Sepsis en una unidad de terapia intensiva polivalente: revisión de 2 años

Se analizaron retrospectivamente todas las historias clínicas de los pacientes ingresados al Servicio de Tera­pia Intensiva del Hospital Escuela desde enero de 2006 a diciembre de 2007, con el objetivo de evaluar inciden­ cia, factores de riesgo, foco infeccioso, fallos orgánicos, esquemas antibióticos y mortalidad relacionados a la sepsis. Ingresaron al estudio 531 pacientes, 156 tuvie­ron sepsis, de los cuales 108 pacientes (69,2%) tuvieron sepsis a la admisión y 48 pacientes (30,7%) desarrollaron el cuadro en UTI, con edad promedio de 45 años. Los focos infecciosos más frecuentes fueron pulmón (53,2%), abdomen (48%)y sistema nervioso central (SNC), (12,8%). En 51 pacientes (32,5%) se aislaron gérmenes Gram posi­tivos (32,5%), siendo el Staphylococco aureus oxacilino resistente (SAOR) y el neumococo los más frecuentes. Los Gram negativos se aislaron en 48 pacientes (29,3%), siendo los más frecuentes Pseudomona sp y Klebsiella sp. Los esquemas antibióticos empíricos más utilizados fueron vancomicina/ imipenem (27%) y ciprofloxacina/ clindamicina (16%). La antibióticoterapia dirigida más usada fue vancomicina/ imipenem (14,1%) y ceftriaxona/ metronidazol (13,4%). Los factores de riesgo asociados fueron injuria cerebral, edad mayor a 60 años, hipertensión arterial y diabetes. Los fallos orgánicos, fueron en orden de frecuencia: pulmonar, neurológico, cardiovascular, renal, hepático y hematológico. El SOFA (secuential organ failure assessments) promedio fue 6,78, el APACHE II (acute physiology and chronic health evaluation) prome­ dio fue 20, con una mortaliuad de 51%.

Gastric tonometry versus cardiac index as resuscitation goals in septic shock: A multicenter, randomized, controlled trial

Introduction: Resuscitation goals for septic shock remain controversial. Despite the normalization of systemic hemodynamic variables, tissue hypoperfusion can still persist. Indeed, lactate or oxygen venous saturation may be difficult to interpret. Our hypothesis was that a gastric intramucosal pH-guided resuscitation protocol might improve the outcome of septic shock compared with a standard approach aimed at normalizing systemic parameters such as cardiac index (CI). Methods: The 130 septic-shock patients were randomized to two different resuscitation goals: CI ≥ 3.0 L/min/m2 (CI group: 66 patients) or intramucosal pH (pHi) ≥ 7.32 (pHi group: 64 patients). After correcting basic physiologic parameters, additional resuscitation consisting of more fluids and dobutamine was started if specific goals for each group had not been reached. Several clinical data were registered at baseline and during evolution. Hemodynamic data and pHi values were registered every 6 hours during the protocol. Primary end point was 28 days' mortality. Results: Both groups were comparable at baseline. The most frequent sources of infection were abdominal sepsis and pneumonia. Twenty-eight day mortality (30.3 vs. 28.1%), peak Therapeutic Intervention Scoring System scores (32.6 ± 6.5 vs. 33.2 ± 4.7) and ICU length of stay (12.6 ± 8.2 vs. 16 ± 12.4 days) were comparable. A higher proportion of patients exhibited values below the specific target at baseline in the pHi group compared with the CI group (50% vs. 10.9%; P < 0.001). Of 32 patients with a pHi < 7.32 at baseline, only 7 (22%) normalized this parameter after resuscitation. Areas under the receiver operator characteristic curves to predict mortality at baseline, and at 24 and 48 hours were 0.55, 0.61, and 0.47, and 0.70, 0.90, and 0.75, for CI and pHi, respectively. Conclusions: Our study failed to demonstrate any survival benefit of using pHi compared with CI as resuscitation goal in septic-shock patients. Nevertheless, a normalization of pHi within 24 hours of resuscitation is a strong signal of therapeutic success, and in contrast, a persistent low pHi despite treatment is associated with a very bad prognosis in septic-shock patients.Facultad de Ciencias Médica

Lamina X of the spinal cord in motor neuron disease

A number of plastic events were described in the spinal cord in the course of amyotrophic lateral sclerosis (ALS). These consist of various morphological effects, involving neurons, glia, and inflammatory cells, as well. Among plastic changes, an increase in neuronal progenitor cells (NPC) occurs within ependymal cells layer of lamina X. This stem cell-like activity is known to be weak in baseline conditions but it is known to increase significantly during spinal cord disorders, when it preferentially generates glial cells, due to the strong gliogenic effect of the spinal cord “milieu”. In the present work, we used immunohistochemistry and electron microscopy to analyze cell number within lamina X at the end stage of disease in the G93A mouse model of ALS in baseline conditions and following chronic lithium administration. These cells were identified by using GFAP, bIII-tubulin, NeuN, and calbindin- D28K immunostaining. In the absence of lithium we observed an increase of lamina X cells in ALS mice with a glial phenotype, while in G93A mice treated with lithium these cells differentiate towards neuronal-like phenotype. These effects of lithium are concomitant with slowed disease progression and are reminiscent of the neurogenetic effects described in the sub-ependymal ventricular zone of the hippocampus. The present data confirm the scarce NPC activity in the intact spinal cord which is enhanced by disease conditions; in the presence of chronic lithium, such increased NPCs differentiate towards a neuron-like rather than a glial phenotype

Further steps in the role of autophagy in methamphetamine toxicity

Methamphetamine (METH) abuse is known to cause a variety of disorders Incluing depression and psychosis. METH induces nigrostriatal damage in animal models and in humans consisting of intracellular alterations in nigral DA cell bodies, degeneration of DA terminals and decreased striatal DA levels. Following METH exposure, the number of nigral cell bodies is quite preserved but autophagy-like vacuoles and cytoplamic accumulation of misfolded proteins are observed. The DA-containing PC12 cell lines represent a simple model of METH toxicity and are commonly used in vitro to understand the pathophysiology of DA neurons. We analyzed at morphological level the effects of plasmid-dependent autophagy modulation on METH toxicity in PC12 cell line. We profited from the high number of authophagic like vacuoles induced by low doses of METH in order to isolate cell fraction in which to study their origin, dynamic structure and molecular composition. We found that authophagy-like vacuoles are positive both for autophagy and proteasome markers. The modulation of autophagy via a p62 containing plasmid protected from METH toxicity, while the inhibition of autophagy machinery worsened METH neurotoxicity. The present data substantiate the protective role of the autophagy machinery in METH-induced DA toxicity where the pro-autophagy protein p62 possesses a key role

Gastric tonometry versus cardiac index as resuscitation goals in septic shock: A multicenter, randomized, controlled trial

Introduction: Resuscitation goals for septic shock remain controversial. Despite the normalization of systemic hemodynamic variables, tissue hypoperfusion can still persist. Indeed, lactate or oxygen venous saturation may be difficult to interpret. Our hypothesis was that a gastric intramucosal pH-guided resuscitation protocol might improve the outcome of septic shock compared with a standard approach aimed at normalizing systemic parameters such as cardiac index (CI). Methods: The 130 septic-shock patients were randomized to two different resuscitation goals: CI ≥ 3.0 L/min/m2 (CI group: 66 patients) or intramucosal pH (pHi) ≥ 7.32 (pHi group: 64 patients). After correcting basic physiologic parameters, additional resuscitation consisting of more fluids and dobutamine was started if specific goals for each group had not been reached. Several clinical data were registered at baseline and during evolution. Hemodynamic data and pHi values were registered every 6 hours during the protocol. Primary end point was 28 days' mortality. Results: Both groups were comparable at baseline. The most frequent sources of infection were abdominal sepsis and pneumonia. Twenty-eight day mortality (30.3 vs. 28.1%), peak Therapeutic Intervention Scoring System scores (32.6 ± 6.5 vs. 33.2 ± 4.7) and ICU length of stay (12.6 ± 8.2 vs. 16 ± 12.4 days) were comparable. A higher proportion of patients exhibited values below the specific target at baseline in the pHi group compared with the CI group (50% vs. 10.9%; P < 0.001). Of 32 patients with a pHi < 7.32 at baseline, only 7 (22%) normalized this parameter after resuscitation. Areas under the receiver operator characteristic curves to predict mortality at baseline, and at 24 and 48 hours were 0.55, 0.61, and 0.47, and 0.70, 0.90, and 0.75, for CI and pHi, respectively. Conclusions: Our study failed to demonstrate any survival benefit of using pHi compared with CI as resuscitation goal in septic-shock patients. Nevertheless, a normalization of pHi within 24 hours of resuscitation is a strong signal of therapeutic success, and in contrast, a persistent low pHi despite treatment is associated with a very bad prognosis in septic-shock patients.Facultad de Ciencias Médica