[Perioperative fluid management: A relay race of knowledge].
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Biomedical subjects
Publications and source records attributed to M Rehm.
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About twenty years ago, Peter Stewart had already published his modern quantitative approach to acid-base chemistry. According to his interpretations, the traditional concepts of the mechanisms behind the changes in acid-base balance are considerably questionable. The main physicochemical principle which must be accomplished in body fluids, is the rule of electroneutrality. There are 3 components in biological fluids which are subject to this principle: a)Water, which is only in minor parts dissociated into H+ and OH-, b)"strong", i.e. completely dissociated, electrolytes, which thus do not interact with other substances, and body substances, such as lactate, and c)"weak", i.e. incompletely dissociated, substances. Peter Stewart strictly distinguished between dependent and independent variables and thus indeed described a new order of acid-base chemistry. The 3 dependent variables (bicarbonate concentration [Bic(-)], pH, and with this also hydrogen ion concentration [H(+)]) can only change if the 3 independent variables allow this change. These 3 independent variables are: 1. Carbon dioxide partial pressure, 2.the total amount of all weak acids ([A-] (Stewart called these ATOT), and 3.strong ion difference (SID). [A(-)] can be calculated from the albumin (Alb) and the phosphate concentration (Pi): [A(-)]=[Alb x (0.123 x pH - 0.631)] + [Pi x (0.309 x pH - 0.469)]. An apparent SID (or "bedside" SID) can be calculated using measurable ion concentrations: SID=[Na(+)] + [K(+)] - [Cl(-)]-lactate. Regarding the metabolic disturbances of acid-base chemistry, according to Stewart's terminology, changes in pH, [H(+)], and [Bic(-)] are only possible if either SID or [A(-)] itself changes. If, for example, SID decreases (e.g. in case of hyperchloremia), this increase in independent negative charges leads to a decrease in dependent negative charges in terms of [Bic(-)] resulting in acidosis (and vice versa). Therefore, according to Stewart, the decrease in SID during hyperchloremic acidosis results from the increase in serum chloride concentration and is the causal mechanism behind this acidosis. Contrary for example, a decrease in [A(-)] (e. g. during hypoalbuminemia) leads to an increase in [Bic(-)] and therefore to an alcalosis (and vice versa). Thus, by Stewart's approach, completely new acid-base disturbances, like "hyperchloremic acidosis" or "hypoalbuminemic alcalosis" (which, of course, can also exist in combination) can be detected, which had been unrecognised by the classic acid-base concepts. Consequently, Stewart's analysis can lead to a better understanding of the mechanisms behind the changes in acid-base balance.
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We report the case of a 37-year-old primigravida with an extreme cerebral arteriovenous malformation which displaced almost the complete left hemisphere and was inoperable. The woman had already suffered an intracerebral bleeding from this malformation many years previously. In the 26th gestational week the perfusion of the umbilical artery decreased and therefore a cesarean section became necessary. During direct measurement of arterial blood pressure an epidural catheter was inserted. Mean blood pressure always remained between 90 and 110 mmHg, the neurologic state did not deteriorate perioperatively. The mother was monitored in the intensive care unit for 24 h and was then sent back to the maternity ward in a good condition. Two months later she came back to hospital with an acute severe headache. After CT-diagnosis of an acute subarachnoid hemorrhage she underwent an emergency craniotomy.
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.
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QUESTION: What is the impact of acute preoperative normovolemic hemodilution (ANH) on blood volume, intravascular colloid, and loss of red cells in the perioperative period? METHODS: In 20 patients undergoing radical hysterectomy, preoperative ANH was performed to a hematocrit of 22% using 5% albumin (albumin group; n = 10) or 6% hydroxyethylstarch solution (HES group; n = 10). Intraoperative retransfusion of ANH blood was started at a hematocrit of 18%. Plasma volume (indocyanine green-dilution technique), hematocrit, and plasma protein concentration were measured before and after ANH, before retransfusion, and postoperatively. Red cell volume (labelling erythrocytes with fluorescein) was determined before and after ANH and postoperatively. In the HES group hydroxyethylstarch concentrations were measured in plasma and urine. RESULTS: After removal of about 1,500 ml of blood and replacement with 15% more colloid solution, the blood volume was maintained in both groups after ANH. After a mean blood loss of about 1,800 ml, an average of 150 ml of red cells were saved due to ANH in both groups. CONCLUSIONS: Double label measurements of blood volume demonstrated that with the colloids used a surplus of 15% of colloid infusion in relation to blood removal was necessary to generate isovolemia after ANH.
We report the case of a 23-year-old rower who suffered from an exertional heatstroke while trying to lose 2 kg in weight by jogging before a competition. The development of this illness was favoured by clothes that were inappropriate for the environmental conditions and which the sportsman wore intentionally to enhance sweating. The maximum core temperature was over 43 degrees C. As a consequence the comatose patient developed a fulminant multi-organ failure with the liver ceasing its function, renal failure, massive rhabdomyolysis, and disseminated intravascular coagulation. In addition, he suffered from pericardial effusion and acute pulmonary failure (ARDS). In spite of maximum intensive care with an extensive substitution of blood products, continuous hemodiafiltration, and inhalative administration of nitrous oxide the young sportsman died 48 h after his admission to the intensive care unit. This tragic course demonstrates the danger of the widespread habit of losing weight by vigorously exercising with inappropriate clothes. In this article, potential risk factors, symptomatology, therapy, and methods of preventing an exertional heatstroke are shown and discussed.
The term blood volume (BV) measurement can be understood as the exact volumetric definition of both components of blood, the red cell volume (RCV) and the plasma volume (PV) using tracer dilution methods. The tracer used to measure the RCV must be bound to the erythrocytes and for the PV to plasma proteins, in order to label the distribution space of each carrier (i.e. erythrocytes and albumin molecules). To differentiate this there are indirect methods to estimate the BV, such as measurement of the diastolic pressure or transoesophageal echocardiography, which will not be discussed here. Alterations in the RCV and PV cannot be routinely measured, or at most only roughly estimated by means of the haematocrit (Hc) or haemoglobin (Hb) concentration which can lead to serious errors when large changes have occurred. At present measurements of the RCV and PV are not carried out in routine clinical practice. The introduction of nonradioactive tracers with a faster elimination now renders possible a relatively exact measurement of both volumes under certain clinical situations, albeit with a high technical outlay. The RCV is measured using the tracer sodium fluorescein (SoF) and the PV with the dye indocyanine green (ICG). The RCV measurement seems to be suitable for certain clinical situations, such as characterization of the preoperative condition of a patient or quantification of surgical blood loss after an operation, because it is less invasive and has a high precision. However, the results of the RCV measurement can only be delivered after 1 h which makes it more suitable for clinically stable situations. In contrast the PV estimation is based on the measurement of the ICG concentration in the arterial bloodstream after a bolus injection of the dye in the central veins and is used more in intensive care because of the invasivity. The results can be obtained 5 min after injection of the dye and therefore even rapid changes in the PV can be monitored.
QUESTION: Is polygeline (Haemaccel) a suitable colloid to perform preoperative acute normovolemic hemodilution (ANH) and to replace a large intraoperative blood loss? METHODS: In a sixty-eight-year-old patient undergoing radical hysterectomy preoperative ANH was performed to a hematocrit of 23% using 3.5% polygeline (Haemaccel). Intraoperative retransfusion of ANH blood was started at a hematocrit of 13%. Plasma volume (indocyanine green-dilution technique) and hematocrit were measured before and after ANH, 3 times intraoperatively (once before retransfusion) and postoperatively. Red cell volume (by labelling erythrocytes with fluorescein) was determined before and after ANH, before retransfusion, and postoperatively. RESULTS: After removal of 1,940 ml of blood and replacement with 15% more of colloid, blood volume decreased by 760 ml. After a mean blood loss of 4,600 ml, 290 ml and 260 ml of red cells were saved due to ANH and use of a cell saver, respectively. CONCLUSIONS: The exact double label measurements of blood volume demonstrated that polygeline, which has a volume effect of only 50%, cannot be considered to be a suitable colloidal substitute during ANH.
This essay provides an explanation and interpretation of the undertreatment of pain by discussing some of the scientific, clinical, cultural, and philosophical aspects of this problem. One reason why pain continues to be a problem for medicine is that pain does not conform to the scientific approach to health and disease, a philosophy adopted by most health care professionals. Pain does not fit this philosophical perspective because (1) pain is subjective, not objective; (2) the causal basis of pain is often poorly understood; (3) pain is often regarded as a "mere" symptom, not as a disease; (4) there often are no "magic bullets" for pain; (5) pain does not fit the expert knowledge model. In order for health care professionals to do a better job of treating pain, some changes need to occur in medical philosophy, education, and practice.
BACKGROUND: The impact of acute preoperative volume loading with colloids on blood volume has not been investigated sufficiently. METHODS: Before surgery, in 20 patients undergoing major gynecologic procedures, volume loading was performed during anesthesia by infusing approximately 20 ml/kg of colloid at a rate of 90 ml/min (group I: 5% albumin solution; group II: 6% hetastarch solution; n = 10 each). Plasma volume (indocyanine green dilution technique), erythrocyte volume (labeling erythrocytes with fluorescein), hematocrit, total protein, and hetastarch plasma concentrations (group II) were measured before and 30 min after the end of infusion. RESULTS: More than 1,350 ml of colloid (approximately 50% of the baseline plasma volume) were infused within 15 min. Thirty minutes after the infusion had been completed, blood volume was only 524 +/- 328 ml (group I) and 603 +/- 314 ml (group II) higher than before volume loading. The large vessel hematocrit (measured by centrifugation) dropped more than the whole body hematocrit, which was derived from double-label measurements of blood volume. CONCLUSIONS: The double-label measurements of blood volume performed showed that 30 min after the infusion of approximately 20 ml/kg of 5% albumin or 6% hetastarch solution (within 15 min), only mean 38 +/- 21% and 43 +/- 26%, respectively, of the volume applied remained in the intravascular space. Different, i.e., earlier or later, measuring points, different infusion volumes, infusion rates, plasma substitutes, or possibly different tracers for plasma volume measurement might lead to different results concerning the kinetics of fluid or colloid extravasation.
AIM: Connective tissue growth factor (ccn; ctgf) gene expression is upregulated in fibrotic renal glomeruli. Therefore, the regulation and pharmacological modulation of ccn2 (ctgf) mRNA expression was investigated in a human renal mesangial cell line. METHODS: A human renal mesangial cell line was cultured in vitro under standard conditions. After stimulation, RNA was extracted and ccn2 (ctgf) mRNA expression assessed by northern blot analysis. RESULTS: The expression of ccn2 (ctgf) mRNA was transiently upregulated by fetal calf serum. Very rapid onset but short lasting ccn2 (ctgf) mRNA expression was observed after stimulation with lysophosphatidic acid, a bioactive lipid, which activates G protein coupled receptors. Induction of ccn2 (ctgf) mRNA expression by transforming growth factor beta (TGF-beta) was more prolonged and lasted for more than one day. The small GTPases of the Rho family were essential for basal as well as induced ccn2 (ctgf) expression: preincubation of the cells with toxin B from Clostridium difficile abrogated ccn2 (ctgf) mRNA expression. HMG CoA reductase inhibitors, which are therapeutically used as lipid lowering drugs, interfere with the isoprenylation and thus activation of Rho proteins. Simvastatin, an HMG CoA reductase inhibitor, inhibited ccn2 (ctgf) mRNA expression in a concentration dependent manner (IC(50): 1-2 microM). CONCLUSION: Statins were identified as potent inhibitors of ccn2 (ctgf) mRNA expression in mesangial cells, and therefore might be of potential use to modulate the excessive ccn2 (ctgf) expression in mesangial cells related to glomerular fibrosis.
Glucocorticoids are potent inhibitors of cyclooxygenase-2 (prostaglandin G/H synthase-2, COX-2) expression. The focus of this work was to investigate the molecular mechanisms, by which glucocorticoids interfere with platelet-derived growth factor (PDGF)-mediated induction of COX-2 with special emphasis on the role of the transcription factors NF-kappaB/IkappaB alpha. In rat renal mesangial cells, PDGF induced a rapid and transient increase of COX-2 mRNA and protein, which reached maximal levels after 1-2 and 4 h, respectively. The in vivo half-life of COX-2 mRNA, which was estimated to be less than 1 h, was reduced by dexamethasone. Kinetic studies and COX-2 promoter activity assays indicated that dexamethasone also interfered with COX-2 transcription. Inhibition of COX-2 induction by dexamethasone was abrogated by cycloheximide, an inhibitor of translation, indicating dependence on de novo protein synthesis. As a possible mediator of dexamethasone action, the NF-kappaB/IkappaB alpha system of transcription factors was investigated. Dexamethasone doubled IkappaB alpha protein levels within 1 h and reduced complex formation of nuclear NF-kappaB proteins with DNA. Newly synthesized IkappaB alpha may thus bind to NF-kappaB and interfere with gene activation. PDGF-induced signalling, however, barely affected the NF-kappaB/IkappaB alpha system: IkappaB alpha protein remained unaltered for 30 min after treatment of mesangial cells with PDGF and was only reduced by 30% after 1 h. Concomitantly, binding of NF-kappaB proteins to DNA, detected by electrophoretic mobility shift assays, was slightly increased by 30%. Furthermore, stably transfected COX-2 promoter constructs with and without the NF-KB binding site were comparably activated by PDGF (2.5-fold increase of luciferase activity). Taken together, these data indicate that although dexamethasone interferes with the NF-kappaB/IkappaB alpha system of transcription factors, this mechanism is not essential for the inhibition of PDGF-induced COX-2 expression.
BACKGROUND: Glomerular inflammation is characterized by a consecutive infiltration of immunoreactive cells. To mimic the early phase of glomerular injury, a coculture system of platelets and rat renal mesangial cells was established. As prototypes, the inflammation-related proteins cyclooxygenase-2 (Cox-2) and the chemotactic protein osteopontin (OPN) were investigated. METHODS: The expression of OPN and Cox-2 mRNA and protein was determined by Northern and Western blot analyses. RESULTS: Coincubation of platelets and mesangial cells led to a rapid, transient induction of Cox-2 mRNA, which peaked at two hours, whereas OPN and monocyte chemoattractant protein-1 (MCP-1) were induced at later time points. The induction of Cox-2 mRNA was concentration dependent and highly reproducible when platelets of different donors were investigated. Partial Cox-2 induction was observed when supernatants of preactivated platelets were incubated with mesangial cells. The inhibition of the signaling pathways of platelet-derived growth factor (PDGF) and epidermal growth factor (EGF) or interference with Gi-protein signaling partially inhibited platelet-induced Cox-2 expression. Down-regulation of protein kinase C (PKC), which is a common signaling module in many pathways leading to Cox-2 induction, almost completely abrogated platelet-induced Cox-2 expression. The time pattern of Cox-2 and OPN expression suggested that Cox-2 might play a role in OPN induction. The up-regulation of OPN was dependent on de novo protein synthesis and was induced by high levels of exogenous prostaglandin E2 (PGE2; 10 micromol/L). Endogenous PGE2, however, proved not to be essential for OPN mRNA expression, because inhibition of Cox activity did not change OPN mRNA levels. Dexamethasone inhibited Cox-2 mRNA induction but increased OPN mRNA and protein expression. CONCLUSION: These data indicate that Cox-2 and OPN are independently up-regulated upon interaction of platelets and mesangial cells.
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BACKGROUND: Changes in blood volume during acute normovolemic hemodilution (ANH) and their consequences for the perioperative period have not been investigated sufficiently. METHODS: In 15 patients undergoing radical hysterectomy, preoperative ANH to a hematocrit of 24% was performed using 5% albumin solution. Intraoperatively, saline 0.9% solution was used for volume substitution, and intraoperative retransfusion was started at a hematocrit of 20%. Plasma volume (indocyanine green dilution technique), hematocrit, and plasma protein concentration were measured before and after ANH, before retransfusion, and postoperatively. Red cell volume (labeling erythrocytes with fluorescein) was determined before and after ANH and postoperatively. RESULTS: Mean normal plasma volumes (1,514 +/- 143 ml/m2) and reduced red cell volumes (707 +/- 79 ml/m2) were measured preoperatively. Blood (1,150 +/- 196 ml) was removed and replaced with 1,333 +/- 204 ml of colloid. Blood volume before and after ANH was equal and amounted to 3,740 ml. Intraoperatively, plasma volume did not increase until retransfusion despite infusing 3,389 +/- 1,021 ml of crystalloid (corrected for urine output) to compensate for an estimated surgical blood loss of 727 +/- 726 mi. Postoperatively, after retransfusion of all autologous blood, blood volume was 255 +/- 424 ml higher than preoperatively before ANH. Despite mean calculated blood loss of 1,256 +/- 892 ml, only one patient received allogeneic blood. CONCLUSIONS: During ANH, normovolemia was exactly maintained. After surgical blood loss of 1,256 +/- 892 ml, crystalloid and colloid supplies of 5,752 +/- 1,462 ml and 1,667 +/- 548 ml, respectively, and complete intraoperative retransfusions of autologous blood in every patient, mean blood volume was 250 ml higher than preoperatively before ANH.
BACKGROUND: Preoperative acute normovolemic hemodilution (ANH) is an excellent model for evaluating the effects of different colloid solutions that are free of bicarbonate but have large chloride concentrations on acid-base equilibrium. METHODS: In 20 patients undergoing gynecologic surgery, ANH to a hematocrit of 22% was performed. Two groups of 10 patients each were randomly assigned to receive either 5% albumin or 6% hydroxyethyl starch solutions containing chloride concentrations of 150 and 154 mm, respectively, during ANH. Blood volume (double label measurement of plasma and red cell volumes), pH, Paco2, and serum concentrations of sodium, potassium, chloride, lactate, ionized calcium, phosphate, albumin, and total protein were measured before and 20 min after completion of ANH. Strong ion difference was calculated as serum sodium plus serum potassium minus serum chloride minus serum lactate. The amount of weak plasma acid was calculated using a computer program. RESULTS: After ANH, blood volume was well maintained in both groups. ANH caused slight metabolic acidosis with hyperchloremia and a concomitant decrease in strong ion difference. Plasma albumin concentration decreased after hemodilution with 6% hydroxyethyl starch solution and increased after hemodilution with 5% albumin solution. Despite a three-times larger decrease in strong ion difference after ANH with 6% hydroxyethyl starch solution, the decrease in pH was nearly the same in both groups. CONCLUSIONS: ANH with 5% albumin or 6% hydroxyethyl starch solutions led to metabolic acidosis. A dilution of extracellular bicarbonate or changes in strong ion difference and albumin concentration offer explanations for this type of acidosis.