You are in: eMedicine Specialties > Physical Medicine and Rehabilitation > SPINAL CORD INJURY Autonomic Dysreflexia in Spinal Cord InjuryArticle Last Updated: Oct 5, 2006AUTHOR AND EDITOR INFORMATIONSection 1 of 10
  Author: Denise I Campagnolo, MD, MS, Director of Multiple Sclerosis Clinical Research and Staff Physiatrist, Barrow Neurology Clinics, St. Joseph's Hospital and Medical Center; Investigator for Barrow Neurology Clinics; Director, NARCOMS Project for Consortium of MS Centers, Phoenix Denise I Campagnolo is a member of the following medical societies: Alpha Omega Alpha, American Association of Neuromuscular and Electrodiagnostic Medicine, American Paraplegia Society, Association of Academic Physiatrists, and Consortium of Multiple Sclerosis Centers Editors: Milton J Klein, DO, MBA, Consulting Physiatrist, Sewickley Valley Hospital, Allegheny General Hospital, Harmarville Rehabilitation Center, Ohio Valley General Hospital and Aliquippa Community Hospital; Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine; Kat Kolaski, MD, Assistant Professor, Departments of Orthopedics and Pediatrics, Wake Forest University School of Medicine; Kelly L Allen, MD, Consulting Staff, Department of Physical Medicine and Rehabilitation, Lourdes Regional Rehabilitation Center, Our Lady of Lourdes Medical Center; Robert H Meier III, MD, Director, Amputee Services of America, Presbyterian St Luke's Hospital; Consulting Staff, North Valley Rehabilitation Hospital, Kindred Hospital, North Suburban Hospital Author and Editor Disclosure Synonyms and related keywords: autonomic hyperreflexia, paroxysmal hypertension, hypertensive autonomic crisis, visceroautonomic stress syndrome, autonomic spasticity, sympathetic hyperreflexia, mass reflex INTRODUCTIONSection 2 of 10
  BackgroundAutonomic dysreflexia (AD) is a syndrome of massive imbalanced reflex sympathetic discharge occurring in patients with spinal cord injury (SCI) above the splanchnic sympathetic outflow (T5-T6). Anthony Bowlby first recognized this syndrome in 1890 when he described profuse sweating and erythematous rash of the head and neck initiated by bladder catheterization in an 18-year-old patient with SCI. Guttmann and Whitteridge completed a full description of the syndrome in 1947. This condition represents a medical emergency, so recognizing and treating the earliest signs and symptoms efficiently can avoid dangerous sequelae of elevated blood pressure. SCI patients, caregivers, and medical professionals must be knowledgeable about this syndrome and its management. PathophysiologyThis phenomenon occurs after the phase of spinal shock in which reflexes return. Individuals with injury above the major splanchnic outflow may develop AD. Below the injury, intact peripheral sensory nerves transmit impulses that ascend in the spinothalamic and posterior columns to stimulate sympathetic neurons located in the intermediolateral gray matter of the spinal cord. The inhibitory outflow above the SCI from cerebral vasomotor centers is increased, but it is unable to pass below the block of the SCI. This large sympathetic outflow causes release of various neurotransmitters (norepinephrine, dopamine-b-hydroxylase, dopamine), causing piloerection, skin pallor, and severe vasoconstriction in arterial vasculature. The result is sudden elevation in blood pressure and vasodilation above the level of injury. Patients commonly have a headache caused by vasodilation of pain sensitive intracranial vessels. Vasomotor brainstem reflexes attempt to lower blood pressure by increasing parasympathetic stimulation to the heart through the vagus nerve to cause compensatory bradycardia. This reflex action cannot compensate for severe vasoconstriction, explained by the Poiseuille formula, where pressure in a tube is affected to the fourth power by change in radius (vasoconstriction) and only linearly by change in flow rate (bradycardia). Parasympathetic nerves prevail above the level of injury, which may be characterized by profuse sweating and vasodilation with skin flushing. Cameron and colleagues have found that site-directed genetic manipulation of fiber sprouting in the spinal dorsal horns in a cord compression rat model could alter the extent of hyperreflexia after bowel distention, indicating that endogenous spinal cord circuitry/neural sprouting plays a role in the pathophysiology of AD (Cameron, 2006). FrequencyUnited StatesReported prevalence rates vary, but the generally accepted rate is 48-90% of all individuals who are injured at T6 and above. Some incidence has been reported in SCI as low as T10. AD occurs during labor in approximately two thirds of pregnant women with SCI above the level of T6. The occurrence of AD increases as the patient evolves out of spinal shock. With the return of sacral reflexes, the possibility of AD increases. Mortality/MorbidityMorbidity is associated with the hypertension, which can cause retinal/cerebral hemorrhage, myocardial infarction, or seizures. Mortality is rare. SexThe male-to-female ratio for sustaining SCI is 4:1; therefore, AD is primarily a male phenomenon. AgeNo specific relationship has been documented between AD and age. CLINICALSection 3 of 10
HistoryThe patient generally gives a history of blurry vision, headaches, and a sense of anxiety. Feelings of apprehension or anxiety over an impending physical problem commonly are exhibited. PhysicalA patient may have one or more of the following findings on physical examination:
CausesEpisodes of AD can be triggered by many potential causes. Essentially any painful, irritating, or even strong stimulus below the level of the injury can cause an episode of AD. Although the list is not comprehensive, the following events or conditions all can cause episodes of AD:
DIFFERENTIALSSection 4 of 10
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| Drug Name | Nifedipine (Procardia) |
|---|---|
| Description | Calcium ion influx inhibitor (slow-channel blocker or calcium ion antagonist); inhibits transmembrane influx of calcium ions into cardiac and smooth muscle. Reduces arterial pressure at rest and at a given level of exercise by dilating peripheral arterioles and reducing the total peripheral resistance (afterload). |
| Adult Dose | 10 mg cap initially, bite and swallow |
| Pediatric Dose | Not recommended |
| Contraindications | Documented hypersensitivity |
| Interactions | Concomitant administration with beta-blocking agents usually well tolerated; may increase likelihood of congestive heart failure, severe hypotension, or exacerbation of angina; concomitant administration with nitrates safe, but no controlled studies evaluate antianginal effectiveness Isolated reports of patients with elevated digoxin levels; possible interaction between digoxin and nifedipine; monitor digoxin levels when initiating, adjusting, and discontinuing Rare reports of interaction between quinidine and nifedipine with a decreased plasma level of quinidine Rare reports of increased prothrombin time in patients taking Coumadin anticoagulants and nifedipine; relationship uncertain Significant increase in peak plasma levels (80%) and area-under-the-curve (74%) after 1 week of cimetidine at 1000 mg/d and nifedipine at 40 mg/d Smaller nonsignificant increases with ranitidine; effect possibly mediated by known inhibition of cimetidine on hepatic cytochrome P-450, enzyme systemprobably responsible for first-pass metabolism Cautious titration advised if nifedipine therapy initiated in patient receiving cimetidine |
| Pregnancy | C - Safety for use during pregnancy has not been established. |
| Precautions | Decreases peripheral vascular resistance; careful monitoring of BP advised during initial administration and titration Mild-to-moderate peripheral edema seen in 1/10 patients, associated with arterial vasodilation, not from left ventricular dysfunction Occasional significant elevations of enzymes (eg, alkaline phosphatase, CPK, LDH, SGOT, SGPT); rarely associated with clinical symptoms; cholestasis with or without jaundice reported; allergic hepatitis; decreases platelet aggregation in vitro; moderate but statistically significant decrease in platelet aggregation and increase in bleeding time in some patients; probably function of inhibition of calcium transport across platelet membrane; no clinical significance demonstrated for these findings; positive direct Coombs test with or without hemolytic anemia reported but causal relationship not determined |
| Drug Name | Nitroglycerine (Depo-Nit, Nitrostat, Nitrol, Nitro-Bid) |
|---|---|
| Description | Principal pharmacologic action of nitroglycerin is relaxation of vascular smooth muscle, producing vasodilator effect on both peripheral arteries and veins with more prominent effects on the latter. Dilation of postcapillary vessels, including large veins, promotes peripheral pooling of blood and decreases venous return to the heart, thereby reducing left ventricular end-diastolic pressure (preload). Arteriolar relaxation reduces systemic vascular resistance and arterial pressure (after-load). |
| Adult Dose | 0.4 mg per metered spray for SL use or 2% nitroglycerine ointment Start with 0.5-in strip to chest wall and titrate as necessary; alternatively, 0.15-0.6 mg tab SL or 5 mcg/min IV |
| Pediatric Dose | Not established |
| Contraindications | Documented hypersensitivity; concurrent use of sildenafil (Viagra) |
| Interactions | Alcohol may enhance sensitivity to hypotensive effects of nitrates (acts directly on vascular muscle); other agents that depend on vascular smooth muscle as final common path may have decreased or increased effect depending upon agent; symptomatic orthostatic hypotension reported when calcium channel blockers and oral controlled-release nitroglycerin concomitantly administered; dose adjustments sometimes necessary |
| Pregnancy | C - Safety for use during pregnancy has not been established. |
| Precautions | Caution in severe hypotension, particularly with upright posture, possible; use with caution in subjects with volume depletion from diuretic therapy or with low systolic blood pressure; paradoxic bradycardia and increased angina pectoris from nitroglycerin-induced hypotension; may aggravate angina caused by hypertrophic cardiomyopathy; tolerance and cross-tolerance to other nitrates possible; tolerance to vascular and antianginal effects of nitrates demonstrated in clinical trials, occupational exposure, and tissue experiments in laboratory; tolerance in industrial workers demonstrated; physical dependence occurs since chest pain, acute myocardial infarction, and sudden death occur in industrial workers during withdrawal |
| Drug Name | Phenoxybenzamine hydrochloride (Dibenzyline) |
|---|---|
| Description | Long-acting, adrenergic, alpha-receptor blocking agent that can produce and maintain chemical sympathectomy by oral administration; increases blood flow to skin, mucosae, and abdominal viscera and lowers both supine and erect blood pressures No effect on parasympathetic system |
| Adult Dose | Adjust dose to fit needs of each patient Slowly increase dose until desired effect obtained or side effects from blockade problematic Observe patient on each level before instituting increase Dosage should provide symptomatic relief and/or objective improvement, but not to where side effects from blockage are troublesome Initially, administer 10 mg of Dibenzyline (phenoxybenzamine hydrochloride) bid; increase dose qod, usually to 20-40 mg 2 or 3 times/d, until an optimal dosage is obtained, as judged by blood pressure control |
| Pediatric Dose | Not established |
| Contraindications | Documented hypersensitivity; those to whom a fall in blood pressure would be undesirable |
| Interactions | Alpha-adrenergic blockade leaves beta-adrenergic receptors unopposed; compounds stimulating both types of receptors associated with exaggerated hypotensive response and tachycardia; caution in patients with marked cerebral or coronary arteriosclerosis or renal damage; may aggravate symptoms of respiratory infections; may interact with compounds that stimulate both alpha-adrenergic and beta-adrenergic receptors (eg, epinephrine) to produce exaggerated hypotensive response and tachycardia; blocks hyperthermia production by levarterenol and hypothermia production by reserpine |
| Pregnancy | C - Safety for use during pregnancy has not been established. |
| Precautions | Caution in cerebral or coronary arteriosclerosis and renal impairment; can worsen symptoms of respiratory tract infections Adverse effects include postural hypotension, tachycardia, inhibition of ejaculation, nasal congestion, miosis, gastrointestinal irritation, drowsiness, fatigue |
| Drug Name | Mecamylamine (Inversine) |
|---|---|
| Description | Potent oral secondary amine, antihypertensive agent, and ganglion blocker. Produces smooth and predictable reduction of blood pressure with small oral dose. Antihypertensive effect predominantly orthostatic, but supine blood pressure also significantly reduced. Used for management of moderately severe-to-severe essential hypertension and in uncomplicated cases of malignant hypertension. |
| Adult Dose | 2.5 mg PO prn |
| Pediatric Dose | Not established |
| Contraindications | Documented hypersensitivity; coronary insufficiency, pyloric stenosis, glaucoma, uremia, recent myocardial infarction, unreliable/uncooperative patients |
| Interactions | Antibiotics and sulfonamides; may be potentiated by anesthesia, other antihypertensive drugs, and alcohol |
| Pregnancy | C - Safety for use during pregnancy has not been established. |
| Precautions | Caution in impaired renal function, previous CNS abnormalities, prostatic hypertrophy, bladder obstruction, patients receiving sulfonamides or antibiotics that cause neuromuscular blockade; adverse effects include dizziness, lightheadedness (getting up slowly is advised) Interstitial pulmonary edema and fibrosis, urinary retention, impotence, decreased libido, weakness, fatigue, sedation, marked cerebral and coronary arteriosclerosis, recent cerebral accident may occur No restriction of sodium intake necessary, but adjustment of dosage of ganglion blocker if necessary Caution in prostatic hypertrophy, bladder neck obstruction, and urethral stricture Frequent loose bowel movements with abdominal distention and decreased borborygmi are first signs of paralytic ileus (discontinue immediately and take remedial steps) |
| Drug Name | Diazoxide (Hyperstat) |
|---|---|
| Description | Nondiuretic benzothiadiazine antihypertensive agent; achieves prompt reduction of blood pressure by relaxing smooth muscle in peripheral arterioles; cardiac output increases as blood pressure is reduced. |
| Adult Dose | 1-3 mg/kg IV to maximum dose of 150 mg in single injection; repeat at 5-15 min intervals until reduction of BP is satisfactory (eg, diastolic pressure <100 mm Hg) |
| Pediatric Dose | Administer as in adults |
| Contraindications | Documented hypersensitivity; aortic coarctation, pheochromocytoma, arteriovenous shunts, and aortic aneurysm; compensatory hypertension (eg, that associated with aortic coarctation or arteriovenous shunt) |
| Interactions | Highly bound to serum protein, can be expected to displace other substances also bound to protein (eg, bilirubin or coumarin and derivatives, resulting in higher blood levels of these substances) Hypotension may result when administered to patients who have received other antihypertensive medication within 6 h Excessive hypotension in 1 patient after concomitant administration with hydralazine and methyldopa may occur Maternal hypotension and fetal bradycardia occurred in patient in labor who received both reserpine and hydralazine prior to administration Neonatal hyperglycemia following intrapartum administration after injection also reported; should not be administered IV within 6 h of administration of hydralazine, reserpine, alphaprodine, methyldopa, beta-blockers, prazosin, minoxidil, nitrites Concomitant administration with thiazides or other commonly used diuretics may potentiate hyperuricemic and antihypertensive effects Hyperglycemic and hyperuricemic effects of diazoxide preclude proper assessment of metabolic states Increased renin secretion, IgG concentrations, decreased cortisol secretion noted Inhibits glucagon-stimulated insulin release and causes false-negative insulin response to glucagon Increased serum free fatty acids and decreased plasma insulin levels in rat, dog, monkey |
| Pregnancy | C - Safety for use during pregnancy has not been established. |
| Precautions | Transient hyperglycemia in most patients usually requires treatment only in patients with diabetes mellitus; responds to usual management measures, including insulin Monitor blood glucose levels, especially in patients with diabetes and in those requiring multiple injections Cataracts observed in animals receiving repeated daily doses of intravenous diazoxide May precipitate edema and congestive heart failure if injected frequently Increased volume of extracellular fluid may cause treatment failure in nonresponsive patients because of increased extracellular fluid Increase in fluid volume responds to diuretics if renal function adequate Concurrent administration of thiazide diuretics may potentiate antihypertensive and hyperuricemic actions of diazoxide (see Interactions above) Should be administered only into peripheral vein Alkalinity of solution irritates tissue, so avoid extravascular injection or leakage SC administration produces inflammation and pain without subsequent necrosis; if leakage into subcutaneous tissue occurs, area should be treated with warm compresses and rest |
Deterrence/Prevention:
Patient Education:
| Media file 1: Autonomic dysreflexia in spinal cord injury. A. A strong sensory input (not necessarily noxious) is carried into the spinal cord via intact peripheral nerves. The most common origins are bladder and bowel. B. This strong sensory input travels up the spinal cord and evokes a massive reflex sympathetic surge from the thoracolumbar sympathetic nerves, causing widespread vasoconstriction most significantly in the subdiaphragmatic (or splanchnic) vasculature. Thus peripheral arterial hypertension occurs. C. The brain detects this hypertensive crisis through intact baroreceptors in the neck delivered to the brain through cranial nerves IX and X (Vagus). D. The brain attempts 2 maneuvers to halt the progression of this hypertensive crisis. First, the brain attempts to shut down the sympathetic surge by sending descending inhibitory impulses. These impulses do not get to most sympathetic outflow levels because of the spinal cord injury at T6 or above. Inhibitory impulses are blocked in the injured spinal cord. In the second maneuver, the brain attempts to bring down peripheral blood pressure by slowing the heart rate through an intact vagus (parasympathetic) nerve; however, this compensatory bradycardia is inadequate and hypertension continues. In summary, the sympathetics prevail below the level of neurologic injury, and the parasympathetic nerves prevail above the level of injury. Once the inciting stimulus is removed, reflex hypertension resolves. | |
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Autonomic Dysreflexia in Spinal Cord Injury excerpt
Article Last Updated: Oct 5, 2006
