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1.  Persistence of Psychological Distress in Surgical Patients with Interest in Psychotherapy: Results of a 6-Month Follow-Up 
PLoS ONE  2012;7(12):e51167.
Objectives
This prospective observational study investigated whether self-reported psychological distress and alcohol use problems of surgical patients change between preoperative baseline assessment and postoperative 6-month follow-up examination. Patients with preoperative interest in psychotherapy were compared with patients without interest in psychotherapy.
Methods
A total of 1,157 consecutive patients from various surgical fields completed a set of psychiatric questionnaires preoperatively and at 6 months postoperatively, including Patient Health Questionnaire-4 (PHQ-4), Brief Symptom Inventory (BSI), Center for Epidemiologic Studies Depression Scale (CES-D), World Health Organization 5-item Well-Being Index (WHO-5), and Alcohol Use Disorder Identification Test (AUDIT). Additionally, patients were asked for their interest in psychotherapy. Repeated measure ANCOVA was used for primary data analysis.
Results
16.7% of the patients were interested in psychotherapy. Compared to uninterested patients, they showed consistently higher distress at both baseline and month 6 regarding all of the assessed psychological measures (p’s between <0.001 and 0.003). At 6-month follow-up, neither substantial changes over time nor large time x group interactions were found. Results of ANCOVA’s controlling for demographic variables were confirmed by analyses of frequencies of clinically significant distress.
Conclusion
In surgical patients with interest in psychotherapy, there is a remarkable persistence of elevated self-reported general psychological distress, depression, anxiety, and alcohol use disorder symptoms over 6 months. This suggests high and chronic psychiatric comorbidity and a clear need for psychotherapeutic and psychiatric treatment rather than transient worries posed by facing surgery.
doi:10.1371/journal.pone.0051167
PMCID: PMC3515556  PMID: 23227250
2.  Managing End-Of-Life Decision Making in Intensive Care Medicine – A Perspective from Charité Hospital, Germany 
PLoS ONE  2012;7(10):e46446.
Introduction
End-of-life-decisions (EOLD) have become an important part of modern intensive care medicine. With increasing therapeutic possibilities on the one hand and many ICU-patients lacking decision making capacity or an advance directive on the other the decision making process is a major challenge on the intensive care unit (ICU). Currently, data are poor on factors associated with EOLD in Germany. In 2009, a new law on advance directives binding physicians and the patient´s surrogate decision makers was enacted in Germany. So far it is unknown if this law influenced proceedings of EOLD making on the ICU.
Methods
A retrospective analysis was conducted on all deceased patients (n = 224) in a 22-bed surgical ICU of a German university medical center from 08/2008 to 09/2010. Patient characteristics were compared between patients with an EOLD and those without an EOLD. Patients with an EOLD admitted before and after change of legislation were compared with respect to frequencies of EOLD performance as well as advance directive rates.
Results
In total, 166 (74.1%) of deaths occurred after an EOLD. Compared to patients without an EOLD, comorbidities, ICU severity scores, and organ replacement technology did not differ significantly. EOLDs were shared within the caregiverteam and with the patient´s surrogate decision makers. After law enacting, no differences in EOLD performance or frequency of advance directives (8.9% vs. 9.9%; p = 0.807) were observed except an increase of documentation efforts associated with EOLDs (18.7% vs. 43.6%; p<0.001).
Conclusions
In our ICU EOLD proceedings were performed patient-individually. But EOLDs follow a standard of shared decision making within the caregiverteam and the patient´s surrogate decision makers. Enacting a law on advance directives has not affected the decision making-process in EOLDs nor has it affected population´s advance care planning habits. However, it has led to increased EOLD-associated documentation on the ICU.
Trail Registration
ClinicalTrials.gov NCT01294189.
doi:10.1371/journal.pone.0046446
PMCID: PMC3462175  PMID: 23049701
3.  Mortality after surgery in Europe: a 7 day cohort study 
Lancet  2012;380(9847):1059-1065.
Summary
Background
Clinical outcomes after major surgery are poorly described at the national level. Evidence of heterogeneity between hospitals and health-care systems suggests potential to improve care for patients but this potential remains unconfirmed. The European Surgical Outcomes Study was an international study designed to assess outcomes after non-cardiac surgery in Europe.
Methods
We did this 7 day cohort study between April 4 and April 11, 2011. We collected data describing consecutive patients aged 16 years and older undergoing inpatient non-cardiac surgery in 498 hospitals across 28 European nations. Patients were followed up for a maximum of 60 days. The primary endpoint was in-hospital mortality. Secondary outcome measures were duration of hospital stay and admission to critical care. We used χ2 and Fisher's exact tests to compare categorical variables and the t test or the Mann-Whitney U test to compare continuous variables. Significance was set at p<0·05. We constructed multilevel logistic regression models to adjust for the differences in mortality rates between countries.
Findings
We included 46 539 patients, of whom 1855 (4%) died before hospital discharge. 3599 (8%) patients were admitted to critical care after surgery with a median length of stay of 1·2 days (IQR 0·9–3·6). 1358 (73%) patients who died were not admitted to critical care at any stage after surgery. Crude mortality rates varied widely between countries (from 1·2% [95% CI 0·0–3·0] for Iceland to 21·5% [16·9–26·2] for Latvia). After adjustment for confounding variables, important differences remained between countries when compared with the UK, the country with the largest dataset (OR range from 0·44 [95% CI 0·19–1·05; p=0·06] for Finland to 6·92 [2·37–20·27; p=0·0004] for Poland).
Interpretation
The mortality rate for patients undergoing inpatient non-cardiac surgery was higher than anticipated. Variations in mortality between countries suggest the need for national and international strategies to improve care for this group of patients.
Funding
European Society of Intensive Care Medicine, European Society of Anaesthesiology.
doi:10.1016/S0140-6736(12)61148-9
PMCID: PMC3493988  PMID: 22998715
4.  Effects of intensivist coverage in a post-anaesthesia care unit on surgical patients' case mix and characteristics of the intensive care unit 
Critical Care  2012;16(4):R126.
Introduction
There is an increasing demand for intensive care in hospitals, which can lead to capacity limitations in the intensive care unit (ICU). Due to postponement of elective surgery or delayed admission of emergency patients, outcome may be negatively influenced. To optimize the admission process to intensive care, the post-anaesthesia care unit (PACU) was staffed with intensivist coverage around the clock. The aim of this study is to demonstrate the impact of the PACU on the structure of ICU-patients and the contribution to overall hospital profit in terms of changes in the case mix index for all surgical patients.
Methods
The administrative data of all surgical patients (n = 51,040) 20 months prior and 20 months after the introduction of a round-the-clock intensivist staffing of the PACU were evaluated and compared.
Results
The relative number of patients with longer length of stay (LOS) (more than seven days) in the ICU increased after the introduction of the PACU. The average monthly number of treatment days of patients staying less than 24 hours in the ICU decreased by about 50% (138.95 vs. 68.19 treatment days, P <0.005). The mean LOS in the PACU was 0.45 (± 0.41) days, compared to 0.27 (± 0.2) days prior to the implementation. The preoperative times in the hospital decreased significantly for all patients. The case mix index (CMI) per hospital day for all surgical patients was significantly higher after the introduction of a PACU: 0.286 (± 0.234) vs. 0.309 (± 0.272) P <0.001 CMI/hospital day.
Conclusions
The introduction of a PACU and the staffing with intensive care staff might shorten the hospital LOS for surgical patients. The revenues for the hospital, as determined by the case mix index of the patients per hospital day, increased after the implementation of a PACU and more patients can be treated in the same time, due to a better use of resources.
doi:10.1186/cc11428
PMCID: PMC3580709  PMID: 22809294
5.  Thawed solvent/detergent-treated plasma: too precious to be wasted after 6 hours? 
Blood Transfusion  2012;10(3):360-367.
Background.
Coagulopathy associated with trauma and bleeding requires early administration of haemostatic agents. Solvent/detergent-treated plasma (S/D-plasma) requires thawing and its availability for clinical use is, therefore, delayed. The long-term stability of clotting factors in thawed S/D-plasma has not been thoroughly investigated. The purpose of this study was to evaluate stability of clotting factors and inhibitors in thawed S/D-plasma stored at 4 °C for 6 days.
Materials and methods.
Clotting factor levels and bacterial contamination were investigated using 20 units of S/D-plasma. Fibrinogen, factor (F) II, FV, FVII, FVIII, FIX, FX, FXI, FXII, FXIII, antithrombin, von Willebrand antigen (VWF-Ag), plasmin inhibitor, protein C and free protein S were analysed over time.
Results.
After 6 days of storage the results were as follows: fibrinogen 270 mg/dL (−10 mg/dL, p=0.0204), FII 75% (−5%, p<0.0001), FV 88% (−14%, p<0.0001), FVII 81% (−24%, p<0.0001), FVIII 70% (−16%, p<0.0001), FIX 96% (−8, p<0.0001), FX 92% (−1%, p<0.0001), FXI 119% (−4%, p=0.3666), FXII 94% (−2%, p=0.3602), FXIII 89% (−1%, p 0.0019), free protein S 76% (−4%, p<0.0001), protein C 96% (+1%, p=0.0371), antithrombin 92% (−3%, p<0.0001), plasmin inhibitor 29% (−4%, p<0.0299), VWF-Ag 137% (+2%, p=0.2205). FVII and FVIII showed a critical drop of more than 20% or approached the lower quality assurance threshold after storage for more than 24 hours. No S/D-plasma showed bacterial contamination.
Conclusion.
All clotting factors in thawed S/D plasma remained stable for up to 24 hours when stored at 4 °C. Storage of thawed S/D plasma may improve the availability of this product in emergency situations.
doi:10.2450/2012.0092-11
PMCID: PMC3417736  PMID: 22507858
S/D-plasma; massive transfusion; plasma storage; clotting factors
6.  The paediatric Confusion Assessment Method for the Intensive Care Unit (pCAM-ICU): Translation and cognitive debriefing for the German-speaking area 
GMS German Medical Science  2012;10:Doc07.
Purpose: To date there are only a few studies published, dealing with delirium in critically ill patients. The problem with these studies is that prevalence rates of delirium could only be estimated because of the lack of validated delirium assessment tools for the paediatric intensive care unit (PICU). The paediatric Confusion Assessment Method for the Intensive Care Unit (pCAM-ICU) was specifically developed and validated for the detection of delirium in PICU patients. The purpose of this study was the translation of the English pCAM-ICU into German according to international validated guidelines.
Methods: The translation process was performed according to the principles of good practice for the translation and cultural adaptation process for patient reported outcomes measures: From three independently created German forward-translation versions one preliminary German version was developed, which was then retranslated to English by a certified, state-approved translator. The back-translated version was submitted to the original author for evaluation. The German translation was evaluated by clinicians and specialists anonymously (German grades) in regards to language and content of the translation.
Results: The results of the cognitive debriefing revealed good to very good results. After that the translation process was successfully completed and the final version of the German pCAM-ICU was adopted by the expert committee.
Conclusion: The German version of the pCAM-ICU is a result of a translation process in accordance with internationally acknowledged guidelines. Particularly, with respect to the excellent results of the cognitive debriefing, we could finalise the translation and cultural adaptation process for the German pCAM-ICU.
doi:10.3205/000158
PMCID: PMC3334933  PMID: 22557940
delirium; paediatric; pCAM-ICU; intensive care unit; translation
7.  Gastrointestinal function in intensive care patients: terminology, definitions and management. Recommendations of the ESICM Working Group on Abdominal Problems 
Intensive Care Medicine  2012;38(3):384-394.
Purpose
Acute gastrointestinal (GI) dysfunction and failure have been increasingly recognized in critically ill patients. The variety of definitions proposed in the past has led to confusion and difficulty in comparing one study to another. An international working group convened to standardize the definitions for acute GI failure and GI symptoms and to review the therapeutic options.
Methods
The Working Group on Abdominal Problems (WGAP) of the European Society of Intensive Care Medicine (ESICM) developed the definitions for GI dysfunction in intensive care patients on the basis of the available evidence and current understanding of the pathophysiology.
Results
Definitions for acute gastrointestinal injury (AGI) with its four grades of severity, as well as for feeding intolerance syndrome and GI symptoms (e.g. vomiting, diarrhoea, paralysis, high gastric residual volumes) are proposed. AGI is a malfunctioning of the GI tract in intensive care patients due to their acute illness. AGI grade I = increased risk of developing GI dysfunction or failure (a self-limiting condition); AGI grade II = GI dysfunction (a condition that requires interventions); AGI grade III = GI failure (GI function cannot be restored with interventions); AGI grade IV = dramatically manifesting GI failure (a condition that is immediately life-threatening). Current evidence and expert opinions regarding treatment of acute GI dysfunction are provided.
Conclusions
State-of-the-art definitions for GI dysfunction with gradation as well as management recommendations are proposed on the basis of current medical evidence and expert opinion. The WGAP recommends using these definitions for clinical and research purposes.
Electronic supplementary material
The online version of this article (doi:10.1007/s00134-011-2459-y) contains supplementary material, which is available to authorized users.
doi:10.1007/s00134-011-2459-y
PMCID: PMC3286505  PMID: 22310869
Gastrointestinal function; Failure; Symptoms; Feeding intolerance; Intensive care; Definitions; Classification
8.  Validation of core competencies during residency training in anaesthesiology 
Background and goal: Curriculum development for residency training is increasingly challenging in times of financial restrictions and time limitations. Several countries have adopted the CanMEDS framework for medical education as a model into their curricula of specialty training. The purpose of the present study was to validate the competency goals, as derived from CanMEDS, of the Department of Anaesthesiology and Intensive Care Medicine of the Berlin Charité University Medical Centre, by conducting a staff survey. These goals for the qualification of specialists stipulate demonstrable competencies in seven areas: expert medical action, efficient collaboration in a team, communications with patients and family, management and organisation, lifelong learning, professional behaviour, and advocacy of good health. We had previously developed a catalogue of curriculum items based on these seven core competencies. In order to evaluate the validity of this catalogue, we surveyed anaesthetists at our department in regard to their perception of the importance of each of these items. In addition to the descriptive acquisition of data, it was intended to assess the results of the survey to ascertain whether there were differences in the evaluation of these objectives by specialists and registrars.
Methods: The questionnaire with the seven adapted CanMEDS Roles included items describing each of their underlying competencies. Each anaesthetist (registrars and specialists) working at our institution in May of 2007 was asked to participate in the survey. Individual perception of relevance was rated for each item on a scale similar to the Likert system, ranging from 1 (highly relevant) to 5 (not at all relevant), from which ratings means were calculated. For determination of reliability, we calculated Cronbach’s alpha. To assess differences between subgroups, we performed analysis of variance.
Results: All seven roles were rated as relevant. Three of the seven competency goals (expert medical action, efficient collaboration in a team, and communication with patients and family) achieved especially high ratings. Only a few items differed significantly in their average rating between specialists and registrars.
Conclusions: We succeeded in validating the relevance of the adapted seven CanMEDS competencies for residency training within our institution. So far, many countries have adopted the Canadian Model, which indicates the great practicability of this competency-based model in curriculum planning. Roles with higher acceptance should be prioritised in existing curricula. It would be desirable to develop and validate a competency-based curriculum for specialty training in anaesthesiology throughout Germany by conducting a national survey to include specialists as well as registrars in curriculum development.
doi:10.3205/000146
PMCID: PMC3172723  PMID: 21921997
clinical competence; physicians; medical education; questionnaires; attitude of health personnel; curriculum
9.  Laboratory models available to study alcohol-induced organ damage and immune variations; choosing the appropriate model 
The morbidity and mortality resulting from alcohol-related diseases impose a substantive cost to society globally. To minimize the financial burden on society and improve the quality of life for individuals suffering from the ill effects of alcohol abuse, researchers in the alcohol field are focused on understanding the mechanisms by which alcohol-related diseases develop and progress. Since ethical concerns and inherent difficulties limit the amount of alcohol abuse research that can be performed in humans, most is performed in laboratory animals. This article summarizes the various laboratory models of alcohol abuse that are currently available and are used to study the mechanisms by which alcohol abuse induces organ damage and immune defects. The strengths and weaknesses of each of the models are discussed. Integrated into the review are the presentations that were made in the symposium “Methods of Ethanol Application in Alcohol Model – How Long is Long Enough” at the joint 2008 Research Society on Alcoholism (RSA) and International Society for Biomedical Research on Alcoholism (ISBRA) meeting, Washington, DC, emphasizing the importance not only of selecting the most appropriate laboratory alcohol model to address the specific goals of a project but also of ensuring that the findings can be extrapolated to alcohol-induced diseases in humans.
doi:10.1111/j.1530-0277.2010.01234.x
PMCID: PMC2929290  PMID: 20586763
animal models; acute and chronic alcohol abuse; immune defects; organ damage
10.  Gender-related outcome difference is related to course of sepsis on mixed ICUs: a prospective, observational clinical study 
Critical Care  2011;15(3):R151.
Introduction
Impact of gender on severe infections is in highly controversial discussion with natural survival advantage of females described in animal studies but contradictory to those described human data. This study aims to describe the impact of gender on outcome in mixed intensive care units (ICUs) with a special focus on sepsis.
Methods
We performed a prospective, observational, clinical trial at Charité University Hospital in Berlin, Germany. Over a period of 180 days, patients were screened, undergoing care in three mainly surgical ICUs. In total, 709 adults were included in the analysis, comprising the main population ([female] n = 309, [male] n = 400) including 327 as the sepsis subgroup ([female] n = 130, [male] n = 197).
Results
Basic characteristics differed between genders in terms of age, lifestyle factors, comorbidities, and SOFA-score (Sequential Organ Failure Assessment). Quality and quantity of antibiotic therapy in means of antibiotic-free days, daily antibiotic use, daily costs of antibiotics, time to antibiotics, and guideline adherence did not differ between genders. ICU mortality was comparable in the main population ([female] 10.7% versus [male] 9.0%; P = 0.523), but differed significantly in sepsis patients with [female] 23.1% versus [male] 13.7% (P = 0.037). This was confirmed in multivariate regression analysis with OR = 1.966 (95% CI, 1.045 to 3.701; P = 0.036) for females compared with males.
Conclusions
No differences in patients' outcome were noted related to gender aspects in mainly surgical ICUs. However, for patients with sepsis, an increase of mortality is related to the female sex.
doi:10.1186/cc10277
PMCID: PMC3219025  PMID: 21693012
11.  Peer reviewing critical care: a pragmatic approach to quality management 
Critical care medicine frequently involves decisions and measures that may result in significant consequences for patients. In particular, mistakes may directly or indirectly derive from daily routine processes. In addition, consequences may result from the broader pharmaceutical and technological treatment options, which frequently involve multidimensional aspects. The increasing complexity of pharmaceutical and technological properties must be monitored and taken into account. Besides the presence of various disciplines involved, the provision of 24-hour care requires multiple handovers of significant information each day. Immediate expert action that is well coordinated is just as important as a professional handling of medicine's limitations.
Intensivists are increasingly facing professional quality management within the ICU (Intensive Care Unit). This article depicts a practical and effective approach to this complex topic and describes external evaluation of critical care according to peer reviewing processes, which have been successfully implemented in Germany and are likely to gain in significance.
doi:10.3205/000112
PMCID: PMC2975265  PMID: 21063473
peer review; quality management; intensive care medicine; evidence based medicine; effectiveness
12.  Quality indicators in intensive care medicine: why? Use or burden for the intensivist 
In order to improve quality (of therapy), one has to know, evaluate and make transparent, one’s own daily processes. This process of reflection can be supported by the presentation of key data or indicators, in which the real as-is state can be represented. Quality indicators are required in order to depict the as-is state.
Quality indicators reflect adherence to specific quality measures. Continuing registration of an indicator is useless once it becomes irrelevant or adherence is 100%.
In the field of intensive care medicine, studies of quality indicators have been performed in some countries. Quality indicators relevant for medical quality and outcome in critically ill patients have been identified by following standardized approaches.
Different German societies of intensive care medicine have finally agreed on 10 core quality indicators that will be valid for two years and are currently recommended in German intensive care units (ICUs).
doi:10.3205/000111
PMCID: PMC2975264  PMID: 21063472
quality indicators; quality management; intensive care medicine; quality of therapy; outcome
13.  Mortality associated with administration of high-dose tranexamic acid and aprotinin in primary open-heart procedures: a retrospective analysis 
Critical Care  2010;14(4):R148.
Introduction
Antifibrinolytic agents are commonly used during cardiac surgery to minimize bleeding. Because of safety concerns, aprotinin was withdrawn from the market in 2007. Since then, tranexamic acid (TXA) has become the antifibrinolytic treatment of choice in many heart centers. The safety profile of TXA has not been extensively studied. Therefore, the aim of this study was to evaluate safety and efficiency of TXA compared with aprotinin in cardiac surgery.
Methods
Since July 1, 2006, TXA has been administered at a dose of 50 mg/kg tranexamic acid before cardiopulmonary bypass (CPB) and 50 mg/kg into the priming fluid of the CPB. Prior to this, all patients were treated with aprotinin at a dose of 50,000 KIU per kilogram body weight. Safety was evaluated with mortality, biomarkers, and the diagnosis of myocardial infarction, ischemic stroke, convulsive seizures, and acute renal failure in the intensive care unit (ICU), intermediate care unit (IMCU), and hospital stay. Efficiency was evaluated by the need for transfusion of blood products and total postoperative blood loss.
Results
After informed consent, 893 patients were included in our database (557 consecutive patients receiving aprotinin and 336 patients receiving TXA). A subgroup of 320 patients undergoing open-heart procedures (105 receiving TXA and 215 receiving aprotinin) was analyzed separately. In the aprotinin group, a higher rate of late events of ischemic stroke (3.4% versus 0.9%; P = 0.02) and neurologic disability (5.8% versus 2.4%; P = 0.02) was found. The rate of postoperative convulsive seizures was increased in tendency in patients receiving TXA (2.7% versus 0.9%; P = 0.05). The use of TXA was associated with higher cumulative drainage losses (PANOVA < 0.01; Ptime < 0.01) and a higher rate of repeated thoracotomy for bleeding (6.9% versus 2.4%; P < 0.01). In the subgroup of patients with open-chamber procedures, mortality was higher in the TXA group (16.2% TXA versus 7.5% aprotinin; P = 0.02). Multivariate logistic regression identified EURO score II and CPB time as additional risk factors for this increased mortality.
Conclusions
The use of high-dose TXA is questioned, as our data suggest an association between higher mortality and minor efficiency while the safety profile of this drug is not consistently improved. Further confirmatory prospective studies evaluating the efficacy and safety profile of TXA are urgently needed to find a safe dosage for this antifibrinolytic drug.
doi:10.1186/cc9216
PMCID: PMC2945131  PMID: 20682059
14.  Risk factors in critical illness myopathy during the early course of critical illness: a prospective observational study 
Critical Care  2010;14(3):R119.
Introduction
Non-excitable muscle membrane indicates critical illness myopathy (CIM) during early critical illness. We investigated predisposing risk factors for non-excitable muscle membrane at onset of critical illness.
Methods
We performed sequential measurements of muscle membrane excitability after direct muscle stimulation (dmCMAP) in 40 intensive care unit (ICU) patients selected upon a simplified acute physiology (SAPS-II) score ≥ 20 on 3 successive days within 1 week after ICU admission. We then investigated predisposing risk factors, including the insulin-like growth factor (IGF)-system, inflammatory, metabolic and hemodynamic parameters, as well as suspected medical treatment prior to first occurrence of abnormal dmCMAP. Nonparametric analysis of two-factorial longitudinal data and multivariate analysis were used for statistical analysis.
Results
22 patients showed abnormal muscle membrane excitability during direct muscle stimulation within 7 (5 to 9.25) days after ICU admission. Significant risk factors for the development of impaired muscle membrane excitability in univariate analysis included inflammation, disease severity, catecholamine and sedation requirements, as well as IGF binding protein-1 (IGFBP-I), but did not include either adjunctive hydrocortisone treatment in septic shock, nor administration of neuromuscular blocking agents or aminoglycosides. In multivariate Cox regression analysis, interleukin-6 remained the significant risk factor for the development of impaired muscle membrane excitability (HR 1.006, 95%-CI (1.002 to 1.011), P = 0.002).
Conclusions
Systemic inflammation during early critical illness was found to be the main risk factor for development of CIM during early critical illness. Inflammation-induced impairment of growth-factor mediated insulin sensitivity may be involved in the development of CIM.
doi:10.1186/cc9074
PMCID: PMC2911767  PMID: 20565863
16.  Infections of respiratory or abdominal origin in ICU patients: what are the differences? 
Critical Care  2010;14(2):R32.
Introduction
There are few data related to the effects of different sources of infection on outcome. We used the Sepsis Occurrence in Acutely ill Patients (SOAP) database to investigate differences in the impact of respiratory tract and abdominal sites of infection on organ failure and survival.
Methods
The SOAP study was a cohort, multicenter, observational study which included data from all adult patients admitted to one of 198 participating intensive care units (ICUs) from 24 European countries during the study period. In this substudy, patients were divided into two groups depending on whether, on admission, they had abdominal infection but no respiratory infection or respiratory infection but no abdominal infection. The two groups were compared with respect to patient and infection-related characteristics, organ failure patterns, and outcomes.
Results
Of the 3,147 patients in the SOAP database, 777 (25%) patients had sepsis on ICU admission; 162 (21%) had abdominal infection without concurrent respiratory infection and 380 (49%) had respiratory infection without concurrent abdominal infection. Age, sex, and severity scores were similar in the two groups. On admission, septic shock was more common in patients with abdominal infection (40.1% vs. 29.5%, P = 0.016) who were also more likely to have early coagulation failure (17.3% vs. 9.5%, P = 0.01) and acute renal failure (38.3% vs. 29.5%, P = 0.045). In contrast, patients with respiratory infection were more likely to have early neurological failure (30.5% vs. 9.9%, P < 0.001). The median length of ICU stay was the same in the two groups, but the median length of hospital stay was longer in patients with abdominal than in those with respiratory infection (27 vs. 20 days, P = 0.02). ICU (29%) and hospital (38%) mortality rates were identical in the two groups.
Conclusions
There are important differences in patient profiles related to the site of infection; however, mortality rates in these two groups of patients are identical.
doi:10.1186/cc8909
PMCID: PMC2887138  PMID: 20230620
17.  Evidence and consensus-based German guidelines for the management of analgesia, sedation and delirium in intensive care – short version 
Targeted monitoring of analgesia, sedation and delirium, as well as their appropriate management in critically ill patients is a standard of care in intensive care medicine. With the undisputed advantages of goal-oriented therapy established, there was a need to develop our own guidelines on analgesia and sedation in intensive care in Germany and these were published as 2nd Generation Guidelines in 2005. Through the dissemination of these guidelines in 2006, use of monitoring was shown to have improved from 8 to 51% and the use of protocol-based approaches increased to 46% (from 21%).
Between 2006–2009, the existing guidelines from the DGAI (Deutsche Gesellschaft für Anästhesiologie und Intensivmedizin) and DIVI (Deutsche Interdisziplinäre Vereinigung für Intensiv- und Notfallmedizin) were developed into 3rd Generation Guidelines for the securing and optimization of quality of analgesia, sedation and delirium management in the intensive care unit (ICU). In collaboration with another 10 professional societies, the literature has been reviewed using the criteria of the Oxford Center of Evidence Based Medicine. Using data from 671 reference works, text, diagrams and recommendations were drawn up. In the recommendations, Grade “A” (very strong recommendation), Grade “B” (strong recommendation) and Grade “0” (open recommendation) were agreed.
As a result of this process we now have an interdisciplinary and consensus-based set of 3rd Generation Guidelines that take into account all critically illness patient populations.
The use of protocols for analgesia, sedation and treatment of delirium are repeatedly demonstrated. These guidelines offer treatment recommendations for the ICU team. The implementation of scores and protocols into routine ICU practice is necessary for their success.
doi:10.3205/000091
PMCID: PMC2830566  PMID: 20200655
guideline; evidence; analgesia; sedation; delirium; monitoring; treatment; intensive care
18.  Perioperative indocyanine green clearance is predictive for prolonged intensive care unit stay after coronary artery bypass grafting - an observational study 
Critical Care  2009;13(5):R149.
Introduction
During cardiac surgery with cardiopulmonary bypass (CPB) haemodilution occurs. Hepatic dysfunction after CPB is a rare, but serious, complication. Clinical data have validated the plasma-disappearance rate of indocyanine green (PDR ICG) as a marker of hepatic function and perfusion. Primary objective of this analysis was to investigate the impact of haemodilutional anaemia on hepatic function and perfusion by the time course of PDR ICG and liver enzymes in elective CABG surgery. Secondary objective was to define predictors of prolonged ICU treatment like decreased PDR ICG after surgery.
Methods
60 Patients were subjected to normothermic CPB with predefined levels of haemodilution anaemia (haemotacrit (Hct) of 25% versus 20% during CPB). Hepatic function and perfusion was assessed by PDR ICG, plasma levels of aspartate aminotransferase (ASAT) and α-GST. Prolonged ICU treatment was defined as treatment ≥ 48 hours.
Results
Logistic regression analysis showed that all postoperative measurements of PDR ICG (P < 0.01), and the late postoperative ASAT (P < 0.01) measurement were independent risk factors for prolonged ICU treatment. The predictive capacity for prolonged ICU treatment was best of the PDR ICG one hour after admission to the ICU. Furthermore, the time course of PDR ICG as well as ASAT and α-GST did not differ between groups of haemodilutional anaemia.
Conclusions
Our study provides evidence that impaired PDR ICG as a marker of hepatic dysfunction and hypoperfusion may be a valid marker of prolonged ICU treatment. Additionally this study provides evidence that haemodilutional anaemia to a Hct of 20% does not impair hepatic function and perfusion.
Trial registration
[ISRCTN35655335]
doi:10.1186/cc8045
PMCID: PMC2784368  PMID: 19747406
19.  A positive fluid balance is associated with a worse outcome in patients with acute renal failure 
Critical Care  2008;12(3):R74.
Introduction
Despite significant improvements in intensive care medicine, the prognosis of acute renal failure (ARF) remains poor, with mortality ranging from 40% to 65%. The aim of the present observational study was to analyze the influence of patient characteristics and fluid balance on the outcome of ARF in intensive care unit (ICU) patients.
Methods
The data were extracted from the Sepsis Occurrence in Acutely Ill Patients (SOAP) study, a multicenter observational cohort study to which 198 ICUs from 24 European countries contributed. All adult patients admitted to a participating ICU between 1 and 15 May 2002, except those admitted for uncomplicated postoperative surveillance, were eligible for the study. For the purposes of this substudy, patients were divided into two groups according to whether they had ARF. The groups were compared with respect to patient characteristics, fluid balance, and outcome.
Results
Of the 3,147 patients included in the SOAP study, 1,120 (36%) had ARF at some point during their ICU stay. Sixty-day mortality rates were 36% in patients with ARF and 16% in patients without ARF (P < 0.01). Oliguric patients and patients treated with renal replacement therapy (RRT) had higher 60-day mortality rates than patients without oliguria or the need for RRT (41% versus 33% and 52% versus 32%, respectively; P < 0.01). Independent risk factors for 60-day mortality in the patients with ARF were age, Simplified Acute Physiology Score II (SAPS II), heart failure, liver cirrhosis, medical admission, mean fluid balance, and need for mechanical ventilation. Among patients treated with RRT, length of stay and mortality were lower when RRT was started early in the course of the ICU stay.
Conclusion
In this large European multicenter study, a positive fluid balance was an important factor associated with increased 60-day mortality. Outcome among patients treated with RRT was better when RRT was started early in the course of the ICU stay.
doi:10.1186/cc6916
PMCID: PMC2481469  PMID: 18533029
21.  Recombinant activated factor VIIa for the treatment of bleeding in major abdominal surgery including vascular and urological surgery: a review and meta-analysis of published data 
Critical Care  2008;12(1):R14.
Background
The purpose of this study was to determine the role of recombinant activated factor VII (rFVIIa) in abdominal, vascular, and urological surgery.
Methods
We conducted meta-analyses of case series and placebo-controlled studies reporting on the treatment or prophylaxis of bleeding with rFVIIa regarding 'reduction or cessation of bleeding', 'mortality', and 'thromboembolism'.
Results
All case reports (n = 15 case reports and 17 patients) documented an effect of rFVIIa in the treatment of bleeding. A meta-analysis of 10 case series revealed a reduction or cessation of bleeding in 39 out of 50 patients after administration of rFVIIa (estimated mean effect 73.2%, 95% confidence interval [CI] 51.0% to 95.4%) and a mean probability of survival of 53.0% (95% CI 26.4% to 79.7%). Among the rFVIIa responders, 19 out of 29 patients (66%) survived versus 1 out of 10 rFVIIa nonresponders (P = 0.003). Six out of 36 patients from the case series had a thromboembolic complication (estimated mean probability 16.5%, 95% CI 1.2% to 31.8%). Compared with a meta-analysis of eight placebo-controlled studies, no increased risk of thromboembolism was seen after administration of rFVIIa.
Conclusion
The meta-analysis of case series showed that, in a mean of 73% patients, rFVIIa achieved at least a reduction of bleeding and that the probability of survival is increased in patients responding to rFVIIa. rFVIIa was not associated with an increased risk of thromboembolism compared with placebo.
doi:10.1186/cc6788
PMCID: PMC2374636  PMID: 18279513
22.  Changes in sedation management in German intensive care units between 2002 and 2006: a national follow-up survey 
Critical Care  2007;11(6):R124.
Background
The aim of this study, conducted in 2006, was to find out whether changes in sedation management in German intensive care units took place in comparison with our survey from 2002.
Methods
We conducted a follow-up survey with a descriptive and comparative cross-sectional multi-center design. A postal survey was sent between January and May 2006, up to four times, to the same 269 hospitals that participated in our first survey in 2002. The same questionnaire as in 2002 was used with a few additional questions.
Results
Two hundred fourteen (82%) hospitals replied. Sixty-seven percent of the hospitals carried out changes in sedation management since the 2002 survey. Reasons for changes were published literature (46%), national guidelines (29%), and scientific lectures (32%). Sedation protocols (8% versus 52%) and a sedation scale (21% versus 46%) were used significantly more frequently. During sedation periods of up to 24 hours, significantly less midazolam was used (46% versus 35%). In comparison to 2002, sufentanil and epidural analgesia were used much more frequently in all phases of sedation, and fentanyl more rarely. For periods of greater than 72 hours, remifentanil was used more often. A daily sedation break was introduced by 34% of the hospitals, and a pain scale by 21%.
Conclusion
The increased implementation of protocols and scoring systems for the measurement of sedation depth and analgesia, a daily sedation break, and the use of more short-acting analgesics and sedatives account for more patient-oriented analgesia and sedation in 2006 compared with 2002.
doi:10.1186/cc6189
PMCID: PMC2246220  PMID: 18062820
23.  Prediction of volume response under open-chest conditions during coronary artery bypass surgery 
Critical Care  2007;11(6):R121.
Introduction
Adequate fluid loading is the first step of hemodynamic optimization in cardiac patients undergoing surgery. Neither a clinical approach alone nor conventional parameters like central venous pressure (CVP) and pulmonary capillary wedge pressure (PCWP) are thought to be sufficient for recognizing fluid deficiency or overload. The aim of this study was to evaluate the suitability of CVP, PCWP, global end-diastolic volume index (GEDVI), pulse pressure variation (PPV), and stroke volume variation (SVV) for predicting changes in the cardiac index (CI) and stroke volume index (SVI) after sternotomy.
Methods
In 40 patients, CVP, PCWP, GEDVI, PPV, SVV, and the CI were measured at two points of time. One measurement was performed after inducing anesthesia and one after sternotomy.
Results
A significant increase in heart rate, CI, and GEDVI was observed during the study period. CVP, SVV, and PPV decreased significantly. There were no significant correlations between CVP and PCWP and changes in CI. In contrast, GEDVI, SVV, and PPV significantly correlated with CI changes. Only relative changes of GEDVI, SVV, and PPV predicted changes in SVI.
Conclusion
During cardiac surgery and especially after sternotomy, CVP and PCWP are not suitable for monitoring fluid status. Direct volume measurement like GEDVI and dynamic volume responsive measurements like SVV and PPV may be more suitable for monitoring the volume status of patients, particularly under open-chest conditions.
doi:10.1186/cc6181
PMCID: PMC2246213  PMID: 18034888
24.  Comparison of uncalibrated arterial waveform analysis in cardiac surgery patients with thermodilution cardiac output measurements 
Critical Care  2006;10(6):R164.
Introduction
Cardiac output (CO) monitoring is indicated only in selected patients. In cardiac surgical patients, perioperative haemodynamic management is often guided by CO measurement by pulmonary artery catheterisation (COPAC). Alternative strategies of CO determination have become increasingly accepted in clinical practice because the benefit of guiding therapy by data derived from the PAC remains to be proven and less invasive alternatives are available. Recently, a device offering uncalibrated CO measurement by arterial waveform analysis (COWave) was introduced. As far as this approach is concerned, however, the validity of the CO measurements obtained is utterly unclear. Therefore, the aim of this study was to compare the bias and the limits of agreement (LOAs) (two standard deviations) of COWave at four specified time points prior, during, and after coronary artery bypass graft (CABG) surgery with a simultaneous measurement of the gold standard COPAC and aortic transpulmonary thermodilution CO (COTranspulm).
Methods
Data from 30 patients were analysed during this prospective study. COPAC, COTranspulm, and COWave were determined in all patients at four different time points prior, during, and after CABG surgery. The COPAC and the COTranspulm were measured by triple injection of 10 ml of iced isotone sodium chloride solution into the central venous line of the PAC. Measurements of COWave were simultaneously taken at these time points.
Results
The overall correlation showed a Spearman correlation coefficient between COPAC and COWave of 0.53 (p < 0.01) and 0.84 (p < 0.01) for COPAC and COTranspulm. Bland-Altman analysis showed a mean bias and LOAs of 0.6 litres per minute and -2.2 to +3.4 litres per minute for COPAC versus COWave and -0.1 litres per minute and -1.8 to +1.6 litres per minute for COPAC versus COTranspulm.
Conclusion
Arterial waveform analysis with an uncalibrated algorithm COWave underestimated COPAC to a clinically relevant extent. The wide range of LOAs requires further evaluation. Better results might be achieved with an improved new algorithm. In contrast to this, we observed a better correlation of thermodilution COTranspulm and thermodilution COPAC measurements prior, during, and after CABG surgery.
doi:10.1186/cc5103
PMCID: PMC1794471  PMID: 17118186
25.  Effects of dopexamine on the intestinal microvascular blood flow and leucocyte activation in a sepsis model in rats 
Critical Care  2006;10(4):R117.
Introduction
Dopexamine may be a therapeutic option to improve hepatosplanchnic perfusion in sepsis. To investigate this possibility, we administered dopexamine in an experimental sepsis model in rats.
Methods
This prospective, randomized, controlled laboratory study was conducted in 42 Wistar rats. The animals were divided into three groups. Group 1 served as the control group (CON group). The animals in both groups 2 (LPS group) and 3 (DPX group) received an endotoxin (lipopolysaccharide from Escherichia coli – LPS) infusion (20 mg/kg for 15 minutes). DPX group additionally received dopexamine (0.5 μg/kg per minute over four hours). One half of the animals in each group underwent studies of intestinal microvascular blood flow (IMBF) using laser Doppler fluxmetry. In the other half an intravital microscopic evaluation of leucocyte-endothelial cell interaction in intestinal microcirculation was conducted. Functional capillary density (FCD) in the intestinal mucosa and in the circular as well as longitudinal muscle layer was estimated.
Results
One hour after endotoxin challenge, IMBF decreased significantly in LPS group to 51% compared with baseline (P < 0.05). In DPX group (endotoxin plus dopexamine) we found IMBF values significantly higher than those in LPS group (approximately at the level of controls). The impaired FCD following endotoxin challenge was improved by dopexamine in the longitudinal muscle layer (+33% in DPX group versus LPS group; P < 0.05) and in the circular muscle layer (+48% in DPX group versus LPS group; P < 0.05). In DPX group, dopexamine administration reduced the number of firmly adherent leucocytes (-31% versus LPS group; P < 0.05). Plasma levels of tumour necrosis factor-α were reduced by dopexamine infusion (LPS group: 3637 ± 553 pg/ml; DPX group: 1933 ± 201 pg/ml) one hour after endotoxin challenge.
Conclusion
Dopexamine administration improved IMBF and FCD (markers of intestinal microcirculation) and reduced leucocyte activation (a marker of inflammation) in experimental sepsis.
doi:10.1186/cc5011
PMCID: PMC1750974  PMID: 16893450

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