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Biomedical subjects

G Hempelmann

Publications and source records attributed to G Hempelmann.

At least 145 records · Page 8Linked to original sources

Changes in blood lymphocyte populations after multiple trauma: association with posttraumatic complications.

OBJECTIVE: To study the frequency of several lymphocyte subsets, circulating cytokines, and prostaglandin plasma values at their time course over a period of 14 days in severely injured trauma patients in relation to the development of sepsis and multiple organ failure (MOF). DESIGN: Prospective study. SETTING: An operative intensive care unit (ICU) of a university hospital. PATIENTS: Sixty-eight consecutive severely injured trauma patients. INTERVENTIONS: Patients were separated into patients without sepsis and MOF (group 1, n = 51), and patients who developed sepsis and MOF (group 2, n = 17) during their stay in the ICU. Therapy was adjusted to the standards of modern intensive care management by physicians who were not involved in the study. MEASUREMENTS AND MAIN RESULTS: In arterial blood samples, the profile of lymphocyte subset frequencies was performed by flow cytometry and, together with interleukin (IL)-1, IL-10, tumor necrosis factor (TNF)-alpha soluble TNF-alpha receptor 1 (sTNF-alpha r1 [p55]), and prostaglandin E2 (PGE2alpha)-alpha, serially measured after arrival in the ICU (baseline value) and during the next 14 days. Mean plasma IL-1 (29.3 +/- 5.8 [SD] pg/mL), TNF-alpha (138.5 +/- 22.4 pg/mL), and soluble TNF-alpha r1 (6.1 +/- 0.3 ng/mL) values were significantly higher in group 2 patients before clinical evidence of sepsis and MOF. With the onset of severe infections in group 2 patients, IL-1, TNF-alpha, and sTNF-alpha r1 values decreased, while immunosuppressive IL-10 (191.7 +/- 29.1 pg/mL) and PGE2alpha (87.7 +/- 20.4 pg/mL) values further increased and remained elevated during the time course. Analysis of lymphocyte subsets revealed a fall in total lymphocyte levels, in CD4+ T lymphocytes, and natural killer (NK) cells, but no change in CD8+ T lymphocyte subset. Despite a marked change in the T helper (CD4+) to T suppressor (CD8+) ratio (from 1:1.72 to 1:1.10), patients without MOF (group 1) had no significant difference in any of the markers tested compared with baseline values. In addition to the inverse CD4+/CD8+ T cell ratio (from 1:1.75 to 1:0.91) and increased activated T cells, each of these markers was significantly elevated and peaked before the onset of MOF in group 2 patients. CONCLUSIONS: A severely depressed cellular immune response associated with increased suppressive mediators might be closely related to the development of severe sepsis and MOF in trauma patients. Therefore, an in-depth understanding of the deficits in host defense following multiple trauma will provide the basis for therapeutic interventions.

Adult↗

Effects of low-dose dopexamine on splanchnic oxygenation during major abdominal surgery.

OBJECTIVE: To study the influence of low-dose dopexamine on splanchnic oxygenation during major abdominal surgery. DESIGN: Prospective, randomized, placebo-controlled study. SETTING: University hospital. PATIENTS: Eighteen adult patients undergoing elective major abdominal surgery. INTERVENTIONS: The patients received either dopexamine at 1 microg/kg/min (group A, n = 9) or 0.90% saline as control (group B, n = 9). MEASUREMENTS AND RESULTS: To assess the splanchnic oxygenation, intestinal tissue PO2 (PtissO2) and gastric intramucosal Pco2 (PmucCO2) were measured, and the PCO2 gap (PmucCO2 - PaCO2) was calculated at baseline (T1) and after an infusion period of 60 mins (T2). There was no difference between the groups in the global oxygen transport parameters. Low-dose dopexamine increases PtissO2 on the serosal side of the small bowel (deltaPtissO2, 17+/-24 mm Hg in group A vs. -5+/-10 in group B). The changes in PtissO2 at the serosal side of the colon after dopexamine demonstrated a nonsignificant increase (deltaPtissO2, 7+/-11 mm Hg in group A vs. -11+/-23 mm Hg in group B). In both groups, the Pco2 gap (group A, 6+/-7 mm Hg [T1] and 5+/-6 mm Hg [T2], vs. group B, 9+/-10 mm Hg [T1] and 12+/-10 mm Hg [T2]) remained unchanged compared with the baseline. CONCLUSION: It is concluded that low-dose dopexamine improves PtissO2 at the serosal side of the gut, preferably at the small bowel. However, low-dose dopexamine did not improve gastric PmucCO2.

Abdomen↗

Continuous heparinization and circulating adhesion molecules in the critically ill.

Endothelial activation and damage are common endpoints of a complex process that may result in multiple organ dysfunction syndrome (MODS). The influence of continuous intravenous heparinization on plasma levels of circulating adhesion molecules was studied in 28 trauma patients (injury severity score between 15 and 25 points) and 28 sepsis patients secondary to abdominal surgery. According to a prospective, randomized sequence the patients received either unfractionated heparin (aim: activated partial thromboplastin time (aPTT) approximately 2 x normal) (trauma-heparin (n = 14); sepsis-heparin (n = 14)) or not (trauma (n = 14); sepsis (n = 14)). Plasma levels of circulating soluble endothelial leukocyte adhesion molecule-1 (sELAM-1), vascular cell adhesion molecule-1 (sVCAM-1), intercellular adhesion molecule-1 (slCAM-1), and granule membrane protein-140 (sGMP-140) were serially measured from arterial blood samples for 5 days. Approximately 600 U/h of heparin were given to increase aPTT to approximately 60 s. Plasma levels of all adhesion molecules increased in all groups. This increase was significantly (p < .05) highest in both sepsis groups (sepsis: sELAM-1: from 50+/-11 to 84+/-19 ng/mL; slCAM-1: 410+/-68 to 700+/-95 ng/mL), but did not differ significantly between the treated and nontreated patients (sepsis-heparin: sELAM-1: from 60+/-131 to 88+/-20 ng/mL; slCAM-1: from 398+/-99 to 686+/-119 ng/mL). Trauma patients showed a less pronounced increase in all adhesion molecules without differences between the two subgroups. Only sGMP-140 increased significantly (p < .05) more in the trauma (from 102+/-20 to 169+/-16 ng/mL) than in the trauma-heparin group (from 109+/-19 to 132+/-17 ng/mL). It is summarized that continuous heparinization with approximately 600 U/h did not attenuate the rise in circulating adhesion molecules in sepsis and trauma patients. The study findings suggest that heparin in this dose regimen may be unlikely to influence endothelial inflammation or endothelial function in critically ill patients.

Adult↗

Unrecognized renal damage in critically ill patients.

INTRODUCTION: The objective of this study was to evaluate the percentage of unrecognized renal damage in patients with normal creatinine and urea in serum and normal creatinine clearance and to evaluate the usefulness of various proteins and enzymes as supplementary procedures for the investigation of renal function. MATERIAL AND METHODS: Forty critically ill male patients (APACHE II-score > 20, injury severity score > 15) were daily screened for a period of five days. In the 1st group there were 30 patients with normal creatinine and urea in serum and with normal creatinine clearances. In the second group there were ten patients with increased values of these parameters. The base-line condition of all patients and any changes in hemodynamic, nutrition and ventilation were noted. Clearances of inulin, para-aminohippuric acid, and creatinine were measured and the Cockcroft-Gault equation was calculated daily for a period of five days. Excretion of alpha-1-microglobulin. Tamm-Horsfall-protein, alanine aminopeptidase, angiotensinase A, albumin and immunoglobulin G were also measured daily. RESULTS: 21 Patients of group 1 and all patients of group 2 showed the expected correlation between the routine parameters of creatinine and urea in serum and the level of protein and enzyme excretion. Nine patients of group 1 (30%) showed normal glomerular filtration rates but pathological excretion fractions of all proteins and enzymes. CONCLUSIONS: Although all routine parameters of renal function (creatinine and urea in serum, creatinine clearance both by 24-h collection period and from the Cockcroft-Gault equation), and additionally inulin and para-aminohippuric acid clearance were measured, no references on tubular and glomerular damage were found in 30% of the investigated patients.

Acute Kidney Injury↗

Thrombin generation and activation of the thrombomodulin protein C system in open heart surgery depend on the underlying cardiac disease.

The exposure of blood to foreign surfaces during extracorporeal circulation (ECC) leads to an activation of the coagulation system. In arteriosclerotic patients thrombin activation is increased and plasma fibrinogen is elevated, while protein C levels are reduced. In this study we investigated the influence of different cardiac diseases on ECC-induced thrombin generation and activation of the thrombomodulin-protein C system. Twenty-four patients undergoing either elective coronary artery bypass grafting (CABG) or elective aortic valve replacement (AVR) were included in the study. Blood samples were taken at different time intervals before, during and after ECC, and in the postoperative period. Plasma concentrations of thrombin-antithrombin III-complex (TAT), modified antithrombin (ATM), prothrombin fragment F1+2, free protein S, thrombomodulin, and protein C-antigen were determined by ELISA. Fibrinogen and antithrombin III levels were detected by nephelometry. Both groups were comparable with respect to biometric and ECC-related data. TAT concentrations were elevated in both groups after induction and increased during surgery (p<0.001). As a marker of thrombin generation levels of F1+2 were higher in the CABG group during cardiopulmonary bypass (p=0.003). In CABG patients ATM peaks were higher during ECC (p=0.0024). Significantly higher plasma thrombomodulin concentrations were found in CABG patients after induction (p<0.001), while protein S concentrations were higher in the AVR group (p=0.002). Protein C levels and antithrombin III concentrations did not differ between the groups. Patients undergoing CABG were found to have lower protein S levels and increased plasma thrombomodulin concentrations as markers of endothelial damage. In these patients contact activation and as a consequence thrombin generation takes place at a higher level, indicating a hypercoagulable state. Thromboembolic events in the perioperative period may be caused by different hemostatic changes in CABG patients.

Aged↗

[Perfusion and metabolism of liver and splanchnic nerve area under sevoflurane anesthesia].

In common with other halogenated volatile anaesthetics, sevoflurane causes a dose-related cardiovascular depression and therefore the affection of blood flow of different organ systems is suggested. So far known, sevoflurane is not different compared to isoflurane in affecting liver and splanchnic blood flow. Concluded from former published studies there was no case of hepatic toxicity of sevoflurane been published so that this substance can be used in patients with reduced hepatic function. The primary organic metabolite of sevoflurane is hexafluorisopropanol (HFIP), which is readily and rapidly conjugated with glucuronic acid. No reactive intermediates are formed and HFIP appears to be an unlikely compound to form liver protein adducts. For this reasons sevoflurane "hepatitis" is not expected. Like most other inhalation agents sevoflurane increase the neuromuscular blockade after treatment with muscle relaxants in anaesthesia. The MAC values of Sevoflurane where reduced after the application of nitrous oxide, benzodiazepines and opiates. From human studies we know that chronic drug therapy with isoniazid induces the metabolism of sevoflurane, enflurane and isoflurane, markedly increasing peak plasma fluoride concentrations. However, barbiturates as well as phenytoin do not influence the metabolism of sevoflurane because these agents do not induce the major hepatic defluorinating enzyme cytochrome P450 2E1. Obesity, untreated diabetes mellitus and alcohol abuse increase the hepatic content and activity of cytochrome P450 2E1 and therefore enhanced anaesthetic defluorination is to be suspected. Until now, there are no studies about sevoflurane anaesthesia in patients after liver transplantation but the extremely low hepatotoxic potential as compared to isoflurane provides no argument to avoid this substance for anesthesia in liver transplanted patients.

Anesthetics, Inhalation↗

[Acute kidney failure. Non-invasive diagnosis of acute kidney failure in operative intensive care patients].

UNLABELLED: Acute renal failure is a common and severe complication in ICU. Renal laboratory examinations like creatinine and urea are late signs of renal dysfunction: Most of the functional abilities are reduced and there is no time for therapeutical interventions. The aim of this study was to find some earlier sensitive parameters of renal dysfunction and the order of appearance, the cause of acute renal failure and the value of the measured parameters. METHODS: After agreement of the local ethic committee, 21 patients of the ICU were investigated. They were divided into two groups: 1st (n = 14) with no signs of renal dysfunction and were regarded as control group and 2nd (n = 7) were examined until the beginning of acute renal failure. For five days the glomerular filtration rate, proteinuria (immunoglobulin G, Tamm-Horsfall protein, alpha-1- and beta-2 microglobulin, lysozyme), the brush border enzymes angiotensinase A and the lysosomal enzyme N-acetyl-beta-d-glucosaminidase were daily measured and compared with clinical standards like the excretion of albumin, the clearances of creatinine and urea and the fractional excretion of sodium. RESULTS: Both groups were comparable with respect to drug therapy, APACHE-II-score (with the exception of the last day before ARF), and infusion therapy. There were differences in tubular functions between the 2 groups. Patients developing renal insufficiency showed an increased excretion of alpha-1-microglobulin, and decreased excretions of Tamm-Horsfall-protein, angiotensinase A as well as a low renal blood flow. Significant differences were also detectable in glomerular functions (glomerular filtration rate), albumin, and immunoglobulin G. DISCUSSION: Only a short time interval (1 to 2 days) between tubular and glomerular damage were detectable in patients with renal insufficiency. Renal failure must be due to circulatory problems because of the nearly simultaneous increase of tubular and glomerular parameters after RPF decreased. The parameters alpha 1-microglobulin, angiotensinase A and Tamm-Horsfall-protein gave early indications for the acute renal failure. They showed satisfactory sensitivity and specificity, but the positive predictive value was poor.

Acute Disease↗

[Dose-response relationship of clonidine with epidural administration of ropivacaine in orthopedic procedures of the lower extremities].

OBJECTIVE: The aim of this study was to investigate preliminarydose-range effects of clonidine added to ropivacaine for epidural analgesia in elective orthopedic surgery of the lower limbs with doses, causing a minimum of cardiovascular side effects. METHODS: 60 patients were randomly assigned to receive in a double-blind fashion a mixture of 1 mg/cm height ropivacaine plus saline or 1 mg/cm ropivacaine plus 25 micrograms, 50 micrograms, 75 micrograms, 100 micrograms or 150 micrograms clonidine for epidural analgesia. The sensory and motor function were determined at defined time intervals for 30 minutes. Heart rate and blood pressure were controlled and sedation score was judged. The postoperative 2-segment-regression of pin-prick and the onset of pain were recorded. RESULTS: The six groups were comparable in demographic data and in term of onset time. The prolongation of analgesia reached 513 +/- 92 min (p = 0.002) for 150 micrograms clonidine, 460 +/- 148 min (p = 0.073) for 100 micrograms clonidine, 440 +/- 86 min (p = 0.057) for 75 micrograms clonidine compared with 347 +/- 114 min for saline. In an equal manner, 2-segment-regression for pin-prick was extended to 251 +/- 47 min (p = 0.018) for 150 micrograms clonidine, 238 +/- 33 min (p = 0.034) for 100 micrograms clonidine, 229 +/- 29 min (p = 0.027) for 75 micrograms clonidine and 178 +/- 43 min for saline. Heart rate dropped down in all groups. Mean arterial pressure decreased significantly in the groups with 75, 100 and 150 micrograms clonidine. Sedation score increased continuously from 0.6 +/- 0.5 (saline) to 1.8 +/- 0.8 (150 micrograms clonidine). CONCLUSION: We conclude that 150 micrograms clonidine significantly enhances the duration of analgesia of epidurally administered ropivacaine in a mean of 171 mg. This time interval is longer than the one with 200 mg ropivacaine alone. But, there are side effects in form of decrease of arterial pressure. Cardiovascular monitoring seems to be essential. Because of the enhanced analgesia duration, the time interval for reloading epidural anaesthesia are increased.

Adrenergic alpha-Agonists↗

[Risk factors and frequency of adverse effects after autologous blood donation].

OBJECTIVE: Autologous blood donation before elective surgery decreases the perioperative risk although donation itself can cause adverse effects. Are there specific donor characteristics, which influence the frequency and severity of adverse effects? METHODS: We investigated in a prospective study 3603 autologous blood donations including registration of patient's age, gender, height, weight, medical record and risk-score by Böcker. The adverse effects were divided into severity groups (SG). The investigation took place in a Department of Anaesthesiology and Intensive Care Medicine in an university hospital. 1041 patients with preoperative autologous blood donation were investigated between January 1995 and April 1997. RESULTS: 7.4% of patients had adverse effects. Hypotension and bradycardia were the most frequent adverse effects. 4.3% of the adverse effects were graded as minimal (SG 1), 2.4% as mild (SG 2) and 0.7% as moderate (SG 3). The rate was higher in young donors (< 25 years). For all other donor characteristics including older age, cardiac or pulmonary diseases and high risk-score no higher donation risk was observed. CONCLUSIONS: Adverse effects during and after autologous blood donation are rare. Predictor for reaction seems to be young age (< 25 years). Referring to donor's characteristics and predonation risk factors it is hardly possible to predict adverse effects. Thus, all autologous blood donors require adequate monitoring by a physician. Under these circumstances the autologous blood donation is a safe procedure even in patients with severe risk factors.

Adolescent↗

Volume therapy in the critically ill: is there a difference?

OBJECTIVE: There are still several concerns about the extensive and prolonged use of hydroxyethylstarch solution (HES) in critically ill patients. The effects of volume replacement with HES over 5 days on hemodynamics, laboratory data, and organ function were compared with volume therapy using human albumin (HA). DESIGN: Prospective, randomized study. SETTING: Clinical investigations on a surgical intensive care unit (ICU) of a university hospital. PATIENTS: 150 traumatized patients (injury severity score > 15) and 150 postoperative patients with sepsis were analyzed. INTERVENTIONS: Either 10% low-molecular weight HES (HES-trauma, n = 75; HES-sepsis, n = 75) or 20% HA (HA-trauma, n = 75; HA-sepsis, n = 75) was given for 5 days to maintain the pulmonary capillary wedge pressure (PCWP) between 12 and 15 torr. The entire management of therapy of the patients was performed by physicians who were not involved in the study and blinded to the infusion regimen. MEASUREMENTS AND RESULTS: In addition to extensive cardiorespiratory monitoring, several routine laboratory parameters for assessing pulmonary, renal, hepatic, and coagulation function were analyzed from arterial blood samples on the day of admission to the ICU and on the day of sepsis diagnosis, respectively ("baseline" value) and daily over the following 5 days. Mortality during and after the study did not differ significantly between the infusion groups. There were also no differences between the incidence of pulmonary, renal, or hepatic failure in the two subgroups. Mean arterial pressure, heart rate, and PCWP were similar in both subgroups, whereas cardiac index, oxygen delivery index, oxygen consumption index, and the ratio between the partial pressure of oxygen in arterial blood and fractional inspired oxygen were higher in the HES- than in the HA-treated groups. Standard coagulation parameters did not differ, albumin concentration increased significantly in both HA groups, and lactate concentrations decreased only in the HES-sepsis patients (from 2.8 +/- 0.5 to 1.5 +/- 0.4 mg/dl). Volume replacement using albumin was significantly (p < 0.001) more costly than therapy with HES. CONCLUSIONS: Volume therapy with 10% HES for 5 days in the ICU patient showed no disadvantages compared with an infusion regimen using 20% albumin. Volume replacement using HES may even be associated with improved hemodynamics. HES appears to be a valuable and significantly cheaper alternative to albumin--even for prolonged volume therapy in the critically ill patient.

Adult↗

Are circulating adhesion molecules specifically changed in cardiac surgical patients?

BACKGROUND: Soluble adhesion molecules are considered to be markers of inflammation, endothelial activation, or damage. This study was designed to assess whether adhesion molecules are specifically altered in patients undergoing cardiac surgical procedures. METHODS: Three groups of 20 patients each were prospectively studied: patients undergoing elective coronary artery bypass grafting; patients scheduled for a Whipple pancreatoduodenectomy; and patients undergoing elective pneumonectomy for lung cancer. Plasma levels of soluble adhesion molecules (endothelial leukocyte adhesion molecule-1, intercellular adhesion molecule-1, vascular cell adhesion molecule-1, and granule membrane protein 140) were measured from arterial blood samples after induction of anesthesia (baseline), at the end of the operation, 2 hours and 5 hours after operation, and on the morning of the first postoperative day. RESULTS: Duration of operation was longest in the group having a Whipple operation (289 +/- 50 minutes) and did not differ between the other two groups. Plasma levels of all measured adhesion molecules at baseline were within normal ranges. After cardiopulmonary bypass, levels of adhesion molecules were significantly increased in the cardiac surgical patients (soluble endothelial leukocyte adhesion molecule-1, from 38 +/- 11 ng/mL at baseline to 68 +/- 12 ng/mL; soluble intercellular adhesion molecule-1, from 241 +/- 50 ng/mL to 498 +/- 78 ng/mL; and granule membrane protein 140, from 69 +/- 12 ng/mL to 150 +/- 25 ng/mL). On the morning of the first postoperative day, all levels had returned to baseline except that of soluble vascular cell adhesion molecule-1, which was still elevated (p < 0.05). In both the other groups, concentrations of adhesion molecules remained almost unchanged. CONCLUSIONS: Cardiac operation was associated with increased plasma levels of soluble adhesion molecules, a finding indicating endothelial activation or dysfunction. In contrast, in patients undergoing complex, long-lasting abdominal or lung operations, soluble adhesion molecules remained unchanged. Activation of proinflammatory cascades, ischemia/reperfusion phenomenon, and microcirculatory dysfunction appear to be the most likely reasons for this difference between groups. Whether modulation of adhesion molecules may influence organ function after cardiopulmonary bypass remains to be elucidated in further studies.

Aged↗

Cardiovascular effects of Org 9487 under isoflurane anaesthesia in man.

The cardiovascular effects of Org 9487 during isoflurane anaesthesia have been evaluated using three doses around its ED90 for neuromuscular blockade, i.e. 1 mg kg-1, 2 mg kg-1 and 3 mg kg-1. Heart rate increased to 110%, 115% and 118% in patients receiving 1 mg kg-1, 2 mg kg-1 and 3 mg kg-1 respectively. There were no significant effects on systolic and diastolic blood pressures for the two lower dose groups. Patients receiving Org 9487 3 mg kg-1 displayed significant decreases in systolic and diastolic blood pressures (91% and 82% of the control values respectively). Except for heart rate in the group receiving 3 mg kg-1, all measurements returned to baseline after a maximum of 15 min. Six patients experienced a transient increase in airway pressure after administration of Org 9487, which was accompanied by a decrease in oxygen saturation in two out of six subjects, but there was no audible wheezing. These episodes were self-limiting and required no treatment. There were no other adverse reactions to this drug during this study.

Adult↗

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Anesthesiology↗

[Volume replacement solutions--pharmacology and clinical use].

PHYSIOLOGY AND PATHOPHYSIOLOGY: Total body water represents 60% of body weight (BW), consisting of 40% BW intra- and 20% BW extracellular fluid. Extracellular fluid is divided into 16% BW interstitial fluid and 4% BW plasma volume (Fig. 1). The colloid oncotic pressure (COP) of the plasma proteins, which is about 25 mmHg (Fig. 2), is the main factor for the retention of intravascular volume and the prevention of interstitial edema. Within a defined range, oxygen transport capacity can be improved by normovolaemic haemodilution. Under strictly normovolaemic conditions ("controlled haemodilution"), the critical haemoglobin concentration for intensive care patients is about 10.0 g/dl, and 8-6 g/dl in patients with satisfactory compensatory mechanisms under stable clinical conditions. Larger blood volume deficits are replaced step by step with volume replacement solutions (crystalloids and synthetic colloids), packed red cells, fresh-frozen plasma, and platelets (Fig. 3). VOLUME REPLACEMENT WITH CRYSTALLOID AND COLLOID SOLUTIONS: Crystalloid solutions do not contain any macromolecules. Due to their lack of intrinsic COP, they spread rapidly over the intravascular and interstitial space. To achieve a comparable volume effect like colloid solutions, a fourfold infusion volume is necessary. Thus, crystalloids should be used in addition to colloid solutions to compensate the interstitial fluid deficit. Hyperosmotic-hyperoncotic solutions have not yet been established, and their benefit seems doubtful. Synthetic colloid solutions contain gelatin, dextran, or hydroxyethyl starch (HES) molecules. Due to their intrinsic COP, fluid is fixated in the intravascular space (Fig. 4). Solutions with high COP increase the intravascular volume due to resorption of interstitial fluid (plasma expanders). Pharmacological characterisation of synthetic colloids includes concentration [%], mean molecular weight [x1,000 Dalton] and degree and position of substitution (HES only). Main clinical features are the maximal volume effect and the duration of a 100% and a 50% volume effect (Fig. 5). For economic reasons, 5% albumin should not be used for volume replacement. The use of 20% albumin in intensive care patients is also limited and recommended only if a capillary leck is unlikely and the dose limits of synthetic colloids are reached. Gelatin is a polypeptide of bovine origin and achieves a shortlasting isovolaemic volume effect. When compared with dextran or HES, negative effects on haemostatis are less, and the renal function is not impaired. Thus, gelatin is first of all indicated in patients with limited volume demand, and secondly in situations with massive blood losses, when the dose limits of HES are reached. Dextran has no specific benefits. HES is a polysaccharide of maize or potato origin. By substitution of glucose molecules with hydroxyethyl groups, starch molecules are protected against fast amylase degradation. Metabolism depends on the degree and position of substitution and mean molecular weight. Smaller molecules are eliminated via the kidneys, but a certain amount of larger molecules is stored in the reticulo-endothelial system. HES is available in very different preparations (concentration 3-10%, mean molecular weight 70,000-450,000 Dalton, substitution 50-70%). Special indications of 10% HES 200/0.5 are rapid hypervolaemic replacement of massive blood losses and increase of COP in intensive care patients without capillary leak. Synthetic colloids as well as albumin may lead to adverse reactions, which are generally very rare. In large-scala studies, no significant differences have been found with regard to incidence and severity.

Animals↗

Fundamental properties of local anesthetics: half-maximal blocking concentrations for tonic block of Na+ and K+ channels in peripheral nerve.

UNLABELLED: Local anesthetics suppress excitability by interfering with ion channel function. Ensheathment of peripheral nerve fibers, however, impedes diffusion of drugs to the ion channels and may influence the evaluation of local anesthetic potencies. Investigating ion channels in excised membrane patches avoids these diffusion barriers. We investigated the effect of local anesthetics with voltage-dependent Na+ and K+ channels in enzymatically dissociated sciatic nerve fibers of Xenopus laevis using the patch clamp method. The outside-out configuration was chosen to apply drugs to the external face of the membrane. Local anesthetics reversibly blocked the transient Na+ inward current, as well as the steady-state K+ outward current. Half-maximal tonic inhibiting concentrations (IC50), as obtained from concentration-effect curves for Na+ current block were: tetracaine 0.7 microM, etidocaine 18 microM, bupivacaine 27 microM, procaine 60 microM, mepivacaine 149 microM, and lidocaine 204 microM. The values for voltage-dependent K+ current block were: bupivacaine 92 microM, etidocaine 176 microM, tetracaine 946 microM, lidocaine 1118 microM, mepivacaine 2305 microM, and procaine 6302 microM. Correlation of potencies with octanol:buffer partition coefficients (logP0) revealed that ester-bound local anesthetics were more potent in blocking Na+ channels than amide drugs. Within these groups, lipophilicity governed local anesthetic potency. We conclude that local anesthetic action on peripheral nerve ion channels is mediated via lipophilic drug-channel interactions. IMPLICATIONS: Half-maximal blocking concentrations of commonly used local anesthetics for Na+ and K+ channel block were determined on small membrane patches of peripheral nerve fibers. Because drugs can directly diffuse to the ion channel in this model, these data result from direct interactions of the drugs with ion channels.

Anesthetics, Local↗