. To use thiopental as a sedative, titrate in dosage increments of 25 mg (adjust to lower dose in children).
Etomidate (Amidate)
Amidate is a nonbarbiturate imidazole compound with sedative properties. It is short-acting and has a rapid onset of action; the duration of action is dose dependent (15-30 minutes). Its most useful feature as an induction agent is that it produces deep sedation while causing minimal cardiovascular effects.
The major application of amidate is induction for endotracheal intubation, particularly in patients with, or at risk for, hemodynamic compromise. Amidate has been shown to depress adrenal cortical function; however, this effect is not significant clinically during short-term administration. Since the drug is mixed in propylene glycol, continuous infusion not recommended.
Anxiolytics, Benzodiazepines
Class Summary
By binding to specific receptor sites, these agents appear to potentiate the effects of gamma-aminobutyrate (GABA) and to facilitate inhibitory GABA neurotransmission, as well as other inhibitory transmitters.
Midazolam
Midazolam is a shorter-acting benzodiazepine sedative-hypnotic that is useful in patients requiring acute or short-term sedation. It is also useful for its amnestic effects.
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CT scan reveals subarachnoid hemorrhage in the right sylvian fissure; no evidence of hydrocephalus is apparent.
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CT scan reveals subarachnoid hemorrhage in the sylvian fissure, right more than left.
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A 47-year-old woman presented with headache and vomiting; her CT scan in the emergency department revealed subarachnoid hemorrhage.
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Cerebral angiogram reveals a middle cerebral artery aneurysm.
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Cerebral angiogram reveals a middle cerebral artery aneurysm.
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Cerebral angiogram (lateral view) reveals a large aneurysm arising from the left anterior choroidal artery.
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Cerebral angiogram (anteroposterior view) reveals a large aneurysm arising from the left anterior choroidal artery.
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Brain CT scan showing subtle finding of blood at the area of the circle of Willis consistent with acute subarachnoid hemorrhage. Image courtesy of Dana Stearns, MD, Massachusetts General Hospital.
