Autonomic Dysreflexia

Etiology

The etiology is a spinal cord injury, almost always at or above the T6 level. Objectively, an episode is defined as an increase in systolic blood pressure of at least 25 mm Hg or more above baseline.[8] A significant episode would usually have a systolic blood pressure of at least 150 mmHg or more than 40mmHg above the patient's baseline. The higher the injury level, the greater the severity of the cardiovascular dysfunction. The severity and frequency of autonomic dysreflexia episodes are also associated with the completeness of the spinal cord injury as well as the level. Patients with a complete spinal cord injury are more than three times more likely to develop autonomic dysreflexia than those with incomplete injuries (91% to 27%).[10] 

Although autonomic dysreflexia has been described in the first days or weeks after the original trauma, it generally does not develop until after the period of spinal shock when reflexes have recovered.[8] The earliest reported case appeared on the fourth-day post-injury. Most of the patients (92%) who will ultimately develop autonomic dysreflexia will do so within the first year after their injury.[11] 

Epidemiology

Autonomic dysreflexia develops in 48% to 70% of patients with a spinal cord injury above the T6 level and is quite unlikely to develop if the injury is below T10.[12] It has also been infrequently reported in non-traumatic spinal cord injury cases, such as radiation myelopathy and cisplatin-induced polyneuropathy.[13] 

Patients prone to this disorder will usually have a documented or personal history of prior episodes, but health professionals need to be alert to an initial presentation without any known prior history of autonomic dysreflexia.[8]

Pathophysiology

Cutaneous or visceral stimulation below the level of the injury initiates afferent impulses to the intermediolateral grey columns of the spinal cord that elicit abnormal reflex sympathetic nervous system activity from T6 to L2. The sympathetic response is exaggerated due to a lack of compensatory descending parasympathetic stimulation and intrinsic post-traumatic hypersensitivity. This 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 injury. In an intact autonomic system, this increased blood pressure activates the carotid sinus and aortic arch baroreceptors leading to a parasympathetic response slowing the heart rate via vagal nerve activity and causing diffuse vasodilation to correct the original increased sympathetic tone.[12]

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 generalized vasoconstriction affecting the splanchnic, muscular, vascular, and cutaneous arterial circulatory networks continues, ultimately leading to systemic hypertension which is often severe and potentially dangerous. The compensatory vagal and parasympathetic stimulation leads to bradycardia and vasodilation, but only above the level of the spinal cord injury.[8]

The most common stimuli are distention of a hollow viscus, usually the bladder but could also be the rectum. Bladder distention is responsible for about 85% of all cases and is by far the most common trigger followed by fecal impaction.[14] Pressure ulcers or other injuries such as fractures and urinary tract infections are other common causes. Sexual intercourse can also be a stimulus for autonomic dysreflexia. Medical procedures, surgeries, constipation, gastric ulcers, fecal impaction, boils, fractures, dislocations, infections such as epididymitis, pancreatitis, cholecystitis, and labor & delivery are all potential triggering causes of autonomic dysreflexia.[8] Pregnancy, in particular, becomes very complicated in patients with a history of autonomic dysreflexia. Such patients should optimally be under the care of an obstetrician with experience in these difficult and complicated cases.

Pharmacological causes of autonomic dysreflexia are rare, but recently a case was reported in a patient receiving combination therapy with duloxetine and amitriptyline.[15]

Spinal cord injuries below T10 rarely result in autonomic dysreflexia because the splanchnic innervation remains intact and allows for compensatory parasympathetic dilation of the splanchnic vascular network.[16] Detrusor sphincter dyssynergia is common in patients with spinal cord injuries at risk for autonomic dysreflexia. Such patients would have lesions at or above T6 and void only in small amounts. 

History and Physical

The manifestations are variable and include:

• Severe headache
• Hypertension
• Profuse diaphoresis and flushing above the level of injury
• Piloerection above the level of injury
• Cool, pale skin below the level of injury because of severe vasoconstriction
• Visual disturbances
• Constricted pupils
• Nasal stuffiness
• Anxiety or feelings of doom
• Nausea and vomiting
• Dizziness

The initial presenting symptom is typically a severe headache. The headache is usually sudden, severe, throbbing, and bilateral. It may be frontal, temporal, or occipital. This is caused by significant vasodilation superior to the level of injury. When this cerebral vasodilation is combined with dangerously high blood pressure, a potentially lethal stroke may occur. Symptoms may not necessarily correlate with the severity of the blood pressure elevation. 

Hypertension may be asymptomatic or severe enough to cause a hypertensive crisis complicated by pulmonary edema, left ventricular dysfunction, retinal detachment, intracranial hemorrhage, seizures, or death. Patients with T6 level injuries tend to have systolic blood pressures between 90 and 110 mmHg, but readings should be compared with the patient's usual baseline levels.[8] Bradycardia may also range from minor to resulting in cardiac arrest. Tachycardia is less common than bradycardia but may also occur along with cardiac arrhythmias and atrial fibrillation or flutter. If the patient has coronary artery disease, an episode of autonomic dysreflexia may cause a myocardial infarction.

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.[17][18]

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 and comparing it to their baseline level. Systolic blood pressure >150 mmHg or >40 mmHg above baseline should be considered highly suggestive of autonomic dysreflexia and appropriate measures should be taken.

Evaluation

The evaluation includes obtaining a history of previous autonomic dysreflexia episodes with the triggering event if known, monitoring vital signs, and watching for any developing signs and symptoms. The baseline blood pressure should be known and documented for future reference. Many patients with spinal cord injuries will have hypotension. Orthostatic hypotension is found in over 50% of patients with autonomic dysreflexia.[19]

Start by identifying patients at risk (spinal cord injury at or above the T6 level) and recognize the key initial symptom, which is usually a severe headache from cerebral vasodilation. Should this be encountered, the next step would be to check the blood pressure. If elevated above the patient's usual baseline, then the patient is at high risk for an episode of autonomic dysreflexia. A systolic blood pressure >150 mmHg or >40 mmHg above baseline levels should be considered indicative of autonomic dysreflexia.

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.

Treatment / Management

Ask the Patient and Caregiver: Since most patients will have endured previous episodes, it is reasonable to ask them what their most common precipitating event is and the usual remedy. Most patients with a history of autonomic dysreflexia will be quite knowledgeable about the condition and are prepared to implement a treatment plan. It is strongly recommended that patients prone to this condition 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 emergency situations.[8] 

Immediate First Steps: In the event of an episode, the immediate first step is to sit the patient upright with their legs dangling and remove any tight clothing or constrictive devices, which will help lower their blood pressure orthostatically by inducing the pooling of blood in the abdominal and lower extremity vessels as well as eliminating possible triggering stimuli.[20] Vital signs should be closely monitored, and identification of the triggering stimulus should be immediately attempted. Blood pressure should be checked at least every 5 minutes, and an arterial line should be considered. The noxious stimuli should be corrected as soon as possible.

Bladder and/or bowel distension are the most common triggering causes, with bladder over-distension being the most likely. Therefore, checking and restoring bladder drainage is immediately recommended as the first source to be investigated. If the patient has an indwelling catheter, it should be evaluated for obstruction, malfunction, or malpositioning, and a workup for a urinary tract infection should be performed. 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 question about the functionality of the Foley catheter, it should be changed immediately. Avoid undue suprapubic pressing, tapping, or palpating the bladder as this may exacerbate the dysreflexia. If the patient does not have a Foley catheter, one should be placed immediately. Prior to placement, anesthetic gel should be administered directly into the urethra and left for a minimum of two minutes if possible. Placement of a Foley catheter in a patient suffering from autonomic dysreflexia may be challenging as the increased sympathetic tone can tighten the urethral sphincter. Use of a coude catheter or a guidewire is recommended if difficulty is encountered in the initial placement of the Foley.[21]

Patients with significantly overdistended bladders are at a markedly increased risk of rebound hypotension, especially if they have already received antihypertensive medication. In such cases, a bladder scan can be used to 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.[20] 

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 (botox) can be helpful.[22] A urinary tract infection may also cause bladder spasms without catheter blockage, but such spasms are usually transient and disappear when the UTI is successfully treated. (B3)

If the blood pressure remains elevated despite optimal bladder management, consideration should be given to a potential bowel problem as the triggering etiology, especially if the blood pressure is <150 mmHg. A rectal exam 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, but recently this has been called into question by a randomized clinical trial that suggested this prolongs care routines and may actually worsen autonomic dysreflexia.[8][23][24] A suppository can be used, but large volume enemas and vigorous manual or digital rectal stimulation should be avoided. If the systolic blood pressure is >150 mmHg or more than 40 mmHg above the patient's baseline, pharmacological therapy should be utilized to reduce the systolic pressure prior to the rectal examination.(A1)

If neither bladder nor bowel problems appear to be the triggering stimulus, a systematic search for other causes should be undertaken. Relatively frequent triggers include skin lesions, infected or ingrown toenails, infected decubitus ulcers, hip dislocations, fractures, venous thromboses, rectal fissures or abscesses, medication effects (nasal decongestants, sympathomimetic drugs, misoprostol, etc.), gastric or bowel disorders, cholelithiasis, testicular problems such as epididymitis or torsions, sunburn or insect bites, and recent traumas which may be previously unrecognized, among others.[8]

Rarely, pyocystis can cause autonomic dysreflexia in susceptible spinal cord injured patients. (Pyocystis is a lower urinary tract infection in anuric patients 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 the pyocystis, based on culture and sensitivity testing, after initial bladder drainage and irrigation of infected debris and mucus.[25][26] Another rare cause of autonomic dysreflexia would be a "silent" myocardial infarct, particularly in quadriplegic patients.(A1)

It is important to document the underlying triggering event for the autonomic dysreflexia if possible, especially if it is something uncommon or unusual.

"Boosting" refers to the deliberate triggering of an episode of autonomic dysreflexia to enhance athletic performance for a sporting event such as the Paralympics. Such activities are strongly discouraged due to the extremely high-risk dangers and hazards it presents to the athletes. While athletic performance can be improved, possibly by up to 10%, boosting is very dangerous, and most sporting events for the disabled, including the Paralympics and the International Paralympic Committee, ban such intentional acts.[27][28][29](B3)

Emergency Antihypertensive Pharmacological Treatment: If the triggering event cannot be identified and initial maneuvers do not improve the systolic blood pressure below 150 mmHg or less than 40 mmHg 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 initial emergency treatment of severe hypertension in patients with autonomic dysreflexia.[30] One to two inches of nitroglycerine 2% paste should be placed on the skin above the level of the spinal cord injury.[30] It can easily be removed when the hypertensive crisis is over.[30] 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 it and hold it in place. Nitrates should not be administered to patients who may 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. Nitrate therapy has a relatively high risk of rebound hypotension.

Immediate-release nifedipine 10 mg has also been recommended as the initial medical pharmacotherapy when required. This should be reduced to 5 mg in the elderly and those already taking other antihypertensive medications.[31] The capsule should be administered with a "bite and swallow" technique. The treatment should be repeated every 20 to 30 minutes as needed up to a maximum of 40 mg/24 hours. Nifedipine is not recommended in patients with coronary artery disease. Sublingual nifedipine is not recommended due to its unpredictable absorption.[8]  

Other examples of acceptable antihypertensive treatment would 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 to 20 mg slow IV PRN), intravenous labetalol (if the heart rate is not too slow), phentolamine 5 mg IV PRN, sodium nitroprusside (0.5 to 3 mcg/kg/min PRN), diazoxide (20 mg IV bolus), prazosin, and terazosin, among others.[23] 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.[8] Rebound hypotension can occur for five hours after administration of antihypertensive medications, particularly nitrates, so these drugs should be used with caution in this population with frequent monitoring.[8](B3)

Summary of Preferred Initial Pharmacological Antihypertensive Therapies for Emergency Use in Autonomic Dysreflexia:

• 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. The duration of action is 8 hours. The maximum dose is 5 inches.
• Nifedipine "Bite and Swallow": Dosage 10 mg. - Onset of activity: 10 to 20 minutes - Peak activity in 1 hour - May repeat every 20 to 30 minutes. The duration of action is 4 hours. The maximum dose is 40 mg./24 hours.
• Sublingual Captopril: Dosage 25 mg. - Onset of activity: 20 to 30 minutes - May repeat in 1 hour as needed. Peak activity in 1 hour. The duration of action is 4 hours. The maximum dose is 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 activity in 1 hour. The duration of action is 12 hours. The maximum dose is 0.8 mg.

After emergency hypertensive treatment, the patient's blood pressure should be monitored for at least an additional two 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 particularly dangerous and potentially lethal. Patients should be warned about potential side 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, the underlying etiology of the episode remains unknown or in pregnancy. Transfer to an intensive care unit should be considered if control of the autonomic dysreflexia and its associated hypertensive crisis has not been achieved within 30 minutes. Discharge is dependent on identifying the underlying cause and/or the episodes cease. Those 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 are able to comfortably treat the condition outside the hospital.[31] 

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. In women with spinal cord injuries, the symptoms of labor may only be some abdominal discomfort, increased spasticity, and autonomic dysreflexia. Epidural anesthesia has been reportedly the best choice for controlling autonomic dysreflexia during labor. 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 for autonomic dysreflexia. 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 the complications related to such injuries.

Procedures: Patients with spinal cord injuries and autonomic dysreflexia often undergo medical procedures and surgeries, such as urologic instrumentation, that can trigger dysreflexic episodes. 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/placement of the regional anesthetic may be challenging in patients with spinal cord injuries. An epidural catheter may also be considered for longer cases as it has the advantage of being able to be "topped off." Epidurals are subject to incomplete blocks and might be even more difficult to place. 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.[14][30] Emergency pharmacotherapy for autonomic dysreflexia should be immediately available.[17][30][32] If a patient develops autonomic dysreflexia during a urologic study or examination, the activity should be immediately terminated and the bladder promptly drained.[30] Hemodynamic monitoring should be maintained with appropriate pharmacotherapy if the condition continues despite these measures.[30]

Prophylaxis: Optimal management of patients with spinal cord injuries who are prone to autonomic dysreflexia is usually achieved by a multidisciplinary team which may include a spinal rehabilitation specialist, urologist, gastroenterologist, 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) than similar patients with neurogenic bladders who are not as susceptible to autonomic dysreflexia. Bowel management may include abdominal massage, periodic careful digital rectal stimulation, regular suppositories, and routine laxatives. Additional prophylactic measures include careful positioning, seating guidelines, use of appropriate pads along with pressure-relieving cushions and mattresses, as well as periodic inspections for skin lesions to minimize ulcers and breakdowns.[8] Daily antihypertensive medication solely for autonomic dysreflexia prophylaxis is generally not recommended.[30]

The use of 10 ml of 2% lidocaine administered intravesically 4-6 minutes prior to routine Foley catheter changes has been shown to significantly reduce episodes of autonomic dysreflexia in patients at high risk.[33] Botulinum toxin injections for chemical denervation of the bladder muscle have also been shown to reduce the incidence of autonomic dysreflexia in susceptible individuals.[22][34][35] (B3)

Minocycline has been shown to have a neuroprotective effect in animal testing models but has not yet been shown to have a similar clinical benefit in humans.[31][36][37][38]

While not the current standard of care, there is some evidence that gabapentin might be somewhat beneficial as a prophylactic agent in some spinal cord injured patients, particularly when a low dose is used before scheduled procedures to help mitigate the expected autonomic dysreflexic response.[39][40][41] (B3)

Noninvasive transcutaneous spinal cord stimulation has been shown in a limited study to significantly mitigate the degree of hypertension during a period of autonomic dysreflexia and even prevent it altogether.[42] Although this was an early, preliminary study, this Canadian report describes a promising new tool to help minimize or even prevent dangerous hypertensive episodes of autonomic dysreflexia in susceptible individuals.

Differential Diagnosis

• Acute glomerulonephritis

• Anxiety

• Cushing's syndrome

• Drug use or overdose (e.g., stimulants, especially alcohol, cocaine, or levothyroxine)

• Hyperaldosteronism

• Hyperthyroidism

• Intracranial hemorrhage

• Ischemic stroke

• Nephritic and nephrotic syndrome

• Polycystic kidney disease

Prognosis

The prognosis of autonomic dysreflexia is usually 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

The most serious complication of autonomic dysreflexia is a hemorrhagic stroke which can be serious and even deadly. If not adequately treated, autonomic dysreflexia causes a sustained, severe hypertension which can result in a variety of problems such as a 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. 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.[17]

Other potential complications are related to their underlying spinal injury such as pressure sores, decubiti, constipation, and urinary tract infections. But in patients prone to significant autonomic dysreflexia episodes, such problems can potentially lead to a dysreflexic episode.