Abstract
Porcine model of peritonitis-induced sepsis is a well-established clinically relevant model of human disease. Interindividual variability of the response often complicates the interpretation of findings. To better understand the biological basis of the disease variability, the progression of the disease was compared between animals with sepsis and septic shock. Peritonitis was induced by inoculation of autologous feces in fifteen anesthetized, mechanically ventilated and surgically instrumented pigs and continued for 24 h. Cardiovascular and biochemical parameters were collected at baseline (just before peritonitis induction), 12 h, 18 h and 24 h (end of the experiment) after induction of peritonitis. Analysis of multiple parameters revealed the earliest significant differences between sepsis and septic shock groups in the sequential organ failure assessment (SOFA) score, systemic vascular resistance, partial pressure of oxygen in mixed venous blood and body temperature. Other significant functional differences developed later in the course of the disease. The data indicate that SOFA score, hemodynamical parameters and body temperature discriminate early between sepsis and septic shock in a clinically relevant porcine model. Early pronounced alterations of these parameters may herald a progression of the disease toward irreversible septic shock.
Highlights
Sepsis is a major health problem worldwide, the incidence of sepsis continues to rise, and despite the various options of the spectrum of available interventions, the progression of sepsis to severe refractory septic shock remains a severe clinical condition with high mortality [1,2,3,4]
The rise of sequential organ failure assessment (SOFA) score values was found in the group of septic shock, followed by increased plasma levels of lactate (Figure 1b) and cytokines
Mean arterial pressure remained stable throughout the entire experiment (Figure 2d), probably due to vasopressor support in the group of septic shock (Figure 2e) and a shift of autonomic nervous control toward sympathetic dominance in both groups as documented by the frequency domain analysis of heart rate variability
Summary
Sepsis is a major health problem worldwide, the incidence of sepsis continues to rise, and despite the various options of the spectrum of available interventions, the progression of sepsis to severe refractory septic shock remains a severe clinical condition with high mortality [1,2,3,4]. A meta-analysis of studies from developed high-income countries revealed global annual estimates of 31.5 million sepsis and 19.4 million severe sepsis cases, with potentially 5.3 million deaths in the hospital setting [5]. The rate of severe sepsis hospitalizations doubled during the last decade, resulting in more than 250,000 deaths in the United States yearly [6,7]. Despite intensive experimental and clinical efforts, the precise mechanisms of sepsis progression and transition into refractory septic shock remain unclear, limiting the optimal timing and success of therapeutic interventions. Diagnosis of sepsis and a mechanistic understanding of the progression of septic disease, based on a monitoring of the functions of various organ systems, could allow effective early therapeutic interventions and prevent refractory septic shock [8,9,10].
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