Management of Orthostatic Hypotension from Autonomic Dysfunction in Diabetics on Peritoneal Dialysis

A utonomic neuropathy occurs in over 50% of chronic dialysis patients (1). Since the autonomic nervous system innervates almost every organ of the body, the clinical features may be diverse and widespread. Most of the nerve fibers in the autonomic nervous system are small myelinated or unmyelinated fibers that are affected early in diabetes mellitus (2). Neurogenic orthostatic hypotension is the most common, challenging, and often frustrating manifestation of autonomic dysfunction secondary to diabetes mellitus that we encounter in patients on peritoneal dialysis (PD). Orthostatic hypotension, which can also occur from nonneurogenic causes, is defined as a “fall in systolic blood pressure of over 20 mmHg or diastolic blood pressure of over 10 mmHg within 3 minutes of standing or head up position at an angle of 60°” (3). This is accompanied by reflex tachycardia in individuals with intact autonomic function. In neurogenic orthostatic hypotension from various causes, including diabetes mellitus, because of parasympathetic dysfunction from autonomic neuropathy there is a lack of this reflex tachycardia upon standing. While evaluating a diabetic patient on PD with orthostatic hypotension, it is important that we exclude nonneurogenic causes before attributing it to autonomic neuropathy. Intravascular volume depletion, low cardiac output states and conduction abnormalities, severe anemia, and medications can all lead to blood pressure drop on standing. A significant proportion of diabetic dialysis patients are on various combinations of diuretics, antihypertensives, phenothiazines, antidepressants, nitrates, and a host of other medications that can cause orthostatic hypotension (4). Unfortunately there is no known specific or effective treatment for neurogenic orthostatic hypotension. The principles of management in dialysis and nondialysis patients are the same. In nondialysis patients it has been suggested that the goal of treatment should be to improve functional capacity, and not just achieve a target blood pressure. To that end, both nonpharmacologic and pharmacologic modalities of treatment have been used independently or in combination. Prior to use of drugs, various nonpharmacologic interventions, including patient education, should be attempted as listed in Table 1. Frequently, patients have intravascular volume depletion, and it has been recommended that diabetic patients with orthostatic hypotension on dialysis be kept slightly overhydrated by reducing diuretic dosage and decreasing ultrafiltration (5). Other nonpharmacological measures that have found favor in neurogenic orthostatic hypotension from all causes are the use of compression garments, which reduce venous pooling when upright, and eating small frequent meals rather than large meals rich in carbohydrates (6). It is essential that such garments extend up to the waist to minimize splanchnic venous pooling. The other maneuver that may be effective is leg crossing while standing on both legs (7,8). Squatting also has been shown to have similar benefits. The common offending drugs mentioned above should be avoided if possible. Nonpharmacologic agents are often insufficient to improve symptoms of orthostatic hypotension; drugs may have to be used in such cases. Pharmacologic agents used for the treatment of neurogenic orthostatic hypotension from any cause in patients with or without renal disease are generally helpful but do not restore normotension. These agents are listed in Table 2 (6). Fludrocortisone, a synthetic mineralocorticoid, is currently the most commonly used agent in the treatment of patients on PD (5). It increases circulating blood volume, enhances sensitivity to circulating catecholamines, and enhances release of norepinephrine. Caffeine, an adenosine receptor blocker, causes vasoconstriction in the dose of 250 mg, or two cups of coffee prior to meals, and improves orthostatic and postprandial hypotension in patients with autonomic dysfunction. Midodrine, a selective alpha-1 adrenergic receptor agonist, was recently ap-