Rafael Sierra

Intensive care adult patients with severe respiratory failure caused by Influenza A (H1N1)v in Spain

IntroductionPatients with influenza A (H1N1)v infection have developed rapidly progressive lower respiratory tract disease resulting in respiratory failure. We describe the clinical and epidemiologic characteristics of the first 32 persons reported to be admitted to the intensive care unit (ICU) due to influenza A (H1N1)v infection in Spain.MethodsWe used medical chart reviews to collect data on ICU adult patients reported in a standardized form. Influenza A (H1N1)v infection was confirmed in specimens using real-time reverse transcriptase-polymerase-chain-reaction (RT PCR) assay.ResultsIllness onset of the 32 patients occurred between 23 June and 31 July, 2009. The median age was 36 years (IQR = 31 - 52). Ten (31.2%) were obese, 2 (6.3%) pregnant and 16 (50%) had pre-existing medical complications. Twenty-nine (90.6%) had primary viral pneumonitis, 2 (6.3%) exacerbation of structural respiratory disease and 1 (3.1%) secondary bacterial pneumonia. Twenty-four patients (75.0%) developed multiorgan dysfunction, 7 (21.9%) received renal replacement techniques and 24 (75.0%) required mechanical ventilation. Six patients died within 28 days, with two additional late deaths. Oseltamivir administration delay ranged from 2 to 8 days after illness onset, 31.2% received high-dose (300 mg/day), and treatment duration ranged from 5 to 10 days (mean 8.0 ± 3.3).ConclusionsOver a 5-week period, influenza A (H1N1)v infection led to ICU admission in 32 adult patients, with frequently observed severe hypoxemia and a relatively high case-fatality rate. Clinicians should be aware of pulmonary complications of influenza A (H1N1)v infection, particularly in pregnant and young obese but previously healthy persons.

Ventilator-Associated Pneumonia: Impact of Organisms on Clinical Resolution and Medical Resources Utilization

BACKGROUND Clinical resolution of ventilator-associated pneumonia (VAP) determines the duration of treatment and mechanical ventilation. The aim of this study was to evaluate the influence of organisms and their susceptibility to treatment on outcomes. METHODS Prospective observational study in three teaching ICUs. Sixty episodes of VAP with appropriate therapy (Haemophilus influenzae, 15 episodes; methicillin-sensitive Staphylococcus aureus [MSSA], 15 episodes; Pseudomonas aeruginosa, 15 episodes; and methicillin-resistant S aureus [MRSA], 15 episodes), and 30 episodes with initial inappropriate therapy, all due to P aeruginosa, were compared. The main outcome measures were clinical resolution variables and, in survivors, length of mechanical ventilation after VAP onset. RESULTS A significant delay in the resolution of hypoxemia was observed in VAP episodes due to MRSA and P aeruginosa with inappropriate antibiotic therapy (IAT) (median time to resolution, 10 and 8 days, respectively) when compared with the remaining pathogens (median time to resolution, 2 days). A multiple regression model, adjusted for disease severity, confirmed the delayed clinical resolution for MRSA and P aeruginosa with IAT. Similar associations were documented for defervescence. Among survivors, the median duration of mechanical ventilation after VAP onset was significantly longer for MRSA (17 days) and P aeruginosa IAT (11 days) when compared with episodes due to H influenzae or MSSA (6 days). Multiple regression analysis, adjusted for disease severity, confirmed that MRSA required significantly (R(2) = 0.132; p < 0.01) longer respiratory support than other organisms. CONCLUSIONS When treated promptly, the resolution of VAP due to MSSA, H influenzae, and P aeruginosa was comparable. The resolution of MRSA VAP, regardless of the appropriateness of initial antibiotic therapy, was associated with longer respiratory support.

Antiseptic chamber-containing hub reduces central venous catheter-related infection: a prospective, randomized study.

ObjectiveThe hub connecting the catheter and the infusion equipment is a common portal of entry for bacteria causing catheter-related sepsis. We assessed the efficacy of a new hub model (Segur-Lock) that incorporates an antiseptic chamber filled with 3% iodinated alcohol in preventing endoluminal catheter contamination and catheter-related bloodstream infection arising at the hub. DesignProspective, randomized, multicenter study. SettingSeven medical and surgical adult intensive care units in Spain. PatientsA total of 230 patients aged 18 yrs or older requiring the insertion of a nontunneled central venous catheter for ≥6 days from January 1, 1998, to April 30, 1999. InterventionsPatients were randomized at the time of catheter insertion to receive catheters with standard Luer-lock connector (control group, n = 114) or catheters with the new hub model (n = 116). Measurements and Main ResultsSkin, catheter tip, and hub cultures were performed at the time the catheter was withdrawn because therapy was terminated or due to suspicion of sepsis, in which case peripheral blood and infusate cultures were simultaneously taken. Catheter-related bloodstream infection was diagnosed in 19 (8.3%) patients. Catheters were more often withdrawn because of suspicion of infection in the control group (43.8%) than in the new hub model group (30.1%, p < .035). The prevalence of culture-positive catheter hubs without associated bacteremia (colonization) was higher in the control group (14.4% vs. 4.3%, p < .001). Catheter-related bloodstream infection from the catheter hub also occurred more frequently in controls than in patients assigned to the new hub model (7% vs. 1.7%;p < .049; relative risk, 4.14; 95% confidence interval, 0.8–19). ConclusionsThis new antiseptic chamber–containing hub has proved to be effective in preventing endoluminal bacterial colonization and catheter-related bloodstream infection from hub contamination in intensive care unit patients with central venous catheters inserted for ≥6 days.

Severe pandemic (H1N1)v influenza A infection: Report on the first deaths in Spain

Background and objective:  The impact of pandemic influenza A (H1N1)v infection is still unknown but it is associated with a high case‐fatality rate.

Improvement of antibiotic therapy and ICU survival in severe non-pneumococcal community-acquired pneumonia: a matched case-control study

IntroductionWe aimed to compare intensive care unit mortality due to non-pneumococcal severe community-acquired pneumonia between the periods 2000–2002 and 2008–2014, and the impact of the improvement in antibiotic strategies on outcomes.MethodsThis was a matched case–control study enrolling 144 patients with non-pneumococcal severe pneumonia: 72 patients from the 2000–2002 database (CAPUCI I group) were paired with 72 from the 2008–2014 period (CAPUCI II group), matched by the following variables: microorganism, shock at admission, invasive mechanical ventilation, immunocompromise, chronic obstructive pulmonary disease, and age over 65 years.ResultsThe most frequent microorganism was methicillin-susceptible Staphylococcus aureus (22.1 %) followed by Legionella pneumophila and Haemophilus influenzae (each 20.7 %); prevalence of shock was 59.7 %, while 73.6 % of patients needed invasive mechanical ventilation. Intensive care unit mortality was significantly lower in the CAPUCI II group (34.7 % versus 16.7 %; odds ratio (OR) 0.78, 95 % confidence interval (CI) 0.64–0.95; p = 0.02). Appropriate therapy according to microorganism was 91.5 % in CAPUCI I and 92.7 % in CAPUCI II, while combined therapy and early antibiotic treatment were significantly higher in CAPUCI II (76.4 versus 90.3 % and 37.5 versus 63.9 %; p < 0.05). In the multivariate analysis, combined antibiotic therapy (OR 0.23, 95 % CI 0.07–0.74) and early antibiotic treatment (OR 0.07, 95 % CI 0.02–0.22) were independently associated with decreased intensive care unit mortality.ConclusionsIn non-pneumococcal severe community-acquired pneumonia , early antibiotic administration and use of combined antibiotic therapy were both associated with increased intensive care unit survival during the study period.

Cefotaxima, 20 años después. Estudio observacional en pacientes críticos

Objetivo Conocer, tras 20 anos de la comercializacion de cefotaxima, los motivos y formas de su utilizacion, las dosis a las que se administra asi como su efectividad y tolerancia en pacientes criticos ingresados en Servicios de Medicina Intensiva (UCI) de nuestro pais. Diseno Estudio abierto, prospectivo, observacional y multicentrico. SUJETOS. Se han incluido como casos todos los pacientes a los que se ha prescrito cefotaxima en monoterapia o en combinacion con otros antibioticos. Resultados Se han incluido 624 pacientes en 44 UCI (media de 14 casos). Cefotaxima se ha indicado para tratamiento de 274 infecciones comunitarias (43,9%), 194 profilaxis (31,1%) y 156 infecciones nosocomiales (25,0%). Destacan las neumonias, tanto las comunitarias (149, 34,7%) como las relacionadas con ventilacion mecanica (62, 14,4%), seguido de las traqueobronquitis (60, 13,9%) y de las infecciones del sistema nervioso central (42, 9,8%). Mas de la mitad de las infecciones (222, 51,6%) se han presentado como sindrome de respuesta inflamatoria sistemica (SIRS), mientras que 133 (30,9%) como sepsis grave y 75 (17,4%) como shock septico. En 374 (87,0%) de los 430 casos de tratamiento de infecciones la prescripcion se ha realizado de forma empirica y en 150 de ellos (40,1%) se ha logrado la confirmacion posterior de la etiologia. En 120 (27,9%) casos se ha administrado en monoterapia y en el resto en asociacion con uno o mas antibioticos. La utilizacion de cefotaxima en profilaxis se ha valorado como fracaso en 31 (16,0%) de los 194 casos, mientras que en tratamiento se han considerado como fracaso en 98 (22,8%) de los 430 casos, 51 casos (18,6%) infecciones comunitarias, 27 (27,3%) infecciones adquiridas en UCI y 20 (35,1%) infecciones nosocomiales adquiridas fuera de UCI. En 127 (29,5%) de los 430 tratamientos de infecciones se ha modificado el tratamiento inicial, en 36 (28,3%) ocasiones por fracaso clinico, en 40 (31,5%) por aislamiento de un patogeno no cubierto, en 28 (22,0%) por aparicion de patogenos multirresistentes, en 7 (5,5%) para reducir el espectro terapeutico y 16 casos por otras razones. Tambien se ha modificado en 21 (6,0%) de los 194 casos en los que se utilizo como profilaxis. En 32 (5,1%) pacientes se han detectado 37 efectos adversos que se relacionaron de forma posible o probable con la utilizacion de cefotaxima. Los mas importantes han sido diarreas en 15 (2,4%) ocasiones y rash cutaneo en 6 (1,0%) casos. Conclusiones Cefotaxima continua siendo uno de los tratamientos de eleccion en infecciones comunitarias y nosocomiales asi como en diferentes profilaxis. Se utiliza preferentemente de forma empirica y asociado a otros antibioticos. La eficacia clinica y microbiologica es elevada mientras que los efectos adversos relacionados con su uso han sido escasos.

Sepsis and the kidney: will the leaves fall off the tree?*.

2247 Sepsis often induces organ dysfunction. Lungs and kidneys are the organs that mostly fail when sepsis occurs (1, 2). Furthermore, although acute renal failure (ARF) is a prevalent complication that frequently affects many patients in the intensive care unit, severe sepsis, and septic shock account for nearly half of all cases of ARF in the intensive care unit (3). Sepsis-induced acute kidney injury (AKI) has a significant clinical impact. ARF complicating sepsis is associated with a high mortality rate (2, 3). Several processes can contribute to the pathogenesis of AKI in general, and that of sepsis in particular, including generalized vasodilatation, local changes in microvascular blood flow, tubular obstruction, and immunological alterations along with endothelial and epithelial cell death. However, quantity of cell necrosis found in histopathological analyses appears to be little compared with the loss of renal function (4, 5). Besides, renal biopsies in patients with septic shock have shown epithelial cell apoptosis (6). For theses reasons, alternative ways of cell death have been considered. Apoptosis, one of the three recognized types of mammalian cell death (7), has been found to be involved in pathogenesis of sepsis-induced AKI (5). Apoptosis is a Greek term that refers to the “dropping off” or “falling off” of petals or leaves from plants or trees. Apoptosis differs from necrosis as cell-membrane integrity persists in the former and is early lost in necrosis resulting in whole cell swelling (7). It has been defined as a “controlled demolition at the cellular level” (8). Apoptosis prepares cells for removal by phagocytes and minimizes damage to adjoining cells. The agents of such “demolition” are enzymes named caspases. Any stimuli that prompt apoptosis activate caspases through one of three convergent pathways (8). The members of the tumor necrosis factor superfamily (FasL or tumor necrosis factor-) activate the extrinsic pathway by binding to cell-membrane death receptors that are members of the tumor necrosis factorreceptor superfamily. These extracellular ligands activate caspase-8 through Fasassociated death domain proteins. The intrinsic pathway is initiated by intracellular triggers and affects membrane permeability of mitochondria. These stress signals activate BH3-only protein family that overcomes the inhibitory effect of antiapoptotic proteins named B-cell lymphoma-2 (BCL-2) family. Activation of caspase-9 by this pathway induces release of proapoptotic proteins from mitochondria into cytosol that in turn activate other caspases. Such proteases cleave proteins and pull down the cell (7, 8). Many of the biological mediators released during the inflammatory response of sepsis, such as cytokines, reactive oxygen species, and danger-associated molecular patterns in short, can trigger apoptosis. Contrary to uncontrolled cell death of necrosis, apoptosis is a programmed cell death because it is a process that is genetically controlled (7). Risk and outcomes of sepsis are influenced by host predisposition. An increasing number of genetic variants are linked to sepsis outcome (9). Sepsis is a complex disease that cannot be attributed to a single gene. Many people become ill with sepsis but their clinical manifestations and outcomes are varied. Genetic variants such as single nucleotide polymorphisms (SNPs) could account for such variability. A systematic review found 16 studies that analyzed 35 polymorphisms, mostly SNPs, in 21 genes, to be associated to AKI in diverse clinical settings (10). Only one SNP, apolipoprotein E e2/e3/e4 was significantly associated with the phenotype in more than a study. Apolipoprotein E plays a role in inflammation. Three of these 16 studies were carried out in patients with sepsis and a significant association of cytokine-gene polymorphisms combinations with septic AKI was found in two studies. Frank and colleagues report in this issue of Critical Care Medicine (11) the findings of a genetic association study done retrospectively in a cohort of 1,264 patients diagnosed of septic shock. The authors searched for clinical predictors of AKI in this cohort. They also analyzed the blood of 887 patients using a multisample genotyping panel (Human-CVD BeadChip) involving around 2,100 genes, to find SNPs that could predict AKI occurrence in septic shock. This large-scale gene-centric genotyping disclosed three intron variants in chromosomes 18 and 14 (two SNPs in the BCL2 gene and a SNP in the SERPINA4 gene) that were signifi cantly associated with a lesser risk of AKI development. However, patients with an intronic SNP in the SIK3 gene exhibited an increased risk of septic AKI. Because BCL2 and SERPINA4 genes, respectively, encode two proteins (Bcl-2 and kallistatin) involved in apoptosis which inhibit, and programmed cell death is genetically controlled, the authors conclude that apoptosis is involved in the pathogenesis of sepsis-induced AKI. The underlying cause and mechanisms of AKI in patients with septic shock may be varied. Sepsis is a complex disease subject to significant gene-environment interactions including the coexistence of other phenotypes such as cardiac and vascular reserves. Phenotype definition should be precise in a genetic association study to establish a real genotypephenotype association (12). Intermediate phenotypes could have been measured (13). Neither messenger RNA expression of these proteins nor blood levels of Bcl2 and kallistatin were evaluated in this genetic association study. An association was only analyzed between three SNPs and a clinical outcome as a sepsis-induced organ failure. Such an outcome was defined by criteria from an expert panel consensus, the Acute Kidney Injury Network (14). The Acute Kidney Injury Network classification modified the previous Risk-Injury-Failure-Loss-End-stage renal disease definitions (15) although both classifications have demonstrated to be useful to predict mortality. Given the heterogeneity of sepsis disease, other covariates (including appropriate antimicrobial *See also p. 2116.