Hyperoxaemia in extreme haemodilution.
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Animals↗
Biomedical subjects
O Habler
Publications and source records attributed to O Habler.
[Reply to the remarks of S.-M. Kasper].
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Blood Transfusion, Autologous↗
Biochemical and cellular composition of alveolar epithelial lining fluid in anesthetized healthy lambs.
Pulmonary toxicity of inhaled materials is often evaluated by (repetitive) assessment of the composition of bronchoalveolar lavage (BAL) fluid or of epithelial lining fluid (ELF) in sheep and lambs. Knowledge of the typical constituents of these fluids obtained from healthy animals is essential for identification of pathologic changes. Few studies have dealt with normal constituents of BAL fluid or ELF in sheep and lamb. The comparability of these studies, however, is limited for reasons concerning the choice of model and BAL technique. The biochemical and cellular composition of alveolar ELF obtained by a standardized BAL procedure was examined in 15 pento-barbital anesthetized 4 months old Merino lambs unexposed to inhaled substances. ELF volume was calculated by using the urea dilution method. We found 20.3 x 10(5) leucocytes per ml ELF, 87.5% of which were alveolar macrophages. Basophils and neutrophils were practically absent while 5% of the counted cells were lymphocytes. 76% of recovered cells were viable. The ELF contained 7 mg/ml total protein; enzyme activities of LDH and AP were 1692 U/l and 145 U/l, respectively.
Anesthesia, Inhalation↗
Effects of hemodilution on splanchnic perfusion and hepatorenal function. I. Splanchnic perfusion.
Perfusion of intestinal organs increases in response to acute normovolemic hemodilution (ANH). However, detailed studies on distribution of regional splanchnic organ perfusion during ANH are lacking. We therefore carried out this study to test the hypothesis that ANH does not cause disturbance of physiologic patterns of regional splanchnic organ blood flow. After governmental permission, 22 anesthetized dogs were instrumented to allow invasive hemodynamic measurements and intracardial injection of radioactive microspheres (diameter 15 micro m) for determination of regional organ perfusion. Measurements were made at baseline (hematocrit 37 +/- 3%) and after ANH with 6% hydroxyethyl starch (mol. wt. 200000 / 0.5) to hct 20 +/- 1%. After completion of the protocol, splanchnic organs were removed and dissected into small samples according to anatomical and functional principles. Regional perfusion was determined based on the microsphere content of each sample. Hepatic, intestinal, and pancreatic blood flow increased with ANH. Hepatic arterial blood flow rose by 86%, whereas portal venous perfusion increased by 28%. Small intestine mucosal perfusion was augmented by 68% while the non-mucosal tissue compartment of the gut wall received 32% more blood flow after ANH which is in proportion to the increase in cardiac index after ANH. This redistribution of intestinal flow might be the basis for the preservation of tissue oxygenation during moderate isovolemic anemia.
Animals↗
Effects of hemodilution on splanchnic perfusion and hepatorenal function. II. Renal perfusion and hepatorenal function.
Hepatorenal perfusion and function were assxssed in 22 dogs undergoing acute normovolemic hemodilution (ANH) to a hematocrit (Hct) of 20% using 6% hydroxyethyl starch (200.000/0.5) as the diluent. Organ perfusion was determined with the radioactive microspheres method. Renal function was assessed by urinary output, creatinine clearance and fractional sodium excretion. Blood volume as well as hepatic function were derived from indocyanine green (ICG) dilution kinetics. Hepatocellular integrity was determined by serum enzymatic activity of glutamate-oxalacetate-transaminase (GOT) and glutamate-pyruvate- transaminase (GPT). ANH to Hct 20% did not change blood volume and mean aortic pressure, while heart rate was slightly elevated (p<0.05) by 5 beats per minute and cardiac output increased by 29% (p<0.05). In contrast to the liver, where arterial and portal venous blood flow increased (86% and 28%, respectively; p<0.05), total renal blood flow as well as intraorgan distribution of renal blood flow remained unchanged post-ANH. While creatinine clearance remained unchanged following ANH, urinary output and fractional urinary excretion increased (p<0.05). In response to enhanced hepatic blood flow after ANH, intravascular half-life of ICG was reduced (p<0.05) and ICG clearance increased (p<0.05). Serum enzymatic activity of GPT decreased upon ANH (p<0.05), while GOT activity remained unchanged. ANH to a Hct 20% does not impair hepatorenal function. Increased urinary output points out the necessity for proper adjustment of crystalloid infusion to maintain normal intravascular volume and avoid hypovolemia and the associated risk of tissue hypoxia.
Animals↗
[Small-volume resuscitation for hypovolemic shock. Concept, experimental and clinical results].
The concept of small-volume resuscitation, the rapid infusion of a small volume (4 ml/kg BW) of hyperosmolar 7.2-7.5% saline solution for the initial therapy of severe hypovolemia and shock was advocated more than a decade ago. Numerous publications have established that hyperosmolar saline solution can restore arterial blood pressure, cardiac index and oxygen delivery as well as organ perfusion to pre-shock values. Most prehospital studies failed to yield conclusive results with respect to a reduction in overall mortality. A meta-analysis of preclinical studies from North and South America, however, has indicated an increase in survival rate by 5.1% following small-volume resuscitation when compared to standard of care. Moreover, small-volume resuscitation appears to be of specific impact in patients suffering from head injuries with increased ICP and in severest trauma requiring immediate surgical intervention. Results from clinical trials in Austria, Germany and France have demonstrated positive effects of hyperosmolar saline solutions when used for fluid loading or fluid substitution in cardiac bypass and in aortic aneurysm surgery, respectively. A less positive perioperative fluid balance, a better hemodynamic stability and improved pulmonary function were reported. In septic patients oxygen consumption could significantly be augmented. The most important mechanism of action of small-volume resuscitation is the mobilisation of endogenous fluid primarily from oedematous endothelial cells, by which the rectification of shock-narrowed capillaries and the restoration of nutritional blood, flow is efficiently promoted. Moreover, after ischemia reperfusion a reduction in sticking and rolling leukocytes have been found following hyperosmolar saline infusion. Both may be of paramount importance in the long-term preservation of organ function following hypovolemic shock. An increased myocardial contractility in addition to the fluid loading effects of hyperosmolar saline solutions has been suggested as a mechanism of action. This, however, could not be confirmed by pre-load independent measures of myocardial contractility. Some concerns have been raised regarding the use of hyperosmolar saline solutions in patients with a reduced cardiac reserve. A slower speed of infusion and adequate monitoring is recommended for high risk patients. Recently, hyperosmolar saline solutions in combination with artificial oxygen carriers have been proposed to increase tissue oxygen delivery through enhanced O2 content. This interesting perspective, however, requires further studies to confirm the potential indications for such solutions. Many hyperosmolar saline colloid solutions have been investigated in the past years, from which 7.2-7.5% sodium chloride in combination with either 6-10% dextran 60/70 or 6-10% hydroxyethyl starch 200,000 appear to yield the best benefit-risk ratio. This has led to the registration of the solutions in South America, Austria, The Czech Republic, and is soon awaited for North America.
Dextrans↗
[Methods for reduction of homologous blood transfusions in operative medicine].
For ethical and socio-economical reasons (cost-explosion in transfusion-medicine, patient's individual destiny), development and consistent application of allogeneic transfusion sparing techniques in surgery is a challenge to anesthesiologists, surgeons and blood-bankers. The combination of different techniques, i.e. autologous predonation, hemodilution, choice of anesthetic regimen, deliberate hypotension, application of antifibrinolytic agents and autotransfusion of intraoperatively saved blood allow for avoidance of allogeneic blood transfusion even in patients presenting important intraoperative hemorrhage. The present article summarizes (1) risks associated with transfusion of allogeneic blood, (2) actually applied pre- and intraoperative techniques to reduce transfusion of allogeneic blood and (3) new concepts (administration of erythropoietin, hyperoxic ventilation and administration of artificial oxygen carries) to further increase the efficacy of autologous predonation and preoperative normovolemic hemodilution.
Humans↗
[Avoidance of homologous blood transfusion despite extreme blood loss].
We report the case of a 22-year-old woman who underwent two-step scoliosis surgery without allogeneic transfusion, although the intraoperative blood loss (3500 ml) during the first procedure was higher than the calculated blood volume (3250 ml). Preoperatively the patient had donated four units of autologous blood. Intraoperatively blood-saving methods were combined. During the first operation acute normovolemic hemodilution (target hemoglobin 9.0 g/dl) was applied and during the second operation controlled hypotension (systolic blood pressure 80 mmHg). Intraoperative auto-transfusion was used in both procedures. During the first operation severe normovolemic anemia (minimal hemoglobin 3.5 g/dl) was accepted while the patient was ventilated with FiO2 1.0. The hemoglobin concentration was 8.6 g/dl after the first procedure and had increased to 11.6 g/dl 4 weeks after the second procedure. No severe complications occurred during the postoperative phase. This case report shows that also in surgical procedures with extreme blood loss any allogenic transfusion can be avoided by the combination of blood-saving methods, acceptance of low intraoperative transfusion trigger and ventilation with 100% oxygen.
Adult↗
A tool for balancing activity from isotopes used for the radioactive microsphere method.
The radioactive microsphere method for determination of regional organ blood flow is widely used in experimental studies. The measurement error of this method in part depends on balanced activities from the set of nuclides used. Achieving even distribution of half-life corrected activity is tedious due to the many calculations needed and is limited by minimal and maximal allowable amounts of microspheres per injection. In two experiments we showed that incorrect planning of microspheres numbers can lead to invalidation of results. Therefore, we developed a program that allows optimization of half-life corrected activities and tested it on an experimental series of 16 dogs. Despite large discrepancies of specific activities of nuclides, storage times and half-lives, balancing activities with the program succeeded: on the average, the accumulated gamma spectra consisted of 22.3 +/- 6.9 85Sr, 18.9 +/- 6.8 141Ce, 10.7 +/- 6.2 51Cr, 23.9 +/- 6.7 95Nb, 16.9 +/- 7.2 46Sc, and 7.3 +/- 2.7% 114mIn radiation, respectively.
Animals↗
Effect of hypertonic saline/dextran on post-stenotic myocardial perfusion, metabolism, and function during resuscitation from hemorrhagic shock in anesthetized pigs.
Resuscitation using small volumes of hypertonic saline solutions normalizes cardiac output without fully restoring arterial pressure. This study compared the efficacy of either 7.2% saline/10% dextran 60 (HSDex) or the identical sodium load of normal saline (NS) to improve regional myocardial blood flow (MBF), contractile function, and oxygen metabolism in the presence of a critical coronary stenosis. Fourteen anesthetized, open-chest pigs (25 +/- 3.6 kg) were instrumented to assess left anterior descending coronary artery (LAD) flow, post-stenotic oxygen, and lactate metabolism, regional myocardial segment shortening (SS, sonomicrometry), and MBF (radioactive microspheres). After implementation of a critical LAD-stenosis, shock was induced by hemorrhage (mean arterial pressure (MAP) 45-50 mmHg for 75 min). Resuscitation was started by infusion (2 min) of either HSDex (n = 7,10% of blood loss) or NS (n = 7, 80% of blood loss); 30 min later 6% dextran 60 (10% of blood loss) was administered in both groups. The LAD-stenosis did not affect myocardial metabolism, SS, or MBF at rest. After hemorrhage, MBF remained unchanged from baseline in non-stenotic but decreased by 53% in post-stenotic myocardium (p < .05). The endo-epicardial flow ratio fell below 1.0 in both areas. SS decreased by 10-15% only in post-stenotic myocardium (p < .05). Resuscitation with both HSDex and NS restored cardiac index (CI) but not MAP. MBF increased above baseline values with either solution in non-stenotic while it remained at shock levels in post-stenotic myocardium, where ischemia persisted as evidenced by lactate production and depressed SS. Neither in non-stenotic nor in post-stenotic myocardium was the epi-endocardial flow ratio normalized upon resuscitation with HSDex or NS. We conclude that in the presence of a flow-limiting coronary stenosis, initial fluid resuscitation with both HSDex and the identical sodium load of NS failed to restore perfusion pressure, redistributed MBF in favor of normally perfused myocardium, and did not reverse ischemia in post-stenotic myocardium.
Animals↗
Myocardial blood flow heterogeneity in shock and small-volume resuscitation in pigs with coronary stenosis.
Myocardial blood flow heterogeneity in shock and small-volume resuscitation in pigs with coronary stenosis. J. Appl. Physiol. 83(6): 1832-1841, 1997.-We analyzed the effects of shock and small-volume resuscitation in the presence of coronary stenosis on fractal dimension (D) and spatial correlation (SC) of regional myocardial perfusion. Hemorrhagic shock was induced and maintained for 1 h. Pigs were resuscitated with hypertonic saline-dextran 60 [HSDex, 10% of shed blood volume (SBV)] or normal saline (NS; 80% of SBV). Therapy was continued after 30 min with dextran (10% SBV). At baseline, D was 1.39 +/- 0.06 (mean +/- SE; HSDex group) and 1.34 +/- 0.04 (NS group). SC was 0.26 +/- 0.07 (HSDex) and 0.26 +/- 0.04 (NS). Left anterior descending coronary artery stenosis changed neither D nor SC. Shock significantly reduced D (i.e., homogenized perfusion): 1.26 +/- 0.06 (HSDex) and 1.23 +/- 0.05 (NS). SC was increased: 0.41 +/- 0.1 (HSDex) and 0.48 +/- 0.07 (NS). Fluid therapy with HSDex further decreased D to 1.22 +/- 0.05, whereas NS did not change D. SC was increased by both HSDex (0.56 +/- 0.1) and NS (0.53 +/- 0.06). At 1 h after resuscitation, SC was constant in both groups, and D was reduced only in the NS group (1.18 +/- 0.02). We conclude that hemorrhagic shock homogenized regional myocardial perfusion in coronary stenosis and that fluid therapy failed to restore this.
Acid-Base Equilibrium↗
Clinical potential of intravenously administered perfluorocarbons.
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Blood Loss, Surgical↗
Aerosol production and aerosol droplet size distribution during mechanical ventilation (IPPV) with a new ultrasonic nebulizer.
Administration of drugs via the airway is increasingly practiced in ICU- and surgical patients. For this purpose, aerosols may be produced by either jet nebulization or ultrasonic droplet generation. In mechanically ventilated patients, aerosol delivery is often insufficient. The influence of the ventilatory pattern on nebulizer efficacy is poorly understood. In the present in vitro study we determined the efficacy of a new ultrasonic nebulizer in delivering aerosolized epoprostenol using defined ventilator settings. We determined aerosol delivery rates, the aerosol droplet size distribution and the impact of the connection tubing on drug delivery, applying adult and infant ventilation patterns. Aerosol production rates ranged from 0.28 to 0.57 ml per minute. Using an adult ventilator setting volume controlled ventilation (CMV) led to a higher aerosol production rate than pressure controlled ventilation (PCV) at identical tidal volumes and mean airway pressures (0.57 ml/min,CMV vs 0.39 ml/min, PCV). With an infant ventilator setting, nebulizer rates were lower than those found for the adult ventilator setting, but did not differ substantially between CMV and PCV mode (0.29 ml/min, CMV vs 0.28 ml/min, PCV). Aerosol delivery rates distal to the endotracheal tube changed according to aerosol production rates (adult mode: 0.18 ml/min, CMV vs 0.10 ml/min, PCV; infant mode: 0.03 ml/min, both CMV and PCV). In the infant ventilation mode, a higher percentage of the aerosol was trapped in the catheter mount as compared to the adult ventilation mode. Mass median droplet diameters for each of the four ventilator settings were almost identical (4.63 to 5.09 micron) and smaller than indicated in the product specifications (8 micron). Delivery rates and sizes of droplets delivered by the new ultrasonic nebulizer SUN 345(R) agree well with previously reported data from comparable settings using diverse nebulizer devices.
Adult↗
Eight hours' inhalation of prostacyclin (PGI2) in healthy lambs: effects on tracheal, bronchial, and alveolar morphology.
OBJECTIVE: To study potential toxic effects of long-term (8 h) inhaled prostacyclin (PGI2) on respiratory tract tissues. DESIGN: In a prospective, randomized order, either PGI2 (n =7) or normal saline (n = 7) was aerosolized during a time period of 8 h in healthy lambs. SETTING: Institute for Surgical Research of the Ludwig-Maximilians University of Munich. ANIMALS: 14 health, anesthetized, ventilated lambs. INTERVENTIONS: All animals were endotracheally intubated followed by tracheotomy. PGI2 solution or normal saline was administered with a jet nebulizer (delivery rate 4-10 ml/h; mass median diameter of aerosol particles 3.1 microns). MEASUREMENTS AND RESULTS: Histomorphological changes after 8-h inhalation of PGI2 solution were compared to those after 8-h inhalation of normal saline. Tracheal and bronchoalveolar tissues were examined by light and electron microscopy in order to assess tissue damage induced by inhaled PGI2. Pathological changes were ranked by a blinded observer following a graduation system ranging from "absence of pathological changes" to "maximal pathological changes". Abnormalities were restricted to the trachea (focal flattening of the epithelium, loss of cilia, slight inflammatory cell infiltration) and alveolar tissue (focal alveolar septal thickening with slight inflammatory cell infiltration), but no statistically significant differences between the PGI2 and control groups were encountered. CONCLUSION: Our findings indicate the absence of PGI2 aerosol-related respiratory tissue damage after 8-h inhalation of PGI2.
Aerosols↗
Inhalation of prostacyclin (PGI2) for 8 hours does not produce signs of acute pulmonary toxicity in healthy lambs.
OBJECTIVE: To study the potential side effects and toxicity of inhaling prostacyclin (PGI2) aerosol for 8 h. DESIGN: In a prospective, randomized study 14 healthy lambs received either PGI2 (n = 7) or 0.9% NaCl (n = 7) as an aerosol for 8 h. SETTING: Institute for Surgical Research of the Ludwig-Maximilians-University of Munich. INTERVENTIONS: All animals were studied under general anesthesia in a prone position. They were first intubated endotracheally and later tracheotomized. PGI2 solution (median dose 28 ng/kg per min) or 0.9% NaCl was administered with a jet nebulizer (delivery rate 4-10 ml/h; mass median diameter of aerosol particles 3.1 microns). Bronchoalveolar lavage was performed before and after the inhalation period to collect epithelial lining fluid of alveoli. MEASUREMENTS AND RESULTS: Hemodynamic and respiratory parameters, systemic resorption (plasma levels of 6-keto-prostaglandin-F 1 alpha), in vitro bleeding time, collagen-induced platelet aggregation and global biochemical and cellular composition of the epithelial lining fluid were examined in order to assess the side effects and signs of acute pulmonary toxicity induced by inhaled PGI2. No statistically significant differences were found between the PGI2 and the control groups for any of the parameters examined. CONCLUSION: Inhalation of PGI2 (28 ng/kg per min) over a period of 8 h in healthy lambs does not produce major side effects or acute pulmonary toxicity.
Acute Disease↗
Effects of hemodilution on gastric regional perfusion and intramucosal pH.
UNLABELLED: Acute normovolemic hemodilution (ANH) has been shown to be a cost-effective method of reducing allogenic blood transfusion during elective surgery. ANH has been implicated with impaired oxygenation in isolated canine gastric flaps. The present study was designed to investigate the effects of ANH on gastric mucosal oxygenation using a model closely imitating the clinical situation. Sixteen splenectomized anesthetized beagles were isovolemically hemodiluted to a hematocrit of 20 +/- 1% (6% hydroxyethyl starch; mol wt 200,000; substitution ratio 0.45-0.55). Blood volume (indocyanine green), cardiorespiratory parameters, gastric intramucosal pH (pHi), and gastric regional blood flow (radioactive microspheres; 15 microns) were measured before and after ANH. RESULTS: blood volume was unchanged (87 +/- 8 ml/kg before and 88 +/- 7 ml/kg after ANH). Median total gastric mucosal blood flow at baseline was 0.51 +/- 0.35 ml.min-1.g-1 and did not change significantly upon ANH. The mean pHi was 7.29 +/- 0.05 before and 7.28 +/- 0.05 after hemodilution. There was a homogenization of blood flow distribution in gastric mucosa. Severe hemodilution to a hematocrit of 20% does not impair gastric mucosal oxygenation and poses no risk to gastric mucosal integrity.
Animals↗
Inhaled prostacyclin (PGI2) versus inhaled nitric oxide in adult respiratory distress syndrome.
Inhalation of nitric oxide (NO) and prostacyclin (PGI2) may induce selective pulmonary vasodilation and-by improving ventilation-perfusion ratio in ventilated areas of the lung-increase Pao2 in patients with acute lung injury. To assess the therapeutic efficacy of both compounds, dose-response curves were established in patients with adult respiratory distress syndrome (ARDS). Patients received both PGI2 (doses of 1, 10, and 25 ng/kg/min) and NO (concentrations of 1, 4, and 8 ppm). Cardiorespiratory parameters were assessed at control, at each drug concentration, and after withdrawal of NO and PGI2. PGI2 resulted in a significant, dose-dependent and selective reduction of pulmonary artery pressure (PAP) from 35.1 +/- 6.3 mm Hg at control to 33.1 +/- 4.8 (1 ng/kg/min), 31.3 +/- 4.8 mm Hg (10 ng/kg/min) and 29.6 +/- 4.5 mm Hg (25 ng/kg/min), respectively. Inhaled NO reduced PAP from 34.5 +/- 5.6 to 32.1 +/- 5.9 mm Hg at 4 ppm, and to 31.8 +/- 6.1 mm Hg at 8 ppm, respectively, with no effect at 1 ppm. Pao2/Flo2 ratio increased from 105 +/- 37 to 125 +/- 56 mm Hg (range of increase: 0 to 57 mm Hg) at PGI2 10 ng/kg/min and to 131 +/- 63 mm Hg (range: -5 to 89 mm Hg) at 25 ng/kg/min with no effect at 1 ng/kg/min. NO improved Pao2 (e.g., from 116 +/- 47 to 167 +/- 86 mm Hg at 8 ppm) and reduced intrapulmonary shunt at all doses tested. We conclude that both inhaled PGI2 and NO may induce selective pulmonary vasodilation and increase Pao2 in severe ARDS.
APACHE↗
Inhaled sodium nitroprusside. Non-selective reduction of thromboxane analogue-induced pulmonary vasoconstriction in healthy sheep.
Both inhaled nitric oxide (NO) and inhaled prostacyclin have been shown to selectively decrease pulmonary hypertension of various origin. The aim of the present study was to assess the potential of the NO donor sodium nitroprusside (SNP) to elicit selective pulmonary vasodilation. SNP spontaneously liberates nitric oxide in the presence of reducing substances like cysteine or glutathione, ubiquitous in many different tissues. Inhaled as an aerosol in 3 healthy lambs presenting pulmonary hypertension induced by infusion of a thromboxane analogue, low concentrations of SNP (0.02-0.6 mg/ml) revealed no effect at all. In contrast, high concentrations of SNP (1.0-20.0 mg/ml) lowered pulmonary artery pressure in conjunction with systemic arterial hypotension, suggesting systemic resorption of SNP with subsequent release of its nitroso-group. Selective pulmonary vasodilation was never observed. In conclusion, the present results do not support a selective effect of inhaled SNP in the pulmonary circulation.
Administration, Inhalation↗