[What lipid emulsion should be administered to ICU patients?].

The review deals with a question what lipid emulsion should be administered to ICU patients according to recently published official parenteral and enteral nutrition guidelines. Classic lipid emulsions based on omega-6 fatty acids are immunosuppressive and should not be used with ICU patients. The olive/soy emulsion is immunoneutral and can be used for most patients. Many ICU patients are in an inflammatory state (e.g. sepsis, ARDS, pancreatitis). A common belief is that this "hyperinflammed patient population" would profit from an anti-inflammatory lipid component of their parenteral nutrition solution, such as fish oil. On the other hand, every anti-inflammatory therapy has the disadvantage of also being immunosuppressive. Inflammation is a necessary part of the host defense against infection and any correct anti-inflammatory medication presupposes the exact immunologic knowledge that there is too much inflammation for a given situation. This "too much" is certainly not fulfilled in every patient with sepsis, ARDS or pancreatitis. At the bedside it is nearly impossible to determine the degree of "hyper" inflammation. In reality, a number of these patients may be adequately inflamed or, in fact, even hypoinflammed. Specific emulsions which can be used in hyper- or hypoinflammation should be developed in the future. As long as these difficulties in the immunologic diagnosis prevail, the clinician might be best advised to use an immunoneutral lipid emulsion when choosing a lipid preparation for the ICU patients.

Prevention, diagnosis, therapy and follow-up care of sepsis: 1st revision of S-2k guidelines of the German Sepsis Society (Deutsche Sepsis-Gesellschaft e.V. (DSG)) and the German Interdisciplinary Association of Intensive Care and Emergency Medicine (Deutsche Interdisziplinäre Vereinigung für Intensiv- und Notfallmedizin (DIVI)).

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 1(st) 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.

Intensive medicine - Guidelines on Parenteral Nutrition, Chapter 14.

In intensive care patients parenteral nutrition (PN) should not be carried out when adequate oral or enteral nutrition is possible. Critically ill patients without symptoms of malnutrition, who probably cannot be adequately nourished enterally for a period of <5 days, do not require full PN but should be given at least a basal supply of glucose. Critically ill patients should be nourished parenterally from the beginning of intensive care if they are unlikely to be adequately nourished orally or enterally even after 5-7 days. Critically ill and malnourished patients should, in addition to a possible partial enteral nutrition, be nourished parenterally. Energy supply should not be constant, but should be adapted to the stage, the disease has reached. Hyperalimentation should be avoided at an acute stage of disease in any case. Critically ill patients should be given, as PN, a mixture consisting of amino acids (between 0.8 and 1.5 g/kg/day), carbohydrates (around 60% of the non-protein energy) and fat (around 40% of the non-protein energy) as well as electrolytes and micronutrients.

Carbohydrates - Guidelines on Parenteral Nutrition, Chapter 5.

The main role of carbohydrates in the human body is to provide energy. Carbohydrates should always be infused with PN (parenteral nutrition) in combination with amino acids and lipid emulsions to improve nitrogen balance. Glucose should be provided as a standard carbohydrate for PN, whereas the use of xylite is not generally recommended. Fructose solutions should not be used for PN. Approximately 60% of non-protein energy should be supplied as glucose with an intake of 3.0-3.5 g/kg body weight/day (2.1-2.4 mg/kg body weight/min). In patients with a high risk of hyperglycaemia (critically ill, diabetes, sepsis, or steroid therapy) an lower initial carbohydrate infusion rate of 1-2 g/kg body weight/day is recommended to achieve normoglycaemia. One should aim at reaching a blood glucose level of 80-110 mg/dL, and at least a glucose level <145 mg/dL should be achieved to reduce morbidity and mortality. Hyperglycaemia may require addition of an insulin infusion or a reduction (2.0-3.0 g/kg body weight/day) or even a temporary interruption of glucose infusion. Close monitoring of blood glucose levels is highly important.

Energy expenditure and energy intake - Guidelines on Parenteral Nutrition, Chapter 3.

The energy expenditure (24h total energy expenditure, TEE) of a healthy individual or a patient is a vital reference point for nutritional therapy to maintain body mass. TEE is usually determined by measuring resting energy expenditure (REE) by indirect calorimetry or by estimation with the help of formulae like the formula of Harris and Benedict with an accuracy of +/-20%. Further components of TEE (PAL, DIT) are estimated afterwards. TEE in intensive care patients is generally only 0-7% higher than REE, due to a low PAL and lower DIT. While diseases, like particularly sepsis, trauma and burns, cause a clinically relevant increase in REE between 40-80%, in many diseases, TEE is not markedly different from REE. A standard formula should not be used in critically ill patients, since energy expenditure changes depending on the course and the severity of disease. A clinical deterioration due to shock, severe sepsis or septic shock may lead to a drop of REE to a level only slightly (20%) above the normal REE of a healthy subject. Predominantly immobile patients should receive an energy intake between 1.0-1.2 times the determined REE, while immobile malnourished patients should receive a stepwise increased intake of 1.1-1.3 times the REE over a longer period. Critically ill patients in the acute stage of disease should be supplied equal or lower to the current TEE, energy intake should be increased stepwise up to 1.2 times (or up to 1.5 times in malnourished patients) thereafter.

[Immunoglobulins in primary antibody deficiency: should they also be used in sepsis and other indications?]. / Immunglobuline bei Antikörpermangelsyndrom: Einsatz auch bei Sepsis und anderen Indikationen?

Immunoglobulin is a blood product prepared from the plasma of healthy donors. The therapeutic use of polyvalent immunoglobulins is an established therapy in primary antibody deficiencies, in idiopathic thrombocytopenic purpura (ITP) and in Guillain-Barré syndrome. However, there is an ongoing debate about the efficacy of polyvalent immunoglobulins as adjunctive therapy for sepsis. The paper presented here critically discusses the modern studies investigating the use of immunoglobulins in different diseases. The main focus is the use of immunoglobulins in patients with sepsis or septic shock.

[Diagnosis and therapy of sepsis: guidelines of the German Sepsis Society Inc. and the German Interdisciplinary Society for Intensive and Emergency Medicine]. / Diagnose und therapie der sepsis: S2-Leitlinien der Deutschen Sepsis-Gesellschaft e.V. (DSG) und der Deutschen Interdisziplinären Vereinigung für Intensiv- und Notfallmedizin (DIVI).

A recent survey conducted by the publicly funded Competence Network Sepsis (SepNet) 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 approximately 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 approximately 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 organization 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 the requirements of the Working Group of Scientific Medical Societies (AWMF).

[Diagnosis and therapy of sepsis]. / Diagnose und Therapie der Sepsis - S-2 Leitlinien der Deutschen Sepsis-Gesellschaft e.V. (DSG) und der Deutschen Interdisziplinären Vereinigung für Intensiv- und Notfallmedizin (DIVI).

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).

[Targeted cardiovascular therapy: shock treatment in ambulance, emergency room and intensive care unit]. / Zielgerichtete Kreislauftherapie. Schockbehandlung in Notarztwagen, Notaufnahme und Intensivstation.

Since the prognosis for all forms of shock essentially depends on immediate and effective therapy, early diagnosis and determination of the underlying cause are of central importance to the disease course. Except for cardiogenic shock, all forms of shock require early and adequate fluid substitution. It has previously been shown that septic shock treatment guided by central venous oxygen saturation may lead to a reduction in mortality in patients with septic shock. Similar therapeutic strategies are currently being developed for the more invasive monitoring procedures used in intensive care, but their effectiveness has to yet to be proven. Novel therapeutic approaches for the treatment of septic shock include improved adjunctive sepsis therapy and the use of vasopressin. However, the effectiveness of the latter treatment option cannot yet be conclusively assessed.

[Diagnosis and therapy of sepsis. Guidelines of the German Sepsis Society Inc. and the German Interdisciplinary Society for Intensive and Emergency Medicine]. / Diagnose und Therapie der Sepsis. S2-Leitlinien der Deutschen Sepsis-Gesellschaft e.V. (DSG) und der Deutschen Interdisziplinären Vereinigung für Intensiv- und Notfallmedizin (DIVI).

A recent survey conducted by the publicly funded Competence Network Sepsis (SepNet) 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 approximately 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 approximately 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 organization 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 the requirements of the Working Group of Scientific Medical Societies (AWMF).

[Pylephlebitis with air in the portal vein system. An unusual focus in a patient with sepsis]. / Pylephlebitis mit Luft im Pfortadersystem. Ungewöhnlicher Fokus bei einem Patienten mit Sepsis.

HISTORY AND CLINICAL FINDINGS: A 30-year-old male was transferred to the intensive care unit with worsening sepsis of unknown origin and a known history of Crohn's disease. The patient presented with a five-day history of nausea, fever, and serous diarrhea. Clinical examination of the abdomen was unremarkable except for mild epigastric pain on palpation. INVESTIGATIONS: Computed tomography (CT) of the abdomen revealed gas within the intrahepatic branches of the portal venous system, thickening of the wall of the neoterminal ileum, and mild ascites. In addition, ultrasonography showed acute thrombosis of the portal vein and the superior mesenteric vein. No wall perfusion was seen in either the neoterminal ileum or the ascending colon on color Doppler sonography. DIAGNOSIS, TREATMENT AND COURSE: Based on the combination of portal vein thrombosis along with venous gas in the portal venous system and absence of intestinal perfusion, the diagnosis of pylephlebitis with septic shock was suspected and a laparotomy was performed. Intraoperative exploration revealed phlegmonous terminal ileitis, a significant amount of cloudy fluid, and thrombosis of the mesenteric vein. A right-sided hemicolectomy with ileotransversostomy was performed. Histologic examination confirmed Crohn's disease that was associated with vasculitis and, in particular, with thrombophlebitis and subsequent transmural bowel necrosis. Antibiotic and anticoagulation therapy was resumed without further complications. CONCLUSION: In the differential diagnosis of sepsis, especially in combination with abdominal pain or gas in the portal venous system, pylephlebitis should be taken into account. Because of the high mortality, immediate further diagnostic testing and appropriate therapy of this rare diagnosis are necessary.

[Lysis therapy in aortic dissection: by hypertrophic cardiomyopathy simulated myocardial infarct]. / Lysetherapie bei Aortendissektion: Durch hypertrophe Kardiomyopathie vorgetäuschter Myokardinfarkt.

A 52-year-old patient presenting with severe thoracic pain of more than 30 minutes duration and ST-segment elevation > 1 mV in leads V1-3 was given 100 mg rt-PA. With persisting thoracic pain and ST-segment elevation, coronary angiography was performed 90 minutes after administration of thrombolytic therapy. Surprisingly, angiography revealed normal coronary arteries in presence of marked hypertrophic cardiomyopathy. New onset of thoracic pain after four hours led to a chest radiograph demonstrating increased mediastinal widening and new pleural effusion as compared to a baseline chest film prior to rt-PA. Spiral computed tomography revealed overt Type B aortic dissection with an intimal flap and communication distal to the origin of the left subclavian artery with signs of a mediastinal hematoma. Immediate cardiac surgery with replacement of the dissected aortic segment was successfully performed. A literature review revealed 4% of aortic dissection to present with electrocardiographic signs of acute myocardial infarction and 13% to have concomitant coronary artery disease; moreover 34 cases of aortic dissection were misdiagnosed as infarction and subjected to thrombolytic agents with a mortality of 64% underlining the importance of exclusion of dissection prior to thrombolytic therapy.

[Pro-inflammatory cytokines IL-1 beta and TNF-alpha reduce growth hormone receptor mRNA concentration in cultivated rat hepatocytes after stimulation with growth hormone]. / Die proinflammatorischen Zytokine IL-1 beta und TNF-alpha vermindern die Wachstumshormonrezeptor-mRNA-Konzentration in kultivierten Rattenhepatozyten nach Stimulation durch Wachstumshormon.

Critical illness is associated with catabolism caused by the alteration of several hormonal systems. Low levels of insulin-like growth factor I (IGF-I) in critical illness are observed despite increased or normal levels of growth hormone (GH). The mechanisms for this apparent GH resistance have not been elucidated. Since proinflammatory cytokines mediate many of the acute responses in critical illness, we evaluated the effects of IL-1 beta and TNF-alpha on growth hormone receptor-(GHR-)mRNA in cultured rat hepatocytes. Diminished GHR-mRNA concentrations in response to cytokine stimulation indicate that low IGF-I levels in the beginning of severe illness, may at least be partially a cause of GHR synthesis suppression by proinflammatory cytokines.

Emergency room triage of patients with acute chest pain by means of rapid testing for cardiac troponin T or troponin I.

BACKGROUND: Evaluation of patients with acute chest pain in emergency rooms is time-consuming and expensive, and it often results in uncertain diagnoses. We prospectively investigated the usefulness of bedside tests for the detection of cardiac troponin T and troponin I in the evaluation of patients with acute chest pain. METHODS: In 773 consecutive patients who had had acute chest pain for less than 12 hours without ST-segment elevation on their electrocardiograms, troponin T and troponin I status (positive or negative) was determined at least twice by sensitive, qualitative bedside tests based on the use of specific monoclonal antibodies. Testing was performed on arrival and four or more hours later so that one sample was taken at least six hours after the onset of pain. The troponin T results were made available to the treating physicians. RESULTS: Troponin T tests were positive in 123 patients (16 percent), and troponin I tests were positive in 171 patients (22 percent). Among 47 patients with evolving myocardial infarction, troponin T tests were positive in 44 (94 percent) and troponin I tests were positive in all 47. Among 315 patients with unstable angina, troponin T tests were positive in 70 patients (22 percent), and troponin I tests were positive in 114 patients (36 percent). During 30 days of follow-up, there were 20 deaths and 14 nonfatal myocardial infarctions. Troponin T and troponin I proved to be strong, independent predictors of cardiac events. The event rates in patients with negative tests were only 1.1 percent for troponin T and 0.3 percent for troponin I. CONCLUSIONS: Bedside tests for cardiac-specific troponins are highly sensitive for the early detection of myocardial-cell injury in acute coronary syndromes. Negative test results are associated with low risk and allow rapid and safe discharge of patients with an episode of acute chest pain from the emergency room.

Proinflammatory cytokines interleukin 1 beta and tumor necrosis factor alpha inhibit growth hormone stimulation of insulin-like growth factor I synthesis and growth hormone receptor mRNA levels in cultured rat liver cells.

Low levels of insulin-like growth factor I (IGF-I) in critical illness are observed despite increased or normal levels of growth hormone (GH). The mechanisms for this apparent GH resistance have not been elucidated. As many of the acute inflammatory responses in critical illness are mediated by the proinflammatory cytokines interleukin 1 beta (IL-1 beta) and tumor necrosis factor alpha (TNF-alpha), the present studies evaluated IL-1 beta and TNF-alpha effects on steady-state and GH-stimulated IGF-I synthesis and GH receptor mRNA levels. In rat hepatocytes in primary culture, IGF-I released into culture medium was determined by radioimmunoassay, and quantitative competitive polymerase chain reaction was used to measure IGF-I mRNA and GH receptor mRNA concentrations. Growth hormone increased GH receptor mRNA, IGF-I mRNA and IGF-I protein secreted into the culture medium. In cells not stimulated with GH, modest inhibitory effects of IL-1 beta on GH receptor mRNA, IGF-I mRNA and IGF-I protein levels were seen. However, the stimulatory effects of GH were inhibited in a dose-dependent manner both by IL-1 beta and TNF-alpha, and at higher cytokine concentrations no stimulatory effects of GH were observed. Both IL-1 beta and TNF-alpha in submaximal dose had additive inhibitory effects on IGF-I protein concentrations but these effects did not result in irreversible damage to cells, as indicated by restoration of IGF-I and GH receptor mRNA levels to normal after withdrawal of cytokines. In conclusion, we demonstrated that in rat hepatocytes in primary culture IL-1 beta and TNF-alpha inhibited GH-stimulated IGF-I synthesis. Diminished GH receptor mRNA concentrations in response to IL-1 beta and TNF-alpha indicate that low IGF-I levels during severe illness, despite high circulating GH levels, may at least partially be a consequence of suppression of hepatic GH receptor synthesis by IL-1 beta and TNF-alpha.

[History and definition of sepsis--do we need new terminology?]. / Geschichte und Definition der Sepsis--Brauchen wir eine neue Terminologie?

The history of sepsis demonstrates that despite current knowledge about its pathogenesis the definition of sepsis is more contested than ever. However, a definite terminology is necessary to define the entrance criteria for future clinical studies concerning patients with sepsis or septic shock. For this purpose, in 1991 a consensus conference was held in the US, but its recommendations have not found unequivocal acceptance. These recommendations and their historical background are presented and their consequences discussed.

Body composition and energy expenditure in thyroidectomized patients during short-term hypothyroidism and thyrotropin-suppressive thyroxine therapy.

Thyroid hormone levels are a major determinant of energy balance and are thought to modify body composition by their effects on metabolism of lipids, carbohydrate and protein. The present study evaluates changes of body composition and basal energy expenditure (BEE) in thyroidectomized patients studied during short-term profound hypothyroidism while off all thyroid hormone before diagnostic whole-body (131)I-imaging and while on thyrotropin-suppressive thyroxine therapy. Basal energy expenditure was assessed by indirect calorimetry, and four-point body impedance analysis was used to estimate body composition. Patients were compared with healthy controls matched with respect to sex, age, height and weight. Compared to healthy controls the percentages of body water and body cell mass were significantly lower while the percentage of fat was significantly higher in patients during short-term hypothyroidism. Weight did not change significantly when patients were put on thyroxine treatment, but body fat (-0.95 +/- 2.25 kg, p < 0.01) decreased while body water (+0.94 +/- 1.31 kg, p < 0.01) and body cell mass (+0.9 +/- 2.5 kg, p < 0.05) increased. With thyroxine replacement, body composition was not significantly different between patients and controls. Compared to healthy controls, BEE was significantly lower in patients without thyroxine replacement (5265 +/- 766 kJ/24h vs 6362 +/- 992 kJ/24h; p < 0.001). With thyroxine treatment, BEE increased (6492 +/- 967 kJ/24h) but was not significantly different from the controls (p > 0.05). Neither body composition nor BEE was significantly different in a subgroup of thyroxine-treated patients with free triiodothyronine or thyroxine values above the normal range. In conclusion, both body composition and energy expenditure showed significant changes when patients were deprived of thyroid hormone. However, no evidence of excess metabolic effects of thyroid hormone during thyrotropin-suppressive thyroxine therapy was found.

[Primary diagnosis and follow-up in acute pulmonary embolism: comparison of digital subtraction angiography and spiral CT]. / Primärdiagnostik und Verlaufskontrolle der akuten Lungenembolie: Vergleich zwischen digitaler Subtraktionsangiographie und Spiral-CT.

The aim of this prospective study was to evaluate Spiral CT in the primary diagnosis of acute pulmonary emboli and for follow-up after thrombolytic treatment. Digital subtraction angiography of the lung was used as the reference method. 38 patients were subjected to both procedures. 79% of Spiral CT and 63% of DSA examinations were optimal. The two methods agreed in the diagnosis of thrombo-embolism in 30 patients and excluded it in eight patients. Spiral CT verified thrombi in a total of 213 cases; of these 23 were in a main pulmonary artery (11%), 88 in lobar arteries (41%), and 102 in segmental arteries (48%). DSA demonstrated 180 thrombi. 17% of the adherent and partially occlusive thrombi were not shown. 38 pulmonary infarcts were found in 18 patients. In 15 patients resolution of thrombi following thrombolytic treatment was shown by Spiral CT. Spiral CT is an excellent alternative to DSA and its use in the diagnosis of pulmonary emboli is entirely appropriate.