Clinical Autonomic Research

, Volume 10, Issue 1, pp 35–42 | Cite as

Fludrocortisone and sleeping in the head-up position limit the postural decrease in cardiac output in autonomic failure

  • Johannes J. van Lieshout
  • A. Derk Jan ten Harkel
  • Wouter Wieling
Research Paper


Treatment with head-up tilt sleeping and low-dose fludrocortisone effectively minimizes orthostatic symptoms and increases orthostatic blood pressure in patients with neurogenic orthostatic hypotension. The aim of the present study was to examine whether the improvement in orthostatic blood pressure during combined treatment with low-dose fludrocortisone and nocturnal head-up tilt in patients with neurogenic orthostatic hypotension can be attributed to expansion of plasma volume or to increased total peripheral resistance.

The effects of a 3-week treatment with fludrocortisone and nocturnal head-up tilting on the postural changes in arterial pressure, heart rate, and cardiac output (pulse contour) were evaluated in eight consecutive patients with orthostatic hypotension.

The period during which the patients were able to remain in the standing position without orthostatic complaints increased minimally from 3 to 10 minutes. The decrease in arterial pressure after 1 minute of standing—(means with standard deviations in parentheses) systolic, 49 (20) mm Hg; diastolic, 18 (11) mm Hg—before treatment was produced by a greater than normal decrease in cardiac output: 37% (10%) in patients with neurogenic orthostatic hypotension versus-14% (8%) in control subjects. Treatment increased upright arterial pressure from 83 (19) mm Hg systolic and 55 (13) mm Hg diastolic to 114 (22) mm Hg systolic and 60 (16) mm Hg diastolic by limiting the decrease in cardiac output. Body weight increased but hematocrit did not change. Leg pressure-volume relationship decreased in the two patients studied. The responses of plasma renin activity and aldosterone to orthostatic stress prior to treatment were subnormal and became even lower after treatment.

The improvement in upright blood pressure in orthostatic hypotension during treatment with fludrocortisone and nocturnal head-up sleeping is the result of a reduction in the orthostatic decrease in cardiac output. Preliminary data suggest that the expanded body fluid volume is allocated to the perivascular space rather than to the intravascular space.

Key words

blood pressure stroke volume vascular resistance body fluids hormones plethysmography 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Robertson D, Davis TL. Recent advances in the treatment of orthostatic hypotension.Neurology 1995; 45(suppl 5):S26-S32.Google Scholar
  2. 2.
    Ten Harkel ADJ, van Lieshout, JJ, Wieling W. Treatment of orthostatic hypotension with sleeping in the head-up tilt position, alone and in combination with fludrocortisone.J Intern Med 1992; 232:139–145.Google Scholar
  3. 3.
    Wieling W, van Lieshout JJ. Investigation and treatment of autonomic circulatory failure.Curr Opin Neurol Neurosurg 1993; 6:537–543.Google Scholar
  4. 4.
    Wieling W, Cortelli P, Mathias CJ. Treating neurogenic orthostatic hypotension. In:The autonomic nervous system, part II,Dysfunction. Appenzeller O, ed.Handbook of clinical neurology; vol 75. Elsevier Science, 1999.Google Scholar
  5. 5.
    Chobanian AV, Volicer L, Tifft CP, Gavras H, Liang CS, Faxon D. Mineralocorticoid-induced hypertension in patients with orthostatic hypotension.N Engl J Med 1979; 301:68–73.Google Scholar
  6. 6.
    Davies IB, Bannister RG, Sever PS, Wilcox CS. Fludrocortisone in the treatment of postural hypotension: altered sensitivity to pressor agents.Br J Clin Pharmacol 1978; 6:444P-445P.Google Scholar
  7. 7.
    Bannister R, Mathias CJ. The management of postural hypotension. In:Autonomic failure. A textbook of clinical disorders of the autonomic nervous system. Bannister R, Mathias CJ, eds. Oxford: Oxford University Press; 1992. pp. 622–646.Google Scholar
  8. 8.
    Hoeldtke RD, Streeten DHP. Treatment of orthostatic hypotension with erythropoietin.N Engl J Med 1993; 329:611–615.Google Scholar
  9. 9.
    Mion D, Jr., Rea RF, Anderson EA, Kahn D, Sinkey CA, Mark AL. Effects of fludrocortisone on sympathetic nerve activity in humans.Hypertension 1994; 23:123–130.Google Scholar
  10. 10.
    Wieling W, van Lieshout JJ. Maintenance of postural normotension in humans. In:Clinical autonomic disorders. 2nd ed. Low PA, ed. Boston: Little Brown and Co; 1997. pp. 73–82.Google Scholar
  11. 11.
    van Lieshout JJ, Wieling W, Van Montfrans GA, Settels JJ, Speelman JD, Endert E etal. Acute dysautonomia associated with Hodgkin's disease.J Neurol Neurosurg Psychiatry 1986; 49:830–832.Google Scholar
  12. 12.
    van Lieshout JJ, Wieling W, Wesseling KH, Endert E, Karemaker JM. Orthostatic hypotension caused by sympathectomies performed for hyperhidrosis.Neth J Med 1990; 36:53–57.Google Scholar
  13. 13.
    Ten Harkel ADJ, van Lieshout JJ, Wieling W. Circulatory autonomic failure 50 years after acute poliomyelitis.Clin Auton Res 1991; 1:215–217.Google Scholar
  14. 14.
    Ten Harkel ADJ, van Lieshout JJ, van Lieshout EJ, Wieling W. Assessment of cardiovascular reflexes: influence of posture and period of preceding rest.J Appl Physiol 1990; 68:147–153.Google Scholar
  15. 15.
    Lundvall J, Bjerkhoel P. Failure of hemoconcentration during standing to reveal plasma volume decline induced in the erect posture.J Appl Physiol 1994; 77:2155–2162.Google Scholar
  16. 16.
    Van Beaumont W. Evaluation of haemoconcentration from haematocrit measurements.J Appl Physiol 1972; 3:712–713.Google Scholar
  17. 17.
    Wesseling KH. Finapres, continuous non-invasive finger arterial pressure based on the method of Peñáz. In:Blood pressure measurements. Meyer-Sabellek W, Anlauf M, Gotzen R, Steinfeld L, eds. Darmstadt: Steinkopf Verlag; 1991. pp. 161–172.Google Scholar
  18. 18.
    Imholz BPM, Settels JJ, Van der Meiracker AH, Wesseling KH, Wieling W. Non invasive continuous finger blood pressure measurement during orthostatic stress compared to intra-arterial pressure.Cardiovasc Res 1990; 24:214–221.Google Scholar
  19. 19.
    Friedman DB, Jensen FB, Matzen S, Secher NH. Non-invasive blood pressure monitoring during head-up tilt using the Penaz principle.Acta Anaesthesiol Scand 1990; 34:519–522.Google Scholar
  20. 20.
    Petersen ME, Williams TR, Sutton R. A comparison of noninvasive continuous finger blood pressure measurement (Finapres) with intra-arterial pressure during prolonged head-up tilt.Eur Heart J 1995; 16:1641–1654.Google Scholar
  21. 21.
    Jellema WT, Imholz BPM, Van Goudoever J, Wesseling KH, van Lieshout JJ. Finger arterial versus intrabrachial pressure and continuous cardiac output during head-up tilt testing in healthy subjects.Clin Sci (Colch) 1996; 91:193–200.Google Scholar
  22. 22.
    Wesseling KH, De Wit B, Weber JAP, Smith NT. A simple device for the continuous measurement of cardiac output.Adv Cardiovasc Physics 1983; 5–II:16–52.Google Scholar
  23. 23.
    Jansen JRC, Wesseling KH, Settels JJ, Schreuder JJ. Continuous cardiac output monitoring by pulse contour during cardiac surgery.Eur Heart J 1990; 11(suppl 1):26–32.Google Scholar
  24. 24.
    Stok WJ, Baisch F, Hillebrecht A, Schulz H, Meyer M, Karemaker JM. Noninvasive cardiac output measurement by arterial pulse analysis compared with inert gas rebreathing.J Appl Physiol 1993; 74:2687–2693.Google Scholar
  25. 25.
    Wesseling KH, Jansen JRC, Settels JJ, Schreuder JJ. Computation of aortic flow from pressure in humans using a nonlinear, three-element model.J Appl Physiol 1993; 74:2566–2573.Google Scholar
  26. 26.
    Jellema WT, Imholz BPM, Oosting H, Wesseling KH, van Lieshout JJ. Estimation of beat-to-beat changes in stroke volume from arterial pressure: a comparison of two pressure wave analysis techniques during head-up tilt testing in young healthy males.Clin Auton Res 1999; 9:185–192.Google Scholar
  27. 27.
    Jellema WT, Wesseling KH, Groeneveld ABJ, Stoutenbeek CP, Thijs LG, van Lieshout JJ. Continuous cardiac output in septic shock by simulating a model of the aortic input impedance. A comparison with bolus injection thermodilution.Anesthesiology 1999; 90:1317–1328.Google Scholar
  28. 28.
    Harms MPM, Wesseling KH, Pott F, Jenstrup M, Van Goudoever J, Secher NH, van Lieshout JJ. Continuous stroke volume monitoring by modelling flow from non-invasive measurement of arterial pressure in humans under orthostatic stress.Clin Sci 1999; 97:291–301.Google Scholar
  29. 29.
    Buckey JC, Lane LD, Plath G, Gaffney FA, Baisch F, Blomqvist CG. Effect of head down tilt for 10 days on the compliance of the leg.Acta Physiol Scand 1992; 144(S604):53–60.Google Scholar
  30. 30.
    Bevington PR.Data reduction and error analysis for the physical sciences. New York: McGraw-Hill Book Co; 1969.Google Scholar
  31. 31.
    Wieling W. Non-invasive recording of heart rate and blood pressure in the evaluation of neurocardiovascular control. In:Autonomic failure, a textbook of clinical disorders of the autonomic nervous system. 3rd ed. Bannister R, Mathias CJ, eds. Oxford: Oxford University Press; 1992. pp. 291–311.Google Scholar
  32. 32.
    Tanaka H, Sjöberg BJ, Thulesius O. Cardiac output and blood pressure during active and passive standing.Clin Physiol 1996; 16:157–170.Google Scholar
  33. 33.
    Rowell LB.Human cardiovascular control. 2nd ed. New York: Oxford University Press; 1993; 441–483.Google Scholar
  34. 34.
    van Lieshout JJ, Secher NH. Orthostatic stress and autonomic dysfunction. In:Exercise and circulation in health and disease. Saltin B, Secher NH, Mitchell JH, Boushel R, eds. Champaign, IL: Human Kinetics; 1999. pp. 305–324.Google Scholar
  35. 35.
    Smit AAJ, Halliwill JR, Low PA, Wieling W. Pathophysiological basis of orthostatic hypotension in autonomic failure. Topical review.J Physiol 1999; 519:1–10.Google Scholar
  36. 36.
    Meredith IT, Esler MD, Lambert GW, Jennings GL, Eisenhofer G. Biochemical evidence of sympathetic denervation of the heart in pure autonomic failure.Clin Auton Res 1991; 1:187–194.Google Scholar
  37. 37.
    Ibrahim MM, Tarazi RC, Dustan HP, Bravo EL. Idiopathic orthostatic hypotension: circulatory dynamics in chronic autonomic insufficiency.Am J Cardiol 1974; 34:288–294.Google Scholar
  38. 38.
    van Lieshout JJ, Wieling W, Wesseling KH, Karemaker JM. Pitfalls in the assessment of cardiovascular reflexes in patients with sympathetic failure but intact vagal control.Clin Sci 1989; 76:523–528.Google Scholar
  39. 39.
    Sagnella GA, Markandu ND, Shore AC, Forsling ML, MacGregor GA. Plasma atrial natriuretic peptide: its relationship to changes in sodium intake, plasma renin activity and aldosterone in man.Clin Sci 1987; 72:25–30.Google Scholar
  40. 40.
    Wang BC, Sundet WD, Hakumaki MOK, Goetz KL. Vasopressin and renin responses to hemorrhage in conscious, cardiacdenervated dogs.Am J Physiol 1983; 245:H399-H405.Google Scholar
  41. 41.
    DiBona GF, Wilcox CS. The kidney and the sympathetic nervous system. In:Autonomic failure. 3rd ed. Bannister R, Mathias CJ, eds. Oxford: Oxford University Press; 1992. pp. 178–196.Google Scholar
  42. 42.
    van Lieshout JJ, Ten Harkel ADJ, Van Leeuwen AM, Wieling W. Contrasting effects of acute and chronic volume expansion on orthostatic blood pressure control in a patient with autonomic circulatory failure.Neth J Med 1991; 39:72–83.Google Scholar
  43. 43.
    Hohenbleicher H, Klosterman F, Schorr U, Seyfert S, Persson PB, Sharma AM. Identification of a renin threshold and its relationship to salt intake in a patient with pure autonomic failure.Hypertension 1997; 30:1068–1071.Google Scholar
  44. 44.
    Rose BD.Clinical physiology of acid-base and electrolyte disorders. 3rd ed. New York: McGraw-Hill; 1989; 589–600.Google Scholar
  45. 45.
    Wilcox CS, Puritz R, Lightman SL, Bannister R, Aminoff MJ. Plasma volume regulation in patients with progressive autonomic failure during changes in salt intake or posture.J Lab Clin Med 1984; 104:331–339.Google Scholar
  46. 46.
    Wilcox CS. Body fluids and renal function in autonomic failure. In:Autonomic failure, a textbook of clinical disorders of the autonomic nervous system. Bannister R, ed. Oxford: Oxford University Press, 1985:115–154.Google Scholar
  47. 47.
    MacLean AR, Allen EV. Orthostatic hypotension and orthostatic tachycardia; treatment with the “head-up” bed.JAMA 1940; 115:2162–2167.Google Scholar
  48. 48.
    MacLean AR, Allen EV, Magath TB. Orthostatic tachycardia and orthostatic hypotension: defects in the return of venous blood to the heart.Am Heart J 1944; 27:145–163.Google Scholar
  49. 49.
    Mahar LJ, Frewin DB, Dunn DE. Idiopathic orthostatic hypotension controlled with a monoamine oxidase inhibitor and 9-alphafluorohydrocortisone.Med J Aust 1975; 2:940–943.Google Scholar
  50. 50.
    Jordan J, Shannon JR, Pohar B, Paranjape SY, Robertson D, Robertson RM, etal. Contrasting effects of vasodilators on blood pressure and sodium balance in the hypertension of autonomic failure.J Am Soc Nephrol 1999; 10:35–42.Google Scholar
  51. 51.
    Jankovic J, Gilden JL, Hiner BC, Kaufmann H, Brown DC, Coghlan CH, etal. Neurogenic orthostatic hypotension: a doubleblind, placebo-controlled study with midodrine.Am J Med Sci 1993; 95:38–48.Google Scholar

Copyright information

© Lippincott Williams & Wilkins 2000

Authors and Affiliations

  • Johannes J. van Lieshout
    • 1
    • 2
  • A. Derk Jan ten Harkel
    • 2
  • Wouter Wieling
    • 1
    • 2
  1. 1.Cardiovascular Research Institute AmsterdamThe Netherlands
  2. 2.Department of Internal MedicineAcademic Medical Centre, University of AmsterdamAmsterdamThe Netherlands

Personalised recommendations