H. Burchardi

A Pilot-controlled Study Of A Polymyxin B-immobilized Hemoperfusion Cartridge In Patients With Severe Sepsis Secondary To Intra-abdominal Infection

Endotoxin is an important pathogenic trigger for sepsis. The polymyxin B-immobilized endotoxin removal hemoperfusion cartridge, Toraymyxin (hereafter PMX), has been shown to remove endotoxin in preclinical and open-label clinical studies. In a multicenter, open-label, pilot, randomized, controlled study conducted in the intensive care unit in six academic medical centers in Europe, 36 postsurgical patients with severe sepsis or septic shock secondary to intra-abdominal infection were randomized to PMX treatment of 2 h (n = 17) or standard therapy (n = 19). PMX was well tolerated and showed no significant side effects. There were no statistically significant differences in the change in endotoxin levels from baseline to 6 to 8 h after treatment or to 24 h after treatment between the two groups. There was also no significant difference in the change in interleukin (IL)-6 levels from baseline to 6 to 8 h after treatment or to 24 h after treatment between the two groups. Patients treated with PMX demonstrated significant increases in cardiac index (CI; P = 0.012 and 0.032 at days 1 and 2, respectively), left ventricular stroke work index (LVSWI, P = 0.015 at day 2), and oxygen delivery index (DO2I, P = 0.007 at day 2) compared with the controls. The need for continuous renal replacement therapy (CRRT) after study entry was reduced in the PMX group (P = 0.043). There was no significant difference between the groups in organ dysfunction as assessed by the Sequential Organ Failure Assessment (SOFA) scores from day 0 (baseline) to day 6. Treatment using the PMX cartridge is safe and may improve cardiac and renal dysfunction due to sepsis or septic shock. Further studies are needed to prove this effectiveness.

Predicting outcome in ICU patients

ConclusionsConsiderable time and energy has been invested in the conception, modelling and evaluation of sophisticated severity scoring systems for ICU patients. These systems are created to enhance the precise estimation of hospital mortality for large ICU patient populations. Their current low sensitivity precludes their use for predicting out-come for individual ICU patients. However, severity scores can already be valuable for predicting mortality in groups of general ICU patients, and are very useful in the clinical trial setting.Outcome of ICU therapy, however, should incorporate more than mortality. Morbidity, disability and quality of life should also be taken into account; these factors were not taken into consideration in the design of the currently available severity scoring systems.At present, the severity scores have a very limited or no role in clinical decision-making for an individual patient, because they are based on a number of physiological and disease-oriented variables collected during the first 24 h after ICU admission. Future developments and subsequent validation of the dynamic process of clinical, physiological and organ-specific variables could improve the sensitivity and the value of severity scoring. Further collaborative developmental work in this field should be encouraged and supported across Europe and North America.

Effects of early treatment with immunoglobulin on critical illness polyneuropathy following multiple organ failure and gram-negative sepsis

Objective: The evaluation of incidences and relating factors of severe persisting critical illness polyneuropathy (CIP) in survivors of multiple organ failure (MOF). Design: Prospective study with an entry period of 24 months. Electrophysiological studies for the diagnosis of CIP were performed 1 or 2 days before the patients were discharged from the intensive care unit (ICU). Factors which might have been related to the development of CIP were identified by a retrospective chart analysis.Setting: The interdisciplinary ICU of a university hospital.Patients: Thirty-three patients who survived MOF. Sixteen of these critically ill patients developed severe sepsis due to nosocomial infections with gram-negative bacteria.Results: In seven survivors of MOF and sepsis typical electrophysiological features of CIP, like spontaneous fibrillations and low compound muscle action potentials, were detectable at the time of discharge from the ICU. Seventeen patients with MOF following multiple trauma who developed no sepsis, and nine survivors of MOF with sepsis showed no signs of persisting CIP at the end of their ICU stay. Chart analysis revealed that eight survivors of MOF with sepsis and without the development of CIP had been treated with intravenous immunoglobulin (IVIG) with a dosage of 0.3 g/kg per day for 3 days immediately (within 24 h) after the diagnosis of sepsis. Four out of seven patients with MOF and sepsis who developed CIP were transferred to our ICU after the onset of sepsis and had not received IVIG treatment. The IVIG treatment in three patients was delayed for more than 24 h after the diagnosis of sepsis and was then omitted. Obviously not related to the development of CIP were aminoglycoside antibiotics, steroids, nutritional disturbances and episodes of hypotension or hypoxia. Neuromuscular blocking agents were not used during intensive care treatment.Conclusions: A high incidence of severe CIP persisting until the day of discharge from the ICU was related to gram-negative sepsis but not to MOF alone. Retrospective chart analysis suggested that early application of IVIG may prevent or mitigate this severe complication. However, these results have to be confirmed in a prospective, placebo-controlled study.

Hydrogen peroxide in expired breath condensate of patients with acute respiratory failure and with ARDS

ObjectiveMeasurement of hydrogen peroxide concentrations in breath condensate of mechanically ventilated patients with ARDS and with risk factors for developing ARDS.DesignOpen study in intensive care patients.SettingIntensive care units of the Clinics of the University of Goettingen, a primary care center.Patients10 post-operatively ventilated patients as a control group and 26 patients with acute respiratory failure, 7 of them with ARDS, 12 with polytrauma, 4 with pneumonia, 3 with cardiogenic or nephrogenic pulmonary edema.InterventionsNone.MeasurementsBreath condensate was collected by a special cold trap and was analysed for H2O2 by a chemiluminescence method. Daily measurements were performed for 4.2±2.6 days (mean±SD) as soon as possible after manifestation of respiratory failure.ResultsPatients with acute respiratory failure exhibited higher H2O2 concentrations than control patients (median 95 nmol/l, range 76–144 nmol/l), with the highest median value found in the ARDS group (552 nmol/l, range 154–893). After clinical improvement, H2O2 concentrations decreased to the range of the control group.ConclusionSince high concentrations of H2O2 in breath condensate were only found in patients with ARDS or with risk factors for ARDS, the results add to the existing evidence that reactive oxygen species are associated with some acute lung diseases.

A German national prevalence study on the cost of intensive care: an evaluation from 51 intensive care units

IntroductionIntensive care unit (ICU) costs account for up to 20% of a hospitals costs. We aimed to analyse the individual patient-related cost of intensive care at various hospital levels and for different groups of disease.MethodsData from 51 ICUs all over Germany (15 primary care hospitals and 14 general care hospitals, 10 maximal care hospitals and 12 focused care hospitals) were collected in an observational, cross-sectional, one-day point prevalence study by two external study physicians (January–October 2003). All ICU patients (length of stay > 24 hours) treated on the study day were included. The reason for admission, severity of illness, surgical/diagnostic procedures, resource consumption, ICU/hospital length of stay, outcome and ICU staffing structure were documented.ResultsAltogether 453 patients were included. ICU (hospital) mortality was 12.1% (15.7%). The reason for admission and the severity of illness differed between the hospital levels of care, with a higher amount of unscheduled surgical procedures and patients needing mechanical ventilation in maximal care hospital and focused care hospital facilities. The mean total costs per day were €791 ± 305 (primary care hospitals, €685 ± 234; general care hospitals, €672 ± 199; focused care hospitals, €816 ± 363; maximal care hospitals, €923 ± 306), with the highest cost in septic patients (€1,090 ± 422). Differences were associated with staffing, the amount of prescribed drugs/blood products and diagnostic procedures.ConclusionThe reason for admission, the severity of illness and the occurrence of severe sepsis are directly related to the level of ICU cost. A high fraction of costs result from staffing (up to 62%). Specialized and maximum care hospitals treat a higher proportion of the more severely ill and most expensive patients.

Economic Aspects of Severe Sepsis: A Review of Intensive Care Unit Costs, Cost of Illness and Cost Effectiveness of Therapy

AbstractSevere sepsis remains both an important clinical challenge and an economic burden in intensive care. An estimated 750 000 cases occur each year in the US alone (300 cases per 100 000 population). Lower numbers are estimated for most European countries (e.g. Germany and Austria: 54–116 cases per year per 100 000).Sepsis patients are generally treated in intensive care units (ICUs) where close supervision and intensive care treatment by a competent team with adequate equipment can be provided. Staffing costs represent from 40% to >60% of the total ICU budget. Because of the high proportion of fixed costs in ICU treatment, the total cost of ICU care is mainly dependent on the length of ICU stay (ICU-LOS). The average total cost per ICU day is estimated at approximately €1200 for countries with a highly developed healthcare system (based on various studies conducted between 1989 and 2001 and converted at 2003 currency rates).Patients with infections and severe sepsis require a prolonged ICU-LOS, resulting in higher costs of treatment compared with other ICU patients. US cost-of-illness studies focusing on direct costs per sepsis patient have yielded estimates of €34 000, whereas European studies have given lower cost estimates, ranging from €23 000 to €29 000. Direct costs, however, make up only about 20–30% of the cost of illness of severe sepsis. Indirect costs associated with severe sepsis account for 70–80% of costs and arise mainly from productivity losses due to mortality.Because of increasing healthcare cost pressures worldwide, economic issues have become important for the introduction of new innovations. This is evident when introducing new biotechnology products, such as drotrecogin-α (activated protein C), into specific therapy for severe sepsis. Data so far suggest that when drotrecogin-α treatment is targeted to those patients most likely to achieve the greatest benefit, the drug is cost effective by the standards of other well accepted life-saving interventions.

Monitoring perioperative changes in distribution of pulmonary ventilation by functional electrical impedance tomography

Background: Electrical impedance tomography (EIT) is a noninvasive technique providing cross‐sectional images of the thorax. We have tested an extended evaluation procedure, the functional EIT (f‐EIT), to identify the local shifts of ventilation known to occur during the transition between spontaneous, controlled and assisted ventilation modes.

IMPROVED DETERMINATION OF STATIC COMPLIANCE BY AUTOMATED SINGLE VOLUME STEPS IN VENTILATED PATIENTS

A new method for determination the static compliance of the respiratory system is described (“static compliance by automated single steps”-SCASS). In 12 ventilated patients pressure/volume (P/V) curves were determined by automated repetitive occlusion (6 s) at single volume steps and compared to the conventional syringe method (SM). All measurements were corrected for effects of temperature, humidity and pressure (THP). SM was found to be significantly influenced by intrapulmonary gas exchange causing an effective mean volume deficit of 217.4±65.7 ml (BTPS) at the end of the deflation. In contrast to that, the short duration of occlusion in SCASS minimize the gas exchange effects. The methodical differences between both methods result in overestimation of the inflation compliance in the uncorrected SM (SMuncorr: 83.4±12.6; SCASS: 76.0±11.9 ml/cmH2O.p<0.01) and underestimation of the deflation compliance resp. (SMuncorr: 58.3±7.5; SCASS: 79.1±15.0 ml/cmH2O.p<0.005). In contrast to the P/V curves by SM no significant hysteresis was found by SCASS. Gas exchange seems to be the main reason for the hysteresis. Even after correcting gas exchange and THP effects a significant hyseresis remained. The SCASS method avoids these problems and allows furthermore an accurate checking of leaks.

High-dose intravenous magnesium sulfate in the management of life-threatening status asthmaticus

In severe status asthmaticus basic medical treatment often fails to improve the patients condition. Mechanical ventilation in this situation is associated with a high incidence of serious complications. After the bronchodilating effect of moderate-dose magnesium sulfate in asthmatic patients had been demonstrated in previous studies we treated five mechanically ventilated patients with refractory status asthmaticus successfully with high dosages of MgSO4 IV (10–20 g within 1 h depending on the bronchodilating effect). MgSO4 resulted in a significant decrease of peak airway pressure (43.0±6.8 to 32.0±8.0 cmH2O) and inspiratory flow resistance (22.7±7.0 to 11.9±6.0 cmH2O·l−1·s−1) within 1 h. The resulting serum magnesium levels after one hour were up to threefold of the normal serum levels. Although a main-tainance dose of 0.4 g/h had been administered continuously during the following 24 h serum magnesium decreased towards normal values within this time. The only relevant side-effect was a mild to moderate arterial hypotension in two of the five patients during the high dose administration period of MgSO4 which responded readily to dopamine treatment.

Do we need intermediate care units

Since its inception during the severe outbreak of poliomyelitis almost 50 years ago, the intensive care unit (ICU) has become a key feature in almost every hospital. Increasingly sick patient populations, improved life-support systems, newer, more effective therapeutic agents, and greater understanding of the pathophysiology of many disease processes have led to a growing need for ICU beds, with the ICU increasingly accounting for a larger and larger proportion of the hospital budget [1]. Intensive care is unquestionably expensive care [2, 3] and resources are not always readily available. As an example, there are frequently insufficient ICU beds available to cater for demand. Indeed, in a recent questionnaire survey of 504 ICUs in 16 Western European countries, 46% of respondents stated that ICU admissions were generally or commonly affected by bed shortages [4]. With increasingly expensive technology being developed, ICU spending is likely further to exceed available funding, and the need for explicit rationing is rapidly becoming a reality. However rationing is applied, the aim must be to provide, without restriction, high-quality intensive care for those who will benefit from it. To this end, several suggestions have been made to limit ICU costs and improve the efficiency of the service. These include the development and implementation of strict admission and discharge criteria, and the use of intermediate care units. These intermediate care units, also termed high-dependency or astepdowno, units, generally have a higher nurse/patient ratio and greater facilities for intensive monitoring than would be found on a general ward, but fewer staff and less invasive equipment than on an ICU [5, 6] (Fig. 1). Such areas cater for patients who do not require full ICU care but are thought to need more care than could be offered on the general ward. Intermediate care units have been adopted by some hospitals, particularly for specific patient groups, such as cardiac [7], neurosurgical [8], or respiratory [9] patients. The use of such units has been promoted as a means of enabling the earlier discharge of some ICU patients and of providing an alternative to intensive care for patients who merely require intensive monitoring, thus freeing ICU beds. However, such units are not necessarily the solution to overutilization of ICU beds and may merely divert the issue rather than solve it [10]. They may also have negative effects on patient care and staff morale. Importantly, there are few, if any, prospective studies on the benefits of intensive care versus intermediate care which provide objective and hence comparable, admission and discharge criteria. In addition, the literature that is available comes predominantly from the United States, where intensive care training, organisation and management are very different than Europe. In this paper, we will discuss the pros and cons of intermediate care units and conclude with our thoughts and recommendations on the appropriate place of such units in our hospitals today.