Management of Myocardial Dysfunction in Severe Sepsis

ABSTRACT

Sepsis-induced cardiac dysfunction is a frequent and severe complication of septic shock. The mechanisms responsible for its development are complex and intricate. Echocardiography is the best method to make the diagnosis of cardiac dysfunction. Biomarkers (B-type natriuretic peptides and cardiac troponins) can alert clinicians of the possibility of cardiac dysfunction. Low plasma levels can serve to rule out a severe cardiac dysfunction. By contrast, high levels should prompt the performance of an echocardiographic examination. The transpulmonary thermodilution monitor and the pulmonary artery catheter can also be used to alert clinicians or to monitor the effects of inotropic therapy. Dobutamine is the first-line therapy. Its administration remains a matter of debate and should be carefully monitored in terms of efficacy and tolerance.

KEYWORDS

Sepsis - myocardial depression - echocardiography - B-type natriuretic peptide - dobutamine - levosimendan

REFERENCES

• 1 Dellinger R P, Levy M M, Carlet J M International Surviving Sepsis Campaign Guidelines Committee et al. Surviving Sepsis Campaign: international guidelines for management of severe sepsis and septic shock: 2008.  Crit Care Med. 2008;  36 (1) 296-327
• 2 Vieillard-Baron A, Caille V, Charron C, Belliard G, Page B, Jardin F. Actual incidence of global left ventricular hypokinesia in adult septic shock.  Crit Care Med. 2008;  36 (6) 1701-1706
• 3 Parker M M, Shelhamer J H, Bacharach S L et al.. Profound but reversible myocardial depression in patients with septic shock.  Ann Intern Med. 1984;  100 (4) 483-490
• 4 Parrillo J E. Pathogenetic mechanisms of septic shock.  N Engl J Med. 1993;  328 (20) 1471-1477
• 5 Zanotti Cavazzoni S L, Guglielmi M, Parrillo J E, Walker T, Dellinger R P, Hollenberg S M. Ventricular dilation is associated with improved cardiovascular performance and survival in sepsis.  Chest. 2010;  138 (4) 848-855
• 6 Bouhemad B, Nicolas-Robin A, Arbelot C, Arthaud M, Féger F, Rouby J J. Acute left ventricular dilatation and shock-induced myocardial dysfunction.  Crit Care Med. 2009;  37 (2) 441-447
• 7 Jardin F, Fourme T, Page B et al.. Persistent preload defect in severe sepsis despite fluid loading: a longitudinal echocardiographic study in patients with septic shock.  Chest. 1999;  116 (5) 1354-1359
• 8 Poelaert J, Declerck C, Vogelaers D, Colardyn F, Visser C A. Left ventricular systolic and diastolic function in septic shock.  Intensive Care Med. 1997;  23 (5) 553-560
• 9 Bouhemad B, Nicolas-Robin A, Arbelot C, Arthaud M, Féger F, Rouby J J. Isolated and reversible impairment of ventricular relaxation in patients with septic shock.  Crit Care Med. 2008;  36 (3) 766-774
• 10 Etchecopar-Chevreuil C, François B, Clavel M, Pichon N, Gastinne H, Vignon P. Cardiac morphological and functional changes during early septic shock: a transesophageal echocardiographic study.  Intensive Care Med. 2008;  34 (2) 250-256
• 11 Parker M M, McCarthy K E, Ognibene F P, Parrillo J E. Right ventricular dysfunction and dilatation, similar to left ventricular changes, characterize the cardiac depression of septic shock in humans.  Chest. 1990;  97 (1) 126-131
• 12 Vieillard Baron A, Schmitt J M, Beauchet A et al.. Early preload adaptation in septic shock? A transesophageal echocardiographic study.  Anesthesiology. 2001;  94 (3) 400-406
• 13 Rabuel C, Mebazaa A. Septic shock: a heart story since the 1960s.  Intensive Care Med. 2006;  32 (6) 799-807
• 14 Hunter J D, Doddi M. Sepsis and the heart.  Br J Anaesth. 2010;  104 (1) 3-11
• 15 Cunnion R E, Schaer G L, Parker M M, Natanson C, Parrillo J E. The coronary circulation in human septic shock.  Circulation. 1986;  73 (4) 637-644
• 16 Dhainaut J F, Huyghebaert M F, Monsallier J F et al.. Coronary hemodynamics and myocardial metabolism of lactate, free fatty acids, glucose, and ketones in patients with septic shock.  Circulation. 1987;  75 (3) 533-541
• 17 Lamia B, Chemla D, Richard C, Teboul J L. Clinical review: interpretation of arterial pressure wave in shock states.  Crit Care. 2005;  9 (6) 601-606
• 18 Lefer A M. Role of a myocardial depressant factor in the pathogenesis of circulatory shock.  Fed Proc. 1970;  29 (6) 1836-1847
• 19 Parrillo J E, Burch C, Shelhamer J H, Parker M M, Natanson C, Schuette W. A circulating myocardial depressant substance in humans with septic shock: septic shock patients with a reduced ejection fraction have a circulating factor that depresses in vitro myocardial cell performance.  J Clin Invest. 1985;  76 (4) 1539-1553
• 20 Kumar A, Kumar A, Paladugu B, Mensing J, Parrillo J E. Transforming growth factor-beta1 blocks in vitro cardiac myocyte depression induced by tumor necrosis factor-alpha, interleukin-1beta, and human septic shock serum.  Crit Care Med. 2007;  35 (2) 358-364
• 21 Chensue S W, Terebuh P D, Remick D G, Scales W E, Kunkel S L. In vivo biologic and immunohistochemical analysis of interleukin-1 alpha, beta and tumor necrosis factor during experimental endotoxemia: kinetics, Kupffer cell expression, and glucocorticoid effects.  Am J Pathol. 1991;  138 (2) 395-402
• 22 Abi-Gerges N, Tavernier B, Mebazaa A et al.. Sequential changes in autonomic regulation of cardiac myocytes after in vivo endotoxin injection in rat.  Am J Respir Crit Care Med. 1999;  160 (4) 1196-1204
• 23 Tavernier B, Li J M, El-Omar M M et al.. Cardiac contractile impairment associated with increased phosphorylation of troponin I in endotoxemic rats.  FASEB J. 2001;  15 (2) 294-296
• 24 Reithmann C, Hallström S, Pilz G, Kapsner T, Schlag G, Werdan K. Desensitization of rat cardiomyocyte adenylyl cyclase stimulation by plasma of noradrenaline-treated patients with septic shock.  Circ Shock. 1993;  41 (1) 48-59
• 25 Silverman H J, Penaranda R, Orens J B, Lee N H. Impaired beta-adrenergic receptor stimulation of cyclic adenosine monophosphate in human septic shock: association with myocardial hyporesponsiveness to catecholamines.  Crit Care Med. 1993;  21 (1) 31-39
• 26 Tang C, Liu M S. Initial externalization followed by internalization of beta-adrenergic receptors in rat heart during sepsis.  Am J Physiol. 1996;  270 (1 Pt 2) R254-R263
• 27 Kumar A, Paladugu B, Mensing J, Kumar A, Parrillo J E. Nitric oxide-dependent and -independent mechanisms are involved in TNF-alpha -induced depression of cardiac myocyte contractility.  Am J Physiol Regul Integr Comp Physiol. 2007;  292 (5) R1900-R1906
• 28 Vona-Davis L, Wearden P, Hill J, Hill R. Cardiac response to nitric oxide synthase inhibition using aminoguanidine in a rat model of endotoxemia.  Shock. 2002;  17 (5) 404-410
• 29 Lancel S, Tissier S, Mordon S et al.. Peroxynitrite decomposition catalysts prevent myocardial dysfunction and inflammation in endotoxemic rats.  J Am Coll Cardiol. 2004;  43 (12) 2348-2358
• 30 Ahmad R, Rasheed Z, Ahsan H. Biochemical and cellular toxicology of peroxynitrite: implications in cell death and autoimmune phenomenon.  Immunopharmacol Immunotoxicol. 2009;  31 (3) 388-396
• 31 Carlson D L, Willis M S, White D J, Horton J W, Giroir B P. Tumor necrosis factor-alpha-induced caspase activation mediates endotoxin-related cardiac dysfunction.  Crit Care Med. 2005;  33 (5) 1021-1028
• 32 Nevière R, Fauvel H, Chopin C, Formstecher P, Marchetti P. Caspase inhibition prevents cardiac dysfunction and heart apoptosis in a rat model of sepsis.  Am J Respir Crit Care Med. 2001;  163 (1) 218-225
• 33 Vieillard-Baron A. Assessment of right ventricular function.  Curr Opin Crit Care. 2009;  15 (3) 254-260
• 34 Combes A, Berneau J B, Luyt C E, Trouillet J L. Estimation of left ventricular systolic function by single transpulmonary thermodilution.  Intensive Care Med. 2004;  30 (7) 1377-1383
• 35 Jabot J, Monnet X, Bouchra L, Chemla D, Richard C, Teboul J L. Cardiac function index provided by transpulmonary thermodilution behaves as an indicator of left ventricular systolic function.  Crit Care Med. 2009;  37 (11) 2913-2918
• 36 Charpentier J, Luyt C E, Fulla Y et al.. Brain natriuretic peptide: a marker of myocardial dysfunction and prognosis during severe sepsis.  Crit Care Med. 2004;  32 (3) 660-665
• 37 Brueckmann M, Huhle G, Lang S et al.. Prognostic value of plasma N-terminal pro-brain natriuretic peptide in patients with severe sepsis.  Circulation. 2005;  112 (4) 527-534
• 38 Maeder M, Fehr T, Rickli H, Ammann P. Sepsis-associated myocardial dysfunction: diagnostic and prognostic impact of cardiac troponins and natriuretic peptides.  Chest. 2006;  129 (5) 1349-1366
• 39 Ma K K, Ogawa T, de Bold A J. Selective upregulation of cardiac brain natriuretic peptide at the transcriptional and translational levels by pro-inflammatory cytokines and by conditioned medium derived from mixed lymphocyte reactions via p38 MAP kinase.  J Mol Cell Cardiol. 2004;  36 (4) 505-513
• 40 Pirracchio R, Deye N, Lukaszewicz A C et al.. Impaired plasma B-type natriuretic peptide clearance in human septic shock.  Crit Care Med. 2008;  36 (9) 2542-2546
• 41 Fernandes Jr C J, Akamine N, Knobel E. Cardiac troponin: a new serum marker of myocardial injury in sepsis.  Intensive Care Med. 1999;  25 (10) 1165-1168
• 42 Røsjø H, Varpula M, Hagve T A The FINNSEPSIS Study Group et al. Circulating high sensitivity troponin T in severe sepsis and septic shock: distribution, associated factors, and relation to outcome.  Intensive Care Med. 2011;  37 (1) 77-85
• 43 Ammann P, Maggiorini M, Bertel O et al.. Troponin as a risk factor for mortality in critically ill patients without acute coronary syndromes.  J Am Coll Cardiol. 2003;  41 (11) 2004-2009
• 44 Turner A, Tsamitros M, Bellomo R. Myocardial cell injury in septic shock.  Crit Care Med. 1999;  27 (9) 1775-1780
• 45 Merx M W, Weber C. Sepsis and the heart.  Circulation. 2007;  116 (7) 793-802
• 46 Hayes M A, Timmins A C, Yau E H, 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 (24) 1717-1722
• 47 Boyd J H, Forbes J, Nakada T A, Walley K R, Russell J A. Fluid resuscitation in septic shock: a positive fluid balance and elevated central venous pressure are associated with increased mortality.  Crit Care Med. 2011;  39 (2) 259-265
• 48 Monnet X, Teboul J L. Volume responsiveness.  Curr Opin Crit Care. 2007;  13 (5) 549-553
• 49 Rivers E, Nguyen B, Havstad S Early Goal-Directed Therapy Collaborative Group et al. Early goal-directed therapy in the treatment of severe sepsis and septic shock.  N Engl J Med. 2001;  345 (19) 1368-1377
• 50 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 (6) 1007-1010
• 51 Kumar A, Schupp E, Bunnell E, Ali A, Milcarek B, Parrillo J E. Cardiovascular response to dobutamine stress predicts outcome in severe sepsis and septic shock.  Crit Care. 2008;  12 (2) R35
• 52 Barraud D, Faivre V, Damy T et al.. Levosimendan restores both systolic and diastolic cardiac performance in lipopolysaccharide-treated rabbits: comparison with dobutamine and milrinone.  Crit Care Med. 2007;  35 (5) 1376-1382
• 53 Morelli A, De Castro S, Teboul J L et al.. Effects of levosimendan on systemic and regional hemodynamics in septic myocardial depression.  Intensive Care Med. 2005;  31 (5) 638-644
• 54 Morelli A, Teboul J L, Maggiore S M et al.. Effects of levosimendan on right ventricular afterload in patients with acute respiratory distress syndrome: a pilot study.  Crit Care Med. 2006;  34 (9) 2287-2293
• 55 Hamzaoui O, Georger J F, Monnet X et al.. Early administration of norepinephrine increases cardiac preload and cardiac output in septic patients with life-threatening hypotension.  Crit Care. 2010;  14 (4) R142
• 56 Annane D, Vignon P, Renault A CATS Study Group et al. Norepinephrine plus dobutamine versus epinephrine alone for management of septic shock: a randomised trial.  Lancet. 2007;  370 (9588) 676-684
• 57 Levy B, Bollaert P E, Charpentier C et al.. Comparison of norepinephrine and dobutamine to epinephrine for hemodynamics, lactate metabolism, and gastric tonometric variables in septic shock: a prospective, randomized study.  Intensive Care Med. 1997;  23 (3) 282-287
• 58 Levy B, Mansart A, Bollaert P E, Franck P, Mallie J P. Effects of epinephrine and norepinephrine on hemodynamics, oxidative metabolism, and organ energetics in endotoxemic rats.  Intensive Care Med. 2003;  29 (2) 292-300
• 59 Duranteau J, Sitbon P, Teboul J L et al.. Effects of epinephrine, norepinephrine, or the combination of norepinephrine and dobutamine on gastric mucosa in septic shock.  Crit Care Med. 1999;  27 (5) 893-900
• 60 Creagh-Brown B C, Quinlan G J, Evans T W, Burke-Gaffney A. The RAGE axis in systemic inflammation, acute lung injury and myocardial dysfunction: an important therapeutic target?.  Intensive Care Med. 2010;  36 (10) 1644-1656