Autonomic Dysreflexia

Etiology

The primary cause of autonomic dysreflexia is typically a spinal cord injury at or above the T6 level. Common triggering stimuli include urinary tract infections, bladder overdistension, constipation, and fecal impactions. However, a variety of other stimuli, including pressure ulcers, skin infections, ingrown toenails, burns, bone fractures, tight clothing, significant temperature changes, certain medical and urological procedures, menstrual cramps, labor and delivery, hemorrhoids, anal fissures, digital rectal stimulation, sexual activity, and even tight shoelaces, can also provoke an episode.[15][16][17][18][19] By far, the overwhelming majority of cases in susceptible patients with spinal cord injuries, about 85%, are caused by bladder and urinary disorders, typically distension.[16][6]

Autonomic dysreflexia may also occur without any spinal cord injuries. In such cases, the underlying causes include stimulant drugs, such as cocaine and amphetamines; head trauma; subarachnoid hemorrhage; post-neurosurgical procedures; multiple sclerosis; brain and spinal cord tumors; Guillain–Barré syndrome, radiation myelopathy, post-cerebrovascular accident events, and cisplatin-induced polyneuropathy.[15][20][21][22]

An episode of autonomic dysreflexia is objectively defined as an increase in systolic blood pressure of at least 20 mm Hg above baseline in adults and 15 mm Hg in children.[14][23] A significant episode typically has a systolic blood pressure of at least 150 mm Hg or >40 mm Hg above the patient's baseline. The higher the injury level, the greater the severity of the cardiovascular dysfunction.[3][24]

The frequency and severity of autonomic dysreflexia episodes depend on both the completeness and level of the spinal cord injury. Patients with a complete spinal cord injury are more than 3 times as likely to develop autonomic dysreflexia than those with incomplete injuries (91%-27%).[3][24][25]  

Autonomic dysreflexia is uncommon during the first month following a spinal cord injury but has been reported as early as the fourth day post-injury.[26] However, it generally does not develop until after the period of spinal shock resolves, typically within 1 year of the original injury.[14][27][28] Approximately 92% of individuals who eventually develop autonomic dysreflexia experience their first episode within the first year following spinal cord injury.[29]

Epidemiology

The estimated frequency of autonomic dysreflexia ranges from 20% to 70% in patients with spinal cord lesions at or above T6 and is unlikely to develop if the injury is below T10.[15][30] The risk increases to over 90% in patients with cervical or upper thoracic spinal cord injuries.[3][4][5]

Autonomic dysreflexia has also been infrequently reported in nontraumatic spinal cord injury cases, such as radiation myelopathy and cisplatin-induced polyneuropathy.[22]  

Pathophysiology

Strong cutaneous or visceral noxious stimulation below the level of the spinal injury—where the injury is above the splanchnic sympathetic outflow at T5-T6—initiates afferent impulses to the intermediolateral grey columns of the spinal cord that elicit abnormal reflex sympathetic nervous system activity from T6 to L2.[1][16][23][31][32][33][34]

Involvement at or above the T6 spinal level is critical in the pathogenesis of autonomic dysreflexia. The greater splanchnic nerve is a sympathetic nerve trunk originating between T5 and T9, which modulates the body's largest circulatory fluid reserve. Spinal cord lesions at or above T6 cause intense sympathetic stimulation to constrict the splanchnic vasculature, resulting in the characteristic severe hypertension associated with autonomic dysreflexia. 

The sympathetic response is exaggerated due to a lack of compensatory descending parasympathetic stimulation and intrinsic posttraumatic hypersensitivity. This exaggerated sympathetic response leads to diffuse vasoconstriction, typically to the lower two-thirds of the body, and a significant rise in blood pressure despite maximum parasympathetic vasodilatory efforts above the level of the spinal injury.[1][16][23][31][32][33][34]

In an intact autonomic system, this increased blood pressure activates the carotid sinus and aortic arch baroreceptors, leading to a parasympathetic vasodilatory response to correct the increased sympathetic tone and reduce the blood pressure while slowing the heart rate through vagal nerve activity.[30]  

However, in the setting of a spinal cord injury, the normal corrective parasympathetic response from the medullary vasomotor center cannot travel below the level of the spinal injury, and the severe, generalized vasoconstriction affecting the splanchnic, muscular, vascular, and cutaneous arterial circulatory networks overwhelms the limited parasympathetic opposition and causes potentially lethal malignant hypertension. The compensatory vagal and parasympathetic stimulation leads to bradycardia and vasodilation, but only above the level of the spinal cord injury.[1][14][16][23][31][32][33][34]

The diverse consequences of autonomic dysreflexia can be attributed to its complex pathophysiology. Under normal conditions, sympathetic preganglionic neurons are modulated by supraspinal vasomotor pathways. In spinal cord injuries, supraspinal inhibitory inputs are disrupted, causing the spinal sympathetic reflex to become unregulated. When the primary afferents transmit sensory information from the skin and visceral organs to sympathetic preganglionic neurons through the propriospinal interneurons, this sensory information activates postganglionic sympathetic neurons to induce vasoconstriction on target vasculature. 

Following a spinal cord injury, there is aberrant sprouting of primary afferents and propriospinal interneurons because of the upregulation of endogenous nerve growth factor and intraspinal soluble tumor necrosis factor-alpha, a proinflammatory cytokine. This maladaptive plasticity increases the excitability of the sympathetic spinal reflex, resulting in more severe bouts of autonomic dysreflexia once triggered.[32]

The loss of descending 5-HT fibers promotes the development of maladaptive plasticity by enabling a state of overexcitation that can fuel cell death and foster the development of autonomic dysreflexia. This dampening effect has been traditionally linked to the direct consequences of engaging the 5-HT1A receptor, which has an inhibitory effect on neural activity. More recent work has revealed a secondary consequence of interrupting 5-HT function, related to an alteration in how the neurotransmitter gamma-aminobutyric acid affects neural excitability, which may help to explain its broad effect on spinal function.[35] 

Studies have shown that blocking serotonin signaling facilitates an increase in hypertension during induced autonomic dysreflexia in rats with spinal cord injuries.[32][35] This finding suggests that the lack of serotonergic transmission to the intermediolateral column is related to the development of autonomic dysreflexia. Overall, the evident involvement of serotonin in resting and autonomic dysreflexia conditions implies that transplantation of this neuronal subtype may be pivotal to restoring cardiovascular function after spinal cord injuries.[32]

Another contributory mechanism is the hypersensitivity of vascular alpha-adrenergic receptors below the level of the spinal cord lesion. This hypersensitivity is believed to be due to the reduced baseline level of catecholamine release in patients with spinal cord injuries, as this causes the alpha-receptors to become hypersensitive to adrenergic stimuli—a form of denervation hypersensitivity—resulting in a disproportionate vasoconstriction response and an even greater degree of blood pressure elevation than otherwise.[36][37][38]

Autonomic dysreflexia is most commonly triggered by distention of a hollow viscus, typically the bladder, but it may also involve the bowel or rectum.[23][39] Bladder distention is responsible for about 85% of all cases and is by far the most common trigger, followed by fecal impaction and even defecation.[6][16][23][39] Pressure ulcers or other injuries, such as fractures and urinary tract infections, are other common causes.[23]

Sexual intercourse can also be a stimulus for autonomic dysreflexia.[40] Other potential triggering causes of autonomic dysreflexia medical procedures; surgeries; constipation; gastric ulcers; fecal impaction; boils; fractures; dislocations; infections, such as epididymitis, pancreatitis, and cholecystitis; and labor and delivery.[14][23] Pregnancy, in particular, becomes very complicated in patients with a history of autonomic dysreflexia.[41][42][43][44][45] These patients should optimally be under the care of an obstetrician experienced in high-risk spinal cord injury cases.[41]

Pharmacological causes of autonomic dysreflexia are rare; however, a recent case was reported in a patient receiving combination therapy with duloxetine and amitriptyline.[46] 

Spinal cord injuries below T10 rarely result in autonomic dysreflexia because the splanchnic innervation remains intact, allowing for compensatory parasympathetic dilation of the splanchnic vascular network.[47] 

Detrusor sphincter dyssynergia is common in patients with spinal cord injuries at risk for autonomic dysreflexia.[16][48][49] These patients have lesions at or above T6 and void only in small amounts.[16] 

History and Physical

Although the clinical manifestations of autonomic dysreflexia may be variable, patients most commonly present with a sudden, severe headache associated with very significant hypertension. Susceptible individuals are predominantly patients with spinal cord injuries whose neurological lesion is at or above T6.[16][23]

The headache is often bilateral and may localize to the frontal, temporal, or occipital regions, resulting from significant vasodilation superior to the level of injury. When cerebral vasodilation is combined with dangerously high blood pressure, a potentially lethal stroke may occur. Symptoms may not necessarily correlate with the severity of blood pressure elevation. 

Autonomic dysreflexia events can be silent and not present with clinical symptoms.[23] Individuals who experience these asymptomatic episodes still have potentially dangerous hypertension and are at risk of serious complications from their excessively high blood pressure, such as a stroke, intracranial hemorrhage, or a myocardial infarction.[23][32]

Hypertension from autonomic dysreflexia may be asymptomatic or severe enough to constitute a hypertensive crisis, resulting in pulmonary edema, left ventricular dysfunction, retinal detachment, intracranial hemorrhage, seizures, confusion, cerebrovascular accident, or death.[50]

Patients with injuries at T6 or higher levels generally tend to have systolic blood pressures between 90 and 110 mm Hg. However, readings should be compared with the individual's usual baseline levels.[14] Bradycardia may range from mild to severe, potentially progressing to recurrent ventricular fibrillation and cardiac arrest.[51] Tachycardia is less common than bradycardia but may also occur along with various other cardiac arrhythmias, such as atrial fibrillation or flutter.[23] If the patient has coronary artery disease, an episode of autonomic dysreflexia may cause a myocardial infarction.[52]

The combination of dangerously high blood pressure and cerebral vasodilation puts the patient at high risk for a hemorrhagic stroke that can be life-threatening.[53][54]

Other clinical signs and symptoms of autonomic dysreflexia include the following: [16][23]

• Anxiety, apprehension, or feelings of impending doom (foreboding)
• Bradycardia
• Cardiac arrhythmias (atrial fibrillation, atrioventricular conduction abnormalities, and premature ventricular contractions)
• Cold, pale skin below the level of injury due to severe sympathetic-induced vasoconstriction
• Confusion
• Constricted pupils
• Dizziness
• Nasal stuffiness and congestion
• Nausea and vomiting
• Orthostatic hypotension
• Piloerection (goose bumps) below the level of the spinal injury
• Profuse sweating (diaphoresis) and flushing above the level of injury—typically involving the face, neck, and shoulders—due to compensatory parasympathetic vasodilation
• Silent or asymptomatic autonomic dysreflexia (except for significant hypertension)
• Thermodysregulation (easily susceptible to hypothermia in a cold environment)
• Visual disturbances, such as blurred vision or visual field defects

Patients prone to this disorder typically have a documented medical or personal history of prior episodes. However, health professionals must be alert to an initial presentation without any known history of autonomic dysreflexia.[14]

Any patient with paraplegia or quadriplegia who complains of a severe headache or is found unconscious should immediately undergo screening for possible autonomic dysreflexia by checking their blood pressure. Systolic blood pressure >150 mm Hg or >40 mm Hg above their baseline should be considered highly suggestive of autonomic dysreflexia, and appropriate treatment should be initiated immediately.[23]

Evaluation

The evaluation of autonomic dysreflexia involves obtaining a history of previous autonomic dysreflexia episodes with the triggering event, if known, monitoring vital signs, and watching for any developing clinical signs and symptoms. The baseline blood pressure should be known and documented for future reference. Most patients with spinal cord injuries have hypotension, and orthostatic hypotension is found in over 50% of patients with autonomic dysreflexia.[55]

A systolic blood pressure >150 mm Hg or >40 mm Hg above baseline levels in susceptible individuals generally indicates autonomic dysreflexia. Arterial blood pressure in autonomic dysreflexia can reach up to 300 mm Hg.[56]

The likelihood of autonomic dysreflexia is independently predicted by the level of the spinal cord lesion, whether it is complete or incomplete, and the presence of neurogenic detrusor overactivity.[3][24]

Patients at risk of autonomic dysreflexia due to T6 or higher spinal cord lesions are also prone to orthostatic hypotension.[23] This condition is defined as a decrease in systolic blood pressure of 20 mm Hg or more when assuming an upright position after lying supine.[23] Such orthostatic hypotension may or may not cause clinical symptoms.[23] A definitive diagnosis can be established through orthostatic challenge testing, such as the sit-up or head-up tilt test.[23]

Thermodysregulation

Thermodysregulation refers to an abnormal difficulty in maintaining the core body temperature when exposed to suboptimal thermal environments and includes both hypothermia and hyperthermia.[57] Patients with autonomic dysreflexia tend to be particularly susceptible to this problem.[23][57][58][59] Skin temperature determinations are unreliable in these situations, so a core temperature reading from an oral, tympanic, or rectal probe is needed.

• Hypothermia (core body temperature of less than 35.0 °C/95 °F) can occur when patients are exposed to a cold environment.[23] This effect is exacerbated by alcohol consumption and certain medications, including alpha agonists, such as clonidine; antidepressants, such as norepinephrine and serotonin reuptake inhibitors; gabapentin; oxybutynin; narcotics; and oxybutynin.[23] Warming should be done cautiously with ambient temperature regulation, insulated clothing, blankets, and the intake of warmed fluids and blankets without using heating devices to avoid inadvertent skin damage.

• Hyperthermia (core body temperature of more than 37.8 °C/100 °F) can occur when patients are exposed to excessively warm environments.[23] Decreasing the patient's body temperature can be done by moving them to a cooler, air-conditioned setting; drinking cool liquids; washing with cool water; using cold water-drenched towels to the abdomen and extremities; and resting. A 3-way Foley catheter with cold irrigation can help quickly reduce the core body temperature.[60] Ice baths should generally be avoided unless the core body temperature is 40 °C/104 °F or higher.[61] 

Patients at risk of autonomic dysreflexia (spinal cord injury at or above the T6 level) should be informed and fully educated about the disorder. Patients' potential susceptibility to autonomic dysreflexia should be noted in the medical record. Patients and their caregivers should be taught to quickly recognize any key initial symptoms, typically a severe headache from cerebral vasodilation. The patient's blood pressure should be checked immediately. If significantly elevated above the patient's usual baseline, then the patient is at high risk for experiencing an episode of autonomic dysreflexia, and immediate corrective steps should be taken as outlined below.

Treatment / Management

Since most patients have experienced previous episodes, they should be asked about their most common precipitating event and their usual remedy. Patients who have experienced autonomic dysreflexia are well-informed about the condition, including its triggers and the treatments that have been effective in the past. Patients prone to this condition are strongly advised to carry an emergency treatment pack or kit with appropriate pharmacological therapies and a card or summary of autonomic dysreflexia to explain the condition and its acute treatment to those unfamiliar with it in emergencies.[14] Patients should also have home blood pressure monitoring devices.[23]

Bladder and bowel distension are the most common triggering causes, with bladder distension being by far the most likely.[16][23] Therefore, immediate evaluation and restoration of bladder drainage is recommended as the first and most likely potential triggering source to investigate. If the patient has an indwelling catheter, it should be evaluated for obstruction, malfunction, blockage, or malpositioning, and a workup for a urinary tract infection should be performed.[23] Irrigation of the catheter with normal saline, warmed if possible, can be performed to determine patency. Minimal volumes of irrigation should be used.

If there is any concern about Foley catheter function, it should be changed immediately.[23] Avoid undue suprapubic pressing, tapping, or palpating the bladder, as this may exacerbate dysreflexia. If the patient does not have a Foley catheter, one should be placed immediately.[23] Anesthetic gel should be administered directly into the urethra and left for at least 2 minutes before insertion, if possible. Placement of a Foley catheter in a patient with autonomic dysreflexia may be challenging, as the increased sympathetic tone can tighten the urethral sphincter. A coude catheter or a guidewire and a council tip catheter are recommended if difficulty is encountered in the initial placement of the Foley.[62]

Patients with significantly overdistended bladders are at a markedly increased risk of rebound hypotension, especially if they have already received antihypertensive medications.[23] In such cases, a bladder scan can identify patients at risk with significantly elevated bladder volumes. Blood pressure should be monitored carefully during bladder drainage in patients with known bladder overdistension. Warmed normal saline should be used for catheter irrigation, as cold fluids could trigger further dysreflexic reactions.[63]

Urine leakage around unobstructed catheters is often due to bladder spasms that may be associated with dysreflexia episodes. Acutely, a belladonna and opium (B & O) suppository is often the most effective, immediate treatment for bladder spasms. Overactive bladder medications such as oxybutynin, trospium, vibegron, and mirabegron can be used both therapeutically and prophylactically. In severe cases, bladder wall injections of botulinum toxin can be helpful [64]. Urinary tract infections may also cause bladder spasms in the absence of catheter blockage; however, these spasms are typically transient and resolve with successful treatment of the infection.(B3)

If blood pressure remains elevated despite optimal bladder management, a bowel-related trigger should be considered, particularly when systolic pressure is <150 mm Hg.[23] A rectal examination should be considered to evaluate for impaction; however, this should be done with care as it can precipitate a worsening dysreflexic crisis due to the rectal stimulation. A topical anesthetic gel applied directly into the rectum has long been recommended to minimize unnecessary stimulation; however, a recent randomized clinical trial has questioned its use, suggesting it may prolong care routines and potentially worsen autonomic dysreflexia.[14][65][66] A suppository can be used, but large-volume enemas and vigorous manual or digital rectal stimulation should be avoided.(A1)

If the systolic blood pressure is >150 mm Hg or >40 mm Hg above the patient's baseline, pharmacological therapy should be initiated to reduce it before rectal examinations.

If neither bladder nor bowel problems appear to be the triggering stimulus, a systematic search for other causes should be undertaken. Common triggers include skin lesions; infected or ingrown toenails; infected decubitus ulcers; hip dislocations; fractures; venous thromboses; rectal fissures or abscesses; medication effects, such as nasal decongestants, sympathomimetic drugs, and misoprostol; gastric or bowel disorders; cholelithiasis; testicular problems, such as epididymitis or torsions; sunburn or insect bites; and previously unrecognized trauma, among others [14].

Rarely, pyocystis can cause autonomic dysreflexia in susceptible patients with spinal cord injury. Pyocystis is a lower urinary tract infection in patients with anuria, where the bladder interior contains purulent material. In pyocystis, oral and intravenous antibiotics do not adequately reach the bladder interior. In such situations, an aminoglycoside instillation into the bladder of amikacin (25 mg/100 mL) or gentamicin (80 mg/50-60 mL) has been used successfully to treat pyocystis, based on culture and sensitivity testing, after initial bladder drainage and irrigation of infected debris and mucus.[67][68] Another rare cause of autonomic dysreflexia is silent myocardial infarction, particularly in patients with quadriplegia.(A1)

If possible, it is essential to document the underlying triggering event for autonomic dysreflexia, especially if it is something unusual.

Boosting refers to deliberately triggering an episode of autonomic dysreflexia to enhance athletic performance for a sporting event such as the Paralympics.[69][70][71] This practice is strongly discouraged due to the significant risks and potential harm to the athlete. Although athletic performance can be improved, possibly by up to 10%, boosting is very dangerous, and most sporting events for individuals with disability, including the Paralympics and the International Paralympic Committee, ban such intentional acts.[69][70][72] (B3)

Emergency Antihypertensive Pharmacological Treatment

If the triggering event cannot be identified and initial maneuvers do not improve the systolic blood pressure to <150 mm Hg or <40 mm Hg above the patient's usual baseline, emergency antihypertensive pharmacologic management should be initiated. Hypertension should be promptly corrected with agents that optimally have a rapid onset but short duration of action.

Nitroglycerine 2% paste is the recommended first-line treatment for severe hypertension in patients experiencing autonomic dysreflexia, especially if their systolic blood pressure exceeds 150 mm Hg.[23][73] Approximately 1 to 2 inches of nitroglycerine 2% paste should be placed on the skin above the level of the spinal cord injury.[23][73] The nitroglycerine paste can easily be removed when the hypertensive crisis is over.[73] When applying the nitroglycerine paste, spread the gel lightly on the skin and avoid rubbing it in. The application area should be covered with plastic wrapping or waterproof tape to protect and hold it in place.[23] Nitrate therapy has a relatively high risk of rebound hypotension.

Nitrate-based medications should not be administered to patients who have taken sildenafil or similar medications within 24 hours (or within 48 hours of taking tadalafil) due to the potential for severe hypotension as they act synergistically.[23][74][75][76][77]

Immediate-release nifedipine 10 mg is also recommended as an appropriate initial medical pharmacotherapy when such treatment is necessary.[23][78] The dose should be reduced to 5 mg in older individuals and those taking other antihypertensive medications.[79] The capsule should be administered using a bite-and-swallow technique.[80] The treatment should be repeated every 20 to 30 minutes, up to a maximum of 40 mg/24 hours.[78] Nifedipine is not recommended in patients with coronary artery disease.[78] Sublingual nifedipine is not recommended due to its unpredictable absorption.[14]

Other acceptable antihypertensive treatments include sublingual and chewable nitrates, sublingual captopril (25 mg), sublingual clonidine (0.2 mg initially followed by 0.1 mg hourly as needed), intravenous hydralazine (10-20 mg slow intravenous (IV) PRN), intravenous labetalol (if the heart rate is not too slow), phentolamine (5 mg IV PRN), sodium nitroprusside (0.5-3 mcg/kg/min PRN), diazoxide (20 mg IV bolus), prazosin, and terazosin, among others.[65](B3)

Intravenous infusions, such as nitroglycerine or clevidipine, are also options; however, placement of an arterial line is recommended for close monitoring and optimal titration of the infusion.[14] Rebound hypotension can occur for 5 hours after administration of antihypertensive medications, particularly nitrates, so these drugs should be used with caution in this population with frequent blood pressure monitoring.[14] 

Preferred initial pharmacological antihypertensive therapies for emergency use in autonomic dysreflexia include:

• Nitroglycerine 2% paste
  • Dosage: 1 to 2 inches placed on the non-hairy chest or elsewhere above the level of spinal injury
  • Onset of activity: 3 to 5 minutes
  • Duration of action: 8 hours
  • Maximum dose: 5 inches
• Nifedipine (bite-and-swallow method)
  • Dosage 10 mg
  • Onset of activity: 10 to 20 minutes
  • Peak effect: 1 hour
  • Repeat dose: May repeat every 20 to 30 minutes
  • Duration of action: 4 hours
  • Maximum dose: 40 mg/24 hours
• Sublingual captopril
  • Dosage: 25 mg
  • Onset of activity: 20 to 30 minutes
  • Repeat dose: May repeat in 1 hour as needed
  • Peak effect: 1 hour
  • Duration of action: 4 hours
  • Maximum dose: 50 mg
• Sublingual clonidine
  • Dosage: 0.2 mg initially, followed by 0.1 mg hourly as needed
  • Onset of activity: 10 to 20 minutes
  • Peak effect: 1 hour
  • Duration of action: 12 hours
  • Maximum dose: 0.8 mg

After emergency hypertensive treatment, the patient's blood pressure should be monitored for at least an additional 2 hours. The need for ongoing blood pressure monitoring should not deter clinicians from using pharmacological agents when necessary, as uncontrolled high blood pressure combined with cerebral vasodilation is hazardous and potentially lethal. Patients should be warned about potential adverse effects of medical therapy, including tachycardia, rebound hypotension, nausea, vomiting, drowsiness, flushing, and cardiac arrhythmias.

Hospital Admission: Hospital admission is recommended if the patient is responding poorly to treatment, if the underlying etiology of the episode remains unknown, or if the patient is pregnant. Transfer to an intensive care unit should be considered if autonomic dysreflexia and its associated hypertensive crisis are not controlled within 30 minutes. Discharge depends on identifying and addressing the underlying cause or on the cessation of episodes. Patients with continuing or frequent episodes of autonomic dysreflexia should be well prepared with an emergency treatment kit, including necessary supplies and instructions, and only when their caregivers can comfortably treat the condition outside the hospital.[79]

Pregnancy: Women with a T6 or higher spinal cord injury who become pregnant are at risk for developing a dysreflexia episode during labor and delivery.[23] In women with spinal cord injuries, the symptoms of labor may include only some abdominal discomfort, increased spasticity, and autonomic dysreflexia. Epidural anesthesia has been reportedly the best choice for controlling autonomic dysreflexia during labor.[81] For cesarean sections or instrumentally assisted deliveries, a spinal or epidural anesthetic may be used. The anesthetic level should be extended to T10 to minimize the risk of autonomic dysreflexia.[82][83] The American College of Obstetrics and Gynecology states that it is vital that any obstetrician caring for a pregnant patient with a spinal cord injury be familiar with this complication.[41](A1)

Procedures: Patients with spinal cord injuries and autonomic dysreflexia often undergo medical procedures and surgeries, such as urologic instrumentation, that can trigger dysreflexic episodes.[19] General or regional anesthesia may be used for these procedures when feasible. Regional anesthesia in the form of a spinal anesthetic has the advantage of blocking both limbs of the reflex arc and thereby avoids autonomic dysreflexia. However, determining the level of anesthesia can be difficult, and administration or placement of the regional anesthetic may be challenging in patients with spinal cord injuries. An epidural catheter may also be considered for longer procedures, as it has the advantage of being able to be topped off. Epidurals are subject to incomplete blocks and might be even more challenging to place.(A1)

If general anesthesia is used and hypertension or other evidence of a dysreflexic episode develops, deepening the level of anesthesia by increasing the anesthetic agent often alleviates the episode. If hypertension remains unresolved by deepening the anesthetic, antihypertensive medications should be used until the stimulus is withdrawn.

Patients susceptible to autonomic dysreflexia undergoing routine urological diagnostic procedures, such as cystoscopy and urodynamics, should be continuously monitored.[6][73] Emergency pharmacotherapy for autonomic dysreflexia should be immediately available.[53][73][84] If a patient develops autonomic dysreflexia during a urologic study or examination, the activity should be immediately terminated and the bladder promptly drained.[73] Pharmacological management may be needed.[23] Hemodynamic monitoring should be maintained with appropriate pharmacotherapy if the condition continues despite these measures.[73]

The following precautions are recommended in susceptible individuals before any surgical procedures: [23]

• Patients should take their regular, prescribed medications but avoid any drugs that could elevate blood pressure, such as ephedrine, or preclude the administration of nitrates, such as phosphodiesterase inhibitors, if autonomic dysreflexia should occur.
• If the patient's blood pressure is >150 mm Hg or >20 mm Hg above their usual baseline, evaluate for possible autonomic dysreflexia and treat appropriately.[23]
• Apply transurethral lidocaine gel 5 minutes before urethral instrumentation.
• Consider using prophylactic pharmacological agents in high-risk patients.
• Monitor blood pressure either continuously or at least every 2 minutes in susceptible individuals undergoing procedures that could induce autonomic dysreflexia. 
• Avoid bladder distension during urological procedures or urodynamics testing.

Prophylaxis: Optimal treatment of patients with spinal cord injuries who are prone to autonomic dysreflexia is typically achieved by a multidisciplinary team, which may include a spinal rehabilitation specialist, urologist, gastroenterologist, neurologist, neurosurgeon, and other specialists who are experienced in these cases. For example, patients may be asked to perform intermittent self-catheterization more often (5-6 times a day) compared to similar patients with neurogenic bladders who are not as susceptible to autonomic dysreflexia. This practice minimizes dysreflexic episodes by minimizing bladder overdistension.

Anticholinergic agents and botulinum toxin bladder injections can be used to minimize episodes of bladder-induced autonomic dysreflexia.[7][85][86][87][88] Botulinum toxin injections for chemical denervation of the bladder muscle have been shown to reduce the incidence of autonomic dysreflexia in susceptible individuals for prolonged periods.[7][64][89] (B2)

Bowel management may include abdominal massage, periodic careful digital rectal stimulation, regular suppositories, and routine laxatives. Additional prophylactic measures include careful positioning, seating guidelines, the use of appropriate pads along with pressure-relieving cushions and mattresses, and periodic inspections for skin lesions to minimize ulcers and skin breakdowns.[14][23] Daily antihypertensive medication solely for autonomic dysreflexia prophylaxis is generally not recommended.[73]

Sexual activity is a known trigger for autonomic dysreflexia.[23] Indications for the use of prophylactic medication before sexual activity in selected individuals include the following: [23]

• There is no prior history of symptomatic orthostatic hypotension.
• Not currently taking any routine medication that could potentiate hypotension.
• Positive history of autonomic dysreflexia with a systolic blood pressure of >150 mm Hg or a systolic blood pressure of >150 mm Hg before sexual activity.

Patients should have their blood pressure checked 5 minutes after completing sexual activity.[23]

Nifedipine is the most commonly used and studied prophylactic therapy, which can also be used to treat acute episodes.[40] Clonidine has long been used for clinical prophylaxis in such situations; however, no randomized clinical trials have evaluated its use specifically for preventing episodes related to sexual activity. Captopril has only been studied in acute episodes, and prazosin requires pretreatment 12 hours before intercourse, making it unsuitable for spontaneous, unplanned sexual activities.[40] Sperm retrieval procedures for male infertility may also trigger an episode of autonomic dysreflexia.[90]

The use of at least 10 mL of 2% lidocaine administered intravesically 5 minutes before routine Foley catheter changes has been shown to significantly reduce episodes of autonomic dysreflexia in patients at high risk.[91] 

Minocycline has been shown to have a neuroprotective effect in animal testing models but has not yet shown a similar clinical benefit in humans.[79][92][93][94]

Although not the current standard of care, some evidence suggests that gabapentin may offer prophylactic benefit in some patients with spinal cord injury, particularly when a low dose is used before scheduled procedures to help mitigate the expected autonomic dysreflexic response.[95][96][97](B3)

A limited study has shown that noninvasive transcutaneous spinal cord stimulation significantly mitigates the degree of hypertension during a period of autonomic dysreflexia and even prevents it altogether.[98] Although this was an early, preliminary study, the Canadian report describes a promising new tool to help minimize or even prevent dangerous hypertensive episodes of autonomic dysreflexia in susceptible individuals.

Recent clinical trials have demonstrated that spinal cord stimulation can promote the restoration of various motor functions previously thought to have been permanently lost.[99] The prevalence of autonomic dysreflexia in patients undergoing spinal cord stimulation through percutaneous epidural and dorsal root ganglia implants for lower extremity motor activation and stimulation is about 22%, with most episodes (97%) being asymptomatic.[99] Such motor rehabilitation sessions in patients with spinal cord injuries are becoming increasingly popular research tools but may carry an underappreciated risk of autonomic dysreflexia in a significant number of otherwise asymptomatic patients.[99] Continuous blood pressure monitoring and appropriate treatment are suggested in patients undergoing these treatments.[99] 

Summary of Emergency Management and Immediate First Steps

In the event of a suspected episode of autonomic dysreflexia, the following steps should be initiated immediately without delay: [23]

• Sit the patient upright with their legs dangling and remove or release any tight clothing, shoes, belts, binders, or constrictive devices. Sitting up helps lower their blood pressure orthostatically by inducing blood pooling in the abdominal and lower extremity vessels and eliminating possible triggering stimuli.[23][63]

• Vital signs should be closely monitored, such as every 2 to 3 minutes, until stable.[23]

• If the blood pressure is over 150 mm Hg, a rapid-onset/short-duration pharmacological antihypertensive medication, such as 1 to 2 inches of 2% nitroglycerin paste, nifedipine 10 mg, sublingual clonidine 0.2 mg, or sublingual captopril 25 mg, should be administered.[23]
  • Before administering a nitrate-based antihypertensive, determine whether the patient has recently taken a phosphodiesterase inhibitor, such as sildenafil, which can potentiate and exaggerate the hypotensive effect of nitrates.[74][75][76][77]

• The triggering noxious stimuli should be identified and corrected as soon as possible.[23]

• If the patient does not have an indwelling Foley, immediate catheterization of the bladder should be performed.[23]

• If the patient has an indwelling Foley: [23] 
  • Check the catheter and tubing carefully for blockages, constrictions, folds, kinks, stones, or obstructions.
  • Make sure the catheter is placed correctly and positioned.
  • Gently irrigate the catheter with a small volume of sterile irrigation fluid, preferably at body temperature.
  • If the Foley catheter does not irrigate easily, change it immediately![23]

• When inserting or changing the Foley, inject urethral lidocaine gel and wait at least 2 or, optimally, up to 5 minutes, if possible.[23]

• Intravesical instillation of at least 10 mL of 2% lidocaine about 5 minutes before scheduled Foley catheter exchanges diminishes episodes of autonomic dysreflexia.[91] This precaution is typically only necessary in patients at very high risk.[91]

• If there is a history of difficulty in Foley placement or insertion is difficult, use a coude or council tip catheter and a guide wire to facilitate rapid and atraumatic placement.[23]

• If the bladder is not distended and the Foley catheter is draining adequately, but the autonomic dysreflexic episode persists, a bowel issue, such as fecal impaction, is the most likely cause.[23]
  • Relieving a fecal impaction is done manually, but lidocaine gel should be administered first and left in place for 3 to 5 minutes.[23]
  • If this cannot be done, antihypertensive medication should be administered until the systolic blood pressure is <150 mm Hg before proceeding.[23]

• The placement of an arterial line should be considered.[23]

• Monitoring of the patient's blood pressure and vital signs should continue for at least 2 hours after the autonomic dysreflexic episode is resolved.

• Hospital admission is recommended if the patient responds poorly to the above therapeutic measures or the underlying precipitating cause cannot be determined.

Differential Diagnosis

When evaluating a patient with autonomic dysreflexia, it is crucial to consider a broad range of differential diagnoses. The following list encompasses various conditions that can mimic autonomic dysreflexia. Consideration of these differential diagnoses helps to ensure accurate diagnosis and appropriate management.

• Acute glomerulonephritis and renal parenchymal disease
• Anxiety or a sense of foreboding
• Cardiac arrest, infarction, or arrhythmia
• Coarctation of the aorta
• Cushing syndrome
• Drug use or overdose, such as stimulants, especially alcohol, cocaine, caffeine, decongestants, amphetamines, phencyclidine, cyclosporine, or levothyroxine
• Head injury
• Hemolytic-uremic syndrome
• Hyperaldosteronism and elevated renin levels (renin-secreting tumors)
• Hyperthyroidism
• Intracranial hemorrhage
• Ischemic stroke
• Nephritic and nephrotic syndrome
• Nutcracker syndrome
• Orthostatic hypotension
• Pheochromocytoma
• Polyarteritis nodosa
• Polycystic kidney disease
• Posterior reversible encephalopathy syndrome
• Renal artery stenosis
• Renovascular disease
• Systemic lupus erythematosus
• Withdrawal of antihypertensive medications

Prognosis

The prognosis of autonomic dysreflexia is typically good as long as the condition is recognized, patients and caregivers are adequately educated, proper precautions are taken, and emergency corrective treatment is initiated promptly. However, unrecognized or untreated autonomic dysreflexia can result in potentially catastrophic consequences. Fortunately, mortality is relatively rare. 

Complications

A hemorrhagic stroke is considered the most serious complication of autonomic dysreflexia, as it can be severe and even fatal. If not adequately treated, autonomic dysreflexia causes sustained, severe hypertension, leading to various complications such as myocardial ischemia or infarction, renal failure, pulmonary edema, retinal hemorrhage, or a cerebral bleed resulting in a potentially disabling or lethal stroke. 

A literature review of patients with autonomic dysreflexia who developed serious complications from the disorder found 32 reported cases.[53] Of these, 22% died as an immediate result of problems directly related to an episode of autonomic dysreflexia. Most (72%) of the serious complications involved the central nervous system; 22% were cardiovascular, and 6% were pulmonary.[53]

Other potential complications are related to their underlying spinal injury and may include pressure sores, decubiti, constipation, bladder disorders, and urinary tract infections. In patients prone to significant autonomic dysreflexia episodes, such seemingly relatively harmless problems can potentially lead to a hypertensive, dysreflexic episode with catastrophic consequences.