use-central-venous-line-for-fluids-drugs-nutrient-administration

Use of a Central Venous Line for Fluids, Drugs and Nutrient Administration in a Mouse Model of Critical Illness

This protocol describes a centrally catheterized mouse model of prolonged critical illness. We combine the cecal ligation and puncture method to induce ...

KU Leuven

Sepsis is often associated with cholestatic liver dysfunction caused by changes in the expression profile of hepatic bile salt transporters. However, in rodent endotoxin models, the role of ischemic hepatitis caused by liver hypoperfusion cannot be delineated. We hypothesized that hepatocytes change their expression pattern of bile salt transporters during early severe sepsis despite adequate resuscitation. Fifteen anesthetized and instrumented pigs were randomized to either fecal peritonitis (n = 8) or control (n = 7). Resuscitation was performed by hydroxyethyl starch and norepinephrine infusion. Hemodynamic parameters and markers of cholestatic and ischemic hepatic dysfunction were recorded. At baseline and after 21 h, messenger RNA (mRNA) and protein expression of bile salt transporters was determined by quantitative real-time polymerase chain reaction and immunohistochemistry, respectively, on in vivo liver biopsies. All resuscitated septic pigs developed a normotensive hyperdynamic circulation with increased portal flow. After 21 h of peritonitis, no signs of biochemical or histological cholestasis were present. Na-taurocholate cotransporting polypeptide and bile salt export pump mRNA were downregulated by 83% (P = 0.001) and 67% (P = 0.001), respectively, in comparison with controls, whereas multidrug resistance-associated protein 4 (MRP4) mRNA was upregulated by 85% (P = 0.02). Bile salt export pump and MRP2 staining were downregulated in septic pigs. During early porcine fluid-resuscitated sepsis, hepatic basolateral influx (Na-taurocholate cotransporting polypeptide) and canalicular efflux (bile salt export pump) of bile salts were downregulated without hemodynamic signs of hepatic hypoperfusion or biochemical signs of cholestasis. In parallel, the basolateral escape transport (MRP4) was markedly upregulated, possibly as an early adaptive response to counteract hepatocellular accumulation of toxic bile acids.

The impact of resuscitated fecal peritonitis on the expression of the hepatic bile salt transporters in a porcine model.

Critical illness is characterized by lean tissue wasting, whereas adipose tissue is preserved. Overweight and obese critically ill patients may have a lower risk of death than lean patients, suggestive of a protective role for adipose tissue during illness.

Alterations in adipose tissue during critical illness: An adaptive and protective response?

Perioperative hyperglycemia, aggravated by cardiopulmonary bypass, is associated with adverse outcome in adult and pediatric patients. Whereas hyperglycemia was originally perceived as an adaptive response to surgical stress, it is now clear that glycemic control is a strategy to reduce adverse outcomes after cardiac surgery and cardiopulmonary bypass. The optimal blood glucose target, whether or not glycemic control should be initiated already intraoperatively, and whether or not perioperative glucose administration affects the impact of glycemic control on ischemia-reperfusion damage remain open questions. Hypoglycemia, the risk of which is increased with glycemic control, is also associated with adverse outcomes. However, it remains controversial whether brief episodes of hypoglycemia, rapidly corrected during glycemic control, have adverse effects on outcome. This review gives an overview of the currently available literature on glycemic control during and after cardiac surgery and focuses on the indicated open questions about this intervention for this specific patient population.

Glycemic control and outcome related to cardiopulmonary bypass.

Critical illness is hallmarked by mitochondrial damage, which is attenuated by targeting normoglycemia. Mitochondrial dysfunction induces fibroblast growth factor-21 (FGF21) via the integrated stress response (ISR).

FGF21 Response to Critical Illness: Effect of Blood Glucose Control and Relation With Cellular Stress and Survival.

The 'obesity paradox' of critical illness refers to better survival with a higher body mass index. We hypothesized that fat mobilized from excess adipose tissue during critical illness provides energy more efficiently than exogenous macronutrients and could prevent lean tissue wasting.

Premorbid obesity, but not nutrition, prevents critical illness-induced muscle wasting and weakness.

Patients with critical illness-induced multiple organ failure suffer from a very high morbidity and mortality, despite major progress in intensive care. The pathogenesis of this condition is complex and incompletely understood. Inadequate tissue perfusion and an overwhelming inflammatory response with pronounced cellular damage have been suggested to play an important role, but interventions targeting these disturbances largely failed to improve patient outcome. Hence, new therapeutic perspectives are urgently needed. Cellular dysfunction, hallmarked by mitochondrial dysfunction and endoplasmic reticulum stress, is increasingly recognized as an important contributor to the development of organ failure in critical illness. Several cellular defense mechanisms are normally activated when the cell is in distress, but may fail or respond insufficiently to critical illness. This insight may open new therapeutic options by stimulating these cellular defense mechanisms. This review summarizes the current understanding of the role of mitochondrial dysfunction and endoplasmic reticulum stress in critical illness-induced multiple organ failure and gives an overview of the corresponding cellular defense mechanisms. Therapeutic perspectives based on these cellular defense mechanisms are discussed. This article is part of a Special Issue entitled: Immune and Metabolic Alterations in Trauma and Sepsis - edited by Raghavan Raju.

Article	Year
The impact of resuscitated fecal peritonitis on the expression of the hepatic bile salt transporters in a porcine model. Shock (Augusta, Ga.)\| PubMed ID: 20357697	2010
Alterations in adipose tissue during critical illness: An adaptive and protective response? American journal of respiratory and critical care medicine\| PubMed ID: 20442437	2010
Glycemic control and outcome related to cardiopulmonary bypass. Best practice & research. Clinical anaesthesiology\| PubMed ID: 26060029	2015
FGF21 Response to Critical Illness: Effect of Blood Glucose Control and Relation With Cellular Stress and Survival. The Journal of clinical endocrinology and metabolism\| PubMed ID: 26274346	2015
Premorbid obesity, but not nutrition, prevents critical illness-induced muscle wasting and weakness. Journal of cachexia, sarcopenia and muscle\| PubMed ID: 27897405	2017
Mitochondrial and endoplasmic reticulum dysfunction and related defense mechanisms in critical illness-induced multiple organ failure. Biochimica et biophysica acta\| PubMed ID: 28219766	2017

Steven Thiessen

Biography

JoVE Journal Publications

Other Publications