Autonomic Hyperreflexia Case File

Autonomic Hyperreflexia Case File

Lydia Conlay, MD, PhD, MBA, Julia Pollock, MD, Mary Ann Vann, MD, Sheela Pai, MD, Eugene C. Toy, MD

Case 32

A 64-year-old man with C6 quadriplegia secondary to a spinal cord injury 1 year ago is scheduled to undergo cystoscopy for urolithiasis. Although he is insensate throughout much of his body, he still has some patchy areas of sensation, and experiences significant pain when a stone is passed. His past medical history is significant for hypertension treated with hydrochlorothiazide, and type II diabetes mellitus.

His physical examination is remarkable for atrophy of his limbs, but is otherwise normal. He is 67 in tall, and weighs 90 kg. His laboratory results, including a cardiac stress test, are normal as well. A general anesthetic is planned.

Anesthesia is induced with etomidate, the patient is paralyzed using a nondepolarizing neuromuscular agent and intubated, and surgery commences. About 30 minutes into the procedure the patient suddenly develops severe bradycardia (heart rate in the low 30’s bpm range), hypertension, and diaphoresis. You ask the surgeon to stop the procedure.

➤ What is the most likely diagnosis?

➤ How can this situation be prevented?

➤ How should this patient be managed?

➤ Is it safe to continue surgery?

ANSWERS TO CASE 32:

Autonomic Hyperreflexia

Summary: This is a patient with quadriplegia who has developed signs of bradycardia, hypertension, and diaphoresis following surgical manipulation of the urinary tract.

➤ Most likely diagnosis: Autonomic hyperreflexia (AH), which occurs in patients with high spinal cord injuries and can be precipitated by a range of stimuli including manipulation of the bladder during surgery.

➤ Prevention: The best way to prevent an episode of AH is to avoid the offending stimulus. The patient is often aware of the episodes, and usually knows what factors are problematic for him. If the procedure necessitates a situation which can trigger AH (such as a cystoscopy requiring bladder distension), then careful monitoring can detect the episode early in its course, and the offending stimulus removed.

➤ Treatment: When AH occurs during surgery, management begins with removal of the precipitating stimulus. This alone may be sufficient and blood pressure often returns back to baseline levels immediately. In addition to removing the stimulus, AH is best treated by increasing the depth of anesthesia (eg, giving a bolus of intravenous anesthetic or increasing the concentration of inspired volatile agent).

➤ Proceed with surgery: Surgery cannot proceed until you stabilize the patient. Most episodes of AH are brief and self-limiting. After stabilizing the patient and having increased the depth of general anesthesia, it is reasonable to allow surgery to continue whilst carefully monitoring the patient.

ANALYSIS

Objectives

1. Become familiar with the syndrome of autonomic hyperreflexia.

2. Know the precipitating factors, clinical features, and complications of autonomic hyperreflexia.

3. Understand the anesthetic options and consideration for patients with AH.

4. Review additional anesthetic issues in quadriplegics such as truncal obesity, precautions when using succinylcholine, and the possibility of sleep apnea, difficult mask airway, and difficult intubation.

Considerations

Several considerations are warranted in this patient. First, he has patchy areas of sensation which may be normal or abnormal, so he will require an anesthetic for his surgery. This is in contrast with some patients with spinal cord injuries, who are totally insensate. In insensate patients, it may be possible to perform minor procedures without any anesthesia as long as the patient does not have AH. This patient states that he does have AH, and that it is triggered by fecal impaction or urinary retention. He knows when a triggering event has occurred because he gets a severe headache.

This patient is mildly obese, and intravenous access appears to be challenging. He is also quite anxious, warranting pretreatment with a benzodiazepine. Although he has had a cervical fusion, his airway examination shows a Mallampati class 1 airway and no problems with airway management are anticipated. Like many patients with chronic spinal cord injuries, he is plagued by painful muscle spasms which he cannot control.

With the notable exception of AH and spinal cord injury, this patient is remarkably healthy, NPO, and does not have gastric reflux. Thus, following premedication with a benzodiazepine, a general anesthetic with a laryngeal mask airway is planned.

APPROACH TO

Autonomic Hyperreflexia

DEFINITIONS

AUTONOMIC HYPERREFLEXIA: Autonomic hyperreflexia (AH) is a phenomenon that occurs after spinal cord transection. It is characterized by a massive and disordered autonomic response to certain stimuli below the level of the lesion.

QUADRIPLEGIA: Also known as tetraplegia, is a symptom in which a human experiences paralysis affecting all four limbs, although not necessarily total paralysis or loss of function. It is caused by injuries to the cervical (and occasionally thoracic) spine, and results in an impairment of limb function, bowel and bladder control, sexual function, digestion, respiration, and other autonomic functions. Sensation is usually impaired in affected areas, and can manifest as numbness, reduced sensation, or burning neuropathic pain.

CLINICAL APPROACH

What is autonomic hyperreflexia?

Autonomic hyperreflexia (AH) is a phenomenon that typically occurs after spinal cord injury. It was first recognized in 1860, and in 1917, Head and Riddoch described the effects of bladder distension on soldiers with spinal cord injury. AH is characterized by a massive and disordered autonomic response to certain stimuli below the level of the lesion. This response is thought to be due to sympathetic and parasympathetic activity, unopposed by the normal central modulatory pathways. AH can occur in up to 85% of patients with spinal cord lesions above the level of T6.

Major advances in the care of spinal cord injury patients have led to an improved survival rate, an increase in the number of spinal cord injury patients presenting for elective surgery, and thus an increase in the frequency of AH. In addition, quadriplegic patients are medically complicated due to obesity, risk of DVTs, sleep apnea, and challenges with airway management. An understanding of the relevant pathophysiology allows the anesthesiologist to provide safe perioperative care. The complications associated with spinal cord injury are listed in Table 32–1.

Clinical Features and Complications of AH

The most common clinical feature of AH is hypertension, which is typically paroxysmal and may be severe. Systolic blood pressures may exceed 260 mm Hg and diastolic pressures range from 170 to 220 mm Hg. Hypertensive crises can lead to intracranial and retinal hemorrhages, seizures, coma, myocardial ischemia, pulmonary edema, and death.

Headache is also a common feature of AH, and may be the first sign to herald the onset of an episode of AH. Profuse sweating, flushing or pallor above the level of the lesion, and reflex bradycardia are seen in the majority of cases. Other reported features include papillary changes, Horner syndrome, nausea, anxiety, and penile erections. The clinical features of AH are summarized in Table 32–2.

The neurophysiological changes in AH reflect both loss of descending inhibition from higher centers, and alterations in connections within the distal spinal cord. This results in a widespread inappropriate sympathetic response that lacks the usual descending inhibitory influences, leading to profound vasoconstriction. Circulating norepinephrine levels remain low following spinal cord transection, presumably as a result of the reduced sympathetic activity. Thus, patients post spinal cord injury are typically more sensitive to the effects of exogenous catecholamines than normal individuals.

AH occurs more frequently in the OR in patients who have experienced the syndrome in their daily lives. A range of stimuli can trigger a mass autonomic response, not just those that occur in the operating room. However, bladder 

Table 32–1 COMPLICATIONS ASSOCIATED WITH SPINAL CORD INJURY
BODY SYSTEM	POTENTIAL COMPLICATIONS
Cardiovascular	• Blood volume is typically reduced in tetraplegics. • Orthostatic hypotension: head-up tilt causes a fall in stroke volume and cardiac output.Venous return is impaired and pooling of blood occurs in the lower limbs. • Elevated renin and aldosterone levels lead to salt and water retention.
Respiratory	• Obesity can cause obstructive sleep apnea and increased neck girth leading to a potentially difficult intubation. • Reduced vital capacity. • Impaired ability to cough. • Reduced respiratory drive and ventilatory response to hypercapnia. • Respiratory insufficiency: mainly due to muscle weakness (diaphragmatic, intercostals, abdominal wall and accessory muscles). Quadriplegics with central apnea due to high spinal cord lesions may potentially benefit from phrenic nerve pacing (diaphragmatic stimulators). Diaphragmatic pacing can be considered for patients who have cord lesions above the C2-C3 level since pacing of the diaphragm by phrenic nerve stimulation is possible only if the nerve cell bodies (located in the anterior horns of C3-C5) are viable.
Musculoskeletal	• In acute spinal cord injury: acetylcholine receptors proliferate over the entire muscle membrane.The use of depolarizing muscle relaxants can lead to massive ion fluxes and fatal hyperkalemia. • Spinal cord injury can lead to spasms and contractures. • Treatments include drug therapy and passive physiotherapy. • Osteoporosis due to a significant reduction in bone density below the level of the spinal cord injury is common.
Temperature regulation	• High spinal cord injuries impair normal mechanisms of thermoregulation by preventing shivering in response to cold and sweating or vasodilatation in response to heat. Patients become partially poikilothermic and body temperature reflects environmental temperature.
Skin care	• Decubitus ulcers occur in up to 60% of patients with cervical lesions. Left untreated, pressure sores can lead to chronic infection,osteomyelitis, septicemia,amyloidosis and can trigger AH.
Blood disorders	• Anemia of chronic disease is common in this patient population. • The risk of deep vein thrombosis formation is greatly increased in the early stages following a cord injury. Untreated, 80%-85% of patients will develop deep vein thrombosis.
Genitourinary	• Spinal cord injury leads to incomplete voiding, high intravesical pressures and vesicoureteric reflux. • Urinary tract infections are common as a result of high residual volumes and the use of urethral catheters. • Renal calculi form easily.
Gastrointestinal	• Acute gastroparesis and ileus is common immediately after spinal cord injury. • Patients with spinal cord injury have residual delayed gastric emptying.
Pain	• Chronic pain may occur in up to 60% of patients with spinal cord injury and can be difficult to manage.

or bowel distension, uterine contractions, acute abdominal pathology, handling of bowel or bladder manipulations during surgery, and urinary tract infection are the most common precipitating factors. Cutaneous and proprioceptive stimuli are less commonly implicated. Thus, in patients with a high cord lesion, AH occurs most often during urological surgery, and is less common during body surface surgery. It is important to remember that these triggers may occur intraoperatively, or in the immediate postoperative period.

The Anesthetic Plan

When performing the preoperative anesthetic assessment and formulating the anesthetic plan in a cord injury patient, special consideration should be given to the following factors:

• Ask the patient whether he or she gets AH, and if so, how does he/she know?

• Sensory level, site of surgery, and completeness of lesion.

Table 32–2 CLINICAL FEATURES OF AUTONOMIC HYPERREFLEXIA
COMMON FEATURES	OTHER FEATURES
Hypertension Headache Sweating Pallor Bradycardia	Nausea Anxiety Pupillary changes Horner syndrome Penile erections

• Patient preference for anesthesia, and/or the type of anesthetic technique (general/regional/monitored anesthesia care/or no anesthesia).

• Time elapsed since spinal cord injury: The risk of a hyperkalemic response to succinylcholine is greatest from 3 days to 9 months post injury.

• Prior anesthetic history: Previous anesthetic records should be located. Many cord-injured patients have often had multiple prior procedures and may regularly undergo surgery without anesthesia.

• Airway and neck motion, which may be affected by previous cervical spine surgery.

• History of respiratory tract infections, obstructive sleep apnea, intensive care unit admissions, tracheostomy past or present, and respiratory sufficiency, or the need for respiratory enhancements such as a diaphragmatic stimulator or chronic ventilation.

• Vital capacity should be measured in all patients with lesions above C7; chest x-ray and arterial blood gases may also be indicated preoperatively.

• Cardiovascular assessment: Baseline blood pressure, heart rate, history of postural hypotension, history of prior AH.

• Musculoskeletal deformities: Spasms, contractures, pressure sores.

• Medications: Use of anticoagulants, muscle relaxants.

• Laboratory tests (complete blood count, electrolytes and renal function). Anemia is common. Electrolytes, BUN, and creatinine to exclude renal impairment.

Choice of Anesthesia

Loss of sensation below the level of the lesion following a spinal cord injury means that these patients could theoretically undergo surgery without anesthesia and without feeling pain from the operative site, as they often do. However, the decision as to whether anesthesia is required for a procedure depends on the surgery, the level of the spinal cord lesion, the completeness of the lesion and very importantly, patient preference. Patients who experience muscle spasms may require anesthesia for positioning and control during surgery, since spasms are often triggered by proprioceptive and cutaneous stimuli.

An anesthesiologist should be present, venous access secured, and standard monitoring used throughout the procedure for all operations on cord injury patients, regardless of anesthetic technique.

Premedication and i.v. Access

Patients with spinal cord injuries have typically undergone multiple surgeries and procedures since their original injury. They are also particularly susceptible to preprocedure anxiety, which should be treated with benzodiazepines. 

Obesity is a secondary effect of spinal cord injury due to inactivity. The typical body habitus is that of truncal obesity with wasting of the lower limbs. The upper limbs may also display muscle wasting and fat accumulation leading to difficulties obtaining i.v. access.

The absence of reflex sympathetic activity reduces the ability to compensate for the myocardial depressant effects of anesthetic agents. Placement of a large-bore intravenous cannula is recommended and preoperative fluid loading with 500 to 1000 mL of crystalloid reduces the likelihood and severity of hypotension after induction.

General Anesthesia

Patients with spinal cord injury often have a lower blood volume with a reduced lean tissue mass secondary to muscle wasting. This leads to a smaller volume of distribution for intravenous anesthetic agents which explains the greater observed sensitivity of these patients to intravenous induction agents. Spinal cord injury is also associated with renal impairment, which may result in reduced clearance of certain drugs.

Succinylcholine may be used safely in cord injury patients within the first 72 hours of injury and after 9 months. The choice of airway technique is largely the same as for normal patients, and the use of the laryngeal mask airway in cord injured patients has been widely described. The theoretical risks of aspiration associated with the use of a laryngeal mask airway in this patient population have not been substantiated.

Positioning is of even greater importance in the in the cord injured patient compared with normal individuals due to the high incidence of pressure sores and spasmodic movements. Patients with spinal cord injuries also become poikilothermic, so the prevention of heat loss during surgery is of great importance. Passive humidifiers, fluid warming devices, hot air blankets, and operating in a warm room are all recommended in this patient population.

Regional Anesthesia

The use of regional anesthesia in cord injured patients is well established, particularly spinal anesthesia for urological surgery and epidural anesthesia for labor. The advantages of spinal anesthesia in cord injured patients are the reliable prevention of AH, and avoidance of risks associated with general anesthesia. However, disadvantages of spinal anesthesia include the inability to determine the level of the block and difficulty in determining the appropriate dose of medications to administer. In some patients, the level of the block may be determined by observing the level at which spastic paresis becomes flaccid, the disappearance of ankle or knee reflexes, temperature changes in the lower limbs, or the ability to elicit muscle spasm to ethyl chloride spray.

Placing a spinal may be technically challenging due to kyphoscoliosis, truncal obesity, prior spinal surgery, and inability to flex the spine due to spasms and bony deformities. Although spinal anesthesia can cause hypotension in normal patients, in spinal cord injured patients, spinal anesthesia is associated with cardiovascular stability, perhaps because cord injured patients have low baseline sympathetic tone. Alderson et al. recommend the use of 1.5 to 2.0 mL of hyperbaric 0.5% bupivacaine for use as a spinal anesthetic in urologic surgery.

Epidural anesthesia has been reported as being less effective in blocking AH than spinal anesthesia. Problems with epidural anesthesia in this population also include the inability to assess the block accurately, correctly verifying the effect of the test dose, the failure to block sacral spinal cord segments, and the very real possibility of missed segments due to distortion of the epidural space.

Management of AH in the OR

If AH occurs during surgery, management should begin with removal of the precipitating stimulus if at all possible. This alone may be sufficient to terminate the episode and blood pressure often returns back to baseline levels immediately. Most episodes of AH are brief and self-limiting and may not require

specific treatment. During general anesthesia, AH is best treated by increasing the depth of anesthesia. Additional treatment options include calcium channel blockers, nitrates, and assumption of the upright position. If the stimulus is not obvious, bladder distension and fecal impaction should be ruled out. In the non-OR setting, a urinary catheter should be checked for blockage and urinary tract infection excluded. Tight clothing and footwear should also be loosened.

Comprehension Questions

32.1. In which of the following patients is it safe to use succinylcholine?

A. 24 hours after a spinal cord injury

B. 1 month after a spinal cord injury

C. 1 week after a spinal cord injury

D. 2 months after a spinal cord injury

E. 6 months after this injury

32.2. A patient with C6 quadriplegia develops hypertension (BP = 240/118) under general anesthesia for laparoscopic cholecystectomy. Therapeutic maneuvers that can be initiated do not include which of the following?

A. Increase concentration and delivery of volatile agent.

B. Nitroglycerin infusion.

C. Phenoxybenzamine.

D. A propofol bolus.

E. Nitroprusside infusion.

32.3. The patient described in question 32.2 is noted to be tachycardic with HR = 95 bpm. Which of the following is the most likely etiology?

A. Hypercarbia

B. Pheochromocytoma

C. Thyroid storm

D. Spinal dysreflexia

E. Awareness

ANSWERS

32.1. A. Following the development of spinal cord injuries, extra-junctional cholinergic receptors develop after 48 to 72 hours. A severe hyperkalemic response to succinylcholine may be seen up to 9 to 12 months after the injury.

32.2. C. Presuming that this hypertension is a result of autonomic hyperreflexia, short-acting agents should be used to correct the hypertension. Long-acting agents like phenoxybenzamine are not appropriate as they may result in prolonged hypotension following the cessation of the stimulus, particularly in a patient with low baseline sympathetic tone.

32.3. A. Of these syndromes, hypercarbia is both most likely, and most easily manipulated so it should be excluded from the differential first. Answer D, autonomic hyperreflexia, is characterized by reflex bradycardia as long as there is a functional carotid sinus. The anesthesiologist should also be careful not to miss other causes of intraoperative hypertension such as pheochromocytoma, thyroid storm, and awareness (Answers B, C and E).

Clinical Pearls

➤ Autonomic hyperreflexia is common in individuals with spinal cord injuries above T6.

➤ It is characterized by paroxysmal reflex autonomic activity in response to noxious stimuli below the level of the neurologic lesion, and can lead to pulmonary edema,myocardial ischemia, cerebral hemorrhage, and death.

➤ Headache, diaphoresis, flushing, bradycardia, and paroxysmal hypertension are most commonly observed.

➤ Bladder and bowel distention, and surgical manipulations are the most common intraoperative precipitating factors.

➤ Removal of the offending stimulus is key to restore the baseline autonomic activity.

➤ Regional anesthesia and deep general anesthesia both treat and prevent hyperreflexia.

References

AK Karlsson. Autonomic dysreflexia. Spinal Cord. 1999;37:383-391. 

Colachis SC. Autonomic hyperreflexia with spinal cord injury. J Am Paraplegia Soc. 1992;15(3):171-186. 

DiMarco AF, Takaoka Y, Kowalski KE. Combined intercostal and diaphragm pacing to provide artificial ventilation in patients with tetraplegia. Arch Phys Med Rehabil. 2005;86:1200. 

Elefteriades JA, Hogan JF, Handler A, Loke JS. Long-term follow-up of bilateral pacing of the diaphragm in quadriplegia. N Engl J Med. 1992;326:1433. 

Hambly PR, Martin B. Anaesthesia for chronic spinal cord lesions. Anaesthesia. 1998;53:273-289. 

Lee BY, Karmakar MG, Herz BL, Sturgill RA. Autonomic dysreflexia revisited. J Spinal Cord Med. 1995;18(2):75-87. 

Trop CS, Bennett CJ. Autonomic dysreflexia and its urological implications: A review. J Urol . 1991;146(6):1461-1469.

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