Autonomic Dysreflexia: Be Aware and Be Prepared

  Abstract: Autonomic dysreflexia (AD) is an acute, life-threatening syndrome of uncontrolled sympathetic discharge that occurs in patients with spinal cord injury at T6 or higher. Despite a high incidence in tetraplegics, the condition is under-recognized, putting both the practitioner and patient at risk. This report presents a case of AD triggered by debridement of a pressure ulcer. To advance the understanding among wound care practitioners, the authors review the literature, describe the common clinical presentations and scenarios leading to AD, delineate a protocol to guide management, and conclude with a discussion of potential preventative measures.

Introduction

  Traumatic spinal cord injury (SCI) affects 200,000 people in the United States, with an average rate of 10,000 new cases developing each year.¹ While both the severity of neurological injury and the existence of comorbid diseases are predictors of long-term mortality in patients with SCI, secondary complications of SCI are also associated with adverse outcomes.² Autonomic dysreflexia (AD) and pressure ulcers are of particular importance because of the high incidence rates and fatalities attributed to each.   Autonomic dysreflexia is an acute, life-threatening syndrome of uncontrolled sympathetic discharge that occurs, in response to stimuli, in patients with SCI above the splanchnic outflow tract (level T6). Clinically, AD is characterized by a sudden elevation in blood pressure (BP) of at least 20 mmHg above baseline, and one of the following signs/symptoms: bradycardia, headache, flushing, and/or profuse sweating above the lesion level.^3,4 Left untreated, the sympathetic surges can progress to hypertensive crises with serious sequelae, including intracranial or retinal hemorrhage, seizures, myocardial infarction, arrhythmias, and death.^3,5-9The reported incidence of AD varies greatly, but is as high as 91% in patients with complete tetraplegia.¹⁰ Despite this high incidence, AD is an often unrecognized phenomenon.¹¹ The paroxysmal hypertensive episodes of AD occur in response to a variety of organic and iatrogenic stimuli below the level of SCI. Although bladder and bowel etiologies are most commonly reported,^12-16 integumentary system deficits, such as pressure ulcers and their management, might also prompt a dysreflexic reaction.^5,16-19   Pressure ulcers occur in 23% to 40% of patients with SCI during acute rehabilitation,^20,21 and then recur in 35%–80% of patients,^22-24 contributing significantly to increased morbidity and diminished quality of life.²⁵ In concert with the patient’s primary care physician, the wound care team plays an integral role in the evaluation and management of pressure ulcers. The approach to treatment varies depending on ulcer stage and risk factors for poor wound healing. It often involves a spectrum from removal of devitalized tissue by bedside debridement to surgical closure with flap reconstruction.²⁶ These procedures induce strong stimuli beneath the level of SCI, and therefore, might trigger AD.   This report presents a case of AD triggered by sharp debridement of a pressure ulcer. To advance the understanding of AD among wound care practitioners, the authors review the literature and describe the clinical presentation to recognize the most common presenting phenomena, delineate a protocol to guide management, and conclude with a discussion of potential preventative measures.

Case Report and Methods

  A 57-year-old man with C5 tetraplegia was being followed by the plastic surgery service for management of a Stage IV sacral pressure ulcer, complicated by devitalized and macerated wound edges. Sharp debridement and excision of this tissue was planned, under local anesthesia in the minor procedures room, to promote further wound healing. As scalpel debridement and excision of the circumferential edges of a 5 cm x 2.5 cm wound began, the patient reported a sense of uneasiness and a headache. At that time, debridement was stopped and additional 1% lidocaine was injected at the site. After allowing time for local anesthesia to take effect, sharp debridement continued. Immediately, the patient began to sweat, his face appeared flushed, and he became hypertensive with a BP elevation to 210/180 from 105/67 before the procedure. The treatment team, now suspecting AD, initiated the institution’s (James A. Haley Veterans Hospital) AD protocol (Figure 1). The procedure ceased, the head of the bed was elevated, his clothes were loosened and his catheter was inspected for kinks or obstructions to rule out a bladder etiology. Despite the previous interventions, the patient’s BP remained elevated (200/170). Accordingly, 1-in of 2% nitroglycerin ointment was applied. His BP remained elevated (> 150 mmHg systolic) 5 minutes later, thus a 10 mg oral dose of nifedipine was administered. His BP then began to return to baseline and stabilized at 110/55 15 minutes later. He was inspected for bowel triggers (eg, fecal impaction), and other possible cutaneous triggers (eg, paronychia), with none detected. The episode was documented and the patient’s history was reviewed. It was known that the patient had a history of AD associated with bladder distension and bowel manipulation; however, there was no history of AD associated with pressure ulcers. The patient was followed over the next 2 years and his wound required 4 further procedures—3 involving sharp debridement and 1 involving surgical debridement with flap closure. All of these procedures were performed under general anesthesia, and the patient did not experience another AD episode.

Discussion

  Pathogenesis. To appreciate the clinical presentation of AD and the relationship to surgical procedures, it is paramount to understand the pathogenesis of AD. Autonomic dysreflexia develops following SCI from dysfunctional sympathetic regulation, spinal cord reorganization, and an abnormal disconnect between the parasympathetic and sympathetic autonomic nervous systems (ANS).³ Sensory stimuli are carried by primary afferent fibers to the dorsal grey matter (DGM) of spinal cord segments. These afferents synapse, with interneurons in the DGM, before ascending into the dorsal and spinothalamic tracts.²⁷ Normally, these ascending impulses activate higher brain centers that induces a descending inhibitory input to modulate sympathetic output from interomediolateral (IML) cell column (preganglionic neurons).²⁸ Following spinal cord transection, sympathetic output below the lesion is functionally separated from inhibitory input above the lesion.^29-31 Spinal reorganization then occurs with aberrant intraspinal afferent fiber sprouting and is correlated with the development of AD.^27,32-34 It is postulated that increased afferent sprouting into the lumbosacral spinal cord heightens the response to stimuli and contributes to plasticity of lumbosacral propriospinal neurons.^27,35 This relationship is crucial, as it is the propriospinal projections that relay primary afferent input rostrally to sympathetic preganglionic neurons in the IML.^35-37   Clinical presentation. The massive, unregulated sympathetic discharge from these preganglionic neurons, in direct response to afferent stimuli, underlies the clinical presentation of AD. Sympathetic activity above the splanchnic outflow tract (T5–L2) results in severe vasoconstriction causing sudden BP elevations.³ In the able-bodied, the ANS regulates this homeostatic imbalance through compensatory pathways. Specifically, baroreceptors detect pressure changes and alter their firing rates to send signals to the vasomotor center of the brain. A compensatory parasympathetic response of bradycardia and vasomotor dilation ensues to reduce BP. However, in patients with SCI, this vasomotor pathway is severed at the lesion level creating an anatomical and physiological demarcation between sympathetic and parasympathetic activity.^30,31 The most commonly reported symptoms of AD are manifestations of this disjunction. The first subjective indication of AD in the patient described in this report was a severe, pounding headache secondary to vasodilation. Parasympathetic activity above the lesion also presents as facial flushing, profuse sweating, blurred vision, and bradycardia. In addition to the paroxysmal hypertensive episodes, vasoconstriction may cause pallor below the lesion.¹² A combination of excessive catecholamine levels and peripheral alpha-adrenoreceptor hyper-responsiveness to catecholamines has been experimentally verified, and further implicates the role of sympathetic overactivity in AD.^29,38-40   Causes. Being cognizant of the role sensory stimuli play in instigating the AD cascade makes it possible to appreciate how several precipitants have been reported to cause AD. While, theoretically, any noxious stimuli applied below the SCI level can travel on primary afferents and lead to an amplified sympathetic response, this is not always true clinically.⁴¹ The authors’ understanding of which noxious cutaneous or visceral stimuli are capable of triggering AD is evolving and is not yet definitive. However, to date, the most commonly reported precipitants are bladder distension from obstructed catheters and rectosigmoid distension from fecal impaction.^12,14-16 Several other urogenital and anorectal stimuli are known to provoke AD, including catheterization, urinary tract infections, sexual activity, hemorrhoids, urodynamic studies, cystoscopy, extracorporeal shock wave lithotripsy, flexible endoscopy, and other colorectal manipulations.¹⁹ Musculoskeletal etiologies of fracture, hip dislocation, Charcot arthropathy, and functional electrical stimulation (FES) of the musculature are also supported by case reports.^42-44Pregnancy and labor in women with SCI above T6 are known obstetric causes of AD.³ Surgical interventions are particularly potent stimuli for the development of AD, with reports that 65%–85% of patients with T6 or higher SCI had symptoms consistent with AD when undergoing surgical procedures below the level of lesion.¹⁸ It also follows, because noxious cutaneous stimuli have been experimentally proven to cause AD,³⁶ that precipitants, such as contact with sharp objects, sunburns, blisters, ingrown toenails, constrictive clothing, and pressure ulcers, are noted in the literature. ^4,5,16-19   Pressure ulcers and AD. Pressure ulcer debridement is a common procedure in patients with SCI. The high incidence, significant morbidity, and potential mortality associated with pressure ulcers makes wound care an essential component of the interdisciplinary approach to SCI.45 The initial evaluation of ulcers includes a risk assessment for potential wound healing complications and ulcer staging (I–IV), according to the National Pressure Ulcer Advisory Panel (NPUAP) system.^26,45,46 The presence of necrotic or infected tissue delays wound healing, leads to failure of surgical closure, and may be fatal.26,47 Thus, debridement is pivotal and may require a surgical consultation. A variety of debridement methods exist, and the choice of method is dependent upon the clinical situation.⁴⁷ Nonsurgical debridement is generally performed for Stage I and II ulcers. Stage III or IV ulcers that have high bacterial burdens or extensive necrosis often require operative debridement to stimulate wound healing, remove sources of sepsis, and prepare the wound bed for surgical closure.^26,45Plastic surgeons are able to reconstruct tissue deficits with fasciocutaneous and musculocutaneous flaps, which are the preferred methods for surgical closure.²⁶ If patients are not optimized for surgical closure, electrical stimulation and negative pressure wound therapy are adjunctive strategies that promote healing in Stage III or IV ulcers.^45,47All of these procedures, because they involve a noxious stimulation of peripheral afferent fibers, carry an inherent risk of provoking AD.   Diagnosis and treatment. The importance of recognizing AD is to prevent potentially catastrophic consequences of uncontrolled sympathetic activity. Several reports have studied hypertensive intracerebral hemorrhage with AD.^5-9The resulting mass effect from the volume of hemorrhage can lead to herniation and subsequent death.⁴⁸ Excessive sympathetic activity can also cause arrhythmia, atrial fibrillation, left ventricular failure, and myocardial ischemia.^3,29,49Other dangerous complications that have been reported are retinal hemorrhage, seizures, and pulmonary edema.^3,50   The avoidance of life-threatening sequelae is achieved through early recognition and immediate treatment. The principle step in the management of AD is to recognize the constellation of symptoms that define the syndrome.⁴ Systolic BP elevation of 20 mmHg or more above baseline should initiate suspicion of AD. Accompanying signs of bradycardia, flushing above SCI level, pallor below SCI level, and/or symptoms of sudden onset headache or blurred vision, necessitate management for AD.³ The Consortium for Spinal Cord Medicine (CSCM) has published recommendations for the acute treatment of AD that have been adapted by many centers into institutional protocols to guide clinicians.⁴ Dr. Gould and Dr. Pope’s facility, the James A. Haley Veterans Hospital (Tampa, FL), has implemented a protocol that accounts for these recommendations and is both evidenced-based and expert-opinion supported (Figure 1). The treatment team’s goal is to normalize BP once an AD episode is apparent. Immediately placing the patient in an upright, seated position, and loosening constrictive clothing may prevent BP elevations.⁴ Blood pressure should then be monitored in 2- to 5-minute intervals, because levels may suddenly elevate as high as 250 mmHg–300 mmHg systolic and 200 mmHg–250 mmHg diastolic.^5,12,14,31   Prompt identification and removal of triggering stimuli is the next step in management, as it arrests the peripheral afferent barrage. As alluded to previously, the most likely precipitants encountered during active management of a pressure ulcer are cutaneous insults from surgeries, debridement procedures, and dressing changes. However, given that bladder and bowel distension are most commonly responsible for AD, it is not without precedent for wound care providers to encounter coexisting precipitants.^5,7Therefore, it is essential to investigate for urological causes. If an indwelling urinary catheter is present, it should be inspected for correct placement, kinks, obstructions, and proper drainage with swift corrections made for any abnormalities. If obstruction is suspected, gentle irrigation of the bladder with 15 mL to 30 mL of normal saline is warranted. If a catheter is not in place or replacement is necessary, 2% lidocaine jelly placed into the urethra followed by catheterization should be performed.^4,15   A patient whose BP persists above 150 mmHg, in spite of these interventions, requires pharmacological intervention. Achieving BP control now takes priority over identifying other potential triggers, such as fecal impaction.⁴ Several medications have been used to manage hypertension in AD. The CSCM guidelines do not specify a preference, as long as the agent has a rapid onset and is short acting. The calcium channel blocker (CCB) nifedipine, administered in 10 mg bite and swallow doses, is supported by the highest level of evidence,⁵¹ and is therefore, the preferred initial agent by 48% and 58% of physicians in managing mild/moderate and severe AD, respectively.¹¹ If oral administration is not possible, as would be the case in an anesthetized patient, intravenous (IV) CCBs can be used to stabilize BP.⁵² Though no adverse events have been reported with its use in the treatment of AD, immediate release nifedipine has known cardiovascular side effects in the non-SCI population and should be avoided in cases of stroke or MI.⁵³ A recent systematic review of existing interventions also supports the use of nitroglycerin topical paste or IV sodium nitroprusside for initial management.⁵¹ Keeping in mind that nitrates are contraindicated in patients taking PDE5 inhibitors, captopril is suggested as a possible alternative agent.⁵¹ After initiation of an antihypertensive, BP should be frequently reassessed for therapeutic benefit and to avoid significant hypotension. The authors prefer nitroglycerin ointment as the first line agent because the ease of removal reduces the potential for life-threatening hypotension (Figure 1). If symptoms persist despite addressing urological and cutaneous sources, it is recommended to examine the patient for an anorectal stimulus.⁴ This is prudent, as fecal impaction may be the cause of AD, even in patients with SCI who have comorbid pressure ulcers.⁵⁴ For disimpaction, the CCSM guidelines propose gentle manual evacuation after instilling copious 2% topical lidocaine gel into the rectum. Once the AD episode has resolved, documenting the precipitant will make future preventative measures more effective.   Prevention. It has been proposed that the most effective approach to AD is prevention.¹¹ An integral part of prevention is improving awareness of AD among specialists so that they may prophylactically thwart pressure ulcer occurrence and eliminate AD triggers with proper bladder and bowel routines. However, these methods are only partially effective; despite improved risk assessment and preventative procedures, pressure ulcers develop with a high frequency in the SCI population.²¹ When eliminating the source is not possible, eliminating the increased afferent stimulation and subsequent sympathetic overactivity triggered by the source should be attempted, which requires a multidisciplinary approach. Several studies in the urology literature have focused on preventing urogenital stimuli from triggering AD.⁵¹ Particularly pertinent among these studies is evidence that alpha-1 adrenoreceptor blockers limit recurrent AD.^51-55This may also be applicable to the treatment of patients with recurrent pressure ulcers who have previously incurred an episode of AD from wound debridement. In addition to limiting the predictable sympathetic overactivity, an emphasis must be placed on abolishing the afferent signaling to the spinal cord.   It is logical to assume that a local anesthetic would retard noxious stimuli, thereby preventing the AD reaction. However, the literature and the authors’ experience do not support this assumption. While there are no studies that specifically evaluate anesthesia in preventing AD during debridement procedures, there are studies that address the efficacy of anesthesia in interventions that simulate the noxious stimuli expected in these procedures. For example, observational studies have demonstrated that a significantly higher percentage of SCI patients develop AD when undergoing surgery with no anesthesia or local anesthesia compared to patients with SCI undergoing surgery with general or spinal anesthesia.^18-56Additionally, a recent report described recurrent AD, in response to surgical interventions, which was limited in severity when the patient was under general anesthesia, but was fatal when local anesthesia was used.¹⁹ There is also evidence from randomized controlled trials that intrasphincter lidocaine anal block, not topical lidocaine, is effective at preventing AD triggered by anorectal procedures.⁵⁷ Similarly, topical anesthesia has limited utility in even some noninvasive procedures. It is important to note that there was no difference between topical anesthesia and a placebo cream in limiting AD episodes during FES (where an electrical current is passed through the skin and into the muscle).⁴³ Comparatively, it is standard in the obstetric management of patients with SCI to administer regional anesthesia early in labor because of its known efficacy in preventing AD.⁵⁸ When comparing regional anesthesia methods in the nonpregnant population, spinal anesthesia is more effective than epidural anesthesia at preventing AD.⁵⁹ Regarding general anesthesia, it appears that the depth of anesthesia is more important than the anesthetic agent used. Severe hypertension during general anesthetic is an indication that the subcortical structures are still responding to noxious stimuli. Recent literature suggest that supplementing inhalational anesthetics with other adjuncts, such as opioids or nitrous oxide, may enhance blockade of the hyper-reflexic response, while avoiding severe hypotension.^59-61

Conclusion

  These studies are relevant to the preoperative decisions a practitioner must make regarding the need for anesthesia and method of anesthesia to employ. It is often suggested that sharp bedside debridement procedures can be performed without anesthesia in asensate patients or with only local anesthesia in sensate patients.^26-47The authors’ experience does not support this belief, as the patient in the presented case developed AD under local anesthesia when undergoing sharp debridement, but did not develop AD under general anesthesia even when subjected to more extensive operative debridement. Therefore, the present case supports the conclusion that spinal or general anesthesia should be preferred over local anesthesia for patients with a documented history of AD undergoing noxious wound care procedures. This applies to apparently minor sharp scalpel debridement, as well as reconstructive flap closure. Therefore, it is imperative that the wound care practitioner elicits whether the patient has a history of AD prior to considering debridement in the outpatient setting, with modifications to the debridement strategy made based upon this risk assessment. The anesthesiologist and surgeon must consider the potential complications of general and regional anesthesia when determining which technique to use. Further studies incorporating larger patient populations are warranted to compare the efficacy of local, regional, and general anesthesia in preventing AD. Ultimately, regardless of the choice of anesthetic, careful hemodynamic monitoring during debridement, and knowledge among the surgical staff of how to recognize and rapidly treat AD, is necessary to prevent adverse outcomes.

References

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Sevoflurane concentrations required to block autonomic hyperreflexia during transurethral litholapaxy in patients with complete spinal cord injury. Anesthesiology. 2008;108(5):858–863. 61. Yoo KY, Jeong CW, Kim SJ, et al. Remifentanil decreases sevoflurane requirements to block autonomic hyperreflexia during transurethral litholapaxy in patients with high complete spinal cord injury. Anesth Analg. 2011;112(1):191–197. Rajiv P. Parikh, MD and Matthew Franzen, MD are from the University of South Florida, Tampa, FL. Cecille Pope, MD and Lisa Gould, MD are from the James A. Haley Veterans Hospital, Tampa, FL. Address correspondence to: Lisa Gould, MD James A. Haley Veterans Hospital 13000 Bruce B. Downs Blvd. Tampa, FL 33612 lisa.gould@va.gov