The cause of intraoperative hypotension is often multifactorial, including, for example, myocardial depression, hypovolemia, anesthetic overdose, infection, autoimmune reactions, and endocrine disorders. We describe a case in which a patient presented with severe intraoperative hypertension. The patient received labetalol and, subsequently, hydralazine. Profound hypotension followed hydralazine administration which was unresponsive to IV fluid, ephedrine, and phenylephrine administration. The blood pressure (BP) eventually responded to vasopressin. Severe hypertension in the supine position and orthostatic hypotension responsive to oral fluids are often manifestations of patients with multiple system atrophy (MSA), also known as Shy-Drager syndrome, a neurodegenerative disorder associated with autonomic dysfunction.
We describe the first case of Shy-Drager syndrome diagnosed on the basis of intraoperative hemodynamic changes. The initial hypertension in the supine position followed by severe hypotension after hydralazine administration, ultimately responsive to vasopressin, led to a diagnosis of Shy-Drager syndrome. We suggest that vasopressin may be the drug of choice in patients with Shy-Drager syndrome with refractory hypotension.
A 65-yr-old man was admitted for elective incision and drainage of a right ankle ulceration. His medical history revealed that he had a history of peripheral neuropathy (with areas of numbness, hyperalgesia, and allodynia in the lower extremities, with no dermatomal distribution), peripheral vascular disease, chronic obstructive pulmonary disease, iron deficiency anemia, and gait ataxia. The patient also had a history of multiple admissions to exclude intestinal obstruction. Previous medical records showed no history of hypertension or autonomic dysfunction. Possible causes for peripheral neuropathy, including diabetes, nutritional deficiencies, acquired immune deficiency syndrome, and nerve injury, were excluded.
The patient was positioned supine on the operating room (OR) table, and initial BP was 210/110 mm Hg, with a heart rate (HR) of 110 bpm. No cause could be determined. The patient received IV labetalol 10 mg repeated twice at 5-min intervals, but hypertension persisted (BP = 170/100 mm Hg; HR = 75 bpm). As the BP slowly decreased, we considered that the benefits outweighed the risks in favor of performing the procedure. A popliteal nerve block was performed with 30 mL of plain mepivacaine 1.5%, without complications.
Since the patient remained hypertensive despite labetalol administration, hydralazine 4 mg was administered IV in two separate doses (total of 8 mg) 30 min apart. After the second dose, the BP was 130/80 mm Hg. This remained unchanged until the end of the surgery (approximately 30 min later). When the patient was about to be transferred from the OR and was still in the supine position, his BP decreased abruptly to 65/48 mm Hg, with HRs of approximately 70 bpm. The patient complained of nausea and dizziness. The administration of isotonic IV fluid (1.5 L total) and ephedrine IV boluses of 10–20 mg (total of 150 mg) produced no response.
Phenylephrine IV boluses of 100–200 μg were given at the same time (total of 1 mg), but systolic BP remained at approximately 80 bpm. Finally, a vasopressin 2-U IV bolus was administered, and the BP returned to 130/80 mm Hg. Throughout the event, the patient was awake and alert, with no electrocardiogram signs of ischemia. In the intensive care unit (ICU), the BP had unexplained paroxysmal increases to 170/90 mm Hg in the absence of pain, and there were no further episodes of hypotension. The next day, at the time of discharge (48 h after surgery), the patient developed an acute hypotensive (80/40 mm Hg) episode while he was being transferred from his bed to the wheelchair. He responded to IV fluids and was readmitted to the ICU.
No further hypotensive episodes occurred. A neurology consult diagnosed MSA with associated peripheral neuropathy. A focused history revealed urinary incontinence and occasional dizziness when changing from sitting or the supine position to a standing position.
Multiple causes may lead to BP lability in the perioperative period. The initial differential diagnosis in our patient included an exaggerated response to hydralazine, sepsis, pheochromocytoma, and autonomic dysfunction. Mepivacaine toxicity was not considered, because the dose was smaller than described toxic doses. Systemic absorption after regional blocks of the lower extremity is relatively small, and changes in the central nervous system would have been more prominent before any significant cardiovascular event (1,2). Direct IV local anesthetic injection is also unlikely, because it took almost an hour after hypotension developed.
Gilman et al. (3) reported the results of a consensus conference on the diagnosis of MSA. They included four domains: autonomic failure/urinary dysfunction, parkinsonism, cerebellar ataxia, and cortical-spinal dysfunction. “Possible MSA” requires one criterion plus one feature from separate domains. “Probable MSA” requires autonomic failure/urinary dysfunction plus poorly responsive parkinsonism or cerebellar ataxia. Pathologic confirmation is required for a definitive diagnosis (3). Our patient had a history of urinary incontinence and bowel dysfunction. He also presented with dizziness and orthostatic hypotension, confirmed by measurement of supine and standing pulse and BP with a 2-min interval (systolic BP decreased from 170 mm Hg supine to 130 mm Hg in the standing position and diastolic BP from 95 to 70 mm Hg, with a constant HR of 75 bpm during the change in position) and a long history of cerebellar ataxia, manifested by a broad-based gait. Although peripheral neuropathy is not considered a diagnostic criterion for MSA, its association has been suggested (4).
MSA is a neurodegenerative disease that affects oligodendrocytes. Dejerine described it in 1900 in patients with ataxia (olivopontocerebellar atrophy) (5). Shy and Drager (6) described a neurological syndrome with autonomic failure and parkinsonism in which orthostatic hypotension was a prominent clinical manifestation. Approximately 80% of these patients present with Parkinson’s disease, and 20% present with cerebellar dysfunction. Degeneration of the sacral anterior horn cells (Onuf’s nucleus) in patients with MSA has been associated with urinary, sexual, and anorectal dysfunction (7–9).
Common manifestations of autonomic dysfunction are orthostatic hypotension, bladder and bowel dysfunction, and impotence. Paradoxically, many patients present with severe supine hypertension (10,11) that is often undetected because the BP is normally measured in the seated position. Lack of compensatory HR increases during the hypotensive episode and unresponsiveness to IV norepinephrine are other characteristics associated with this disorder. Although the lack of HR response associated with intraoperative hypotension may be explained by the effects of β-blockade, the same finding was seen the following day in the ICU while the patient was not receiving β-blockers. The hypertensive episodes are particularly responsive to transdermal nitroglycerin (12). Our patient did present with severe hypertension while in the supine position on the OR table.
There was minimal response to α- and β-blockade (labetalol) but marked response to hydralazine, a direct relaxant of arteriolar smooth muscle. Although the mechanism of action is unclear, hydralazine may exert its hypotensive effects via nitric oxide (13). The subsequent severe hypotension did not respond to ephedrine or phenylephrine, a common finding in MSA, but finally responded to vasopressin, which produces direct smooth muscle vasoconstriction independent of adrenergic response (14). The increase in BP also depends on the reactivity of baroreceptors. Patients with Shy-Drager syndrome may present with defects in the baroregulatory reflex arc (15). The use of vasopressin analogs at small doses markedly increases BP and systemic vascular resistance (16,17). Vasopressin also produces blood flow diversion from nonvital to vital organ beds (18). Our patient did not respond to fluid administration. IV fluids usually produce a significant BP increase in hypotensive patients with Shy-Drager syndrome. In our patient, the vasodilatory effect of hydralazine may have been overcome by vasopressin with restoration of hemodynamic stability.
In summary, this patient presented with signs of autonomic dysfunction. The initial hypertension was treated with a direct vasodilator (hydralazine) which resulted in severe hypotension unresponsive to adrenergic agonists. The hypotension responded only to vasopressin. Further attempts to correct the BP with epinephrine or norepinephrine were not made because of the previous lack of response to direct and indirect adrenergic agonists. The use of vasopressin for severe hypotension in patients with autonomic dysfunction unresponsive to vasopressors should be considered.
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