Sepsis and septic shock: pathophysiological and cardiovascular background as basis for therapy

Sepsis and septic shock are common causes for admission to intensive care units. The morbidity and mortality remain unacceptably high despite the advanced treatments.

To review the most commonly reported underlying mechanisms of sepsis and septic shock, besides discussion of sepsis-induced cardiovascular dysfunction. Therapeutic strategies for sepsis-induced myocardial depression are briefly discussed.

The development of sepsis and septic shock is multifactorial. Two major mechanisms contribute to the haemodynamic collapse. The extrinsic and intrinsic mechanisms induce a complex cascade which results in the release of pro- and anti-inflammatory mediators. Sepsis develops when the initial, appropriate host response to an infection becomes amplified and then dysregulated leading to haemodynamic and circulatory changes. The pro-inflammatory mediators tumour necrosis factor alpha, interleukin-beta and nitric oxide play a significant role in sepsis-related hypotension, shock and depression of cardiomyocyte contractility. Septic cardiac dysfunction can be explained by various mechanisms: changes in circulating volume, down-regulation of beta-adrenergic receptors, depressed post-receptor signalling pathways, reduced calcium release from the sarcoplasmic reticulum and impaired electromechanical coupling and reduced calcium sensibility at the myofibrillar level. Mitochondrial derangement seems to be of great importance in tissue injury and sepsis-associated multi organ failure. There is no consistent protocol for treating sepsis and septic shock. Guidelines include early goal-directed therapy, source control and haemodynamic supportive measures.

Further studies are needed to distinguish the importance of these various mechanisms. We recommend that further investigational work should focus on the recovery of the mitochondria-related bio-energetic shut down as the mitochondria could play a key role in the understanding of apoptosis and protective measures. Understanding the pathophysiology of sepsis and septic shock will inevitably lead to a more accurate treatment of these still too often fatal syndromes.