Normovolemic hemodilution improves oxygen extraction capabilities in endotoxic shock (original) (raw)

JL: Normovolemic hemodilution improves oxygen extraction capabilities in endotoxic shock

2015

We studied the effects of normovolemic hemodilution on tissue oxygen extraction capabilities in a canine model of endotoxic shock. Eighteen anesthetized and mechanically ventilated dogs underwent normovolemic hemodilution with 6% hydroxyethyl starch solution to reach hematocrit (Hct) levels around 40, 30, or 20% before the administration of 2 mg/kg of Escherichia coli endotoxin. Cardiac tamponade was then induced by repeated injections of normal saline into the pericardial sac to reduce cardiac output and study whole body oxygen extraction capabilities. Whole body critical oxygen delivery was lower in the Hct 20% and 30% groups (8.4 Ϯ 0.4 and 10.4 Ϯ 0.7 ml ⅐ kg Ϫ1 ⅐ min Ϫ1 , respectively) than in the Hct 40% group (12.8 Ϯ 0.8 ml ⅐ kg Ϫ1 ⅐ min Ϫ1) (both P Ͻ 0.005). The whole body critical oxygen extraction ratio was higher in the Hct 30% and 20% groups (49.1 Ϯ 8.2 and 55.2 Ϯ 4.6%, respectively) than in the Hct 40% group (37.1 Ϯ 4.4 %) (both P Ͻ 0.05). Liver critical oxygen extraction ratio was also higher in the Hct 30% and 20% groups than in the Hct 40% group. The arterial lactate concentrations and the gradient between ileum mucosal PCO2 and arterial PCO2 were lower in the Hct 20% and 30% groups than in the Hct 40% group. We conclude that, during an acute reduction in blood flow during endotoxic shock in dogs, normovolemic hemodilution is associated with improved tissue perfusion and increased oxygen extraction capabilities. sepsis; hypoxia; oxygen availability; dog experiment; tonometry SEPTIC SHOCK IS ASSOCIATED with significant alterations in cellular oxygen utilization (1, 18, 26), even though oxygen delivery (Ḋ O 2) to the tissues is typically maintained or even increased. Microregional zones of hypoxia (8, 23), secondary to microcirculatory disturbances (12), have been incriminated in these alterations, in addition to altered cellular metabolism. A complex interaction between an increased release of many mediators, leukocyte activation, endothelial injury, and interstitial edema has been largely implicated in this

Hemodynamic effects of fluid resuscitation with 6% hydroxyethyl starch and whole blood in experimental hypovolemic shock in Beagle dogs

Turkish Journal of Veterinary & Animal Sciences

Th e short-term eff ects of 6% hydroxyethyl starch (HES) and whole blood (WB) resuscitations in hypovolemic shock (HS) on invasive and noninvasive hemodynamic variables were studied from the clinical point of view in 20 mature healthy male Beagle dogs. Aft er anesthesia, the animals were randomly divided into 2 groups, HES (n = 10) and WB (n = 10), and were surgically instrumented with an arterial catheter and a thermodilution cardiac output catheter. For induction of HS, the right carotid artery was catheterized and approximately 40% of the blood volume was drawn over a period of 30 min, until a mean arterial blood pressure (MAP) of about 50 mmHg was reached. Aft er that, the HES group received 6% HES and the WB group received autologous whole blood resuscitation (30 mL/kg/h). Th e measurement of hemodynamic variables was performed in normovolemic (baseline, BL), severe hypovolemic, and resuscitation state (from R1 to R4 at an interval of 30 min). Signifi cant changes in some of the hemodynamic variables systolic arterial pressure (SAP), diastolic arterial pressure (DAP), MAP, central venous pressure (CVP), cardiac output (CO), cardiac index (CI), stroke volume (SV), stroke volume index (SVI), oxygen delivery (DO 2), and oxygen consumption (VO 2) were observed during hypovolemic shock and resuscitation, which could refl ect the condition of the patient. Resuscitation with WB seemed to resolve the hemodynamic variables to or above BL, whereas that with HES could resolve most but not all of the hemodynamic variables. Th e WB was found to be superior to restore the hemodynamic variable to the BL or above in comparison to that of the HES, for the clinical management of HS in dogs. Th e fi ndings of this study suggest that dogs in HS can be successfully resuscitated with HES and WB.

Comparative efficacy of hypertonic saline and normal saline solutions in experimentally induced endotoxic shock in dogs

Pakistan Veterinary …, 2009

This study was contemplated to determine the comparative beneficial effects of hypertonic saline solution and sterile saline solution in induced endotoxic shock in dogs. For this purpose, 12 healthy Mongrel dogs were randomly divided into two equal groups (A and B). All the animals were induced endotoxaemia by slow intravenous administration of Escherichia coli endotoxins 0111:B4. Group A was treated with normal saline solution @ 90 ml/kg BW, while group B was given hypertonic saline solution @ 4 ml/kg BW, followed by normal saline solution @ 10 ml/kg BW. Different parameters were observed for evaluation of these fluids including clinical and haematological parameters, serum electrolytes, mean arterial pressure, and blood gases at different time intervals up to 24 hours post treatments. After infusion of respective fluids, all parameters returned to baseline values in both the groups but group B showed better results than group A except bicarbonates, which better recovered in group A. Thus, it was concluded that a small-volume of hypertonic saline solution could be effectively used in reversing the endotoxaemia. Moreover, it provides a rapid and inexpensive resuscitation from endotoxic shock.

Hyperoxic ventilation improves survival in pigs during endotoxaemia at the critical hemoglobin concentration

Resuscitation, 2011

Aim of the study: Recently it has been demonstrated that short term hyperoxic ventilation (HV) can improve glucose metabolism, reduce pulmonary and hepatic apoptosis, and improve gastrointestinal perfusion during acute sepsis. However, it is unknown whether additional O 2 improves survival. Therefore we investigated the effects of increased plasma O 2 on survival during extreme anaemia and concomitant endotoxaemia in order to quantify the efficacy of HV. Methods: Endotoxaemia (Salmonella abortus equi-LPS) was induced in 14 anesthetized pigs ventilated with room air (FiO 2 = 0.21). Simultaneously, animals were haemodiluted by exchange of whole blood for 6% hydroxyethyl starch (200,000:0.5) until the individual critical hemoglobin concentration (Hb crit) was achieved (outermost limit of tissue oxygenation). Subsequently, animals were either ventilated with an FiO 2 of 0.21 (NOX, n = 7) or an FiO 2 of 1.0 (HOX, n = 7), and observed thereafter for 6 h without further intervention. Results: HV significantly prolonged survival time at Hb crit (NOX, 30 [27/35] min; HOX, 172 [111/235] min, p < 0.05). In contrast to the NOX group, HV maintained MAP, and improved DO 2 and tissue oxygenation in the HOX group. Conclusion: The improvement of survival, oxygen transport and tissue oxygenation seems to underline the efficacy of HV during endotoxaemia and concomitant acute anaemia. Further studies are needed to transfer these results into daily clinical practice.

Dose-Dependent Hemodynamic, Biochemical, and Tissue Oxygen Effects of OC99 following Severe Oxygen Debt Produced by Hemorrhagic Shock in Dogs

Critical Care Research and Practice, 2014

We determined the dose-dependent effects of OC99, a novel, stabilized hemoglobin-based oxygen-carrier, on hemodynamics, systemic and pulmonary artery pressures, surrogates of tissue oxygen debt (arterial lactate7.2±0.1 mM/L and arterial base excess−17.9±0.5 mM/L), and tissue oxygen tension (tPO2) in a dog model of controlled severe oxygen-debt from hemorrhagic shock. The dose/rate for OC99 was established from a pilot study conducted in six bled dogs. Subsequently twenty-four dogs were randomly assigned to one of four groups (n=6per group) and administered: 0.0, 0.065, 0.325, or 0.65 g/kg of OC99 combined with 10 mL/kg lactated Ringers solution administered in conjunction with 20 mL/kg Hextend IV over 60 minutes. The administration of 0.325 g/kg and 0.65 g/kg OC99 produced plasma hemoglobin concentrations of0.63±0.01and1.11±0.02 g/dL, respectively, improved systemic hemodynamics, enhanced tPO2, and restored lactate and base excess values compared to 0.0 and 0.065 g/kg OC99. The admi...

Effect of Hemodiafiltration on Pulmonary Hemodynamics in Endotoxic Shock

Artificial Organs, 2003

Hemofiltration can improve pulmonary hemodynamics during septic shock. The main objective of the study was to determine whether hemodiafiltration (HDF) would also have beneficial effects on pulmonary hemodynamics during septic shock. In the Endo group, six anesthetized pigs received a 0.5 mg/kg endotoxin infusion over 30 min. In the HDF group (n = 6), HDF was started 30 min after the end of the endotoxin infusion, while in the Control group (n = 4) they received HDF but no endotoxin infusion. Pulmonary hemodynamics were analyzed in detail with a four-element windkessel model. Although in the Control group, HDF did not alter pulmonary hemodynamic parameters, in the HDF group, it was responsible for an amplification of the deleterious pulmonary vascular response to endotoxin insult. Our results show that HDF must be used cautiously in septic shock since it can precipitate right heart failure by increasing pulmonary vascular resistance.

The Effects of Decreasing Low-Molecular Weight Hemoglobin Components of Hemoglobin-Based Oxygen Carriers in Swine With Hemorrhagic Shock

Journal of Trauma: Injury, Infection & Critical Care, 2008

Background: Some hemoglobinbased oxygen carriers (HBOCs) improve outcome in animal models of hemorrhagic shock (HS) in comparison with standard asanguinous resuscitation fluids. Nevertheless, concern about intrinsic vasoactivity, linked in part to low-molecular weight (MW) hemoglobin (Hb), has slowed HBOC development. We assessed the impact of decreasing the low-MW Hb component of bovine HBOC on vasoactivity in severe HS. Methods: Anesthetized invasively monitored swine were hemorrhaged 55% blood volume and resuscitated with bovine HBOC containing 31% (31 TD [HBOC-301]), 2% (2 TD [HBOC-201]), or 0.4% (0.4 TD) low-MW Hb. Pigs received four 10 mL/kg infusions over 60 minutes, hospital arrival was simulated at 75 minutes, organ blood flow (BF) was evaluated by microsphere injection, and monitoring was continued for 4 hours followed by complete necrotic evaluation. Results: There were few differences between 2 TD and 0.4 TD. Thirty-one TD pigs had higher systemic and pulmonary blood pressure (BP), systemic vascular resistance index, and pulmonary artery wedge pressure, compared with 2 TD or 0.4 TD (p < 0.01); however, pigs in all groups had at least mildly elevated BP. Transcutaneous tissue oxygenation, base excess, and mixed venous oxygen saturation were similar across groups; lactate and methemoglobin were highest with 0.4 TD (p < 0.03). There were no group differences in BF. Over time, myocardial BF increased and hepatic BF decreased in all groups (for 31 TD, p < 0.05); renal BF was unchanged in all groups. There were no group differences in heart, lung, or liver histopathology, and survival. Conclusions: Although purification from 31% to 2% low-MW Hb content significantly decreased vasoactive responses, further purification to 0.4% had no additional clinically measurable effects in severe HS. If further diminution in HBOC vasoactivity is desired for use in HS, additional technical approaches may be required.

Unintended Consequences; Fluid Resuscitation Worsens Shock in an Ovine Model of Endotoxemia

American journal of respiratory and critical care medicine, 2018

Fluid resuscitation is widely considered a life saving intervention in septic shock however recent evidence has questioned both its safety and efficacy in sepsis. This study sought to compare fluid resuscitation with vasopressors with vasopressors alone in a hyperdynamic model of ovine endotoxemia. Endotoxemic shock was induced in sixteen sheep after which they received fluid resuscitation with 40mls/kg of 0.9% saline or commenced haemodynamic support with protocolized noradrenaline and vasopressin. Microdialysis catheters were inserted into the arterial circulation, heart, brain, kidney and liver to monitor local metabolism. Blood samples were recovered to measure serum inflammatory cytokines, creatinine, troponin, ANP, BNP and hyaluronan. All animals were monitored and supported for 12 hours after fluid resuscitation. After resuscitation animals receiving fluid resuscitation required significantly more noradrenaline to maintain the same mean arterial pressure in the subsequent 12 ...