[New therapeutic alternatives for severe sepsis in the critical patient. A review]. / Nuevas alternativas terapéuticas para la sepsis grave en el paciente crítico. Revisión.

BACKGROUND: Despite efforts to establish uniform protocols for the management of severe sepsis, this condition continues to have high morbidity and mortality. This is due, among other factors, to the many barriers for the development of the protocols and the application time. That is why new therapeutic measures are continuing to be investigated and developed. OBJECTIVE: To review the literature on the new and future therapeutic alternatives available in the management of sepsis in critically ill patients. DATA SOURCE AND SEARCH METHOD: A search was made for articles consistent with evidence- based medicine guidelines published between 2004 and 2009 in different databases (Cochrane Plus Library, National Guideline Clearinghouse, Clinical Evidence, REMI and PubMed) and the NIH Clinical Trails database (ClinicalTrials.gov) using the TRIP meta-search engine. STUDY SELECTION: A total of 357 documents were retrieved, selecting 48 of which included systematic reviews, meta-analyses, clinical practice guidelines, structured abstracts of original articles, and clinical trials. The selection criteria followed the peer review process. DATA EXTRACTION: Data were extracted by two independent reviewers. CONCLUSIONS: Based on the 2004-2009 study period, sufficient evidence was not obtained to make further recommendations on the treatment of sepsis. Although the abundant evidence needed to suggest the utility of these therapeutic measures, inhaled nitric oxide, statins, and immunoglobulins are probably good options for the adjuvant treatment of sepsis. However, we must wait for the results of different ongoing clinical trials on new treatment modalities. Stem cells and gene therapy will probably emerge as novel therapies in the future.

Candidemia in non-neutropenic critically ill patients: analysis of prognostic factors and assessment of systemic antifungal therapy. Study Group of Fungal Infection in the ICU.

OBJECTIVE: To determine the incidence and prognosis of candidemia in non-neutropenic critically ill patients, to define mortality-related factors, and to evaluate the results of systemic antifungal therapy. DESIGN: A prospective multicenter survey in which medical and/or surgical intensive care units (ICUs) in 28 hospitals in Spain participated. PATIENTS: All critically ill patients with positive blood cultures for Candida species admitted to the participating ICUs over a 15-month period were included. INTERVENTIONS: Candidemia was defined as the presence of at least one positive blood culture containing Candida species. The follow-up period was defined as the time elapsed from the first positive blood culture for Candida species to discharge or death during hospitalization. Antifungal therapy was considered to be "early" when it was administered within 48 h of the date when the first positive blood culture was obtained and "late" when it was administered more than 48 h after the first positive blood culture. MEASUREMENTS AND MAIN RESULTS: Candidemia was diagnosed in 46 patients (mean age 59 years), with an incidence of 1 critically ill patient per 500 ICU admissions. The species most frequently isolated were Candida albicans (60%) and C. parapsilosis (17%). Fluconazole alone was given to 27 patients, amphotericin B alone to 10, and sequential therapy to 6. Three patients did not receive antifungal therapy. The overall mortality was 56% and the attributable mortality 21.7%. In the univariate analysis, mortality was significantly associated with a higher Acute Physiology and Chronic Health Evaluation (APACHE) II score at the onset of candidemia (p = 0.04) and with the time elapsed between the episode of candidemia and the start of antifungal therapy 48 h or more later (p < 0.02). Patients with an APACHE II score lower than 21 at the onset of candidemia had a higher probability of survival than patients who were more seriously ill (p = 0.04). Patients with "early" antifungal therapy (< or = 48 h between the onset of candidemia and the start of antifungal therapy) had a higher probability of survival compared with patients with late therapy (p = 0.06). No significant differences were noted between the two groups on different antifungal therapy. CONCLUSIONS: The incidence of candidemia in ICU patients was very low. An APACHE II score > 20 at the time of candidemia was associated with a higher mortality. Further studies with a large number of patients are needed to assess the effect of early antifungal therapy on the decrease in mortality associated with candidemia and to determine the appropriate dosage of fluconazole and duration of treatment.

Prospectively defined indicators to improve the safety and quality of care for critically ill patients: a report from the Task Force on Safety and Quality of the European Society of Intensive Care Medicine (ESICM).

OBJECTIVES: To define a set of indicators that could be used to improve quality in intensive care medicine. METHODOLOGY: An European Society of Intensive Care Medicine Task Force on Quality and Safety identified all commonly used key quality indicators. This international Task Force consisted of 18 experts, all with a self-proclaimed interest in the area. Through a modified Delphi process seeking greater than 90% consensual agreement from this nominal group, the indicators were then refined through a series of iterative processes. RESULTS: A total of 111 indicators of quality were initially found, and these were consolidated into 102 separate items. After five discrete rounds of debate, these indicators were reduced to a subset of nine that all had greater than 90% agreement from the nominal group. These indicators can be used to describe the structures (3), processes (2) and outcomes (4) of intensive care. Across this international group, it was much more difficult to obtain consensual agreement on the indicators describing processes of care than on the structures and outcomes. CONCLUSION: This document contains nine indicators, all of which have a high level of consensual agreement from an international Task Force, which could be used to improve quality in routine intensive care practice.

[Pandemic influenza A in the ICU: experience in Spain and Latin America. GETGAG/SEMICYUC/(Spanish Working Group on Severe Pandemic Influenza A/SEMICYUC)]. / Gripe A pandémica en una unidad de cuidados intensivos: experiencia en España y Latinoamérica (Grupo Español de Trabajo de Gripe A Grave/Sociedad Española de Medicina Intensiva, Crítica y Unidades Coronarias).

INTRODUCTION: Pandemic Influenza A (H1N1)v infection is the first pandemic in which intensive care units (ICU) play a fundamental role. It has spread very rapidly since the first cases were diagnosed in Mexico with the subsequent spread of the virus throughout the Southern Cone and Europe during the summer season. OBJECTIVE: This study has aimed to compare the clinical presentation and outcome among the critical patients admitted to the ICU until July 31, 2009 in Spain with some series from Latin America. MATERIAL AND METHOD: Six series of critically ill patients admitted to the ICU were considered. Clinical characteristics, complications and outcome were compared between series. RESULTS: Young patients (35-45 years) with viral pneumonia as a predominant ICU admission cause with severe respiratory failure and a high need of mechanical ventilation (60-100%) were affected. Obesity, pregnancy and chronic lung disease were risk factors associated with a worse outcome, however there was a high number of patients without comorbidities (40-50%). Mortality rate was between 25-50% and higher in the Latin America series, demonstrating the specific potential pathogenesis of the new virus. The use of antiviral treatment was delayed (between 3 and 6 days) and not generalized, with greater delay in Latin America in regards to Spain. CONCLUSIONS: These data suggest that a more aggressive treatment strategy, with earlier and easier access to the antiviral treatment might reduce the number of ICU admissions and mortality.

[Prevention of bacteriema related with ICU catheters by multifactorial intervention: a report of the pilot study]. / Prevención de la bacteriemia relacionada con catéteres en UCI mediante una intervención multifactorial. Informe del estudio piloto.

OBJECTIVE: to assess the applicability on a national level of the interventions proposed by Peter Pronovost et al in Michigan state for the prevention of central vascular catheter-related bacteremia (B-CVC) in patients admitted to the ICU. DESIGN: pilot, prospective and comparative study. SETTING: eighteen ICUs (9 control and 9 intervention) from three autonomous communities in Spain during 3 months in 2007 participated in the study. INTERVENTION: the following activities were included: a) training program for health care personnel, b) introduction of specific measures related to the insertion and care of CVC (catheter insertion checklist, basic recommendations for maintenance of central catheters, dedicated cart for venous accesses, information poster with the five procedures proposed to reduce bacteremias: hands hygiene, use of maximal aseptic barriers during insertion, asepsis of the skin at the insertion point with chlorhexidine, avoidance of the femoral access, and removal of all CVC) and c) measures aiming to promote the culture of safe daily work (daily objectives, learning from mistakes, safety rounds). RESULTS: the rate of B-CVC expressed as mean values has shown a half reduction as compared with historical registers. Different problems in the implementation of specific measures related to catheters and safety tools were identified. CONCLUSIONS: the intervention project assessed in the pilot study may be viable on the national level. It is necessary to modify and adapt to the Spanish reality the interventions proposed.

Economic impact of Candida colonization and Candida infection in the critically ill patient.

The objective of the study presented here was to assess the economic impact of Candida colonization and Candida infection in critically ill patients admitted to intensive care units (ICUs). For this purpose, a prospective, cohort, observational, and multicenter study was designed. A total of 1,765 patients over the age of 18 years who were admitted for at least 7 days to 73 medical-surgical ICUs in 70 Spanish hospitals between May 1998 and January 1999 were studied. From day 7 of ICU admission to ICU discharge, samples of tracheal aspirates, pharyngeal exudates, gastric aspirates and urine were collected every week for culture. Prolonged length of stay was associated with severity of illness, Candida colonization or infection, infection by other fungi, antifungal therapy, treatment with more than one antifungal agent, and toxicity associated with this therapy. Compared to non-colonized, non-infected patients (n=720), patients with Candida colonization (n=880) had an extended ICU stay of 6.2 days (OR, 1.69; 95%CI, 1.53-1.87; P<0.001) and an extended hospital stay of 8.6 days (OR, 1.27; 95%CI, 1.16-1.40; P<0.001). The corresponding figures for patients with Candida infection (n=105) were 12.7 days for ICU stay (OR, 2.13; 95%CI, 1.72-2.64; P<0.001) and 15.5 days for hospital stay (OR, 1.23; 95%CI, 0.99-1.52; P=0.060). Candida colonization resulted in an additional 8,000 EUR in direct costs and Candida infection almost 16,000 EUR. Both Candida colonization and Candida infection had an important economic impact in terms of cost increases due to longer stays in both the ICU and in the hospital.

Treatment of severe nosocomial pneumonia: a prospective randomised comparison of intravenous ciprofloxacin with imipenem/cilastatin.

BACKGROUND: A prospective multicentre study was undertaken to compare the efficacy of intravenous ciprofloxacin or imipenem in the treatment of severe nosocomial pneumonia requiring mechanical ventilation. METHODS: Patients with a clinical suspicion of pneumonia were randomised to receive either ciprofloxacin (800-1200 mg/day) or imipenem (2-4 g/day) in doses adjusted for renal function and specimens of the lower respiratory tract were taken. Patients were included in the study when specimens showed significant growth for potentially pathogenic microorganisms in quantitative bacterial cultures (n = 75, ciprofloxacin 41/75 (55%); imipenem 34/75 (45%)). The clinical and bacteriological success rates were the primary and secondary efficacy variables. An intent-to-treat analysis was performed for all randomised patients who received at least one dose of the study medication (n = 149, ciprofloxacin 72/149 (48%), imipenem 77/149 (52%)). RESULTS: The success rates were generally good, but neither the clinical success rates (ciprofloxacin, 29/41 (71%), imipenem, 27/34 (79%); 95% CI -10.8 to 28.1; p = 0.435) nor the bacteriological response rate (ciprofloxacin, 20/41 (49%), imipenem, 17/34 (50%); 95% CI -21.5 to 23.9; p = 1.0) were significantly different between the study arms. Pseudomonas aeruginosa was recovered in 26/75 patients (35%) and clinical (ciprofloxacin, 10/14 (71%), imipenem, 8/12 (67%); 95% CI -40.4 to 30.9; p = 1.0) and bacteriological response rates (ciprofloxacin, 7/14 (50%), imipenem, 3/12 (25%), 95% CI -60.9 to 10.9, p = 0.247) were not significantly different in this subgroup of patients. Resistance of Pseudomonas aeruginosa developed in 5/26 cases (19%), 1/14 (7%) to ciprofloxacin and 4/12 (33%) to imipenem (p = 0.147), and the mortality was 12/75 (16%) with no difference between treatment groups (ciprofloxacin, 8/41(24%), imipenem 4/34 (17%); p = 0.362). The clinical response was evaluable in 109/149 patients (73%) in the intent-to-treat analysis and was successful in 74/109 patients (68%). The clinical response rates were also not significantly different in the intent-to-treat analysis (ciprofloxacin, 34/52 (65%), imipenem, 40/57 (70%); 95% CI -12.8 to 22.3; p = 0.746). CONCLUSIONS: Treatment with either ciprofloxacin or imipenem was effective in a selected group of patients with microbiologically confirmed, severe nosocomial pneumonia requiring mechanical ventilation. Although no differences between the study medication could be documented in this trial, smaller differences between treatment arms may have been missed because of sample size limitations.

[The role of meropenem in the treatment of pneumonia in the critical patient]. / Papel del meropenem en el tratamiento de la neumonía en el paciente crítico.

Pneumonia in critical ill patients, most of them associated with insaturation of an artificial a way and the use of mechanical ventilation, involves important morbi/mortality in the Intensive Care Units. Knowledge of pathogenesis, risk factors, and implicated microorganisms in developing of this major infectious complication, in the context of infections which rise in the critically ill patients, allow us to apply prophylaxis measures which could decrease its incidence, and establish antimicrobial therapy, which permit us to cover all the etiologic possibilities. Availability in the arsenal of the powerful antimicrobial, of a new carbapenemic, meropenem, and based on the different studies and clinic assays, allow to recommend its use with warranties and efficacy, in the empirical or's in concretely those due to Pseudomonas aeruginosa, enterobacteriaceae, (in general or producers of ample spectrum beta-lactamases), and Acinetobacter spp., in monotherapy or combined therapy, with aminoglycosides.

[Necrotizing infections of the soft tissues. Apropos of 40 cases]. / Infecciones necrosantes de partes blandas. A propósito de 40 casos.

The diagnosis of necrotizing soft tissue infection (NSTI) is based on a high suspicion index and/or clinical experience. Mortality is associated with delayed diagnosis and use of early surgical treatment, and also with the underlying disease and the patient's age. Usually they are mixed infections; therefore, in addition to surgical therapy an adequate antibiotic coverage is required. The latter, in cases of severe renal failure, might consist in monotherapy. All these guidelines can be modified on the basis of bacteriological findings. The Gram stain of a surgical sample can be very useful to select an appropriate empirical therapy. From a clinical point of view, we suggest to pay extreme attention to the findings consistent with NSTI: tenderness and/or crackling of soft tissue, rapid expansion through natural planes, or visualization of gas in the x-ray film of the involved zone, particularly if associated with a rapid deterioration of the general condition of the patient.