eMedicine Specialties > Emergency Medicine > Neurology

Subarachnoid Hemorrhage

Rami C Zebian, MD, Resident Physician, Department of Internal Medicine, University of Texas Medical School at Houston
A Antoine Kazzi, MD, Chair and Medical Director, Department of Emergency Medicine, American University of Beirut, Lebanon

Updated: Feb 25, 2009

Introduction

Background

Subarachnoid hemorrhage (SAH) implies the presence of blood within the subarachnoid space from some pathologic process. The common medical use of the term SAH refers to the nontraumatic types of hemorrhages, usually from rupture of a berry aneurysm or arteriovenous malformation (AVM). The scope of this article is limited to these nontraumatic hemorrhages.

Frequency

United States

Annual incidence of nontraumatic aneurysmal subarachnoid hemorrhage is 6-25 cases per 100,000. More than 27,000 Americans suffer ruptured intracranial aneurysms each year. Annual incidence increases with age and probably is underestimated because death is attributed to other reasons that are not confirmed by autopsies.

International

Varying incidences of subarachnoid hemorrhage have been reported in other areas of the world (2-49 cases per 100,000).

Mortality/Morbidity

• An estimated 10-15% of patients die before reaching the hospital. Mortality rate reaches as high as 40% within the first week. About half die in the first 6 months.
• Mortality and morbidity rates increase with age and poorer overall health of the patient.
• Advances in the management of subarachnoid hemorrhage have resulted in a relative reduction in mortality rate that exceeds 25%. However, more than one third of survivors have major neurologic deficits.

Race

Blacks have a higher risk for subarachnoid hemorrhage than whites (2.1:1).¹

Sex

Incidence of aneurysmal subarachnoid hemorrhage is higher in women than in men.

Age

Mean age of those experiencing subarachnoid hemorrhage is 50 years.

Clinical

History

• Headaches
  • Patient experiences sudden onset of a severe headache.
  • Prodromal (warning) headache(s) from minor blood leakage (referred to as sentinel headache) is reported in 30-50% of aneurysmal subarachnoid hemorrhages.
    • Sentinel headaches may occur a few hours to a few months before the rupture, with a reported median of 2 weeks prior to diagnosis of SAH.
    • Minor leaks commonly do not demonstrate signs of elevated intracranial pressure (ICP) or meningeal irritation.
    • Minor leaks are not a feature of AVM.
    • More than 25% of patients experience seizures close to the acute onset; the location of a seizure focus has no relationship to the location of the aneurysm.
• Nausea and/or vomiting
• Symptoms of meningeal irritation (eg, neck stiffness, low back pain, bilateral leg pain): These are seen in more than 75% of cases of subarachnoid hemorrhage, but many take several hours to develop.
• Photophobia and visual changes
• Loss of consciousness: About half of patients experience this at the time of bleeding onset.

Physical

Physical examination findings may be normal, or the clinician may find some of the following:

• Global or focal neurologic abnormalities in more than 25% of patients
• Syndromes of cranial nerve compression
  • Oculomotor nerve palsy (posterior communicating artery aneurysms) with or without ipsilateral mydriasis
  • Abducens nerve palsy
  • Monocular vision loss (ophthalmic artery aneurysm compressing the ipsilateral optic nerve)
• Motor deficits from middle cerebral artery aneurysms in 15% of patients
• No localizing signs in 40% of patients
• Seizures
• Ophthalmologic signs
  • Subhyaloid retinal hemorrhage (small round hemorrhage, perhaps with visible meniscus, near the optic nerve head); other retinal hemorrhage
  • Papilledema
• Vital signs
  • About half of patients have mild-to-moderate blood pressure (BP) elevation.
  • BP may become labile as ICP increases.
  • Fever is unusual at presentation but becomes common after the fourth day from blood breakdown in the subarachnoid space.
  • Tachycardia may be present for several days after the occurrence of a hemorrhage.
• Grade SAH according to the following scheme:
  • Grade I - Mild headache with or without meningeal irritation
  • Grade II - Severe headache and a nonfocal examination, with or without mydriasis
  • Grade III - Mild alteration in neurologic examination, including mental status
  • Grade IV - Obviously depressed level of consciousness or focal deficit
  • Grade V - Patient either posturing or comatose

Causes

• Primary subarachnoid hemorrhage may result from rupture of the following types of pathologic entities (the first 2 are most common):
  • Saccular aneurysm
  • AVM
  • Mycotic aneurysmal rupture
  • Angioma
  • Neoplasm
  • Cortical thrombosis
• Subarachnoid hemorrhage may reflect a secondary dissection of blood from an intraparenchymal hematoma (eg, bleeding from hypertension or neoplasm).
• Two thirds of cases of nontraumatic subarachnoid hemorrhage are caused by rupture of saccular aneurysms.
• Congenital causes also may be responsible for subarachnoid hemorrhage.
  • Occasional familiar occurrence
  • Frequency of multiple aneurysms
  • Association of aneurysms with specific systemic diseases, including Ehlers-Danlos syndrome, Marfan syndrome, coarctation of the aorta, and polycystic kidney disease
• Environmental factors associated with acquired vessel wall defects include age, hypertension, smoking, and arthrosclerosis.

Differential Diagnoses

Workup

Laboratory Studies

• Complete blood count
• Prothrombin time, activated partial thromboplastin time
• Blood typing and screening
  • Blood bank typing is indicated when subarachnoid hemorrhage is identified or a severe bleed is suspected.
  • Intraoperative transfusions may be required.
• Troponin I (cTnI): cTnI measurement is a powerful predictor for the occurrence of pulmonary and cardiac complications, but it does not carry additional prognostic value for clinical outcome in patients with aneurysmal subarachnoid hemorrhage.²

Imaging Studies

• The initial study of choice is an urgent CT scan without contrast (see Media file 1).

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.

• Sensitivity decreases with time from onset and with older resolution scanners.
• In one study published by the New England Journal of Medicine, good quality CT scanning revealed subarachnoid hemorrhage in 100% of cases within 12 hours of onset and 93% within 24 hours of onset.³ Other studies traditionally report 90-95% sensitivity within 24 hours of onset of bleeding, 80% at 3 days, and 50% at 1 week.
• CT also can detect intracerebral hemorrhage, mass effect, and hydrocephalus.
• A falsely negative CT scan can result from severe anemia or small-volume subarachnoid hemorrhage.
• Distribution of subarachnoid hemorrhage can provide information about the location of an aneurysm and prognosis.
  • Intraparenchymal hemorrhage may occur with middle communicating artery and posterior communicating artery aneurysms. Interhemispheric and intraventricular hemorrhages may occur with anterior communicating artery aneurysms.
  • Outcome is worse for patients with extensive clots in basal cisterns than for those with a thin, diffuse hemorrhage.
• Cerebral angiography is performed once the subarachnoid hemorrhage diagnosis is made.
  • This study assesses the following:
    • Vascular anatomy
    • Current bleeding site
    • Presence of other aneurysms
  • This study helps plan operative options.
  • Angiography findings are negative in 10-20% of patients with subarachnoid hemorrhage.
  • If negative, some advocate repeating angiography a few weeks later.
• Magnetic resonance imaging (MRI) is performed if no lesion is found on angiography.
  • Its sensitivity in detecting blood is considered equal or inferior to that of CT scan.
  • The higher cost, lower availability, and longer study time make it less optimal for detecting SAH.
  • MRI mostly is used to identify possible AVMs that are not visible on angiography.
  • MRI may miss small symptomatic lesions that have not yet ruptured.
• Magnetic resonance angiography (MRA) is less sensitive than angiography in detecting vascular lesions; however, many believe CT angiography and/or MRA one day will play a more central role.
• Multidetector computed tomography angiography (MD-CTA) of the intracranial vessels is now a routine examination, and it is becoming fully integrated into the imaging and treatment algorithm of patients presenting with acute subarachnoid hemorrhage in many centers in the United Kingdom and Europe.⁴ Digital-subtraction cerebral angiography has been the criterion standard for the detection of cerebral aneurysm, but CT angiography has gained more popularity and is frequently used owing to its noninvasiveness and a sensitivity and specificity comparable to that of cerebral angiography.⁵

Other Tests

• Electrocardiogram
  • About 20% of subarachnoid hemorrhage cases have myocardial ischemia from the increased circulation of catecholamines.
  • Typical results are nonspecific ST-and T-wave changes, prolonged QRS segments, U waves, and increased QT intervals.
  • ECG changes reflect myocardial ischemia or infarction and should be treated in the usual manner. Suspicion of subarachnoid hemorrhage is a contraindication to thrombolytic and anticoagulant therapy.

Procedures

• Lumbar puncture
  • Lumbar puncture (LP) is indicated if the patient has possible subarachnoid hemorrhage and negative CT scan findings.
  • Perform CT scan prior to LP to exclude any significant intracranial mass effect or obvious intracranial bleed.
  • LP may be negative less than 2 hours after the bleed; LP is most sensitive at 12 hours after symptom onset.
  • Red blood cells (RBCs) in the cerebrospinal fluid (CSF) remain consistently elevated in 2 sequential tubes or punctures in SAH, whereas the number of RBCs in technically traumatic punctures decrease over time.
  • Xanthochromia (yellow-to-pink CSF supernatant) usually is seen by 12 hours after the onset of bleeding; ideally this is measured spectrographically, although many laboratories rely on visual inspection.
  • LP findings were thought to be positive in 5-15% of all subarachnoid hemorrhage presentations that are not evident on the CT scan. This number may be no longer valid with the advent of newer generations of CT scans. A recent small retrospective chart review about patients presenting to the emergency department undergoing fifth generation CT scans and LP showed no patients with positive LP and negative CT scan.⁶

Treatment

Prehospital Care

• Address the ABCs.
• Triage and transport patients with altered level of consciousness or an abnormal neurologic examination to the closest medical center with a CT scan and neurosurgical backup.
• Ideally, avoid sedating these patients en route.

Emergency Department Care

• In patients with a suspected grade I or II subarachnoid hemorrhage, ED care essentially is limited to diagnosis and supportive therapy.
  • Early identification of sentinel headaches is key to reduced mortality and morbidity rates.
  • Use sedation judiciously.
  • Secure intravenous (IV) access during ED stay and closely monitor the patient's neurologic status.
• In patients with a grade III, IV, or V subarachnoid hemorrhage (ie, altered neurologic examination), ED care is more extensive.
  • Address the ABCs.
  • Endotracheal intubation of obtunded patients protects from aspiration caused by depressed airway protective reflexes.
  • Intubate to hyperventilate patients with signs of herniation.
    • Thiopental and etomidate are the optimal induction agents in subarachnoid hemorrhage during an intubation. Thiopental is short-acting and has a barbiturate cytoprotective effect. It should be used only in hypertensive patients because of its propensity to drop systolic blood pressure (SBP), which is the leading cause of secondary brain injury. In hypotensive and normotensive patients, use etomidate.
    • Use rapid sequence intubation if possible. In the process, to blunt ICP increase, ideally use sedation, defasciculation, short-acting neuromuscular blockade, and other agents with ICP-blunting properties (such as IV lidocaine).
    • Avoid excessive or inadequate hyperventilation. Target the pCO₂ at 30-35 mm Hg to reduce elevated ICP. Excessive hyperventilation may be harmful to areas of vasospasm.
  • Avoid excessive sedation. It makes serial neurologic exams more difficult and has been reported to increase ICP directly.
• Reliable neurologic examinations before and after initial treatment are critically important to optimizing management and to deciding on the appropriate neurosurgical intervention.
• Use the following interventions early and judiciously to decrease elevated ICP when herniation is suspected:
  • Use osmotic agents, such as mannitol, which reduces ICP 50% in 30 minutes, peaks after 90 minutes, and lasts 4 hours.
  • Loop diuretics, such as furosemide, also decrease ICP without increasing serum osmolality.
  • IV steroid therapy to control brain edema is controversial and debated.
• Monitoring
  • Monitor cardiac activity, oximetry, automated BP, and end-tidal carbon dioxide, when applicable.
  • End-tidal carbon dioxide monitoring of intubated patients enables the clinician to avoid excessive or inadequate hyperventilation. Target the pCO₂ at about 30-35 mm Hg to reduce elevated ICP.
  • Invasive arterial line monitoring is indicated when dealing with labile BP (common in high-grade subarachnoid hemorrhage).
• Antihypertensive agents
  • Antihypertensive agents previously were advocated for an SBP greater than 160 mm Hg or diastolic BP (DBP) greater than 90 mm Hg.
  • Keep systolic blood pressure 90-140 mm Hg before aneurysm treatment, then allow hypertension to keep systolic blood pressure less than 200 mm Hg.³
  • Consult critical care providers who will be involved in ongoing care of the patient, as individual practices vary.
  • Use medications that can be titrated rapidly.
  • Vasopressors may be indicated to keep SBP over 120 mm Hg; this avoids CNS damage in the ischemic penumbra from the reactive vasospasm seen in SAH.
• Adjunctive therapies and measures
  • Provide supplemental oxygen for all patients with CNS impairment.
  • Elevate the head of the bed 30° to facilitate intracranial venous drainage.
  • Fluids and hydration
    • Maintain euvolemia (CVP, 5-8 mm Hg); if cerebral vasospasm is present, maintain hypervolemia (CVP 8-12 mm Hg, or PCWP, 12-16 mm Hg).³
    • Do not overhydrate patients because of risks of hydrocephalus.
    • Patients with SAH also may have hyponatremia from cerebral salt wasting.
  • Serum glucose: Maintain level at 80-120 mg/dL; use sliding or continuous infusion of insulin if necessary.³
  • Core body temperature: Keep at 37.2°C; administer acetaminophen (325-650 mg PO q4-6h) and use cooling devices if necessary.³
  • Consider antiemetics for nausea or vomiting.
  • Sedate cautiously to avoid masking the neurologic examination, which may jeopardize the reliability of the findings. However, avoid any increase in ICP due to excessive agitation from pain and discomfort.
• Seizures
  • Prophylactic use of anticonvulsants does not acutely prevent seizures after subarachnoid hemorrhage, but use anticonvulsants in patients who have had a seizure or if local practice dictates routine use.
  • Begin with anticonvulsants that do not change the level of consciousness (ie, phenytoin first; barbiturates or benzodiazepines only to stop active seizures).
• Calcium channel blockers decrease the incidence and severity of cerebral vasospasm.
  • Judicious use is essential because of the risk of detrimental primary or secondary hypotension.
  • Short-acting medication is recommended; discuss this intervention with the neurosurgeon.
• Statins
  • Statins may improve cerebral vasomotor reactivity through cholesterol-dependent and cholesterol-independent mechanisms.
  • Their use is still controversial, but 2 small studies have shown promise. Acute treatment with statins ameliorated cerebral vasospasm and reduced vasospasm-related delayed ischemic deficits.^7,8
• Magnesium
  • New trials are now evaluating the role of magnesium sulfate to prevent delayed cerebral ischemia. It is a neuroprotective agent that acts as an NMDA-receptor antagonist and a calcium channel blocker. Phase 2 studies have shown a beneficial effect, and phase 3 trials are underway.⁹
• Use of antifibrinolytics, such as epsilon aminocaproic acid, is controversial.
  • They competitively inhibit plasminogen activation and have been reported to reduce the incidence of rebleeding.
  • Other reports warn of their detrimental vasospastic effect and increased occurrence of hydrocephalus. Consult a neurosurgeon concerning their use.
• Emergent ventricular drainage by the neurosurgeon may be necessary.

Consultations

• Obtain emergent neurosurgical consultation for definitive treatment.
• Interventional radiology may be needed when surgical intervention is deemed necessary by the neurosurgical consultant (eg, a large clot causing a mass effect is present and needs to be evacuated emergently).
• Many centers opt for early angiography in all patients.

Medication

The goals of therapy are to reduce pain, edema, and severity of cerebral vasospasm, relieve nausea and vomiting, and prevent convulsions.

Analgesics

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 have sustained trauma.

Fentanyl citrate (Sublimaze)

A synthetic opioid that is 75-200 times more potent and much shorter half-life than morphine sulfate. Has less hypotensive effects and is safer in patients with hyperactive airway disease than morphine because of minimal-to-no associated histamine release. By itself, it causes little cardiovascular compromise, although addition of benzodiazepines or other sedatives may result in decreased cardiac output and blood pressure.
Highly lipophilic and protein-bound. Prolonged exposure leads to accumulation in fat and delays weaning process.
Consider continuous infusion because of the short half-life of fentanyl. Parenteral form is DOC for conscious sedation analgesia. Ideal for analgesic action of short duration during anesthesia and immediate postoperative period.
Excellent choice for pain management and sedation with short duration (30-60 min) and easy to titrate. Easily and quickly reversed by naloxone.
After initial parenteral dose, subsequent parenteral doses should not be titrated more frequently than q3h or q6h thereafter.
Transdermal form is used only for chronic pain conditions in opioid-tolerant patients. When using transdermal dosage form, most patients are controlled with 72-h dosing intervals; however, some patients require dosing intervals of 48 h.
Easily and quickly reversed by naloxone.

Dosing

Adult

2-3 mcg/kg IV; not to exceed 50 mcg

Pediatric

<12 years: Not established
>12 years: Administer as in adults

Interactions

Phenothiazines may antagonize analgesic effects of opiate agonists; tricyclic antidepressants may potentiate adverse effects of fentanyl when both drugs are used concurrently

Contraindications

Documented hypersensitivity; hypotension or potentially compromised airway where it would be difficult to establish rapid airway control

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Caution in hypotension, respiratory depression, constipation, nausea, emesis, and urinary retention; idiosyncratic reaction, known as chest wall rigidity syndrome, may require neuromuscular blockade in order to increase ventilation

Antiemetics

These agents are used for the treatment of nausea or vomiting.

Promethazine (Phenergan)

Antidopaminergic agent effective in treatment of emesis. Blocks postsynaptic mesolimbic dopaminergic receptors in brain and reduces stimuli to brainstem reticular system.

Dosing

Adult

12.5 mg PO/PR tid; 25 mg hs
25 mg IV/IM; repeat in 2 h prn

Pediatric

<2 years: Contraindicated
>2 years: 0.25-1 mg/kg PO/IV/IM/PR 4-6 times/d prn

Interactions

Other CNS depressants or anticonvulsants may have additive effects; with epinephrine, may cause hypotension

Contraindications

Documented hypersensitivity; children younger than 2 y (incidences of death due to respiratory depression)

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Caution in cardiovascular disease, impaired liver function, seizures, sleep apnea, and asthma

Anticonvulsants

These agents are used to prevent posttraumatic seizures. Use in patients with SAH who have not had seizures is controversial and dependent on individual neurosurgical preference; they usually are used only in patients who have had seizures. Conventional loading doses may be employed.

Phenytoin (Dilantin)

Appears to act in motor cortex, where it may inhibit spread of seizure activity; activity of brainstem centers responsible for tonic phase of grand mal seizures also may be inhibited.
Individualize dose; administer larger dose before retiring if dose cannot be divided equally.

Dosing

Adult

Loading dose: 15-20 mg/kg PO/IV once or divided, followed by 100-150 mg/dose at 30-min intervals
Initial dose: 100 mg (125 mg susp) PO/IV tid
Maintenance dosage: 300-400 mg/d PO/IV divided tid (qd/bid if ER); increase to 600 mg/d (625 mg/d susp) prn; not to exceed 1500 mg/d; rate of infusion not to exceed 50 mg/min

Pediatric

Loading dose: 15-20 mg/kg PO/IV once or in divided doses
Initial dose: 5 mg/kg/d PO/IV divided bid/tid
Maintenance dose: 4-8 mg/kg PO/IV divided bid/tid
>6 years: May require minimum adult dose (300 mg/d); not to exceed 300 mg/d

Interactions

Amiodarone, benzodiazepines, chloramphenicol, cimetidine, fluconazole, isoniazid, metronidazole, miconazole, phenylbutazone, succinimides, sulfonamides, omeprazole, phenacemide, disulfiram, ethanol (acute ingestion), trimethoprim, and valproic acid may increase toxicity
Barbiturates, diazoxide, ethanol (chronic ingestion), rifampin, antacids, charcoal, carbamazepine, theophylline, and sucralfate may decrease effects
May decrease effects of acetaminophen, corticosteroids, dicumarol, disopyramide, doxycycline, estrogens, haloperidol, amiodarone, carbamazepine, cardiac glycosides, quinidine, theophylline, methadone, metyrapone, mexiletine, oral contraceptives, and valproic acid

Contraindications

Documented hypersensitivity; due to effect on ventricular automaticity, do not use in sinoatrial block, sinus bradycardia, second- and third-degree AV block, or Adams-Stokes syndrome

Precautions

Pregnancy

D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus

Precautions

Perform blood counts and urinalysis when therapy begins and at monthly intervals for several months to monitor for blood dyscrasias; discontinue use if skin rash appears—if rash is exfoliative, bullous, or purpuric do not resume use; death from cardiac arrest after too-rapid IV administration may occur (sometimes preceded by marked QRS widening); hypotension and arrhythmias can occur if rate of infusion (adults) exceeds 50 mg/min; administer cautiously to patients with acute intermittent porphyria; exercise caution when administering to patients with diabetes as it may raise blood glucose levels; discontinue if hepatic dysfunction occurs

Fosphenytoin (Cerebyx)

Diphosphate ester salt of phenytoin that acts as water-soluble prodrug of phenytoin; plasma esterases convert fosphenytoin to phosphate, formaldehyde, and phenytoin; phenytoin, in turn, stabilizes neuronal membranes and decreases seizure activity.
Dose expressed as phenytoin equivalents (PE) to avoid need to perform molecular weight-based adjustments when converting between fosphenytoin and phenytoin sodium doses.
IV is route of choice and should be used in emergency situations.

Dosing

Adult

Loading dose: 15-20 mg PE/kg IV/IM at 100-150 mg PE/min
Maintenance dose: 4-6 mg PE/kg/d IV/IM at 150 mg PE/min to minimize risk of hypotension

Pediatric

Loading dose: 15-20 mg PE/kg IV/IM
Initial dose: 5 mg PE/kg/d IV/IM
Maintenance dose: 4-8 mg PE/kg IV/IM
>6 years: May require minimum adult dose (300 mg PE/d); not to exceed 300 mg PE/d

Interactions

Amiodarone, benzodiazepines, chloramphenicol, cimetidine, disulfiram, ethanol (acute ingestion), fluconazole, isoniazid, metronidazole, miconazole, omeprazole, phenacemide, phenylbutazone, succinimides, sulfonamides, trimethoprim, and valproic acid may increase toxicity
Barbiturates, carbamazepine, diazoxide, ethanol (chronic ingestion), rifampin, theophylline, antacids, charcoal, and sucralfate may decrease effects
May decrease effects of acetaminophen, amiodarone, carbamazepine, cardiac glycosides, corticosteroids, dicumarol, disopyramide, doxycycline, estrogens, haloperidol, methadone, metyrapone, mexiletine, oral contraceptives, quinidine, theophylline, and valproic acid

Contraindications

Documented hypersensitivity; due to effect on ventricular automaticity, do not use in sinoatrial block, sinus bradycardia, second- and third-degree AV block, or Adams-Stokes syndrome

Precautions

Pregnancy

D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus

Precautions

Perform blood counts and urinalysis when therapy is begun and at monthly intervals for several months thereafter, as blood dyscrasias have occurred; discontinue use if skin rash appears—if rash is exfoliative, bullous, or purpuric, do not resume use; death from cardiac arrest has occurred after too-rapid IV administration, sometimes preceded by marked QRS widening; administer cautiously to patients with acute intermittent porphyria; caution when administering to patients with diabetes, as it may raise blood glucose levels; discontinue if hepatic dysfunction occurs; coadministration of IV benzodiazepine usually necessary to control status epilepticus; full antiepileptic effect of phenytoin, whether given as fosphenytoin or parenteral phenytoin, not immediate

Osmotic agents

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, Resectisol)

May reduce subarachnoid space pressure by creating osmotic gradient between CSF in arachnoid space and plasma; not for long-term use.

Dosing

Adult

Initially assess for adequate renal function by administering test dose of 200 mg/kg IV over 3-5 min (should produce urine flow of at least 30-50 mL/h of urine over 2-3 h)
1.5-2 g/kg as 20% solution (7.5-10 mL/kg) or 15% solution (10-13 mL/kg) IV for as little as 30 min

Pediatric

Initially assess for adequate renal function by administering test dose of 200 mg/kg IV over 3-5 min; should produce a urine flow of at least 1 mL/kg/h over 1-3 h; if adequate renal function observed, administer as follows:
0.5-1 g/kg IV, followed by maintenance dose of 0.25-0.5 g/kg IV q4-6h

Interactions

None reported

Contraindications

Documented hypersensitivity; anuria; severe pulmonary congestion; progressive renal damage; severe dehydration; active intracranial bleeding; progressive heart failure

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Carefully evaluate cardiovascular status before rapid administration, since sudden increase in extracellular fluid may lead to fulminating CHF; to avoid pseudoagglutination when blood given simultaneously, add at least 20 mEq of sodium chloride to each liter of mannitol solution; do not give electrolyte-free mannitol solutions with blood

Diuretics

These agents are used to decrease plasma volume and edema by causing diuresis.

Furosemide (Lasix)

Used in acute setting for reduction of increased ICP. Proposed mechanisms in lowering ICP include following: (1) suppression of cerebral sodium uptake, (2) carbonic anhydrase inhibition resulting in decreased CSF production, and (3) inhibition of cellular membrane cation-chloride pump, thereby affecting transport of water into astroglial cells. Dose must be individualized.

Dosing

Adult

20-40 mg/d IV/IM given slowly; depending on response, administer at increments of 20-40 mg, no sooner than 6-8 h after previous dose, until desired diuresis occurs

Pediatric

Neonates: 1 mg/kg IV/IM slowly under close supervision; titrate with 1 mg/kg/dose increments, no sooner than 2 h following initial dose, until satisfactory effect achieved
Children: 1 mg/kg IV/IM slowly under close supervision; not to exceed 6 mg/kg

Interactions

Metformin decreases concentrations; interferes with hypoglycemic effect of antidiabetic agents; antagonizes muscle-relaxing effect of tubocurarine; aminoglycosides appear to increase auditory toxicity—hearing loss of varying degrees may occur; may enhance anticoagulant activity of warfarin; may increase lithium plasma levels and toxicity

Contraindications

Documented hypersensitivity; hepatic coma; anuria; severe electrolyte depletion

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Observe for blood dyscrasias and liver or kidney damage; may increase urinary excretion of magnesium and calcium

Calcium channel blockers

These agents may attenuate deleterious effects of calcium influx in patients with acute neurotrauma. Unfortunately, experimental studies using conventional calcium channel blockers in head injury models have been disappointing overall; however, some studies have suggested that calcium channel blockers may be effective in attenuating cerebral edema and postinjury cognitive dysfunction compared to placebo.

Nimodipine (Nimotop)

Used for improvement of neurologic impairments resulting from spasms following SAH caused by ruptured congenital intracranial aneurysm in patients in good neurologic condition postictus. While studies show such benefit, no evidence indicates drug either prevents or relieves spasms of cerebral arteries; thus, actual mechanism of action unknown.
Begin therapy within 96 h of SAH. If patient cannot swallow capsule because undergoing surgery or unconscious, make holes at both ends of capsule with 18-gauge needle and extract contents into syringe, empty contents into patient's in situ nasogastric tube, and wash it down tube with 30 mL isotonic saline.

Dosing

Adult

60 mg PO/NG q4h for 21 d

Pediatric

Not established

Interactions

Beta-blockers, although advantageous in some patients, may result in increased adverse effects due to depressant effects on myocardial contractility or AV conduction; fentanyl may cause severe hypotension or increased fluid volume requirements; cimetidine may increase blood levels

Contraindications

Documented hypersensitivity; hypotension (SBP <90 mm Hg); sick sinus syndrome; second- or third-degree AV block except in patients with pacemaker

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

In rare cases, LDH, alkaline phosphatase, and ALT may be elevated

Hemostatic agents

These agents are potent inhibitors of fibrinolysis and can reverse states that are associated with excessive fibrinolysis. Use is controversial; consultation with admitting physicians is urged prior to use.

Aminocaproic acid (Amicar)

Inhibits fibrinolysis via inhibition of plasminogen activator substances and, to lesser degree, through antiplasmin activity. Main problem with use is that thrombi that form during treatment are not lysed and effectiveness is uncertain. Has been used to prevent recurrence of SAH.

Dosing

Adult

36 g/d PO/IV in 6 divided doses; not to exceed 30 g/d

Pediatric

5-30 g/d PO/IV q3-6h divided; not to exceed 18 g/m²/d

Interactions

Estrogens or oral contraceptives increase clotting factors, which may lead to hypercoagulable state

Contraindications

Documented hypersensitivity; active intravascular clotting process; DIC

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

If administered to patient with DIC, may produce thrombus that can be fatal, thus important to differentiate between hyperfibrinolysis and DIC
Do not administer in absence of definite diagnosis or if laboratory findings do not show hyperfibrinolysis (hyperplasminemia); caution in cardiac, hepatic, or renal disease

Antihypertensive agents

These agents are used to attempt to reduce ICP by reducing peripheral PB.

Nitroprusside (Nitropress)

Produces vasodilation and increases inotropic activity of heart. Short-acting and potent. Close monitoring essential.

Dosing

Adult

Starting dose: 0.3-0.5 mcg/kg/min IV; increase in increments of 0.5 mcg/kg/min, titrating to desired hemodynamic effect
Average dose 3 mcg/kg/min

Pediatric

Administer as in adults

Interactions

None reported

Contraindications

Documented hypersensitivity; idiopathic hypertrophic subaortic stenosis; atrial fibrillation or flutter

Precautions

Pregnancy

D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus

Precautions

Caution in patients with ICP, hepatic failure, severe renal impairment, or hypothyroidism; in renal or hepatic insufficiency, levels may increase and can cause cyanide toxicity; sodium nitroprusside can lower BP and thus should be used only in patients with MBP >70 mm Hg

Labetalol (Trandate, Normodyne)

Blocks alpha-, beta1-, and beta2-adrenergic receptor sites, decreasing BP.

Dosing

Adult

20-30 mg IV over 2 min followed by 40-80 mg at 10-min intervals; not to exceed 300 mg/dose

Pediatric

Suggested dose: 0.4-1 mg/kg/h IV; not to exceed 3 mg/kg/h

Interactions

Decreases effects of diuretics; increases toxicity of methotrexate, lithium, and salicylates; may diminish reflex tachycardia resulting from nitroglycerin use without interfering with hypotensive effects; cimetidine may increase blood levels; glutethimide may decrease effects by inducing microsomal enzymes

Contraindications

Documented hypersensitivity; cardiogenic shock; pulmonary edema; bradycardia; AV block, uncompensated CHF; reactive airway disease; severe bradycardia

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Caution in patients with impaired hepatic function; discontinue if signs of liver dysfunction; older patients may have lower response rate and higher incidence of toxicity

General anesthetics

These agents provide sedation when neuromuscular blocking agents are used for intubation.

Thiopental (Pentothal)

Short-acting barbiturate sedative-hypnotic with rapid onset and duration of action of 5-20 min. Like methohexital, most commonly used as induction agent for intubation. Depresses consciousness and diminishes or terminates seizure effects; facilitates transmission or impulses from thalamus to cortex of brain, resulting in imbalance in central inhibitory and facilitatory mechanisms. To use as sedative, titrate in dosage increments of 25 mg (adjust to lower dose in children).

Dosing

Adult

2-4 mg/kg IV; may use lower doses in critically ill or elderly patients

Pediatric

2-3 mg/kg/dose IV; repeat prn

Interactions

CNS depressants, salicylates, and sulfisoxazole increase toxicity

Contraindications

Documented hypersensitivity (rare); porphyria; severe hypovolemia or unstable hemodynamics; lack of familiarity with drug; inability to manage airway

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Caution in hepatic or renal insufficiency, asthma, severe cardiovascular disease, unstable aneurysm, hypotension, laryngospasm, or bronchospasm

Amidate (Etomidate)

Nonbarbiturate imidazole compound with sedative properties. Short-acting and rapid onset of action; duration of action is dose dependent (15-30 min). Most useful feature as induction agent is that it produces deep sedation while causing minimal cardiovascular effects. Major application is induction for endotracheal intubation, particularly in patients with, or at risk for, hemodynamic compromise. Has been shown to depress adrenal cortical function; however, effect is not significant clinically during short-term administration. Since drug mixed in propylene glycol, continuous infusion not recommended.

Dosing

Adult

0.3 mg/kg/dose IV; repeat prn

Pediatric

Administer as in adults

Interactions

None reported

Contraindications

Documented hypersensitivity

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Patients undergoing severe stress may require exogenous corticosteroid replacement

Follow-up

Further Inpatient Care

• Admit to ICU for serial neurologic examinations and for hemodynamic monitoring.
  • Arrange for a darkened, quiet, private room to minimize stimuli that may lead to an elevation of ICP.
  • Closely monitor BP and treat appropriately.
  • Some centers favor volume expansion to treat vasospasm that develops days after the initial bleeding episode.
• Prevention of rebleeding 
  • The main issue in prevention of rebleeding is treatment of the aneurysm. This is usually done through clipping (surgery) or coiling (endovascular).
  • The choice between coiling and clipping usually depends on the location of the lesion, neck of the aneurysm, as well as availability and experience of hospital staff.
  • Koivisto et al did not show any difference between the two techniques at 1 year; however, the International Subarachnoid Aneurysm Trial (ISAT) showed superiority of coiling at 1 year with extended benefit up to 7 years.^10,11
  • For patients in good clinical condition with ruptured aneurysms of either the anterior or posterior circulation, there is firm evidence that, if the aneurysm is considered suitable for both surgical clipping and endovascular treatment, coiling is associated with a better outcome.¹²
  • Although the timing of surgery has been debated, most neurovascular surgeons recommend early operation. Evidence from clinical trials suggests that patients undergoing early surgery (within 72 h) have a lower rate of rebleeding and tend to fair better than those treated later.¹³
  • Emergent imaging and intervention may be necessary if mass effect or rebleeding develops.

Transfer

• Patients with possible ruptured or leaking SAH should be transferred emergently to the closest center with CT scan and neurosurgical staff.
• Stabilize patients promptly for transfer in an advanced cardiac life support (ACLS)–monitored unit. Address airway and the possible need for intubation or other emergent interventions, such as mannitol and hyperventilation, prior to transfer.

Deterrence/Prevention

• Screening is generally not recommended in the general population. Even in special population, such as patients with polycystic kidney disease, studies have failed to show any benefit to screening.¹⁴
• In general, screening patients with previous subarachnoid hemorrhage (SAH) cannot be recommended. However, there is a subset of patients with a relatively high risk of both aneurysm formation and rupture. In the latter, screening can save costs and increase quality-adjusted life-years (QALYs). Also, in patients with fear of recurrence, screening may increase QALYs at acceptable costs.¹⁵ Nevertheless, more data are needed to (1) identify risk factors for aneurysm formation and rupture in patients with previous subarachnoid hemorrhage and (2) manage fear for a recurrence to identify patients who can benefit from screening.
• Patients with more than one first-degree relative may benefit from screening with CT or MR angiography.¹⁶

Complications

• Hydrocephalus may develop within the first 24 hours because of obstruction of CSF outflow in the ventricular system by clotted blood.
• Rebleeding of subarachnoid hemorrhage occurs in 20% of patients in the first 2 weeks. Peak incidence of rebleeding occurs the day after subarachnoid hemorrhage. This may be from lysis of the aneurysmal clot.
• Vasospasm from arterial smooth muscle contraction is symptomatic in 36% of patients.
• Neurologic deficits from cerebral ischemia peak at days 4-12.
• Hypothalamic dysfunction causes excessive sympathetic stimulation, which may lead to myocardial ischemia or labile detrimental BP.
• Hyponatremia may result from cerebral salt wasting.
• Aspiration pneumonia and other complications of critical care may occur.
• Left ventricular systolic dysfunction: LV systolic dysfunction in humans with subarachnoid hemorrhage is associated with normal myocardial perfusion and abnormal sympathetic innervation. These findings may be explained by excessive release of norepinephrine from myocardial sympathetic nerves, which could damage both myocytes and nerve terminals.¹⁷

Prognosis

• Cognitive deficits are present, even in many patients considered to have a good outcome.
• More than one third of survivors have major neurologic deficits.
• Factors that affect morbidity and mortality rates are as follows:
  • Severity of hemorrhage
  • Degree of cerebral vasospasm
  • Occurrence of rebleeding
  • Location of bleeding
  • Age and overall health of the patient
  • Presence of comorbid conditions and the hospital course (eg, infections, myocardial infarction)
• Survival correlates with the grade of subarachnoid hemorrhage upon presentation. Reported figures include a 70% survival rate for grade I, 60% for grade II, 50% for grade III, 40% for grade IV, and 10% for grade V.

Miscellaneous

Medicolegal Pitfalls

• Failure to detect a sentinel bleed or an actual low-grade SAH
• Failure to address severe hypertension or hypotension
• Failure to monitor or stabilize patient with SAH
• Delay in detecting herniation or a worsening neurologic picture
• Delay in mobilizing adequate neurosurgical backup

Multimedia

Media file 1: 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.

References

1. Broderick JP, Brott T, Tomsick T. The risk of subarachnoid and intracerebral hemorrhages in blacks as compared with whites. N Engl J Med. Mar 12 1992;326(11):733-6. [Medline].

2. Schuiling WJ, Dennesen PJ, Tans JT. Troponin I in predicting cardiac or pulmonary complications and outcome in subarachnoid haemorrhage. J Neurol Neurosurg Psychiatry. Nov 2005;76(11):1565-9. [Medline].

3. Suarez JI, Tarr RW, Selman WR. Aneurysmal subarachnoid hemorrhage. N Engl J Med. Jan 26 2006;354(4):387-96. [Medline].

4. Goddard AJ, Tan G, Becker J. Computed tomography angiography for the detection and characterization of intra-cranial aneurysms: current status. Clin Radiol. Dec 2005;60(12):1221-36. [Medline].

5. Jayaraman MV, Mayo-Smith WW, Tung GA. Detection of intracranial aneurysms: multi-detector row CT angiography compared with DSA. Radiology. Feb 2004;230(2):510-8. [Medline].

6. Boesiger BM, Shiber JR. Subarachnoid hemorrhage diagnosis by computed tomography and lumbar puncture: are fifth generation CT scanners better at identifying subarachnoid hemorrhage?. J Emerg Med. Jul 2005;29(1):23-7. [Medline].

7. [Best Evidence] Tseng MY, Czosnyka M, Richards H. Effects of acute treatment with pravastatin on cerebral vasospasm, autoregulation, and delayed ischemic deficits after aneurysmal subarachnoid hemorrhage: a phase II randomized placebo-controlled trial. Stroke. Aug 2005;36(8):1627-32. [Medline].

8. Lynch JR, Wang H, McGirt MJ. Simvastatin reduces vasospasm after aneurysmal subarachnoid hemorrhage: results of a pilot randomized clinical trial. Stroke. Sep 2005;36(9):2024-6. [Medline].

9. Dorhout Mees SM; MASH-II study group. Magnesium in aneurysmal subarachnoid hemorrhage (MASH II) phase III clinical trial MASH-II study group. Int J Stroke [serial online]. Feb 2008;3:63-5. Available at http://www3.interscience.wiley.com/cgi-bin/fulltext/119422961/HTMLSTART.

10. Koivisto T, Vanninen R, Hurskainen H, Saari T, Hernesniemi J, Vapalahti M. Outcomes of early endovascular versus surgical treatment of ruptured cerebral aneurysms. A prospective randomized study. Stroke. Oct 2000;31(10):2369-77. [Medline].

11. Molyneux A, Kerr R, Stratton I, Sandercock P, Clarke M, Shrimpton J, et al. International Subarachnoid Aneurysm Trial (ISAT) of neurosurgical clipping versus endovascular coiling in 2143 patients with ruptured intracranial aneurysms: a randomised trial. Lancet. Oct 26 2002;360(9342):1267-74. [Medline].

12. van der Schaaf I, Algra A, Wermer M, Molyneux A, Clarke M, van Gijn J, et al. Endovascular coiling versus neurosurgical clipping for patients with aneurysmal subarachnoid haemorrhage. Cochrane Database Syst Rev. Oct 19 2005;CD003085. [Medline].

13. Whitfield PC, Kirkpatrick PJ. Timing of surgery for aneurysmal subarachnoid haemorrhage. Cochrane Database Syst Rev. 2001;CD001697. [Medline].

14. Hughes PD, Becker GJ. Screening for intracranial aneurysms in autosomal dominant polycystic kidney disease. Nephrology (Carlton). Aug 2003;8(4):163-70. [Medline].

15. Wermer MJ, Koffijberg H, van der Schaaf IC. Effectiveness and costs of screening for aneurysms every 5 years after subarachnoid hemorrhage. Neurology. May 27 2008;70(22):2053-62. [Medline].

16. Bederson JB, Awad IA, Wiebers DO, Piepgras D, Haley EC Jr, Brott T, et al. Recommendations for the management of patients with unruptured intracranial aneurysms: A statement for healthcare professionals from the Stroke Council of the American Heart Association. Circulation. Oct 31 2000;102(18):2300-8. [Medline]. [Full Text].

17. Naidech AM, Kreiter KT, Janjua N, Ostapkovich ND, Parra A, Commichau C, et al. Cardiac troponin elevation, cardiovascular morbidity, and outcome after subarachnoid hemorrhage. Circulation. Nov 1 2005;112(18):2851-6. [Medline]. [Full Text].

18. Banki NM, Kopelnik A, Dae MW. Acute neurocardiogenic injury after subarachnoid hemorrhage. Circulation. Nov 22 2005;112(21):3314-9. [Medline].

19. Chyatte D, Tindall G, Cooper P. Diagnosis and management of aneurysmal SAH. In: The Practice of Neurosurgery. Williams and Wilkins; 1996.

20. Inagawa T. What are the actual incidence and mortality rates of subarachnoid hemorrhage?. Surg Neurol. Jan 1997;47(1):47-52; discussion 52-3. [Medline].

21. Juvela S. Minor leak before rupture of an intracranial aneurysm and subarachnoid hemorrhage of unknown etiology. Neurosurgery. Jan 1992;30(1):7-11. [Medline].

22. Sawin PD, Loftus CM. Diagnosis of spontaneous subarachnoid hemorrhage. Am Fam Physician. Jan 1997;55(1):145-56. [Medline].

23. Schievink W, Shaffrey C, Lanzino G. Nonoperative treatment of aneurysmal subarachnoid hemorrhage. In: Neurological Surgery. WB Saunders; 1996.

24. Weaver JP, Fisher M. Subarachnoid hemorrhage: an update of pathogenesis, diagnosis and management. J Neurol Sci. Sep 1994;125(2):119-31. [Medline].

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Keywords

SAH, subarachnoid hemorrhage, berry aneurysm, arteriovenous malformation, AVM, nontraumatic brain hemorrhage, nontraumatic aneurysmal subarachnoid hemorrhage, ruptured intracranial aneurysms, aneurysmal subarachnoid hemorrhage, sentinel headaches, elevatedintracranial pressure, meningeal irritation, seizures, neck stiffness, photophobia, loss of consciousness, oculomotor nerve palsy, posterior communicating artery aneurysms, ipsilateral mydriasis, abducens nerve palsy, monocular vision loss, ophthalmic artery aneurysm, middle cerebral artery aneurysms, subhyaloid retinal hemorrhage, retinal hemorrhage, papilledema,saccular aneurysm, mycotic aneurysmal rupture, angioma, cortical thrombosis, intraparenchymal hematoma, hypertension, Ehlers-Danlos syndrome, Marfan syndrome, coarctation of the aorta, polycystic kidneydisease, smoking, arthrosclerosis

Contributor Information and Disclosures

Author

Rami C Zebian, MD, Resident Physician, Department of Internal Medicine, University of Texas Medical School at Houston
Rami C Zebian, MD is a member of the following medical societies: American College of Physicians
Disclosure: Nothing to disclose.

Coauthor(s)

A Antoine Kazzi, MD, Chair and Medical Director, Department of Emergency Medicine, American University of Beirut, Lebanon
A Antoine Kazzi, MD is a member of the following medical societies: American Academy of Emergency Medicine
Disclosure: Nothing to disclose.

Medical Editor

Richard S Krause, MD, Senior Faculty, Department of Emergency Medicine, State University of New York at Buffalo School of Medicine
Richard S Krause, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Emergency Medicine, American College of Emergency Physicians, and Society for Academic Emergency Medicine
Disclosure: Nothing to disclose.

Pharmacy Editor

Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine
Disclosure: Nothing to disclose.

Managing Editor

J Stephen Huff, MD, Associate Professor, Emergency Medicine and Neurology, Department of Emergency Medicine, University of Virginia Health Sciences Center
J Stephen Huff, MD is a member of the following medical societies: American Academy of Emergency Medicine, American Academy of Neurology, American College of Emergency Physicians, and Society for Academic Emergency Medicine
Disclosure: Nothing to disclose.

CME Editor

John D Halamka, MD, MS, Associate Professor of Medicine, Harvard Medical School, Beth Israel Deaconess Medical Center; Chief Information Officer, CareGroup Healthcare System and Harvard Medical School; Attending Physician, Division of Emergency Medicine, Beth Israel Deaconess Medical Center
John D Halamka, MD, MS is a member of the following medical societies: American College of Emergency Physicians, American Medical Informatics Association, Phi Beta Kappa, and Society for Academic Emergency Medicine
Disclosure: Nothing to disclose.

Chief Editor

Rick Kulkarni, MD, Medical Director, Assistant Professor of Surgery, Section of Emergency Medicine, Yale-New Haven Hospital
Rick Kulkarni, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Emergency Medicine, American College of Emergency Physicians, American Medical Association, American Medical Informatics Association, Phi Beta Kappa, and Society for Academic Emergency Medicine
Disclosure: WebMD Salary Employment

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