Biomedical subjects
W Bronsveld
Publications and source records attributed to W Bronsveld.
[The patient with pseudotumor cerebri and disseminated lupus erythematosus].
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Predictive value of complement profiles and anti-dsDNA in systemic lupus erythematosus.
In a prospective study of 143 patients with systemic lupus erythematosus (SLE) the relation between clinical exacerbations, anti-dsDNA levels, and serum levels of complement components, C1q, C4, C3, C5, and C9 was investigated. In 33 out of these 143 patients a major clinical exacerbation of the disease developed. Evaluation of anti-dsDNA levels in relation to disease activity confirmed our earlier finding that anti-dsDNA levels rose before a major exacerbation and decreased after it. In the remaining 110 SLE patients a nearly constant anti-dsDNA level was seen, but none of these patients experienced a major exacerbation. In the 21 SLE patients who developed deterioration in renal function a decrease of C4 followed by decreases of C1q and C3 levels was seen first, starting about 25 to 20 weeks before the first signs of renal involvement. In the 12 SLE patients who developed an exacerbation without renal involvement an inconsistent profile of the complement components C4, C1q, and C3 was observed. C5 levels were hardly affected at all, while C9 levels were in general higher than normal during the exacerbation, irrespective of the type of exacerbation. These results show that, by following the complement and anti-dsDNA profiles, not only can exacerbations be predicted but also a pointer can be obtained about the pattern of disease well before the first clinical signs of an exacerbation appear.
Comparison of two types of nonbarbiturate anesthetics during endotoxemia in dogs.
In dogs anesthetized with etomidate (n = 8) or droperidol-methadone-atropine (n = 5), we measured before (t = 0) and after (t = 90 min) endotoxin (1.5 mg X kg-1 IV as a bolus) systemic and pulmonary blood pressures, cardiac output and its distribution (microspheres), blood gases, blood glucose, and lactate. The effects of endotoxin depended little on the type of anesthetic. The differences between the two groups were quantitative rather than qualitative. The influence of the type of anesthesia during endotoxin shock studies should thus not be overestimated.
Regional blood flow and metabolism in canine endotoxin shock before, during, and after infusion of glucose-insulin-potassium (GIK).
Glucose-insulin-potassium infused (GIK) during endotoxin shock causes increased cardiac output (CO) accompanied by decreased systemic vascular resistance. We have studied the effects of GIK on the distribution of cardiac output with radioactive microspheres to see if this decrease in resistance is equally distributed over all organs. GIK resulted in increased CO and increased flow to heart, splanchnic bed, kidneys, adrenals, and skeletal muscle, but fractional flow to these organs did not change. Thirty minutes after the GIK infusion, CO and organ flow had fallen again and differences between the endotoxin and control groups were no longer significant. GIK thus increases CO during endotoxin shock but does not influence its distribution. Systemic oxygen transport increased after GIK, but oxygen extraction decreased. Myocardial and splanchnic oxygen consumption did not change significantly. Oxygen extraction also diminished in these areas after GIK. GIK did not influence serum lactate: In both groups lactate increased significantly.
Hemodynamic determinants of mortality in human septic shock.
To assess the relative importance of cardiac versus peripheral vascular failure in patients dying of septic shock, a series of 42 patients with documented septic shock was retrospectively evaluated. Patients were included in the study if serial hemodynamic and metabolic studies had been performed: the first one within 12 hours after onset of septic shock and the last one within 12 hours (median 2 hours; range 0.1 to 12 hours) before death in nonsurvivors. Nonsurvivors were included only if they died in shock. From the patient records the first, highest, and last measured cardiac indexes (CI) (t = 1, t = 2, and t = 3) with concomitant hemodynamic and metabolic variables were obtained. Group I (n = 21) consisted of survivors and group II (n = 21) of nonsurvivors. Group II was divided into three subgroups: group IIa (n = 4) consisted of nonsurvivors with liver cirrhosis, group IIb (n = 9) patients with final CI less than 4 1 X min-1 X m-2, and group IIc (n = 8) patients with final CI greater than 4 1 X min-1 X m-2. At t = 1 no significant differences in hemodynamic variables were found between groups I and II, and all patients, whether surviving or not, were able to increase CI to similar levels. At t = 3 group II showed a marked decrease in mean arterial pressure and systemic vascular resistance index compared with group I (p less than 0.001), whereas CI did not differ significantly. The nonsurvivors showed progressive lactic acidemia. Even group IIb patients showed persistent vasodilation despite a decrease in CI. Our data suggest that many patients in septic shock die as a result of peripheral vascular rather than cardiac failure, since persistent vasodilation, irrespective of CI, was a major hemodynamic determinant in nonsurvivors, of whom 57% maintained a high CI until shortly before death.
Adult respiratory distress syndrome in leptospira icterohaemorrhagiae infection.
A 55-year-old man was admitted to our Intensive Care Unit with symptoms and signs of Weil's disease. Respiratory failure developed. Radiological and haemodynamic features were consistent with the adult respiratory distress syndrome. The patient recovered after mechanical ventilation with positive end-expiratory pressure. This case confirms that the adult respiratory distress syndrome may occur in leptospirosis.
Skeletal muscle perfusion and metabolism during canine endotoxin shock.
Conflicting data exist in literature about the effects of endotoxin on skeletal muscle perfusion and metabolism during canine endotoxin shock. In 12 dogs we therefore studied (six control and six endotoxin treated, 1.5 mg X kg-1) under etomidate (4 mg X kg-1 X h-1) anaesthesia muscle blood flow (radioactive microspheres) in fore limb, thorax, diaphragm and hind limb (five different muscles) and skin blood flow before (t = 0) and 90 and 120 min after endotoxin. We also measured blood flow in the femoral artery and vein (electromagnetic flow transducers) and the arteriovenous differences of oxygen, lactate, glucose and FFA over the femoral vascular bed (at t = 0, 30, 90 and 120 min). Endotoxin administration caused a fall of flow in the femoral artery and vein (by 65 and 63%, respectively at t = 15). After t = 60 flow in the femoral artery and vein increased slowly but the flows were still below the preshock values at t = 20 (by 33 and 50%, respectively). Skeletal muscle and skin flow did not decrease or even increased after endotoxin but decreased in the control group. Percentage of cardiac output distributed to brachial, intercostal and hind limb muscle and skin increased after endotoxin (by 163, 167, 111 and 120%, respectively at t = 20). The five muscles of the hind limb did not respond differently to endotoxin. In spite of diminished arterial inflow, skeletal muscle perfusion was thus maintained in the hind limb, probably due to closing of shunts and redistribution of blood away from bone. Oxygen extraction but also lactate release by the femoral bed had increased during endotoxin shock. After endotoxin femoral glucose extraction was only elevated at t = 30 when arterial glucose concentration had also increased. The femoral bed produced free fatty acids (FFA) but during endotoxin shock the arteriovenous concentration difference of FFA decreased. Our data suggest that skeletal muscle flow nor oxygen consumption and glucose metabolism is affected during 2 h of canine endotoxin shock. Lactate production, however, tended to increase.
Myocardial metabolic and morphometric changes during canine endotoxin shock before and after glucose-insulin-potassium.
Glucose-insulin-potassium (GIK) improves myocardial function during endotoxin shock but the mechanism of this action is not clear. We have studied in open chest dogs the effects of GIK (n = 9) on haemodynamics, myocardial biochemistry (repeated drill biopsies; glucose-6-phosphate, G-6-P; fructose-6-phosphate, F-6-P; adenosine triphosphate, ATP; creatinine phosphate, CP; glycogen) and myocardial histomorphometry. The animals were anaesthetised (etomidate 4 mg X kg-1 X h-1) and artificially ventilated (N2O:O2 = 2:1). After endotoxin (1.5 mg X kg-1) cardiac output (CO) and mean arterial pressure (MAP) fell rapidly, with a temporary recovery followed by gradual circulatory collapse. Coronary blood flow (cbf; radioactive microspheres) decreased, but this was not significant. G-6-P tended to fall, as did ATP levels while CP levels were unaltered. Histomorphometrical analysis showed myocardial cell swelling with compression of capillaries and decreased interstitial volume. GIK infusion (50% glucose, 2 g X kg-1bw, 8 mmol KCl and 3 U insulin kg-1bw) increased CO and coronary blood flow. Glycogen and G-6-P levels did not change, while F-6-P tended to increase. ATP levels were not influenced by ATP/CP ratio decreased. Myocardial cell swelling markedly decreased; average capillary cross-sectional area, as an index of capillary compression, returned to control value. In two dogs, which died before the end of the experiment, myocardial oedema, with disturbed capillary volume and reduced interstitial volume was unaltered after GIK. The initial effects of GIK are most likely due to restoration of myocardial perfusion. Improved perfusion, and the influence of elevated serum osmolality and insulin levels on excitation-contraction coupling may help to improve myocardial function.
Continuous arteriovenous hemofiltration as an adjunctive therapy for septic shock.
The effects of continuous arteriovenous hemofiltration were studied in septic patients with acute renal failure and gross fluid overload. Hemofiltration was performed for a mean of 7 days per patient (range 1 to 14 days). The mean filtration volume was 3.64 L/day. The mean total ultrafiltration volume per patient was 25.5 L. The patients were hemodynamically stable during hemofiltration, as indicated by measurements of arterial blood pressure, CVP, pulmonary artery pressure, pulmonary artery wedge pressure, and cardiac output. Multiple simultaneous measurements in both serum and ultrafiltrate showed a very close correlation for sodium, potassium, phosphorus, urea and creatinine levels. There was no detectable protein in the ultrafiltrate. The calcium concentration in the ultrafiltrate was relatively low. Finally, antibiotic levels in the ultrafiltrate were almost equal to serum levels. There were no significant complications; in this series of patients hemofiltration was a safe and effective treatment of fluid overload.
Use of glucose-insulin-potassium (GIK) in human septic shock.
Fifteen patients with septic shock and perfusion failure received a 20-min infusion of glucose-insulin-potassium (GIK, glucose 50%, 1 g/kg body weight; insulin 1.5 U/kg, potassium, 10 mMol) after volume loading and vasoactive medication had failed to eliminate hypotension and lactacidemia. Hemodynamic and oxygen measurements were obtained before, immediately and 30 min after GIK infusion. GIK improved hemodynamic status, at least temporarily, in 14 of 15 patients. Cardiac index (CI) increased simultaneously with an increase in cardiac filling pressure. Systemic vascular resistance decreased, particularly in patients with an initially low CI (less than 4 L/min X m2). Mean arterial and pulmonary artery pressures did not change. After 30 min, cardiac filling pressure fell while CI was still elevated, but this decrease was only significant for those with an initially low CI. Although arterial oxygen content decreased after GIK, oxygen consumption did not fall. Serum lactate increased. Six patients died because of ongoing sepsis. Nine patients survived at least 48 h, showing further clinical improvement. Only four patients were hospital survivors. Because GIK increased cardiac output and possibly oxygen consumption, its administration may be considered in the treatment of septic shock when conventional therapy fails.
Intermittent abdominal compression during cardiopulmonary resuscitation.
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Problems in the treatment of septic shock.
A small review is presented on the problems encountered in the treatment of septic shock. The discussion is focussed on haemodynamic problems. At least three and possibly four haemodynamic mechanisms seem to be involved: peripheral pooling, increased vascular permeability, myocardial failure (right and/or left heart failure) and probably peripheral vascular failure. A method is indicated to study some of these mechanisms.
Distribution of cardiac output, oxygen consumption and lactate production in canine endotoxin shock.
Endotoxin causes shock accompanied by compensatory changes such as redistribution of cardiac output and increased oxygen extraction. We studied these effects in anaesthetised dogs (etomidate: 4 mg X kg-1 X h-1, n = 14) randomly assigned to a control (n = 6) and a shock group (endotoxin 1.5 mg X kg-1; n = 8). We measured left ventricular pressure, LVEDP and LVdP/dt (Millar microtip), mean systemic, central venous and pulmonary artery pressure (Statham P23Db), cardiac output (thermodilution), organ flow (microspheres, 15 micron, 5 labels), bloodgases (PO2, PCO2), pH and lactate. All measurements were performed before and at 60, 90, 120 and 150 min after endotoxin or saline. Sixty minutes after endotoxin mean systemic pressure, LVdP/dt and cardiac output had decreased (by 60, 50 and 35%), while heart rate had increased (by 30%). Arterial PO2 was lower after endotoxin (-29%), haematocrit and mixed venous PCO2 were higher (+16 and +38%) and arterial pH had decreased from 7.34 to 7.14. After endotoxin perfusion of heart and adrenals did not change but muscle perfusion increased (by 33% at t = 90). Endotoxin caused vasoconstriction in spleen and kidneys: the percentage of cardiac output to these organs thus decreased (by 50 and 69%). Sixty minutes after endotoxin we found vasodilatation in the hepatic arterial, pancreatic, and gastrointestinal beds. Later the percentage of cardiac output to these beds decreased. Systemic arterio-venous shunting fell (from 6.5 to 0.7%). Systemic and splanchnic oxygen extraction increased (by 66 and 71% at t = 60): oxygen consumption hardly changed; 60 min after endotoxin it tended to decrease. During shock serum lactate rose (by 167% at t = 60) before oxygen consumption fell. Myocardial oxygen consumption did not alter during shock but the tension time index decreased.
Effects of glucose-insulin-potassium (GIK) on myocardial blood flow and metabolism in canine endotoxin shock.
Glucose-insulin-potassium (GIK) has beneficial effects during endotoxin shock, possibly through improvement of myocardial function, but the mechanism is not clear. We have studied the effects of GIK on left ventricular function, coronary flow, and oxygen consumption in controls and dogs treated with endotoxin (1.5 mg/kg-1). The animals were anaesthetized (etomidate 4 mg/kg-1/hr-1) and ventilated (N2O:O2 = 2:1). We have measured left ventricular pressure, left ventricular end-diastolic pressure (LVEDP) and LVdP/dt, systemic blood pressure, cardiac output (CO; thermodilution), coronary blood flow (CBF; radioactive microspheres), and oxygen content and lactate in arterial and coronary sinus blood. Endotoxin caused a rapid fall of CO and blood pressure with a temporary recovery followed by gradual circulatory collapse. GIK infusion (50% glucose, 2 g/kg-1 bw, 8 mmol KCl, and 3 U insulin/kg-1 bw) increased CO (56%), CBF (61%), blood pressure (21%), LVEDP (77%), and LVdP/dt (28%), and systemic vascular resistance decreased (23%). Stroke work (80%) and tension time index (42%) decreased during shock, but GIK temporarily improved these variables. The ratio of stroke work, respectively tension time index to oxygen consumption, suggests that myocardial efficiency decreased during shock and improved after GIK. Endotoxin decreased the ratio of endo- to epicardial flow. GIK did not change this ratio. However, for the same endo to epi ratio, increased CBF implies increased flow to endocardium.
Effects of glucose-insulin-potassium (GIK) on the position of the oxyhemoglobin dissociation curve, 2.3-diphosphoglycerate, and oxygen consumption in canine endotoxin shock.
The effects of glucose-insulin-potassium (GIK) on hemodynamics, oxygen transport, P50, 2,3-diphosphoglycerate (2.3-DPG), and adenosine triphosphate (ATP) were evaluated in canine endotoxin shock. Ten dogs were studied under general anesthesia and controlled ventilation. Shock was induced with Escherichia coli endotoxin (1.5 mg/kg body wt). Thereafter two groups of five dogs each were formed by randomization. The one group received GIK (glucose 50%, 2 g/kg, insulin 3 U/kg, and 10 mmole K) in the period between 90 and 120 min after endotoxin. The other group received an equal amount of NaCl infusion and served as a control group. Observations were completed at 180 min after endotoxin. GIK resulted in a significant increase of cardiac output, stroke volume, mean arterial pressure, and oxygen consumption. Serum phosphate levels decreased. No changes were observed of P50 in vitro (at 37 degrees C and pH 7.40) and of P50 in vivo, nor of 2.3-DPG and ATP in the red cells. The data suggest that the increased oxygen consumption after GIK in canine endotoxin shock is caused only by improvement of cardiac output and oxygen availability and not by an effect on oxygen unloading capacity of hemoglobin.
Effect of volume loading and dopamine on hemodynamics and red-cell redistribution in canine endotoxin shock.
We studied in 20 anesthetized dogs (11-15 kg) the effect of volume loading and dopamine in the period between 90 and 120 min after injection of E Coli endotoxin (1.5 mg/kg). Changes in red-cell distribution were estimated from changes in regional radioactivity emitted by autologous 99mTc tagged red cells. Four groups of five animals were formed by randomization, such that effects of dopamine (15 micrograms/kg/min) and isotonic gelation solution (40 ml/kg/30 min) could be analyzed separately and in combination. Ninety minutes after endotoxin a significant decrease in cardiac output, arterial, and pulmonary arterial wedge pressures were observed. Thoracic radioactivity decreased by 26% and an increase in abdominal (11%) and hindlimb (17%) activity was measured, while the changes in hepatic activity were variable. No interaction between dopamine and volume for any parameter was found. Dopamine resulted in an increase in heart rate, while the other hemodynamic parameters did not change significantly. Dopamine resulted only in a slight increase in abdominal radioactivity. Volume loading produced an increase in cardiac output to greater than 200% of the value before endotoxin. This increase was accompanied by a considerable decrease in systemic resistance. No major changes in red-cell distribution were observed. We concluded that volume loading and dopamine did not affect red-cell redistribution in a later phase of canine endotoxin shock. Furthermore, our results suggest that correction of the volume deficit in this model results in a high-cardiac-output-low-systemic-resistance hemodynamic pattern.