Treating patients with severe sepsis.
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Catecholamines↗
Biomedical subjects
K Reinhart
Publications and source records attributed to K Reinhart.
Interrelations between EEG frequency components in sedated intensive care patients during burst-suppression period.
The EEG during basic sedation and burst patterns during electroencephalic burst-suppression patterns (BSP) were analyzed. The aim of EEG analysis was the characterization and quantification of the interrelations between distinct frequency components in both states of sedation. The data for the investigations were derived from the routine EEG derivations of 12 patients with various neurosurgical diseases. It can be demonstrated that the degree of interrelation (amplitude modulation) between a low-frequency component (0-2.5 Hz) and oscillations with higher frequency (3-7.5 and 8-12 Hz) is increased in burst patterns during BSP compared with the EEG during basic sedation. It can be concluded that the degree of interrelations depends on the sedation depth induced by hypnotic drugs.
Adolescent↗
Microtubule formation and kinesin-driven microtubule gliding in vitro in the presence of lipopolysaccharide.
Lipopolysaccharide (LPS) is a main trigger substance for the development of septic shock and multiple organ failure. We showed by turbidity measurements that LPS inhibits microtubule formation in a pH-dependent manner. Inhibition was found to be not only due to sequestration of MAP2 by LPS, but also of MAP1 and tau MAPs, indicating that LPS is able to react with a broad variety of MAPs. LPS-induced inhibition of microtubule formation could be compensated by additional tau or by addition of taxol. Dot blots revealed that LPS binds directly to tau, but seems not to bind to tubulin. As tau is expressed in various tissue types involved in multiorgan failure, it might be regarded as a further target for LPS action. In contrast, kinesin-dependent microtubule gliding was not affected by LPS. The toxin neither blocked the cargo (vesicle) nor the microtubule binding site of kinesin, suggesting a certain specificity of LPS-MAP interaction.
Animals↗
HepG2 human hepatoma cells express multiple cytokine genes.
Although cytokines are known to be involved in the regulation of a variety of hepatocellular functions, hepatocytes themselves are generally considered only targets but not producers of these important mediators. In order to investigate whether cells of hepatocellular linages are a potential source of various regulatory cytokines we have estimated the multiple cytokine gene expression in the culture of well differentiated human HepG2 hepatoma cells using RT-PCR. Our findings demonstrate that HepG2 cells express mRNAs for interferon gamma (IFN-gamma), tumour necrosis factor alpha (TNF-alpha), transforming growth factor beta (TGF-beta), macrophage colony-stimulating factor (M-CSF), oncostatin-M (OSM), intercellular adhesion molecule (ICAM-1), interleukin 4 (IL-4), IL-5, IL-7, IL-10, IL-11, IL-12 and IL-6 receptor (IL-6R). At the same time the expression of IL-1, IL-2, IL-3, IL-6, CD40 ligand and IL-2R genes was not detected. It was concluded that hepatocytes are potential producers of a variety of cytokines, some of them being able to regulate hepatocellular functions directly, while others are important regulators of leukocyte activity. Thus, on the one hand, hepatocytes may express autoregulatory cytokines and on the other hand, influence the functions of other liver cells like Kupffer, Ito or endothelial cells. Due to their large amount, liver parenchymal cells could be an important source of sytemically acting pro- and anti-inflammatory and other regulatory cytokines.
CD40 Antigens↗
Comparison of pulmonary artery and arterial thermodilution cardiac output in critically ill patients.
OBJECTIVE: We studied the agreement between cardiac output measurements via pulmonary artery thermodilution [CO(PA)], regarded as the current clinical gold standard, and aortic transpulmonary thermodilution [CO(AORTA)]. DESIGN: Prospective clinical study. SETTING: Surgical intensive care unit of a university hospital. PATIENTS: 37 patients with sepsis or septic shock (n = 34) and subarachnoid haemorrhage (n = 3). MEASUREMENTS AND RESULTS: We analysed 449 simultaneous cardiac output measurements. All patients were deeply sedated and mechanically ventilated in a pressure controlled mode. Each patient received a 7.5-F five-lumen pulmonary artery catheter and a 4-F aortic catheter with an integrated thermistor. The thermistors of the two different catheters were connected to one computer system (COLD-Z021, Pulsion Medical Systems, Munich, Germany). Linear regression analysis revealed: CO(AORTA) = 0.96. CO(PA) + 1.02 (l/min) (r = 0.97, p < 0.0001). CO(AORTA) was consistently higher than CO(PA) with a bias of 0.68 (l/min) and a standard deviation of 0.62 (l/min). CONCLUSION: Cardiac output derived from aortic transpulmonary thermodilution is suitable for measurement in the intensive care unit. Measurements of CO(AORTA) are consistent with, but slightly higher than, those obtained from pulmonary artery thermodilution.
Adult↗
Glycosylphosphatidylinositol-specific phospholipase D in blood serum: is the liver the only source of the enzyme?
In cases of systemic inflammatory response syndrome, sepsis, and septic shock, the activity of glycosylphosphatidylinositol-specific phospholipase D (GPI-PLD) in serum amounts to 20 to 25% of the activity found in a healthy control group. The activity of serum GPI-PLD is positively correlated with inflammatory markers and counts of monocytes and stab cells (bands) and negatively correlated with polymorphonuclear neutrophils and lymphocytes in severe diseases. This indicates a yet unknown involvement of the inflammatory system in GPI-PLD liberation and suggests that the liver is not the only source of the plasma enzyme. Plasma was shown to contain an effective inhibitor of GPI-PLD which is soluble in organic solvents. Its concentration in capillary plasma is 20-fold higher than in venous plasma. To find possible other sources of plasma GPI-PLD besides the liver, the GPI-degrading activity was measured in different organs of the rat. Product formation was analysed using [125I]TID-labeled GPI-AP.
Alkaline Phosphatase↗
Procalcitonin expression in human peripheral blood mononuclear cells and its modulation by lipopolysaccharides and sepsis-related cytokines in vitro.
Procalcitonin (PCT), the precursor of calcitonin, was recently put forward as a diagnostic marker of systemic bacterial infection and sepsis. The major PCT production site in sepsis still remains unclear. Because of a certain association between increased levels of PCT and leukocyte-derived cytokines during sepsis, we assessed the possible expression of PCT in human peripheral blood mononuclear cells (PBMCs) and the modulation of PCT by lipopolysaccharides (LPS) and various sepsis-related cytokines by reverse transcriptase-polymerase chain reaction (RT-PCR) by using a novel primer set and flow cytometric analysis with intracellular staining with antibodies to the PCT components calcitonin and katacalcin. RT-PCR and flow cytometric analysis demonstrated that PBMCs express PCT both on mRNA and on protein levels. LPS and various proinflammatory cytokines (interleukin-1beta (IL-1beta), IL-6, tumor necrosis factor-alpha (TNF-alpha), IL-2) had pronounced stimulatory effects on the expression of PCT mRNA. Under identical experimental conditions the anti-inflammatory cytokine IL-10 had no effect on the expression of mRNA for PCT. Flow cytometric analysis demonstrated increased intracellular amounts of PCT components after LPS stimulation. Thus we demonstrate for the first time that PCT is expressed in PBMCs. This expression is modulated by bacterial LPS and sepsis-related cytokines. Therefore PBMCs may be among the sources of elevated PCT levels in patients with sepsis.
Base Sequence↗
Katacalcin and calcitonin immunoreactivity in different types of leukocytes indicate intracellular procalcitonin content.
PURPOSE: Procalcitonin is a new marker of severity of nonviral, in particular, bacterial infections. In respect of sepsis its site of production remains unknown. This study was carried out to determine whether subsets of human leukocytes contain procalcitonin. MATERIALS AND METHODS: Blood samples of 17 patients who had demonstrated various degrees of serum procalcitonin levels on the day before evaluation were analyzed for serum procalcitonin by immunoluminometry and for intracellular reaction of monocytes, granulocytes, B-, and T-lymphocytes against katacalcin- or calcitonin-sensitive antibodies. Katacalcin and calcitonin are part of the procalcitonin molecule. Associations of these reactions with serum procalcitonin levels as well as differences between groups with a normal or elevated serum level were analyzed. RESULTS: Intracellular antibody reaction against katacalcin was demonstrated in all cell types. We also found a lower rate of intracellular antibody reaction against calcitonin. Associations of serum procalcitonin with the two antibody reactions were demonstrated. Differences in intracellular reactions in the group with elevated serum procalcitonin were seen with both antibodies compared with a normal control. CONCLUSION: Intracellular antibody reaction against katacalcin supports the notion that various types of leukocytes contain procalcitonin.
Antibody Formation↗
Comparison between intrathoracic blood volume and cardiac filling pressures in the early phase of hemodynamic instability of patients with sepsis or septic shock.
PURPOSE: The purpose of this study was to analyze three different variables of cardiac preload; central venous pressure (CVP), pulmonary artery occlusion pressure (PAOP), and intrathoracic blood volume index (ITBVI) that served as the best indicator of cardiac function, that is, cardiac index (C1) or stroke index (SI). MATERIALS AND METHODS: This was a prospective study in 57 critically ill patients with sepsis or septic shock in whom 581 hemodynamic profiles were analyzed. One patient was included a second time after a period of 6 weeks. All patients were sedated and mechanically ventilated. Each patient had a 7.5-Frfive-lumen pulmonary artery catheter (PAC) and a 4-Fr catheter with an integrated thermistor and fiberoptic that was advanced into the descending aorta via a femoral artery sheath. The study was performed in the surgical intensive care unit of a university hospital. RESULTS: Linear regression analysis of the first profile for each case (n = 58) revealed a significant correlation between ITBVI and SI (r = 0.66). For comparison, correlations for PAOP/SI (r = 0.06) and CVP/SI (r = 0.10) were poor. The analysis of all second profiles showed that only the change in ITBVI reflected the change in SI (r = 0.67), whereas PAOP (r = 0.07) and CVP (r = 0.05) failed. Furthermore, a positive change in SI (n = 265) was most often associated with an increase in ITBVI (n = 189, 71.3%), less for PAOP (n = 122, 46.0%) and CVP (n = 137, 51.7%). A reduction in SI (n = 256) was accompanied by a decrease in ITBVI (n = 176, 68.8%), PAOP (n = 119, 46.5%), and CVP (n = 118, 46.1%). An increase in ITBVI (n = 269) was accompanied by an increase in SI in 189 cases (70.3%). In these, PAOP increased only in 91 (48.1%) and CVP in 101 cases (53.4%), respectively. Accordingly, a positive change in PAOP (n = 218) was associated with an increase in SI in 122 cases (56.0%). ITBVI increased in 91 (74.6%) and CVP in 84 (68.9%) of these cases. A decrease in ITBVI (n = 250) was associated with a decrease in SI in 176 cases (70.4%). Decreases in PAOP (n = 89, 50.6%) and CVP (n = 91, 51.7%) did not reflect these changes. However, when PAOP (n = 229) and SI decreased (n = 119, 52.0%), ITBVI decreased in 89 (74.8%) and CVP in 73 cases (61.3%). CONCLUSIONS: In comparison with cardiac filling pressures, ITBVI seems to be the more reliable indicator of cardiac preload in patients with sepsis or septic shock.
Adult↗
Hypothermia related changes in electrocortical activity at stepwise increase of intracranial pressure in piglets.
Recent experimental studies have demonstrated that mild hypothermia can be effective in the control of intracranial hypertension. However, investigations to analyze the effects of hypothermia on changes in brain oxygen metabolism and electrocortical activity caused by increased intracranial pressure (ICP) are lacking. We examined the effects of mild hypothermia on electrocorticogram (ECoG) in combination with measurement of regional cerebral blood flow (CBF) and estimation of brain oxygen metabolism during stepwise increase of ICP. For this purpose thirteen female piglets (14 days old, 4-5 kg b.w.) were anaesthetized and mechanically ventilated. An epidural balloon was gradually inflated in order to increase ICP to 25 mmHg, 35 mmHg and 45 mmHg every 30 minutes at adjusted mean arterial blood pressures (MAP). This procedure resulted in gradual cerebral perfusion pressure (CPP) reduction of about 70%, 50%, and 30% of baseline [baseline CPP: normothermia (NT) 80+/-3 mmHg; hypothermia (HT) 84+/-3 mmHg]. Control animals were maintained in a normothermic state (38.6+/-0.2 degrees C). HT animals were surface cooled and maintained at 31.9+/-0.1 degrees C. ECoG, regional CBF, cerebral oxygen delivery (cDO2) and the cerebral metabolic rate of oxygen (CMRO2) were estimated during the normothermic period, after hypothermic stabilization, and after the gradual CPP reductions. The baseline ECoG showed the typical delta-dominated frequency pattern for isoflurane anaesthesia. At the hypothermic level, a frequency shift was seen from delta activity towards the higher frequencies (theta- and alpha activity) and the total spectral power was significantly reduced (56+/-17% from baseline, p < 0.05). the cortical CBF decreased markedly to 67+/-10% (p < 0.05), whereas the medulla oblongata blood flow increased slightly. During controlled increase of ICP by regional mass expansion from epidural balloon inflation, we found at mild and moderate stages of ICP increase (25 and 35 mmHg) only minimal changes in the ECoG in hypothermic animals compared to the hypothermic baseline, whereas the ECoG in normothermic animals showed a marked decrease in frequency, amplitude and total spectral power. We conclude that mild hypothermia produces an arousal-like ECoG activity with marked frequency shift to alpha activity and a change from high to low voltage activity. Furthermore, the hypothermic brain showed a preserved neuronal function at moderate stages of ICP. Obviously, hypothermia improves the functional tolerance of the brain to impaired oxygen supply.
Animals↗
Procalcitonin--a novel biochemical marker for the mediator-directed therapy of sepsis.
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Amino Acid Sequence↗
New approaches for the detection and analysis of electroencephalographic burst-suppression patterns in patients under sedation.
An automatic EEG pattern detection unit was developed and tested for the recognition of burst-suppression periods and for the separation of burst from suppression patterns. The median, standard deviation and the 95% edge frequency were computed from single channels of the EEG within a moving window and completed by the continuous computation of frequency band power via an adapted Hilbert resonance filter. These parameters were given to the inputs of two hierarchically arranged artificial neural networks (NNs). The output signals of NNs indicate the suppression and burst phases. The burst recognition was focused on the precise recognition of the burst onset. In subsequent processing steps the time course of percentages of burst patterns within their corresponding burst-suppression-phases was calculated and the time locations of burst onsets can be used to trigger an averaging for a burst-related analysis. The data for our investigations were derived from the routine EEG derivations of 12 patients with various neurosurgical diseases. A group-related training of the NNs was realized. For the group-related trained NNs EEG data for 6 patients were used for training and the data of 6 other patients for testing the classification performance of the pattern recognition units. Additionally, the reliability of the detection algorithm was tested with data of two patients with convulsive state, resistant to treatment, and burst-suppression like pattern EEC.
Adolescent↗
[Serum level-adjusted dosage of once-daily aminoglycoside therapy in critical illness: results of a prospective study].
OBJECTIVE: In critically ill patients, the adjustment of target peak and trough levels of tobramycin was investigated because aminoglycoside pharmacokinetics can be changed by multiple influences. Sufficient but not too high peak serum concentrations and low trough levels, however, should be achieved to ensure a therapeutic effect and to minimize toxicity. METHODS: 70 critically ill patients of 51 +/- 18 years were monitored daily during their aminoglycoside treatment on the intensive care unit targeting a peak of about 12 micrograms/ml 30 minutes after infusion and a trough level below 1 to 2 micrograms/ml. Dose recommendations were given daily, taking into consideration serum levels, dose predictions (Bayesian method, ABBOTTBASE), creatinine clearance and clinical findings. Creatinine clearance was estimated according to the Cockcroft-Gault-formula as well as directly by the urine collection method. RESULTS: The standardized initial dose of 400 mg tobramycin led to average peak serum levels of 14.2 +/- 3.9 micrograms/ml in the patients with an apparent distribution volume of 0.345 +/- 0.074 L/kg. In 95% of the patients, the initial peak was higher than 8.5 micrograms/ml; levels higher than 20 micrograms/ml were observed in 7%, extremely low concentrations (below 5 micrograms/ml) in 2%. With individually adjusted doses between 160 and 560 mg, a mean peak of 11.5 +/- 2.7 micrograms/ml was measured subsequently. The levels amounted to 96 +/- 23% of the predicted values, deviations greater than 50% occurred in 5%. The target trough level was achieved in 99%, in less than 3% the dosing interval was extended up to 72 hours. A tobramycin clearance below 80 ml/min/1.73 m2 was associated with average 80% and 33% higher creatinine clearance values according to the Cockcroft-method and the direct method, respectively. CONCLUSION: Target peak and trough aminoglycoside levels are adjustable even in critically ill patients. Reduced tobramycin clearance can be associated with normal creatinine clearance. Assuming an exact methodology, a reduced "direct" creatinine clearance, however, indicates a reduced drug clearance.
Anti-Bacterial Agents↗
[Intensive care medicine and intensive care medicine research in Germany--difference between appearance and reality].
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Critical Care↗
Sensitivity and specificity of various markers of inflammation for the prediction of tumor necrosis factor-alpha and interleukin-6 in patients with sepsis.
OBJECTIVES: To determine correlations and predictive strength of surrogate markers (body temperature, leukocyte count, C-reactive protein [CRP], and procalcitonin [PCT]) with elevated levels of tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) in septic patients. DESIGN: Prospective consecutive case series. SETTING: Surgical intensive care unit (ICU) of a university hospital. PATIENTS: A total of 175 patients experiencing intensive care unit stays >48 hrs categorized for sepsis according to ACCP/ SCCM Consensus Conference criteria. MEASUREMENTS AND MAIN RESULTS: CRP and PCT were both significantly correlated with TNF-alpha and IL-6. Based on the area-under-the-curve of the receiver operating characteristics curves, predicting capability was highest for PCT (0.814 for TNF-alpha >40 pg/mL and 0.794 for IL-6 >500 pg/mL), moderate with CRP (0.732 and 0.716, respectively), and lowest for leukocyte count (0.493 and 0.483, respectively) and body temperature (0.587 and 0.589, respectively). Sensitivity, specificity, positive, and negative predictive values and test effectiveness all followed this same pattern of being highest for PCT followed by CRP, with leukocyte count and body temperature being lowest. CONCLUSION: PCT may be an early and better marker of elevated cytokines than the more classic criteria of inflammation.
Adolescent↗
Dopexamine increases splanchnic blood flow but decreases gastric mucosal pH in severe septic patients treated with dobutamine.
OBJECTIVE: To assess the effects of dopexamine on splanchnic blood flow and splanchnic oxygen uptake in septic patients. DESIGN: A prospective, controlled trial. SETTING: A ten-bed intensive care unit (ICU) in a university hospital. PATIENTS: Twelve patients with severe sepsis (according to the criteria of the 1992 American College of Chest Physicians/Society of Critical Care Medicine consensus conference) being stabilized by volume loading and treated to an elevated oxygen delivery by dobutamine infusion. INTERVENTIONS: Infusion of increasing dosages of dopexamine (0.5, 1.0, 2.0, and 4.0 microg/kg/min). MEASUREMENTS AND MAIN RESULTS: Systemic and splanchnic hemodynamic and oxygen transport parameters as well as gastric mucosal pH (pHi) were measured. A hepatic venous catheter technique with indocyanine green dye dilution was used to determine splanchnic blood flow. Dopexamine increased global and splanchnic oxygen delivery without affecting oxygen consumption (VO2). Splanchnic blood flow increased proportionally to cardiac output, indicating that there was no selective effect of dopexamine on the splanchnic flow. Dopexamine decreased pHi in a dose-dependent fashion in all 12 patients. CONCLUSIONS: In hemodynamically stable, hyperdynamic septic patients being treated with dobutamine, dopexamine has no selective effect on splanchnic blood flow. In fact, a decreased pHi suggests a harmful effect on gastric mucosal perfusion.
Adult↗
Acute left ventricular dysfunction and subarachnoid hemorrhage.
OBJECTIVE: Severe left ventricular (LV) dysfunction associated with acute subarachnoid hemorrhage (SAH) due to cerebral aneurysm rupture. SETTING: An adult 12-bed surgical intensive care unit of a university hospital. PATIENT: A female patient presenting with SAH (Hunt & Hess grade III) and severe left ventricular dysfunction. INTERVENTIONS: Central venous pressure, arterial blood pressure, extravascular lung water catheter, transesophageal echocardiography, blood gas analysis, electrocardiograms, and chest x-ray for clinical management. MEASUREMENTS AND MAIN RESULTS: On admission to the district hospital, an electrocardiogram (ECG) revealed a sinus rhythm with transient ST elevations. A transesophageal echocardiography showed a left ventricular ejection fraction (LV-EF) of approximately 10%. Severe LV dysfunction required inotropic and vasopressor support to maintain mean arterial pressure above 60 mmHg, while the first measurement of an extravascular lung water catheter revealed a cardiac index of 2.0 L/min/m2 and moderate hypovolemia. Despite stepwise volume loading that increased intrathoracic blood volume--an indicator of cardiac preload--from 719 mL/m2 to 927 mL/m2, cardiac index remained poor. Enoximone lead to a marked increase of cardiac index up to 3.9 L/min/m2 and LV-EF to about 30%, but had to be stopped due to thrombopenia. Surgical clipping of an intracranial aneurysm was postponed because of the impaired cardiac function and was performed on day 18 after admission. Interestingly, neurologic outcome was not as poor as might be expected from the literature. CONCLUSION: Severe left ventricular dysfunction may occur in acute SAH and may necessitate delay of aneurysm surgery.
Acute Disease↗
A piglet model for evaluation of cerebral blood flow and brain oxidative metabolism during gradual cerebral perfusion pressure decrease.
A piglet model was developed to study the effect of epidural volume expansion on cerebral perfusion pressure (CPP) by stepwise elevating intracranial pressure (ICP). Mean arterial blood pressure (ABP) was strictly maintained using an extracorporeal ABP controller. Two-week-old piglets (n = 10) were studied by surgically placing an epidural balloon over the right parietal region and gradually increasing the inflation to increase ICP to 25, 35 and 45 mm Hg, maintaining each pressure level for 30 min. Regional cerebral blood flow was measured using the colored microsphere technique, and cerebral oxygen delivery and cerebral metabolic rate of oxygen were calculated at baseline conditions and after reaching ICP levels of 25, 35 and 45 mm Hg. The results showed that this model of epidural volume expansion reproducibly reduces CPP to 70, 50 and 33% of baseline CPP values with elevation of ICP, and that the physiological variables remained stable throughout each increase in ICP. We conclude that the model simulates the effects of an acute intracranial focal mass expansion and is well suited for the evaluation of different therapeutical strategies for increased ICP in newborns and infants.
Animals↗