Liver as a focus of impaired oxygenation and cytokine production in a porcine model of endotoxicosis.

OBJECTIVES: To determine whether the liver is a focus of insufficient oxygenation and whether liver is a source of tumor necrosis factor (TNF) and interleukin-6 (IL-6) in a porcine model of endotoxicosis. DESIGN: In vivo, prospective, controlled, repeated-measures, experimental study. SETTING: Experimental physiology laboratory in a university. SUBJECTS: Juvenile pigs, weighing 22 to 35 kg. INTERVENTIONS: Catheters for blood sampling were inserted into the carotid artery, portal vein, hepatic vein, and pulmonary artery of anesthetized animals. Ultrasonic flow probes were placed on the portal vein and the hepatic artery. During surgery, normal saline was infused intravenously at 25 mL/kg/hr. Following stabilization, animals were allocated randomly to one of two groups. The endotoxemic group (n = 6) received 50 mg/kg of purified Escherichia coli lipopolysaccharide infused into the external jugular vein over 1 hr. The control group (n = 6) received a sham saline infusion infused over 1 hr. Once the endotoxin or sham infusion was initiated, the rate of the intravenous saline infusion was increased to 48 mL/kg/hr for the remainder of the experiment. Measurements were obtained before the endotoxin or sham infusion, immediately after the infusion, and every 30 mins thereafter for 4 hrs. MEASUREMENTS AND MAIN RESULTS: Blood gases, lactate, and bioactive TNF and IL-6 concentrations were measured from the carotid artery, portal vein, hepatic vein, and pulmonary artery. The porcine model is characterized by systemic hypotension, pulmonary hypertension, and maintenance of cardiac output. Despite decreased hepatic oxygen delivery in endotoxemic animals (p < .02), there was no change in hepatic oxygen consumption compared with controls. Throughout the experiment, there was net hepatic consumption of lactate in both groups. There was no significant hepatic production (or consumption) of TNF or IL-6 in either group. CONCLUSIONS: In this porcine model of endotoxicosis, there is a reduction of hepatic oxygen delivery but dysoxia is not present. The liver is not a source of TNF or IL-6 in this model of endotoxicosis.

Venous gas embolism--a comparison of carbon dioxide and helium in pigs.

PURPOSE: The use of helium for insufflation during laparoscopic surgery avoids hypercarbia and acidosis associated with absorbed CO2, but the effects of helium gas embolism are unknown. We compared the effects of CO2 with He gas embolism on survival, haemodynamic variables, oxygenation, and ventilation in pigs. METHODS: Anaesthetized juvenile pigs were given progressively larger boluses of either CO2 (n = 5) or He (n = 4) into the right atrium. Measurements of haemodynamic variables, oxygenation, and PETCO2 were made before and after each gas injection. RESULTS: All animals survived injection of 300 ml CO2 while no animal survived more than 120 ml He (P < 0.01). Mean arterial pressure decreased more after 60 ml He (99 +/- 14 to 44 +/- 20 mmHg) than after 60 ml CO2 (110 +/- 12 to 88 +/- 14 mmHg, P < 0.001). Cardiac output did not change at any injection volume. The PETCO2 decreased more after 60 ml He (30 +/- 2 to 3 +/- 6 mmHg) than after 60 ml CO2 (35 +/- 3 to 30 +/- 3 mmHg, P < 0.001). Only the He group showed a decrease in PaO2 (190 +/- 51 to 68 +/- 22 mmHg at 60 ml, P < 0.05). CONCLUSION: Helium gas embolism has a greater deleterious effect than CO2 gas embolism on survival, MAP, PETCO2, and PaO2. These different effects of gas embolism should be recognized when considering the use of helium or other insoluble gases for abdominal laparoscopic insufflation.

Gut is not a source of cytokines in a porcine model of endotoxicosis.

BACKGROUND: We sought to determine whether ischemic gut is a source of endotoxin, tumor necrosis factor (TNF), and interleukin-6 (IL-6) in a porcine model of endotoxicosis. METHODS: Under general anesthesia pigs underwent neck dissection and laparotomy for placement of catheters in the carotid artery and portal vein and application of an ultrasonic flow probe around the portal vein. Endotoxin, TNF, and IL-6 levels were measured from the carotid artery and the portal vein during a 4 hour period in animals given endotoxin (50 mg/kg; n = 6) and in animals in the control group (n = 6). Gut fluxes of the substances of interest were calculated as the product of concentration and portal venous flow. A tonometer placed in the terminal ileum was used to monitor mucosal pH. RESULTS: Small bowel mucosal pH was significantly depressed in endotoxemic animals (6.8 +/- 0.1) when compared with baseline (7.1 +/- 0.1; p < 0.05) and control levels. In the control group portal venous levels of endotoxin, TNF, and IL-6 did not change significantly from baseline levels (1.5 +/- 0.4 endotoxin units (EU)/ml, 24 +/- 3 pU/ml, and 1.3 +/- 0.4 nU/ml, respectively). In the endotoxemic animals portal venous endotoxin and TNF levels peaked immediately after the endotoxin infusion (2186 +/- 437 EU/ml, and 293 +/- 125 pU/ml, respectively), and portal venous IL-6 levels peaked at 180 minutes (168 +/- 21 nU/ml). At no time did endotoxin, TNF, or IL-6 levels differ between arterial and portal venous blood, and at no time did efflux from the gut significantly exceed gut influx in either the control or endotoxemic animals. CONCLUSIONS: Ischemic gut as indicated by decreased mucosal pH is not associated with gut release of endotoxin, IL-6, or TNF in this porcine model of endotoxicosis.

Effect of subcutaneous carbon dioxide insufflation on arterial pCO2.

PURPOSE: Subcutaneous emphysema following laparoscopy could result in postoperative respiratory acidosis from prolonged CO2 absorption. We studied the magnitude and duration of alterations in PaCO2 coincident with direct CO2 insufflation into the subcutaneous fat of the anterior abdominal wall of 5 anesthetized juvenile pigs. METHODS: First, each pig was insufflated with 6 L of CO2 to produce moderate emphysema over the trunk. Following return to baseline PaCO2, each pig was re-insufflated with 12 L of CO2 to produce severe emphysema over lower limbs, neck, head, and trunk. Measurements of arterial blood gases were performed every 5 or 10 min. Minute ventilation was held constant to represent the worst case scenario. RESULTS: From baseline PaCO2 of 41.8 +/- 2.3 mm Hg, PaCO2 peaked at 68.3 +/- 8.6 (P < 0.02) and 92.9 +/- 10.7 (P < 0.01) mm Hg for the 6- and 12-L volumes, respectively, 20 to 25 minutes following insufflation. From baseline arterial pH of 7.40 +/- 0.02, respective nadirs of pH were 7.21 +/- 0.06 (P < 0.02) and 7.08 +/- 0.05 (P < 0.01). PaCO2 and arterial pH took approximately 100 minutes to return to baseline after insufflation with both 6 and 12 L volumes. CONCLUSIONS: When minute ventilation is fixed, subcutaneous CO2 insufflation causes increased PaCO2 and decreased pH that may persist for a prolonged period of time. Therefore, patients with subcutaneous emphysema after laparoscopy should be observed in postanesthetic recovery until PaCO2 and pH approach baseline.

Carbon dioxide absorption is not linearly related to intraperitoneal carbon dioxide insufflation pressure in pigs.

BACKGROUND: Carbon dioxide absorption into the blood during laparoscopic surgery using intraperitoneal carbon dioxide insufflation may lead to respiratory acidosis, increased ventilation requirements, and possible serious cardiovascular compromise. The relationship between increased carbon dioxide excretion (VCO2) and intraperitoneal carbon dioxide insufflation pressure has not been well defined. METHODS: In 12 anesthesized pigs instrumented for laparoscopic surgery, intraperitoneal carbon dioxide (n = 6) or helium (n = 6) insufflation pressure was increased in steps, and VCO2 (metabolic cart), dead space, and hemodynamics were measured during constant minute ventilation. RESULTS: VCO2 increases rapidly as intraperitoneal insufflation pressure increases from 0 to 10 mmHg; but from 10 to 25 mmHg, VCO2 does not increase much further. PaCO2 increases continuously as intraperitoneal insufflation pressure increases from 0 to 25 mmHg. Hemodynamic parameters remained stable. CONCLUSIONS: By considering Fick's law of diffusion, the initial increase in VCO2 is likely accounted for by increasing peritoneal surface area exposed during insufflation. The continued increase in PaCO2 without a corresponding increase in VCO2 is accounted for by increasing respiratory dead space.