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

Abstract

This protocol describes a centrally catheterized mouse model of prolonged critical illness. We combine the cecal ligation and puncture method to induce sepsis with the use of a central venous line for fluids, drugs and nutrient administration to mimic the human clinical setting. Critically ill patients require intensive medical support in order to survive. While the majority of patients will recover within a few days, about a quarter of the patients need prolonged intensive care and are at high risk of dying from non-resolving multiple organ failure. Furthermore, the prolonged phase of critical illness is hallmarked by profound muscle weakness, and endocrine and metabolic changes, of which the pathogenesis is currently incompletely understood. The most widely used animal model in critical care research is the cecal ligation and puncture model to induce sepsis. This is a very reproducible model, with acute inflammatory and hemodynamic changes similar to human sepsis, which is designed to study the acute phase of critical illness. However, this model is hallmarked by a high lethality, which is different from the clinical human situation, and is not developed to study the prolonged phase of critical illness. Therefore, we adapted the technique by placing a central venous catheter in the jugular vein allowing us to administer clinically relevant supportive care, to better mimic the human clinical situation of critical illness. This mouse model requires an extensive surgical procedure and daily intensive care of the animals, but it results in a relevant model of the acute and prolonged phase of critical illness.

Adipose tissue protects against sepsis-induced muscle weakness in mice: from lipolysis to ketones

“…Male, 24-week-old mice were anesthetized and a catheter was placed in the central jugular vein, followed by cecal ligation and puncture to induce sepsis [33,34]. Unless indicated, 57BL/6JRj mice (Janvier SAS, Chassal, France) were used.…”

“…As a general hypothesis, we state that the protection against ICU-acquired weakness in overweight/obese critically ill patients can be explained by their enhanced ability to release and metabolize fatty acids from their excess adipose tissue. This hypothesis was tested with four consecutive studies in a mouse model of prolonged abdominal sepsis [33]. Of note, this centrally catheterized, fluidresuscitated, and antibiotic-treated mouse model results in muscle wasting and weakness that is comparable to ICUacquired weakness in patients [15].…”

On the Role of Illness Duration and Nutrient Restriction in Cholestatic Alterations that Occur During Critical Illness

“…Both surgical and septic critically ill animals underwent extensive surgery, in which a central venous catheter was placed in the left jugular vein, as reported previously ( 9 ). Mice allocated to “surgical critical illness” received a combination of the placement of a central venous catheter, which is an extensive surgical procedure that requires prolonged anesthesia, and a sham laparotomy for which the abdomen is opened, the cecum is manipulated, but not punctured.…”

“…Mice allocated to “surgical critical illness” received a combination of the placement of a central venous catheter, which is an extensive surgical procedure that requires prolonged anesthesia, and a sham laparotomy for which the abdomen is opened, the cecum is manipulated, but not punctured. Mice allocated to the “septic critical illness” group additionally received CLP with an 18-gauge needle to induce a polymicrobial sepsis ( 9 ). All critically ill mice received intravenous fluid resuscitation (colloids/crystalloids 1:4 at 0.3 mL/h) for 24 h, from then onward intravenous partial parenteral nutrition at 0.2 mL/h (Oliclinomel N7E, Baxter, Braine-l’Alleud, Belgium) via the central venous catheter ( 9 ).…”

“…Mice allocated to the “septic critical illness” group additionally received CLP with an 18-gauge needle to induce a polymicrobial sepsis ( 9 ). All critically ill mice received intravenous fluid resuscitation (colloids/crystalloids 1:4 at 0.3 mL/h) for 24 h, from then onward intravenous partial parenteral nutrition at 0.2 mL/h (Oliclinomel N7E, Baxter, Braine-l’Alleud, Belgium) via the central venous catheter ( 9 ). To match the human intensive care setting of reduced nutrient intake, we used mixed parenteral nutrition instead of normal chow to allow careful control of the nutritional intake.…”