CONTRASTING ACTIONS OF PRESSOR AGENTS IN SEVERE AUTONOMIC FAILURE

BACKGROUND: Orthostatic hypotension is the most disabling symptom of a utonomic failure. The choice of a presser agent is largely empiric, an d it would be of great value to define predictors of a response. PATIE NTS AND METHODS: In 35 patients with severe orthostatic hypotension du e to multiple system atrophy or pure autonomic failure, we determined the effect on seated systolic blood pressure (SBP) of placebo, phenylp ropanolamine (12.5 mg and 25 mg), yohimbine (5.4 mg), indomethacin (50 mg), ibuprofen (600 mg), caffeine (250 mg), and methylphenidate (5 mg ). In a subgroup of patients, we compared the presser effect of midodr ine (5 mg) with the effect of phenylpropanolamine (12.5 mg). RESULTS: There were no significant differences in the presser responses between patients with multiple system atrophy or pure autonomic failure. When compared with placebo, the presser response was significant for pheny lpropanolamine, yohimbine, and indomethacin. In a subgroup of patients , we confirmed that this presser effect of phenylpropanolamine, yohimb ine, and indomethacin corresponded to a significant increase in standi ng SEP. The presser responses to ibuprofen, caffeine, and methylphenid ate were not significantly different from placebo. Phenylpropanolamine and midodrine elicited similar presser responses. There were no signi ficant associations between drug response and autonomic function testi ng, postprandial hypotension, or plasma catecholamine levels. CONCLUSI ONS: We conclude that significant increases in systolic blood pressure can be obtained in patients with orthostatic hypotension due to prima ry autonomic failure with phenylpropanolamine in low doses or yohimbin e or indomethacin in moderate doses. The response to a presser agent c annot be predicted by autonomic function testing or plasma catecholami nes. Therefore, empiric testing with a sequence of medications, based on the risk of side effects in the individual patient and the probabil ity of a response, is a useful approach. (C) 1998 by Excerpta Medica, Inc.