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Traumatic brain injury (TBI) and hemorrhagic shock due to uncontrolled bleeding are the major causes of death after severe trauma. Mortality rates are threefold higher in patients suffering from multiple injuries and additionally TBI. Factors known to impair outcome after TBI, namely hypotension, hypoxia, hypercapnia, acidosis, coagulopathy and hypothermia are aggravated by the extent and severity of extracerebral injuries. The mainstays of TBI intensive care may be, at least temporarily, contradictory to the trauma care concept for multiple trauma patients. In particular, achieving normotension in uncontrolled bleeding situations, maintenance of normocapnia in traumatic lung injury and thromboembolic prophylaxis are prone to discussion. Due to an ongoing uncertainty about the definition of normotensive blood pressure values, a cerebral perfusion pressure-guided cardiovascular management is of key importance. In contrast, there is no doubt that early goal directed coagulation management improves outcome in patients with TBI and multiple trauma. The timing of subsequent surgical interventions must be based on the development of TBI pathology; therefore, intensive care of multiple trauma patients with TBI requires an ongoing and close cooperation between intensivists and trauma surgeons in order to individualize patient care.

History and Admission Findings: A 70-year-old female patient was admitted with progressive dyspnea and peripheral edema. The patient had a medical history of myocardial hypertrophy, diastolic dysfunction and concomitant pulmonary hypertension (PH)., Investigations: The physical exam was suggestive of cardiac decompensation. Echocardiography showed myocardial hypertrophy, an enlarged left atrium as well as enlarged right-sided heart chambers. A prominent tricuspid regurgitation jet was present, and the estimated systolic right ventricular pressure was 65 mmHg. Invasive hemodynamic measurements showed a marked pressure elevation in the pulmonary circulation (mean PAP 51 mmHg), combined with an elevated left ventricular end-diastolic pressure (LVEDP) of 30 mmHg and a profound increase in the transpulmonary gradient (TPG, 21 mmHg)., Treatment and Course: The synopsis of these findings led to the diagnosis of postcapillary PH with a prominent precapillary involvement and cardiac decompensation. Due to signs of volume overload, an adequate diuretic therapy was initiated. The patient was recompensated and lost 7 kg of weight, which was associated with substantial clinical improvement. At invasive follow-up hemodynamic measurement, the patient's PAP was substantially decreased and almost reached normal values. The previously diagnosed precapillary involvement had disappeared., Conclusion: PH is a frequent phenomenon in patients with systolic and diastolic heart failure, and might initially appear as a combination of pre- and postcapillary involvement. The patients' volume status has a major influence on pulmonary hemodynamics. An adequate therapy of the underlying heart failure, especially an adequate diuresis, may have marked beneficial effects on pulmonary hemodynamics. Hemodynamic measurements should always be performed in compensated status., (© Georg Thieme Verlag KG Stuttgart · New York.)

Volume retention is the hallmark of progressive heart failure, both systolic and diastolic (heart failure with preserved ejection fraction). It represents the cause of the main symptoms (dyspnea, edema, liver synthesis) and also the main target of drug therapy. Antagonizing excessive volume retention is also the most important therapy element. Many patients can be stabilized with sequential nephron blockade (thiazide + loop diuretics) combined with afterload reduction [blockade of the RAAS (renin-angiotensin-aldosterone) system]. Personal patient coaching combined with telemetric components (weight, blood pressure) has evolved as another cornerstone of treatment in heart failure patients. If these measures are insufficient to control volume retention, renal replacement therapy is effective and can improve quality of life. More specifically, aquaresis via peritoneal dialysis has been shown to be effective and adequate to control volume overload. Many patients may qualify for this evolving therapy as it effectively prevents repeat hospitalization for heart failure decompensation, can be performed in an out-patient setting and has a low complication rate, thus significantly improving quality of life.

This article summarizes improvements in diagnosis and therapy in patients with symptomatic hyponatremia. The available treatment options for hyponatremia have been limited, and consisted mainly of isotonic or hypertonic saline, urea, and fluid restriction. Vasopressin receptor antagonists, also known as vaptans or aquaretics are a new class of drugs that now offer an additional treatment option for hyponatremic patients with euvolemic hyponatremia due to SIADH in Europe. In short and long term studies, tolvaptane has been shown to be effective in raising serum sodium levels in a predictable fashion in patients with SIADH with only few side effects, when serum sodium was frequently monitored and dosage of tolvaptans was properly adjusted. Further studies are needed to find out which patients benefit from treatment with respect to morbidity and mortality. Until now, therapy is limited to the treatment of moderate symptomatic hyponatremia in SIADH due to the high cost of therapy., (© Georg Thieme Verlag KG Stuttgart · New York.)

Background: With broad acceptance of Stewart's acid-base model "hyperchloremic acidosis" is regarded as an independent form of metabolic disorder. It is unknown whether hypernatremia plays a corresponding role with respect to the development of alkalosis., Methods: A total of 201 artificially ventilated, critically ill patients were monitored for hypernatremic episodes. Inclusion criterion was a serum sodium concentration above 145 mmol/l., Results: In 20 patients a total of 78 periods of elevated plasma sodium levels lasting at least 24 h were observed. In 86% of these cases sodium and chloride concentrations were simultaneously increased. The development of alkalosis correlated with the strong ion difference (r=0.80, p<0.01) but not with the serum sodium concentration (r=-0.031, p=0.78). In cases without accompanying hyperchloremia (13%) metabolic alkalosis regularly occurred and a correlation between serum sodium concentration and base excess could be verified (r=0.66, p=0.03). Alkalosis occurred in 84.8% of cases where the strong on difference exceeded 39 mmol/l., Conclusion: From the available data hypernatremic alkalosis could not be defined as an independent metabolic disorder. In would seem more appropriate to use the term "strong ion alkalosis" in this context.

The future of shock treatment depends on the importance of scientific results, and the willingness of physicians to optimize, and to reconsider established treatment protocols. There are four major potentially promising approaches to advanced trauma life support. First, control of hemorrhage by administration of local hemostatic agents, and a better, target-controlled management of the coagulation system. Second, improving intravascular volume by recruiting blood from the venous vasculature by preventing mistakes during mechanical ventilation, and by employing alternative spontaneous (i.e. use of the inspiratory threshold valve) or artificial ventilation strategies. In addition, artificial oxygen carriers may improve intravascular volume and oxygen delivery. Third, pharmacologic support of physiologic, endogenous mechanisms involved in the compensation phase of shock, and blockade of pathomechanisms that are known to cause irreversible vasoplegia (arginine vasopressin and K(ATP) channel blockers for hemodynamic stabilization). Fourth, employing potentially protective strategies such as mild or moderate hypothermia. Finally, the ultimate vision of trauma resuscitation is the concept of "suspended animation" as a form of delayed resuscitation after protection of vital organ systems.

Objectives: To evaluate the effect of dopexamine and iloprost on the plasma disappearance rate (PDR) of indocyanine green (ICG) in patients in septic shock in a prospective clinical trial., Methods: In 40 consecutive patients in septic shock, a femoral arterial fiberoptic catheter (COLD system) and a gastrotonometric probe were placed. Patients received either dopexamine infusion (0.5 microgram/kg body weight/min) or iloprost (1 ng/kg body weight/min) for 24 h i.v. PDR, intramucosal pH of stomach wall (pHi), cardiac index (HI) and intrathoracic blood volume (ITBV) were determined before, 1, 6, and 24 h after dopexamine or iloprost infusion and 1 h after end of infusion., Results: PDR was significantly increased 24 h after starting dopexamine infusion from 12.2 +/- 1.8%/min to 17.8 +/- 2.2%/min (+45.9%) and 1 h after the end of infusion PDR decreased to baseline values. PDR increased to 16.4 +/- 2.1%/min, 1 h after starting iloprost infusion and increased to a maximum value of 18.6 +/- 2.2%/min (+33.8%, p < 0.05) 24 h after start of infusion compared to the baseline (13.9 +/- 1.7%/min). After the end of infusion PDR decreased to baseline values. Baseline values of pHi were in normal ranges in all groups and there was no change during the observation period. Cardiac index and ITBV were stable during the study. Dosage of norepinephrine could be reduced by dopexamine infusion., Conclusions: Dopexamine and iloprost have a positive effect on the plasma disappearance rate of ICG and therefore have a protective effect on splanchnic perfusion and liver function, respectively.

Background: What is the effect of preoperative acute normovolemic hemodilution (ANH) with 6% hydroxyethyl starch (HES) 130/0.4 (Voluven) on blood volume?, Methods: In 10 patients undergoing radical hysterectomy, ANH was performed to a hematocrit of 21% using 6% HES 130/0.4 (Voluven) whereby a replacement of blood with 115% of colloid was planned. Plasma volume (indocyanine green dilution technique) and hematocrit were determined before, 30 and 60 min after ANH. Red cell volume (labelling erythrocytes with fluorescein) was determined before and 30 min after ANH., Results: After removal of 1,431+/-388 ml of blood and simultaneous replacement with 1,686+/-437 ml of colloid, blood volumes were 218+/-174 ml higher than before (at 105+/-4%). The volume effect was 98+/-12%, 30 min after ANH. Even 60 min after ANH, mean blood volumes were with 4,228+/-986 ml slightly higher than before ANH (102+/-5%). The hematocrit decreased disproportionally in relation to the residual intravascular volume. Consequently, estimating the volume effect from the changes in hematocrit led to an overestimation (about +30%)., Conclusion: Double label measurements of blood volume demonstrated that the volume effect of 6% HES 130/0.4 (Voluven) is about 100% in the course of ANH. The reason for the disproportionally large decrease in hematocrits could be the mobilization of a fraction of the plasma volume which was retained within the endothelial glycocalyx.

Purpose: We wanted to know whether topical Metipranolol has any effect on ocular blood flow. Before starting this investigation using the Heidelberg Retina Flowmeter, we studied the reproducibility of this device., Method: Retinal blood flow was determined in 15 healthy volunteers. Altogether, each volunteer was measured 20 times (4 different days with 5 pictures each). Coefficients of variation were calculated for both, the short term fluctuation and the long term fluctuation. After that, the effect of metipranolol was tested in 14 of the 15 volunteers mentioned above. This was done in a randomized, placebo controlled, double masked and crossover designed study., Results: The mean coefficients of variation were 21% for the short term fluctuation and 13% for the long term fluctuation. There was a significant effect of learning, i.e. coefficients of variation decreased with increasing experience of the investigator (MVR). Blood flow values did not differ significantly between metipranolol and placebo., Conclusions: 1. The reproducibility of blood flow values measured with the Heidelberg Retina flowmeter are sufficient, at least if the device is used in clinical studies. When performing those studies, the learning curve of the investigator should be taken into account. 2. The topical application of metipranolol does not alter the retinal blood flow in healthy volunteers.

Even complex diagnostic tests may not establish aetiology and degree of erectile dysfunction (ED) in many patients. Therefore, we evaluated a self-report method with a restrictive focus to quality of erections which may yield information sufficient to make an aetiologic diagnosis. We studied 74 patients 25 to 75 years of age with untreated ED. Sexually stimulated erections were quantified and compared to duplexsonographically and clinically evaluated data from pharmacostimulated erections. Patients reported that there was a marked decrease in ability to penetrate the partner, to sustain an erection and of penile rigidity (p < 0.001). Parameters from duplexsonography and clinically assessed response to pharmacostimulation correlated (r = 0.72). Direct comparison of these data with quantified history showed no relation (r = 0.05). Using change in penile volume due to erection as a basis to compare with, showed significant correlation with quantified data from history (r = 0.26-0.34; p < 0.03) and measured parameters from pharmacostimulated erections (r = 0.44-0.55; p < 0.0001). Sexually- and pharmacostimulated erections are proportional to change in penile volume. Although there is a relation between erections emerging from both stimulations, quantifying history on sexually stimulated erections does not qualify to make an aetiologic diagnosis without using complex tests.

Background: The present study was designed to investigate the effect of topical antiglaucoma drugs on Peak Pulse Blood Volume (PPBV; German abbreviation: PGBV) in cynomolgus monkey eyes without (CMNG; German abbreviation: RA-KTL) and with lasersurgically induced glaucoma (CMG; German abbreviation: RA-LHDG)., Methods: CMG unilaterally received 2-3 laser treatments so as to develop the lasered-eye glaucoma model. Intraocular pressure (IOP; German abbreviation: IOD) and Ocular Pulse Amplitude were measured and PPBV was determined until the glaucoma model had stabilized. Consecutively topical antiglaucoma drugs (epinephrine, paraaminoclonidine, pilocarpine, timolol) were investigated in 4-8 animals in CMNG and CMG eyes., Results: IOP and PPBV were not significantly altered in CMNG. In the CMG eyes epinephrine and paraaminoclonidine did not significantly alter IOP or PPBV, whereas pilocarpine and timolol sig. (p < 0.01) reduced IOP and significantly (p < 0.05) increased PPBV., Conclusion: With respect to improved PPBV in the CMG eye the rank order of drug effectiveness is timolol > pilocarpine > paraaminoclonidine > epinephrine.

Aim: The Müller-Casty flow index (FI) is recommended for use in transcranial Doppler sonography (TCD) to measure relative changes in volume flow. We examined the ability of the FI to assess the volume flow during diameter changes of basal cerebral arteries., Method: Nitroglycerin (NTG) was used to induce dilation of basal cerebral arteries without affecting cerebral blood flow. Transverse and sagittal sections of the middle cerebral artery (MCA) were obtained by magnetic resonance imaging (MRI) and blood flow velocities in the MCA were measured by TCD. The FI was calculated by multiplying Doppler shift frequency and signal power., Results: NTG induced an increase of MCA-diameter in MRI. The mean FI remained approximately constant (-2.6 +/- 6%), while the mean blood flow velocity dropped significantly (-15 +/- 6%)., Conclusion: The FI can be used to estimate volume flow in basal cerebral arteries even in case of diameter change.

14 pregnant women receiving continuous intravenous tocolysis for threatened miscarriage were studied for an effect of beta 2-mimetics on erythropoiesis in humans. After tocolytic therapy for 48 h, the hematokrit fell by 14%; conversely erythropoietin levels rose by 88.7%. Increased erythropoiesis was reflected in increased reticulocyte (and reticulocyte subpopulation) counts. There was a significant correlation between cumulative tocolytic dose and erythropoietin elevation at 48 h. The hypervolemia evidenced by the decreased hematocrit was due to the increased oral fluid intake and fluid retention, and was the presumed main cause of the elevated erythropoietin levels. This effect could enhance understanding of the control of erythropoietin secretion. A similar mechanism may account for the increase in erythropoietin levels in pregnancy.

Hypertonic-hyperoncotic solutions are a supplementary possibility in the acute treatment of hypovolemia. The main mechanism of action of this solution is, induced by the tonicity of the infusion (approximately 2400 mOsm/l), the transcapillary fluid shift from the intracellular and interstitial to the intravascular compartment. Additionally the fluidity of blood is improved (due to an increase in the diameter of the capillaries), the adherence of leucocytes to the endothelial wall is reduced, and the arteriolar vasomotion is restarted. Due to the available prehospital and clinical results it can be concluded, that hypertonic-hyperoncotic solutions offer advantages compared to conventional fluid therapy regimes: rapid stabilization of hemodynamics, reduction of posttraumatic volume deficiency, of posttraumatic edema and of posttraumatic complications and an improvement of the outcome of the patients. If the therapeutic recommendations are followed, such as a dose of 4 ml/kg body weight, infusion time of about 3-5 minutes and after the end of the infusion application of colloids or crystalloids in an amount as needed, no side effects will occur. Only immediately after the end of infusion sodium, chloride and osmolarity will slightly increase, however these parameters will normalize within the first posttraumatic day. Hypertonic-hyperoncotic solutions are trigger-solutions, as with the infusion of these types of solution it is possible to restore hemodynamics adequately and to prevent shock-induced complications.

The aim of the study was to investigate the influence on coagulation and platelet function of two 6% medium molecular weight hydroxyethylstarch solutions (HES, MW 200,000, DS 0.5) made of potato (K) and corn (M) starch. Twenty patients undergoing elective vertebral disc surgery were randomly assigned to one of the groups. Haemoglobin, haematocrit, protein concentration, fibrinogen, antithrombin III, factor VIII:C, von-Willebrand-factor, prothrombin time, activated partial thromboplastin time and platelet maximum aggregation and maximum gradient of aggregation (inductors: ADP, epinephrine, collagen and ristocetin) were measured before infusion and 30, 240 minutes and one day after infusion. The reduction of the prothrombin time (Quick) and antithrombin III and the decrease in fibrinogen and protein concentration, haemoglobin and haematocrit were due to haemodilution. The prolongation of the activated partial thromboplastin time (38.3 s K-group and 38.0 s M-group) and the decrease in factor VIII:C (71% K-group and 84% M-group) and von-Willebrand-factor (72% K group and 79% M group) were similar in both groups within 30 minutes of infusion of 1,000 ml HES. There was no change in platelet function within the groups. The infusion of a medium molecular weight solution is an effective and cost-saving method in volume therapy. Despite the physicochemical differences of the two HES solutions, there were no clinically apparent effects on coagulation and platelet function. Both preparations of HES up to a volume of 1,000 ml can be used equally in the clinical setting.

Unlabelled: Deferoxamine is known to reduce the iron-dependent generation of toxic oxygen-derived radicals during reperfusion of ischaemic tissue. The present study investigates the antioxidative properties of a deferoxamine-conjugated hydroxyethyl starch solution and its effects on the hepatic microcirculation in a haemorrhagic-shock rat model., Methods: Anaesthetized Sprague-Dawley rats were tracheotomized, prepared for invasive haemodynamic monitoring, and subject to haemorrhagic shock (MAP = 40 mmHg during 60 min). The animals were resuscitated blood-free with lactated Ringer's (RILA, n = 10), gelatin (GELA, n = 10), hydroxyethyl starch (HES, n = 10), or deferoxamine-conjugated HES (DFO, n = 8) solution (MAP > or = 70 mmHg). After 1 h of resuscitation the hepatic microcirculation was investigated by intravital microscopy, the glutathione concentration was measured in liver homogenate, and the thiobarbituric acid reactive substances (TBARS) were determined as markers of lipid peroxidation., Results: Resuscitation resulted in restoration of MAP to > or = 70 mmHg within a short time. The volume required to stabilise the arterial pressure during 1 h of resuscitation was significantly less in the DFO group compared with HES, GELA, and RILA. Significantly higher glutathione levels in liver homogenate as well as decreased TBARS levels were observed in the DFO group. The shock-induced increase of leukocyte adhesion in liver sinusoids was significantly attenuated by DFO., Conclusion: DFO significantly attenuates shock-induced oxidative stress, thereby reducing the early inflammatory reaction and improving the hepatic microcirculation.

Cerebral blood flow autoregulation, CO2 reactivity and the pressure-volume relationship may be impaired or abolished in patients with intracranial mass lesions, brain trauma, cerebral vasospasm or increased cerebral elastance. Sedatives, analgetics, and anesthetics may induce major changes in cerebral blood flow, cerebral metabolism and intracranial pressure (ICP). The inadequate use of these drugs may aggravate the preexisting intracranial pathology and may worsen outcome. Thus it is important to understand the effects of sedatives, analgetics, and anaesthetics on intracranial hemodynamics and metabolism during physiological and pathological conditions. Hypnotics (barbiturates, etomidate, propofol), benzodiazepines, opioids (fentanyl, alfentanil, sufentanil) and alpha-2-adrenergic agonists (clonidine, dexmedetomidine) reduce cerebral blood flow. With ketamine, cerebral blood flow changes in a regionally specific fashion, with some territories showing increases and others showing decreases in cerebral blood flow. Cerebral metabolism is decreased during sedation and analgesia with hypnotics, benzodiazepines, and opioids, while infusion of ketamine produces stimulation as well as suppression of cerebral metabolism. This suggests that the changes in cerebral blood flow seen with these drugs occur secondary to their cerebral, metabolic effects. Alpha-2-adrenergic agonists produce no significant changes in cerebral metabolism. However, cerebral blood flow is decreased with clonidine or dexmedetomidine. This suggests uncoupling between cerebral metabolism and flow due to decreases in central catecholamine turnover. Hypnotics and benzodiazepines decrease ICP due to decreases in cerebral blood volume. However, these drugs may also decrease mean arterial blood pressure, which may result in a critical reduction in cerebral perfusion pressure. ICP remains unchanged with the use of opioids as long as mean arterial pressure is maintained constant. However, decreases in mean arterial pressure during infusion of opioids induce autoregulatory cerebral vasodilation, which in turn increases cerebral blood volume and ICP. Ketamine may increase ICP specifically in subjects with spontaneous ventilation. With mechanical hyperventilation and constant systemic hemodynamics, ketamine fails to increase ICP in most of the patients. Alpha-2-adrenergic agonists produce no significant changes in ICP, although there may be a transient decrease in ICP with lower doses.

Purpose: A non-invasive MR-method for the quantification of regional cerebral blood flow (rCBF) and blood volume (rCBV) is used to examine healthy volunteers and patients with cerebrovascular disorders., Materials and Methods: 20 healthy volunteers and 10 patients with severe cerebrovascular disorders were examined. MR imaging was performed on a 1.5 T imaging system. Before, during and following brief antecubital vein bolus injection of Gd-DTPA, a series of 32 rapid T2*-weighted gradient echo images of two different slices ere simultaneously acquired in order to measure th concentration-time-curves in the brain tissue and the arterial input function in the brain feeding arteries. From these series of images the concentration-time-curves were computed. Principles of indicator dilution analysis were applied to compute rCBF and rCBV. The volunteers underwent one examination each. All patients underwent two examinations, one before and the second after azetazolamide stimulation., Results: In volunteers the measured rCBF and rCBV values are in good agreement with data from positron emission tomography studies. In patients with cerebrovascular disorders in the asymptomatic hemisphere a mean increase of rCBF of 43,45 +/- 18.04% was observed after azetazolamide stimulation. In the affected areas of the symptomatic hemisphere in 8 from 10 patients the acetazolamide test reveals a significantly reduced response to azetazolamide stimulation, indicating an exhausted cerebrovascular reserve capacity., Conclusion: Dynamic MR-Imaging can provide quantitative information about rCBF and rCBV. In patients with cerebrovascular disorders, this method can be applied to estimate the cerebrovascular reserve capacity.

We describe the non-invasive assessment of cerebrovascular reserve capacity by means of near-infrared spectroscopy (NIRS) and magnetic resonance imaging. Both methods are compared with transcranial Doppler sonography. There is a good correlation of the three methods in the changes in cerebral oxygen saturation and in blood velocity following acetazolamide stimulation of cerebral blood flow, except found in one patient with unilateral carotid artery occlusion. In this patient we found a decreased cerebrovascular reserve capacity, revealed by a magnetic resonance technique designed to quantify CBV and CBF. We postulate a raised oxygen extraction as the cause of his changes in oxygen saturation.

Hydroxyethylstarch (HES) is today one of the most frequently used artificial plasma substitutes in prehospital, as well as in clinical settings. However, there are no studies comparing the volume effect of different HES solutions. The goals of the present study therefore were to compare the volume effect of three HES solutions, which are similar with regard to mean molecular weight but different in concentration and degree of substitution. The obtained results enable guidelines for fluid resuscitation in hypovolemia to be laid down. In 30 patients fulfilling the ASA physical status classification I and II 500 ml of either 10% HES 200/0.5, 6% HES 200/0.5 or 6% HES 200/0.6-0.66 were infused within 30 min. The effect of each solution was evaluated using the mechanical oscillator technique (MOT). This technique measures precisely density changes of blood and plasma and allows-using standard formulae-calculation of blood and plasma volume changes. All 3 HES solutions showed similar effects in increasing plasma volume. Immediately after the end of infusion plasma volume was increased by about 800 ml with 10% HES and by about 650 ml with 6% HES 200/0.5. The volume expanding effect of 6% HES 200/0.6-0.66 amounted to 700 ml. The volume expanding effect of all starches decreased only slightly during the following two hours; an interesting detail observed was a second volume effect of HES (about 20% of the volume infused). We conclude that for the correlation of fluid deficits due to trauma, hemorrhage and shock HES solutions seem to be most effective artificial plasma substitutes.(ABSTRACT TRUNCATED AT 250 WORDS)

Objectives: To determine the efficacy and safety of intravascular volume augmentation with a hypertonic saline-hyperoncotic HES solution prior to CABG., Design: Randomized, double-blind, clinical trial., Patients: Consecutive sample of 37 patients scheduled for elective CABG; mean age 64.5 (41-80; range) years and weight 74 (51-111) kg., Interventions: Continuous, central-venous infusion of either 250 ml (approx. 3.5 ml/kg) HES (0.9% NaCl/10% hydroxyethyl starch 200.000/0.5) or HT-HES (7.5% NaCl/10% hydroxyethyl starch 200.000/0.5) in 15 minutes, following induction of anesthesia., Measurements and Main Results: Groups were similar with respect to age, weight, and sex. 15 min. after fluid loading, cardiac index, pulmonary artery pressure, and wedge pressure had increased from baseline in both groups (p < 0.05), with a greater increase in the HT-HES-group (p < 0.05). In eight out of 18 patients, who had received HT-HES, transient drops in arterial blood pressure (mean 20% from baseline, range 10-35%) were observed during the first 5 minutes of infusion. Seven of the HT-HES-group patients developed transient left ventricular failure, predominantly 5-20 min. after infusion. No incidence of initial hypotension or LVF was observed in the HES-group., Conclusions: In patients with coronary artery disease, volume augmentation with hypertonic-hyperoncotic solutions may induce transient hypotension and post-infusion hypervolemic left heart failure.

The ideal solution for volume therapy is still under discussion. In cardiac surgery, hemodynamic efficacy as well as the influence of cardiopulmonary bypass (CPB) are of major interest when administering volume. Hypertonic sodium (HS) solutions which have been advocated for resuscitation from hemorrhagic shock may also be of benefit in cardiac surgery patients. Hypertonic saline solution (7.5%) prepared in 6% hydroxyethyl starch solution (HS-HES) were infused in patients undergoing aortocoronary bypass grafting to double reduced baseline pulmonary capillary wedge pressure (PCWP < 4 mmHg). Volume replacement was carried out before (within 15 min), during (within 2 min), and after CPB (within 15 min). Significantly less HS-HES solution than standard 6% HES solution was necessary to double baseline PCWP. Cardiac index (CI) increased more and systemic vascular resistance (SVR) decreased more pronounced in the HS-HES group than in the 6% HES-patients. Fluid requirements in the patients having received hypertonic solution preoperatively were significantly less during CPB. Pulmonary function (paO2, Qs/Qt) was less changed in the HS-HES patients indicating avoidance of (interstitial) fluid overload in these patients. Infusion of HS-HES after weaning from CPB resulted in overall more improved hemodynamics than volume replacement with 6% HES. Rapid infusion of HS-HES during CPB (within 2 min) was followed by a significant, but shortlasting decrease in MAP (-40 mm Hg) and an increase in the oxygenator volume. Preoperative infusion of HS-HES resulted in a significant improvement in skin capillary microcirculation assessed by lased Doppler technique during and after CPB.(ABSTRACT TRUNCATED AT 250 WORDS)

For a more precise understanding of the net effects of acute alterations of pre- and afterload on left-ventricular filling, loading conditions were altered in normal subjects. The specific purpose of this study was to investigate if Dopplerechocardiographically derived transmitral flow patterns are able to differentiate the manner of loading condition. In 24 normal subjects (13 female, 11 male, mean age 44.1 +/- 11.5 years) the following Doppler variables were analyzed at baseline, after rapid infusion of volume (preload increase), nitroglycerine (preload decrease), isometric exercise (afterload increase) and converting enzyme inhibitor (afterload decrease): peak and integrated early (E, Ei) and late (A, Ai) diastolic flow velocities, their ratios (E/A, Ei/Ai), the percentage of atrial contribution (ACON) and the times of acceleration (Az) and deceleration (Dz) of early filling. Preload reduction as well as afterload increase led to a similar filling pattern with a significant decrease (p < 0.05 from baseline) of E and Ei, increase of A and Ai, and, consequently, a reduction of E/A and Ei/Ai. The atrial contribution to filling increased during both alterations; Az and Dz were reduced. Following the increase of preload, only the increase of E and Ei was statistically significant, while afterload reduction showed no significant differences. Different loading conditions alter Doppler-derived diastolic filling patterns. But the transmitral flow profile is not specific enough to differentiate in which manner loading conditions have been altered.

The main goal of the recent study was to evaluate changes in plasma volume due to the application of 6% HES 200/0.6-0.66. 12 patients according to the ASA physical status classification (I, II) undergoing minor surgical interventions received 500 ml of this artificial plasma substitute within 30 min. In a control group (n = 12), 500 ml of lactated Ringer's solution was given within the same period. A further question of the present investigation was the possible influence of 6% HES on coagulation during the following period (1st-3rd postoperative days). 6% HES 200/0.6-0.66 led to an additional augmentation of plasma volume measured via the mechanical oscillator technique of 200 ml (40% of the volume given) immediately at the end of infusion. A second increase in plasma volume of 100 ml (20% of the volume infused) could be observed 1 h later. With exception of the activity of factor VIII, the coagulation parameters had not been altered by infusion of 6% HES. The activity of factor VIII decreased to about 50% of the control level but showed a tendency to normalization within the following observation period. 6% HES 200/0.6-0.66 has a marked volume-expanding effect and exerts no influence on coagulation except a temporary decrease of factor VIII activity.

Changes in blood and plasma volumes were investigated in the course of diagnostic cardiac catheterizations, comparing the effect of a high and a low osmolar contrast medium in 30 patients (5 women and 25 men; mean age 53 [19-76] years) with coronary heart disease (n = 27) or valvular defect (n = 3). Using a randomized, double-blind protocol 15 patients received amidotrizoic acid (2.1 osmol/kg; mean dosage 166 +/- 68 or 2.2 +/- 1.1 ml/kg), while 15 patients received iopamidol (0.8 osmol/kg; mean dosage 154 +/- 78 ml or 2.1 +/- 1.0 ml/kg). The indocyanine-green method and the haematocrit were used to measure blood and plasma volumes immediately before and after the angiocardiography. Blood volume after amidotrizoic acid injection increased by a mean of 4.9% (228 +/- 242 ml) and by 0.4% (17 +/- 197 ml) after iopamidol (P less than 0.05). Plasma volume increased by a mean of 11.8% (331 +/- 150 ml) after amidotrizoic acid and 5.7% (157 +/- 97 ml) after iopamidol (P less than 0.01). The increase in plasma volume correlated with the dose of contrast medium: 2 ml per ml amidotrizoic acid (r = 0.93) and 1 ml per ml iopamidol (r = 0.82).--During angiocardiography blood and plasma volume may increase by up to 500 ml, an increase which depends not only on dosage but also on the osmolality of the injected contrast medium.

After a successful check of a duplex sonographic instrument in a water-bath, the following parameters were measured under standardised conditions in 30 fasting patients: blood flow rate in the mesenterica superior artery, maximal systolic, end-diastolic and average velocity as well as the vessel diameter. From these data the average blood flow rate was calculated. Maximal systolic velocity is on the average 134 +/- 22.8 cm/s, end diastolic 20.8 +/- 4.4 cm/s, average vascular diameter 7.6 +/- 0.7 mm, median blood flow 639 +/- 153 ml/min. Day-to-day variance is for the maximum systolic velocity at 11%, for end diastolic velocity at 9.7% and for the average vascular diameter at 2.2%. Postprandially the average flow velocity increases from 23.4 +/- 5.6 to 46 +/- 7.4 cm/s. The average vascular diameter increases from 7.6 +/- 0.7 to 8.0 +/- 0.8 mm. The median blood flow increases one hour after a non-standardised lunch by 126%. To show that Duplex sonography also covers pharmacodynamic blood flow changes, the maximum systolic, maximum diastolic and average velocity was measured before and 1 hour after ingestion of 20 mg nifedipine in 5 subjects. The measured parameters showed a significant increase.

Unlabelled: In part I of this study [Hessemer and associates, Klin. Mbl. Augenheilk. 199 (1991) 346-355] the phenomenology of the ocular circulatory changes, found during general anesthesia using halothane and nitrous oxide, has been described. These changes are analyzed with respect to their mechanisms.--, Results: There was a significantly (P less than 0.05) linear relation between the anesthesia-induced reduction of the systolic ocular (retinal and ciliary) blood pressures and the decrease of the systolic brachial artery pressure (delta Ps,bra). The same relation was present between the reduction of the systolic ocular (retinal and ciliary) perfusion pressures and delta Ps,bra. The correlation coefficients for the designated relations ranged between 0.37 and 0.58. The relation between the anesthesia-induced intraocular pressure reduction and delta Ps,bra was--in tendency--linear (P = 0.07), at least for the time period 5-15 min after intubation; the correlation coefficient amounted to 0.37. The reduction of both the ocular pulsation volume (PVoc) and the pulsatile ocular blood flow (Fp,oc) did not depend on the systemic blood pressure, but on the arterial CO2 tension (PCO2): Decreasing PCO2--i.e., increasing hyperventilation--was paralleled by decreases of PVoc and Fp,oc. The relations PVoc vs. PCO2 and Fp,oc vs. PCO2 were significantly linear (P less than 0.01), the correlation coefficients ranged between 0.58 and 0.7.(ABSTRACT TRUNCATED AT 250 WORDS)

We measured plasma levels of atrial natriuretic peptide (ANP) in 20 patients with impaired retinal circulation in order to monitor hypervolemic hemodilution. In 18 control subjects, plasma ANP levels averaged 37.4 +/- 7.3 pg/ml and 30.0 +/- 5.4 pg/ml before and after an i.v. infusion of 250 ml of HAES 6% over 3 hours. In 8 of 20 patients, plasma ANP exceeded the highest value of 87 pg/ml in the controls at the end of the first infusion. In the group B, ANP increased from 103 +/- 21.6 pg/ml to 142 +/- 12 pg/ml before and after the infusion. In the remaining 12 patients (group A), plasma levels of ANP were 41.1 +/- 8.6 and 44.8 +/- 6.3 pg/ml at the start and the end of the first infusion of HAES. All patients received 500 ml of HAES daily for 8 days. In group B, hemoglobin was significantly lower on day 8 (11.7 +/- 0.48 versus 13.2 +/- 0.38 mg/100 ml) compared to group A (p less than 0.005). Similarly, hematocrit and serum protein was reduced to a greater extent in group B compared to group A indicating intravascular volume expansion. Measuring plasma ANP-levels might be of value to identify patients with reduced tolerance to hemodilution therapy.

45 consecutive patients suffering from peripheral arterial occlusive disease (PAOD) stage IIa and b were integrated in a study about the effect of hemorheological parameters due to different application times. The patients were divided into 3 subgroups with different application times: group A received the infusion during 2, group B during 4, and group C during 6 hours. The used substance was 500 ml 6% HES 200,000/0.6-0.66. Except elasticity of group A all hemorheological parameters from group A to group C show a decrease after 6 hours, the trend to the same phenomenon could be observed after 24 hours in group B and C, while group A except plasma viscosity showed even a trend to increasing values compared to onset. As a conclusion of these results, long-time application should be preferred.

The concept of hemodilution bases on the presumed relation between impaired blood flow properties and the development and time course of ischaemic brain lesions. Animal experiments support this concept. However, recent clinical studies are disappointing. In animal experiments, treatment is initiated very early, almost undelayed (within 60 minutes), the experimental conditions are optimal and the animals are healthy. In contrast, there is a substantial delay between the onset of symptoms and the start of treatment in clinical routine conditions; furthermore, the cardiac reserve of elderly patients is limited. Therefore, the crucial question is: how can we create optimal treatment conditions to maximize the efficacy of hemodilution.

The influence of hyper- and isovolaemic hemodilution using HES 200/0.5 6% (HES steril, Fresenius AG) on pain-free walking distance in patients with peripheral arterial occlusive disease stage II according to Fontaine was tested in a randomised investigation involving three groups. The increase in pain-free walking distance was significant both in the hypervolaemic and isovolaemic hemodilution group. The increase in both dilution groups did not differ but compared to a control group (infusion of Ringer lactate) it was significantly higher. Considerable changes concerning rheological parameters (decrease in haematocrit and plasma viscosity) were observed after isovolaemic hemodilution.

An open study was carried out in order to examine therapeutic effectivity of repeated administration of 6% hydroxyethyl starch 200.000/0.60-0.66 (HES). 10 patients aged 63 to 77 years with peripheral arterial occlusive disease Stage II b were given 500 ml Elohaest as a hypervolemic hemodilution for 12 days. Fasting levels of hydroxyethyl starch (HES) in serum, hematocrit, and serum-alpha-amylase were measured. During the first 4 treatment days, HES levels and serum-alpha-amylase increased in a significant manner; then it fluctuated towards a plateau without significant differences. The hematocrit decreased significantly from the beginning to the end of therapy. So it was possible to show, that during repeated application with the chosen dosage of 6% HAES 200.000/0.6-0.66 there is no dangerous cumulation of HAES.