- Email: [email protected]
Pheochromocytoma in quadriplegia
ORIGINAL REPORT
Pheochromocytoma in Quadriplegia Giselle G. Hamad, MD,* and Ronald C. Merrell, MD† *Department of Surgery, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, and †Department of Surgery, Medical College of Virginia Campus at Virginia Commonwealth University, Richmond, Virginia KEY WORDS: quadriplegia, pheochromocytoma, adrenalec-
tomy, autonomic dysreflexia
INTRODUCTION Autonomic dysreflexia affects patients with spinal cord injury and has the potential for catastrophic sequelae from hypertensive crises. It is characterized by a sudden increase in blood pressure and bradycardia in response to stimuli developing below the level of the spinal cord injury. The differential diagnosis includes migraine headaches, essential hypertension, posterior fossa tumors, toxemia of pregnancy, and pheochromocytoma, which also may cause severe hypertension, headaches, and diaphoresis. We describe the case of a 50-year-old male C-7 quadriplegic, who presented with severe hypertension and headaches. Initially, he was thought to have signs and symptoms of autonomic dysreflexia. Subsequent diagnostic examination revealed a 5-cm left adrenal pheochromocytoma. After alpha- and beta-adrenergic blockade, the patient underwent open left adrenalectomy. He required a brief postoperative infusion of phenylephrine to maintain his blood pressure. The patient’s preoperative preparation, operative management, and postoperative course are discussed. This is the first report of a quadriplegic patient undergoing excision of a pheochromocytoma.
METHODS The patient is a 50-year-old man with labile hypertension and C-7 quadriplegia secondary to a fall in 1990. He had been treated with felodipine 5 mg daily for hypertension. Over a 1-month period, he developed severe headaches associated with episodic hypertension. The episodes lasted from 2 to 4 minutes and were accompanied by headaches, palpitations, chest discomfort, and a “warm sensation” in his face. He presented to the emergency room for these symptoms. He was afebrile. Pulse was 70, and blood pressure was 210/110 mm Hg. Examination of the head, neck, chest, and abdomen was unremarkable. Neurologic examination revealed 3 out of 5 strength in the upper Correspondence: Ronald C. Merrell, MD, Department of Surgery, Chairman’s Office, West Hospital, 16th Floor, West Wing, 1200 East Broad Street, P.O. Box 980645, Richmond, VA 23298-0645; fax: (804) 827-1016; e-mail: [email protected]
206
extremities. His white blood cell count was 19.4 ⫻ 103/mm3, and hemoglobin was 16 g/L. Serum potassium was 2.9 mEq/L, and serum calcium was 10.7 mg/dL. Blood urea nitrogen (BUN) was 22 mg/dL, and serum creatinine was 1.3 mg/dL. He was admitted to the spinal cord injury service for blood pressure control. In addition, antibiotics were administered for a urinary tract infection. A tap water enema was given for fecal retention, and a Foley catheter was inserted. At that time, he was felt to have signs and symptoms of autonomic dysreflexia; he had undergone multiple orthopedic procedures in the past, which were often complicated by presumed autonomic dysreflexia. He was initially treated with prazosin 1 mg twice a day and felodipine 10 mg daily for hypertension with some improvement in his symptoms. However, his blood pressure lability persisted, with pressures ranging from 80/60 to 240/130 mm Hg. Thyroid function tests were normal. Computerized tomography (CT) was performed to eliminate the possibility of a post-traumatic spinal cord cyst that could account for the increase in blood pressure. Computerized tomography did not demonstrate any new pathology at his spinal fracture. However, CT of the abdomen demonstrated a 3.5 ⫻ 4.0 ⫻ 5.0-cm heterogeneous enhancing mass of the left adrenal gland, most likely caused by either primary or metastatic neoplasm, possibly pheochromocytoma. The right adrenal gland appeared normal radiographically (Fig. 1). Endocrine evaluation revealed urine metanephrine of 3036 mg/24 hours (normal, 35 to 460 mg/24 hours), urine normetanephrine of 5834 mg/24 hours (normal, 110 to 1050 mg/24 hours) urinary vanillylmandelic acid of 11.9 mg/24 hours (normal, 1.8 to 6.7 mg/24 hours), urine catecholamines of 624 mg/24 hours (normal, 0 to 140 mg/24 hours), and urine norepinephrine of 504 mg/24 hours (normal, 0 to 140 mg/24 hours). Urine epinephrine and dopamine were within normal range. Increases in plasma catecholamines of 2093 pg/ml (normal, 0 to 643 pg/ml), plasma epinephrine of 268 pg/ml (normal, 0 to 100 pg/ml), plasma norepinephrine of 1626 pg/ml (normal, 0 to 400 pg/ml), and plasma dopamine of 199 pg/ml (normal, 0 to143) occurred. Serum aldosterone and cortisol were within normal limits. Because the increase in urinary catecholamines may have been caused by autonomic dysregulation from quadriplegia, a clonidine suppression test was performed. Oral clonidine was administered (0.3 mg), and plasma cat-
CURRENT SURGERY • © 2002 by the Association of Program Directors in Surgery Published by Elsevier Science Inc.
0149-7944/02/$22.00 PII S0149-7944(01)00586-4
continued on postoperative day 6. Customarily volume expansion alone is sufficient after resection of pheochromocytoma. However, the spinal cord transection patient has a sympathectomy and may respond like a patient in spinal shock. Therefore, phenylephrine was useful and required for the very surprising 6 days until he stabilized. The postoperative course was complicated by pneumonia necessitating reintubation on day 3. Pancreatitis and a fluid collection required a drainage by a percutaneous catheter that was removed when the output ceased.
DISCUSSION
FIGURE 1. Computed tomography scan of the abdomen demonstrates a 3.5 ⫻ 4.0 ⫻ 5.0-cm heterogeneous enhancing mass of the left adrenal gland, most likely caused by either primary or metastatic neoplasm, possibly pheochromocytoma. The right adrenal gland appears normal.
echolamines are measured before and 3 hours after the clonidine dose. Clonidine is an alpha-2 adrenergic agonist, which inhibits sympathetic outflow from the brain, thereby lowering plasma catecholamines below 500 pg/mL in AD but not in pheochromocytoma. Serum epinephrine, norepinephrine, and total catecholamines failed to reduce significantly in response to clonidine. The diagnosis was most likely pheochromocytoma, and preoperative pharmacologic blockade was then initiated. The patient was treated with phenoxybenzamine to achieve alpha-blockade and intravenous fluids to expand the intravascular volume. Electrocardiograms were negative for arrhythmias. His initial dose of phenoxybenzamine was 10 mg twice a day, and this was gradually increased to 80 mg three times a day, to achieve adequate alpha-blockade. He was also treated with propranolol 10 mg three times a day, for beta blockade.
RESULTS After adequate preoperative adrenergic blockade was achieved, the patient was taken to the operating room and explored through a left subcostal incision. The left adrenal tumor was palpable and found to be about 4 cm in diameter with a dusky gray appearance. The procedure could have been done by laparoscopy. The patient had episodes of hypertension upon induction of anesthesia. The blood pressure fluctuated sharply and intermittently during the procedure, particularly during ligation of the adrenal vein, when he became transiently hypotensive. However, at the conclusion of the procedure, he required neither pressors nor inotropes. On histologic examination, the 4.0 ⫻ 3.5 ⫻ 2.9-cm adrenal mass was found to be a pheochromocytoma (Fig. 2A,B). No intraoperative or histologic evidence of malignancy was found. In the recovery room, a phenylephrine infusion was started for hypotension refractory to fluid resuscitation; this was disCURRENT SURGERY • Volume 59/Number 2 • March/April 2002
Autonomic dysreflexia (AD) is a clinical condition that has life-threatening potential. It affects patients with spinal cord injury and is most commonly seen in patients with lesions at or above T-7. Noxious stimuli below the level of injury, most commonly with manipulation of the perineum or distention of the bladder or rectum, can elicit an autonomic nervous system response characterized by excess sympathetic activity with an insufficient counter-regulatory parasympathetic response. Excess stimulation of the preganglionic sympathetic neurons in the spinal cord leads to paroxysmal hypertension, whereas vagal stimulation causes bradycardia. Patients often complain of severe headaches, chest pain, and profuse sweating and flushing.1 The most common stimuli that trigger AD develop from the lower urinary tract; distention of the bladder accounts for 75% to 85% of episodes of AD. Other stimuli developing from the urinary tract include urinary tract infections, catheterization, obstruction of a urinary catheter, urethral distention, cystitis, and testicular torsion. Anorectal stimuli are the second most common origins for AD. Fecal impaction leading to bowel distention causes 13% to 19% of AD episodes. Manipulation of the anorectal area with fecal disimpaction, colonoscopy, barium enema, or suppository administration may precipitate an episode of AD. Gastrointestinal disorders such as acute appendicitis, bowel perforations, and volvulus can also induce AD.1 Autonomic dysreflexia is characterized by a derangement in the balance of neurotransmitters and neuropeptides. Injury to the spinal cord leads to a profound reduction in the sympathetic outflow below the lesion, resulting in upregulation of noradrenergic receptors. Stimulation of these upregulated receptors leads to the exaggerated sympathetic activity and severe hypertension.2 A reduction in inhibitory neurotransmitter release contributes to the pathophysiology of AD. Gamma amino benzoic acid (GABA), an inhibitory neurotransmitter, decreases in spinal cord injury. Also, a reduction in norepinephrine and serotonin occurs below the level of spinal cord injury. In contrast, an increase in the excitation of neurons is mediated by an accumulation of substance P below the spinal cord lesion.1 Naftchi has attributed the disturbance in the regulation of blood pressure to various factors, including supersensitivity of spinal alpha-adrenoreceptors below the spinal cord injury caused by a lack of norepinephrine, hypersensitivity of peripheral vascular adrenergic receptors, and resetting of barorecep207
FIGURE 2. (A, B) The 4.0 ⫻ 3.5 ⫻ 2.9-cm left adrenal mass was a benign pheochromocytoma.
tors with a resultant insensitivity at high arterial blood pressures.3 Patients presenting with hypertensive crises are at risk of fatal cerebral hemorrhage, seizures, coma, and death. Systolic blood pressure may be as high as 300 mg Hg, and diastolic pressure may exceed 170 mm Hg.4 Anti-hypertensive treatment should 208
be initiated, and the triggering stimulus should be identified promptly. Bladder distention should be addressed by inserting a Foley catheter if the patient does not have an indwelling catheter and a specimen of urine should be sent for urinalysis, culture, and sensitivity. Fecal impaction should be evacuated, if present. CURRENT SURGERY • Volume 59/Number 2 • March/April 2002
The differential diagnosis for autonomic dysreflexia includes migraine headaches, essential hypertension, posterior fossa tumors, toxemia of pregnancy, and pheochromocytoma. Pheochromocytoma is a catecholamine-producing tumor originating from neural crest cells of the adrenal medulla or sympathetic ganglia, which often causes headaches and hypertension. In contrast to the bradycardia seen in autonomic dysreflexia, tachycardia is usually present with pheochromocytoma. In AD, diaphroresis and flushing are present above the spinal cord injury, whereas vasoconstriction is present below the lesion. However, in pheochromocytoma, these symptoms are present throughout the body.1 Both norepinephrine and epinephrine levels are increased in pheochromocytoma, whereas only norepinephrine levels are increased in autonomic dysreflexia.5 Urinary metanephrine, normetanephrine, and vanillylmandelic acid levels are increased in pheochromocytoma but not in autonomic dysreflexia.3 Only 0.05% to 0.1% of hypertensive patients have pheochromocytoma. Fifty percent of patients with pheochromocytoma have persistent hypertension, whereas 45% have paroxysmal hypertension and 5% are normotensive. The most frequent symptoms are headache, excessive perspiration, and palpitations.6 Diagnosis may be established by measurements of plasma epinephrine and norepinephrine and urinary metanephrine, normetanephrine, and vanillylmandelic acid. A clonidine suppression test may help to confirm the diagnosis. In patients with neurogenically induced hypercatecholaminemia, clonidine inhibits sympathetic outflow and reduces plasma catecholamines. However, in the setting of pheochromocytoma, plasma catecholamines are not suppressed.7 If biochemical evidence establishes the diagnosis of pheochromocytoma, imaging studies should be obtained in order to localize tumors. Computerized tomography scan and magnetic resonance imaging are preferred initial studies, whereas metaiodobenzylguanidine (MIBG) imaging is useful in detecting extra-adrenal pheochromocytoma. Preoperative alpha-adrenergic blockade with prazosin or phenoxybenzamine should be initiated to lower blood pressure and increase intravascular volume in patients with severe hypertension and volume depletion. Beta blockade should be administered only after alpha blockade has begun.8 Intravascular volume expansion is instituted to minimize postoperative hypotension. Because of wide variations in blood pressure and potential for cardiac dysrhythmias secondary to intraoperative catecholamine discharge, patients with pheochromocytoma may present a challenge for the anesthesiologist. Laryngoscopy, intubation, and tumor manipulation may provoke release of catecholamines and incite a hypertensive crisis. Conversely, the anesthesiologist may be faced with hypotension once the adrenal vein is ligated because of catecholamine withdrawal.9 Surgical extirpation is the only effective treatment of pheochromocytoma. The surgeon strives to minimize manipulation of the tumor while achieving a complete resection and excellent hemostasis. Several approaches to adrenalectomy have been deCURRENT SURGERY • Volume 59/Number 2 • March/April 2002
scribed. Open methods include the anterior or transabdominal, thoracoabdominal, flank or lateral, and posterior or retroperitoneal approaches. Initially, the transabdominal approach was recommended for pheochromocytoma because of the potential for bilateral or extra-adrenal tumors. The accuracy of preoperative imaging studies has improved, allowing for a more focused exploration.10 Minimally invasive adrenalectomy has been performed since 1992. Laparoscopic approaches to adrenalectomy include transabdominal and retroperitoneal methods. Laparoscopic adrenalectomy is safe and is associated with reductions in length of hospital stay, analgesia requirement, and duration of postoperative ileus.11,12 However, tumor size may limit the utility of this method. Spinal cord injury with quadriplegia is characterized by dysfunction of the sympathetic nervous system caused by the loss of supraspinal control, and it may result in hypotension and bradycardia.13 Therefore, the hemodynamic response to surgical stress and hypovolemia may present a formidable challenge for the anesthesiologist. In the face of volume depletion, vasoconstriction is impaired in the quadriplegic patient. An increase in venous capacitance may lead to a reduction in venous return and a fall in cardiac output. Left ventricular contractility is often impaired; myocardial depressants should be avoided if possible. Inhaled anesthetics increase venous capacitance and decrease myocardial contractility, thereby exacerbating the effects of sympathectomy and worsening hypotension. Intravascular volume replacement is the initial treatment; monitoring fluid balance with a pulmonary artery catheter is particularly useful in guiding therapy, especially because of the susceptibility to pulmonary edema.14 Interestingly, once this patient’s pheochromocytoma was excised and the source of catecholamines was removed, the patient’s underlying physiology as a quadriplegic was then unmasked and was expressed as hypotension. Accordingly, he required not only aggressive fluid resuscitation, but also a brief postoperative infusion of vasopressors.
CONCLUSION Autonomic dysreflexia is a phenomenon that affects patients with spinal cord injury and has life-threatening potential. Its differential diagnosis includes migraine headaches, essential hypertension, posterior fossa tumors, toxemia of pregnancy, and pheochromocytoma, which also may precipitate hypertensive crises and headaches. This is the first report of a quadriplegic patient undergoing excision of a pheochromocytoma.
REFERENCES 1. Lee BY, Karmakar MG, Herz BL, Sturgill RA. Autonomic
dysreflexia revisited. J Spinal Cord Med. 1995;18:75-87. 2. Naftchi NE, Richardson JS. Autonomic dyreflexia: phar-
macologic management of hypertensive crises in spinal cord injured patients. J Spinal Cord Med. 1997;20:355360. 209
3. Naftchi NE. Mechanism of autonomic dysreflexia. Con-
tributions of catecholamines and peptide neurotransmitters. Ann NY Acad Sci. 1990;579:133-148. 4. Kewalramani LS. Autonomic dysreflexia in traumatic my-
elopathy. Am J Phys Med. 1980;59:1-21. 5. Mathias CJ, Christensen NJ, Corbett JL, Frankel HL,
Spalding JM. Plasma catecholamines during paroxysmal neurogenic hypertension in quadriplegic man. Circ Res. 1976;39:204-208. 6. Gifford RW Jr, Manger WM, Bravo EL. Pheochromocy-
toma. Endocrinol Metabolism Clin North Am. 1994;23: 387-404. 7. Bravo EL, et al. Clonidine-suppression test: a useful aid in
9. Jovenich JJ. Anesthesia in adrenal surgery. Urol Clin North
Am. 1989;16:583-587. 10. Kebebew E, Duh Q-Y. Benign and malignant pheochro-
mocytoma. Surg Oncol Clin North Am. 1998;7:765-789. 11. Winfield HN, et al. Laparoscopic adrenalectomy: the pre-
ferred choice? A comparison to open adrenalectomy. J Urol. 1998;160:325-329. 12. Tanaka M, et al. Laparoscopic adrenalectomy for pheo-
chromocytoma: comparison with open adrenalectomy and comparison of laparoscopic surgery for Pheochromocytoma versus other adrenal tumors. J Endourol. 2000;14: 427-431. 13. Teasell RW, Arnold JW, Krassioukov A, Delaney GA.
the diagnosis of pheochromocytoma. N Engl J Med. 1981; 305:623.
Cardiovascular consequences of loss of supraspinal control of the sympathetic nervous system after spinal cord injury. Arch Phys Med Rehabil. 2000;81:506-516.
8. Malone MJ, et al. Preoperative and surgical management
14. Troll GF, Dohrmann GJ. Anaesthesia of the spinal cord-
of pheochromocytoma. Urol Clin North Am. 1989;16: 567-582.
injured patient: cardiovascular problems and their management. Paraplegia. 1975;13:162-171.
210
CURRENT SURGERY • Volume 59/Number 2 • March/April 2002
Pheochromocytoma in Quadriplegia Giselle G. Hamad, MD,* and Ronald C. Merrell, MD† *Department of Surgery, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, and †Department of Surgery, Medical College of Virginia Campus at Virginia Commonwealth University, Richmond, Virginia KEY WORDS: quadriplegia, pheochromocytoma, adrenalec-
tomy, autonomic dysreflexia
INTRODUCTION Autonomic dysreflexia affects patients with spinal cord injury and has the potential for catastrophic sequelae from hypertensive crises. It is characterized by a sudden increase in blood pressure and bradycardia in response to stimuli developing below the level of the spinal cord injury. The differential diagnosis includes migraine headaches, essential hypertension, posterior fossa tumors, toxemia of pregnancy, and pheochromocytoma, which also may cause severe hypertension, headaches, and diaphoresis. We describe the case of a 50-year-old male C-7 quadriplegic, who presented with severe hypertension and headaches. Initially, he was thought to have signs and symptoms of autonomic dysreflexia. Subsequent diagnostic examination revealed a 5-cm left adrenal pheochromocytoma. After alpha- and beta-adrenergic blockade, the patient underwent open left adrenalectomy. He required a brief postoperative infusion of phenylephrine to maintain his blood pressure. The patient’s preoperative preparation, operative management, and postoperative course are discussed. This is the first report of a quadriplegic patient undergoing excision of a pheochromocytoma.
METHODS The patient is a 50-year-old man with labile hypertension and C-7 quadriplegia secondary to a fall in 1990. He had been treated with felodipine 5 mg daily for hypertension. Over a 1-month period, he developed severe headaches associated with episodic hypertension. The episodes lasted from 2 to 4 minutes and were accompanied by headaches, palpitations, chest discomfort, and a “warm sensation” in his face. He presented to the emergency room for these symptoms. He was afebrile. Pulse was 70, and blood pressure was 210/110 mm Hg. Examination of the head, neck, chest, and abdomen was unremarkable. Neurologic examination revealed 3 out of 5 strength in the upper Correspondence: Ronald C. Merrell, MD, Department of Surgery, Chairman’s Office, West Hospital, 16th Floor, West Wing, 1200 East Broad Street, P.O. Box 980645, Richmond, VA 23298-0645; fax: (804) 827-1016; e-mail: [email protected]
206
extremities. His white blood cell count was 19.4 ⫻ 103/mm3, and hemoglobin was 16 g/L. Serum potassium was 2.9 mEq/L, and serum calcium was 10.7 mg/dL. Blood urea nitrogen (BUN) was 22 mg/dL, and serum creatinine was 1.3 mg/dL. He was admitted to the spinal cord injury service for blood pressure control. In addition, antibiotics were administered for a urinary tract infection. A tap water enema was given for fecal retention, and a Foley catheter was inserted. At that time, he was felt to have signs and symptoms of autonomic dysreflexia; he had undergone multiple orthopedic procedures in the past, which were often complicated by presumed autonomic dysreflexia. He was initially treated with prazosin 1 mg twice a day and felodipine 10 mg daily for hypertension with some improvement in his symptoms. However, his blood pressure lability persisted, with pressures ranging from 80/60 to 240/130 mm Hg. Thyroid function tests were normal. Computerized tomography (CT) was performed to eliminate the possibility of a post-traumatic spinal cord cyst that could account for the increase in blood pressure. Computerized tomography did not demonstrate any new pathology at his spinal fracture. However, CT of the abdomen demonstrated a 3.5 ⫻ 4.0 ⫻ 5.0-cm heterogeneous enhancing mass of the left adrenal gland, most likely caused by either primary or metastatic neoplasm, possibly pheochromocytoma. The right adrenal gland appeared normal radiographically (Fig. 1). Endocrine evaluation revealed urine metanephrine of 3036 mg/24 hours (normal, 35 to 460 mg/24 hours), urine normetanephrine of 5834 mg/24 hours (normal, 110 to 1050 mg/24 hours) urinary vanillylmandelic acid of 11.9 mg/24 hours (normal, 1.8 to 6.7 mg/24 hours), urine catecholamines of 624 mg/24 hours (normal, 0 to 140 mg/24 hours), and urine norepinephrine of 504 mg/24 hours (normal, 0 to 140 mg/24 hours). Urine epinephrine and dopamine were within normal range. Increases in plasma catecholamines of 2093 pg/ml (normal, 0 to 643 pg/ml), plasma epinephrine of 268 pg/ml (normal, 0 to 100 pg/ml), plasma norepinephrine of 1626 pg/ml (normal, 0 to 400 pg/ml), and plasma dopamine of 199 pg/ml (normal, 0 to143) occurred. Serum aldosterone and cortisol were within normal limits. Because the increase in urinary catecholamines may have been caused by autonomic dysregulation from quadriplegia, a clonidine suppression test was performed. Oral clonidine was administered (0.3 mg), and plasma cat-
CURRENT SURGERY • © 2002 by the Association of Program Directors in Surgery Published by Elsevier Science Inc.
0149-7944/02/$22.00 PII S0149-7944(01)00586-4
continued on postoperative day 6. Customarily volume expansion alone is sufficient after resection of pheochromocytoma. However, the spinal cord transection patient has a sympathectomy and may respond like a patient in spinal shock. Therefore, phenylephrine was useful and required for the very surprising 6 days until he stabilized. The postoperative course was complicated by pneumonia necessitating reintubation on day 3. Pancreatitis and a fluid collection required a drainage by a percutaneous catheter that was removed when the output ceased.
DISCUSSION
FIGURE 1. Computed tomography scan of the abdomen demonstrates a 3.5 ⫻ 4.0 ⫻ 5.0-cm heterogeneous enhancing mass of the left adrenal gland, most likely caused by either primary or metastatic neoplasm, possibly pheochromocytoma. The right adrenal gland appears normal.
echolamines are measured before and 3 hours after the clonidine dose. Clonidine is an alpha-2 adrenergic agonist, which inhibits sympathetic outflow from the brain, thereby lowering plasma catecholamines below 500 pg/mL in AD but not in pheochromocytoma. Serum epinephrine, norepinephrine, and total catecholamines failed to reduce significantly in response to clonidine. The diagnosis was most likely pheochromocytoma, and preoperative pharmacologic blockade was then initiated. The patient was treated with phenoxybenzamine to achieve alpha-blockade and intravenous fluids to expand the intravascular volume. Electrocardiograms were negative for arrhythmias. His initial dose of phenoxybenzamine was 10 mg twice a day, and this was gradually increased to 80 mg three times a day, to achieve adequate alpha-blockade. He was also treated with propranolol 10 mg three times a day, for beta blockade.
RESULTS After adequate preoperative adrenergic blockade was achieved, the patient was taken to the operating room and explored through a left subcostal incision. The left adrenal tumor was palpable and found to be about 4 cm in diameter with a dusky gray appearance. The procedure could have been done by laparoscopy. The patient had episodes of hypertension upon induction of anesthesia. The blood pressure fluctuated sharply and intermittently during the procedure, particularly during ligation of the adrenal vein, when he became transiently hypotensive. However, at the conclusion of the procedure, he required neither pressors nor inotropes. On histologic examination, the 4.0 ⫻ 3.5 ⫻ 2.9-cm adrenal mass was found to be a pheochromocytoma (Fig. 2A,B). No intraoperative or histologic evidence of malignancy was found. In the recovery room, a phenylephrine infusion was started for hypotension refractory to fluid resuscitation; this was disCURRENT SURGERY • Volume 59/Number 2 • March/April 2002
Autonomic dysreflexia (AD) is a clinical condition that has life-threatening potential. It affects patients with spinal cord injury and is most commonly seen in patients with lesions at or above T-7. Noxious stimuli below the level of injury, most commonly with manipulation of the perineum or distention of the bladder or rectum, can elicit an autonomic nervous system response characterized by excess sympathetic activity with an insufficient counter-regulatory parasympathetic response. Excess stimulation of the preganglionic sympathetic neurons in the spinal cord leads to paroxysmal hypertension, whereas vagal stimulation causes bradycardia. Patients often complain of severe headaches, chest pain, and profuse sweating and flushing.1 The most common stimuli that trigger AD develop from the lower urinary tract; distention of the bladder accounts for 75% to 85% of episodes of AD. Other stimuli developing from the urinary tract include urinary tract infections, catheterization, obstruction of a urinary catheter, urethral distention, cystitis, and testicular torsion. Anorectal stimuli are the second most common origins for AD. Fecal impaction leading to bowel distention causes 13% to 19% of AD episodes. Manipulation of the anorectal area with fecal disimpaction, colonoscopy, barium enema, or suppository administration may precipitate an episode of AD. Gastrointestinal disorders such as acute appendicitis, bowel perforations, and volvulus can also induce AD.1 Autonomic dysreflexia is characterized by a derangement in the balance of neurotransmitters and neuropeptides. Injury to the spinal cord leads to a profound reduction in the sympathetic outflow below the lesion, resulting in upregulation of noradrenergic receptors. Stimulation of these upregulated receptors leads to the exaggerated sympathetic activity and severe hypertension.2 A reduction in inhibitory neurotransmitter release contributes to the pathophysiology of AD. Gamma amino benzoic acid (GABA), an inhibitory neurotransmitter, decreases in spinal cord injury. Also, a reduction in norepinephrine and serotonin occurs below the level of spinal cord injury. In contrast, an increase in the excitation of neurons is mediated by an accumulation of substance P below the spinal cord lesion.1 Naftchi has attributed the disturbance in the regulation of blood pressure to various factors, including supersensitivity of spinal alpha-adrenoreceptors below the spinal cord injury caused by a lack of norepinephrine, hypersensitivity of peripheral vascular adrenergic receptors, and resetting of barorecep207
FIGURE 2. (A, B) The 4.0 ⫻ 3.5 ⫻ 2.9-cm left adrenal mass was a benign pheochromocytoma.
tors with a resultant insensitivity at high arterial blood pressures.3 Patients presenting with hypertensive crises are at risk of fatal cerebral hemorrhage, seizures, coma, and death. Systolic blood pressure may be as high as 300 mg Hg, and diastolic pressure may exceed 170 mm Hg.4 Anti-hypertensive treatment should 208
be initiated, and the triggering stimulus should be identified promptly. Bladder distention should be addressed by inserting a Foley catheter if the patient does not have an indwelling catheter and a specimen of urine should be sent for urinalysis, culture, and sensitivity. Fecal impaction should be evacuated, if present. CURRENT SURGERY • Volume 59/Number 2 • March/April 2002
The differential diagnosis for autonomic dysreflexia includes migraine headaches, essential hypertension, posterior fossa tumors, toxemia of pregnancy, and pheochromocytoma. Pheochromocytoma is a catecholamine-producing tumor originating from neural crest cells of the adrenal medulla or sympathetic ganglia, which often causes headaches and hypertension. In contrast to the bradycardia seen in autonomic dysreflexia, tachycardia is usually present with pheochromocytoma. In AD, diaphroresis and flushing are present above the spinal cord injury, whereas vasoconstriction is present below the lesion. However, in pheochromocytoma, these symptoms are present throughout the body.1 Both norepinephrine and epinephrine levels are increased in pheochromocytoma, whereas only norepinephrine levels are increased in autonomic dysreflexia.5 Urinary metanephrine, normetanephrine, and vanillylmandelic acid levels are increased in pheochromocytoma but not in autonomic dysreflexia.3 Only 0.05% to 0.1% of hypertensive patients have pheochromocytoma. Fifty percent of patients with pheochromocytoma have persistent hypertension, whereas 45% have paroxysmal hypertension and 5% are normotensive. The most frequent symptoms are headache, excessive perspiration, and palpitations.6 Diagnosis may be established by measurements of plasma epinephrine and norepinephrine and urinary metanephrine, normetanephrine, and vanillylmandelic acid. A clonidine suppression test may help to confirm the diagnosis. In patients with neurogenically induced hypercatecholaminemia, clonidine inhibits sympathetic outflow and reduces plasma catecholamines. However, in the setting of pheochromocytoma, plasma catecholamines are not suppressed.7 If biochemical evidence establishes the diagnosis of pheochromocytoma, imaging studies should be obtained in order to localize tumors. Computerized tomography scan and magnetic resonance imaging are preferred initial studies, whereas metaiodobenzylguanidine (MIBG) imaging is useful in detecting extra-adrenal pheochromocytoma. Preoperative alpha-adrenergic blockade with prazosin or phenoxybenzamine should be initiated to lower blood pressure and increase intravascular volume in patients with severe hypertension and volume depletion. Beta blockade should be administered only after alpha blockade has begun.8 Intravascular volume expansion is instituted to minimize postoperative hypotension. Because of wide variations in blood pressure and potential for cardiac dysrhythmias secondary to intraoperative catecholamine discharge, patients with pheochromocytoma may present a challenge for the anesthesiologist. Laryngoscopy, intubation, and tumor manipulation may provoke release of catecholamines and incite a hypertensive crisis. Conversely, the anesthesiologist may be faced with hypotension once the adrenal vein is ligated because of catecholamine withdrawal.9 Surgical extirpation is the only effective treatment of pheochromocytoma. The surgeon strives to minimize manipulation of the tumor while achieving a complete resection and excellent hemostasis. Several approaches to adrenalectomy have been deCURRENT SURGERY • Volume 59/Number 2 • March/April 2002
scribed. Open methods include the anterior or transabdominal, thoracoabdominal, flank or lateral, and posterior or retroperitoneal approaches. Initially, the transabdominal approach was recommended for pheochromocytoma because of the potential for bilateral or extra-adrenal tumors. The accuracy of preoperative imaging studies has improved, allowing for a more focused exploration.10 Minimally invasive adrenalectomy has been performed since 1992. Laparoscopic approaches to adrenalectomy include transabdominal and retroperitoneal methods. Laparoscopic adrenalectomy is safe and is associated with reductions in length of hospital stay, analgesia requirement, and duration of postoperative ileus.11,12 However, tumor size may limit the utility of this method. Spinal cord injury with quadriplegia is characterized by dysfunction of the sympathetic nervous system caused by the loss of supraspinal control, and it may result in hypotension and bradycardia.13 Therefore, the hemodynamic response to surgical stress and hypovolemia may present a formidable challenge for the anesthesiologist. In the face of volume depletion, vasoconstriction is impaired in the quadriplegic patient. An increase in venous capacitance may lead to a reduction in venous return and a fall in cardiac output. Left ventricular contractility is often impaired; myocardial depressants should be avoided if possible. Inhaled anesthetics increase venous capacitance and decrease myocardial contractility, thereby exacerbating the effects of sympathectomy and worsening hypotension. Intravascular volume replacement is the initial treatment; monitoring fluid balance with a pulmonary artery catheter is particularly useful in guiding therapy, especially because of the susceptibility to pulmonary edema.14 Interestingly, once this patient’s pheochromocytoma was excised and the source of catecholamines was removed, the patient’s underlying physiology as a quadriplegic was then unmasked and was expressed as hypotension. Accordingly, he required not only aggressive fluid resuscitation, but also a brief postoperative infusion of vasopressors.
CONCLUSION Autonomic dysreflexia is a phenomenon that affects patients with spinal cord injury and has life-threatening potential. Its differential diagnosis includes migraine headaches, essential hypertension, posterior fossa tumors, toxemia of pregnancy, and pheochromocytoma, which also may precipitate hypertensive crises and headaches. This is the first report of a quadriplegic patient undergoing excision of a pheochromocytoma.
REFERENCES 1. Lee BY, Karmakar MG, Herz BL, Sturgill RA. Autonomic
dysreflexia revisited. J Spinal Cord Med. 1995;18:75-87. 2. Naftchi NE, Richardson JS. Autonomic dyreflexia: phar-
macologic management of hypertensive crises in spinal cord injured patients. J Spinal Cord Med. 1997;20:355360. 209
3. Naftchi NE. Mechanism of autonomic dysreflexia. Con-
tributions of catecholamines and peptide neurotransmitters. Ann NY Acad Sci. 1990;579:133-148. 4. Kewalramani LS. Autonomic dysreflexia in traumatic my-
elopathy. Am J Phys Med. 1980;59:1-21. 5. Mathias CJ, Christensen NJ, Corbett JL, Frankel HL,
Spalding JM. Plasma catecholamines during paroxysmal neurogenic hypertension in quadriplegic man. Circ Res. 1976;39:204-208. 6. Gifford RW Jr, Manger WM, Bravo EL. Pheochromocy-
toma. Endocrinol Metabolism Clin North Am. 1994;23: 387-404. 7. Bravo EL, et al. Clonidine-suppression test: a useful aid in
9. Jovenich JJ. Anesthesia in adrenal surgery. Urol Clin North
Am. 1989;16:583-587. 10. Kebebew E, Duh Q-Y. Benign and malignant pheochro-
mocytoma. Surg Oncol Clin North Am. 1998;7:765-789. 11. Winfield HN, et al. Laparoscopic adrenalectomy: the pre-
ferred choice? A comparison to open adrenalectomy. J Urol. 1998;160:325-329. 12. Tanaka M, et al. Laparoscopic adrenalectomy for pheo-
chromocytoma: comparison with open adrenalectomy and comparison of laparoscopic surgery for Pheochromocytoma versus other adrenal tumors. J Endourol. 2000;14: 427-431. 13. Teasell RW, Arnold JW, Krassioukov A, Delaney GA.
the diagnosis of pheochromocytoma. N Engl J Med. 1981; 305:623.
Cardiovascular consequences of loss of supraspinal control of the sympathetic nervous system after spinal cord injury. Arch Phys Med Rehabil. 2000;81:506-516.
8. Malone MJ, et al. Preoperative and surgical management
14. Troll GF, Dohrmann GJ. Anaesthesia of the spinal cord-
of pheochromocytoma. Urol Clin North Am. 1989;16: 567-582.
injured patient: cardiovascular problems and their management. Paraplegia. 1975;13:162-171.
210
CURRENT SURGERY • Volume 59/Number 2 • March/April 2002