Nutritional screening for risk prediction in patients scheduled for abdominal operations.

BACKGROUND: Increased risks related to surgery might reflect the nutritional status of some patients. Such a group might benefit from perioperative nutritional support. The purpose of this study was to identify the relative importance of nutritional risk screening along with established medical, anaesthetic and surgical predictors of postoperative morbidity and mortality. METHODS: This prospective observational study enrolled consecutive eligible patients scheduled for elective abdominal operations. Data were collected on nutritional variables (body mass index, weight loss, food intake), age, sex, type and extent of operation, underlying disease, American Society of Anesthesiologists grade and co-morbidities. A modified composite nutritional screening tool (Nutritional Risk Screening, NRS 2002) currently recommended by European guidelines was used. Relative complication rates were calculated with multiple logistic regression and cumulative proportional odds models. RESULTS: Some 653 patients were enrolled of whom 132 (20.2 per cent) sustained one or more postoperative complications. The frequency of this event increased significantly with a lower food intake before hospital admission. No other individual or composite nutritional variable provided comparable or better risk prediction (including NRS 2002). Other factors significantly associated with severe postoperative complications were ASA grade, male sex, underlying disease, extent of surgical procedure and volume of transfused red cell concentrates. CONCLUSION: In abdominal surgery, preoperative investigation of feeding habits may be sufficient to identify patients at increased risk of complications. Nutritional risk alone, however, is not sufficient to predict individual risk of complications reliably.

[Secondary peritonitis]. / Sekundäre Peritonitis.

BACKGROUND: There is some controversy regarding concepts currently propagated for an optimal surgical and antibiotic therapy in patients with secondary peritonitis and organ failure. It is not known whether the recent general progress in critical care ("Surviving Sepsis Campaign") has also improved outcome of this particular patient group. METHODS: MEDLINE, EMBASE and Cochrane databases were non-systematically searched from 1985 through January 2010 using the words "source control", "peritonitis", "operation", "critical care" and "antibiotics". We also present experiences in corresponding high risk patients from our institution. RESULTS: The inability to obtain source control and an inadequate initial antibiotic therapy were -associated with a clearly higher mortality. De-pending on the initial intraoperative finding, planned and on demand relaparotomy do not conflict, but complement one another. The importance of the number of surgical revisions remains to be determined. Treatment after 2002 was associated with an improved prognosis. In contrast to source control, the mechanisms of increasing mortality with an inadequate initial antibiotic therapy remain controversial. CONCLUSION: Source control is the most important determinant for acute survival and has to be placed on top of the therapeutic priority list. The number of revisions needed to obtain source control, however, does not vary with survival and cannot guide decisions on therapy withdrawal or continuation. The recent prognostic improvement indicates the efficiency of new adjuvant therapeutic measures in unselected surgical high-risk patients.

Protocol for a prospective cohort study on the use of clinical nutrition and assessment of long-term clinical and functional outcomes in critically ill adult patients.

BACKGROUND AND AIMS: Limited data are available on the impact of clinical nutrition over the course of critical illness and post-discharge outcomes. The present study aims to characterize the use of nutrition support in patients admitted to European intensive care units (ICUs), and its impact on clinical outcomes. Here we present the procedures of data collection and evaluation. METHODS: Around 100 medical, surgical, or trauma ICUs in 11 countries (Austria, Belgium, Czech Republic, Germany, France, Hungary, Italy, Poland, Spain, Sweden, United Kingdom) participate in the study. In defined months between November 2019 and April 2020, approximately 1250 patients are enrolled if staying in ICU for at least five consecutive days. Data from ICU day 1-4 are collected retrospectively, followed by a prospective observation period from day 5-90 after ICU admission. Data collection includes patient characteristics, nutrition parameters, complications, ICU and hospital length of stay, discharge status, and functional outcomes. For data analysis, the target is 1000 patients with complete data. Statistical analyses will be descriptive, with multivariate analyses adjusted for potential confounders to explore associations between nutritional balance and change in functional status, time-to-weaning from invasive mechanical ventilation, time to first clinical complication, and overall 15, 30 and 90-day survival. ETHICS AND DISSEMINATION: This non-interventional study was reviewed and approved by the ethics committee of the Medical University Vienna, Vienna, Austria (approval number 1678/2019), and the respective ethical committees from participating sites at country and/or local level, as required. Results will be shared with investigators on a country level, and a publication and results presentation at the 2021 ESPEN Congress is planned. TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT04143503.

Fluid resuscitation after severe trauma injury : U-shaped associations between tetrastarch dose and survival time or frequency of acute kidney failure.

BACKGROUND: Using tetrastarch for fluid resuscitation after a severe trauma injury may increase risks of death and acute kidney injury. The importance of tetrastarch dose, however, is unknown. METHODS: A retrospective observational study was performed in two trauma centres using data on type and amount of fluids (balanced crystalloids or tetrastarch) used for pre- and acute in-hospital shock management. We evaluate independent associations between the relative and absolute volumes of tetrastarch and 90-day survival time or the frequency of severe acute kidney failure (AKF). RESULTS: We studied 271 patients who had sustained a severe blunt trauma injury (average predicted mortality according to the Revised Injury Severity Classification Score (RISC) 15.1 ± 1.4% [mean, standard deviation]), and who had required more than 2 days of intensive care therapy. In all, 75.3% of patients had received tetrastarch with a crystalloid/colloid ratio of 2.93 ± 2.60. The 90-day mortality was 11.1%, and 7.8% of the patients developed severe AKF. After adjusting for confounders, we found a U-shaped, nonlinear association between absolute or relative volumes of tetrastarch and survival time (p = 0.003 and 0.025, respectively). Optimal relative volumes of tetrastarch approximately ranged from 20 to 30% of total fluids. Giving less than about 1000 ml, or more than about 2000 ml tetrastarch was significantly associated with an increased risk of developing severe AKF (p = 0.023). CONCLUSIONS: There was a complex U­shaped association between the tetrastarch dose and morbidity/mortality of patients after a severe trauma injury. The optimal crystalloid/tetrastarch ratio for acute shock management appears to range from about 2.5 to 4.0.

Interlaboratory trial on the analysis of alkylphenols, alkylphenol ethoxylates, and bisphenol A in water samples according to ISO/CD 18857-2.

ISO/CD 18857-2 (International Organization for Standardization, Geneva) describes a new international standard method for the determination of octylphenol, nonylphenol, their mono- and diethyoxylates, and bisphenol A in nonfiltered samples of drinking, ground, surface, and wastewater. The method is based on the extraction of the analytes from an acidified water sample by solid phase extraction, solvent elution, derivatization, and determination by gas chromatography with mass spectrometric detection. For validation of this method, 14 laboratories from 4 different countries in Europe and Canada participated in an interlaboratory trial to determine the performance characteristics of the method, which are intended for publication in the corresponding standard. The interlaboratory trial was evaluated according to ISO 5725-2 and included two duplicate nonfiltered water samples: surface water containing the target compounds in an analyte concentration range from 0.05 to 0.4 microg/L and wastewater containing the target compounds in a concentration ranged from 0.1 to 5 microg/L. The repeatability variation coefficients (within-laboratory precision) varied for all samples and compounds between 1.9 and 7.8%, showing a sufficiently high repeatability of the method. The reproducibility variation coefficients (between-laboratory precision) were found to vary within a satisfactory range of 10.0-29.5% for surface water and 10.8-22.5% for wastewater. The recoveries as a measure of accuracy varied from 98.0 to 144.1% for surface water and from 95.4 to 108.6% for wastewater. The determined concentrations of the samples compared well to the "true" values, thus showing very satisfactory accuracy of the method. In the chromatogram of the surface water sample, a high unresolved background made up of coextractable matrix compounds was apparent. It is conceivable that compounds from this background may be responsible for enhanced recoveries of 144.1% for 4-nonylphenol (mixture of isomers) and of 123.4% for 4-nonylphenol monoethoxylate (mixture of isomers) in the surface water samples. The isotope-marked standard compounds developed in this context proved to be reliable internal standards that allow a precise and accurate quantitation of all compounds specified in ISO/CD 18857-2. The results of the interlaboratory trial confirmed that the analytical method is robust and reliable and can be used as a standard method to analyze the target compounds in water samples.

[Diabetes mellitus - perioperative management]. / Perioperatives Management bei Diabetes mellitus.

The prevalence of diabetes in hospitalized adults is conservatively estimated at 12-25% and rising. Poor glucose control and presence of diabetes complications (e.g. diabetic nephropathy, diabetic neuropathy, atherosclerosis) are commonly regarded as risk factors for perioperative morbidity and mortality. Thus it is crucial to determine diabetes comorbidities preoperatively in order to avoid perioperative renal and cardiovascular complications. Perioperative glycemic control is challenging due to preoperative changes in diabetes treatment and the effects of surgery-associated stress hyperglycemia. For patients in general surgical units, evidence for specific glycemic goals is based on epidemiologic and physiologic data rather than clinical trials. According to guidelines of the German Society of Nutrition, the approximation of normoglycemia is reasonable as long as hypoglycemia is avoided (suggested range for plasma glucose 80-145 mg/dL).

[Cost analysis as a tool for assessing the efficacy of intensive care units]. / Kosten als Instrument zur Effizienzbeurteilung intensivmedizinischer Funktionseinheiten.

BACKGROUND: The German "Hospital Structure Act" intends to align the state hospital planning on quality criteria. Within this process cost-utility analyses (CUAs) shall be used to assess the efficacy of medical care. To be objective, CUAs of intensive care units (ICUs) require standardization (adjustment) of costs. The present study analyzed the extent to which treatment costs are related to patient-specific baseline variables (such as type and severity of the primary disease). METHODS: From 2000-2004, a bottom-up procedure was used to quantify total costs on 14 ICUs in nine German university hospitals. Results were combined with demographic data, and data indicating type (ICD-10 codes) and severity (ICU scoring systems) of the primary disease at ICU admission. Various statistical models were tested to identify that which best described the associations between baseline variables and costs. RESULTS: In all, 3803 critically ill patients could be examined. The median of treatment costs per patient was 3199 € (IQR 1768-6659 €). No model allowed an acceptably precise adjustment of costs; the estimated mean absolute prognostic error was at least 3860 € (mean relative prognostic error 66%), when we tested an Extreme Gradient Boosting Model. CONCLUSION: Instruments which are currently available (cost adjustment based on patient-specific baseline variables) do not allow a standardization of costs, and an objective CUA of ICUs. Factors unknown at baseline may cause a large portion of treatment costs.

Activity in fetal bovine serum that stimulates erythroid colony formation in fetal mouse livers is insulinlike growth factor I.

In the present study, the erythropoietic activity of fetal serum was characterized. Using fetal bovine serum (FBS) as a source of the erythropoietic activity and serum-free cultures of fetal mouse livers (FMLC assay) as a detection system, we found that FBS stimulated colony formation from late erythroid progenitor cells (CFU-E) in a dose-dependent fashion. The slope of the dose-response curve, however, was significantly different from that for erythropoietin (Ep), the best-characterized erythropoietic activity so far. The erythropoietic activity of FBS was found in the 120-160- and 40-70-kD range at neutral pH. In the presence of 1 M acetic acid, however, the erythropoietic activity had an apparent molecular mass between 3 and 13 kD. From ion exchange experiments with DEAE-cellulose, the isoionic point of the activity was estimated to about pH 5. Furthermore, the erythropoietic activity of FBS was found to be co-eluted on Sephadex G-150 with the binding proteins of insulinlike growth factors (IGF). The IGF I concentration determined by radioimmunoassay was 70 ng IGF I/ml. The Ep activity of FBS was less than 5 mU/ml when determined with the posthypoxic polycythemic mouse assay for Ep. These results suggest that the erythropoietic activity of FBS is related to IGF and not to Ep. The erythropoietic activity of FBS was abolished by an antiserum against IGF I. Furthermore, IGF I was a factor of approximately 40 more potent than IGF II in stimulating erythroid colony formation. All of these findings suggest that the erythropoietic activity of FBS is IGF I.

[Quality of dying processes after commencement of the German Living Will Act : Experiences of a surgical intensive care unit]. / Versterben vor und nach dem "Patientenverfügungsgesetz" : Erfahrungen einer chirurgischen Intensivstation.

BACKGROUND: There is so far no information on how the third act on amendment of the German guardianship law from 29 July 2009 has affected dying processes of critically ill patients. METHODS: This retrospective study analyzed the patterns of dying processes in postoperative critically ill patients treated from 2009 to 2012 (period II after the commencement of the German Living Will Act) and 10 years before (period I, 1999-2002). Independent associations were calculated by logistic regression. RESULTS: In the observation period II (n = 137 dying patients) time until death significantly decreased to 19.3 days (95% CI 14.8-23.8, p = 0.008) vs. 29.2 days (95% CI 23.7-34.6) in period I (n = 163). In period II respect of the patient's will preceded death in 42.3% of the dying patients (period I: 8.6%, p < 0.001). Simultaneously, the frequency of patients with a severe preoperative comorbidity (failure of more than one organ) increased (26.8% of dying patients vs. 5.5% in period I, p = 0.001). The treatment during period II was, in addition to high age and a severe comorbidity, a significant independent predictor for the possibility that respect of the patient's will preceded death (odds ratio 7.42; 95% CI 3.77-14.60). CONCLUSION: Independent of various covariables, treatment after the commencement of the German Living Will Act was associated with a broader and earlier respect of the patient's will, thereby shortening the time until death.

ESPEN Guidelines on Enteral Nutrition: Intensive care.

Enteral nutrition (EN) via tube feeding is, today, the preferred way of feeding the critically ill patient and an important means of counteracting for the catabolic state induced by severe diseases. These guidelines are intended to give evidence-based recommendations for the use of EN in patients who have a complicated course during their ICU stay, focusing particularly on those who develop a severe inflammatory response, i.e. patients who have failure of at least one organ during their ICU stay. These guidelines were developed by an interdisciplinary expert group in accordance with officially accepted standards and are based on all relevant publications since 1985. They were discussed and accepted in a consensus conference. EN should be given to all ICU patients who are not expected to be taking a full oral diet within three days. It should have begun during the first 24h using a standard high-protein formula. During the acute and initial phases of critical illness an exogenous energy supply in excess of 20-25 kcal/kg BW/day should be avoided, whereas, during recovery, the aim should be to provide values of 25-30 total kcal/kg BW/day. Supplementary parenteral nutrition remains a reserve tool and should be given only to those patients who do not reach their target nutrient intake on EN alone. There is no general indication for immune-modulating formulae in patients with severe illness or sepsis and an APACHE II Score >15. Glutamine should be supplemented in patients suffering from burns or trauma.

[Nutritional therapy. Indication and approaches]. / Enterale Ernährung. Indikation und Zugangswege.

Appropriate nutritional therapy of surgical patients intends to supply calories for the maintenance of essential body functions. Beyond this goal, nutritional support may also significantly reduce nosocomial morbidity if applied properly and to the right patients. In surgical patients, nutritional therapy should start preoperatively by identifying and treating malnutrition and be continued postoperatively as a patient-tailored supportive measure. Oral/enteral nutrition is feasible in the majority of patients. Rare exceptions are patients with intestinal leakage, overt ileus, and circulatory shock. If the upper gastrointestinal tract is not functioning (as in swallowing disorders or after construction of surgical anastomoses), tube systems may be used. They can be placed endoscopically or at the time of surgery (needle catheter jejunostomy) to allow continuous enteral nutrition. If oral/enteral nutrition cannot completely meet caloric requirements of the patient, additional parenteral supply is indispensable to reach the intended caloric goal.

[Trends in surgical intensive care. Experience in one centre over 12 years]. / Trends in der chirurgischen Intensivmedizin. Zwölf Jahre Erfahrung an einer einzelnen Institution.

BACKGROUND: For critically ill medical patients until the year 2000, increases in patient age and severity of disease but also acute prognosis have been described. Since then, further improvement appears possible. Several controlled studies have recently demonstrated that acute mortality may be further lowered by new adjuvant therapies such as aggressive glycemic control. However, it is still unknown whether demographic changes and progress in intensive care can be reproduced in surgical critically ill patients outside of a controlled trial setting. METHODS: We performed a retrospective, observational cohort study using data prospectively collected from the surgical intensive care unit (ICU) of the LMU Department of Surgery in Munich, Germany, Grosshadern Campus, from March 1 1993 through February 28 2005. Since 1999 we have successively introduced a variety of new therapies to daily routine. A cohort of 5,495 patients was analysed. RESULTS: We identified reduced ICU mortality during the observation period, although age rose simultaneously and disease severity remained constant. Results from multivariate analysis suggest that improvements in prognosis essentially result from the implementation of new therapies after 2001. After adjusting for more than 20 covariables, treatment received after 2001 was identified as an independent factor linked with reduced risk of death. CONCLUSIONS: General demographic trends and progress in intensive care can be demonstrated also in unselected surgical cohorts. Furthermore, the results here confirm the efficacy of new therapeutic modifications in routine therapy.

Blood concentrations of polycyclic musks in healthy young adults.

Knowledge on the concentration of polycyclic musk fragrance compounds in human blood is sparse. This study examined the concentrations of six polycyclic musks in blood samples from healthy volunteers. Blood was taken from hundred healthy students of the Medical University of Vienna. The lipophilic fraction was extracted and after purification analyzed by GC-MS. Study participants also completed a questionnaire on the use of cosmetics, about nutrition and other life-style aspects. Two compounds -- galaxolide and tonalide -- were identified in higher percentages of the blood plasma samples. Maximum plasma levels over 100 ng/l were also only found for galaxolide (4100 ng/l) and tonalide (800 ng/l). Women showed significantly higher levels than men. In a statistical multivariate approach only use of body lotion and age were predictive of positive galaxolide concentrations. For tonalide no significant predictor could be found. The findings mirror the replacement of nitro musk fragrances by polycyclic musks, mainly galaxolide. The high concentrations of galaxolide in human blood raise concern since few toxicological data are available.

Effect of antithrombin III supplementation on inflammatory response in patients with severe sepsis.

Antithrombin III (AT III) is an important inhibitor of thrombin activity, as well as of many other proteases of the coagulation system. AT III administration showed beneficial effects on septic multiple organ dysfunction in clinical and experimental studies. It was the aim of this study to determine whether continuous long-term AT III supplementation alters the systemic inflammatory response in patients with severe sepsis. In a prospective study, 29 surgical patients with severe sepsis were randomly assigned to receive either conventional intensive care treatment (n = 15, control group) or additional AT III supplementation to achieve a plasma AT III activity >120% during a 14 day study period (n = 14, AT III group). Plasma concentrations of interleukin (IL)-6 and IL-8 and of the circulating soluble adhesion molecules sICAM-1 and sE-selectin, as well as of PMN elastase, were determined daily. Additionally, total leukocyte count and C-reactive protein (CRP) were measured daily, and body temperature was registered. Compared to control patients, a down-regulation of plasma IL-6 was observed in the AT III group (p < or = .01). AT III supplementation prevented the continuous increase in sICAM-1 plasma concentration observed in control patients and led to a significant fall in soluble sE-selectin and CRP concentration (p < or = .01). This fall corresponded to a down-regulation of body temperature over time (p < or = .01). There was no AT III effect on IL-8, PMN-elastase concentration, or total leukocyte count. Our results show that long-term AT III supplementation attenuates the systemic inflammatory response in patients with severe sepsis. The down-regulation of IL-6 may also explain the fall in endothelium-derived adhesion molecules and may represent the molecular basis by which AT III exerts its beneficial effects on organ function.

Hemofiltrate from patients with severe sepsis and depressed left ventricular contractility contains cardiotoxic compounds.

Myocardial dysfunction due to sepsis is common in patients with multiple organ dysfunction syndrome and is believed to be produced by inflammatory mediators. Some of these mediators may be eliminated by continuous hemofiltration, which is a standard procedure in an ICU for renal replacement therapy. This study was designed to directly compare the effects of ultrafiltrates from patients with sepsis (UFs) with ultrafiltrates from healthy volunteers (UFh) in well-characterized cardiomyocyte culture systems. Isovolemic hemofiltration (filtration rate: 2 L/h, polyamide membrane) was performed during 12 hours in 5 patients with severe sepsis (Elebute Score >20) and simultaneously reduced left ventricular contractility (left ventricular stroke work index [LVSWI] <30 g m/m2) and in 5 healthy volunteers. Inflammatory mediator concentrations (interleukin [IL]-1beta, IL-6, IL-8, tumor necrosis factor [TNF] alpha, C3a, and C5a) were measured in plasma and ultrafiltrate samples taken shortly after the beginning of the hemofiltration procedure. Cell culture experiments were done comparing UFs with UFh by using spontaneously beating or electrically driven neonatal rat cardiomyocyte cultures. UFs contained significantly higher amounts of IL-1, IL-8, and C3a when compared to UFh. Simultaneously, UFs induced a decrease in the contraction frequency of electrically-stimulated cardiomyocytes, whereas UFh had no effect. The cardiotoxic effect could be reversed by the addition of a high concentration (2.4 mM) of Ca++. Hemofiltration did not alter parameters of cardiac performance during 12 hours in patients with sepsis. UFs induced significant cardiotoxic effects in rat cardiomyocytes, whereas UFh showed no cardiotoxicity. Contact of blood with the hemofiltration membrane did not induce activation of cardiotoxic mediators. Significantly higher filtration rates may be required to improve left ventricular contractility in patients with sepsis by hemofiltration.

Antithrombin III supplementation in severe sepsis: beneficial effects on organ dysfunction.

Activation of thrombin and of the coagulation system plays an important role in the pathophysiology of sepsis-associated organ dysfunction. Antithrombin III (AT III) is a natural inhibitor of thrombin, a central procoagulatory factor with pleiotropic activities. Experimental supplementation of AT III improved coagulation parameters and ameliorated organ dysfunction. To determine whether long-term AT III supplementation has beneficial effects on organ function, we conducted a randomized, prospective study in surgical patients with severe sepsis. The study evaluated the long-term effect of AT III supplementation (duration of treatment: 14 days). After randomization (AT III vs. control group), AT III was infused continuously over 14 days to obtain plasma AT III activities > 120%. Forty consecutive patients were recruited (20 AT III/20 control group). Eleven patients had a rapid fatal course and did not met the criterion of a 14 day treatment period. From these 11 patients, 8 patients (5 AT III/3 control group) died within 72 h due to septic shock. The remaining 14 AT III patients and 15 controls survived 14 days and showed no differences in baseline parameters of organ function. AT III caused a disappearance of disseminated intravascular coagulation (DIC) in all patients with DIC, whereas in control patients, the frequency of DIC remained constant (p < .05). In AT III patients a progressive increase in oxygenation index (PaO2/FiO2 ratio) and a continuous decrease in pulmonary hypertension index (mean pulmonary artery pressure/mean arterial pressure (PAP/MAP) ratio) indicated an improvement of lung function (p < .05 vs. control). AT III prevented the continuous rise in total serum bilirubin concentration observed in control patients and diminished the frequency of artificial renal support therapy (p < .05). Long-term supplementation with AT III may improve lung function and prevent the development of septic liver and kidney failure in patients with severe sepsis.

Combined use of magnetic resonance imaging (MRI) and spectroscopy (MRS) by whole body magnets in studying skeletal muscle morphology and metabolism.

As a pilot study, 31-P-spectra of the quadriceps femoris muscle (1.5T) and proton images of the right thigh (.5T) were performed in two cyclists (T) and two untrained (UT) subjects. During ischemia, while MRI did not show any change, phosphocreatine (PCr) concentration decreased and inorganic phosphate (Pi) increased. Recovery occurred within 3 minutes. Ergometric bicycle tests were performed outside the magnet. Submaximal workload (UT 150W/T 260W, 3.5 minutes) caused transient minimal changes in phosphorus metabolites. Supramaximal, partially anaerobic exercise (UT 320W/T 350W, 3.5 minutes) induced similar changes in heart rate, oxygen uptake rate, and plasma lactate in both groups. Decrease of the PCr/Pi ratio, however, was more pronounced in UT subjects and clearly lasted longer. If methodical problems can be resolved, combined MRS and MRI in whole body magnets may become a standard noninvasive modality, adding unique information on morphology (organ volume) and local metabolism to classic mechanical and global physiologic data.

Reactive hyperemia in patients with septic conditions.

In a prospective study microvascular reactivity was examined in 12 patients with septic conditions by means of the provocation of reactive hyperemia (RH) for evaluation of microcirculatory function. Data were compared with data from 10 nonseptic, postsurgical patients. At the time of the initial measurement, an adequate hyperemic response could be produced in all patients. In the further course of the disease, in nine of the 12 patients severe multiple organ failure developed. In spite of sufficient values for arterial blood pressure, oxygenation, and the clotting system, RH was absent in these patients (8 +/- 2 days after the initial measurement). Subsequently, seven of these nine patients died (4 +/- 2 days after the onset of microvascular nonreactivity). Until death, RH was absent in each patient, and at this time therapy-resistant hypoxemia, hypotension, and severe disturbances of the clotting system were present. In the two surviving patients RH was restored completely. These results indicate that (1) the septic state per se is not necessarily combined with impaired microvascular reactivity (rather, the absence of RH may be a sign of generally poor clinical conditions); (2) the absence of RH is not related to therapy-resistant hypotension, hypoxia, and severe clotting disorders but precedes these changes; and (3) provocation of RH may be of clinical use for early detection of microcirculatory malfunction in high-risk patients.

Effect of hemofiltration on hemodynamics and systemic concentrations of anaphylatoxins and cytokines in human sepsis.

OBJECTIVE: To determine whether hemofiltration (HF) can eliminate cytokines and complement components and alter systemic hemodynamics in patients with severe sepsis. DESIGN: Prospective observation study. SETTING: Surgical intensive care unit of a university hospital. PATIENTS: 16 patients with severe sepsis. INTERVENTIONS: Continuous zero-balanced HF without dialysis (ultrafiltrate rate 2 l/h) was performed in addition to pulmonary artery catheterization, arterial cannulation, and standard intensive care treatment. MEASUREMENTS AND MAIN RESULTS: Plasma and ultrafiltrate concentrations of cytokines (the interleukins IL-1 beta, IL-6, IL-8, and tumor necrosis factor alpha) and of complement components (C3adesArg, C5adesArg) were measured after starting HF (t0) and 4 h (t4) and 12 h later (t12). Hemodynamic variables including mean arterial pressure (MAP), mean central venous pressure, mean pulmonary artery pressure, pulmonary capillary wedge pressure, and cardiac output were serially determined. During HF, cytokine plasma concentrations remained constant. However, C3adesArg and C5adesArg plasma concentrations showed a significant decline during 12-h HF (C3adesArg: t0 = 676.9 +/- 99.7 ng/ml vs t12 = 467.8 +/- 71, p < 0.01; C5adesArg: 26.6 +/- 4.7 ng/ml vs 17.6 +/- 6.2, p < 0.01). HF resulted in a significant increase over time in systemic vascular resistance (SVR) and MAP (SVR at t0: 669 +/- 85 dyne.s/cm5 vs SVR at t12: 864 +/- 75, p < 0.01; MAP at t0: 69.9 +/- 3.5 mmHg vs MAP at t12: 82.2 +/- 3.7, p < 0.01). CONCLUSIONS: HF effectively eliminated the anaphylatoxins C3adesArg and C5adesArg during sepsis. There was also a significant rise in SVR and MAP during high volume HF. Therefore, HF may represent a new modality for removal of anaphylatoxins and may, thereby, deserve clinical testing in patients with severe sepsis.