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Biomedical subjects

Robert G Hahn

Publications and source records attributed to Robert G Hahn.

14 recordsLinked to original sources
PubMed2003

Natriuresis and the extracellular volume expansion by hypertonic saline.

BACKGROUND: The mechanisms governing the duration of the extracellular fluid volume (ECF) expansion as a result of intravenous infusion of hypertonic saline solution are poorly understood. We hypothesized that the duration is closely related to the sodium excretion. MATERIALS AND METHODS: Six conscious splenectomized ewes with a mean body weight of 30 kg were given an intravenous infusion of 4 ml x kg(-1) of 7.5% saline solution on two occasions, one over a period of 5 min and another over a period of 20 min. Mass balance and volume kinetic calculations of the distribution and elimination of fluid were performed after repeated sampling of the plasma sodium concentration and the urinary excretion of water and sodium during 3 h. RESULTS: On considering the addition of sodium to and its excretion from the body, the plasma sodium concentration indicated a 10% dilution of the extracellular space. The volume expansion decayed at an average rate of 20% of the volume expansion per hour, which, however, varied greatly in the animals, depending on their capacity to excrete sodium. After 1 h, increasing natriuresis promoted translocation of water into the cells, which amounted to 25-35% of the total elimination. Computer simulations indicated that tripled natriuresis (up to approximately 750 mmol l(-1)) would increase the rate of elimination to 45% of the volume expansion per hour. CONCLUSION: The sodium excretion was inversely proportional to the duration of the extracellular volume expansion by 7.5% saline.

Animals↗
PubMed2003

Nitrous oxide as a marker for irrigating fluid absorption--an experimental study in the pig.

OBJECTIVE: To study whether tracer amounts of a gas, nitrous oxide (N(2)O), might be a suitable marker for absorption of irrigating fluid during endoscopic procedures. MATERIAL AND METHODS: N(2)O was dissolved to a concentration of 10% in a commercially available irrigating fluid containing 3% mannitol and 1% ethanol. Seven experiments involving administration of the fluid via either the i.v. or i.p. route were performed in three pigs under general anesthesia. The N(2)O concentration and, in one pig, the ethanol concentration, were measured in the expired breath. RESULTS: The N(2)O method readily detected i.v. bolus injections of 2, 10 and 20 ml quantities of irrigating fluid. Continuous administration of the fluid over a 20-min period showed that the N(2)O concentration increased and decreased very rapidly when the infusions were turned on and off, while a quasi-steady state was reached after approximately 2 min. The maximum breath N(2)O concentration during a 600-ml infusion was 0.05%. The breath ethanol concentration rose as fast as the N(2)O level but decreased more slowly when the infusion was turned off. As with ethanol, the N(2)O responses were much slower when the fluid was given by i.p. infusion, and the maximum concentration was only one-third of that during i.v. infusion. CONCLUSIONS: Dissolving N(2)O in irrigating fluid offers the possibility of detecting an administered fluid volume in the exhaled breath in the same way as for ethanol. The advantages of N(2)O include better resolution, lower toxicity and rapid elimination.

Absorption↗
PubMed2003

Nitric oxide and endothelin concentrations during intravenous infusion of urological irrigating fluid.

OBJECTIVE: To study the possible role of two vasoactive mediators, nitric oxide (NO) and endothelin, in the hemodynamic alterations following absorption of irrigating fluid. MATERIAL AND METHODS: Twelve male volunteers received an intravenous administration of 1.5% glycine, given at a rate of 0.5 ml/kg/min for 30 min. Infusions of 3% mannitol served as controls. Blood pressure, heart rate and the plasma levels of endothelin and nitrite/nitrate (an index of NO activity) were measured before, during and after the infusions. RESULTS: The endothelin concentration at baseline correlated inversely with the systolic arterial pressure (p<0.01). No qualitative differences were found between the two fluids with respect to the NO and endothelin responses, but the observed variations indicated the role of the two fluids during volume loading. In general, an elevation of blood pressure during the infusions was associated with an increase in the endothelin concentration, while a sustained elevation 30 min later was accompanied by a decrease in the NO activity. Reductions in the blood pressure and heart rate were associated with decreased NO concentrations. CONCLUSION: The endothelin/NO axis may increase blood pressure in response to volume loading; it also acts to stabilize the circulation at baseline and probably also when the blood pressure decreases.

Adult↗
PubMed2003

Isoflurane but not mechanical ventilation promotes extravascular fluid accumulation during crystalloid volume loading.

BACKGROUND: The combination of isoflurane anesthesia and mechanical ventilation reduces urinary output and promotes redistribution of a crystalloid bolus into the extravascular space. The authors hypothesized that mechanical ventilation rather than isoflurane causes this alteration. METHODS: The fate of a 25-ml/kg, 20-min, 0.9% saline fluid bolus was studied in four different experiments per sheep: while conscious and spontaneously ventilating (CSV), while conscious and mechanically ventilated (CMV), while anesthetized with isoflurane and mechanical ventilated (ISOMV), and while anesthetized with isoflurane and spontaneously ventilating (ISOSV). RESULTS: By calculations based on the indicator dilution and mass balance principles, plasma expansion was similar between protocols. Isoflurane but not mechanical ventilation reduced urinary output and increased interstitial fluid volume (P < 0.001): At 180 min, mean total urinary outputs were 15.6 +/- 2.1 and 15.9 +/- 2.9 ml/kg in the CSV and CMV protocols and 2.7 +/- 0.6 and 3.1 +/- 1.1 ml/kg in the ISOSV and ISOMV protocols, respectively. The net changes in extravascular volume, assumed to be interstitial fluid volume, were 8.6 +/- 3.3 and 8.1 +/- 3.1 ml/kg, and 22.5 +/- 1.5 and 22.1 +/- 1.6 ml/kg in the corresponding protocols. Volume kinetic analysis demonstrated extravascular fluid accumulation associated with isoflurane anesthesia similar to the calculated interstitial accumulation of 20.2 +/- 0.5 and 26.5 +/- 0.3 ml/kg in the ISOSV and ISOMV protocols, respectively. CONCLUSION: Isoflurane, but not mechanical ventilation, decreased urinary excretion and increased interstitial fluid volume. Volume kinetic analysis indicated "third-space" losses due to isoflurane. Perioperative fluid retention may be associated not only with surgical tissue manipulation, but with anesthesia per se.

Anesthetics, Inhalation↗
PubMed2003

Endotoxin boosts the vascular endothelial growth factor (VEGF) in rabbits.

Vascular endothelial growth factor (VEGF) is a cytokine that greatly increases vascular permeability and thereby promotes hypovolemia. The present study examines whether the plasma VEGF concentration is increased by a bolus injection of endotoxin 20 microg/kg in 30 rabbits, and whether the response is modified by vitamin A, which doubles the endotoxin clearance. The results show that endotoxin stimulates a gradual increase in the VEGF concentration to a peak 5 h later which is approximately 100 times higher than the baseline concentration. No statistically significant difference was found between the rabbits that received no further treatment (n = 10) and the ones that were given 1000 IE/kg of vitamin A intravenously 1 h before (n = 10) or after (n = 10) the endotoxin. The rise in VEGF correlated with the development of fever, and the VEGF concentrations were higher in animals with a severely affected physical status as judged by the breathing pattern and changes in posture or reactivity. In conclusion, release of VEGF is part of the cytokine response to endotoxin with a peak occurring 5 h after a bolus injection, and the rise is pronounced also in the presence of a high endotoxin clearance.

Animals↗
PubMed2003

Role of variability in explaining ethanol pharmacokinetics: research and forensic applications.

Variability in the rate and extent of absorption, distribution and elimination of ethanol has important ramifications in clinical and legal medicine. The speed of absorption of ethanol from the gut depends on time of day, drinking pattern, dosage form, concentration of ethanol in the beverage, and particularly the fed or fasting state of the individual. During the absorption phase, a concentration gradient exists between the stomach, portal vein and the peripheral venous circulation. First-pass metabolism and bioavailability are difficult to assess because of dose-, time- and flow-dependent kinetics. Ethanol is transported by the bloodstream to all parts of the body. The rate of equilibration is governed by the ratio of blood flow to tissue mass. Arterial and venous concentrations differ as a function of time after drinking. Ethanol has low solubility in lipids and does not bind to plasma proteins, so volume of distribution is closely related to the amount of water in the body, contributing to sex- and age-related differences in disposition. The bulk of ethanol ingested (95-98%) is metabolised and the remainder is excreted in breath, urine and sweat. The rate-limiting step in oxidation is conversion of ethanol into acetaldehyde by cytosolic alcohol dehydrogenase (ADH), which has a low Michaelis-Menten constant (Km) of 0.05-0.1 g/L. Moreover, this enzyme displays polymorphism, which accounts for racial and ethnic variations in pharmacokinetics. When a moderate dose is ingested, zero-order elimination operates for a large part of the blood-concentration time course, since ADH quickly becomes saturated. Another ethanol-metabolising enzyme, cytochrome P450 2E1, has a higher Km (0.5-0.8 g/L) and is also inducible, so that the clearance of ethanol is increased in heavy drinkers. Study design influences variability in blood ethanol pharmacokinetics. Oral or intravenous administration, or fed or fasted state, might require different pharmacokinetic models. Recent work supports the need for multicompartment models to describe the disposition of ethanol instead of the traditional one-compartment model with zero-order elimination. Moreover, appropriate statistical analysis is needed to isolate between- and within-subject components of variation. Samples at low blood ethanol concentrations improve the estimation of parameters and reduce variability. Variability in ethanol pharmacokinetics stems from a combination of both genetic and environmental factors, and also from the nonlinear nature of ethanol disposition, experimental design, subject selection strategy and dose dependency. More work is needed to document variability in ethanol pharmacokinetics in real-world situations.

Algorithms↗
PubMed2002

Induced hypothermia and rewarming after hemorrhagic shock.

BACKGROUND: Recent patient and animal studies have shown protective effects of hypothermia (HT) in traumatic brain injury and hemorrhagic shock. We have demonstrated a reduced stress level and a lack of additive hemodynamic effects of HT. The present work was undertaken to evaluate whether these effects persist during and after rewarming. METHODS: Pigs were quickly exsanguinated of 40% of their individually calculated blood volume and randomized to HT (32.5 degrees C) or normothermia (controls). After 30 min of HT, rewarming to baseline temperature was initiated. All animals were followed for 7 h. Thrombolelastography was used to evaluate blood coagulation. RESULTS: HT did not aggravate the hemodynamic signs of hemorrhagic shock. HT decreased the oxygen uptake, however, which reduced the oxygen extraction ratio to the prehemorrhage level (P < 0.05). Serum levels of potassium were transiently stabilized by cooling. Coagulation was slower, but blood clot strength was normal. HT also delayed fibrinolysis (P < 0.05). Rewarming reversed all physiological changes induced by HT including those involving the coagulation system. CONCLUSIONS: HT produced few hemodynamic effects in the presence of hemorrhagic shock, but created a surplus of oxygen in the core circulation. Blood clotting was delayed by HT.

Acidosis↗
PubMed2002

Influence of rate and volume of infusion on the kinetics of 0.9% saline and 7.5% saline/6.0% dextran 70 in sheep.

UNLABELLED: We examined whether volume kinetic variables obtained during infusion of a short bolus of 0.9% saline (NS) or 7.5% saline/6.0% dextran 70 (HSD) predict the dilution-time curve resulting from a 20-min infusion of the same fluid. Each of six conscious, splenectomized sheep (mean body weight, 36 +/- 3 kg), on 4 different days, in a random order, received each of 4 IV boluses: NS at a rate of 1.2 mL. kg(-1). min(-1) over 5 min or 20 min or 4.0 mL/kg of HSD over 2 min or 20 min. One, 2, and 3-volume kinetic models were fitted to the dilution of the arterial hemoglobin concentration and the urinary excretion as sampled during 180 min. The maximum dilution of arterial plasma at the end of the 5-min and 20-min infusions of NS was approximately 10% and 22%, respectively, and after the 2-min and 20-min infusions of HSD, maximum dilution was 24% and 21%, respectively. The median absolute performance error was virtually identical when the mean variable estimates from the 5-min infusion of NS were used to predict the individual dilution-time curves of the 5-min (mean, 0.027 dilution units) and 20-min (mean, 0.027) infusions and when the 2-min infusion of HSD was used to predict the dilution during the individual 2-min (mean, 0.050) and 20-min infusions (mean, 0.047). Computer simulations indicated that the difference at the end of infusion between the volume effects of NS and HSD is larger after longer infusions. We concluded that the volume kinetic variables obtained during a short infusion can be used to predict the outcome of a longer one, even if the longer infusion also delivers a larger volume. IMPLICATIONS: Kinetic analysis of a short infusion of 7.5% saline/6% dextran or 0.9% saline accurately predicts the effects of a longer infusion of the same volume (7.5% saline/6% dextran) or of a larger volume (0.9% saline).

Animals↗
PubMed2002

Volume kinetic analysis of the distribution of 0.9% saline in conscious versus isoflurane-anesthetized sheep.

BACKGROUND: The distribution and elimination of 0.9% saline given by intravenous infusion has not been compared between the conscious state and during inhalational anesthesia. METHODS: Six adult sheep received an intravenous infusion of 25 ml/kg of 0.9% saline over 20 min in the conscious state and also during isoflurane anesthesia and mechanical ventilation. The distribution and elimination of infused fluid were studied by volume kinetics based on serial analysis of hemoglobin dilution in arterial blood and by mass balance that incorporated volume calculations derived from volume kinetic analysis and measurements of urinary volumes. RESULTS: The mass balance calculations indicated only minor differences in the time course of plasma volume expansion between the conscious and anesthetized states. However, isoflurane anesthesia markedly reduced urinary volume (median, 9 vs. 863 ml; P < 0.03). In conscious sheep, the central and peripheral volume expansion predicted by volume kinetics agreed well with the calculations based on mass balance. However, during isoflurane anesthesia and mechanical ventilation, calculation using volume kinetic analysis of the variable kr, an elimination factor that, in conscious humans and sheep, is closely related to urinary excretion, represented both urinary excretion and peripheral accumulation of fluid. This suggests that the previous assumption that kr approximates urinary excretion of infused fluid requires modification, i.e., kr simply reflects net fluid movement out of plasma. CONCLUSIONS: In both conscious and anesthetized, mechanically ventilated sheep, infusion of 0.9% saline resulted in minimal expansion of plasma volume over a 3-h interval. In conscious sheep, infused 0.9% saline was rapidly eliminated from the plasma volume by urinary excretion; in contrast, the combination of isoflurane anesthesia and mechanical ventilation reduced urinary excretion and promoted peripheral accumulation of fluid.

Algorithms↗
PubMed2002

Kinetics of isotonic and hypertonic plasma volume expanders.

BACKGROUND: Major differences in plasma volume expansion between infusion fluids are fairly well known, but there is a lack of methods that express their dynamic properties. Therefore, a closer description enabled by kinetic modeling is presented. METHODS: Ten healthy male volunteers received, on different occasions, a constant-rate intravenous infusion over 30 min consisting of 25 ml/kg of 0.9% saline, lactated Ringer's solution, acetated Ringer's solution, 5 ml/kg of 7.5% saline, or 3 ml/kg of 7.5% saline in 6% dextran. One-, two-, and three-volume kinetic models were fitted to the dilution of the total venous hemoglobin concentration over 240 min. Osmotic fluid shifts were considered when hypertonic fluid was infused. RESULTS: All fluids induced plasma dilution, which decreased exponentially after the infusions. The ratio of the area under the dilution-time curve and the infused fluid volume showed the following average plasma-dilution dose-effect (efficiency), using 0.9% saline as the reference (= 1): lactated Ringer's solution, 0.88; acetated Ringer's solution, 0.91; hypertonic saline, 3.97; and hypertonic saline in dextran, 7.22 ("area approach"). Another comparison, based on kinetic analysis and simulation, showed that the strength of the respective fluids to dilute the plasma by 20% within 30 min was 0.94, 0.97, 4.44, and 6.15 ("target dilution approach"). Between-subject variability was approximately half as high for the latter approach. CONCLUSIONS: The relative efficiency of crystalloid infusion fluids differs depending on whether the entire dilution-time profile or only the maximum dilution is compared. Kinetic analysis and simulation is a useful tool for the study of such differences.

Adult↗
PubMed2002

Induced hypothermia after high-energy soft-tissue injury and subsequent hemorrhagic shock.

Many cases of hypothermia (HT) occur in trauma victims subjected to soft tissue injury and hemorrhage. The aim of the present study was to study the effects of HT on the combination of these insults. A standardized gunshot wound was inflicted on the right hind leg of 14 anesthetized piglets. They were then exsanguinated of 50% of their blood volume and randomized to normothermia or HT (30 degrees C). The animals were observed for 4 h after the injury with measurements of hemodynamics, oxygen consumption, and of plasma catecholamines and electrolytes. The insults reduced cardiac output and the arterial pressure by approximately 50%, but no further reduction occurred when HT was induced. The oxygen extraction ratio increased from approximately 35% to 75% in both groups. The gradual reduction of oxygen consumption in HT animals (P < 0.05) decreased the oxygen extraction ratio to around 50%. Heart rate, the serum potassium and creatinine concentrations, and the leukocyte counts were all maintained closer to baseline in the presence of HT. Hypothermia tended to decrease oxygen extraction and was associated with less evidence of tissue injury. These effects are potentially beneficial in soft-tissue trauma combined with hypovolemia.

Animals↗
PubMed2002

Lower dose of hypertonic saline dextran reduces the risk of lethal rebleeding in uncontrolled hemorrhage.

To challenge whether the recommended dose of 4 mL/kg of 7.5% sodium chloride in 6% Dextran (HSD) is optimal for fluid resuscitation in uncontrolled hemorrhage, 30 anesthetized pigs were randomized to receive a 5-min intravenous infusion of either 1, 2, or 4 mL/kg of HSD beginning 10 min after inducing a 5-mm laceration in the infrarenal aorta. In addition to conventional hemodynamic monitoring, the blood loss was calculated as the difference in blood flow rates between flow probes placed proximal and distal to the injury. The results show that the bleeding stopped between 3 and 4 min after the injury and amounted to 338+/-92 mL (mean +/- SEM), which corresponds to 28.5%+/-6.6% of the estimated blood volume. After treatment with HSD was started, six rebleeding events occurred in the 1-mL group, 11 in the 2-mL group, and 16 in the 4-mL group. The amount of blood lost due to rebleeding increased significantly with the dose of HSD and was also associated with a fatal outcome. The total blood loss was 408 mL in the survivors and 630 mL in the nonsurvivors (median, P < 0.007). The mortality in the three groups was 20%, 50%, and 50%, respectively. In conclusion, infusing 4 mL/kg of HSD after uncontrolled aortic hemorrhage promoted rebleeding and increased the mortality, while a dose of 1 mL/kg appeared to be more suitable.

Animals↗