Polimorfismos genéticos en la sepsis / Genetic polymorphisms in sepsis

Un polimorfismo genético (PG) es una variante alélica que existe de forma estable en una población. Para ser considerado un PG, debe presentar una frecuencia de al menos el 1%. Son, por lo tanto, diferentes de las mutaciones, que son mucho menos frecuentes y van asociadas, habitualmente, a enfermedades hereditarias. Se han descrito varios PG en la sepsis y en el shock séptico. Pueden asociarse con una mayor incidencia de sepsis en la población general, o con una mayor gravedad y mortalidad una vez que la sepsis se ha presentado. Se han descrito PG de la proteína ligadora de la endotoxina, receptor CD14, factor de necrosis tumoral beta (TNF-ß), TNF-α, interleucina 1 alfa (IL-1α), IL-1ß IL-1 ra, IL-6 e IL-10. Los diversos estudios difieren al definir la relevancia de cada PG en particular, probablemente debido en parte a diferentes momentos en la inclusión de los enfermos, pequeño tamaño muestral, inclusión de enfermos de diferentes etnias y errores metodológicos en la determinación del PG

A genetic polymorphism (GP) is an allelic variation that appears in stable form in a population. An incidence of at least 1% is necessary for a GP to be considered as such. So, GP are different from mutations because mutations are less common, and appear associated usually to hereditary diseases. Several GP have been detected in sepsis and septic shock. GP can be associated to higher incidence of sepsis in general population, and to higher sepsis severity and mortality once the disease is evolving GPs of ligand protein endotoxin, CD14 receptor, TNF-ß, TNF-α, IL-1α, IL-1ß, IL-1 ra, IL-6, IL-10 have been described. Results of various studies have been different with regard to relevance of every GP, probably because of differences in the inclusion of patients in the studies, small samples, inclusion of patients of different ethnic groups, and methodological errors in GP ascertainment

Effects of three intravenous lipid emulsions on the survival and mononuclear phagocyte function of septic rats.

The immunosuppressive effects of intravenous lipid emulsions are a matter of great concern and debate. In a rat model of gram-negative bacteremia, we assessed whether the use of three intravenous lipid emulsions with different triacylglycerol compositions could influence mortality, bacterial clearance, and prostaglandin E(2) (PGE(2)) levels and compared these groups with groups of orally fed rats and rats that received a small amount of calories in form of glucose without enteral feeding (starvation). RATS WERE ASSIGNED TO ONE OF FIVE GROUPS: group 1 (control, n = 15) received rodent chow ad libitum and saline infusion; group 2 (starvation group, n = 12) had no access to chow and received an infusion of 5% glucose; group 3 (n = 17) received total parenteral nutrition (TPN) with long-chain triacylglycerols; group 4 (n = 12) received TPN with medium- and long-chain triacylglycerols; and group 5 (n = 15) received TPN with its emulsion based on olive oil. Animals received isonitrogenous and isocaloric TPN. After 2 d of TPN, a dose of 10(8) colony-forming units of Escherichia coli was introduced via the venous catheter; 2 d later the animals were killed. Blood, spleen, liver, and lungs were cultured. Circulating levels of PGE(2) were measured. Bacterial growth in the liver and lungs were significantly higher in groups 3 and 4 than in group 1, with no differences among the other groups. Rates of bacteremia were significantly higher in groups 3 and 4 than in group 1, with no differences among the other groups. Plasma levels of PGE(2) did not differ, and mortality was unaffected. Bacterial clearance clearly was preserved in orally fed, control rats when compared with rats on TPN with long-chain triacylglycerols or medium- plus long-chain triacylglycerols. However, the use of a lipid emulsion enriched intravenously with oleic acid was a valid way of reducing this disturbance, although plasma levels of PGE(2) and survival were not modified.

Clinical and metabolic effects of two lipid emulsions on the parenteral nutrition of septic patients.

OBJECTIVE: We compared the metabolic and clinical effects of two lipid emulsions, long-chain triacylglycerols (LCT) and a mixture of medium- and long-chain triacylglycerols (MCT/LCT), in septic patients. METHODS: Both groups received total parenteral nutrition (TPN) with a solution enriched with branched-chain amino acids (BCAA). Seventy-two septic patients received TPN with MCT/LCT (group 1) or LCT (group 2). Before starting TPN (basal) and 10 d after (final), various parameters were evaluated. RESULTS: Twenty-six subjects in each group completed the study. Both groups showed an increase in cholestasis enzymes, with no significant changes in lipid parameters. The rise of retinol-binding protein and the recovery of nitrogen balance were significantly greater in group 1. A multivariate analysis of nutritional markers and catabolic parameters showed a better evolution in group 1 (P = 0.002). The MCT/LCT group exhibited a significant increase of insulin levels. Overall mortality and length of stay in the intensive care unit were not affected by the lipid emulsion. CONCLUSIONS: In septic patients who received TPN with a solution enriched with BCAAs, the use of an emulsion containing MCT provided them with a greater recovery of their nutrition status than the traditional LCT formula, without influencing the outcome.

Critical illness polyneuropathy: risk factors and clinical consequences. A cohort study in septic patients.

OBJECTIVE: To determine risk factors and clinical consequences of critical illness polyneuropathy (CIP) evaluated by the impact on duration of mechanical ventilation, length of stay and mortality. DESIGN: Inception cohort study. SETTING: Intensive care unit of a tertiary hospital. PATIENTS: Septic patients with multiple organ dysfunction syndrome requiring mechanical ventilation and without previous history of polyneuropathy. INTERVENTIONS: Patients underwent two scheduled electrophysiologic studies (EPS): on the 10th and 21st days after the onset of mechanical ventilation. RESULTS: Eighty-two patients were enrolled, although nine of them were not analyzed. Forty-six of the 73 patients presented CIP on the first EPS and 4 other subjects were diagnosed with CIP on the second evaluation. The APACHE II scores of patients with and without CIP were similar on admission and on the day of the first EPS. However, days of mechanical ventilation [32.3 (21.1) versus 18.5 (5.8); p=0.002], length of ICU and hospital stay in patients discharged alive from the ICU as well as in-hospital mortality were greater in patients with CIP (42/50, 84% versus 13/23, 56.5%; p=0.01). After multivariate analysis, independent risk factors were hyperosmolality [odds ratio (OR) 4.8; 95% confidence intervals (95% CI) 1.05-24.38; p=0.046], parenteral nutrition (OR 5.11; 95% CI 1.14-22.88; p=0.02), use of neuromuscular blocking agents (OR 16.32; 95% CI 1.34-199; p=0.0008) and neurologic failure (GCS below 10) (OR 24.02; 95% CI 3.68-156.7; p<0.001), while patients with renal replacement therapy had a lower risk for CIP development (OR 0.02; 95% CI 0.05-0.15; p<0.001). By multivariate analysis, CIP (OR 7.11; 95% CI 1.54-32.75; p<0.007), age over 60 years (OR 9.07; 95% CI 2.02-40.68; p<0.002) and the worst renal SOFA (OR 2.18; 95% CI 1.27-3.74; p<0.002) were independent predictors of in-hospital mortality. CONCLUSIONS: CIP is associated with increased duration of mechanical ventilation and in-hospital mortality. Hyperosmolality, parenteral nutrition, non-depolarizing neuromuscular blockers and neurologic failure can favor CIP development.