Browsing by Author "Weiler, Norbert"

The task of physicians is to maintain life, to protect and re-establish health as well as to alleviate suffering and to accompany the dying until death, under consideration of the self-determination rights of patients. Increasingly more and differentiated options for this are becoming available in intensive care medicine. Within the framework of professional responsibility physicians must decide which of the available treatment options are indicated. This process of decision-making is determined by answering the following question: when and under which circumstances is induction or continuation of intensive care treatment justified? In addition to the indications, the advance directive of the patient is the deciding factor. Medical indications represent a scientifically based estimation that a therapeutic measure is suitable in order to achieve a defined therapy target with a given probability. The ascertainment of the patient directive is achieved in a graded process depending on the state of consciousness of the patient. The present article offers orientation assistance to physicians for these decisions which are an individual responsibility.

The task of physicians is to maintain life, to protect and re-establish health as well as to alleviate suffering and to accompany the dying until death, under consideration of the self-determination rights of patients. Increasingly more and differentiated options for this are becoming available in intensive care medicine. Within the framework of professional responsibility physicians must decide which of the available treatment options are indicated. This process of decision-making is determined by answering the following question: when and under which circumstances is induction or continuation of intensive care treatment justified? In addition to the indications, the advance directive of the patient is the deciding factor. Medical indications represent a scientifically based estimation that a therapeutic measure is suitable in order to achieve a defined therapy target with a given probability. The ascertainment of the patient directive is achieved in a graded process depending on the state of consciousness of the patient. The present article offers orientation assistance to physicians for these decisions which are an individual responsibility.

A recent survey conducted by the publicly funded Competence Network Sepsis (Sep- Net) reveals that severe sepsis and/or septic shock occurs in 75,000 inhabitants (110 out of 100,000) and sepsis in 79,000 inhabitants (116 out of 100,000) in Germany annually. This illness is responsible for approx. 60,000 deaths and ranges as the third most frequent cause of death after acute myocardial infarction. Direct costs for the intensive care of patients with severe sepsis alone amount to approx. 1.77 billion euros, which means that about 30% of the budget in intensive care is used to treat severe sepsis. However, until now German guidelines for the diagnosis and therapy of severe sepsis did not exist. Therefore, the German Sepsis Society initiated the development of guidelines which are based on international recommendations by the International Sepsis Forum (ISF) and the Surviving Sepsis Campaign (SSC) and take into account the structure and organisation of the German health care system. Priority was given to the following guideline topics: a) diagnosis, b) prevention, c) causative therapy, d) supportive therapy, e) adjunctive therapy. The guidelines development process was carefully planned and strictly adhered to according to the requirements of the Working Group of Scientific Medical Societies (AWMF).

Objective: To determine the prevalence and mortality of ICU patients with severe sepsis in Germany, with consideration of hospital size. Design: Prospective, observational, cross-sectional 1-day point-prevalence study. Setting: 454 ICUs from a representative nationwide sample of 310 hospitals stratified by size. Data were collected via 1-day on-site audits by trained external study physicians. Visits were randomly distributed over 1 year (2003). Patients: Inflammatory response of all ICU patients was assessed using the ACCP/SCCM consensus conference criteria. Patients with severe sepsis were followed up after 3 months for hospital mortality and length of ICU stay. Measurements and results: Main outcome measures were prevalence and mortality. A total of 3,877 patients were screened. Prevalence was 12.4% (95% CI, 10.9-13.8%) for sepsis and 11.0% (95% CI, 9.7-12.2%) for severe sepsis including septic shock. The ICU and hospital mortality of patients with severe sepsis was 48.4 and 55.2%, respectively, without significant differences between hospital size. Prevalence and mean length of ICU stay of patients with severe sepsis were significantly higher in larger hospitals and universities (<= 200 beds: 6% and 11.5 days, universities: 19% and 19.2 days, respectively). Conclusions: The expected number of newly diagnosed cases with severe sepsis in Germany amounts to 76-110 per 100,000 adult inhabitants. To allow better comparison between countries, future epidemiological studies should use standardized study methodologies with respect to sepsis definitions, hospital size, and daily and monthly variability.

Electrical impedance tomography (EIT) is an attractive method for clinically monitoring patients during mechanical ventilation, because it can provide a non-invasive continuous image of pulmonary impedance which indicates the distribution of ventilation. However, most clinical and physiological research in lung EIT is done using older and proprietary algorithms; this is an obstacle to interpretation of EIT images because the reconstructed images are not well characterized. To address this issue, we develop a consensus linear reconstruction algorithm for lung EIT, called GREIT (Graz consensus Reconstruction algorithm for EIT). This paper describes the unified approach to linear image reconstruction developed for GREIT. The framework for the linear reconstruction algorithm consists of (1) detailed finite element models of a representative adult and neonatal thorax, (2) consensus on the performance figures of merit for EIT image reconstruction and (3) a systematic approach to optimize a linear reconstruction matrix to desired performance measures. Consensus figures of merit, in order of importance, are (a) uniform amplitude response, (b) small and uniform position error, (c) small ringing artefacts, (d) uniform resolution, (e) limited shape deformation and (f) high resolution. Such figures of merit must be attained while maintaining small noise amplification and small sensitivity to electrode and boundary movement. This approach represents the consensus of a large and representative group of experts in EIT algorithm design and clinical applications for pulmonary monitoring. All software and data to implement and test the algorithm have been made available under an open source license which allows free research and commercial use.

Purpose: High-frequency oscillatory ventilation (HFOV) is usually considered not indicated for treatment of patients with chronic obstructive pulmonary disease (COPD) because of the theoretical risk of air trapping and hyperinflation. The aim of our study was to establish whether HFOV can be safely applied in patients with acute exacerbation of COPD and hypercapnic respiratory failure. Methods: Ten patients (age, 63-83 years) requiring intensive care treatment who failed on noninvasive ventilation were studied. After initial conventional mechanical ventilation (CMV) of less than 72 hours, all patients were transferred to HFOV for 24 hours and then back to CMV. Arterial blood gases, spirometry, and hemodynamic parameters were repeatedly obtained in all phases of CMV and HFOV at different settings. Regional lung aeration and ventilation were assessed by electrical impedance tomography. Results: High-frequency oscillatory ventilation was tolerated well; no adverse effects or severe hyperinflation and hemodynamic compromise were observed. Effective CO2 elimination and oxygenation were achieved. Ventilation was more homogeneously distributed during HFOV than during initial CMV. Higher respiratory system compliance and tidal volume were found during CMV after 24 hours of HFOV. Conclusions: Our study indicates that short-term HFOV, using lower mean airway pressures than recommended for acute respiratory distress syndrome, appears safe in patients with COPD while securing adequate pulmonary gas exchange. (C) 2012 Elsevier Inc. All rights reserved.

Background: The role of intensive insulin therapy in patients with severe sepsis is uncertain. Fluid resuscitation improves survival among patients with septic shock, but evidence is lacking to support the choice of either crystalloids or colloids. Methods: In a multicenter, two-by-two factorial trial, we randomly assigned patients with severe sepsis to receive either intensive insulin therapy to maintain euglycemia or conventional insulin therapy and either 10% pentastarch, a low-molecular-weight hydroxyethyl starch (HES 200/0.5), or modified Ringer's lactate for fluid resuscitation. The rate of death at 28 days and the mean score for organ failure were coprimary end points. Results: The trial was stopped early for safety reasons. Among 537 patients who could be evaluated, the mean morning blood glucose level was lower in the intensive-therapy group (112 mg per deciliter [6.2 mmol per liter]) than in the conventional-therapy group (151 mg per deciliter [8.4 mmol per liter], P<0.001). However, at 28 days, there was no significant difference between the two groups in the rate of death or the mean score for organ failure. The rate of severe hypoglycemia (glucose level, <= 40 mg per deciliter [2.2 mmol per liter]) was higher in the intensive-therapy group than in the conventional-therapy group (17.0% vs. 4.1%, P<0.001), as was the rate of serious adverse events (10.9% vs. 5.2%, P=0.01). HES therapy was associated with higher rates of acute renal failure and renal-replacement therapy than was Ringer's lactate. Conclusions: The use of intensive insulin therapy placed critically ill patients with sepsis at increased risk for serious adverse events related to hypoglycemia. As used in this study, HES was harmful, and its toxicity increased with accumulating doses. (ClinicalTrials.gov number, NCT00135473.).

Objective: To simultaneously determine perceived vs. practiced adherence to recommended interventions for the treatment of severe sepsis or septic shock. Design: One-day cross-sectional survey. Setting: Representative sample of German intensive care units stratified by hospital size. Patients: Adult patients with severe sepsis or septic shock. Interventions: None. Measurements and Main Results: Practice recommendations were selected by German Sepsis Competence Network (SepNet) investigators. External intensivists visited intensive care units randomly chosen and asked the responsible intensive care unit director how often these recommendations were used. Responses "always" and "frequently" were combined to depict perceived adherence. Thereafter patient files were audited. Three hundred sixty-six patients on 214 intensive care units fulfilled the criteria and received full support. One hundred fifty-two patients had acute lung injury or acute respiratory distress syndrome. Low-tidal volume ventilation <= 6 mL/kg/predicted body weight was documented in 2.6% of these patients. A total of 17.1% patients had tidal volume between 6 and 8 mL/kg predicted body weight and 80.3% >8 mL/kg predicted body weight. Mean tidal volume was 10.0 +/- 2.4 mL/kg predicted body weight. Perceived ence to low-tidal volume ventilation was 79.9%. Euglycemia 6.1 mmol/L) was documented in 6.2% of 355 patients. A total 33.8% of patients had blood glucose levels <= 8.3 mmol/L and 66.2% were hyperglycemic (blood glucose >8.3 mmol/L. Among 207 patients receiving insulin therapy, 1.9% were euglycemic, 20.8% had blood glucose levels <= 8.3 mmol/L, and 1.0% were hypoglycemic. Overall, mean maximal glucose level was 10.0 +/- 3.6 mmol/L. Perceived adherence to strict glycemic control was 65.9%. Although perceived adherence to recommendations was higher in academic and larger hospitals, actual practice was not significantly influenced by hospital size or university affiliation. Conclusions: This representative survey shows that current therapy of severe sepsis in German intensive care units complies poorly with practice recommendations. Intensive care unit directors perceive adherence to be higher than it actually is. Implementation strategies involving all intensive care unit staff are needed to overcome this gap between current evidence-based knowledge, practice, and perception.

OBJECTIVE: We report on the effect of hemoadsorption therapy to reduce cytokines in septic patients with respiratory failure. METHODS: This was a randomized, controlled, open-label, multicenter trial. Mechanically ventilated patients with severe sepsis or septic shock and acute lung injury or acute respiratory distress syndrome were eligible for study inclusion. Patients were randomly assigned to either therapy with CytoSorb hemoperfusion for 6 hours per day for up to 7 consecutive days (treatment), or no hemoperfusion (control). Primary outcome was change in normalized IL-6-serum concentrations during study day 1 and 7. RESULTS: 97 of the 100 randomized patients were analyzed. We were not able to detect differences in systemic plasma IL-6 levels between the two groups (n = 75; p = 0.15). Significant IL-6 elimination, averaging between 5 and 18% per blood pass throughout the entire treatment period was recorded. In the unadjusted analysis, 60-day-mortality was significantly higher in the treatment group (44.7%) compared to the control group (26.0%; p = 0.039). The proportion of patients receiving renal replacement therapy at the time of enrollment was higher in the treatment group (31.9%) when compared to the control group (16.3%). After adjustment for patient morbidity and baseline imbalances, no association of hemoperfusion with mortality was found (p = 0.19). CONCLUSIONS: In this patient population with predominantly septic shock and multiple organ failure, hemoadsorption removed IL-6 but this did not lead to lower plasma IL-6-levels. We did not detect statistically significant differences in the secondary outcomes multiple organ dysfunction score, ventilation time and time course of oxygenation.

BACKGROUND: Functional magnetic resonance imaging (fMRI) of fluorine-19 allows for the mapping of oxygen partial pressure within perfluorocarbons in the alveolar space (PAO(2)). Theoretically, fMRI-detected PAO(2) can be combined with the Fick principle approach, i.e., a mass balance of oxygen uptake by ventilation and delivery by perfusion, to quantify the ventilation-perfusion ratio (VA/Q) of a lung region: The mixed venous blood and the inspiratory oxygen fraction, which are equal for all lung regions, are measured. In addition, the local expiratory oxygen fraction and the end capillary oxygen content, both of which may differ between the lung regions, are calculated using the fMRI-detected PAO(2). We investigated this approach by numerical simulations and applied it to quantify local VA/Q in the perfluorocarbons during partial liquid ventilation. METHODS: Numerical simulations were performed to analyze the sensitivity of the VA/Q calculation and to compare this approach with another one proposed by Rizi et al. in 2004 (Magn Reson Med 2004;52:65-72). Experimentally, the method was used during partial liquid ventilation in 7 anesthetized pigs. The PAO(2) distribution in intraalveolar perflubron was measured by fluorine-19 MRI. Respiratory gas fractions together with arterial and mixed venous blood samples were taken to quantify oxygen partial pressure and content. Using the Fick principle, the local VA/Q was estimated. The impact of gravity (nondependent versus dependent) of perflubron dose (10 vs 20 mL/kg body weight) and of inspired oxygen fraction (FIO(2)) (0.4-1.0) on VA/Q was examined. RESULTS: In numerical simulations, the Fick principle proved to be appropriate over the VA/Q range from 0.02 to 2.5. VA/Q values were in acceptable agreement with the method published by Rizi et al. In the experimental setting, low mean VA/Q values were found in perflubron (confidence interval [CI] 0.08-0.29 with 20 mL/kg perflubron). At this dose, VA/Q in the nondependent lung was higher (CI 0.18-0.39) than in the dependent lung regions (CI 0.06-0.16; P = 0.006; Student t test). Differences depending on FIO(2) or perflubron dose were, however, small. CONCLUSION: The results show that derivation of VA/Q from local PO(2) measurements using fMRI in perflubron is feasible. The low detected VA/Q suggests that oxygen transport into the perflubron-filled alveolar space is significantly restrained. (Anesth Analg 2010;110:1661-8)

Mortality in intensive care unit (ICU) patients is affected by multiple variables. The possible impact of the mode of ventilation has not yet been clarified; therefore, a secondary analysis of the "epidemiology of sepsis in Germany" study was performed. The aims were (1) to describe the ventilation strategies currently applied in clinical practice, (2) to analyze the association of the different modes of ventilation with mortality and (3) to investigate whether the ratio between arterial partial pressure of oxygen and inspired fraction of oxygen (PF ratio) and/or other respiratory variables are associated with mortality in septic patients needing ventilatory support. A total of 454 ICUs in 310 randomly selected hospitals participated in this national prospective observational 1-day point prevalence of sepsis study including 415 patients with severe sepsis or septic shock according to the American College of Chest Physicians/Society of Critical Care Medicine criteria. Of the 415 patients, 331 required ventilatory support. Pressure controlled ventilation (PCV) was the most frequently used ventilatory mode (70.6 %) followed by assisted ventilation (AV 21.7 %) and volume controlled ventilation (VCV 7.7 %). Hospital mortality did not differ significantly among patients ventilated with PCV (57 %), VCV (71 %) or AV (51 %, p = 0.23). A PF ratio equal or less than 300 mmHg was found in 83.2 % of invasively ventilated patients (n = 316). In AV patients there was a clear trend to a higher PF ratio (204 +/- 70 mmHg) than in controlled ventilated patients (PCV 179 +/- 74 mmHg, VCV 175 +/- 75 mmHg, p = 0.0551). Multiple regression analysis identified the tidal volume to pressure ratio (tidal volume divided by peak inspiratory airway pressure, odds ratio OR = 0.94, 95 % confidence interval 95% CI = 0.89-0.99), acute renal failure (OR = 2.15, 95% CI = 1.01-4.55) and acute physiology and chronic health evaluation (APACHE) II score (OR = 1.09, 95% CI = 1.03-1.15) but not the PF ratio (univariate analysis OR = 0.998, 95 % CI = 0.995-1.001) as independent risk factors for in-hospital mortality. This representative survey revealed that severe sepsis or septic shock was frequently associated with acute lung injury. Different ventilatory modes did not affect mortality. The tidal volume to inspiratory pressure ratio but not the PF ratio was independently associated with mortality.