Kopplung von Herzzeitvolumen bzw. systemischem O₂-Transport und Metabolismus unter Katecholamintherapie

Zusammenfassung.

Katecholamine steigern nicht nur das Herzzeitvolumen (HZV) und damit das Sauerstoffangebot (D˙O₂), sondern auch den Sauerstoffverbrauch (V˙O₂). Für die Auswahl eines Katecholamins zur Therapie ist daher von Relevanz, in welchem Verhältnis das HZV zum V˙O₂ gesteigert wird, da die O₂-Bilanz des Organismus nur durch eine Steigerung des HZV bei möglichst geringem O₂-Mehrverbrauch verbessert wird. Unter diesem Blickwinkel untersuchten wir anhand der Literatur die Beziehung zwischen HZV und V˙O₂ sowohl am gesunden als auch am erkrankten Organismus und verglichen verschiedene Katecholamine auf der Grundlage der Steilheiten der individuellen Regressionsgeraden ihrer HZV/V˙O₂-Beziehung miteinander. Je nach Studienbedingungen variierten allerdings das Ausmaß sowohl der HZV- als auch der V˙O₂-Steigerung um ein Vielfaches schon für ein und dieselbe Substanz. Am gesunden Organismus erhöhen die synthetischen Katecholamine (Dobutamin und Dopexamin) bevorzugt das HZV, während die natürlichen Katecholamine (Adrenalin und Noradrenalin) sowohl V˙O₂ als auch HZV gleichermaßen steigern. Am erkrankten Organismus ist die Literaturlage ebenfalls nicht einheitlich, dennoch lassen sich tendenziell ähnliche Unterschiede zwischen den Substanzen wie am gesunden Organismus erkennen. Bei zurückhaltender Wertung der verfügbaren Informationen eignen sich unter den vorgenannten Aspekten zur Kreislaufunterstützung vor allem die synthetischen Katecholamine Dobutamin und insbesondere Dopexamin, da sie das Herzzeitvolumen und damit das O₂-Angebot über den Stoffwechselbedarf hinaus steigern.

Coupling of Cardiac Output or Systemic O₂ Transport with Metabolism during Catecholamine Therapy.

Catecholamines increase cardiac output (CO) and thus systemic oxygen delivery, but they also increase the tissue's oxygen demand (thermogenic or calorigenic effect). Therefore, it is of particular interest for the choice of a catecholamine as to what extent CO is increased in relation to oxygen demand (V˙O₂), because the tissue's oxygen balance is improved only if CO and thus oxygen delivery increases more than oxygen demand. For this purpose we reviewed the literature and analysed the relation between CO and V˙O₂ during physiological as well as during pathological conditions. In particular, we compared the slopes of the regression lines of the individual CO/V˙O₂-relation for each catecholamine. Dependent on study conditions, the extent of the increases in CO and V˙O₂ varies substantially already for one and the same agent. During physiological conditions, the synthetic agents dobutamine and dopexamine primarily increase CO, whereas the endogenous ones epinephrine and particularly norepinephrine increase both CO and V˙O₂ to about the same extent. During pathological conditions the literature is inconsistent, but it appears that the CO/V˙O₂-relations do not differ substantially from those observed under physiological conditions. With due caution the current information implies that the synthetic catecholamines dobutamine and in particular dopexamine might be preferred in the treatment of low cardiac output states because they increase CO and thus oxygen delivery above the increase in metabolic demand.

Schlüsselwörter:

Katecholamine - Kreislauftherapie - Stoffwechsel - Sauerstoffverbrauch - Sauerstofftransport - Adrenalin - Noradrenalin - Dobutamin - Dopexamin

Key words:

Catecholamine therapy - Cardiac output - Metabolism - Oxygen consumption - Oxygen delivery - Epinephrine - Norepinephrine - Dobutamine - Dopexamine

Literatur

• 1 Schütz W, Anhäupl T, Gauss A. Grundsätze der Katecholamintherapie. Teil 1: Charakterisierung der therapeutisch bedeutsamen Sympathomimetika.  Anästhesiol Intensivmed Notfallmed Schmerzther. 2000;  35 67-81
• 2 Gauss A, Anhäupl T, Schütz W. Grundsätze der Katecholamintherapie. Teil 2: Leitfaden der klinischen Anwendung.  Anästhesiol Intensivmed Notfallmed Schmerzther. 2000;  35 131-136
• 3 Jänig W. Vegetatives Nervensystem. In: Schmidt RF, Thews G, Hrsg. Physiologie des Menschen. Berlin, Heidelberg, New York; Springer 26. Auflage 1995: 340-369
• 4 Tuttle R R, Mills J. Dobutamine - development of a new catecholamine to selectively increase cardiac contractility.  Circ Res. 1975;  36 185-196
• 5 Brown R A, Dixon J, Farmer J B, Hall J C, Humphries R G, Ince F, O'Connor S E, Simpson W T, Smith G W. Dopexamine: A novel agonist at peripheral dopamine receptors and β₂-adrenoceptors.  Br J Pharmacol. 1985;  85 599-608
• 6 Stanford G G. Use of inotropic agents in critical illness.  Surg Clin North Am. 1991;  71 683-698
• 7 Santman F W. Catecholamines in critical care - the commonly used catecholamines: receptor and clinical profile, indications and dosages.  Pharm Weekbl [Sci]. 1992;  14 290-296
• 8 Scheeren T W L, Arndt J O. Different response of oxygen consumption and cardiac output to various endogenous and synthetic catecholamines in awake dogs.  Crit Care Med. 2000;  28 3861-3868
• 9 Svedmyr N. Studies on the mechanism for the calorigenic effect of adrenaline in man.  Acta Physiol Scand. 1966;  68 84-95
• 10 Blaak E E, van Baak M A, Kempen K P G, Saris W H M. Role of α- and β-adrenoceptors in sympathetically mediated thermogenesis.  Am J Physiol. 1993;  264 E 11-E 17
• 11 Griffith F R J. Fact and theory regarding the calorigenic action of adrenaline.  Physiol Rev. 1951;  31 151-187
• 12 MacDonald I A, Bennett T, Fellows I W. Catecholamines and the control of metabolism in man.  Clin Sci. 1985;  68 613-619
• 13 Atgié C, Faintrenie G, Carpéné C, Bukowiecki L J, Géloen A. Effects of chronic treatment with noradrenaline or a specific β₃-adrenergic agonist, CL 316 243, on energy expenditure and epididymal adipocyte lipolytic activity in rat.  Comp Biochem Physiol. 1998;  119A 629-636
• 14 Liu Y-L, Toubro S, Astrup A, Stock M J. Contribution of beta 3-adrenoceptor activation to ephedrine-induced thermogenesis in humans.  Int J Obes Relat Metab Disord. 1995;  19 678-685
• 15 Meyers D S, Skwish S, Dickinson K E, Kienzle B, Arbeeny C M. Beta 3-adrenergic receptor-mediated lipolysis and oxygen consumption in brown adipocytes from cynomolgus monkeys.  J Clin Endocrinol Metab. 1997;  82 395-401
• 16 Douglas C G, Haldane J S. The regulation of the general circulation rate in man.  J Physiol (Lond). 1922;  56 69-100
• 17 Barger A C, Richards V, Metcalfe J, Günther B. Regulation of the circulation during exercise - Cardiac output (direct Fick) and metabolic adjustment in the normal dog.  Am J Physiol. 1956;  184 613-623
• 18 Lieberman J A, Weiskopf R B, Kelley S D, Feiner J, Noorani M, Leung J, Toy P, Viele M. Critical oxygen delivery in conscious humans is less than 7.3 ml O₂ × ml^-1 × min^-1. .  Anesthesiology. 2000;  92 407-413
• 19 Scheeren T W L, Schwarte L A, Arndt J O. Metabolic regulation of cardiac output during inhalation anaesthesia in dogs.  Acta Anaesthesiol Scand. 1999;  43 421-430
• 20 van der Linden P, Rausin I, Deltell A, Bekrar Y, Gilbart E, Bakker J, Vincent J-L. Detection of tissue hypoxia by arteriovenous gradient for PCO₂ and pH in anesthetized dogs during progressive hemorrhage.  Anesth Analg. 1995;  80 269-275
• 21 Danek S J, Lynch J P, Weg J G, Dantzker D R. The Dependence of Oxygen Uptake on Oxygen Delivery in the ARDS.  Am Rev Respir Dis. 1980;  122 387-395
• 22 Gutierrez G, Pohil R J. Oxygen consumption is linearly related to O₂ supply in critically ill patients.  J Crit Care. 1986;  1 45-53
• 23 Nelson D P, Samsel R W, Wood L D H, Schumacker P T. Pathologic supply dependence of systemic and intestinal O₂ uptake during endotoxemia.  J Appl Physiol. 1988;  64 2410-2419
• 24 Dantzker D R, Foresman B, Gutierrez G. Oxygen Supply and Utilization Relationships - A Reevaluation.  Am Rev Respir Dis. 1991;  143 675-679
• 25 Tuchschmidt J, Oblitas D, Fried J C. Oxygen consumption in sepsis and septic shock.  Crit Care Med. 1991;  19 664-671
• 26 Appel P L, Shoemaker W C. Relationship of oxygen consumption and oxygen delivery in surgical patients with ARDS.  Chest. 1992;  102 906-911
• 27 Ensinger H, Georgieff M. Liegt der Sepsis und dem septischen Schock ein globaler Sauerstoffmangel zugrunde? Eine Übersicht in zwei Teilen. Teil 1: Sepsis und Zusammenhang zwischen D˙O₂ und V˙O₂.  Anästhesiol Intensivmed Notfallmed Schmerzther. 1996;  31 131-142
• 28 Archie J P. Mathematical coupling of data - a common source of error.  Ann Surg. 1981;  193 396-303
• 29 Walsh T S, Lee A. Mathematical coupling in medical research: lesson from studies of oxygen kinetics.  Br J Anaesth. 1998;  81 118-120
• 30 Collins S, Caron M G, Lefkowitz R J. Beta-adrenergic receptors in hamster smooth muscle cells are transcriptionally regulated by glucocorticoids.  J Biol Chem. 1988;  263 9067-9070
• 31 Collins S, Bouvier M, Bolanowski M A, Caron M G, Lefkowitz R J. cAMP stimulates transcription of the beta 2-adrenergic receptor gene in response to short-term agonist exposure.  Proc Natl Acad Sci USA. 1989;  86 4853-4857
• 32 Saito T, Takanashi M, Gallagher E, Fuse A, Suzaki S, Inagaki O, Yamada K, Ogawa R. Corticosteroid effect on early beta-adrenergic down-regulation during circulatory shock: hemodynamic study and beta-adrenergic receptor assay.  Intensive Care Med. 1995;  21 204-210
• 33 Romano F D, Jones S B. Alterations in beta-adrenergic stimulation of myocardial adenylate cyclase in endotoxic rats.  Am J Physiol. 1986;  250 R358-364
• 34 Singh M, Notterman D A, Metakis L. Tumor necrosis factor produces homologous desensitization of lymphocyte beta 2-adrenergic responses.  Circ Shock. 1993;  39 275-278
• 35 Manthous C A, Schumacker P T, Pohlman A, Schmidt G A, Hall J B, Samsel R W, Wood L D. Absence of supply dependency of oxygen consumption in patients with septic shock.  J Crit Care. 1993;  8 203-211
• 36 Mira J-P, Fabre J-E, Baigorri F, Coste J, Annat G, Artigas A, Nitenberg G, Dhainaut J F A. Lack of oxygen supply dependency in patients with severe sepsis. A study of oxygen delivery increased by military antishock trouser and dobutamine.  Chest. 1994;  106 1524-1531
• 37 Ronco J J, Phang P T, Walley K R, Wiggs B, Fenwick J C, Russell J A. Oxygen consumption is independent of changes in oxygen delivery in severe adult respiratory distress syndrome.  Am Rev Respir Dis. 1991;  143 1267-1273
• 38 Boothby W M, Sandiford I. The calorigenic action of adrenalin chlorid.  Am J Physiol. 1923;  66 93-123
• 39 Lundholm L, Svedmyr N. Studies on the stimulating effects of adrenaline and noradrenaline on respiration in man.  Acta Physiol Scand. 1966;  67 65-75
• 40 Reale A, Kappert A, Skoglund C-H, Sutton G C. The effect of L-Nor-Adrenaline on the oxygen consumption of human beings.  Acta Physiol Scand. 1950;  20 153-159
• 41 Melchior J C, Pinaud M, Blanloeil Y, Bourreli B, Potel G, Souron R. Hemodynamic effects of continuous norepinephrine infusion in dogs with and without hyperkinetic endotoxic shock.  Crit Care Med. 1987;  15 687-691
• 42 LeBlanc J, Mount L E. Effects of noradrenaline and adrenaline on oxygen consumption rate and arterial blood pressure in the newborn pig.  Nature. 1968;  217 77-78
• 43 Robie N W, Nutter D O, Moody C, McNay J L. In vivo analysis of adrenergic receptor activity of dobutamine.  Circ Res. 1974;  34 663-671
• 44 Tulen J H M, Man in't Veld A J, van Roon A M, Moleman P, van Steenis H G, Blankestijn P J, Boomsma F. Spectral analysis of hemodynamics during infusions of epinephrine and norepinephrine in men.  J Appl Physiol. 1974;  76 1914-1921
• 45 Ruttimann Y, Chioléro R, Jéquier E, Breitenstein E, Schutz Y. Effects of dopamine on total oxygen consumption and oxygen delivery in healthy men.  Am J Physiol. 1989;  257 E541-E546
• 46 Ruttimann Y, Schutz Y, Jéquier E, Lemarchand T, Chioléro R. Thermogenic and metabolic effects of dopamine in healthy men.  Crit Care Med. 1991;  19 1030-1036
• 47 Hansen P D, Coffey S C, Lewis F R. The effects of adrenergic agents on oxygen delivery and oxygen consumption in normal dogs.  J Trauma. 1994;  37 283-293
• 48 Goldberg L I, Rajfer S I. Dopamine receptors: applications in clinical cardiology.  Circulation. 1985;  72 245-248
• 49 Cain S M, Chapler C K. Effects of norepinephrine and α-block on O₂-uptake and blood flow in dog hindlimb.  J Appl Physiol. 1981;  51 1245-1250
• 50 Bevega˚rd S, Jonsson B, Karlöf I. Circulatory response to recumbent exercise and head-up tilting in patients with disturbed sympathetic cardiovascular control (postural hypotension).  Acta Med Scand. 1962;  172 623-636
• 51 Scheeren T W L. Beziehung zwischen Herzminutenvolumen und Sauerstoffverbrauch bei Inhalationsanästhesien und unter dem Einfluss von Katecholaminen.  Anästhesiol Intensivmed Notfallmed Schmerzther. 2000;  35 214-219
• 52 Boorstein S M, Hirschl R B, Riley M K, Kahan B S, Hultquist K A, Bartlett R H. The effect of norepinephrine infusion on oxygen delivery and consumption in the canine model.  J Surg Res. 1994;  56 251-255
• 53 Zhang H, Spapen H, Vincent J-L. Effects of dobutamine and norepinephrine on oxygen availability in tamponade-induced stagnant hypoxia: a prospective, randomized, controlled study.  Crit Care Med. 1994;  22 299-305
• 54 Walsh K M, Adams C, Sinclair A, Leen E, Lean M E J. Influences on adrenaline-induced thermogenesis in obese women and relationship to cardiovascular responses.  Clin Sci. 1998;  94 121-127
• 55 Liang C-S, Hood W Bj. Dobutamine infusion in conscious dogs with and without autonomic nervous system inhibition: effects on systemic hemodynamics, regional blood flows and cardiac metabolism.  J Pharmacol Exp Ther. 1979;  211 698-705
• 56 Abdul-Rasool I H, Chamberlain J H, Swan P C, Ward D S. Cardiorespiratory and metabolic effects of dopamine and dobutamine infusions in dogs.  Crit Care Med. 1987;  15 1044-1050
• 57 Bhatt S B, Hutchinson R C, Tomlinson B, Oh T E, Mak M. Effect of dobutamine on oxygen supply and uptake in healthy volunteers.  Br J Anaesth. 1992;  69 298-303
• 58 Uusaro A, Hartikainen J, Parviainen M, Takala J. Metabolic stress modifies the thermogenic effect of dobutamine in man.  Crit Care Med. 1995;  23 674-680
• 59 De Backer D, Berre J, Moraine J-J, Melot C, Vanfraechem J, Vincent J-L. Effects of dobutamine on the relationship between oxygen consumption and delivery in healthy volunteers: comparison with sodium nitroprusside.  Clin Sci. 1996;  90 105-111
• 60 Meadows D, Edwards J D, Wilkins R G, Nightingale P. Reversal of intractable septic shock with norepinephrine therapy.  Crit Care Med. 1988;  16 663-666
• 61 Bakker J, Vincent J-L. Effects of norepinephrine and dobutamine on oxygen transport and consumption in a dog model of endotoxic shock.  Crit Care Med. 1993;  21 425-432
• 62 Moran J L, O'Fathartaigh M S, Peisach A R, Chapman M J, Leppard P. Epinephrine as an inotropic agent in septic shock: a dose-profile analysis.  Crit Care Med. 1993;  21 70-77
• 63 Jewitt D, Mitchell A, Birkhead J, Dollery C. Clinical cardiovascular pharmacology of dobutamine, a selective inotropic catecholamine.  Lancet. 1974;  II 363-367
• 64 Shoemaker W C, Appel P L, Kram H B. Hemodynamic and oxygen transport effects of dobutamine in critically ill patients.  Crit Care Med. 1986;  14 1032-1037
• 65 Shoemaker W C, Appel P L, Kram H B, Duarte D, Harrier D, Ocampo H A. Comparison of hemodynamic and oxygen transport effects of dopamine and dobutamine in critically ill surgical patients.  Chest. 1989;  96 120-126
• 66 Schwenzer K J, Kopel R F. Hemodynamic and metabolic effects of dobutamine in 18 patients after open heart surgery.  Crit Care Med. 1990;  18 1107-1110
• 67 Shoemaker W C, Appel P L, Kram H B. Oxygen transport measurements to evaluate tissue perfusion and titrate therapy: Dobutamine and dopamine effects.  Crit Care Med. 1991;  19 672-688
• 68 Esen F, Telci L, Apir K, Kesecioglu J, Denkel T, Pembeci K. Oxygen uptake/supply dependency in human sepsis: does it increase the risk of multisystem organ failure?.  Adv Exp Med Biol. 1992;  317 855-861
• 69 Teboul J-L, Graini L, Boujdaria R, Berton C, Richard C. Cardiac index vs oxygen-derived parameters for rational use of dobutamine in patients with congestive heart failure.  Chest. 1993;  103 81-85
• 70 Hayes M A, Timmins A C, Yau E HS, Palazzo M, Hinds C J, Watson D. Elevation of systemic oxygen delivery in the treatment of critically ill patients.  N Engl J Med. 1994;  330 1717-1722
• 71 De Backer D, Moraine J-J, Berre J, Kahn R J, Vincent J-L. Effects of dobutamine on oxygen consumption in septic patients.  Am J Respir Crit Care Med. 1994;  150 95-100
• 72 Hansen P D, Coffey S C, Lewis F R. Changes in oxygen consumption relative to oxygen delivery in endotoxemic dogs given adrenergic agents.  J Surg Res. 1994;  57 156-163
• 73 Teboul J-L, Mercat A, Lenique F, Berton C, Richard C. Value of the venous-arterial PCO₂ gradient to reflect the oxygen supply to demand in humans: Effects of dobutamine.  Crit Care Med. 1998;  26 1007-1010
• 74 Preiser J-C, Armistead C, Le Minh T, Vincent J-L. Increase in oxygen supply during experimental septic shock: the effects of dobutamine versus dopexamine.  J Crit Care. 1989;  4 40-44
• 75 Smithies M, Yee T H, Jackson L, Beale R, Bihari D. Protecting the gut and the liver in the critically ill: effects of dopexamine.  Crit Care Med. 1994;  22 789-795
• 76 Wilson R F, Christensen C, LeBlanc L P. Oxygen consumption in critically-ill surgical patients.  Ann Surg. 1972;  176 801-804
• 77 Bland R D, Shoemaker W C. Common physiologic patterns in general surgical patients: hemodynamic and oxygen transport changes during and after operation in patients with and without associated medical problems.  Surg Clin North Am. 1985;  65 793-809
• 78 Shoemaker W C, Appel P L, Kram H B, Waxman K, Lee T-S. Prospective trial of supranormal values of survivors as therapeutic goals in high-risk surgical patients.  Chest. 1988;  94 1176-1186
• 79 Shoemaker W C, Kram H B, Appel P L, Fleming A W. The efficacy of central venous and pulmonary artery catheters and therapy based upon them in reducing mortality and morbidity.  Arch Surg. 1990;  125 1332-1337
• 80 Yu M, Burchell S, Hasaniya N W M A, Takanishi D M, Myers S A, Takiguchi S A. Relationship of mortality to increasing oxygen delivery in patients ≥ 50 years of age: A prospective, randomized trial.  Crit Care Med. 1998;  26 1011-1019
• 81 Boyd O, Grounds R M, Bennett E D. A randomized clinical trial of the effect of deliberate perioperative increase of oxygen delivery on mortality in high-risk surgical patients.  JAMA. 1993;  270 2699-2707
• 82 Fleming A, Bishop M, Shoemaker W, Appel P, Sufficool W, Kuvhenguwha A, Kennedy F, Wo C-J. Prospective trial of supranormal values as goals of resuscitation in severe trauma.  Arch Surg. 1992;  127 1175-1181
• 83 Gutierrez G, Palizas F, Doglio G, Wainsztein N, Gallesio A, Pacin J, Dubin A, Schiavi E, Jorge M, Pusajo J, Klein F. et al . Gastric intramucosal pH as a therapeutic index of tissue oxygenation in critically ill patients.  Lancet. 1992;  339 195-199
• 84 Tuchschmidt J, Fried J, Astiz M, Rackow E. Elevation of cardiac output aud oxygen delivery improves outcome in septic shock.  Chest. 1992;  102 216-220
• 85 Yu M, Levy M M, Smith P, Takiguchi S A, Miyasaki A, Myers S A. Effects of maximizing oxygen delivery on morbidity and mortality rates in critically ill patients: a prospective, randomized, controlled study.  Crit Care Med. 1993;  21 830-838
• 86 Yu M, Tomasa G. A double-blind, prospective, randomized trial of ketoconazole, a thromboxane synthetase inhibitor, in the prophylaxis of the adult respiratory distress syndrome.  Crit Care Med. 1993;  21 1635-1642
• 87 Bishop M H, Shoemaker W, Appel P L, Meade P, Ordog G J, Wasserberger J, Wo C J, Rimle D A, Kram H B, Umali R. et al . Prospective, randomized trial of survivor values of cardiac index, oxygen delivery, and oxygen consumption as resuscitation endpoints in severe trauma.  J Trauma. 1995;  38 780-787
• 88 Gattinoni L, Brazzi L, Pelosi P, Latini R, Tognoni G, Pesenti A, Fumagalli R. A trial of goal-oriented hemodynamic therapy in critically ill patients.  N Engl J Med. 1995;  33 1025-1032
• 89 Uusaro A, Russell J A. Could anti-inflammatory actions of catechol-amines explain the possible beneficial effects of supranormal oxygen delivery in critically ill surgical patients?.  Intensive Care Med. 2000;  26 299-304