RESUMEN
PURPOSE: Colloids are administered to more patients than crystalloids, although recent evidence suggests that colloids may possibly be harmful in some patients. The European Society of Intensive Care Medicine therefore assembled a task force to compile consensus recommendations based on the current best evidence for the safety and efficacy of the currently most frequently used colloids--hydroxyethyl starches (HES), gelatins and human albumin. METHODS: Meta-analyses, systematic reviews and clinical studies of colloid use were evaluated for the treatment of volume depletion in mixed intensive care unit (ICU), cardiac surgery, head injury, sepsis and organ donor patients. Clinical endpoints included mortality, kidney function and bleeding. The relevance of concentration and dosage was also assessed. Publications from 1960 until May 2011 were included. The quality of available evidence and strength of recommendations were based on the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach. RECOMMENDATIONS AND CONCLUSIONS: We recommend not to use HES with molecular weight ≥ 200 kDa and/or degree of substitution >0.4 in patients with severe sepsis or risk of acute kidney injury and suggest not to use 6% HES 130/0.4 or gelatin in these populations. We recommend not to use colloids in patients with head injury and not to administer gelatins and HES in organ donors. We suggest not to use hyperoncotic solutions for fluid resuscitation. We conclude and recommend that any new colloid should be introduced into clinical practice only after its patient-important safety parameters are established.
Asunto(s)
Coloides/uso terapéutico , Enfermedad Crítica/terapia , Medicina Basada en la Evidencia , Fluidoterapia/normas , Ensayos Clínicos como Asunto , Coloides/efectos adversos , Contraindicaciones , Fluidoterapia/métodos , Humanos , Metaanálisis como Asunto , Literatura de Revisión como Asunto , Medición de Riesgo , Análisis de Supervivencia , Resultado del TratamientoRESUMEN
PURPOSE: To study the value of free versus total cortisol levels in assessing relative adrenal insufficiency during critical illness-related corticosteroid insufficiency. METHODS: A prospective study in a mixed intensive care unit from 2004 to 2007. We consecutively included 49 septic and 63 non-septic patients with treatment-insensitive hypotension in whom an adrenocorticotropic hormone (ACTH) test (250 µg) was performed. Serum total and free cortisol (equilibrium dialysis), corticosteroid-binding globulin (CBG) and albumin were assessed. RESULTS: Although a low CBG resulted in a high free cortisol level relative to total cortisol, free and total cortisol and their increases were well correlated (r = 0.77-0.79, P < 0.001). In sepsis, hypoalbuminemia did not affect total and free cortisol, and increases in total cortisol upon ACTH predicted increases in free cortisol regardless of low binding proteins. In non-sepsis, total cortisol was lower with than without hypoalbuminemia; free cortisol did not differ, since hypoalbuminemia concurred with a low CBG. Increases in total cortisol depended less on binding proteins than on raw levels. The areas under the receiver operating characteristic curve for predicting increases in free from total cortisol were 0.93-0.97 in sepsis and 0.79-0.85 in non-sepsis (P = 0.044 or lower for sepsis vs. non-sepsis). CONCLUSIONS: Although the biologically active free cortisol fraction depends on binding proteins, total cortisol correlates to free cortisol in treatment-insensitive hypotension during critical illness. In sepsis, albumin is not an important binding molecule. Subnormal increments in total cortisol upon ACTH suffice in assessing relative adrenal insufficiency, particularly in sepsis.
Asunto(s)
Insuficiencia Suprarrenal/diagnóstico , Enfermedad Crítica , Hidrocortisona/metabolismo , Unidades de Cuidados Intensivos , Insuficiencia Suprarrenal/complicaciones , Adulto , Anciano , Anciano de 80 o más Años , Albúminas/análisis , Femenino , Humanos , Hidrocortisona/sangre , Masculino , Persona de Mediana Edad , Países Bajos , Estudios Prospectivos , Sepsis/etiología , Sepsis/fisiopatología , Transcortina/análisisRESUMEN
BACKGROUND: Sepsis and acute lung injury (ALI)/acute respiratory distress syndrome (ARDS) are life-threatening syndromes characterised by inflammation and increased vascular permeability. Amongst other factors, the angiopoietin-tyrosine kinase with immunoglobulin-like and EGF-like domains 2 (Tie2) system is involved. OBJECTIVE: To explore whether the angiopoietin-Tie2 system provides suitable targets for the treatment of sepsis and ALI/ARDS. METHODS: Original experimental and patient studies on angiopoietins and sepsis/endotoxemia, inflammation, lung injury, hyperpermeability, apoptosis, organ functions and vital outcomes were reviewed. RESULTS/CONCLUSION: The angiopoietin-Tie2 system controls the responsiveness of the endothelium to inflammatory, hyperpermeability, apoptosis and vasoreactive stimuli. Angiopoietin-2 provokes inflammation and vascular hyperpermeability, while angiopoietin-1 has a protective effect. Targeted angiopoietin-2 inhibition with RNA aptamers or blocking antibodies is a potential anti-inflammatory and anti-vascular hyperpermeability strategy in the treatment of sepsis and ALI/ARDS.
Asunto(s)
Lesión Pulmonar Aguda/tratamiento farmacológico , Angiopoyetinas/antagonistas & inhibidores , Receptor TIE-2/efectos de los fármacos , Sepsis/tratamiento farmacológico , Angiopoyetinas/fisiología , Humanos , Receptor TIE-2/fisiologíaRESUMEN
Stress hyperglycaemia is a common event in acute critical illness. There is increasing evidence that maintaining normoglycaemia and treatment with insulin (or with glucose-insulin-potassium [GIK]), even in non-diabetic persons, is helpful in limiting organ damage after myocardial infarction, stroke, traumatic brain injury and other conditions, even though the conditions may be accompanied by insulin resistance. A landmark study now suggests that maintaining normoglycaemia with intensive insulin treatment in a heterogeneous population of critically ill patients decreases morbidity and mortality. The potential mechanisms that underlie such a beneficial effect are discussed.
Asunto(s)
Cuidados Críticos , Hipoglucemiantes/uso terapéutico , Insulina/uso terapéutico , Animales , Humanos , Factor I del Crecimiento Similar a la Insulina/efectos de los fármacos , RatasRESUMEN
To evaluate the contribution of an imbalance between coagulation activation and fibinolysis activation and inhibition to morbidity and mortality in sepsis, we determined in medical hospitalized patients at inclusion (day 0) for fever (temperature above 38.0 degrees C axillary or 38.3 degrees C rectally), and daily thereafter for two days, circulating thrombin-antithrombin III (TAT) complexes, plasmin-alpha2-antiplasmin (PAP) complexes (day 0 only), tissue-type plasminogen activator (t-PA), plasminogen activator inhibitor-1 (PAI-1) and interleukin (IL)-6, the latter as a marker of the inflammatory host response. Study variables were 1) positive microbiological results for specimens from local sites associated with a clinical infection, positive blood cultures (including parasitemia) or both, within 7 days after inclusion, 2) development of shock, i.e. systolic blood pressure <90 mmHg or a reduction of 40 mmHg from baseline within 7 days after inclusion, and 3) death related to febrile illness within 28 days after inclusion. The peak plasma levels of TAT complexes were elevated in 44% and the PAP complexes in all patients. The t-PA and PAI-1 levels were elevated in 74 and 94% of patients, respectively. Values for TAT and PAP did not differ among subgroups, while peak t-PA and IL-6 levels were higher in patients with positive microbiological results, developing shock or ultimately dying than in those without the complications (p<0.005). Peak PAI-1 levels were elevated in patients developing shock and ultimate death versus those with an uncomplicated course (p <0.05). Peak IL-6 related to PAI-1 and t-PA levels, which interrelated. Patients with elevated TAT levels had increased plasma levels of IL-6, PAP, PAI-1 and t-PA versus those with normal TAT (p <0.05). Our data indicate that inhibition of activated fibrinolysis, which may partly depend on both cytokinemia and activation of coagulation, predicts microbial infection, septic shock and mortality of febrile medical patients. This suggests an early pathogenic role of inhibition of activated fibrinolysis in the downhill course of serious microbial infection.