Intensive Care Medicine

, Volume 21, Issue 3, pp 218–225 | Cite as

Alterations in circulating vasoactive substances in the critically ill —a comparison between survivors and non-survivors

  • J. Boldt
  • T. Menges
  • D. Kuhn
  • C. Diridis
  • G. Hempelmann



Regulation of circulatory homeostasis is based on several factors including various circulating vasoactive substances. Whether these regulators differ between survivors and non-survivors was investigated in critically ill patients.


Prospective study.


Clinical investigation on a surgical intensive care unit of an university hospital.


60 consecutive patients suffering from trauma (n=21) or postoperative complications (n=39) were studied prospectively. The patients were divided into survivors (n=27) and non-survivors (n=33). Therapy was adjusted to the standards of modern intensive care management by physicians who were not involved in the study.

Measurements and results

Endothelin-1, atrial natriuretic peptide (ANP), vasopressin, renin, and catecholamine (epinephrine, norepinephrine) plasma levels were measured from arterial blood samples using radioimmunoassay (RIA) or high-pressure liquid chromatography (HPLC) technique on the day of admission to ICU and during the following 5 days. Various hemodynamic parameters were also monitored during that period. The non-survivors showed elevated pulmonary artery pressure (PAP: 34.1±5.4 mmHg) and pulmonary capillary wedge pressure (PCWP: 20.3±7.3 mmHg) already at the beginning of the study. Cardiac index (CI) did not differ among the groups, whereas right ventricular ejection fraction (RVEF) decreased in the non-survivors. PaO2/FIO2 decreased only in the non-survivors, whereas VO2 increased in the survivors (from 246±48 to 331±43 ml/min). Plasma levels of renin (from 206±40 to 595±81 pg/ml) and vasopressin (from 5.78±0.82 to 7.97±0.69 pg/ml) increased significantly in the non-survivors. Epinephrine and norepinephrine plasma concentrations were elevated in the non-survivors already at baseline and tremendously increased in these patients during the following days. ANP plasma levels significantly increased also only in the non-survivors (from 188±63 to 339±55 pg/ml) (p<0.05). Endothelin-1 decreased in the survivors, whereas it significantly increased in the non-survivors (from 3.62±0.68 to 9.37±0.94 pg/ml) during the study period (p<0.05). Analyses of co-variance revealed overall no significant correlation between circulating vasoactive substances and hemodynamics.


Systemic and regional regulators of the circulation were markedly changed by critical illness. In survivors, these regulators almost normalized within the study period of 5 days, whereas in non-survivors these alterations were even aggravated. It can only be speculated whether these regulator systems were influenced by activation of various mediator systems or whether they themselves influenced the negative outcome in the non-survivors.

Key words

Critical illness Hemodynamics Circulation Vasoactive substances Endothelin Catecholamines Atrial natriuretic peptide Outcome 


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  1. 1.
    Rose BD (1984) Regulation of the effective circulating volume. Rose BD (ed) Clinical physiology of acid-base and electrolyte disorders. McGraw Hill, New York, pp 171–190Google Scholar
  2. 2.
    Kehlet H (1984) The stress response to anaesthesia and surgery: Release mechanisms and modifying factors. Anesth Clin North Am 2:315–339Google Scholar
  3. 3.
    Waxman K, Shoemaker WC (1982) Physiologic responses to massive intraoperative hemorrhage. Arch Surg 117:470–475PubMedGoogle Scholar
  4. 4.
    Turnbull AV, Little RA (1993) Neurohormonal regulation after trauma. Circulating cytokines may also contribute to an activated sympathetic-adrenal control. In: Vincent JL (ed) Update in intensive care and emergency medicine. Springer, Berlin Heidelberg New York Tokyo, pp 574–581Google Scholar
  5. 5.
    Shoemaker WC, Appel PL, Waxman K (1982) Clinical trial of survivor's cardiorespiratory patterns as therapeutic goals in critically ill postoperative patients. Crit Care Med 10:398–403PubMedGoogle Scholar
  6. 6.
    Quintin L, Bonnet F, Macquin I, Szekely B, Becquemin JP, Ghignone M (1990) Aortic surgery: effect of clonidine on intraoperative catecholaminergic and circulatory stability. Acta Anaesth Scand 34:132–137PubMedGoogle Scholar
  7. 7.
    Anand KJ, Hansen DD, Hickey PR (1990) Hormonal-metabolic stress responses in neonates undergoing cardiac surgery. Anesthesiology 73:661–670PubMedGoogle Scholar
  8. 8.
    Lüscher TF (1992) Endothelin: systemic arterial and pulmonary effects of a new peptide with biologic properties. Am Rev Respir Dis 146 [Suppl 2]:S 56-S 60Google Scholar
  9. 9.
    Rushkoaho H, Lang RE, Toth M, Ganten D, Unger T (1987) Release and regulation of atrial natriuretic peptide (ANP). Eur Heart J 8 (Suppl B):99–109Google Scholar
  10. 10.
    Needleman P, Greenwald JE (1986) Atriopeptin: a cardiac hormone intimately involved in fluid, electrolyte, and blood-pressure hemostasis. N Engl J Med 314:828–834PubMedGoogle Scholar
  11. 11.
    Underwood RD, Chan DP, Burnett JC (1991) Endothelin: an endothelium-derived vasoconstrictor peptide and its role in congestive heart failure. Heart Failure 4:50–58Google Scholar
  12. 12.
    Vane JR, Änggard EE, Botting RM (1990) Regulatory functions of the vascular endothelium. N Engl J Med 323:27–36PubMedGoogle Scholar
  13. 13.
    Koller J, Mair P, Wiser C, Pomaroli A, Puschendorf B, Herold M (1991) Endothelin and big endothelin concentration in injured patients. N Engl J Med 21:1518Google Scholar
  14. 14.
    Brenner BM, Troy JL, Ballermann B (1989) Endothelium-dependent vascular responses. J Clin Invest 84:1373–1378PubMedGoogle Scholar
  15. 15.
    Baker SP, O'Neil B (1976) The injury severity score: an update. J Trauma 16:882–888PubMedGoogle Scholar
  16. 16.
    Xuan YT, Whorton AR, Shearer-Poor E, Boyd J, Watkins WD (1989) Determination of immunoreactive endothelin in medium from cultured endothelial cells and human plasma. Biochem Biophys Res Commun 164:326–332PubMedGoogle Scholar
  17. 17.
    Eskay R, Zukowska-Grojec Z, Haass M (1986) Circulating atrial natriuretic peptides in conscious rats: regulation of release by multiple factors. Science 232:636–639PubMedGoogle Scholar
  18. 18.
    Pullan PT, Clappison BH, Johnston CI (1979) Plasma vasopressin and human neurophysins in physiological and pathophysiological states associated with changes in vasopressin secretion. J Clin Endocrinol Metab 49:580–587PubMedGoogle Scholar
  19. 19.
    Thatcher R, Butty JS, Whitworth JA, Fei DT, Skinner SL (1985) Active and inactive renin in critically ill patients. Clin Exp Pharmacol Physiol 12:603–612PubMedGoogle Scholar
  20. 20.
    Krstulovic AM (1982) Investigations of catecholamine metabolism using highperformance liquid chromatography. Analytical methodology and clinical applications. J Chromatogr 229:1–34PubMedGoogle Scholar
  21. 21.
    Thijs LG (1988) Transport and consumption of oxygen in septic shock. In: Vincent JL (ed) Update in intensive care and emergency medicine, vol. 5. Springer, Berlin Heidelberg New York Tokyo, pp 44–50Google Scholar
  22. 22.
    Takala J, Ruokonen E (1991) Blood flow and adrenergic drugs in septic shock. In: Vincent JL (ed) Update in intensive care and emergency medicine, vol 14. Springer, Berlin Heidelberg New York Tokyo, pp 144–152Google Scholar
  23. 23.
    Jones SB, Romano FD (1989) Dose and time-dependent changes in plasma catecholamines in response to endotoxin in conscious rats. Circ Shock 28:59–68PubMedGoogle Scholar
  24. 24.
    Hall RC, Hodge RL (1971) Vasoactive hormones in endotoxin shock: a comparative study in cats and dogs. J Physiol 213:69–84PubMedGoogle Scholar
  25. 25.
    Wilson MF, Brackett DJ (1983) Release of vasoactive hormones and circulatory changes in shock. Circ Shock 11:225–234PubMedGoogle Scholar
  26. 26.
    Felicetta JV, Sowers JR (1987) Endocrine changes with critical illness. Crit Care Clin 5:855–869Google Scholar
  27. 27.
    Carrico CJ, Meakins JL, Marshall JC, Fry D, Maier RV (1986) Multiple organ failure syndrome. Arch Surg 121:196–208PubMedGoogle Scholar
  28. 28.
    Wilson MF, Brackett DJ, Archer LT, Hinshaw LB (1980) Mechanism of impaired cardiac function by vasopressin. Ann Surg 191:494–500PubMedGoogle Scholar
  29. 29.
    Koyama H, Tabata T, Nishzawa Y, Inoue T, Morii H, Yamaji T (1989) Plasma endothelin levels in patients with uremia. Lancet I:991–992Google Scholar
  30. 30.
    Athanassopoulos G, Cokkino DV (1991) Atrial natriuretic factor. Prog Cardiovasc Dis 5:313–328Google Scholar
  31. 31.
    Atlas SA (1986) Atrial natriuretic factor: a new hormone of cardiac origin. Recent Prog Horm Res 42:207–209PubMedGoogle Scholar
  32. 32.
    Weitzberg E, Lundberg JM, Rudehill A (1991) Elevated plasma levels of endothelin in patients with sepsis syndrome. Circ Shock 33:222–227PubMedGoogle Scholar
  33. 33.
    Goetz KL, Wang BC, Madwed JB, Zhu JI, Leadly RJ (1988) Cardiovascular, renal, and endocrine responses to intravenous endothelin in conscious dogs. Am J Physiol 55:R 1064–8Google Scholar
  34. 34.
    Yanagisawa M, Kurihara H, Kimura S (1988) A novel potent vasoconstrictor peptide produced by vascular endothelial cells. Nature 322:411–415Google Scholar
  35. 35.
    Rubanyi GM, Vanhoutte PM (1985) Hypoxia releases a vasoconstrictor substance from the canine vascular endothelium. J Physiol 364:45–56PubMedGoogle Scholar
  36. 36.
    Hartter E, Woloszczuk W (1989) Radioimmunoassay of endothelin. Lancet 1:909Google Scholar
  37. 37.
    Pittet JF, Morel DR, Hemsen A, Gunning, Lacroix JS, Suter PM, Lundberg JM (1991) Elevated endothelin-1 concentrations are associated with severity of illness in patients with sepsis. Ann Surg 213:261–264PubMedGoogle Scholar
  38. 38.
    Sugiura M, Inagami T, Kon V (1989) Endotoxin stimulates endothelin-release in vivo and in vitro as determined by radioimmunoassay. Biochem Biophys Res Commun 161:1220–1227PubMedGoogle Scholar
  39. 39.
    Mitaka C, Hirata Y, Nagura T, Tsunoda Y, Amaha K (1993) Circulating endothelin-1 concentrations in acute respiratory failure. Chest 104:476–480PubMedGoogle Scholar
  40. 40.
    Boarder MR, Marriott DB (1989) Characterization of endothelin-1 stimulation of catecholamine release from adrenal chromaffin cells. J Cardiovasc Pharmacol 13 [Suppl 5]:S 223–224Google Scholar
  41. 41.
    Voerman HJ, Stehouwer DA, van Kamp GJ, Strack van Schijndel JM, Groeneveld J, Thijs LG (1992) Plasma endothelin levels are increased during septic shock. Crit Care Med 20: 1097–1101PubMedGoogle Scholar
  42. 42.
    Dennhardt R, Gramm HJ, Meinhold K, Voigt K (1989) Patterns of endocrine secretion during sepsis. Prog Clin Biol Res 308:751–756PubMedGoogle Scholar

Copyright information

© Springer-Verlag 1995

Authors and Affiliations

  • J. Boldt
    • 1
  • T. Menges
    • 1
  • D. Kuhn
    • 1
  • C. Diridis
    • 1
  • G. Hempelmann
    • 1
  1. 1.Department of Anesthesiology and Intensive Care MedicineJustus-Liebig-Universität GiessenGiessenGermany

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