Skip to main content
Top
Published in: Intensive Care Medicine 3/2005

01-03-2005 | Experimental

The haemodynamic and metabolic effects of epinephrine in experimental hyperdynamic septic shock

Authors: David Di Giantomasso, Rinaldo Bellomo, Clive N. May

Published in: Intensive Care Medicine | Issue 3/2005

Login to get access

Abstract

Objective

To study the effect of epinephrine (EPI) infusion on vital organ blood flow and metabolic variables during sepsis.

Design and setting

Randomised placebo-controlled animal trial in an animal laboratory.

Animals

Seven merino cross-ewes.

Interventions

Chronic implantation of flow probes (aorta, renal, mesenteric and coronary artery and sagittal sinus). Induction of sepsis by intravenous injection of E. coli. Random allocation of sheep to EPI (0.4 µg kg−1 min−1) or vehicle for 6 h.

Measurements and results

E. coli induced hypotension and hyperlactataemia and increased cardiac output, renal, mesenteric and coronary blood flows. Compared to vehicle, EPI restored mean arterial blood pressure (69 vs. 86 mmHg) and further increased cardiac output (6.4 vs. 7.1 l/min). EPI, however, decreased renal blood flow (330 vs. 247 ml/min) and renal conductance. EPI also reduced mesenteric and coronary conductance without changes in flows. Compared to vehicle, EPI increased urine output (293 vs. 544 ml/6 h) but not creatinine clearance. EPI increased lactate (1.8 vs. 15.7 mmol/l) with accompanying acidosis (serum bicarbonate: 25.2 vs. 15.7 mmol/l), hyperglycaemia (2.6 vs. 13.5 mmol/l) and hypokalaemia (4.3 vs. 3.0 mmol/l).

Conclusions

Hyperdynamic sepsis increased blood flow to heart, gut and kidney. Although EPI infusion further increased cardiac output, blood pressure and myocardial performance, it was also associated with potent metabolic effects, decreased mesenteric, coronary and renal conductance and a significant reduction in renal blood flow.
Literature
1.
go back to reference Moran JL, O’Fathartaigh MS, Peisach AR et al (1993) Epinephrine as an inotropic agent in septic shock: a dose-profile analysis. Crit Care Med 21:70–77 Moran JL, O’Fathartaigh MS, Peisach AR et al (1993) Epinephrine as an inotropic agent in septic shock: a dose-profile analysis. Crit Care Med 21:70–77
2.
go back to reference Bollaert PE, Bauer P, Audibert G. Lambert H, Larcan A (1990) Effects of epinephrine on haemodynamics and oxygen metabolism in dopamine resistant septic shock. Chest 98:949–953PubMed Bollaert PE, Bauer P, Audibert G. Lambert H, Larcan A (1990) Effects of epinephrine on haemodynamics and oxygen metabolism in dopamine resistant septic shock. Chest 98:949–953PubMed
3.
go back to reference Lipman J, Roux A, Kraus P (1991) Vasoconstrictor effects of adrenaline in human septic shock. Anaesth Intensive Care 19:61–65 Lipman J, Roux A, Kraus P (1991) Vasoconstrictor effects of adrenaline in human septic shock. Anaesth Intensive Care 19:61–65
4.
go back to reference Mackenzie SJ, Kapadia F, Nimmo GR, Armstrong IR, Grant IS (1991) Adrenaline in treatment of septic shock: effects on hemodynamics and oxygen transport. Intensive Care Med 17:36–39 Mackenzie SJ, Kapadia F, Nimmo GR, Armstrong IR, Grant IS (1991) Adrenaline in treatment of septic shock: effects on hemodynamics and oxygen transport. Intensive Care Med 17:36–39
5.
go back to reference Day NPJ, Phu NH, Bethell DP, Mai NTH, Chau TTH, Hien TT, White NJ (1996) The effects of dopamine and adrenaline infusions on acid-base balance and systemic haemodynamics in severe infection. Lancet 348:219–223 Day NPJ, Phu NH, Bethell DP, Mai NTH, Chau TTH, Hien TT, White NJ (1996) The effects of dopamine and adrenaline infusions on acid-base balance and systemic haemodynamics in severe infection. Lancet 348:219–223
6.
go back to reference Meier-Hellmann A, Reinhart K (1995) Effects of catecholamines on regional perfusion and oxygenation in critically ill patients. Acta Anaesthesiol Scand 39 [Suppl 107]:239–248 Meier-Hellmann A, Reinhart K (1995) Effects of catecholamines on regional perfusion and oxygenation in critically ill patients. Acta Anaesthesiol Scand 39 [Suppl 107]:239–248
7.
go back to reference Rudis MI, Basha MA, Zarowitz BJ (1996) Is it time to reposition vasopressors and inotropes in sepsis? Crit Care Med 24:525–537 Rudis MI, Basha MA, Zarowitz BJ (1996) Is it time to reposition vasopressors and inotropes in sepsis? Crit Care Med 24:525–537
8.
go back to reference Meier-Hellmann A, Reinhart K, Bredle DL, Specht M, Spies CD, Hannemann L (1997) Epinephrine impairs splanchnic perfusion in septic shock. Crit Care Med 25:399–404CrossRefPubMed Meier-Hellmann A, Reinhart K, Bredle DL, Specht M, Spies CD, Hannemann L (1997) Epinephrine impairs splanchnic perfusion in septic shock. Crit Care Med 25:399–404CrossRefPubMed
9.
go back to reference Levy B, Bollaert PE, Charpentier C, Nace L, Audibert G, Bauer P, Nabet P, Larcan A (1997) Comparison of norepinephrine and dobutamine to epinephrine for hemodynamics, lactate, metabolism and gastric tonometry variables in septic shock: a prospective, randomised study. Intensive Care Med 23:282–287CrossRefPubMed Levy B, Bollaert PE, Charpentier C, Nace L, Audibert G, Bauer P, Nabet P, Larcan A (1997) Comparison of norepinephrine and dobutamine to epinephrine for hemodynamics, lactate, metabolism and gastric tonometry variables in septic shock: a prospective, randomised study. Intensive Care Med 23:282–287CrossRefPubMed
10.
go back to reference Grant DA, Franzini C, Wild J, Walker AM (1995) Continuous measurement of blood flow in the superior sagittal sinus of the lamb. Am J Physiol 269:R274–279 Grant DA, Franzini C, Wild J, Walker AM (1995) Continuous measurement of blood flow in the superior sagittal sinus of the lamb. Am J Physiol 269:R274–279
11.
go back to reference Bednarik JA, May CN (1995) Evaluation of a transit-time system for the chronic measurement of blood flow in conscious sheep. J Appl Physiol 78:524–530 Bednarik JA, May CN (1995) Evaluation of a transit-time system for the chronic measurement of blood flow in conscious sheep. J Appl Physiol 78:524–530
12.
go back to reference Matthews JNS, Altman DG, Campbell MJ et al (1990) Analysis of serial measurements in medical research. BMJ 300:230–235PubMed Matthews JNS, Altman DG, Campbell MJ et al (1990) Analysis of serial measurements in medical research. BMJ 300:230–235PubMed
13.
go back to reference Day NP, Phu NH, Mai NTH, et al (2000) Effects of dopamine and epinephrine infusions on renal hemodynamics in severe malaria and severe sepsis. Crit Care Med 28:1353–1362 Day NP, Phu NH, Mai NTH, et al (2000) Effects of dopamine and epinephrine infusions on renal hemodynamics in severe malaria and severe sepsis. Crit Care Med 28:1353–1362
14.
go back to reference Bersten AD, Rutten AJ (1995) Renovascular interaction of epinephrine, dopamine, and intraperitoneal sepsis. Crit Care Med 23:537–544 Bersten AD, Rutten AJ (1995) Renovascular interaction of epinephrine, dopamine, and intraperitoneal sepsis. Crit Care Med 23:537–544
15.
go back to reference Pawlik W, Sheperd AP, Jacobson ED (1975) Effect of vasoactive agents on intestinal oxygen consumption and blood flow in dogs. J Clin Invest 56:484–490 Pawlik W, Sheperd AP, Jacobson ED (1975) Effect of vasoactive agents on intestinal oxygen consumption and blood flow in dogs. J Clin Invest 56:484–490
16.
go back to reference Sheperd AP, Pawlik W, Mailman D, Burks TF, Jacobson ED (1976) Effects of vasoconstrictors on intestinal vascular resistance and oxygen extraction. Am J Physiol 230:298–303 Sheperd AP, Pawlik W, Mailman D, Burks TF, Jacobson ED (1976) Effects of vasoconstrictors on intestinal vascular resistance and oxygen extraction. Am J Physiol 230:298–303
17.
go back to reference Bersten AD, Hersch M, Cheung H, Rutledge FS, Sibbald WJ (1992) The effect of various sympathomimetics on the regional circulation in hyperdynamic sepsis. Surgery 112:549–561 Bersten AD, Hersch M, Cheung H, Rutledge FS, Sibbald WJ (1992) The effect of various sympathomimetics on the regional circulation in hyperdynamic sepsis. Surgery 112:549–561
18.
go back to reference Breslow MJ, Miller CF, Parker SD, Walman AT, Traystman RJ (1987) Effect of vasopressors on organ blood flow during endotoxin shock in pigs. Am J Physiol 252:H291–H300 Breslow MJ, Miller CF, Parker SD, Walman AT, Traystman RJ (1987) Effect of vasopressors on organ blood flow during endotoxin shock in pigs. Am J Physiol 252:H291–H300
19.
go back to reference Cunnion RE, Schaer GL, Parker M, Natanson C, Parrillo JE (1986) The coronary circulation in human septic shock. Circulation 73:637–644 Cunnion RE, Schaer GL, Parker M, Natanson C, Parrillo JE (1986) The coronary circulation in human septic shock. Circulation 73:637–644
20.
go back to reference Dhainaut J-F, Huyghebaert M-F, Monsallier JF et al (1987) Coronary hemodynamics and myocardial metabolism of lactate, free fatty acids, glucose, and ketones in patients with septic shock. Circulation 75:533–541 Dhainaut J-F, Huyghebaert M-F, Monsallier JF et al (1987) Coronary hemodynamics and myocardial metabolism of lactate, free fatty acids, glucose, and ketones in patients with septic shock. Circulation 75:533–541
21.
go back to reference Parker MM, Shelhamer JH, Bacharach SL et al (1984) Profound but reversible myocardial depression in patients with septic shock. Ann Intern Med 100:483–490PubMed Parker MM, Shelhamer JH, Bacharach SL et al (1984) Profound but reversible myocardial depression in patients with septic shock. Ann Intern Med 100:483–490PubMed
22.
go back to reference Lindberg L, Liao Q, Steen S (2000) The effects of epinephrine/norepinephrine on end tidal carbon dioxide concentration, coronary perfusion pressure and pulmonary arterial blood flow during cardiopulmonary resuscitation. Resuscitation 43:129–140 Lindberg L, Liao Q, Steen S (2000) The effects of epinephrine/norepinephrine on end tidal carbon dioxide concentration, coronary perfusion pressure and pulmonary arterial blood flow during cardiopulmonary resuscitation. Resuscitation 43:129–140
23.
go back to reference Lobato EB, Urdaneta F, Martin TD, Gravenstein N (2000) Effects of milrinone versus epinephrine on graded internal mammary artery flow after cardiopulmonary bypass. J Cardiothorac Vasc Anesth 14:9–11 Lobato EB, Urdaneta F, Martin TD, Gravenstein N (2000) Effects of milrinone versus epinephrine on graded internal mammary artery flow after cardiopulmonary bypass. J Cardiothorac Vasc Anesth 14:9–11
24.
go back to reference Jett GK, Arcici JM, Dorsey LM, Hatcher CR Jr, Guyton RA (1988) Vasoactive drug effect on blood flow in internal mammary artery and saphenous vein grafts J Am Coll Cardiol 11:1317–1324 Jett GK, Arcici JM, Dorsey LM, Hatcher CR Jr, Guyton RA (1988) Vasoactive drug effect on blood flow in internal mammary artery and saphenous vein grafts J Am Coll Cardiol 11:1317–1324
25.
go back to reference Myburgh JA, Upton RN, Grant C, Martinez A (1998) A comparison of the effects of norepinephrine, epinephrine, and dopamine on cerebral blood flow and oxygen utilization. Acta Neurochir Suppl (Wien) 71:19–21 Myburgh JA, Upton RN, Grant C, Martinez A (1998) A comparison of the effects of norepinephrine, epinephrine, and dopamine on cerebral blood flow and oxygen utilization. Acta Neurochir Suppl (Wien) 71:19–21
26.
go back to reference Myburgh JA, Upton RN, Grant C, Martinez A (2002) The cerebrovascular effects of adrenaline, noradrenaline and dopamine infusions under propofol and isofluorane anaesthesia in sheep. Anaesth Intensive Care 30:725–733 Myburgh JA, Upton RN, Grant C, Martinez A (2002) The cerebrovascular effects of adrenaline, noradrenaline and dopamine infusions under propofol and isofluorane anaesthesia in sheep. Anaesth Intensive Care 30:725–733
27.
go back to reference Brockman RP (1991) Effects of epinephrine on the net hepatic uptake of lactate, pyruvate, and glycerol in sheep. Can J Physiol Pharmacol 69:475–479 Brockman RP (1991) Effects of epinephrine on the net hepatic uptake of lactate, pyruvate, and glycerol in sheep. Can J Physiol Pharmacol 69:475–479
28.
go back to reference Rizza R, Haymond M, Cryer P, Gerich JE (1979) Differential effects of epinephrine on glucose production and disposal in man. Am J Physiol 237:E356–E362 Rizza R, Haymond M, Cryer P, Gerich JE (1979) Differential effects of epinephrine on glucose production and disposal in man. Am J Physiol 237:E356–E362
29.
go back to reference Issekutz B Jr (1985) Effect of epinephrine on carbohydrate metabolism in exercising dogs. Metabolism 34:457–464 Issekutz B Jr (1985) Effect of epinephrine on carbohydrate metabolism in exercising dogs. Metabolism 34:457–464
30.
go back to reference Rizza R, Haymond M, Miles JM, Verdonk CA, Cryer P, Gerich JE (1980) Effect of alpha-adrenergic stimulation and its blockade on glucose turnover in man. Am J Physiol 238:E467–E472 Rizza R, Haymond M, Miles JM, Verdonk CA, Cryer P, Gerich JE (1980) Effect of alpha-adrenergic stimulation and its blockade on glucose turnover in man. Am J Physiol 238:E467–E472
31.
go back to reference Ribes G, Blayac JP, Loubatieres-Mariani MM (1983) Differences between the effects of adrenaline and noradrenaline on insulin secretion in the dog. Diabetologia 24:107–112 Ribes G, Blayac JP, Loubatieres-Mariani MM (1983) Differences between the effects of adrenaline and noradrenaline on insulin secretion in the dog. Diabetologia 24:107–112
32.
go back to reference Berghe G van den, Wouters P, Weekers F, Verwaest C, Bruyninckx F, Schetz M, Vlasselaers D, Ferdinande P, Lauwers P, Bouillon R (2001) Intensive insulin therapy in the critically ill patients. N Engl J Med 345:1359–1367CrossRefPubMed Berghe G van den, Wouters P, Weekers F, Verwaest C, Bruyninckx F, Schetz M, Vlasselaers D, Ferdinande P, Lauwers P, Bouillon R (2001) Intensive insulin therapy in the critically ill patients. N Engl J Med 345:1359–1367CrossRefPubMed
33.
go back to reference Brown MJ, Brown DC, Murphy MB (1983) Hypokalemia from beta2-receptor stimulation by circulating epinephrine. N Engl J Med 309:1414–1419 Brown MJ, Brown DC, Murphy MB (1983) Hypokalemia from beta2-receptor stimulation by circulating epinephrine. N Engl J Med 309:1414–1419
34.
go back to reference Wahr JA, Parks R, Boisvert D, Comunale M, Fabian J, Ramsay J, Mangano DT (1999) Preoperative serum potassium levels and perioperative outcomes in cardiac surgery patients. Multicenter study of perioperative ischemia research group. JAMA 281:2203–2210 Wahr JA, Parks R, Boisvert D, Comunale M, Fabian J, Ramsay J, Mangano DT (1999) Preoperative serum potassium levels and perioperative outcomes in cardiac surgery patients. Multicenter study of perioperative ischemia research group. JAMA 281:2203–2210
35.
go back to reference Kolendorf K, Moller B (1974) Lactic acidosis in epinephrine poisoning. Acta Med Scand 196:465–466 Kolendorf K, Moller B (1974) Lactic acidosis in epinephrine poisoning. Acta Med Scand 196:465–466
36.
go back to reference Totaro RJ, Raper RF (1997) Epinephrine-induced lactic acidosis following cardiopulmonary bypass. Crit Care Med 25:1693–1699 Totaro RJ, Raper RF (1997) Epinephrine-induced lactic acidosis following cardiopulmonary bypass. Crit Care Med 25:1693–1699
37.
go back to reference Levy B, Mansart A, Bollaert PE, Franck P, Maille JP (2003) Effects of epinephrine and norepinephrine on hemodynamics, oxidative metabolism and organ energetics in endotoxemic rats. Intensive Care Med 29:292–300PubMed Levy B, Mansart A, Bollaert PE, Franck P, Maille JP (2003) Effects of epinephrine and norepinephrine on hemodynamics, oxidative metabolism and organ energetics in endotoxemic rats. Intensive Care Med 29:292–300PubMed
38.
go back to reference James JH, Luchette FA, McCarter FD, Fischer JE (1999) Lactate is an unreliable indicator of tissue hypoxia in injury or sepsis. Lancet 354:505–508CrossRefPubMed James JH, Luchette FA, McCarter FD, Fischer JE (1999) Lactate is an unreliable indicator of tissue hypoxia in injury or sepsis. Lancet 354:505–508CrossRefPubMed
39.
go back to reference Leone M, Vallet B, Teboul JL, Mateo J, Bastien O, Martin C (2004) Survey of the use of catecholamines by French physicians. Intensive Care Med 30:984–988 Leone M, Vallet B, Teboul JL, Mateo J, Bastien O, Martin C (2004) Survey of the use of catecholamines by French physicians. Intensive Care Med 30:984–988
Metadata
Title
The haemodynamic and metabolic effects of epinephrine in experimental hyperdynamic septic shock
Authors
David Di Giantomasso
Rinaldo Bellomo
Clive N. May
Publication date
01-03-2005
Publisher
Springer-Verlag
Published in
Intensive Care Medicine / Issue 3/2005
Print ISSN: 0342-4642
Electronic ISSN: 1432-1238
DOI
https://doi.org/10.1007/s00134-005-2580-x

Other articles of this Issue 3/2005

Intensive Care Medicine 3/2005 Go to the issue