Compliance-guided versus FiO2-driven positive-end expiratory pressure in patients with moderate or severe acute respiratory distress syndrome according to the Berlin definition.

OBJECTIVE: To study the effect of setting positive end-expiratory pressure (PEEP) in an individualized manner (based on highest static compliance) compared to setting PEEP according to FiO2 upon mortality at 28 and 90 days, in patients with different severity acute respiratory distress syndrome (ARDS). SETTING: A Spanish medical-surgical ICU. DESIGN: A post hoc analysis of a randomized controlled pilot study. PATIENTS: Patients with ARDS. INTERVENTIONS: Ventilation with low tidal volumes and pressure limitation at 30cmH2O, randomized in two groups according to the method used to set PEEP: FiO2-guided PEEP group according to FiO2 applied and compliance-guided group according to the highest compliance. PRIMARY VARIABLES OF INTEREST: Demographic data, risk factors and severity of ARDS, APACHE II and SOFA scores, daily Lung Injury Score, ventilatory measurements, ICU and hospital stay, organ failure and mortality at day 28 and 90 after inclusion. RESULTS: A total of 159 patients with ARDS were evaluated, but just 70 patients were included. Severe ARDS patients showed more organ dysfunction-free days at 28 days (12.83±10.70 versus 3.09±7.23; p=0.04) and at 90 days (6.73±22.31 vs. 54.17±42.14, p=0.03), and a trend toward lower 90-days mortality (33.3% vs. 90.9%, p=0.02), when PEEP was applied according to the best static compliance. Patients with moderate ARDS did not show these effects. CONCLUSIONS: In patients with severe ARDS, individualized PEEP selection based on the best static compliance was associated to lower mortality at 90 days, with an increase in organ dysfunction-free days at 28 and 90 days.

Mortality and functional status at one-year of follow-up in elderly patients with prolonged ICU stay. / Mortalidad y estado funcional al año de pacientes ancianos con ingreso prolongado en una unidad de cuidados intensivos.

OBJECTIVE: To evaluate mortality and functional status at one year of follow-up in patients>75 years of age who survive Intensive Care Unit (ICU) admission of over 14 days. DESIGN: A prospective observational study was carried out. SETTING: A Spanish medical-surgical ICU. PATIENTS: Patients over 75 years of age admitted to the ICU. PRIMARY VARIABLES OF INTEREST: ICU admission: demographic data, baseline functional status (Barthel index), baseline mental status (Red Cross scale of mental incapacity), severity of illness (APACHE II and SOFA), stay and mortality. One-year follow-up: hospital stay and mortality, functional and mental status, and one-year follow-up mortality. RESULTS: A total of 176 patients were included, of which 22 had a stay of over 14 days. Patients with prolonged stay did not show more ICU mortality than those with a shorter stay in the ICU (40.9% vs 25.3% respectively, P=.12), although their hospital (63.6% vs 33.8%, P<.01) and one-year follow-up mortality were higher (68.2% vs 41.2%, P=.02). Among the survivors, one-year mortality proved similar (87.5% vs 90.6%, P=.57). These patients presented significantly greater impairment of functional status at hospital discharge than the patients with a shorter ICU stay, and this difference persisted after three months. The levels of independence at one-year follow-up were never similar to baseline. No such findings were observed in relation to mental status. CONCLUSIONS: Patients over 75 years of age with a ICU stay of more than 14 days have high hospital and one-year follow-up mortality. Patients who survive to hospital admission did not show greater mortality, though their functional dependency was greater.

Individualized positive end-expiratory pressure application in patients with acute respiratory distress syndrome.

Current treatment of acute respiratory distress syndrome is based on ventilatory support with a lung protective strategy, avoiding the development of iatrogenic injury, including ventilator-induced lung injury. One of the mechanisms underlying such injury is atelectrauma, and positive end-expiratory pressure (PEEP) is advocated in order to avoid it. The indicated PEEP level has not been defined, and in many cases is based on the patient oxygen requirements for maintaining adequate oxygenation. However, this strategy does not consider the mechanics of the respiratory system, which varies in each patient and depends on many factors-including particularly the duration of acute respiratory distress syndrome. A review is therefore made of the different methods for adjusting PEEP, focusing on the benefits of individualized application.

Advancing allele group-specific amplification of the complete HLA-C gene--isolation of novel alleles from three allele groups (C*04, C*07 and C*08).

A variety of strategies have been designed for sequence-based HLA typing (SBT) and for the isolation of new human leucocyte antigen (HLA) alleles, but unambiguous characterization of complete genomic sequences remains a challenge. We recently reported a simple method for the group-specific amplification (GSA) and sequencing of a full-length C*04 genomic sequence in isolation from the accompanying allele. Here we build on this strategy and present homologous methods that enable the isolation of HLA-C alleles belonging to another two allele groups. Using this approach, which can be applied to sequence-based typing in some clinical settings, we have successfully characterized three novel HLA-C alleles (C*04:128, C*07:01:01:02, and C*08:62).

Role of circulating soluble chemokines in septic shock.

PURPOSE: Chemokines are a large superfamily of small proteins that function not only in leukocyte trafficking, but are also necessary for linkage between innate and adaptive immunity. Little is known about their role in septic shock. We hypothesized that serum levels of the most important chemokines are related to organ failure, disease severity and outcome. DESIGN: A prospective observational study was carried out. SETTING: Surgical-clinical Intensive Care Unit. PATIENTS: Ninety-two patients diagnosed with septic shock using international criteria. Forty patients were excluded due to acquired immunity disturbances. Samples from 36 healthy controls were also analyzed. INTERVENTIONS: None. RESULTS: In 46% of the patients who suffered acute respiratory distress syndrome (ARDS), IL-8 levels were higher than in patients without ARDS (499.9±194.1 vs. 190.8±91.7 pg/ml; P=.039). This molecule was also higher in 36% of the patients with sepsis-induced acute renal failure (ARF) (453.3±181.6 vs. 201.3±95.9 pg/ml; P=.049). Coagulopathy was found in 19% of the septic shock patients with elevated serum IL-8 levels (635.8±292.3 vs. 218.7±87.0 pg/ml; P=.010), elevated MIP-1α (91.4±27.3 vs. 58.8±11.1 pg/ml; P=.044), and low circulating RANTES levels (8162.2±6321.0 vs. 18781.8±11.1 pg/ml; P=.027). No significant differences were found between survivors and non-survivors at any time of follow-up. CONCLUSIONS: Upon admission to the ICU, IL-8 is a reliable biomarker of sepsis-induced AFR, ARDS and coagulopathy. Altered circulating MIP-1α and RANTES levels are also found in patients with septic shock and coagulopathy. However, chemokines do not appear to be good biomarkers of mortality in septic shock.

Allele-specific amplification of the complete HLA-C gene from genomic DNA - a novel Cw4 allele (C*04:71) with a Cw1 motif in the peptide-binding site.

To determine the complete sequence of a newly identified human leukocyte antigen (HLA)-C allele, we designed a method where the full genomic sequence of HLA-C*04 was amplified in isolation from the patient second HLA-C allele in a single polymerase chain reaction (PCR), using primers spanning its 5'- and 3'-untranslated regions. The new allele, officially designated HLA-C*04:71, differs from HLA-C*04:01:01:01 by two single-nucleotide polymorphisms: one determines substitution of phenylalanine for serine 9 at the B pocket of the peptide-binding site; the second substitution is a new polymorphism in intron 5. Phe-9 is characteristic of Cw1 alleles and its presence in C*04:71 most likely affects its peptide-binding repertoire. The principle we have used for C*04:71 isolation could be adapted for unambiguous sequence-based HLA-C typing of selected samples in a clinical setting.

Assessment of copy-number variation in the NKG2C receptor gene in a single-tube and characterization of a reference cell panel, using standard polymerase chain reaction.

Natural killer (NK) and T-lymphocytes monitor human leukocyte antigen (HLA)-E expression through CD94:NKG2 heterodimers. Structural polymorphism is not a hallmark for NK-complex genes on chromosome 12, except for complete NKG2C deletion in some humans. We present a method for fast, simple and accurate assessment of NKG2C copy-number variation - presence or absence in the genome of an NKG2C gene, in homo- or heterozygosis, is detected by a single conventional polymerase chain reaction that yields amplicons of different lengths in each genotype. We have also determined the NKG2C genotypes of a reference cell panel comprising 13 NK- and tumour-cell lines and 39 Epstein-Barr virus transformed cells from the International Histocompatibility Workshop. Our results should facilitate research on the importance of NKG2C and its deletion for immunity.

Mechanical ventilation in Spain, 1998-2016: Changes in the disconnection of mechanical ventilation.

PURPOSE: To evaluate changes in the disconnection of mechanical ventilation in Spain from 1998 to 2016. DESIGN: Post-hoc analysis of four cohort studies. AMBIT: 138 Spanish ICUs. PATIENTS: 2141 patients scheduled extubated. INTERVENTIONS: None. VARIABLES OF INTEREST: Demographics, reason for mechanical ventilation, complications, methods for disconnection, failure on the first attempt at disconnection, duration of weaning, reintubation, post-reintubation tracheotomy, ICU stay and mortality. RESULTS: There was a significant increase (p < 0.001) in the use of gradual reduction of support pressure. The adjusted probability of using the gradual reduction in pressure support versus a spontaneous breathing trial has increased over time, both for the first attempt at disconnection (taking the 1998 study as a reference: odds ratio 0.99 in 2004, 0.57 in 2010 and 2.43 in 2016) and for difficult/prolonged disconnection (taking the 1998 study as a reference: odds ratio 2.29 in 2004, 1.23 in 2010 and 2.54 in 2016). The proportion of patients extubated after the first attempt at disconnection has increased over time. There is a decrease in the ventilation time dedicated to weaning (from 45% in 1998 to 36% in 2016). However, the duration in difficult/prolonged weaning has not decreased (median 3 days in all studies, p = 0.435). CONCLUSIONS: There have been significant changes in the mode of disconnection of mechanical ventilation, with a progressive increase in the use of gradual reduction of pressure support. No relevant changes in outcomes have been observed.

Rapid response to COVID-19, escalation and de-escalation strategies to match surge capacity of Intensive Care beds to a large scale epidemic. / Respuesta rápida a COVID-19, estrategias de escalada y desescalada para ajustar la capacidad suplementaria de camas de UVI a una epidemia de gran magnitud.

BACKGROUND: A major challenge during the COVID-19 outbreak is the sudden increase in ICU bed occupancy rate. In this article we reviewed the strategies of escalation and de-escalation put in place at a large university hospital in Madrid during the COVID-19 outbreak, in order to meet the growing demand of ICU beds. MATERIALS AND METHODS: The data displayed originated from the hospital information system and the hospital contingency plan. RESULTS: The COVID-19 outbreak produced a surge of ICU patients which saturated the available ICU capacity within a few days. A total of four new ICUs had to be opened in order to accommodate all necessary new ICU admissions. Management challenges included infrastructure, material allocation and ICU staffing. Through the strategies put in place the hospital was able to generate a surge capacity of ICU beds of 340%, meet all requirements and also maintain minimal surgical activity. CONCLUSIONS: Hospital surge capacity is to date hardly quantifiable and often has to face physical limitations (material, personnel, spaces). However an extremely flexible and adaptable management strategy can help to overcome some of these limitations and stretch the system capacities during times of extreme need.

Mechanical ventilation in Spain, 1998-2016: changes in the disconnection of mechanical ventilation. / Ventilación mecánica en España, 1998-2016: cambios en la desconexión de la ventilación mecánica.

PURPOSE: To evaluate changes in the disconnection of mechanical ventilation in Spain from 1998 to 2016. DESIGN: Post-hoc analysis of four cohort studies. AMBIT: 138 Spanish ICUs. PATIENTS: 2141 patients scheduled extubated. INTERVENTIONS: None. VARIABLES OF INTEREST: Demographics, reason for mechanical ventilation, complications, methods for disconnection, failure on the first attempt at disconnection, duration of weaning, reintubation, post-reintubation tracheotomy, ICU stay and mortality. RESULTS: There was a significant increase (p<0.001) in the use of gradual reduction of support pressure. The adjusted probability of using the gradual reduction in pressure support versus a spontaneous breathing trial has increased over time, both for the first attempt at disconnection (taking the 1998 study as a reference: odds ratio 0.99 in 2004, 0.57 in 2010 and 2.43 in 2016) and for difficult/prolonged disconnection (taking the 1998 study as a reference: odds ratio 2.29 in 2004, 1.23 in 2010 and 2.54 in 2016). The proportion of patients extubated after the first attempt at disconnection has increased over time. There is a decrease in the ventilation time dedicated to weaning (from 45% in 1998 to 36% in 2016). However, the duration in difficult/prolonged weaning has not decreased (median 3 days in all studies, p=0.435). CONCLUSIONS: There have been significant changes in the mode of disconnection of mechanical ventilation, with a progressive increase in the use of gradual reduction of pressure support. No relevant changes in outcomes have been observed.

Mechanical ventilation in Spain, 1998-2016: Epidemiology and outcomes. / Ventilación mecánica en España, 1998-2016: epidemiología y desenlaces.

PURPOSE: To evaluate changes in the epidemiology of mechanical ventilation in Spain from 1998 to 2016. DESIGN: A post hoc analysis of four cohort studies was carried out. SETTING: A total of 138 Spanish ICUs. PATIENTS: A sample of 4293 patients requiring invasive mechanical ventilation for more than 12h or noninvasive ventilation for more than 1h. INTERVENTIONS: None. VARIABLES OF INTEREST: Demographic variables, reason for mechanical ventilation, variables related to ventilatory support (ventilation mode, tidal volume, PEEP, airway pressures), complications during mechanical ventilation, duration of mechanical ventilation, ICU stay and ICU mortality. RESULTS: There was an increase in severity (SAPSII: 43 points in 1998 vs. 47 points in 2016), changes in the reason for mechanical ventilation (decrease in chronic obstructive pulmonary disease and acute respiratory failure secondary to trauma, and increase in neurological disease and post-cardiac arrest). There was an increase in noninvasive mechanical ventilation as the first mode of ventilatory support (p<0.001). Volume control ventilation was the most commonly used mode, with increased support pressure and pressure-regulated volume-controlled ventilation. A decrease in tidal volume was observed (9ml/kg actual b.w. in 1998 and 6.6ml/kg in 2016; p<0.001) as well as an increase in PEEP (3cmH2O in 1998 and 6cmH2O in 2016; p<0.001). In-ICU mortality decreased (34% in 1998 and 27% in 2016; p<0.001), without geographical variability (median OR 1.43; p=0.258). CONCLUSIONS: A significant decrease in mortality was observed in patients ventilated in Spanish ICUs. These changes in mortality could be related to modifications in ventilation strategy to minimize ventilator-induced lung injury.