[Epidemiology and long-term outcome of sepsis in elderly patients]. / Epidemiología y pronóstico tardío de la sepsis en ancianos.

OBJECTIVES: A study was made of the epidemiological data of sepsis requiring admission to the ICU in patients over 65 years of age, with an evaluation of independent predictors of survival at 2 years. DESIGN: A prospective cohort study was made. PATIENTS: Patients meeting criteria for sepsis upon admission to the ICU. SETTING: A 40-bed ICU in a tertiary hospital. RESULTS: The study group included 237 elderly patients (≥ 65 years of age) and 281 controls (<65 years of age) (n=518). At least one chronic comorbid condition was present in 70% of the elderly patients as compared to only 56.1% of patients under age 65 (P<.01). There were several epidemiological differences between the groups: the prevalence of chronic diseases (diabetes, chronic obstructive pulmonary disease, and chronic heart failure), presentation as septic shock (52.3% vs 42%; P<.05), and the abdomen as the source of sepsis (52% vs 36%; P<.01) were all more frequent in elderly patients. Nine percent of the global patients discharged from hospital died in the 2-year follow-up period, but this rate reached 20% among the elderly. Independent predictors of 2-year mortality in the elderly were: chronic heart failure (adjusted hazard ratio [aHR] 2.24, 95% confidence interval [CI 95%] 1.28-3.94; P<.01), acute renal failure (aHR 3.64, 95%CI 2.10-6.23; P<.01), acute respiratory failure (aHR 3.67, 95%CI 2.31-5.86; P<.01), and inappropriate empirical antimicrobial therapy (aHR 2.19, 95%CI 1.32-3.62; P<.01). CONCLUSIONS: Sepsis showed different demographic characteristics and clinical presentations in the elderly. In the aging cohort, after adjusting for potential confounders, inadequate empirical antimicrobial therapy was associated to a 2-fold decrease in survival at two years.

[Guidelines for specialized nutritional and metabolic support in the critically-ill patient. Update. Consensus of the Spanish Society of Intensive Care Medicine and Coronary Units-Spanish Society of Parenteral and Enteral Nutrition (SEMICYUC-SENPE): patient with sepsis]. / Recomendaciones para el soporte nutricional y metabólico especializado del paciente crítico. Actualización. Consenso SEMICYUC-SENPE: paciente séptico.

Nutritional metabolic management, together with other treatment and support measures used, is one of the mainstays of the treatment of septic patients. Nutritional support should be started early, after initial life support measures, to avoid the consequences of malnutrition, to provide adequate nutritional intake and to prevent the development of secondary complications such as superinfection or multiorgan failure. As in other critically-ill patients, when the enteral route cannot be used to ensure calorie-protein requirements, the association of parenteral nutrition has been shown to be safe in this subgroup of patients. Studies evaluating the effect of specific pharmaconutrients in septic patients are scarce and are insufficient to allow recommendations to be made. To date, enteral diets with a mixture of substrates with distinct pharmaconutrient properties do not seem to be superior to standard diets in altering the course of sepsis, although equally there is no evidence that these diets are harmful. There is insufficient evidence to recommend the use of glutamine in septic patients receiving parenteral nutrition. However, given the good results and absence of glutamine-related adverse effects in the various studies performed in the general population of critically-ill patients, these patients could benefit from the use of this substance. Routine use of omega-3 fatty acids cannot be recommended until further evidence has been gathered, although the use of lipid emulsions with a high omega-6 fatty acid content should be avoided. Septic patients should receive an adequate supply of essential trace elements and vitamins. Further studies are required before the use of high-dose selenium can be recommended.

[Guidelines for specialized nutritional and metabolic support in the critically-ill patient. Update. Consensus of the Spanish Society of Intensive Care Medicine and Coronary Units-Spanish Society of Parenteral and Enteral Nutrition (SEMICYUC-SENPE): introduction and methodology]. / Recomendaciones para el soporte nutricional y metabólico especializado del paciente crítico. Actualización. Consenso SEMICYUC-SENPE: introducción y metodología.

The Recommendations for Specialized Nutritional Support in Critically-Ill patients were drafted by the Metabolism and Nutrition Working Group of the Spanish Society of Intensive Care Medicine and Coronary Units (SEMICYUC) in 2005. Given the time elapsed since then, these recommendations have been reviewed and updated as a Consensus Document in collaboration with the Spanish Society of Parenteral and Enteral Nutrition (SENPE). The primary aim of these Recommendations was to evaluate the best available scientific evidence for the indications of specialized nutritional and metabolic support in critically-ill patients. The Recommendations have been formulated by an expert panel with broad experience in nutritional and metabolic support in critically-ill patients and were drafted between October 2009 and March 2011. The studies analyzed encompassed metaanalyses, randomized clinical trials, observational studies, systematic reviews and updates relating to critically-ill adults in MEDLINE from 1966 to 2010, EMBASE reviews from 1991 to 2010 and the Cochrane Database of Systematic Reviews up to 2010. The methodological criteria selected were those established in the Scottish Intercollegiate Guidelines Network and the Agency for Health Care policy and Research, as well as those of the Jadad Quality Scale. Adjustment for the level of evidence and grade of recommendation was performed following the proposal of the GRADE group (Grading of Recommendations Assessment, Development and Evaluation Working Group). Sixteen pathological scenarios were selected and each of them was developed by groups of three experts. A feedback system was established with the five members of the Editorial Committee and with the entire Working Group. All discrepancies were discussed and consensus was reached over several meetings, with special emphasis placed on reviewing the levels of evidence and grades of recommendation. The Editorial Committee made the final adjustments before the document was approved by all the members of the Working Group. Finally, the document was submitted to the Scientific Committees of the two Societies participating in the Consensus for final approval. The present Recommendations aim to serve as a guide for clinicians involved in the management and treatment of critically-ill patients and for any specialists interested in the nutritional treatment of hospitalized patients.

[Guidelines for specialized nutritional and metabolic support in the critically-ill patient. Update. Consensus of the Spanish Society of Intensive Care Medicine and Coronary Units-Spanish Society of Parenteral and Enteral Nutrition (SEMICYUC-SENPE): critically-burned patient]. / Recomendaciones para el soporte nutricional y metabólico especializado del paciente crítico. Actualización. Consenso SEMICYUC-SENPE: paciente quemado crítico.

The response to severe burns is characterized by hypermetabolism (the most hypermetabolic existing model of aggression) and hypercatabolism, with a high degree of destruction of the skeletal musculature. Metabolic disorders are most evident in the first two weeks after the burn, although they can be prolonged in direct relation to the complications that these patients develop. Nutritional-metabolic support is an essential part of the treatment of these patients and should be started early, preferentially through the enteral route, with parenteral nutrition as complementary support. Exact calculation of calorie-protein requirements in these patients is difficult, even when indirect calorimetry is used, due to the high loss of proteins and CO(2) through the skin. Specific pharmaconutrients are indicated, with a high dose of micronutrients. The use of drugs or medications with anabolic effects is also sometimes indicated.

Superinfection during treatment of nosocomial infections with tigecycline.

We performed a retrospective and observational study of 51 patients treated with tigecycline, as the treatment for nosocomial infections due to multidrug-resistant microorganisms, to evaluate the superinfection rate and their etiologies. Superinfections were diagnosed in 12 (23.5%) patients (seven due to Pseudomonas aeruginosa, 13.7%) and one patient had P. aeruginosa colonization. Five patients with superinfection died (41.6%), three due to superinfections and two to underlying diseases. The superinfection rate observed during tigecycline treatment is higher than that previously reported. Pseudomonas aeruginosa is the most frequent agent, being the cause of 58.5% of all superinfections.

[IV Debate Forum of the SENPE: questions on nutrition research]. / IV Foro de Debate SENPE: problemática de la investigación en nutrición.

The IV Debate Forum of the SENPE values from a multidisciplinary and multi-professional perspective the questions on clinical research in nutrition in Spain, focusing on enteral nutrition due to the lack of legislation on this issue. The concluding remarks point out the SENPE commitment with promoting quality, education and facilitation of research, greater help to emergent groups, looking for financial support, and timely information on the several summons from public systems and reference centers

[Pharmacological treatment neuromuscular impairments in critically ill patients]. / Tratamiento farmacológico de las alteraciones neuromusculares en el paciente crítico.

The use of drugs for treating neuromuscular impairments that present in the patient admitted to the Intensive Care Unit is virtually inexistent. The use of intravenous immunoglobulins for managing polyneuropathy of the critically ill patient (PCIP) is supported by no evidence. More important is prophylactic therapy, as is the administration of insulin perfusion to prevent hyperglycemia that is associated to increased development of PCIP. New data suggest that the protective mechanism of this perfusion, which normalizes glucose levels, is achieved through the modulation of endothelial dysfunction and lowering levels of asymmetrical di-methyl arginine (ADMA). As for myopathy of the critically ill patient or conditions with prolonged neuromuscular blockade, treatment consists in avoiding the use of several drugs known to be associated with development of these conditions, such as muscle relaxants and aminoglycosides. In relation to acute flaccid paralysis -an infection caused by the Western Nile Virus, anecdotic cases have been reported of improvement with the use steroids or interferon, although routine management remains to be established.

Acinetobacter baumannii ventilator-associated pneumonia: epidemiological and clinical findings.

OBJECTIVE: To investigate prognostic factors and predictors of Acinetobacter baumannii isolation in ventilator-associated pneumonia (VAP). We specifically analyzed these issues for imipenem-resistant episodes. DESIGN AND SETTING: All episodes of VAP are prospectively included in a database. Information about risk factors was retrieved retrospectively. PATIENTS: Eighty-one patients exhibiting microbiologically documented VAP: 41 by A. baumannii (26 by imipenem-resistant) and 40 by other pathogens. MEASUREMENTS AND RESULTS: The following variables were noted: underlying diseases, severity of illness, duration of mechanical ventilation and of hospitalization before VAP, prior episode of sepsis, previous antibiotic, corticosteroid use, type of nutrition, renal replacement therapy, reintubation, transportation out of the ICU, micro-organisms involved in VAP, concomitant bacteremia, clinical presentation, Sequential Organ Failure Assessment (SOFA) scale on the day of diagnosis, and adequacy of empirical antibiotic therapy. Prior antibiotic use was found to be associated with development of VAP by A. baumannii (OR 14). Prior imipenem exposure was associated with the isolation of imipenem-resistant strains (OR 4). SOFA score on the day of diagnosis was the only predictor of in-hospital mortality (OR 1.22); adequacy of empirical antibiotic therapy was a protective factor (OR 0.067). CONCLUSIONS: Our results confirm that prior exposure to antimicrobials is an independent predictor for the development of A. baumannii VAP, the prognosis of which is similar to that of infections caused by other pathogens. This study highlights the importance of initial antibiotic choice in VAP or whatever cause.

[Requeriments of macronutrients and micronutrients]. / Requerimientos de macronutrientes y micronutrientes.

Critically ill patients have important modifications in their energetic requirements, in which the clinical situation, treatment applied and the time course take part. Thus, the most appropriate method to calculate the caloric intake is indirect calorimetry. When this test is not available, calculations such as Harris-Benedict's may be used, although not using the so high correction factors as previously recommended in order to avoid hypercaloric intakes. The intake of a fixed caloric amount (comprised between 25-30 KcalKg/min) is adequate for most critically ill patients. Carbohydrates intake must be of 5 g/kg/day) maximum. Glucose plasma levels must be controlled in order to avoid hyperglycemia. With regards to fat intake, the maximum limit should be 1.5 g/kg/day. The recommended protein intake is 1.0-1.5 g/kg/day, according to the clinical situation characteristics. Special care must be taken with micronutrients intake, an issue that is many times undervalued. In this sense, there are data to consider some micronutrients such as Zn, CU, Mn, Cr, Se, Mo and some vitamins (A, B, C, and E) of great importance for patients in a critical condition, although specific requirements for each one of them have not been established.

[Nutritional support in sepsis]. / Nutrición artificial en la sepsis.

Although it is considered that metabolic and nutritional support must be part of the management of septic patients, it has not been conclusively shown that nutritional support will improve survival or complications from sepsis. Specific data on this issue are scarce since there are few studies that have investigated specialized nutritional support in septic patients. Thus, most of the recommendations are based on outcomes obtained in severely ill patients with different pathologies. It is assumed that nutritional support should be carried out through the enteral route whenever possible, as in other critically ill patients. The energetic waste in these patients is highly variable, although in general terms the hypermetabolic situation may be classified as moderate. An adjustment factor of 1.25-1.30 is recommended for the Harris-Benedict's equation to calculate the caloric intake. Septic patients should receive a hyperproteic intake. The amount of glucose administered should not exceed 70% of non-protein calories, and lipids intake should not exceed 40%. With regards to micronutrients, it is recommended to increase the supply of those with antioxidant properties (vitamin E, carotenes, vitamin C, selenium). There are data to consider that the use of diets enriched with pharmaco-nutrients (both with parenteral and enteral routes) may be beneficial in septic patients, although there is some controversy when interpreting the outcomes.

[Artificial nutrition in hematopoietic stem cells transplantation]. / Nutrición artificial en el trasplante de células precursoras hematopoyéticas.

Patients submitted to hematopoietic stem cells transplantation (HSCT) have an increased risk for having hyponutrition, both in the phase prior to transplantation and after this one. The indication of specialized nutritional support is common in allogenic HSCT, whereas patients submitted to auto-HSCT need it in the presence of complications that compromise an adequate nutrients intake. Enteral nutrition through a nasogastric tube has difficulties in these patients; the presence of mucositis delays the indication for enteral nutrition, which usually is poorly tolerated. Thus, frequently parenteral nutrition needs to be used as the route for nutritional support. The use of specific substrates, such as glutamine, is a controversial issue.

[Recommendations for nutritional assessment and specialized nutritional support of critically ill patients]. / Recomendaciones para la valoración nutricional y el soporte nutricional especializado de los pacientes críticos.

Due to the characteristics of critically ill patients, elaborating recommendations on nutritional support for these patients is difficult. Usually the time of onset of nutritional support or its features are not well established, so that its application is based on experts' opinion. In the present document, recommendations formulated by the Metabolism and Nutrition Working Group of the Spanish Society of Intensive and Critical Medicine and Coronary Units (SEMICYUC) are presented. Recommendations are based on the literature analysis and further discussion by the working group members in order to define, consensually, the more relevant issues of metabolic and nutritional support of patients in a critical condition. Several clinical situations have been considered which are developed in the following articles of this publication. The present recommendations aim at providing a guideline for the less experienced clinicians when considering the metabolic and nutritional issues of critically ill patients.

Treatment of multidrug-resistant Acinetobacter baumannii ventilator-associated pneumonia (VAP) with intravenous colistin: a comparison with imipenem-susceptible VAP.

We prospectively evaluated the efficacy and toxicity of intravenously administered colistin in 35 episodes of ventilator-associated pneumonia (VAP) due to multidrug-resistant Acinetobacter baumannii. Microbiological diagnosis was performed with use of quantitative culture. In 21 patients, the episodes were caused by a strain susceptible exclusively to colistin (the CO group) and were all treated with this antimicrobial intravenously. In 14 patients, the episodes were caused by strains that remained susceptible to imipenem and were treated with imipenem-cilastatin (the IM group). Acute Physiology and Chronic Health Evaluation II scores at the time of admission and Sequential Organ Failure Assessment scores at time of diagnosis were similar in both groups. VAP was considered clinically cured in 57% of cases in both groups. In-hospital mortality rates were 61.9% in the CO group and 64.2% in the IM group, and the VAP-related mortality rates were 38% and 35.7%, respectively. Four patients in the CO group and 6 in the IM group developed renal failure. Neurophysiological evaluation was performed during 12 episodes in the CO group, but it revealed no signs of neuromuscular blockade. Intravenous colistin appears to be a safe and effective alternative to imipenem for the management of VAP due to carbapenem-resistant strains of A. baumannii.

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.

Variations in plasma amino acids in septic patients subjected to parenteral nutrition with a high proportion of branched-chain amino acids.

Sepsis is characterized by an increase in the plasma concentration of aromatic amino acids (AAAs) and those containing sulfur and a decrease in the branched-chain amino acids (BCAAs). We studied changes in the plasma aminogram of septic patients given different types of total parenteral nutrition (TPN), analyzing variations in accordance with the type of TPN used and the importance that the use of BCAA may have in these patients. We studied 80 patients with peritonitis divided into two groups of 40 patients each: group 1 was given a solution with 22.5% BCAA and group 2 a solution with 45% BCAA. High BCAA content caused an increase in the plasma concentrations of these amino acids and in the BCAA/AAA quotient and a decrease in AAAs. Plasma concentrations of leucine and valine reached high, potentially toxic levels at 15 days when solutions with high BCAA content were used. Glycine increased in group 1, which may be important because of its tendency to produce hyperammonemia. BCAAs are of unquestioned nutritional importance in view of the evidence of changes that take place in muscle protein catabolism and in plasma amino acids. In the phase of increased protein catabolism, we saw a plasma amino acid pattern in keeping with the existing metabolic situation. The need for BCAA diminishes when the hypercatabolic state disappears.

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.

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.

Prospective study on the efficacy of branched-chain amino acids in septic patients.

The metabolic response to sepsis is characterized by increased proteolysis and gluconeogenesis, reduced protein synthesis, and negative nitrogen balance. The effects of a solution with a high proportion of branched-chain amino acids (BCAA) on the nutritional state of septic patients were evaluated. Eighty patients with peritonitis were divided into two groups of 40 patients; group 1 was administered a solution with 22.5% BCAA and group 2 with 45% BCAA. The following parameters were evaluated: anthropometrics, creatinine/height index, urinary 3-methylhistidine, nitrogen balance, stress index, albumin, prealbumin, transferrin, retinol binding protein, lymphocytes, delayed cutaneous sensitivity tests, studies of hepatic function, and plasma aminogram. In group 2 a more positive nitrogen balance, a greater drop in the stress index, a rise in plasma prealbumin and retinol binding protein levels, an increase in the creatinine/height index, and a more marked fall in the urinary excretion of 3-methylhistidine were found. When solutions with a high BCAA content were administered, there was an increase in the plasma concentrations of these amino acids in the BCAA/aromatic amino acid quotient and a decrease in the aromatic amino acids. Plasma concentrations of leucine and valine achieved very high, potentially toxic, levels at 15 days when solutions with high BCAA content were used. It is concluded that solutions with BCAA are advisable for use in the septic patient in the increased protein catabolic phase, where positive nitrogen balance, a reduction in muscle protein catabolism, and faster recovery of muscle and visceral protein were obtained.

[Artificial enteral nutrition in sepsis patients]. / Nutrición artificial enteral en pacientes con sepsis.

The importance of avoiding bacterial translocation in critical patients in order to reduce the risk of multiorganic failure has led to an insistence on maintaining the enteral nutrition method in different clinical situations. The present study examines the possible alternative of enteral nutrition using an intact protein polymer and medium chain triglyceride diet in critical patients with sepsis. For this purpose, a prospective study was conducted on 20 patients who received this diet for a period of 20 days. In 16 cases, a jejunostomy catheter was used, and in the remaining 4, a nasogastric tube. 6 of the total patients died. The results obtained show a recovery of the visceral markers (prealbumin, transferrin and retinol-binding protein) of significant statistical importance. The improvement in albumin was discarded due to simultaneous intake of seroalbumin received by the patients. The nitrogenated balance and height creatinin index improved, whereas there was no increase in hepatic enzymes. In conclusion, this enteral diet is a perfectly valid alternative to parenteral nutrition in septic patients.