Central Venous-to-Arterial CO 2 Gap Is a Useful Parameter in Monitoring Hypovolemia-Caused Altered Oxygen Balance: Animal Study

Monitoring hypovolemia is an everyday challenge in critical care, with no consensus on the best indicator or what is the clinically relevant level of hypovolemia. The aim of this experiment was to determine how central venous oxygen saturation (ScvO 2 ) and central venous-to-arterial carbon dioxide difference (CO 2 gap) reflect hypovolemia-caused changes in the balance of oxygen delivery and consumption. Anesthetized, ventilated Vietnamese minipigs ( = 10) were given a bolus followed by a continuous infusion of furosemide. At baseline and then in five stages hemodynamic, microcirculatory measurements and blood gas analysis were performed. Oxygen extraction increased significantly, which was accompanied by a significant drop in ScvO 2 and a significant increase in CO 2 gap. There was a significant negative correlation between oxygen extraction and ScvO 2 and significant positive correlation between oxygen extraction and CO 2 gap. Taking ScvO 2 < 73% and CO 2 gap >6 mmHg values together to predict an oxygen extraction >30%, the positive predictive value is 100%; negative predicted value is 72%. Microcirculatory parameters, capillary perfusion rate and red blood cell velocity, decreased significantly over time. Similar changes were not observed in the sham group. Our data suggest that ScvO 2 < 73% and CO 2 gap >6 mmHg can be complementary tools in detecting hypovolemiacaused imbalance of oxygen extraction

Central Venous-to-Arterial CO

Monitoring hypovolemia is an everyday challenge in critical care, with no consensus on the best indicator or what is the clinically relevant level of hypovolemia. The aim of this experiment was to determine how central venous oxygen saturation (ScvO(2)) and central venous-to-arterial carbon dioxide difference (CO(2) gap) reflect hypovolemia-caused changes in the balance of oxygen delivery and consumption. Anesthetized, ventilated Vietnamese minipigs (n = 10) were given a bolus followed by a continuous infusion of furosemide. At baseline and then in five stages hemodynamic, microcirculatory measurements and blood gas analysis were performed. Oxygen extraction increased significantly, which was accompanied by a significant drop in ScvO(2) and a significant increase in CO(2) gap. There was a significant negative correlation between oxygen extraction and ScvO(2) and significant positive correlation between oxygen extraction and CO(2) gap. Taking ScvO(2) < 73% and CO(2) gap >6 mmHg values together to predict an oxygen extraction >30%, the positive predictive value is 100%; negative predicted value is 72%. Microcirculatory parameters, capillary perfusion rate and red blood cell velocity, decreased significantly over time. Similar changes were not observed in the sham group. Our data suggest that ScvO(2) < 73% and CO(2) gap >6 mmHg can be complementary tools in detecting hypovolemia-caused imbalance of oxygen extraction

Mitochondria-Targeted Antioxidants SkQ1 and MitoTEMPO Failed to Exert a Long-Term Beneficial Effect in Murine Polymicrobial Sepsis

Mitochondrial-derived reactive oxygen species have been deemed an important contributor in sepsis pathogenesis. We investigated whether two mitochondria-targeted antioxidants (mtAOX; SkQ1 and MitoTEMPO) improved long-term outcome, lessened inflammation, and improved organ homeostasis in polymicrobial murine sepsis. 3-month-old female CD-1 mice (n=90) underwent cecal ligation and puncture (CLP) and received SkQ1 (5 nmol/kg), MitoTEMPO (50 nmol/kg), or vehicle 5 times post-CLP. Separately, 52 SkQ1-treated CLP mice were sacrificed at 24 h and 48 h for additional endpoints. Neither MitoTEMPO nor SkQ1 exerted any protracted survival benefit. Conversely, SkQ1 exacerbated 28-day mortality by 29%. CLP induced release of 10 circulating cytokines, increased urea, ALT, and LDH, and decreased glucose but irrespectively of treatment. Similar occurred for CLP-induced lymphopenia/neutrophilia and the NO blood release. At 48 h post-CLP, dying mice had approximately 100-fold more CFUs in the spleen than survivors, but this was not SkQ1 related. At 48 h, macrophage and granulocyte counts increased in the peritoneal lavage but irrespectively of SkQ1. Similarly, hepatic mitophagy was not altered by SkQ1 at 24 h. The absence of survival benefit of mtAOX may be due to the extended treatment and/or a relatively moderate-risk-of-death CLP cohort. Long-term effect of mtAOX in abdominal sepsis appears different to sepsis/inflammation models arising from other body compartments

Bidirectional Relationship Between Reduced Blood pH and Acute Pancreatitis: A Translational Study of Their Noxious Combination

Acute pancreatitis (AP) is often accompanied by alterations in the acid-base balance, but how blood pH influences the outcome of AP is largely unknown. We studied the association between blood pH and the outcome of AP with meta-analysis of clinical trials, and aimed to discover the causative relationship between blood pH and AP in animal models. PubMed, EMBASE, and Cochrane Controlled Trials Registry databases were searched from inception to January 2017. Human studies reporting systemic pH status and outcomes (mortality rate, severity scores, and length of hospital stay) of patient groups with AP were included in the analyses. We developed a new mouse model of chronic metabolic acidosis (MA) and induced mild or severe AP in the mice. Besides laboratory blood testing, the extent of pancreatic edema, necrosis, and leukocyte infiltration were assessed in tissue sections of the mice. Thirteen studies reported sufficient data in patient groups with AP (n = 2,311). Meta-analysis revealed markedly higher mortality, elevated severity scores, and longer hospital stay in AP patients with lower blood pH or base excess (P &lt; 0.001 for all studied outcomes). Meta-regression analysis showed significant negative correlation between blood pH and mortality in severe AP. In our mouse model, pre-existing MA deteriorated the pancreatic damage in mild and severe AP and, vice versa, severe AP further decreased the blood pH of mice with MA. In conclusion, MA worsens the outcome of AP, while severe AP augments the decrease of blood pH. The discovery of this vicious metabolic cycle opens up new therapeutic possibilities in AP

Central Venous-to-Arterial CO2 Gap Is a Useful Parameter in Monitoring Hypovolemia-Caused Altered Oxygen Balance: Animal Study

Monitoring hypovolemia is an everyday challenge in critical care, with no consensus on the best indicator or what is the clinically relevant level of hypovolemia. The aim of this experiment was to determine how central venous oxygen saturation (ScvO2) and central venous-to-arterial carbon dioxide difference (CO2 gap) reflect hypovolemia-caused changes in the balance of oxygen delivery and consumption. Anesthetized, ventilated Vietnamese minipigs (n=10) were given a bolus followed by a continuous infusion of furosemide. At baseline and then in five stages hemodynamic, microcirculatory measurements and blood gas analysis were performed. Oxygen extraction increased significantly, which was accompanied by a significant drop in ScvO2 and a significant increase in CO2 gap. There was a significant negative correlation between oxygen extraction and ScvO2 and significant positive correlation between oxygen extraction and CO2 gap. Taking ScvO26 mmHg values together to predict an oxygen extraction >30%, the positive predictive value is 100%; negative predicted value is 72%. Microcirculatory parameters, capillary perfusion rate and red blood cell velocity, decreased significantly over time. Similar changes were not observed in the sham group. Our data suggest that ScvO26 mmHg can be complementary tools in detecting hypovolemia-caused imbalance of oxygen extraction