Treatment of Orthostatic Hypotension

ABSTRACT

Orthostatic hypotension is the most incapacitating symptom of autonomic failure. This disorder occurs with both central autonomic neurodegenerative disorders, such as multiple system atrophy and Parkinson's disease, and peripheral autonomic disorders, such as the autonomic peripheral neuropathies and pure autonomic failure. The hallmark of both central and peripheral causes of neurogenic orthostatic hypotension is the failure to release norepinephrine appropriately upon standing. Patient education is the cornerstone of management. There are several measures that can be implemented to improve orthostatic tolerance prior to pharmacological intervention. Plasma volume expansion is essential to improve orthostatic tolerance, and fluid and sodium chloride intake should be increased. Most patients can be treated successfully with volume expansion or fludrocortisone or both in combination with a sympathomimetic agent. Desmopressin acetate and erythropoietin are useful supplementary agents in patients with more refractory symptoms. There are rare patients who will require additional agents to treat their symptoms. A small group of patients remain refractory to all therapeutic modalities.

KEYWORDS

Orthostatic hypotension - postural hypotension - autonomic failure - autonomic nervous system - sympathetic nervous system

REFERENCES

• 1 Borst C, Weiling W, van Brederode F M J. et al . Mechanisms of initial heart rate response to postural change.  Am J Physiol . 1982;  243 H676-H681
• 2 Smit A A, Halliwill J R, Low P A, Wieling W. Pathophysiological basis of orthostatic hypotension in autonomic failure.  J Physiol . 1999;  519(Pt 1) 1-10
• 3 Position paper. Orthostatic hypotension, multiple system atrophy (the Shy Drager syndrome) and pure autonomic failure.  J Auton Nerv Syst . 1996;  58 123-124
• 4 Goldstein D S, Polinsky R J, Garty M. et al . Patterns of plasma levels of catechols in neurogenic orthostatic hypotension.  Ann Neurol . 1989;  26 558-563
• 5 Goldstein D S, Holmes C, Sharabi Y, Brentzel S, Eisenhofer G. Plasma levels of catechols and metanephrines in neurogenic orthostatic hypotension.  Neurology . 2003;  60 1327-1332
• 6 Omboni S, Smit A A, van Lieshout J J, Settels J J, Langewouters G J, Wieling W. Mechanisms underlying the impairment in orthostatic tolerance after nocturnal recumbency in patients with autonomic failure.  Clin Sci (Lond) . 2001;  101 609-618
• 7 van Lieshout J J, ten Harkel D A, Wieling W. Physical manoeuvres for combating orthostatic dizziness in autonomic failure.  Lancet . 1992;  339 897-898
• 8 Wieling W, van Lieshout J J, van Leeuwen M A. Physical manoeuvres that reduce postural hypotension in autonomic failure.  Clin Auton Res . 1993;  3 57-65
• 9 Shannon J, Jordan J, Costa F, Robertson R M, Biaggioni I. The hypertension of autonomic failure and its treatment.  Hypertension . 1997;  30 1062-1067
• 10 Shannon J R, Jordan J, Diedrich A. et al . Sympathetically mediated hypertension in autonomic failure.  Circulation . 2000;  101 2710-2715
• 11 MacLean A R, Allen B V. Orthostatic hypotension and orthostatic tachycardia. Treatment with the “head-up” bed.  JAMA . 1940;  115 2162-2167
• 12 Jordan J, Shannon J R, Black B K. et al . The pressor response to water drinking in humans: a sympathetic reflex?.  Circulation . 2000;  101 504-509
• 13 Campbell I W, Ewing D J, Clarke B F. 9-Alpha-fluorohydrocortisone in the treatment of postural hypotension in diabetic autonomic neuropathy.  Diabetes . 1975;  24 381-384
• 14 Hickler R B, Thompson G R, Fox L M, Hamlin J T. Successful treatment of orthostatic hypotension with 9-alpha-fluorohydrocortisone.  N Engl J Med . 1959;  261 788-791
• 15 Schatz I J, Miller M J, Frame B. Corticosteroids in the management of orthostatic hypotension.  Cardiology . 1976;  61(Suppl. 1) 280-289
• 16 van Lieshout J J, ten Harkel D A, Wieling W. Fludrocortisone and sleeping in the head-up position limit the postural decrease in cardiac output in autonomic failure.  Clin Auton Res . 2000;  10 35-42
• 17 Chobanian A V, Volicer L, Tifft C P, Gavras H, Liang C S, Faxon D. Mineralocorticoid-induced hypertension in patients with orthostatic hypotension.  N Engl J Med . 1979;  301 68-73
• 18 Low P A, Gilden J L, Freeman R, Sheng K N, McElligott M A. Efficacy of midodrine vs placebo in neurogenic orthostatic hypotension. A randomized, doubleblind multicenter study. Midodrine Study Group.  JAMA . 1997;  277 1046-1051
• 19 Kaufmann H, Brannan T, Krakoff L, Yahr M D, Mandeli J. Treatment of orthostatic hypotension due to autonomic failure with a peripheral alpha-adrenergic agonist (midodrine).  Neurology . 1988;  38 951-956
• 20 Wright R A, Kaufmann H C, Perera R. et al . A double-blind, dose-response study of midodrine in neurogenic orthostatic hypotension.  Neurology . 1998;  51 120-124
• 21 Jordan J, Shannon J R, Biaggioni I, Norman R, Black B K, Robertson D. Contrasting actions of pressor agents in severe autonomic failure.  Am J Med . 1998;  105 116-124
• 22 Ghrist D G, Brown G E. Postural hypertension with syncope: its successful treatment with ephedrine.  Am J Med Sci . 1928;  175 336-349
• 23 Davies B, Bannister R, Sever P. Pressor amines and monoamine-oxidase inhibitors for treatment of postural hypotension in autonomic failure. Limitations and hazards.  Lancet . 1978;  1 172-175
• 24 Biaggioni I, Onrot J, Stewart C K, Robertson D. The potent pressor effect of phenylpropanolamine in patients with autonomic impairment.  JAMA . 1987;  258 236-239
• 25 Freeman R. Treatment of orthostatic hypotension: Midodrine and other pressor drugs. In: Robertson D, Low PA, Polinsky RJ, eds. Primer on the Autonomic Nervous System New York: Academic Press 1996: 326-332
• 26 Fouad-Tarazi F M, Okabe M, Goren H. Alpha sympathomimetic treatment of autonomic insufficiency with orthostatic hypotension.  Am J Med . 1995;  99 604-610
• 27 Kernan W N, Viscoli C M, Brass L M. et al . Phenylpropanolamine and the risk of hemorrhagic stroke.  N Engl J Med . 2000;  343 1826-1832
• 28 Kaufmann H, Oribe E, Miller M, Knott P, Wiltshire-Clement M, Yahr M D. Hypotension-induced vasopressin release distinguishes between pure autonomic failure and multiple system atrophy with autonomic failure.  Neurology . 1992;  42 590-593
• 29 Ozawa T, Oyanagi K, Tanaka H. et al . Suprachiasmatic nucleus in a patient with multiple system atrophy with abnormal circadian rhythm of arginine-vasopressin secretion into plasma.  J Neurol Sci . 1998;  154 116-121
• 30 Mathias C J, Fosbraey P, da Costa F D, Thornley A, Bannister R. The effect of desmopressin on nocturnal polyuria, overnight weight loss, and morning postural hypotension in patients with autonomic failure.  Br Med J (Clin Res Ed) . 1986;  293 353-354
• 31 Sakakibara R, Matsuda S, Uchiyama T, Yoshiyama M, Yamanishi T, Hattori T. The effect of intranasal desmopressin on nocturnal waking in urination in multiple system atrophy patients with nocturnal polyuria.  Clin Auton Res . 2003;  13 106-108
• 32 Biaggioni I, Robertson D, Krantz S, Jones M, Haile V. The anemia of primary autonomic failure and its reversal with recombinant erythropoietin.  Ann Intern Med . 1994;  121 181-186
• 33 Winkler A S, Marsden J, Parton M, Watkins P J, Chaudhuri K R. Erythropoietin deficiency and anaemia in multiple system atrophy.  Mov Disord . 2001;  16 233-239
• 34 Winkler A S, Landau S, Watkins P, Chaudhuri K R. Observations on haematological and cardiovascular effects of erythropoietin treatment in multiple system atrophy with sympathetic failure.  Clin Auton Res . 2002;  12 203-206
• 35 Rao S V, Stamler J S. Erythropoietin, anemia, and orthostatic hypotension: the evidence mounts.  Clin Auton Res . 2002;  12 141-143
• 36 Hoeldtke R D, Streeten D HP, Streeten D H. Treatment of orthostatic hypotension with erythropoietin.  N Engl J Med . 1993;  329 611-615
• 37 Perera R, Isola L, Kaufmann H. Effect of recombinant erythropoietin on anemia and orthostatic hypotension in primary autonomic failure.  Clin Auton Res . 1995;  5 211-213
• 38 Onrot J, Goldberg M R, Biaggioni I, Hollister A S, Kingaid D, Robertson D. Hemodynamic and humoral effects of caffeine in autonomic failure. Therapeutic implications for postprandial hypotension.  N Engl J Med . 1985;  313 549-554
• 39 Robertson D, Goldberg M R, Hollister A S, Wade D, Robertson R M. Clonidine raises blood pressure in idiopathic orthostatic hypotension.  Am J Med . 1983;  74 193-199
• 40 Robertson D, Goldberg M R, Tung C S, Hollister A S, Robertson R M. Use of alpha 2 adrenoreceptor agonists and antagonists in the functional assessment of the sympathetic nervous system.  J Clin Invest . 1986;  78 576-581
• 41 Onrot J, Goldberg M R, Biaggioni I, Wiley R G, Hollister A S, Robertson D. Oral yohimbine in human autonomic failure.  Neurology . 1987;  37 215-220
• 42 Mehlsen J, Trap-Jensen J. Xamoterol, a new selective beta-1-adrenoceptor partial agonist, in the treatment of postural hypotension.  Acta Med Scand . 1986;  219 173-177
• 43 Obara A, Yamashita H, Onodera S, Yahara O, Honda H, Hasebe N. Effect of xamoterol in Shy-Drager syndrome.  Circulation . 1992;  85 606-611
• 44 West J N, Stallard T J, Dimmitt S B, Smith S A, Williams A, Littler W A. Xamoterol in the treatment of orthostatic hypotension associated with multiple system atrophy (Shy-Drager syndrome).  Q J Med . 1990;  74 209-213
• 45 Cleophas T J, Grabowsky I, Niemeyer M G, Makel W M, van der Wall E E. Paradoxical pressor effects of beta-blockers in standing elderly patients with mild hypertension: a beneficial side effect.  Circulation . 2002;  105 1669-1671
• 46 Chobanian A V, Volicer L, Liang C S, Kershaw G, Tifft C. Use of propranolol in the treatment of idiopathic orthostatic hypotension.  Trans Assoc Am Physicians . 1977;  90 324-334
• 47 Man in't Veld J A, Schalekamp M A. Pindolol acts as beta-adrenoceptor agonist in orthostatic hypotension: therapeutic implications.  Br Med J (Clin Res Ed) . 1981;  282 929-931
• 48 Leslie P J, Thompson C, Clarke B F, Ewing D J. A double-blind crossover study of oral xamoterol in postural hypotension due to diabetic autonomic neuropathy.  Clin Auton Res . 1991;  1 119-123
• 49 Hoeldtke R D, Israel B C. Treatment of orthostatic hypotension with octreotide.  J Clin Endocrinol Metab . 1989;  68 1051-1059
• 50 Hoeldtke R D, Horvath G G, Bryner K D, Hobbs G R. Treatment of orthostatic hypotension with midodrine and octreotide.  J Clin Endocrinol Metab . 1998;  83 339-343
• 51 Freeman R, Landsberg L, Young J. The treatment of neurogenic orthostatic hypotension with 3,4-DL-threo- dihydroxyphenylserine: a randomized, placebo-controlled, crossover trial.  Neurology . 1999;  53 2151-2157
• 52 Mathias C J, Senard J M, Braune S. et al . L-threo-dihydroxyphenylserine (L-threo-DOPS; droxidopa) in the management of neurogenic orthostatic hypotension: a multi-national, multi-center, dose-ranging study in multiple system atrophy and pure autonomic failure.  Clin Auton Res . 2001;  11 235-242
• 53 Kaufmann H, Saadia D, Voustianiouk A. et al . Norepinephrine precursor therapy in neurogenic orthostatic hypotension.  Circulation . 2003;  108 724-728
• 54 Freeman R, Young J B, Landsberg L, Lipsitz L A. The treatment of postprandial hypotension in autonomic failure with 3,4-DL-threo-dihydroxyphenylserine.  Neurology . 1996;  47 1414-1420
• 55 Hoeldtke R D, Cavanaugh S T, Hughes J D, Polansky M. Treatment of orthostatic hypotension with dihydroergotamine and caffeine.  Ann Intern Med . 1986;  105 168-173
• 56 Fouad F M, Tarazi R C, Bravo E L. Dihydroergotamine in idiopathic orthostatic hypotension: short- term intramuscular and long-term oral therapy.  Clin Pharmacol Ther . 1981;  30 782-789
• 57 Jennings G, Esler M, Holmes R. Treatment of orthostatic hypotension with dihydroergotamine.  BMJ . 1979;  2 307
• 58 Biaggioni I, Zygmunt D, Haile V, Robertson D. Pressor effect of inhaled ergotamine in orthostatic hypotension.  Am J Cardiol . 1990;  65 89-92
• 59 Watt S J, Tooke J E, Perkins C M, Lee M R. The treatment of idiopathic orthostatic hypotension: a combined fludrocortisone and flurbiprofen regime.  Q J Med . 1981;  50 205-212
• 60 Kochar M S, Itskovitz H D. Treatment of idiopathic orthostatic hypotension (Shy-Drager syndrome) with indomethacin.  Lancet . 1978;  1 1011-1014
• 61 Lopes de Faria R S, Zanella M T, Andriolo A, Ribeiro A B, Chacra A R. Peripheral dopaminergic blockade for the treatment of diabetic orthostatic hypotension.  Clin Pharmacol Ther . 1988;  44 670-674
• 62 Magnifico F, Pierangeli G, Barletta G. et al . The cardiovascular effects of metoclopramide in multiple system atrophy and pure autonomic failure.  Clin Auton Res . 2001;  11 163-168
• 63 Singer W, Opfer-Gehrking T L, McPhee B R, Hilz M J, Bharucha A E, Low P A. Acetylcholinesterase inhibition: a novel approach in the treatment of neurogenic orthostatic hypotension.  J Neurol Neurosurg Psychiatry . 2003;  74 1294-1298