Slow as Compared to Rapid Rewarming After Mild Hypothermia Improves Survival in Experimental Shock.

BACKGROUND: Accidental hypothermia following trauma is an independent risk factor for mortality. However, in most experimental studies, hypothermia clearly improves outcome. We hypothesized that slow rewarming is beneficial over rapid rewarming following mild hypothermia in a rodent model of hemorrhagic shock. MATERIALS AND METHODS: We subjected 32 male Wistar rats to severe hemorrhagic shock (25-30 mmHg for 30 min). Rats were assigned to four experimental groups (normothermia, hypothermia, rapid rewarming [RW], and slow RW). During induction of severe shock, all but the normothermia group were cooled to 34°C. After 60 min of shock, rats were resuscitated with Ringer's solution. The two RW groups were rewarmed at differing rates (6°C/h versus 2°C/h). RESULTS: Slow RW animals exhibit a significantly prolonged survival compared with the rapid RW animals (P < 0.05). Nevertheless, hypothermic animals show a significant survival benefit as compared to all other experimental groups. Whereas seven animals of the hypothermia group survived to the end of the experiment, none of the other animals did (P < 0.001). No significant differences were found regarding acid base status, metabolism, parameters of organ injury, and coagulation. CONCLUSIONS: The results indicate that even slow RW with 2°C/h may be still too fast in the setting of experimental hemorrhage. Too rapid rewarming may result in a loss of the protective effects of hypothermia. As rewarming is ultimately inevitable in patients with trauma, potential effects of rewarming on patient outcome should be further investigated in clinical studies.

The Liver and Small Intestine Can Partly Compensate Severe Normovolemic Hemodilution in a Rat Model.

BACKGROUND: Knowing the individual critical hematocrit for every organ is essential in operative scenarios in which extensive blood losses are expected. In the past, experimental settings were very heterogeneous resulting in the publication of widely differing values even for one organ in the same species. This study aimed to investigate the compensatory capacity of the liver and the small intestine in a rat model of severe normovolemic hemodilution. MATERIALS AND METHODS: Male rats were subjected to a stepwise hemodilution with a succinylated gelatin-containing solution to a final hematocrit of 10%, being observed for additional 150 min. During the course of the experiment, blood glucose and L-lactate, as well as D-lactate and intestinal fatty acid-binding protein-2 measurements, were performed eight times in total. The amino acids alanine and glutamine were measured during dilution and at the end of the experiment (four times in total). Hemodilutional effects on the blood and oxygen supply of the liver and the small intestine were measured in a minimally invasive manner. RESULTS: In the liver and the small intestine, there were no substantial changes in the blood flow of the microcirculation. Plasma glucose and lactate levels rose transiently, whereas lactate values did not exceed the upper threshold of aerobic metabolism. Plasma levels of the amino acids alanine and glutamine rose significantly and stayed elevated, whereas D-lactate and intestinal fatty acid-binding protein-2 were not significantly increased at any point during the whole experimental time compared to the initial value. CONCLUSIONS: Severe hemodilution with a succinylated gelatin-containing solution is tolerated at a profoundly low hematocrit value of 10% during the experimental phase of 150 min.

Postoperative Compensatory Ammonium Excretion Subsequent to Systemic Acidosis in Cardiac Patients.

BACKGROUND: Postoperative acid-base imbalances, usually acidosis, frequently occur after cardiac surgery. In most cases, the human body, not suffering from any severe preexisting illnesses regarding lung, liver, and kidney, is capable of transient compensation and final correction. The aim of this study was to correlate the appearance of postoperatively occurring acidosis with renal ammonium excretion. MATERIALS AND METHODS: Between 07/2014 and 10/2014, a total of 25 consecutive patients scheduled for elective isolated coronary artery bypass grafting with cardiopulmonary bypass were enrolled in this prospective observational study. During the operative procedure and the first two postoperative days, blood gas analyses were carried out and urine samples collected. Urine samples were analyzed for the absolute amount of ammonium. RESULTS: Of all patients, thirteen patients developed acidosis as an initial disturbance in the postoperative period: five of respiratory and eight of metabolic origin. Four patients with respiratory acidosis but none of those with metabolic acidosis subsequently developed a base excess > +2 mEq/L. CONCLUSION: Ammonium excretion correlated with the increase in base excess. The acidosis origin seems to have a large influence on renal compensation in terms of ammonium excretion and the possibility of an overcorrection.

Transient dilutional acidosis but no lactic acidosis upon cardiopulmonary bypass in patients undergoing coronary artery bypass grafting.

INTRODUCTION: Dilutional acidosis may result from the introduction of a large fluid volume into the patients' systemic circulation, resulting in a considerable dilution of endogenous bicarbonate in the presence of a constant carbon dioxide partial pressure. Its significance or even existence, however, has been strongly questioned. Blood gas samples of patients operated on with standard cardiopulmonary bypass (CPB) were analyzed in order to provide further evidence for the existence of dilutional acidosis. MATERIAL AND METHODS: Between 07/2014 and 10/2014, a total of 25 consecutive patients scheduled for elective isolated coronary artery bypass grafting with CPB were enrolled in this prospective observational study. Blood gas samples taken regularly after CPB initiation were analyzed for dilutional effects and acid-base changes. RESULTS: After CPB initiation, hemoglobin concentration dropped from an average initial value of 12.8 g/dl to 8.8 g/dl. Before the beginning of CPB, the mean value of the patients' pH and base excess (BE) value averaged 7.41 and 0.5 mEq/l, respectively. After the onset of CPB, pH and BE values significantly dropped to a mean value of 7.33 (p < 0.0001) and -3.3 mEq/l (p < 0.0001), respectively, within the first 20 min. In the following period during CPB they recovered to 7.38 and -0.5 mEq/l, respectively, on average. Patients did not show overt lactic acidosis. CONCLUSIONS: The present data underline the general existence of dilutional acidosis, albeit very limited in its duration. In patients undergoing coronary artery bypass grafting it seems to be the only obvious disturbance in acid-base homeostasis during CPB.

Hypokalemia during acute metabolic acidosis on hemodilution with succinylated gelatin in rats.

BACKGROUND: Extracellular metabolic acidosis of mineral origin is commonly associated with plasma hyperkalemia. Nevertheless, in previous experiments, animals subjected to acute metabolic acidosis induced by normovolemic hemodilution using a colloidal volume replacement solution containing succinylated gelatin (gelafundin), developed a hypokalemic state with concomitant marked increases in diuresis and renal potassium excretion. In the present study, the succinylated gelatin's impact on diuresis and consequently potassium excretion was studied. MATERIAL AND METHODS: Anesthetized Wistar rats were subjected to acute metabolic acidosis either due to normovolemic hemodilution with gelafundin (group I) or HCl application (groups II and III). Animals of group III received mannitol in addition. Blood gas analyses were performed regularly. Urine was continuously collected, and the excreted volume as well as potassium concentration was measured. RESULTS: In all groups, mean base excess value was about -3.0 mEq/L. Plasma potassium concentration decreased from 5.0 mM to 4.5 mM in group I, whereas it was almost constant in groups II and III. The urine volume amounted to 2300 µL in groups I and III and 1000 µL in group II. Excreted total amount of potassium in urine was 340 µmol (group I), 125 µmol (group II), and 230 µmol (group III), respectively. CONCLUSIONS: The employed volume replacement solution leads to increased diuresis induced by excretion of succinylated gelatin, which also sufficiently accounts for enhanced potassium loss into urine and decreased plasma potassium concentration. Therefore, generalization of the connection between acute metabolic acidosis and plasma hyperkalemia, as often stated in literature, is not justified.

L-Malate's Plasma and Excretion Profile in the Treatment of Moderate and Severe Hemorrhagic Shock in Rats.

Introduction. Malate is a standard component in fluid therapy within a wide range of medical applications. To date, there are insufficient data regarding its plasma distribution, renal excretion, and metabolism after infusion. This study aimed to investigate these three aspects in a rat model of moderate and severe hemorrhagic shock (HS). Methods. Male Wistar rats were subjected to HS by dropping the mean arterial blood pressure to 25-30 mmHg (severe) and 40-45 mmHg (moderate), respectively, for 60 minutes. Subsequently, reperfusion with Ringer-saline or a malate containing crystalloid solution (7 mM, 13.6 mM, and 21 mM, resp.) was performed within 30 minutes, followed by an observation period of 150 minutes. Results. In the present experiments, malate rapidly disappeared from the blood, while only 5% of the infused malate was renally excreted. In the resuscitation interval the urinary citrate and succinate amounts significantly increased compared to control. Conclusion. Malate's half-life is between 30 and 60 minutes in both, moderate and severe HS. Thus, even under traumatic conditions malate seems to be subjected to rapid metabolism with participation of the kidneys.

Histidine and other amino acids in blood and urine after administration of Bretschneider solution (HTK) for cardioplegic arrest in patients: effects on N-metabolism.

Bretschneider (histidine-tryptophan-ketoglutarate, HTK) solution employed for induction of cardioplegic arrest possesses a high histidine concentration (198 mM). Due to the large volume administered, massive amounts of histidine are incorporated. The aim of the study was to evaluate alterations in amino acid and nitrogen metabolism originating from histidine degradation. Between 07/2014 and 10/2014, a total of 29 consecutive patients scheduled for elective isolated coronary artery bypass grafting with cardiopulmonary bypass (CPB) were enrolled in this prospective observational study. The patients received 1.6 L cardioplegic Bretschneider solution on average. Blood gas and urine samples obtained were analyzed for amino acid as well as urea and ammonium concentrations. After CPB initiation, plasma histidine concentration greatly increased to 21,000 µM to reach 8000 µM at the end. Within the operative period, plasma concentrations of aspartate, glutamate, asparagine, alanine, and glutamine increased variable in magnitude. During the same time, urinary analysis revealed histidine excretion of 19,500 µmol in total and marked elevations in glutamate and glutamine excretion. The absolute amounts of urea and ammonium excreted additionally were 3 mmol and 8 mmol, respectively. Already during CPB, distinct amounts of the histidine administered are metabolized, mainly to other amino acids, but only small amounts to urea and ammonia. Thus, the impact of the histidine incorporated on acid-base status in the intraoperative phase is minor. On the other hand, intraoperative provision of several amino acids arising from histidine metabolism might mitigate postaggression syndrome.

Acid-base and electrolyte status during normovolemic hemodilution with succinylated gelatin or HES-containing volume replacement solutions in rats.

BACKGROUND: In the past, several studies have compared different colloidal replacement solutions, whereby the focus was usually on the respective colloid. We therefore systematically studied the influence of the carrier solution's composition of five approved colloidal volume replacement solutions (Gelafundin, Gelafusal, Geloplasma, Voluven and Volulyte) on acid-base as well as electrolyte status during and following acute severe normovolemic hemodilution. The solutions differed in the colloid used (succinylated gelatin vs. HES) and in the presence and concentration of metabolizable anions as well as in their electrolyte composition. METHODS: Anesthetized Wistar rats were subjected to a stepwise normovolemic hemodilution with one of the solutions until a final hematocrit of 10%. Subsequent to dilution (162 min), animals were observed for an additional period (150 min). During dilution and observation time blood gas analyses were performed eight times in total. Additionally, in the Voluven and Volulyte groups as well as in 6 Gelafundin animals, electrolyte concentrations, glucose, pH and succinylated gelatin were measured in urine and histopathological evaluation of the kidney was performed. RESULTS: All animals survived without any indications of injury. Although the employed solutions differed in their respective composition, comparable results in all plasma acid-base and electrolyte parameters studied were obtained. Plasma pH increased from approximately 7.28 to 7.39, the plasma K(+) concentration decreased from circa 5.20 mM to 4.80-3.90 mM and the plasma Cl(-) concentration rose from approximately 105 mM to 111-120 mM. Urinary analysis revealed increased excretion of K(+), H(+) and Cl(-). CONCLUSIONS: The present data suggest that the carrier solution's composition with regard to metabolizable anions as well as K(+), Ca(2+) only has a minor impact on acid-base and electrolyte status after application of succinylated gelatin or HES-containing colloidal volume replacement solutions.

A fatal intoxication by chloroprene.

UNLABELLED: Objective Chloroprene, 2-chloro-1,3 butadiene, is a volatile synthetic liquid. The chloroprene monomer is extremely reactive and is used for the production of latexes and synthetic rubber such as Neoprene. Up to now an acute lethal human exposure has been described only once in the literature [19]. The intoxication is associated with nervous system depression, pulmonary edema, narcosis, and respiratory arrest. Case report A 29-year-old chemistry company worker was found unconscious in an empty vessel (depth: 3m) used for chloroprene. The man was dressed in shoes, trousers, a helmet and a respiratory mask. The upper part of the body was unclothed. In spite of reanimation, the man died three hours later in a hospital. MATERIAL AND METHODS: All analyses were performed by headspace gas chromatography (HS/GC/FID). In addition, brain, muscle and myocardial muscle were analysed by headspace GC-MS. Results and discussion Autopsy findings: The cause of death could not be determined as the macromorphological findings were unspecific. Toxicology findings The calibration curve of chloroprene in serum shows linearity from 1.0 to 200 µg/ml (r(2)=0.9999) using benzene as internal standard. The LOD is 0.28 µg/ml, the LLOQ is 0.99 µg/ml. Tissues and body fluids were stored at -20 °C till the analysis. Chloroprene was quantified after addition of benzene as the internal standard. It was found in nearly all tissues and body fluids except in the urine and lung. The highest concentrations were detected in the kidney, liver, myocardial muscle and especially in the brain. Furthermore, hexanal was found in all samples except in the urine. The amount of hexanal in some specimens is high, especially in the lung, bile, gastric content and myocardial muscle. Conclusion We assume that a significant amount of chloroprene was not only inhaled but also absorbed through the skin because the man wore a respiratory mask. Presumably the accident would not have happened if the works safety protocols had been followed. The reason why high concentrations of hexanal were found in the tissues could not be clarified.