Betablocker im septischen Schock

 

 Buy Article Permissions and Reprints

Zusammenfassung

Die Therapie von Patienten im septischen Schock birgt große Herausforderungen. Die adrenerg vermittelte Stressantwort im Körper ist komplex reguliert – ob Betablocker die Hämodynamik in der Sepsis verbessern können, ist noch offen. Dieser Beitrag gibt einen Überblick über die Pharmakologie des betaadrenergen Systems, die pathophysiologische Rationale und die aktuelle Literatur zum Betablocker-Einsatz in der Sepsis und im septischen Schock.

Abstract

The therapy of patients suffering from sepsis and septic shock is one of the greatest challenges in critical care medicine. In the initial phase of septic shock patients often present with hyperdynamic circulatory conditions with elevated cardiac index, tachycardia and progressive hemodynamic instability. The type of tachycardia differs from atrial fibrillation or flatter to sinus tachycardia. The latter might be persistent even in case of adequate volume therapy according to the surviving sepsis campaign recommendations and may represent an independent pathology due to adrenergic overstimulation. Despite predominantly β₂-mediated immunomodulatory effects the administration of a selective β₁-adrenergic blocker may be beneficial in some cases. On the other hand, incautious administration of beta-blockers especially in case of insufficient volume replacement may result in direct negative inotropic effects rapidly aggravating hypotension and shock. This review focused on pharmacology of the β-adrenergic system, the pathophysiological rationale and current literature on clinical practice of the use of beta-blockers in sepsis and septic shock.

• Literatur

• 1 Poveda-Jaramillo R, Monaco F, Zangrillo A. et al. Ultra-short-acting beta-blockers (esmolol and landiolol) in the perioperative period and in critically ill patients. J Cardiothorac Vasc Anesth 2018; 32: 1415-1425 doi:10.1053/j.jvca.2017.11.039
  CrossrefPubMedGoogle Scholar
• 2 Zaugg M, Schaub MC, Pasch T. et al. Modulation of beta-adrenergic receptor subtype activities in perioperative medicine: mechanisms and sites of action. Br J Anaesth 2002; 88: 101-123
  CrossrefPubMedGoogle Scholar
• 3 de Montmollin E, Aboab J, Mansart A. et al. Bench-to-bedside review: Beta-adrenergic modulation in sepsis. Crit Care 2009; 13: 230 doi:10.1186/cc8026
  CrossrefPubMedGoogle Scholar
• 4 Sanders VM, Baker RA, Ramer-Quinn DS. et al. Differential expression of the beta2-adrenergic receptor by Th1 and Th2 clones: implications for cytokine production and B cell help. J Immunol 1997; 158: 4200-4210
  PubMedGoogle Scholar
• 5 Severn A, Rapson NT, Hunter CA. et al. Regulation of tumor necrosis factor production by adrenaline and beta-adrenergic agonists. J Immunol 1992; 148: 3441-3445
  PubMedGoogle Scholar
• 6 Muthu K, Deng J, Gamelli R. et al. Adrenergic modulation of cytokine release in bone marrow progenitor-derived macrophage following polymicrobial sepsis. J Neuroimmunol 2005; 158: 50-57 doi:10.1016/j.jneuroim.2004.08.003
  CrossrefPubMedGoogle Scholar
• 7 Deng J, Muthu K, Gamelli R. et al. Adrenergic modulation of splenic macrophage cytokine release in polymicrobial sepsis. Am J Physiol Cell Physiol 2004; 287: C730-C736 doi:10.1152/ajpcell.00562.2003
  CrossrefPubMedGoogle Scholar
• 8 Muthu K, Deng J, Romano F. et al. Thermal injury and sepsis modulates beta-adrenergic receptors and cAMP responses in monocyte-committed bone marrow cells. J Neuroimmunol 2005; 165: 129-138 doi:10.1016/j.jneuroim.2005.04.015
  CrossrefPubMedGoogle Scholar
• 9 Pemberton P, Veenith T, Snelson C. et al. Is it time to beta block the septic patient?. Biomed Res Int 2015; 2015: 424308 doi:10.1155/2015/424308
  CrossrefPubMedGoogle Scholar
• 10 Macchia A, Romero M, Comignani PD. et al. Previous prescription of beta-blockers is associated with reduced mortality among patients hospitalized in intensive care units for sepsis. Crit Care Med 2012; 40: 2768-2772 doi:10.1097/CCM.0b013e31825b9509
  CrossrefPubMedGoogle Scholar
• 11 Singer KE, Collins CE, Flahive JM. et al. Outpatient beta-blockers and survival from sepsis: Results from a national cohort of Medicare beneficiaries. Am J Surg 2017; 214: 577-582 doi:10.1016/j.amjsurg.2017.06.007
  CrossrefPubMedGoogle Scholar
• 12 Contenti J, Occelli C, Corraze H. et al. Long-term beta-blocker therapy decreases blood lactate concentration in severely septic patients. Crit Care Med 2015; 43: 2616-2622 doi:10.1097/CCM.0000000000001308
  CrossrefPubMedGoogle Scholar
• 13 Morelli A, Singer M, Ranieri VM. et al. Heart rate reduction with esmolol is associated with improved arterial elastance in patients with septic shock: a prospective observational study. Intensive Care Med 2016; 42: 1528-1534 doi:10.1007/s00134-016-4351-2
  CrossrefPubMedGoogle Scholar
• 14 Wang Z, Wu Q, Nie X. et al. Combination therapy with milrinone and esmolol for heart protection in patients with severe sepsis: a prospective, randomized trial. Clin Drug Investig 2015; 35: 707-716 doi:10.1007/s40261-015-0325-3
  CrossrefPubMedGoogle Scholar
• 15 Rivers E, Nguyen B, Havstad S. et al. Early goal-directed therapy in the treatment of severe sepsis and septic shock. N Engl J Med 2001; 345: 1368-1377 doi:10.1056/NEJMoa010307
  CrossrefPubMedGoogle Scholar
• 16 Morelli A, Ertmer C, Westphal M. et al. Effect of heart rate control with esmolol on hemodynamic and clinical outcomes in patients with septic shock: a randomized clinical trial. JAMA 2013; 310: 1683-1691 doi:10.1001/jama.2013.278477
  CrossrefPubMedGoogle Scholar
• 17 Liu P, Wu Q, Tang Y. et al. The influence of esmolol on septic shock and sepsis: A meta-analysis of randomized controlled studies. Am J Emerg Med 2018; 36: 470-474 doi:10.1016/j.ajem.2017.11.013
  CrossrefPubMedGoogle Scholar
• 18 Rhodes A, Evans LE, Alhazzani W. et al. Surviving Sepsis Campaign: International Guidelines for Management of Sepsis and Septic Shock: 2016. Intensive Care Med 2017; 43: 304-377 doi:10.1007/s00134-017-4683-6
  CrossrefPubMedGoogle Scholar