[Glycemic control in sepsis and septic shock: friend or foe?]. / Blutzuckerkontrolle bei Patienten mit Sepsis und septischem Schock: Freund oder Feind?

INTRODUCTION: Intensive care patients commonly suffer from hyperglycemia. Evidence is growing that strictly maintaining normoglycemia by intensive insulin therapy (IIT) ameliorates outcome in these patients. Whether or not this also holds true for patients with sepsis and septic shock is the issue of this post-hoc analysis of the database (2,748 patients) of 2 recent prospective clinical trials. MATERIAL AND METHODS: A total of 950 patients suffering from sepsis were identified and of these 462 fulfilled the diagnostic criteria of septic shock upon admission to the intensive care unit (ICU). Patients were treated by either IIT [mean glycemia 5.88 mmol/l (106 mg/dl)] or conventional glucose management [mean glycemia 8.44 mmol/l (152 mg/dl)]. RESULTS: Under IIT the mortality of patients treated for more than 3 days in the ICU was lowered by 7.6% (p=0.03) in septic patients and by 8.7% (p=0.08) in septic shock patients. Polyneuropathy occurred less frequently under IIT compared to conventional glucose management (sepsis -9.8%, septic shock -14%; p<0.001). The incidence of acute renal failure was not affected by either treatment regimen (sepsis -3.3%, septic shock -3.1%; p<0.25). Intensive insulin therapy was associated with an increased risk of hypoglycemia (sepsis +16.7%, septic shock +18.8; p<0.0001) which did not, however, directly affect morbidity nor mortality. CONCLUSIONS: These data suggest that IIT improves outcome of patients with sepsis or septic shock. Hypoglycemia is a frequent complication, but its clinical relevance remains to be defined.

[Value of surfactant replacement therapy in the treatment of acute respiratory distress syndrome]. / (K)eine Surfactant-Therapie bei Patienten mit "acute respiratory distress syndrome"? : Bedeutung einer Surfactant-Substitutionstherapie in der Behandlung des akuten Lungenversagens.

Acute respiratory distress syndrome (ARDS) is a common, devastating clinical problem arising from a number of conditions, such as pneumonia, trauma or sepsis. Because of its significant mortality and morbidity, ARDS has been in the focus of extensive experimental and clinical research. Since there is little doubt that alterations of the surfactant system contribute to lung dysfunction and the onset of ARDS, several clinical studies examined the therapeutic safety and efficacy of a surfactant replacement therapy. Clinical experience with exogenous surfactant has proven inconsistent as a therapeutic modality for adult patients with ARDS. This is mainly due to a number of confounding factors, e.g. severity of injury at the time of treatment, dosing regimes and delivery methods used in different trials. However, current data suggest that patients with direct ARDS (e.g. pneumonia, aspiration) could benefit from surfactant replacement therapy rather than patients with indirect ARDS (e.g. sepsis, trauma). Although surfactant replacement therapy has been shown to significantly reduce mortality in neonates with ARDS, there has been no large randomised clinical trial showing that exogenous surfactant improves outcome in adults with respiratory failure. Therefore, surfactant therapy cannot be recommended for routine clinical use in adult patients and has to be considered as a last resort treatment.

[Role of adrenomedullin in the pathogenesis and treatment of cardiovascular dysfunctions and sepsis]. / Bedeutung von Adrenomedullin Pathogenese und Behandlung kardiovaskulärer Dysfunktionen der Sepsis.

Adrenomedullin (AM) is an endogenous vasodilatory peptide hormone, which plays a key role in the regulation and preservation of cardiovascular and pulmonary functions. Clinical and experimental studies have demonstrated that AM represents an alternative therapeutic option in the treatment of pulmonary hypertension. In addition, AM proved to be useful in the treatment of cardiovascular dysfunctions, such as arterial hypertension and congestive heart failure following myocardial infarction. Recent research has also shown that AM plays a pivotal role in the development of sepsis-associated hemodynamic and microcirculatory disorders. Experimental studies also suggest that infusion of exogenous AM might be a rational approach to prevent and treat hypodynamic septic shock. The objectives of this review article are to characterize the regulative properties of AM and to discuss clinical and experimental studies which allow to judge the role of AM in the setting of cardiovascular dysfunction and sepsis.

Role of nitric oxide in sepsis-associated pulmonary edema.

Transient pulmonary hypertension after inhibition of nitric oxide synthase (NOS) does not alter pulmonary reflection coefficients or lymph flows in endotoxemic sheep. To test the effects of persistent pulmonary hypertension induced by N omega-nitro-L-arginine methylester (L-NAME) and of inhaled NO on pulmonary edema, 18 sheep (three groups) were chronically instrumented with pulmonary artery catheters, femoral arterial fiberoptic thermistor catheters, and tracheostomy. The awake, spontaneously breathing animals received Salmonella typhi endotoxin (lipopolysaccharide; LPS) (10 ng/kg/ min) for 28 h. After 24 h, an airflow of 6 L/min was delivered through the tracheostomy. One group of animals (L-NAME/air) received L-NAME intravenously (25 mg/kg + 5 mg/kg/h) and breathed air. The second group (L-NAME/NO) was given L-NAME and NO (40 ppm) was added to the airflow. The third group was given NaCl 0.9% and breathed air (NaCl/air). Extravascular lung water was measured through the double-indicator dilution technique. Endotoxemia caused pulmonary edema, which was aggravated by L-NAME. Breathing of NO normalized pulmonary artery pressure (Ppa) and ameliorated pulmonary edema. Inhalation of NO may therefore be a therapeutic option for pulmonary edema associated with pulmonary hypertension.