Vagus Nerve Stimulation Attenuates Multiple Organ Dysfunction in Resuscitated Porcine Progressive Sepsis.

OBJECTIVES: To investigate the potential benefits of vagus nerve stimulation in a clinically-relevant large animal model of progressive sepsis. DESIGN: Prospective, controlled, randomized trial. SETTING: University animal research laboratory. SUBJECTS: Twenty-five domestic pigs were divided into three groups: 1) sepsis group (eight pigs), 2) sepsis + vagus nerve stimulation group (nine pigs), and 3) control sham group (eight pigs). INTERVENTIONS: Sepsis was induced by cultivated autologous feces inoculation in anesthetized, mechanically ventilated, and surgically instrumented pigs and followed for 24 hours. Electrical stimulation of the cervical vagus nerve was initiated 6 hours after the induction of peritonitis and maintained throughout the experiment. MEASUREMENTS AND MAIN RESULTS: Measurements of hemodynamics, electrocardiography, biochemistry, blood gases, cytokines, and blood cells were collected at baseline (just before peritonitis induction) and at the end of the in vivo experiment (24 hr after peritonitis induction). Subsequent in vitro analyses addressed cardiac contractility and calcium handling in isolated tissues and myocytes and analyzed mitochondrial function by ultrasensitive oxygraphy. Vagus nerve stimulation partially or completely prevented the development of hyperlactatemia, hyperdynamic circulation, cellular myocardial depression, shift in sympathovagal balance toward sympathetic dominance, and cardiac mitochondrial dysfunction, and reduced the number of activated monocytes. Sequential Organ Failure Assessment scores and vasopressor requirements significantly decreased after vagus nerve stimulation. CONCLUSIONS: In a clinically-relevant large animal model of progressive sepsis, vagus nerve stimulation was associated with a number of beneficial effects that resulted in significantly attenuated multiple organ dysfunction and reduced vasopressor and fluid resuscitation requirements. This suggests that vagus nerve stimulation might provide a significant therapeutic potential that warrants further thorough investigation.

[CLINICAL ASPECTS OF THE BLOOD LACTATE DYNAMICS DURING OPERATIONS ON THE HEART AND THE AORTA IN CONDITIONS OF CARDIOPULMONARY BYPASS.]

BACKGROUND: The frequency and the causes for the development of hyperlactatemia during operations on the heart and aorta in conditions of cardiopulmonary bypass (CB) is not adequately described in the literature. THE AIM: To study the clinical significance of the lactate dynamics in arterial blood depending on the source ofpathology, stages of operation, basic parameters of cardiopulmonary bypass, the characteristics of the post-perfusion period, and to identify ways to prevent the development of intraoperative hyperlactatemia in surgical interventions on the heart and aorta. MATERIALS AND METHODS: 420 adult cardiac surgery patients operated on the heart and ascending aorta were examined. All patients were operated on under balanced General anesthesia, CB in hypothermic or normothermic mode. Lactate level in arterial blood and the frequency of hyperlactatemia were analyzed at the following stages of operation: after induction of anesthesia, prebypass period, during CB, in the postbypass period and at the time of admission of the patient in the ICU. During CB we analyzed the duration of the CB, the degree of hemodilution, calculated value of oxygen delivery. Oxygen consumption was recorded in the current mode, the monitor CDI-500. Hyperlactatemia was considered the concentration of lactate above 3 mmol/L. RESULTS: Preperfusion period in all groups of cardiac surgery patients was characterized by a normal level of blood lactate in the absolute majority ofpatients, the frequency of hyperlactatemia did not exceed 1%. Hemodynamic stability was achieved without the use of catecholamines by optimizing volemia and heart rate. While CB showed a trend of increasing lactate on average in comparison with the previous period in patients operated on the heart. Duration CB less than 3 hours was not a factor in the development of hyperlactatemia, provided that oxygen delivery in all patients during perfusion exceeded 300 ml/min/m2, hematocrit ofperfusate at the end of CB was at 25-27% in most patients. To maintain it at a large hemodilution the ultrafiltration hemoconcentration was used. The frequency of hyperlactatemia was 3%. A significant increase in lactate concentration at the end of the CB to 3.39k1,3 mmol/l (range of 2.1-7.2 mmol/l) on the background of metabolic acidosis found only in patients with circulatory arrest due to receipt of blood products of anaerobic glycolysis after the resumption of the CB. They have frequency of hyperlactatemia risen to 29%. The lac- tate average value at admission ofpatients in the ICU with application of 50-60% ofpatients in dopamine/dobutrex at a dose of 5 mcg/kg/min and reaching the targets of transfusion therapy was slightly higher in the baseline period and corresponded to the upper level of normal values. Only during operations on the aortic arch under conditions of circulatory arrest, the concentration of lactate at the end of the operation was 3,4+1,1 mmol/l with a tendency to decrease in comparison with the period of the CB. From 88 to 93% patients during operations on the heart and ascending aorta without circulatory arrest and 64% ofpatients after operations on the aortic arch with circulatory arrest were admitted to the ICU with a normal lactate level in arterial blood Conclusion. The duration ofperfusion less than 3 hours in the conditions of these indicators preservation is not a risk factor for the development of hyperlactatemia. In postbypass period during operations on the heart and aorta without circulatory arrest about 90% ofpatients transferred to the intensive care unit (ICU) with normal values of lactate. During operations on the aortic arch with circulatory arrest about 60% ofpatients have normal levels of lactate at admission from the operating room to the ICU.

Hyperlactatemia in type 2 diabetes: Can physical training help?

Type 2 diabetic patients often exhibit hyperlactatemia in association with a reduced aerobic-oxidative capacity and a restricted lactate transport. Studies suggest a link between increased lactate levels and the manifestation and progression of insulin resistance. However, the specificities of molecular mechanisms remain unclear, and it is not entirely clear whether elevated lactate levels are a cause or consequence of type 2 diabetes. This review focuses on lactate as a key molecule in diabetes and provides an overview of how regular physical activity can be helpful in normalizing elevated lactate levels in type 2 diabetic patients. Physical training may reduce lactate production and reinforce lactate transport and clearance among this particular patient group. We emphasize the crucial role physical training plays in the therapy of type 2 diabetes due to evidence that pharmacological treatment with metformin, which is commonly used in the first-line therapy of type 2 diabetes, does not help reducing lactate levels.

Effect of glucose-insulin-potassium on hyperlactataemia in patients undergoing valvular heart surgery: A randomised controlled study.

BACKGROUND: Hyperlactataemia represents oxygen imbalance in the tissues and its occurrence during cardiac surgery is associated with adverse outcomes. Glucose-insulin-potassium (GIK) infusion confers myocardial protection against ischaemia-reperfusion injury and has the potential to reduce lactate release while improving its clearance. OBJECTIVES: The objective of this study is to compare the effect of GIK on the incidence of hyperlactataemia in patients undergoing valvular heart surgery. DESIGN: A randomised controlled study. SETTING: Single university teaching hospital. PATIENTS: One hundred and six patients scheduled for elective valvular heart surgery with at least two of the known risk factors for hyperlactataemia. INTERVENTION: Patients were randomly allocated to receive either GIK solution (insulin 0.1 IU kg(-1) h(-1) and an infusion of 30% dextrose and 80 mmol l(-1) potassium at 0.5 ml kg(-1) h(-1)) or 0.9% saline (control) throughout surgery. MAIN OUTCOME MEASURES: The primary outcome was the incidence of hyperlactataemia (lactate ≥ 4 mmol l(-1)) during the operation and until 24 h after the operation. Secondary outcomes included haemodynamic parameters, use of vasopressor or inotropic drugs, and fluid balance until 24 h postoperatively. Postoperative morbidity endpoints were also assessed. RESULTS: The incidences of hyperlactataemia were similar in the groups (32/53 patients in each of the control and GIK groups, P > 0.999). There were no intergroup differences in haemodynamic parameters, use of vasopressor and inotropic drugs, or fluid balance. The incidences of postoperative morbidity endpoints were similar in both groups. CONCLUSION: Despite its theoretical advantage, GIK did not provide beneficial effects in terms of the incidence of hyperlactataemia or outcome in patients undergoing valvular heart surgery. TRIAL REGISTRATION: Clinicaltrials.gov identifier: NCT01825720.

[Propranolol and lactatemia during hypovolemic shock: a case report]. / Propranolol et lactatémie durant un choc hypovolémique non septique : à propos d'une observation.

Lactate production results from anaerobic glycolysis. This pathway is recruited physiologically during intense and sustained muscular contractions. Hyperlactatemia may develop when tissue oxygenation is jeopardized such as in shock, its absence having been, however, sometimes reported in sepsis in which interactions between infectious agents and the organism's cells might blunt or disrupt hyperlactatemia development. During the course of acute rotavirus gastroenteritis, a 9-month-old girl developed severe dehydration (capillary-refill time, 5 s) leading to hypovolemic shock without signs of sepsis and with hypotension at 62/21 mmHg Surprisingly, the child failed to develop hyperlactatemia during shock. An etiologic search to understand why hyperlactatemia did not occur revealed that this patient had been receiving propranolol since the age of four months for the treatment of a Cyrano hemangioma. Via its inhibitory action on ß-adrenergic receptors, propranolol antagonizes the stimulation of glycolysis by catecholamines, which may be rationally proposed to have contributed to preventing hyperlactatemia during hypovolemic shock in this patient. Mechanisms by which propranolol can mediate this antihyperlactatemia action are further illustrated and discussed.

Sodium lactate for fluid resuscitation: the preferred solution for the coming decades?

In a recent issue of Critical Care, 0.5 M sodium lactate infusion for 24 hours was reported to increase cardiac output in patients with acute heart failure. This effect was associated with a concomitant metabolic alkalosis and a negative water balance. Growing data strongly support the role of lactate as a preferential oxidizable substrate to supply energy metabolism leading to improved organ function (heart and brain especially) in ischemic conditions. Due to its sodium/chloride imbalance, this solution prevents hyperchloremic acidosis and limits fluid overload despite the obligatory high sodium load. Sodium lactate solution therefore shows many advantages and appears a very promising means for resuscitation of critically ill patients. Further studies are needed to establish the most appropriate dose and indications for sodium lactate infusion in order to prevent the occurrence of severe hypernatremia and metabolic alkalosis.