LETTERS TO THE EOITOR

Sepsis

and Angiotensin

11

To the Editor:

Thaker et al’ and Geary et al* have presented three provocative case studies demonstrating the potential usefulness of angiotensin 11 in raising systemic vascular resistance in patients being weaned from cardiopulmonary bypass (CPB). TWOof their patients had an uneventful recovery. The third died on the fourth postoperative day of refractory hypotension secondary to septic shock. This occurred despite aggressive hemodynamic support, including the administration of additional angiotensin 11. Because a diminished response to exogenous norepinephrine and angiotensin 11 has been demonstrated in septic animals,3 there is no doubt that management of this patient was problematic. Nonetheless, use of a potent and selective splanchnic vasoconstrictor in the setting of sepsis is unusual and merits discussion. It has been known for some time that plasma angiotensin 11 concentrations increase with nonpulsatile flow during CPB. This is associated with a concomitant decrease in splanchnic perfusion that persists into the postoperative period.4-8 There is mounting evidente to suggest that unrecognized splanchnic ischemia secondary to decreased perfusion impacts heavily on cardiac surgery patients. Forty percent of patients who develop gastrointestinal symptoms after cardiac surgery die in the hospital.’ The liver appears to be particularly sensitive to splanchnic vasoconstriction.‘“.” Approximately 25% of cardiac surgical patients with postoperative hyperbilirubinemia die within 30 days of the operation.” Death typically results from overwhelming endotoxemia (ie, sepsis) and multisystem organ failure. Hepatic reticuloendothelial system (RES) uptake and detoxification of endotoxin is the major mechanism limiting the magnitude and duration of systemic endotoxemia.” Beside Kupffer cells (the largest constituent of the RES), hepatocytes also clear endotoxin,14 leukotrienes,” and tumor necrosis factor.16 A recent study indicates that during the hypothermie phase of CPB and for sometime thereafter, there is a significant decline in hepatic venous oxygen tension associated with a sixfold increase in hepatic venous lactate concentration.” These data suggest the presence of splanchnic ischemia.” Studies performed on noncardiac surgical patients demonstrate that hepatic dysfunction greatly influences the severity and markedly impedes the resolution of sepsis-induced multiple organ damage.18.1Y There are no simple solutions to the management of the patient with refractory hypotension. However, we do suggest that adequacy of splanchnic oxygen delivery be monitored whenever angiotensin 11 is administered. One method of determining this is by measurement of gastric intramucosal pH (Tonomitor, Tonometrics Inc, Worcester, MA).“,‘” Laurence Landow, MD

Department of Anesthesiology University of Massachusetts Medical Center Worcester, MA REFERENCES 1. Thaker UN, Geary VM, Chambers PC, Sheikh F: Low systemic vascular resistance during cardiac surgery: Case reports, brief review, and management with angiotensin 11. J Cardiothorac Anesth 4:360-363,199O 2. Geary VM, Thaker UN, Chalmers PC, Sheikh F: The use of angiotensin 11 to treat profound hypotension in a patient taking amiodarone. J Cardiothorac Anesth 4:364-368, 1990 3. Fink MP, Homer LD, Fletcher JR: Diminished pressor response to exogenous norepinephrine and angiotensin 11 in septic unanesthetized rats: Evidente for a prostaglandin mediated effect. J Surg Res 38:335-342,1985 4. Levine FH, Philbin DM, Kono K, et al: Plasma vasopressin levels and urinary sodium excretion during cardiopulmonary bypass with and without pulsatile flow. Ann Thorac Surg32:63-67,198l 5. Taylor KM, Bain WH, Morton JJ: The role of angiotensin 11 in the development of peripheral vasoconstriction during openheart surgery. Am Heart J 100:935-937,198O 6. Taylor KM, Bain WH, Russell M, et al: Peripheral vascular resistance and angiotensin 11 levels during pulsatile and nonpulsatile cardiopulmonary bypass. Thorax 34:594-598, 1979

7. Richardson PDI, Wirthington PG: The effects of intraportal injection of noradrenaline, adrenaline, vasopressin, and angiotensin on the hepatic portal vascular bed of the dog: Marked tachyphylaxis to angiotensin. Br J Pharmacol59:293-301, 1977 8. Hampton WW, Townsend MC, Schirmer WJ, et al: Effective hepatic blood flow during cardiopulmonary bypass. Arch Surg 124:458-459, 1989 9. Aranha GV, Pickleman J, Pifarre R, et al: The reasons for gastrointestinal consultation after cardiac surgev. Am Surg 50:301330,1984 10. Kingsley DPE: Hepatic damage following profound hypothermia and extracorporeal circulation in man. Thorax 21:91-98,1966 ll. Lockey E, Mcintyre N, Ross DN, et al: Early jaundice after open heart surgery. Thorax 22:165-169,1967 12. Collins JD, Bassendine MF, Ferner R: Incidence and prognostic importante of jaundice after cardiopulmonary bypass surgery. Lancet 1:1119-1122,1983 13. Wardle EN: Kupffer cells and their function. Liver 7:63-75, 1987 14. Pranning-van Dalen DP, Brouwer A, Knook DL: Clearance

Journal of Cardiothoracic and Vascular Anesthesia, Vol 5, NO 1 (February), 1991: pp 97-103

97

98

LETTERS TO THE EDITOR

capacity of rat liver Kupffer, endothelial, and parenchymal cells. Gastroenterology 81:1036-1044, 1981 15. Hagmann W, Denzlinger C, Keppler D: Role of peptide leukotrienes and their hepatobiliary elimination in endotoxin action. Circ Shock 14:223-235, 1984 16. Beutler BA, Milsark IW, Cerami A: Cachectin/tumor necrosis factor: Production, distribution, and metabolic fate in vivo. J Immunol 135:3972-3977,198s 17. Landow L, Phillips D, Prevost D, et al: Correlation between gastric intramucosal pH, hepatic venous lactate, and oxygen saturation. Chest 48:533, 1990

Simulation

18. Matuschak CM, Rinaldo JE, Pinsky MR, et al: Effect of end-stage liver failure on the incidence and resolution of the adult respiratory distress syndrome. J Crit Care 2:162-173, 1987 19. Fine J, Rutenberg S, Scbweinburg FB: The role of the reticuloendothelial system in hemorrhagic shock. J Exptl Med 110547-569, 1959 20. Fiddian-Green RG: Studies in splanchnic ischemia and multiple organ failure, in Marston A, Buckley GB, Fiddian-Green RG, et al (eds): Splanchnic Ischemia and Multiple Organ Failure. St Louis, MO, Mosby, 1989, p 352

of Cardiovascular

Oxygen Balance

To the Editor:

The abstract from the paper of Schwid et al states that “. . . tachycardia leads to reduced myocardial oxygen supply and increased demand.“’ It is now a well-established fact that tachycardia, in the presence of coronary artery stenosis, is associated with myocardial ischemia.’ However, there seems to be little reason to believe that tachycardia is associated with an increase in oxygen demand (MVO,), and a paper by Laver questions the validity of this time-honored teaching. Laver reminded the reader of a paper published in German in which the authors indicated that the relationship between MVO, and heart rate (HR) exists only if the volume of the heart remains constant.4 There also are a number of papers that confirm the fact that the MVO, per beat and/or per muscle mass remains constant, or may even decrease during tachycardia.“.” Furthermore, calculations from Fig 5 of the Schwid paper indicate that the MVO, remained constant if expressed per beat. The MVO, may wel1 change during tachycardia if the ventricular volume increases, as could occur during acute failure. Similarly, if the contractile state is increased (increase in the end-systolic pressure-volume relationship), as occurs during an adrenergic-mediated response, the oxygen consumption wil1 increase in relation to the increase in contractility (and HR). Furthermore, if the so-called Treppe effect is in operation, one could expect the MVO, to increase as well. However, these provisos are never mentioned when it is stated that tachycardia increases MVO,. If the tachycardiaper se appears not to cause the increase in MVO,, it is reasonable to suggest that the ischemia is most probably related to the decrease in perfusion time associated with an increase in HR. Should we not consider myocardial energetics on a beat-by-beat principle rather than a minute-by-minute basis? Clearly, the heart, an obligate aerobic muscle, wil1 not wait a minute for perfusion to restore the oxygen deficit incurred during the previous minute. Therefore, 1 would like to suggest that we put the effect of a tachycardia on the oxygen supply side of the supply-demand balance when myocardial oxygenation is discussed. André Coetzee, MD, PhD, FFA (SA), FFARCS

Professor and Chairman Department of Anesthesiology University of Stellenbosch Tygerberg, South Africa REFERENCES

1. Schwid H, Buffington C, Strum DP: Computer simulation of the hemodynamic determinants of myocardial oxygen supply and demand. J Cardiothorac Anesth 4:5-18,199O 2. Slogoff S, Keats AS: Does perioperative myocardial ischemia lead to myocardial infarction? Anesthesiology 62:107-114,1985 3. Laver M: Myocardial ischemia. Dilemma between information available and information demand. Br Heart J 50:222-230, 1983 4. Rohde E: Uber den Einfluss der mechanischen dedingungen auf die Tatigkeit und den sauerstoffverbrauch des warmbluterherzens. Arch Exp Pathol Pharmakol68:401-434,1912 5. Maxwell CM, Castillo CA, White DH, et al: Induced tachycar-

dia: Its effect upon the coronary hemodynamics, myocardial metabolism, and cardiac efficience in the intact dog. J Clin Invest 37:1413-1418,1958 6. Coetzee A, Holland D, Foëx P, et al: Myocardial ischaemia during tachycardia-Not due to an increase in myocardial oxygen demand. S Afr Med J 67:496-499,1985 7. Forrester JS, Helfant RH, Patemac A: Atria1 pacing in coronary heart disease. Effect on hemodynamic metabolism and coronary circulation. Am J Cardiol27:237-243, 1971 8. Neil WA, Phelps NC, Oxendine JM, et al: Effect of heart rate on coronary blood flow distribution in dogs. Am J Cardiol 32:306312,1973