Laboratory Evaluation

The patient with OH should be subjected to a full autonomic evaluation in order to determine the severity and distribution of autonomic failure. The recommended panel is shown in Table 2. The autonomic reflex screen evaluates the severity and distribution of postganglionic sudomotor, cardiovagal, and adrenergic failure. The thermoregulatory sweat test is a useful test in diabetic autonomic neuropathy, as the sweat loss has a number of different patterns (10,28). These can be multifocal, distal, regional, or generalized.

In the evaluation of adrenergic function, the beat-to-beat BP (BP_BB) responses to the Valsalva maneuver and to HUT are the most sensitive and useful tests. There are four main phases in the Valsalva maneuver (29-31). In phase I, there is a transient rise in BP because of increased intrathoracic and intra-abdominal pressure causing mechanical compression of the aorta (32). In early phase II (phase II_E), the reduced preload (venous return) (33) and reduced stroke volume (34) lead to a fall in cardiac output in spite of tachycardia caused by a withdrawal of cardiovagal influence. Total peripheral resistance increases as a result of efferent sympathetic discharge to muscle (35) and within 4 seconds after the increase in sympathetic discharge the fall in BP is arrested. This is late phase II (II_L). In normal subjects phase II_L is so efficient that by the beginning of phase III, MAP is at the resting MAP level or above. Phase III like phase I is mechanical, lasting 1 to 2 seconds during which BP falls. The major mechanism is the sudden fall in intrathoracic pressure. There is a further burst of sympathetic activity during this phase. In phase IV, venous return (36) and cardiac output (34) have returned to normal whereas the arteriolar bed remains vasoconstricted, hence the overshoot of BP above baseline values. In the clinical autonomic laboratory setting, with studies done on the patients lying supine, phase IV may be more dependent on cardiac adrenergic tone than on systemic peripheral resistance. Intravenous phentolamine 10 mg resulted in the expected elimination of late phase II, but augmented rather than blocked phase IV. In contrast, 10 mg intravenous propranolol completely blocked phase IV (30). The use of the phases of the Valsalva maneuver to evaluate adrenergic function has been validated in using pharmacological dissection (30) and by studying its effect on normal subjects and patients with different severities of autonomic failure a CASS has been generated

Table 3

Nonpharmacological Management of OH

1. Patient education

2. Raise head of bed 4 inches

3. Increase salt and fluid intake

4. Compression of capacitance bed with compression garments

5. Physical countermaneuvers to raise orthostatic BP

6. Water bolus therapy that corrects the confounding effects of age and gender (37). The most reliable phases of the maneuver are late phase II and IV. More recently, it has been demonstrated that BP recovery time defined as the duration from phase III to baseline may be a better index (38). It is free of the limitations of late phase II that is lost with even moderate autonomic failure.

Orthostatic BP recordings to tilt are recorded using BP_BB and with a sphygmomanometer cuff with the patient supine and following tilt to 70° using an automated tilt-table. Cuff recordings are obtained at 1 and 5 minutes after tilt up. It is important to perform the upright tilt procedure at a standard time after lying down because the ortho-static reduction in BP is higher following 20 minutes of preceding rest as compared with 1 minute. During upright tilt, normal individuals undergo a transient reduction in systolic, mean, and diastolic BP followed by recovery within 1 minute. The decrement is modest (<10 mmHg, mean BP). Normative data, based on 270 normal subjects aged 10-83 years have been obtained (3). Patients with adrenergic failure have a marked and progressive reduction in BP and pulse pressure. The heart rate response is typically attenuated, but in patients whose cardiac adrenergic innervation is spared, heart rate response is intact and may be increased.

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