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Practice guidelines are systematically developed statements and recommendations that assist the physicians and patients in making decisions about appropriate health care measures for specific clinical circumstances taking into account specific national health care structures. The 1st revision of the S-2k guideline of the German Sepsis Society in collaboration with 17 German medical scientific societies and one self-help group provides state-of-the-art information (results of controlled clinical trials and expert knowledge) on the effective and appropriate medical care (prevention, diagnosis, therapy and follow-up care) of critically ill patients with severe sepsis or septic shock. The guideline had been developed according to the “German Instrument for Methodological Guideline Appraisal” of the Association of the Scientific Medical Societies (AWMF). In view of the inevitable advancements in scientific knowledge and technical expertise, revisions, updates and amendments must be periodically initiated. The guideline recommendations may not be applied under all circumstances. It rests with the clinician to decide whether a certain recommendation should be adopted or not, taking into consideration the unique set of clinical facts presented in connection with each individual patient as well as the available resources.
Leitlinien sind systematisch entwickelte Darstellungen und Empfehlungen mit dem Zweck, Ärzte und Patienten bei der Entscheidung über angemessene Maßnahmen der Krankenversorgung unter spezifischen medizinischen Umständen und unter Berücksichtigung des spezifischen nationalen Gesundheitssystems zu unterstützen. Die erste Revision der S-2k-Leitlinie der Deutschen Sepsis-Gesellschaft in Kooperation mit 17 weiteren wissenschaftlichen medizinischen Fachgesellschaften und einer Selbsthilfegruppe gibt den Stand des Wissens (Ergebnisse von kontrollierten klinischen Studien und Wissen von Experten) über effektive und angemessene Krankenversorgung zum Zeitpunkt der „Drucklegung“ wieder. Die Leitlinienentwicklung erfolgte entsprechend des „Deutschen Instrumentes zur methodischen Leitlinien-Bewertung“ der Arbeitsgemeinschaft der Wissenschaftlichen Medizinischen Fachgesellschaften (AWMF). In Anbetracht der unausbleiblichen Fortschritte wissenschaftlicher Erkenntnisse und der Technik müssen periodische Überarbeitungen, Erneuerungen und Korrekturen unternommen werden. Die Empfehlungen der Leitlinien können nicht unter allen Umständen angemessen genutzt werden. Die Entscheidung darüber, ob einer bestimmten Empfehlung gefolgt werden soll, muß vom Arzt unter Berücksichtigung der beim individuellen Patienten vorliegenden Gegebenheiten und der verfügbaren Ressourcen getroffen werden.
(Based on the definition by the US Agency for Health Care Policy and Research for “Clinical Practice Guidelines”):
“Practice guidelines are systematically developed statements and recommendations that assist the physicians and patients in making decisions about appropriate health care measures (prevention, diagnosis, therapy and follow-up care) for specific clinical circumstances.”
The guidelines provide state-of-the-art information (results of controlled clinical trials and expert knowledge) on the effective and appropriate medical care at the time of “publication”. In view of the inevitable advancements in scientific knowledge and technical expertise, revisions, updates and amendments must be periodically initiated.
The guideline recommendations may not be applied under all circumstances. It rests with the clinician to decide whether a certain recommendation should be adopted or not, taking into consideration the unique set of clinical facts presented in connection with each individual patient as well as the available resources.
In devising these recommendations, the underlying studies were closely reviewed by the expert committee and classified into the following levels of evidence suggested by the Oxford Centre of Evidence Based Medicine:
The “all-or-none principle” (level of evidence Ic) allows for the classification of medical interventions that make an integral part of routine medical care without the requirement of relevant studies on hand because they cannot be conducted for ethical reasons (e.g. oxygen insufflation for hypoxia). Despite growing acceptance of systematic reviews, they must also be critically reviewed. A recent meta-analysis of some trials with a small number of cases has shown a protective effect of a certain therapy regimen , only to be later disproved be a subsequent large prospective trial . It must also be noted that meta-analyses may involve a selection of studies with positive results (publication bias).
Based on the levels of evidence, recommendations of the following level may be argued for a certain clinical issue :
The evidence level of the study is named that leads to the corresponding recommendation level. The expert committee may vote to decide to upgrade or downgrade the level of recommendation by one level. This reassessment must be substantiated (please also see the detailed methodology report).
Preliminary remarks: Sepsis is a complex systemic inflammatory reaction of the host to an infection. Currently, the diagnosis cannot be established based on any single parameter. Sepsis, severe sepsis and septic shock constitute a continuous spectrum of disease, characterized by a combination of vital parameters, laboratory parameters, hemodynamic data and organ functions. Depending on prior antibiotic therapy, bacteremia is found only in approximately 30% of patients with severe sepsis or septic shock , , , , . In approximately 30% of cases, no proof of infection backed by microbiological data can be furnished, although the clinical criteria make an infection likely , . Interpretation of microbiological findings in critically ill patients is often intricate because oftentimes microorganisms are identified that satisfy merely the definition of colonization. Critically ill patients often present with SIRS and multiple organ dysfunction; hence, an infectious cause-effect relationship often cannot be established with certainty.
Preliminary remarks: Ventilator-associated pneumonia (diagnosis of pneumonia established after more than 48 hours of mechanical ventilation in previously pneumonia-free patients) must be differentiated from pneumonia that requires ventilation assistance. The latter may be community-acquired or hospital-acquired (nosocomial pneumonia); diagnostic principles for each disease entity apply , . The previously recommended stratification scheme dividing ventilator-associated pneumonias into “early onset” (days 1–4) and “late onset” (after day 4) VAP and the corresponding different empiric antimicrobial therapy regimens , have been judged no longer indicated in a recent study by the National Reference Center for the Surveillance of Nosocomial Infections because the pathogen spectrum does not differ between the two groups .
Preliminary remarks: Bacterial meningitis occurs either primarily as a result of hematogenous or lymphogenic pathogen dissemination or secondarily by a direct entry of microorganisms into the CNS (most often a spreading infection, e.g. otitis, sinusitis, or iatrogenic, associated with medical procedures) . Of the 696 patients with community-acquired bacterial meningitis, almost all presented with at least 2 of the 4 typical symptoms such as headaches, nuchal rigidity, fever and impaired consciousness . The diagnosis of bacterial meningitis rests on a cytological/biochemical analysis of the cerebrospinal fluid (CSF)  and is confirmed upon detection of pathogens in the CSF , . CSF analysis typically gives a profile of granulocytic pleocytosis (>1,000 cells/µl); protein of >120 mg/dL; glucose of <30 mg/dL or CSF: serum glucose ratio of <0.3; lactate of >3.5 mmol/L , , .
Preliminary remarks: Multiple studies have demonstrated that selective decontamination of the digestive tract (SDD) reduced the rate of nosocomial infections in ICU patients, especially pneumonias and bacteremia cases , , . Moreover, 4 independent prospective randomized clinical trials have shown that SDD reduced mortality in ventilated ICU patients. Selective bowel decontamination consists of a 2- to 4-day intravenous administration of antibiotics, usually cefotaxime (unless the patient is already receiving antibiotic therapy) and topical application of non-resorbable antibiotics in the oropharyngeal cavity, as well as via a gastric tube, during the entire intubation period. In selected studies, a reduction in the incidence of pneumonia could also be achieved by a sole selective oral decontamination (SOD, without intravenous or gastric administration) . One study demonstrated similar positive effects of both SOD and SDD on improved survival .
Preliminary remarks: Thorough control of the septic source of infection is the (main) prerequisite for successful treatment of severe sepsis and septic shock. Inadequate infectious source control goes hand in hand with increased mortality , . Correspondingly, it has been demonstrated for various disease entities that the interval between the onset of septic symptoms and the implementation of adequate measures to control the septic focus is an important determinant of patient outcome , . Surgical infectious source control may be accomplished by one or more measures:
Preliminary remarks: Despite a number of improved supportive and adjuvant therapeutic measures, not much has changed in the last 20 years in respect to high mortality and morbidity caused by severe sepsis and septic shock. The reasons for it primarily include recognized deficits in establishing a timely diagnosis, shortcomings in the surgical (whenever possible) infectious source control and/or in antimicrobial therapy of the infectious source. A worldwide increase in resistance of the most important infectious agents against all standard antibiotics is not being offset by a comparable development of novel anti-infectious substances. Especially in the area of problematic Gram-negative infections caused by non-fermenters such as Pseudomonas aeruginosa, no new substances are to be expected in the foreseeable future. Hence, preventive measures as well as optimization of antimicrobial diagnostic and therapeutic strategies must be emphasized in current clinical practice and research. A broad, high-dose, timely instituted initial therapy, a de-escalation strategy guided by clinical parameters and molecular markers as well as limitation of therapy duration to 7–10 days (with exceptions) are of utmost importance. In view of the fact that the field of infectious diseases is expected to be plagued with dramatic problems in the future, immense weight will be placed on close collaboration among the experts from the fields of microbiology, hygiene and clinical infectious disease. No data on antimicrobial therapy in patients with severe sepsis are available from prospective randomized controlled therapeutic trials. The reason is that due to high mortality, these patients have so far been excluded from the approval studies for new antimicrobial substances. Hence, answers to important questions concerning therapy of sepsis unfortunately cannot be obtained. Statistical records of international surveillance systems list catheter and wound infections, urogenital infections and pneumonias as primary potential nosocomial sources of sepsis , . Substantially increased mortality is primarily associated with sepsis caused by pneumonia, abdominal and skin and soft tissue infections  because these infections more often result in organ dysfunction and hence a more severe course of sepsis. The significance of the site of infection for prognosis and assessment of pathogen epidemiology must be considered in devising a carefully selected antimicrobial therapy scheme. Epidemiological variability of infections, however, is high. Significant differences with regard to important infectious agents and resistance patterns are displayed not only between various countries and regions, but even between hospitals in the same city or between different ICUs of the same facility. Statistical data on pathogens and resistances should therefore be compiled separately for each individual hospital ward and reported at regular intervals.
Preliminary remarks: The goal of hemodynamic stabilization is to achieve an adequate cellular oxygen supply immediately upon recognition of severe sepsis or septic shock .
Preliminary remarks: The appearance of acute kidney injury (AKI) (Table 5 (Tab. 5)) in patients with severe sepsis and septic shock is an independent risk factor for mortality in this patient population . The optimization of the systemic hemodynamics is the most important measure used to positively affect the evolution and progression of AKI.
Adjunctive therapy is treatment used together with and in addition to causal and supportive sepsis therapy.
Preliminary remarks: A most recent meta-analysis  included 27 trials on the use of immunoglobulins. This is the only analysis which ran separate evaluations of trials on adults and on newborns and which created additional subgroups for studies involving IgM-enriched immunoglobulins (ivIgGAM) and non-IgM-enriched immunoglobulins (ivIgG). In adults, eight trials conducted with ivIgGAM on 60 patients revealed a pooled relative risk of mortality of 0.64 (95% CI 0.54–0.84). In contrast, the pooled effect of seven studies conducted with ivIgG on 932 patients was 0.85 (95% CI 0.73–0.99).
Introduction: In addition to the limitations to the health-related quality of life that have been compiled with validated test instruments (e.g. SF-36) , ,  a number of former sepsis patients suffer from functional impairments, which are categorized under the terms Critical Illness Polyneuropathy (CIP) or Critical Illness Myopathy (CIM), which have been in existence for over 20 years now . More than 70% of patients with septic shock and more than 60% of the ventilated patients as well as patients with severe sepsis show significant electrophysiological changes already three days after admission to intensive care . In addition to sepsis and mechanical ventilation, multiple organ dysfunction syndrome (MODS), ARDS, systemic inflammation, corticosteroids, impaired glucose metabolism as well as the duration of ICU inpatient stay also display associations with myopathic or neuropathic changes. In summary, in patients with CIP/CIM, difficulties with weaning from the ventilator (weaning failure) and prolonged post-hospitalization rehabilitation periods have been noted with increased frequency . The issues of delirium during intensive therapy and persistent residual neurocognitive impairments, post-traumatic distress disorder (PTSD) and states of depression ,  related to perihospital functional development have increasingly attracted notice. The degree of functional deficits resulting from sepsis and the actual quality of life of those affected may, however, be influenced by taking appropriate rehabilitation measures. However, currently there exist neither therapeutic rehabilitation standards nor any rehabilitation facilities tailored to the needs of these patients, as the long-term consequences of sepsis following ICU treatments are little known to the physicians responsible for further care of these patients. Before the introduction of DRGs, sepsis patients were treated in an acute hospital up to the point of 'safe discharge'; such settings generally do not have adequate rehabilitation resources. With the introduction of DRGs, these patients continue to be confronted with further problems. Due to the lack of future accounting principles, the acute care hospital is motivated to discharge the patients prematurely in order not to exceed the available per capita budget. Consequently, sepsis patients are now discharged even earlier from acute medical care settings. Targeted studies are needed to improve our understanding of the often long-term neurocognitive and motor/functional impairments in this patient population, and to identify possible preventive or therapeutic approaches .
From age 16 onwards, the following applies:
For a diagnosis of SIRS of infectious etiology without organ complication(s), the following requirements must be met:
The following two combinations are to be distinguished:
For a diagnosis of SIRS of infectious etiology with organ complication(s)* as well as a SIRS of non-infectious etiology with or without organ complication(s), at least two of the following four criteria must be met:
* with respect to the specifications on organ complications, the definitions of the German Sepsis Society apply (see Table 1 (Tab. 1)).
The guidelines have been developed in collaboration with the following medical scientific professional societies:
Deutsche Gesellschaft für Chirurgie (DGCH; [P.K.]), Deutsche Gesellschaft für Anästhesiologie und Intensivmedizin (DGAI; [R.R.]), Deutsche Gesellschaft für Herz-, Thorax- und Gefäßchirurgie (DGHTG; [G.M.]), Deutsche Gesellschaft für Internistische Intensivmedizin und Notfallmedizin (DGIIN; [T.W.]), Deutsche Gesellschaft für Pneumologie und Beatmungsmedizin (DGP; [T.W.]), Deutsche Gesellschaft für Ernährungsmedizin (DGEM; [A.W.]), Deutsche Gesellschaft für Neurologie (DGN; [J.B.]), Deutsche Gesellschaft für Kardiologie (DGK; [K.W]), Deutsche Gesellschaft für Innere Medizin (DGIM; [K.W.]), Deutsche Gesellschaft für Infektiologie (DGI; [W.K.]), Nationales Referenzzentrum für Surveillance von nosokomialen Infektionen (NRZ; [P.G.]), Deutsche Gesellschaft für Nephrologie (DGfN; [S.J., M.O.]), Deutsche Gesellschaft für Hygiene und Mikrobiologie e.V. (DGHM; [H.S.]), Deutsche Gesellschaft für Klinische Chemie und Laboratoriumsmedizin (DGKL), Deutsche Gesellschaft für Neurochirurgie (DGNC), Paul-Ehrlich-Gesellschaft für Chemotherapie e.V. (PEG),
and support groups:
Deutsche Sepsis-Hilfe e.V. (DSH; [F.M.B.])
Approved by the directors of the involved medical scientific societies on February 15th 2010.
The guidelines apply to standard situations and take into account current scientific knowledge. They should not limit the physician’s therapeutic autonomy. These guidelines were developed by the authors with great care; however, no responsibility can be assumed for accuracy – particularly as related to dosing information.
The guidelines are registered in the AWMF register with the no. 079/001 (http://leitlinien.net/079-001.htm).
The declarations of conflict of interest of all authors can be viewed on request.