Assessment of Dynamic Changes in Stressed Volume and Venous Return during Hyperdynamic Septic Shock.

The present work investigated the dynamic changes in stressed volume (Vs) and other determinants of venous return using a porcine model of hyperdynamic septic shock. Septicemia was induced in 10 anesthetized swine, and fluid challenges were started after the diagnosis of sepsis-induced arterial hypotension and/or tissue hypoperfusion. Norepinephrine infusion targeting a mean arterial pressure (MAP) of 65 mmHg was started after three consecutive fluid challenges. After septic shock was confirmed, norepinephrine infusion was discontinued, and the animals were left untreated until cardiac arrest occurred. Baseline Vs decreased by 7% for each mmHg decrease in MAP during progression of septic shock. Mean circulatory filling pressure (Pmcf) analogue (Pmca), right atrial pressure, resistance to venous return, and efficiency of the heart decreased with time (p < 0.001 for all). Fluid challenges did not improve hemodynamics, but noradrenaline increased Vs from 107 mL to 257 mL (140%) and MAP from 45 mmHg to 66 mmHg (47%). Baseline Pmca and post-cardiac arrest Pmcf did not differ significantly (14.3 ± 1.23 mmHg vs. 14.75 ± 1.5 mmHg, p = 0.24), but the difference between pre-arrest Pmca and post-cardiac arrest Pmcf was statistically significant (9.5 ± 0.57 mmHg vs. 14.75 ± 1.5 mmHg, p < 0.001). In conclusion, the baseline Vs decreased by 7% for each mmHg decrease in MAP during progression of hyperdynamic septic shock. Significant changes were also observed in other determinants of venous return. A new physiological intravascular volume existing at zero transmural distending pressure was identified, termed as the rest volume (Vr).

Baseline Values and Kinetics of IL-6, Procalcitonin, and TNF-α in Landrace-Large White Swine Anesthetized with Propofol-Based Total Intravenous Anesthesia.

The baseline levels of various inflammatory mediators and their changes during anesthesia in swine are not known. The aim of this animal study was to measure the baseline values and kinetics of interleukin-6, procalcitonin, and tumor necrosis factor-alpha in healthy Landrace-Large White swine anesthetized with propofol-based total intravenous anesthesia. We included 8 healthy male pigs with an average weight of 19 ± 2 kg (aged 10-15 weeks) that were subjected to propofol-based total intravenous anesthesia for 8 hours. Complete blood count, serum chemistry, and serum levels of interleukin-6, procalcitonin, and tumor necrosis factor-alpha were analyzed, and serum levels were quantified hourly. Blood was also collected for bacterial culturing. Baseline values of interleukin-6 and procalcitonin were 18 pg/ml and 21 ng/ml, respectively, while tumor necrosis factor-alpha was not detectable during collection of baseline samples. A statistically significant difference was observed in interleukin-6 levels between time points (p < 0.0001). Procalcitonin increased with time, but there were no significant differences between time points (p = 0.152). Tumor necrosis factor-alpha increased until the 3rd hour of propofol-based total intravenous anesthesia, while after the 4th hour, it gradually decreased, reaching its baseline undetectable values by the 7th hour (p < 0.001). Our results can serve as the basis for further translational research.

Initial Immune Response in Escherichia coli, Staphylococcus aureus, and Candida albicans Bacteremia.

Sepsis remains a leading cause of mortality worldwide and is characterized by sustained inflammatory responses, reflected as changes in the expression profile of cytokines with time. The aim of the present study was to investigate the dynamic changes in complete blood count, serum chemistry, procalcitonin (PCT), tumor necrosis factor-alpha (TNF-α), and interleukin-6 (IL-6) in Escherichia coli, Staphylococcus aureus, and Candida albicans bacteremia. Study subjects were 32 healthy male Landrace-Large White pigs, aged 10-15 weeks and of average weight 19 ± 2 kg. Bacteremia was induced by continuous intravenous infusion of microbial suspensions during a period of 8 h. E. coli and S. aureus bacteremia were associated with a significant gradual decrease in white blood cells and platelets, respectively (p = 0.002 and p = 0.004), while candidemia was characterized by a significant gradual decrease in lymphocytes (p = 0.009). Serum PCT levels were either undetectable or very low, with no significant changes with time in all groups. E. coli bacteremia elicited a strong pro-inflammatory response, characterized by a significant increase in TNF-α expression from the onset of bacteremia (p = 0.042). C. albicans exhibited a different profile with an early, moderate increase in TNF-α followed by a subsequent marked increase in IL-6 levels (p = 0.03). The differential regulation of inflammatory and hematological responses depending on the pathogenic agent can reveal differences in the underlying inflammatory mechanisms, which may assist in the ongoing quest for the identification of a panel of circulating biomarkers during bacteremia.

Correction to: Initial Immune Response in Escherichia coli, Staphylococcus aureus, and Candida albicans Bacteremia.

The original version of this article contained mistakes, and the authors would like to correct them.

Cardiopulmonary Arrest and Resuscitation in Severe Sepsis and Septic Shock: A Research Model.

Cardiopulmonary resuscitation in patients with severe sepsis and septic shock is challenging and usually unsuccessful. The aim of the present study is to describe our swine model of cardiac arrest and resuscitation in severe sepsis and septic shock. In this prospective randomized animal study, 10 healthy female Landrace-Large White pigs with an average weight of 20 ± 1 kg (aged 19 - 21 weeks) were the study subjects. Septicemia was induced by an intravenous infusion of a bolus of 20-mL bacterial suspension in 2 min, followed by a continuous infusion during the rest of the experiment. After septic shock was confirmed, the animals were left untreated until cardiac arrest occurred. All animals developed pulseless electrical activity between the fifth and sixth hours of septicemia, whereas five (50%) of 10 animals were successfully resuscitated. Coronary perfusion pressure was statistically significantly different between surviving and nonsurviving animals. We found a statistically significant correlation between mean arterial pressure and unsuccessful resuscitation (P = 0.046), whereas there was no difference in end-tidal carbon dioxide (23.05 ± 1.73 vs. 23.56 ± 1.70; P = 0.735) between animals with return of spontaneous circulation and nonsurviving animals. During the 45-min postresuscitation monitoring, we noted a significant decrease in hemodynamic parameters, although oxygenation indices and lactate clearance were constantly increased (P = 0.001). This successful basic swine model was for the first time developed and may prove extremely useful in future studies on the periarrest period in severe sepsis and septic shock.