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Published in: Intensive Care Medicine 7/2011

01-07-2011 | Experimental

Temporal changes in tissue cardiorespiratory function during faecal peritonitis

Authors: Alex Dyson, Alain Rudiger, Mervyn Singer

Published in: Intensive Care Medicine | Issue 7/2011

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Abstract

Purpose

Sepsis affects both macro- and micro-circulatory transport of oxygen to tissues, causing regional hypoxia. However, this relationship is poorly characterized with respect to inter-organ variability, disease severity and the evolution to organ dysfunction. We hypothesized that an early circulatory insult precedes the development of organ dysfunction, and is more severe in predicted non-survivors. Consequently, we assessed temporal changes in myocardial function and regional tissue oxygenation in peripheral and deep organs in a rat model of faecal peritonitis. We also examined the utility of a dynamic oxygen challenge test to assess the microcirculation.

Methods

Awake, tethered, fluid-resuscitated male Wistar rats were randomized to receive intraperitoneal injection of faecal slurry, or to act as controls. At either 6 or 24 h post insult, rats were anaesthetized and underwent echocardiography, arterial cannulation and placement of tissue oxygen probes in peripheral (muscle, bladder) and deep (liver and renal cortex) organ beds. Measurements were repeated during fluid loading and an oxygen challenge test (administration of high oxygen concentrations).

Results

Early sepsis (6 h) was characterized by a fall in global oxygen delivery with concurrent decreases in muscle, renal cortical and, especially, liver tissue PO2. By contrast, during established sepsis (24 h), myocardial and circulatory function had largely recovered despite increasing clinical unwellness, hyperlactataemia and biochemical evidence of organ failure. O2 challenge revealed an early depression of response that, by 24 h, had improved in all organ beds bar the kidney.

Conclusions

This long-term septic model exhibited an early decline in tissue oxygenation, the degree of which related to predicted mortality. Clinical and biochemical deterioration, however, progressed despite cardiovascular recovery. Early circulatory dysfunction may thus be an important trigger for downstream processes that result in multi-organ failure. Furthermore, the utility of tissue PO2 monitoring to highlight the local oxygen supply–demand balance, and dynamic O2 challenge testing to assess microcirculatory function merit further investigation.
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Literature
1.
go back to reference Rudiger A, Singer M (2007) Mechanisms of sepsis-induced cardiac dysfunction. Crit Care Med 35:1599–1608PubMedCrossRef Rudiger A, Singer M (2007) Mechanisms of sepsis-induced cardiac dysfunction. Crit Care Med 35:1599–1608PubMedCrossRef
2.
go back to reference De Backer D, Creteur J, Preiser JC, Dubois MJ, Vincent JL (2002) Microvascular blood flow is altered in patients with sepsis. Am J Respir Crit Care Med 166:98–104PubMedCrossRef De Backer D, Creteur J, Preiser JC, Dubois MJ, Vincent JL (2002) Microvascular blood flow is altered in patients with sepsis. Am J Respir Crit Care Med 166:98–104PubMedCrossRef
3.
go back to reference Brealey D, Brand M, Hargreaves I, Heales S, Land J, Smolenski R, Davies NA, Cooper CE, Singer M (2002) Association between mitochondrial dysfunction and severity and outcome of septic shock. Lancet 360:219–223PubMedCrossRef Brealey D, Brand M, Hargreaves I, Heales S, Land J, Smolenski R, Davies NA, Cooper CE, Singer M (2002) Association between mitochondrial dysfunction and severity and outcome of septic shock. Lancet 360:219–223PubMedCrossRef
4.
go back to reference Rivers E, Nguyen B, Havstad S, Ressler J, Muzzin A, Knoblich B, Peterson E, Tomlanovich M (2001) Early goal-directed therapy in the treatment of severe sepsis and septic shock. N Engl J Med 345:1368–1377PubMedCrossRef Rivers E, Nguyen B, Havstad S, Ressler J, Muzzin A, Knoblich B, Peterson E, Tomlanovich M (2001) Early goal-directed therapy in the treatment of severe sepsis and septic shock. N Engl J Med 345:1368–1377PubMedCrossRef
5.
go back to reference Hayes MA, Timmins AC, Yau EH, Palazzo M, Watson D, Hinds CJ (1997) Oxygen transport patterns in patients with sepsis syndrome or septic shock: influence of treatment and relationship to outcome. Crit Care Med 25:926–936PubMedCrossRef Hayes MA, Timmins AC, Yau EH, Palazzo M, Watson D, Hinds CJ (1997) Oxygen transport patterns in patients with sepsis syndrome or septic shock: influence of treatment and relationship to outcome. Crit Care Med 25:926–936PubMedCrossRef
6.
go back to reference Gattinoni L, Brazzi L, Pelosi P, Latini R, Tognoni G, Pesenti A, Fumagalli R (1995) A trial of goal-oriented hemodynamic therapy in critically ill patients. SvO2 Collaborative Group. N Engl J Med 333:1025–1032PubMedCrossRef Gattinoni L, Brazzi L, Pelosi P, Latini R, Tognoni G, Pesenti A, Fumagalli R (1995) A trial of goal-oriented hemodynamic therapy in critically ill patients. SvO2 Collaborative Group. N Engl J Med 333:1025–1032PubMedCrossRef
7.
go back to reference Rudiger A, Dyson A, Taylor V, Stidwill R, Protti A, Hughes S, Pellerin D, Singer M (2011) Cardiac dysfunction during early sepsis predicts outcome in a rat model of fecal peritonitis. Shock (in press) Rudiger A, Dyson A, Taylor V, Stidwill R, Protti A, Hughes S, Pellerin D, Singer M (2011) Cardiac dysfunction during early sepsis predicts outcome in a rat model of fecal peritonitis. Shock (in press)
8.
go back to reference Dyson A, Stidwill R, Taylor V, Singer M (2007) Tissue oxygen monitoring in rodent models of shock. Am J Physiol Heart Circ Physiol 293:H526–H533PubMedCrossRef Dyson A, Stidwill R, Taylor V, Singer M (2007) Tissue oxygen monitoring in rodent models of shock. Am J Physiol Heart Circ Physiol 293:H526–H533PubMedCrossRef
9.
go back to reference Dyson A, Stidwill R, Taylor V, Singer M (2009) The impact of inspired oxygen concentration on tissue oxygenation during progressive haemorrhage. Intensive Care Med 35:1783–1791PubMedCrossRef Dyson A, Stidwill R, Taylor V, Singer M (2009) The impact of inspired oxygen concentration on tissue oxygenation during progressive haemorrhage. Intensive Care Med 35:1783–1791PubMedCrossRef
10.
go back to reference Boekstegers P, Weidenhofer S, Pilz G, Werdan K (1991) Peripheral oxygen availability within skeletal muscle in sepsis and septic shock: comparison to limited infection and cardiogenic shock. Infection 19:317–323PubMedCrossRef Boekstegers P, Weidenhofer S, Pilz G, Werdan K (1991) Peripheral oxygen availability within skeletal muscle in sepsis and septic shock: comparison to limited infection and cardiogenic shock. Infection 19:317–323PubMedCrossRef
11.
go back to reference Sair M, Etherington PJ, Peter WC, Evans TW (2001) Tissue oxygenation and perfusion in patients with systemic sepsis. Crit Care Med 29:1343–1349PubMedCrossRef Sair M, Etherington PJ, Peter WC, Evans TW (2001) Tissue oxygenation and perfusion in patients with systemic sepsis. Crit Care Med 29:1343–1349PubMedCrossRef
12.
go back to reference Levy B, Gibot S, Franck P, Cravoisy A, Bollaert PE (2005) Relation between muscle Na + K + ATPase activity and raised lactate concentrations in septic shock: a prospective study. Lancet 365:871–875PubMedCrossRef Levy B, Gibot S, Franck P, Cravoisy A, Bollaert PE (2005) Relation between muscle Na + K + ATPase activity and raised lactate concentrations in septic shock: a prospective study. Lancet 365:871–875PubMedCrossRef
13.
go back to reference Rosser DM, Stidwill RP, Jacobson D, Singer M (1995) Oxygen tension in the bladder epithelium rises in both high and low cardiac output endotoxemic sepsis. J Appl Physiol 79:1878–1882PubMed Rosser DM, Stidwill RP, Jacobson D, Singer M (1995) Oxygen tension in the bladder epithelium rises in both high and low cardiac output endotoxemic sepsis. J Appl Physiol 79:1878–1882PubMed
14.
go back to reference Rosser DM, Stidwill RP, Jacobson D, Singer M (1996) Cardiorespiratory and tissue oxygen dose response to rat endotoxemia. Am J Physiol 271:H891–H895PubMed Rosser DM, Stidwill RP, Jacobson D, Singer M (1996) Cardiorespiratory and tissue oxygen dose response to rat endotoxemia. Am J Physiol 271:H891–H895PubMed
15.
go back to reference Singer M, De Santis V, Vitale D, Jeffcoate W (2004) Multiorgan failure is an adaptive, endocrine-mediated, metabolic response to overwhelming systemic inflammation. Lancet 364:545–548PubMedCrossRef Singer M, De Santis V, Vitale D, Jeffcoate W (2004) Multiorgan failure is an adaptive, endocrine-mediated, metabolic response to overwhelming systemic inflammation. Lancet 364:545–548PubMedCrossRef
16.
go back to reference Brealey D, Karyampudi S, Jacques TS, Novelli M, Stidwill R, Taylor V, Smolenski RT, Singer M (2004) Mitochondrial dysfunction in a long-term rodent model of sepsis and organ failure. Am J Physiol Regul Integr Comp Physiol 286:R491–R497PubMedCrossRef Brealey D, Karyampudi S, Jacques TS, Novelli M, Stidwill R, Taylor V, Smolenski RT, Singer M (2004) Mitochondrial dysfunction in a long-term rodent model of sepsis and organ failure. Am J Physiol Regul Integr Comp Physiol 286:R491–R497PubMedCrossRef
17.
go back to reference Slama M, Susic D, Varagic J, Ahn J, Frohlich ED (2003) Echocardiographic measurement of cardiac output in rats. Am J Physiol Heart Circ Physiol 284:H691–H697PubMed Slama M, Susic D, Varagic J, Ahn J, Frohlich ED (2003) Echocardiographic measurement of cardiac output in rats. Am J Physiol Heart Circ Physiol 284:H691–H697PubMed
18.
go back to reference Iwase M, Yokota M, Kitaichi K, Wang L, Takagi K, Nagasaka T, Izawa H, Hasegawa T (2001) Cardiac functional and structural alterations induced by endotoxin in rats: importance of platelet-activating factor. Crit Care Med 29:609–617PubMedCrossRef Iwase M, Yokota M, Kitaichi K, Wang L, Takagi K, Nagasaka T, Izawa H, Hasegawa T (2001) Cardiac functional and structural alterations induced by endotoxin in rats: importance of platelet-activating factor. Crit Care Med 29:609–617PubMedCrossRef
19.
go back to reference Hollenberg SM, Dumasius A, Easington C, Colilla SA, Neumann A, Parrillo JE (2001) Characterization of a hyperdynamic murine model of resuscitated sepsis using echocardiography. Am J Respir Crit Care Med 164:891–895PubMed Hollenberg SM, Dumasius A, Easington C, Colilla SA, Neumann A, Parrillo JE (2001) Characterization of a hyperdynamic murine model of resuscitated sepsis using echocardiography. Am J Respir Crit Care Med 164:891–895PubMed
20.
go back to reference Yu M, Morita SY, Daniel SR, Chapital A, Waxman K, Severino R (2006) Transcutaneous pressure of oxygen: a noninvasive and early detector of peripheral shock and outcome. Shock 26:450–456PubMedCrossRef Yu M, Morita SY, Daniel SR, Chapital A, Waxman K, Severino R (2006) Transcutaneous pressure of oxygen: a noninvasive and early detector of peripheral shock and outcome. Shock 26:450–456PubMedCrossRef
21.
go back to reference Yu M, Chapital A, Ho HC, Wang J, Takanishi D Jr (2007) A prospective randomized trial comparing oxygen delivery versus transcutaneous pressure of oxygen values as resuscitative goals. Shock 27:615–622PubMedCrossRef Yu M, Chapital A, Ho HC, Wang J, Takanishi D Jr (2007) A prospective randomized trial comparing oxygen delivery versus transcutaneous pressure of oxygen values as resuscitative goals. Shock 27:615–622PubMedCrossRef
22.
go back to reference Sakr Y, Dubois MJ, De Backer D, Creteur J, Vincent JL (2004) Persistent microcirculatory alterations are associated with organ failure and death in patients with septic shock. Crit Care Med 32:1825–1831PubMedCrossRef Sakr Y, Dubois MJ, De Backer D, Creteur J, Vincent JL (2004) Persistent microcirculatory alterations are associated with organ failure and death in patients with septic shock. Crit Care Med 32:1825–1831PubMedCrossRef
23.
go back to reference Levy RJ, Piel DA, Acton PD, Zhou R, Ferrari VA, Karp JS, Deutschman CS (2005) Evidence of myocardial hibernation in the septic heart. Crit Care Med 33:2752–2756PubMedCrossRef Levy RJ, Piel DA, Acton PD, Zhou R, Ferrari VA, Karp JS, Deutschman CS (2005) Evidence of myocardial hibernation in the septic heart. Crit Care Med 33:2752–2756PubMedCrossRef
24.
go back to reference Ellrodt AG, Riedinger MS, Kimchi A, Berman DS, Maddahi J, Swan HJ, Murata GH (1985) Left ventricular performance in septic shock: reversible segmental and global abnormalities. Am Heart J 110:402–409PubMedCrossRef Ellrodt AG, Riedinger MS, Kimchi A, Berman DS, Maddahi J, Swan HJ, Murata GH (1985) Left ventricular performance in septic shock: reversible segmental and global abnormalities. Am Heart J 110:402–409PubMedCrossRef
25.
go back to reference Kontani M, Izumiya Y, Shimizu M, Yasuma K, Inada A, Ohta H, Ikeda T (2003) Acute reversible myocardial depression associated with sepsis. Intern Med 42:60–65PubMedCrossRef Kontani M, Izumiya Y, Shimizu M, Yasuma K, Inada A, Ohta H, Ikeda T (2003) Acute reversible myocardial depression associated with sepsis. Intern Med 42:60–65PubMedCrossRef
26.
go back to reference VanderMeer TJ, Wang H, Fink MP (1995) Endotoxemia causes ileal mucosal acidosis in the absence of mucosal hypoxia in a normodynamic porcine model of septic shock. Crit Care Med 23:1217–1226PubMedCrossRef VanderMeer TJ, Wang H, Fink MP (1995) Endotoxemia causes ileal mucosal acidosis in the absence of mucosal hypoxia in a normodynamic porcine model of septic shock. Crit Care Med 23:1217–1226PubMedCrossRef
27.
go back to reference James PE, Madhani M, Roebuck W, Jackson SK, Swartz HM (2002) Endotoxin-induced liver hypoxia: defective oxygen delivery versus oxygen consumption. Nitric Oxide 6:18–28PubMedCrossRef James PE, Madhani M, Roebuck W, Jackson SK, Swartz HM (2002) Endotoxin-induced liver hypoxia: defective oxygen delivery versus oxygen consumption. Nitric Oxide 6:18–28PubMedCrossRef
28.
go back to reference James PE, Bacic G, Grinberg OY, Goda F, Dunn JF, Jackson SK, Swartz HM (1996) Endotoxin-induced changes in intrarenal pO2, measured by in vivo electron paramagnetic resonance oximetry and magnetic resonance imaging. Free Radic Biol Med 21:25–34PubMedCrossRef James PE, Bacic G, Grinberg OY, Goda F, Dunn JF, Jackson SK, Swartz HM (1996) Endotoxin-induced changes in intrarenal pO2, measured by in vivo electron paramagnetic resonance oximetry and magnetic resonance imaging. Free Radic Biol Med 21:25–34PubMedCrossRef
29.
go back to reference Anning PB, Sair M, Winlove CP, Evans TW (1999) Abnormal tissue oxygenation and cardiovascular changes in endotoxemia. Am J Respir Crit Care Med 159:1710–1715PubMed Anning PB, Sair M, Winlove CP, Evans TW (1999) Abnormal tissue oxygenation and cardiovascular changes in endotoxemia. Am J Respir Crit Care Med 159:1710–1715PubMed
30.
go back to reference Sair M, Etherington PJ, Curzen NP, Winlove CP, Evans TW (1996) Tissue oxygenation and perfusion in endotoxemia. Am J Physiol 271:H1620–H1625PubMed Sair M, Etherington PJ, Curzen NP, Winlove CP, Evans TW (1996) Tissue oxygenation and perfusion in endotoxemia. Am J Physiol 271:H1620–H1625PubMed
31.
go back to reference Vallet B, Lund N, Curtis SE, Kelly D, Cain SM (1994) Gut and muscle tissue PO2 in endotoxemic dogs during shock and resuscitation. J Appl Physiol 76:793–800PubMed Vallet B, Lund N, Curtis SE, Kelly D, Cain SM (1994) Gut and muscle tissue PO2 in endotoxemic dogs during shock and resuscitation. J Appl Physiol 76:793–800PubMed
32.
go back to reference Dahn MS, Wilson RF, Lange P, Stone A, Jacobs LA (1990) Hepatic parenchymal oxygen tension following injury and sepsis. Arch Surg 125:441–443PubMed Dahn MS, Wilson RF, Lange P, Stone A, Jacobs LA (1990) Hepatic parenchymal oxygen tension following injury and sepsis. Arch Surg 125:441–443PubMed
33.
go back to reference Dahn MS, Mitchell RA, Lange MP, Smith S, Jacobs LA (1995) Hepatic metabolic response to injury and sepsis. Surgery 117:520–530PubMedCrossRef Dahn MS, Mitchell RA, Lange MP, Smith S, Jacobs LA (1995) Hepatic metabolic response to injury and sepsis. Surgery 117:520–530PubMedCrossRef
34.
go back to reference Rahal L, Garrido AG, Cruz RJ Jr, Rocha e Silva M, Poli-de-Figueiredo LF (2006) Systemic and regional hemodynamic effects of enalaprilat infusion in experimental normotensive sepsis. Braz J Med Biol Res 39:1205–1215PubMedCrossRef Rahal L, Garrido AG, Cruz RJ Jr, Rocha e Silva M, Poli-de-Figueiredo LF (2006) Systemic and regional hemodynamic effects of enalaprilat infusion in experimental normotensive sepsis. Braz J Med Biol Res 39:1205–1215PubMedCrossRef
35.
go back to reference Subramanian RM, Chandel N, Budinger GR, Schumacker PT (2007) Hypoxic conformance of metabolism in primary rat hepatocytes: a model of hepatic hibernation. Hepatology 45:455–464PubMedCrossRef Subramanian RM, Chandel N, Budinger GR, Schumacker PT (2007) Hypoxic conformance of metabolism in primary rat hepatocytes: a model of hepatic hibernation. Hepatology 45:455–464PubMedCrossRef
36.
go back to reference De Backer D, Ortiz JA, Salgado D (2010) Coupling microcirculation to systemic hemodynamics. Curr Opin Crit Care 16:250–254PubMedCrossRef De Backer D, Ortiz JA, Salgado D (2010) Coupling microcirculation to systemic hemodynamics. Curr Opin Crit Care 16:250–254PubMedCrossRef
37.
go back to reference Ellis CG, Jagger J, Sharpe M (2005) The microcirculation as a functional system. Crit Care 9:S3–S8PubMedCrossRef Ellis CG, Jagger J, Sharpe M (2005) The microcirculation as a functional system. Crit Care 9:S3–S8PubMedCrossRef
39.
go back to reference Ince C, Sinaasappel M (1999) Microcirculatory oxygenation and shunting in sepsis and shock. Crit Care Med 27:1369–1377PubMedCrossRef Ince C, Sinaasappel M (1999) Microcirculatory oxygenation and shunting in sepsis and shock. Crit Care Med 27:1369–1377PubMedCrossRef
40.
go back to reference Goeckenjan G, Strasser K (1977) Relation of transcutaneous to arterial pO2 in hypoxaemia, normoxaemia and hyperoxaemia. Investigations in adults with normal circulation and in patients with circulatory insufficiency. Biotelemetry 4:77–87PubMed Goeckenjan G, Strasser K (1977) Relation of transcutaneous to arterial pO2 in hypoxaemia, normoxaemia and hyperoxaemia. Investigations in adults with normal circulation and in patients with circulatory insufficiency. Biotelemetry 4:77–87PubMed
41.
go back to reference Tremper KK, Waxman K, Shoemaker WC (1979) Effects of hypoxia and shock on transcutaneous PO2 values in dogs. Crit Care Med 7:526–531PubMedCrossRef Tremper KK, Waxman K, Shoemaker WC (1979) Effects of hypoxia and shock on transcutaneous PO2 values in dogs. Crit Care Med 7:526–531PubMedCrossRef
42.
go back to reference Thurau K, Boylan JW (1976) Acute renal success. The unexpected logic of oliguria in acute renal failure. Am J Med 61:308–315PubMedCrossRef Thurau K, Boylan JW (1976) Acute renal success. The unexpected logic of oliguria in acute renal failure. Am J Med 61:308–315PubMedCrossRef
Metadata
Title
Temporal changes in tissue cardiorespiratory function during faecal peritonitis
Authors
Alex Dyson
Alain Rudiger
Mervyn Singer
Publication date
01-07-2011
Publisher
Springer-Verlag
Published in
Intensive Care Medicine / Issue 7/2011
Print ISSN: 0342-4642
Electronic ISSN: 1432-1238
DOI
https://doi.org/10.1007/s00134-011-2227-z

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