Diagnosis of sepsis. Novel and conventional parameters.
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Biomarkers↗
Biomedical subjects
K Reinhart
Publications and source records attributed to K Reinhart.
Catecholamines and splanchnic perfusion.
For supportive therapy in sepsis adequate volume loading is probably the first, and possibly the most important step in the treatment of patients with septic shock. An elevated global O2-supply (DO2) may be necessary and beneficial in most of these patients, but the increase in DO2 should be guided by measurement of parameters assessing global and regional oxygenation. Routine strategies for elevating DO2 by the use of very high dosages of catecholamines cannot be recommended. Vasopressors should be used to achieve adequate perfusion pressure. With noradrenaline, no negative effects on regional perfusion have been demonstrated when the patient is adequately volume-resuscitated and the DO2 is normal or even slightly elevated. In contrast, adrenaline should be avoided because it appears to redistribute blood flow away from the splanchnic region. There is controversy as to whether dopamine should still be used as a first-line drug in patients with septic shock, since some clinical and experimental data indicate unfavourable effects on mucosal perfusion of the gut. To date there are no convincing data to support the routine use of low-dose dopamine or dopexamine in patients with sepsis. Neither low-dose dopamine nor dopexamine have been proved to prevent renal failure in septic patients. Furthermore, there is evidence that low-dose dopamine may reduce mucosal perfusion in the gut in some patients. Dopexamine has been suggested for improvement of splanchnic perfusion, but since these effects remain somewhat controversial there are no current grounds for a general recommendation in favour of dopexamine in septic patients. These recommendations are currently limited by the lack of sufficient outcome studies and studies evaluating regional perfusion. Until the various catecholamine regimes are more fully examined, recommendations for catecholamine support in sepsis must be considered "conditional".
Animals↗
Procalcitonin as a marker of the systemic inflammatory response to infection.
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Biomarkers↗
Comparison of invasive and noninvasive measurements of indocyanine green plasma disappearance rate in critically ill patients with mechanical ventilation and stable hemodynamics.
OBJECTIVES: We studied the correlation between invasive (aortic fiberoptic) and noninvasive (transcutaneous sensor) measurements of indocyanine green (ICG) plasma disappearance rate (PDR) in critically ill patients. DESIGN AND SETTING: Prospective clinical study in a surgical intensive care unit of a university hospital. PATIENTS: 16 critically ill patients with adult respiratory distress syndrome (n = 8), sepsis/septic shock (n = 6), subarachnoid hemorrhage (n = 1), or severe head injury (n = 1). MEASUREMENTS AND RESULTS: We analyzed 16 pairs of simultaneous ICG PDR measurements. All patients were deeply sedated and mechanically ventilated. Each patient received a 4-F aortic catheter with an integrated fiberoptic and thermistor connected to a computer system for automatic calculation of invasive ICG PDR (PDRINV). An ICG sensor was also attached to the nose wing and connected to a DDG2001 analyzer for noninvasive measurement (PDRNINV). Linear regression analysis revealed PDRNINV = 0.98 PDRINV +0.11%/min (r = 0.94, p < 0.0001) with a mean bias of 0.2 +/- 2.0%/min. CONCLUSION: Noninvasive measurements of ICG PDR are very highly correlated with values derived from an invasive fiberoptic-based reference technique.
Adolescent↗
The effects of inhibiting leukocyte migration with fucoidin in a rat peritonitis model.
OBJECTIVES: To study the effects of fucoidin on leukocyte rolling and emigration and bacterial colonization in a peritonitis sepsis model in rats. DESIGN AND INTERVENTIONS: A controlled study in 64 male Wistar rats, anesthetized and rendered septic by cecal ligation and puncture (CLP). Immediately after CLP 32 animals received a continuous infusion of fucoidin and 32 a continuous infusion of Ringer's lactate. MEASUREMENTS AND MAIN RESULTS: Systemic leukocyte counts were determined every 2 h after CLP. Surviving animals were anesthetized 24 h after CLP, and intravital measurements of leukocyte rolling in venules in the cremaster muscle were performed. The animals were then killed and their organs harvested for histological and microbiological examinations. The 24-h survival was comparable in the two groups. Fucoidin-treated animals had higher leukocyte counts in the systemic circulation and lower counts in the lungs, liver, abdominal cavity, and brain than control animals. The number of bacterial colony forming units in the abdominal cavity, lungs, liver, brain and blood did not differ in the two groups. Fucoidin treatment changed the type of bacteria predominantly found in the examined organs from Escherichia coli to Pseudomonas aeruginosa. CONCLUSIONS: In an intra-abdominal model of sepsis we found that treatment with fucoidin induces leukocytosis inhibits leukocyte rolling and reduces leukocyte emigration in the abdominal cavity, lungs, and liver. Reduction in the number of emigrating leukocytes was not associated with an increase in bacterial counts found in the examined organs.
Animals↗
Assessment of cardiac preload and extravascular lung water by single transpulmonary thermodilution.
OBJECTIVE: Transpulmonary double-indicator dilution is a useful monitoring technique for measurement of intrathoracic blood volume (ITBV) and extravascular lung water (EVLW). In this study, we compared a simpler approach using single arterial thermodilution derived measurements of ITBV and EVLW with the double-indicator dilution technique. DESIGN: Prospective observational clinical study. SETTING: Surgical intensive care units of two university hospitals. PATIENTS AND METHODS: Global end-diastolic volume (GEDV) derived from single thermodilution was used for calculation of ITBV. Structural regression analysis of the first two thermo-dye dilution measurements in a derivation population of 57 critically ill patients (38 male, 19 female, 18-79 years, 56 +/- 15 years) revealed ITBV = (1.25 x GEDV)-28.4 (ml). This equation was then applied to all first measurements in a validation population of 209 critically ill patients (139 male, 70 female, 10-88 years, mean 53 +/- 19 years), and single-thermodilution ITBV (ITBV(ST)) and EVLW (EVLW(ST)) was calculated and compared to thermo-dye dilution derived values (ITBV(TD), EVLW(TD)). For inter-individual comparison, absolute values for ITBV and EVLW were normalised as indexed by body surface area (ITBVI) and body weight (EVLWI), respectively. MEASUREMENTS AND RESULTS: Linear regression analysis yielded a correlation of ITBVI(ST) = (1.05 x ITBVI(TD))-58.0 (ml/m2), r = 0.97, P < 0.0001. Bias between ITBVI(TD) and ITBVI(ST) was 7.6 (ml/m2) with a standard deviation of 57.4 (ml/m2). Single-thermodilution EVLWI (EVLWI(ST)) was calculated using ITBVI(ST) and revealed the correlation EVLWI(ST) = (0.83 x EVLWI(TD)) + 1.6 (ml/kg), r = 0.96, P < 0.0001. Bias between EVLWI(TD) and EVLWI(ST) was -0.2 (ml/kg) with a standard deviation of 1.4 (ml/kg). In detail, EVLWI(ST) systematically overestimated EVLWI(TD) at low-normal values for EVLWI and underestimated EVLWI at higher values (above 12 ml/kg). CONCLUSION: Determinations of ITBV and EVLW by single thermodilution agreed closely with the corresponding values from the double-indicator technique. Since transpulmonary single thermodilution is simple to apply, less invasive and cheaper, all these features make it a promising technique for the bedside. Nevertheless, further validation studies are needed in the future.
Adolescent↗
Atropine test and circulatory arrest in the fossa posterior assessed by transcranial Doppler.
OBJECTIVE: To evaluate whether a negative atropine test (i.e., increase in heart rate of less than 3% after intravenous administration of 3 mg atropine) correctly predicts circulatory arrest in the fossa posterior during craniocaudal herniation in patients with primary supratentorial lesions. MATERIAL AND METHODS: Prospective, observational clinical study. SETTING: Two surgical intensive care units in a university hospital. PATIENTS: In 45 consecutive patients with suspected brain death, an atropine test (AT) and a transcranial Doppler sonography were performed simultaneously and, if necessary, repeatedly. MEASUREMENTS AND RESULTS: Forty-four patients fulfilled the typical criteria of a supratentorial and infratentorial circulatory arrest as the atropine test became negative. In one patient, who had undergone a decompressive craniectomy for uncontrollable intracranial pressure 4 h prior to the AT testing, we found a negative AT in the presence of an antegrade supratentorial and infratentorial flow. CONCLUSION: A negative atropine test indicates a circulatory arrest in the fossa posterior in patients with primary supratentorial lesions and craniocaudal herniation. In patients with brain-stem lesions, however, a negative atropine test does not unequivocally indicate a circulatory arrest.
Adolescent↗
Late cardiac arrhythmias after blunt chest trauma.
OBJECTIVE: Case reports of two patients who developed fatal cardiac arrhythmias several days after blunt chest trauma. DESIGN: Case reports. SETTING: Surgical intensive care unit of a university hospital. PATIENTS: A 23-year-old man and a 9-year-old girl with blunt chest trauma and multiple further injuries following car crashes were transferred to our institution. Although ECG on admission was normal, both patients developed fatal cardiac arrhythmias after 6 and 4 days, respectively. In both patients, post-mortem analysis confirmed myocardial contusion without coronary artery lesions. Histological findings included severe interstitial oedema, haemorrhages and infiltration of lymphocytes and neutrophils, fresh myocardial necrosis and fatty degeneration. CONCLUSION: Blunt chest trauma with myocardial contusion may lead to fatal cardiac arrhythmias even after several days, particularly when other severe injuries are present. Thus, a normal ECG on admission and absence of cardiac arrhythmias during the first 24 h of intensive care treatment do not necessarily exclude the occurrence of life-threatening arrhythmias in the further course.
Accidents, Traffic↗
Is the placement of a pulmonary artery catheter still justified solely for the measurement of cardiac output?
OBJECTIVE: The authors compared four clinical techniques of measuring cardiac output (CO) in critically ill patients: pulmonary artery thermodilution (CO[PA]), transpulmonary aortic thermodilution (CO[AORTA]), Fick principle-derived (CO[FICK]), and continuous pulmonary artery (CCO) measurements. DESIGN: Prospective clinical study. SETTING: Surgical intensive care unit of a university hospital. PARTICIPANTS: Twelve adult patients suffering from sepsis or septic shock. INTERVENTIONS: All patients were deeply sedated and mechanically ventilated in a pressure-controlled mode. Each patient received a 7.5F five-lumen pulmonary artery catheter for the continuous measurement of cardiac output and a 4F 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). Whole-body oxygen consumption was measured by indirect calorimetry using a metabolic cart (Deltatrac, Datex-Engstroem, Helsinki, Finland) over a 5-minute period, at the end of which arterial and mixed venous blood gases were taken and measured by co-oximetry. During each measuring period, three bolus CO measurements were performed. A total number of 51 CO measurements was analyzed. RESULTS: Linear regression analysis revealed the highest correlation between CO(AORTA) and CO(PA) (r = 0.98), whereas agreement between these two techniques and CCO was lower (r = 0.92 and r = 0.93). All three techniques correlated comparably with CO(FICK) (r = 0.85, r = 0.83, and r = 0.83). CONCLUSION: The correlations among the four CO techniques were high and similar, with CO(PA) and CO(AORTA) techniques showing the highest agreement. Because CO with similar accuracy can be obtained from transpulmonary aortic thermodilution in a less-invasive manner, it appears that the placement of a pulmonary artery catheter solely for the measurement of CO is no longer justified, unless continuous CO measurements are needed.
Adult↗
Lipopolysaccharide induces distinct alterations in the microtubule cytoskeleton of monocytes.
Microtubules are obligate functional elements of almost all eukaryotic cells. They are involved in a broad range of essential cellular functions and structural changes of this system may trigger cell death. Recently, we have reported that lipopolysaccharides inhibit in vitro microtubule formation due to exclusion of microtubule-associated proteins. The distinct epitopes of lipopolysaccharides responsible for these effects and the in vivo relevance of these data are unknown. Therefore, this study was conducted to elucidate the effects of lipid A, the biologically active motif of lipopolysaccharides, on microtubule formation in vitro and to prove whether lipopolysaccharides affect the microtubule architecture of cultured human monocytes in vivo. Despite a dose- and pH-dependent inhibition of microtubule formation by lipopolysaccharides, inhibition of microtubule assembly could be mimicked by lipid A. Near-infrared two-photon microscopy revealed that human peripheral blood monocytes accumulate lipopolysaccharides. A vesicular distribution pattern of lipopolysaccharides within the monocytes was observed. Confocal laser scanning microscopy demonstrated alterations in the microtubule architecture of monocytes after incubation with lipopolysaccharides. Lipid A seems to be responsible for the observed crosstalk between lipopolysaccharides and microtubule proteins. Furthermore, our data indicate that lipopoly-saccharides may affect the microtubule architecture in human monocytes after intracellular accumulation directly. Therefore, we conclude, that the microtubule cytoskeleton is an essential intracellular target for sepsis-relevant bacterial components such as lipopolysaccharides.
Animals↗
Haemodynamic management of a patient with septic shock.
For supportive therapy in sepsis, an adequate volume loading is likely the first step, and possibly the most important step in the treatment of patients with septic shock. However, it is still a matter of debate what kind of fluids, endpoints for resuscitation and monitoring techniques should be used. Nevertheless, therapies which closely control volume loading and regional perfusion are becoming more utilized. An elevated global O2-supply (DO2) may be necessary and beneficial in most of these patients but the increase of DO2 should be guided by the measurement of parameters assessing global and regional oxygenation. Routine strategies for elevating DO2 by the use of very high dosages of catecholamines cannot be recommended. Vasopressors should be used to achieve an adequate perfusion pressure. With norepinephrine, no negative effects on regional perfusion have been demonstrated when the patient is adequately volume resuscitated and the DO2 is normal or even slightly elevated. In contrast, epinephrine should be avoided because it seems to redistribute blood flow away from the splanchnic region. There is controversy whether dopamine should still be used as a first-line drug in patients with septic shock, because there are some clinical and experimental data that indicate unfavourable effects on mucosal perfusion of the gut. To date, there are no convincing data to support the routine use of low-dose dopamine or dopexamine in patients with sepsis. Neither low-dose dopamine nor dopexamine have been proven to prevent renal failure in septic patients. Furthermore, there is evidence that low-dose dopamine may reduce mucosal perfusion in the gut in some patients. Dopexamine has been suggested to improve splanchnic perfusion but because these effects remain somewhat controversial, there is as yet no reason for a general recommendation for dopexamine in septic patients. These recommendations are currently limited by the lack of sufficient outcome studies and studies which evaluate regional perfusion. Until the various catecholamine regimes are more fully examined, recommendations for catecholamine support in sepsis must be considered 'conditional'.
Adrenergic alpha-Agonists↗
Elimination of procalcitonin and plasma concentrations during continuous veno-venous haemodiafiltration in septic patients.
The elimination of procalcitonin and the course of plasma concentrations during continuous veno-venous haemodiafiltration were measured in patients with sepsis or multiple organ dysfunction syndrome, because these patients are a main target group for the measurement of procalcitonin and often require renal replacement therapy. Procalcitonin was measured in the prefilter plasma and the filtrate at 5 min, 15 min and 1, 2, 4, 6, 12, 24 h after set-up of continuous veno-venous haemodiafiltration. In a prospective study, 19 patients with plasma levels of procalcitonin > 3 ng mL-1 and acute oliguric renal failure treated with continuous veno-venous haemodiafiltration using a polysulphone membrane, were evaluated for the study of clearance. Twenty-one control patients (procalcitonin < 2 ng mL-1) were studied to determine whether filtration itself induced a procalcitonin response. No interventions were required. In patients with low procalcitonin concentrations (procalcitonin < 2 ng mL-1) continuous veno-venous haemodiafiltration did not cause a rise in procalcitonin. In patients with increased procalcitonin plasma concentrations (> 3 ng mL-1), the protein was removed through the polysulphone membrane, with a final clearance of 4 mL min-1 after the initial adsorption period (clearance 0.4-0.9 mL min-1 during the first hour of continuous veno-venous haemodiafiltration). Thus, on the average, approximately 10% of plasma concentrations were measurable in the filtrate ultimately. However, procalcitonin plasma levels were not significantly altered during continuous veno-venous haemodiafiltration (86% of the initial concentration after 24 h). Although procalcitonin is removed from the plasma during continuous veno-venous haemodiafiltration in measurable amounts plasma procalcitonin concentrations did not change significantly during haemodiafiltration. Procalcitonin thus can also be used as a diagnostic parameter in patients undergoing continuous veno-venous haemodiafiltration.
Acute Kidney Injury↗
[Left ventricular aneurysm after myocardial contusion caused by blunt chest trauma].
A 30-year old male car-driver was polytraumatized after a frontal collision with another motor vehicle (left-sided rib fractures, right-sided pneumothorax, multiple lung contusions, anterior and posterior pelvic ring fracture, femoral shaft fracture, traumatic subarachnoid hemorrhage. After intubation and hemodynamic stabilization on the scene of accident, he was transported to our institution. Transesophageal echocardiography revealed a left-ventricular anteroseptal akinesia and patchy intramyocardial hyperdensities as indicator of myocardial contusion which was confirmed later by autopsy. In the further course, the patient developed an anteroseptal aneurysm with severe left ventricular dysfunction nad episodes of arrhythmias. Finally, septic shock complicated the case and the patient died 30 days of intensive care from therapy-refractory multiple organ system failure.
Accidents, Traffic↗
Transoesophageal echocardiographic assessment of haemodynamic changes during laparoscopic herniorrhaphy in small children.
Laparoscopic techniques for surgery are gradually becoming established in paediatric surgery. Technical aspects, such as the maximum safe gas insufflation pressure, are still open to discussion. We used transoesophageal echocardiography to study the haemodynamic changes in eight small children undergoing laparoscopic herniorrhaphy, with two different levels of intra-abdominal pressure (IAP), 6 and 12 mm Hg. End-tidal carbon dioxide tension was maintained constant at 4.3-4.7 kPa. After baseline measurements, an IAP of 12 mm Hg was applied for 10 min. Next, IAP was decreased to 6 mm Hg, followed by a second period of 12 mm Hg. Haemodynamic measurements were obtained at each stage. A further measurement was obtained 10 min after abdominal deflation at the end of surgery while anaesthesia was unchanged. Cardiac index (CI) decreased significantly only after the first 12 mm Hg level of IAP. The subsequent decrease in IAP to 6 mm Hg caused return of CI to baseline levels. The second increase in IAP did not cause any reduction in CI. The initial reduction in CI, although statistically significant, did not appear to be clinically important. We conclude that an IAP of up to 12 mm Hg appeared to be safe in healthy small children undergoing laparoscopic herniorrhaphy.
Cardiac Output↗
Do fluid administration and reduction in norepinephrine dose improve global and splanchnic haemodynamics?
We studied global and splanchnic haemodynamics in patients with septic shock, while reducing norepinephrine doses by progressive fluid loading administration. Ten patients (six female, four male, aged 39-86 yr, mean 61 yr) were assessed using a transpulmonary thermo-dye dilution technique to measure cardiac output, intrathoracic blood volume and total blood volume. Splanchnic blood flow was measured by the steady state indocyanine green technique using a hepatic venous catheter. Gastric mucosal blood flow was estimated by regional carbon dioxide tension (PRCO2). Hydroxyethylstarch was infused in two stages while maintaining mean arterial pressure, allowing a reduction in norepinephrine dose from 0.54 to 0.33 to 0.21 microgram kg-1 min-1. Mean (SD) heart rate significantly decreased, from 104 (13) to 94 (15) beats min-1. Total blood volume index (mean (SD)) increased from 2650 (638) to 3655 (885) ml m-2, intrathoracic blood volume index from 888 (204) to 1050 (248) ml m-2 and cardiac index from 3.6 (1.0) to 4.0 (0.9) litres min-1 m-2. Splanchnic blood flow did not change significantly--either absolute (from 0.81 to 0.98 litres min-1 m-2) or fractional (from 22.3% to 23.9%). Gastric mucosal (PRCO2) increased from 7.5 (2.5) to 9.0 (2.8) kPa. The PCO2 gap, i.e. the difference between regional and end-tidal PCO2, increased from 3.1 (2.5) to 4.0 (2.9) kPa. Marked individual variation in responses suggests that norepinephrine dose reduction by fluid loading in patients with stabilized septic shock does not necessarily increase global or splanchnic blood flow.
Adult↗
Effect of mild hypothermia on cerebral oxygen uptake during gradual cerebral perfusion pressure decrease in piglets.
OBJECTIVE: To study the effect of mild hypothermia on cerebral oxygen metabolism and brain function in piglets during reduced cerebral blood flow because of gradual reduction of the effective cerebral perfusion pressure (CPP). DESIGN: Comparison of two randomized treatment groups: normothermic group (NT; n = 7) and hypothermic group (HT; n = 7). SETTING: Work was conducted in the research laboratory of the Institute for Pathophysiology, Friedrich Schiller University, Jena, Germany. SUBJECTS: Fourteen piglets (14 days old) of mixed German domestic breed. INTERVENTION: Animals were anesthetized and mechanically ventilated. An epidural balloon was gradually inflated to increase intracranial pressure to 25 mm Hg, 35 mm Hg, and 45 mm Hg every 30 mins at adjusted mean arterial blood pressures. After determination of baseline CPP (NT, 79+/-14 mm Hg; HT, 84+/-9 mm Hg), CPP was reduced to approximately 70%, 50%, and 30% of baseline (NT, 38.1+/-0.5 degrees C; HT, 31.7+/-0.5 degrees C). MEASUREMENTS AND MAIN RESULTS: Every 25 mins after the gradual CPP reductions. Mild hypothermia induced a reduction of the cerebral metabolic rate of oxygen (CMRO2) to 50%+/-15% of baseline values (baseline values, 352+/-99 micromol x 100 g(-1) x min(-1)) (p < .05). Moreover, the electrocorticogram was altered to a pattern of reduced delta activity (p < .05) but unchanged higher frequency activity. The cerebral oxygen balance in HT animals remained improved until CPP reduction to 50%, indicated by a reduced cerebral arteriovenous difference of oxygen but elevated brain tissue Po2 (p < .05). Further CPP reduction gave rise to a strong CMRO2 reduction (NT, 19+/-21%; HT, 15+/-15%; p < .05). However, the high-frequency band of electrocorticogram was less reduced in hypothermic animals (p < .05). CONCLUSIONS: Mild whole body hypothermia improves cerebral oxygen balance by reduction of brain energy demand in juvenile piglets. The improvement of brain oxygen availability continues during a mild to moderate CPP decrease. A loss of the difference in CMRO2 between the hypothermic and normothermic piglets together with the fact that brain electrical activity was less suppressed under hypothermia during severe cerebral blood flow reduction indicates that hypothermic protection may involve some other mechanisms than reduction of brain oxidative metabolism.
Analysis of Variance↗
Dopamine in septic patients.
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Cardiotonic Agents↗
Clinical experiences with a new semi-quantitative solid phase immunoassay for rapid measurement of procalcitonin.
A self-developing solid-phase immunoassay (B.R.A.H.M.S. PCT-Q, B.R.A.H.M.S.-Diagnostica GmbH, Hennigsdorf, Germany) has recently become available for the semi-quantitative and rapid measurement of procalcitonin (PCT). In this study we examined the validity of this assay at daily clinical routine conditions at five different hospitals in a prospective study. After development of the assay (200 microl plasma, 30 minutes incubation), PCT levels were categorized into four groups (< 0.5 microg/l; > or = 0.5-< 2 microg/l; > or = 2-< 10 microg/l; > or = 10 microg/l) according to the provided reference scale. Samples from patients with suspected elevation of PCT of different etiology (n=237) were read by various analyzers and compared with the results of the Lumitest PCT (B.R.A.H.M.S.-Diagnostica GmbH, Hennigsdorf, Germany). A total of 74.7% of measurements were categorized according to the results of the LumitestPCT, 24.5% were read within the next lower or higher category. Using a +/- 10% range at the reference concentrations (20% at 0.5 microg/l), 82.7% of samples were correctly categorized and 16.4% within the next categories. Using a cut-off value of 2.0 microg/l, 92.0% (94.1% for +/- 10%) of the results were correctly categorized. The semi-quantitative solid phase immunoassay allows a rapid, simple and semi-quantitative measurement of plasma PCT. The validity of the test results and its ease of use are sufficient to support acute diagnostic decisions. However, for the follow-up of PCT concentrations and routine daily measurements, the quantitative luminometric assay should be preferred, when available.
Calcitonin↗