Moderate Traumatic Brain Injury in Adult Population: The Latin American Brain Injury Consortium Consensus for Definition and Categorization.

Moderate traumatic brain injury (TBI) is a diagnosis that describes diverse patients with heterogeneity of primary injuries. Defined by a Glasgow Coma Scale between 9 and 12, this category includes patients who may neurologically worsen and require increasing intensive care resources and/or emergency neurosurgery. Despite the unique characteristics of these patients, there have not been specific guidelines published before this effort to support decision-making in these patients. A Delphi consensus group from the Latin American Brain Injury Consortium was established to generate recommendations related to the definition and categorization of moderate TBI. Before an in-person meeting, a systematic review of the literature was performed identifying evidence relevant to planned topics. Blinded voting assessed support for each recommendation. A priori the threshold for consensus was set at 80% agreement. Nine PICOT questions were generated by the panel, including definition, categorization, grouping, and diagnosis of moderate TBI. Here, we report the results of our work including relevant consensus statements and discussion for each question. Moderate TBI is an entity for which there is little published evidence available supporting definition, diagnosis, and management. Recommendations based on experts' opinion were informed by available evidence and aim to refine the definition and categorization of moderate TBI. Further studies evaluating the impact of these recommendations will be required.

Risk factors for developing ventilator-associated lower respiratory tract infection in patients with severe COVID-19: a multinational, multicentre study, prospective, observational study.

Around one-third of patients diagnosed with COVID-19 develop a severe illness that requires admission to the Intensive Care Unit (ICU). In clinical practice, clinicians have learned that patients admitted to the ICU due to severe COVID-19 frequently develop ventilator-associated lower respiratory tract infections (VA-LRTI). This study aims to describe the clinical characteristics, the factors associated with VA-LRTI, and its impact on clinical outcomes in patients with severe COVID-19. This was a multicentre, observational cohort study conducted in ten countries in Latin America and Europe. We included patients with confirmed rtPCR for SARS-CoV-2 requiring ICU admission and endotracheal intubation. Only patients with a microbiological and clinical diagnosis of VA-LRTI were included. Multivariate Logistic regression analyses and Random Forest were conducted to determine the risk factors for VA-LRTI and its clinical impact in patients with severe COVID-19. In our study cohort of 3287 patients, VA-LRTI was diagnosed in 28.8% [948/3287]. The cumulative incidence of ventilator-associated pneumonia (VAP) was 18.6% [610/3287], followed by ventilator-associated tracheobronchitis (VAT) 10.3% [338/3287]. A total of 1252 bacteria species were isolated. The most frequently isolated pathogens were Pseudomonas aeruginosa (21.2% [266/1252]), followed by Klebsiella pneumoniae (19.1% [239/1252]) and Staphylococcus aureus (15.5% [194/1,252]). The factors independently associated with the development of VA-LRTI were prolonged stay under invasive mechanical ventilation, AKI during ICU stay, and the number of comorbidities. Regarding the clinical impact of VA-LRTI, patients with VAP had an increased risk of hospital mortality (OR [95% CI] of 1.81 [1.40-2.34]), while VAT was not associated with increased hospital mortality (OR [95% CI] of 1.34 [0.98-1.83]). VA-LRTI, often with difficult-to-treat bacteria, is frequent in patients admitted to the ICU due to severe COVID-19 and is associated with worse clinical outcomes, including higher mortality. Identifying risk factors for VA-LRTI might allow the early patient diagnosis to improve clinical outcomes.Trial registration: This is a prospective observational study; therefore, no health care interventions were applied to participants, and trial registration is not applicable.

Managing Severe Traumatic Brain Injury Across Resource Settings: Latin American Perspectives.

Severe traumatic brain injury (sTBI) is a condition of increasing epidemiologic concern worldwide. Outcomes are worse as observed in low- and middle-income countries (LMICs) versus high-income countries. Global targets are in place to address the surgical burden of disease. At the same time, most of the published literature and evidence on the clinical approach to sTBI comes from wealthy areas with an abundance of resources. The available paradigms, including the Brain Trauma Foundation guidelines, the Seattle International Severe Traumatic Brain Injury Consensus Conference, Consensus Revised Imaging and Clinical Examination, and multimodality approaches, may fit differently depending on local resources, expertise, and sociocultural factors. A first step toward addressing heterogeneity in practice is to consider comparative effectiveness approaches that can capture actual practice patterns and record short-term and long-term outcomes of interest. Decompressive craniectomy (DC) decreases intracranial pressure burden and can be lifesaving. Nevertheless, completed randomized controlled trials took place within high-income settings, leaving important questions unanswered and making extrapolations to LMICs questionable. The concept of preemptive DC specifically to address limited neuromonitoring resources may warrant further study to establish a benefit/risk profile for the procedure and its role within local protocols of care.

Weaning Outcomes in Patients with Brain Injury.

BACKGROUND: Despite the need for specific weaning strategies in neurological patients, evidence is generally insufficient or lacking. We aimed to describe the evolution over time of weaning and extubation practices in patients with acute brain injury compared with patients who are mechanically ventilated (MV) due to other reasons. METHODS: We performed a secondary analysis of three prospective, observational, multicenter international studies conducted in 2004, 2010, and 2016 in adults who had need of invasive MV for more than 12 h. We collected data on baseline characteristics, variables related to management ventilator settings, and complications while patients were ventilated or until day 28. RESULTS: Among the 20,929 patients enrolled, we included 12,618 (60%) who started the weaning from MV, of whom 1722 (14%) were patients with acute brain injury. In the acutely brain-injured cohort, 538 patients (31%) did not undergo planned extubation, defined as the need for a tracheostomy without an attempt of extubation, accidental extubation, and death. Among the 1184 planned extubated patients with acute brain injury, 202 required reintubation (17%). Patients with acute brain injury had a higher odds for unplanned extubation (odds ratio [OR] 1.35, confidence interval for 95% [CI 95%] 1.19-1.54; p < 0.001), a higher odds of failure after the first attempt of weaning (spontaneous breathing trial or gradual reduction of ventilatory support; OR 1.14 [CI 95% 1.01-1.30; p = 0.03]), and a higher odds for reintubation (OR 1.41 [CI 95% 1.20-1.66; p < 0.001]) than patients without brain injury. Patients with hemorrhagic stroke had the highest odds for unplanned extubation (OR 1.47 [CI 95% 1.22-1.77; p < 0.001]), of failed extubation after the first attempt of weaning (OR 1.28 [CI 95% 1.06-1.55; p = 0.009]), and for reintubation (OR 1.49 [CI 95% 1.17-1.88; p < 0.001]). In relation to weaning evolution over time in patients with acute brain injury, the risk for unplanned extubation showed a downward trend; the risk for reintubation was not associated to time; and there was a significant increase in the percentage of patients who underwent extubation after the first attempt of weaning from MV. CONCLUSIONS: Patients with acute brain injury, compared with patients without brain injury, present higher odds of undergoing unplanned extubated after weaning was started, lower odds of being extubated after the first attempt, and a higher risk of reintubation.

Effect of High Altitude on the Survival of COVID-19 Patients in Intensive Care Unit: A Cohort Study.

Purpose: The effect of high altitude ( ≥ 1500 m) and its potential association with mortality by COVID-19 remains controversial. We assessed the effect of high altitude on the survival/discharge of COVID-19 patients requiring intensive care unit (ICU) admission for mechanical ventilation compared to individuals treated at sea level. Methods: A retrospective cohort multi-center study of consecutive adults patients with a positive RT-PCR test for COVID-19 who were mechanically ventilated between March and November 2020. Data were collected from two sea-level hospitals and four high-altitude hospitals in Ecuador. The primary outcome was ICU and hospital survival/discharge. Survival analysis was conducted using semi-parametric Cox proportional hazards models. Results: Of the study population (n = 670), 35.2% were female with a mean age of 58.3 ± 12.6 years. On admission, high-altitude patients were more likely to be younger (57.2 vs. 60.5 years old), presented with less comorbidities such as hypertension (25.9% vs. 54.9% with p-value <.001) and diabetes mellitus (20.5% vs. 37.2% with p-value <.001), less probability of having a capillary refill time > 3 sec (13.7% vs. 30.1%, p-value <.001), and less severity-of-illness condition (APACHE II score, 17.5 ± 8.1 vs. 20 ± 8.2, p < .01). After adjusting for key confounders high altitude is associated with significant higher probabilities of ICU survival/discharge (HR: 1.74 [95% CI: 1.46-2.08]) and hospital survival/discharge (HR: 1.35 [95% CI: 1.18-1.55]) than patients treated at sea level. Conclusions: Patients treated at high altitude at any time point during the study period were 74% more likely to experience ICU survival/discharge and 35% more likely to experience hospital survival/discharge than to the sea-level group. Possible reasons for these findings are genetic and physiological adaptations due to exposure to chronic hypoxia.

Clinical characteristics, systemic complications, and in-hospital outcomes for patients with COVID-19 in Latin America. LIVEN-Covid-19 study: A prospective, multicenter, multinational, cohort study.

PURPOSE: The COVID-19 pandemic has spread worldwide, and almost 396 million people have been infected around the globe. Latin American countries have been deeply affected, and there is a lack of data in this regard. This study aims to identify the clinical characteristics, in-hospital outcomes, and factors associated with ICU admission due to COVID-19. Furthermore, to describe the functional status of patients at hospital discharge after the acute episode of COVID-19. MATERIAL AND METHODS: This was a prospective, multicenter, multinational observational cohort study of subjects admitted to 22 hospitals within Latin America. Data were collected prospectively. Descriptive statistics were used to characterize patients, and multivariate regression was carried out to identify factors associated with severe COVID-19. RESULTS: A total of 3008 patients were included in the study. A total of 64.3% of patients had severe COVID-19 and were admitted to the ICU. Patients admitted to the ICU had a higher mean (SD) 4C score (10 [3] vs. 7 [3)], p<0.001). The risk factors independently associated with progression to ICU admission were age, shortness of breath, and obesity. In-hospital mortality was 24.1%, whereas the ICU mortality rate was 35.1%. Most patients had equal self-care ability at discharge 43.8%; however, ICU patients had worse self-care ability at hospital discharge (25.7% [497/1934] vs. 3.7% [40/1074], p<0.001). CONCLUSIONS: This study confirms that patients with SARS CoV-2 in the Latin American population had a lower mortality rate than previously reported. Systemic complications are frequent in patients admitted to the ICU due to COVID-19, as previously described in high-income countries.

Dexamethasone as risk-factor for ICU-acquired respiratory tract infections in severe COVID-19.

PURPOSE: Dexamethasone is the only drug that has consistently reduced mortality in patients with COVID-19, especially in patients needing oxygen or invasive mechanical ventilation. However, there is a growing concern about the relation of dexamethasone with the unprecedented rates of ICU-acquired respiratory tract infections (ICU-RTI) observed in patients with severe COVID-19. METHODS: This was a multicenter, prospective cohort study; conducted in ten countries in Latin America and Europe. We included patients older than 18 with confirmed SARS-CoV-2 requiring ICU admission. A multivariate logistic regression and propensity score matching (PSM) analysis was conducted to determine the relation between dexamethasone treatment and ICU-RTI. RESULTS: A total of 3777 patients were included. 2065 (54.7%) were treated with dexamethasone within the first 24 h of admission. After performing the PSM, patients treated with dexamethasone showed significantly higher proportions of VAP (282/1652 [17.1%] Vs. 218/1652 [13.2%], p = 0.014). Also, dexamethasone treatment was identified as an adjusted risk factor of ICU-RTI in the multivariate logistic regression model (OR 1.64; 95%CI: 1.37-1.97; p < 0.001). CONCLUSION: Patients treated with dexamethasone for severe COVID-19 had a higher risk of developing ICU-acquired respiratory tract infections after adjusting for days of invasive mechanical ventilation and ICU length of stay, suggesting a cautious use of this treatment.

Management of severe traumatic brain injury in regions with limited resources.

IMPORTANCE: Severe traumatic brain injury (sTBI) is a critical health problem in regions of limited resources (RLRs). Younger populations are among the most impacted. The objective of this review is to analyze recent consensus-based algorithms, protocols and guidelines proposed for the care of patients with TBI in RLRs. OBSERVATIONS: The principal mechanisms for sTBI in RLRs are road traffic injuries (RTIs) and violence. Limitations of care include suboptimal or non-existent pre-hospital care, overburdened emergency services, lack of trained human resources, and surgical and intensive care. Low-cost neuromonitoring systems are currently in testing, and formal neurotrauma registries are forming to evaluate both long-term outcomes and best practices at every level of care from hospital transport to the emergency department (ED), to the operating room and intensive care unit (ICU). CONCLUSIONS AND RELEVANCE: The burden of sTBI is highest in RLRs. As working-age adults are the predominantly affected age-group, an increase in disability-adjusted life years (DALYs) generates a loss of economic growth in regions where economic growth is needed most. Four multi-institutional collaborations between high-income countries (HICs) and LMICs have developed evidence and consensus-based documents focused on capacity building for sTBI care as a means of addressing this substantial burden of disease.

Driving Pressure Is a Risk Factor for ARDS in Mechanically Ventilated Subjects Without ARDS.

BACKGROUND: Driving pressure (ΔP) has been described as a risk factor for mortality in patients with ARDS. However, the role of ΔP in the outcome of patients without ARDS and on mechanical ventilation has received less attention. Our objective was to evaluate the association between ΔP on the first day of mechanical ventilation with the development of ARDS. METHODS: This was a post hoc analysis of a multicenter, prospective, observational, international study that included subjects who were on mechanical ventilation for > 12 h. Our objective was to evaluate the association between ΔP on the first day of mechanical ventilation with the development of ARDS. To assess the effect of ΔP, a logistic regression analysis was performed when adjusting for other potential risk factors. Validation of the results obtained was performed by using a bootstrap method and by repeating the same analyses at day 2. RESULTS: A total of 1,575 subjects were included, of whom 65 (4.1%) developed ARDS. The ΔP was independently associated with ARDS (odds ratio [OR] 1.12, 95% CI 1.07-1.18 for each cm H2O of ΔP increase, P < .001). The same results were observed at day 2 (OR 1.14, 95% CI 1.07-1.21; P < .001) and after bootstrap validation (OR 1.13, 95% CI 1.04-1.22; P < .001). When taking the prevalence of ARDS in the lowest quartile of ΔP (≤9 cm H2O) as a reference, the subjects with ΔP > 12-15 cm H2O and those with ΔP > 15 cm H2O presented a higher probability of ARDS (OR 3.65, 95% CI 1.32-10.04 [P = .01] and OR 7.31, 95% CI, 2.89-18.50 [P < .001], respectively). CONCLUSIONS: In the subjects without ARDS, a higher level of ΔP on the first day of mechanical ventilation was associated with later development of ARDS. (ClinicalTrials.gov registration NCT02731898.).

Machine learning predicts mortality based on analysis of ventilation parameters of critically ill patients: multi-centre validation.

BACKGROUND: Mechanical Ventilation (MV) is a complex and central treatment process in the care of critically ill patients. It influences acid-base balance and can also cause prognostically relevant biotrauma by generating forces and liberating reactive oxygen species, negatively affecting outcomes. In this work we evaluate the use of a Recurrent Neural Network (RNN) modelling to predict outcomes of mechanically ventilated patients, using standard mechanical ventilation parameters. METHODS: We performed our analysis on VENTILA dataset, an observational, prospective, international, multi-centre study, performed to investigate the effect of baseline characteristics and management changes over time on the all-cause mortality rate in mechanically ventilated patients in ICU. Our cohort includes 12,596 adult patients older than 18, associated with 12,755 distinct admissions in ICUs across 37 countries and receiving invasive and non-invasive mechanical ventilation. We carry out four different analysis. Initially we select typical mechanical ventilation parameters and evaluate the machine learning model on both, the overall cohort and a subgroup of patients admitted with respiratory disorders. Furthermore, we carry out sensitivity analysis to evaluate whether inclusion of variables related to the function of other organs, improve the predictive performance of the model for both the overall cohort as well as the subgroup of patients with respiratory disorders. RESULTS: Predictive performance of RNN-based model was higher with Area Under the Receiver Operating Characteristic (ROC) Curve (AUC) of 0.72 (± 0.01) and Average Precision (AP) of 0.57 (± 0.01) in comparison to RF and LR for the overall patient dataset. Higher predictive performance was recorded in the subgroup of patients admitted with respiratory disorders with AUC of 0.75 (± 0.02) and AP of 0.65 (± 0.03). Inclusion of function of other organs further improved the performance to AUC of 0.79 (± 0.01) and AP 0.68 (± 0.02) for the overall patient dataset and AUC of 0.79 (± 0.01) and AP 0.72 (± 0.02) for the subgroup with respiratory disorders. CONCLUSION: The RNN-based model demonstrated better performance than RF and LR in patients in mechanical ventilation and its subgroup admitted with respiratory disorders. Clinical studies are needed to evaluate whether it impacts decision-making and patient outcomes. TRIAL REGISTRATION: NCT02731898 ( https://clinicaltrials.gov/ct2/show/NCT02731898 ), prospectively registered on April 8, 2016.

Evolution Over Time of Ventilatory Management and Outcome of Patients With Neurologic Disease.

OBJECTIVES: To describe the changes in ventilator management over time in patients with neurologic disease at ICU admission and to estimate factors associated with 28-day hospital mortality. DESIGN: Secondary analysis of three prospective, observational, multicenter studies. SETTING: Cohort studies conducted in 2004, 2010, and 2016. PATIENTS: Adult patients who received mechanical ventilation for more than 12 hours. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Among the 20,929 patients enrolled, we included 4,152 (20%) mechanically ventilated patients due to different neurologic diseases. Hemorrhagic stroke and brain trauma were the most common pathologies associated with the need for mechanical ventilation. Although volume-cycled ventilation remained the preferred ventilation mode, there was a significant (p < 0.001) increment in the use of pressure support ventilation. The proportion of patients receiving a protective lung ventilation strategy was increased over time: 47% in 2004, 63% in 2010, and 65% in 2016 (p < 0.001), as well as the duration of protective ventilation strategies: 406 days per 1,000 mechanical ventilation days in 2004, 523 days per 1,000 mechanical ventilation days in 2010, and 585 days per 1,000 mechanical ventilation days in 2016 (p < 0.001). There were no differences in the length of stay in the ICU, mortality in the ICU, and mortality in hospital from 2004 to 2016. Independent risk factors for 28-day mortality were age greater than 75 years, Simplified Acute Physiology Score II greater than 50, the occurrence of organ dysfunction within first 48 hours after brain injury, and specific neurologic diseases such as hemorrhagic stroke, ischemic stroke, and brain trauma. CONCLUSIONS: More lung-protective ventilatory strategies have been implemented over years in neurologic patients with no effect on pulmonary complications or on survival. We found several prognostic factors on mortality such as advanced age, the severity of the disease, organ dysfunctions, and the etiology of neurologic disease.

Propensity-Adjusted Comparison of Mortality of Elderly Versus Very Elderly Ventilated Patients.

BACKGROUND: The growing proportion of elderly intensive care patients constitutes a public health challenge. The benefit of critical care in these patients remains unclear. We compared outcomes in elderly versus very elderly subjects receiving mechanical ventilation. METHODS: In total, 5,557 mechanically ventilated subjects were included in our post hoc retrospective analysis, a subgroup of the VENTILA study. We divided the cohort into 2 subgroups on the basis of age: very elderly subjects (age ≥ 80 y; n = 1,430), and elderly subjects (age 65-79 y; n = 4,127). A propensity score on being very elderly was calculated. Evaluation of associations with 28-d mortality was done with logistic regression analysis. RESULTS: Very elderly subjects were clinically sicker as expressed by higher SAPS II scores (53 ± 18 vs 50 ± 18, P < .001), and their rates of plateau pressure < 30 cm H2O were higher, whereas other parameters did not differ. The 28-d mortality was higher in very elderly subjects (42% vs 34%, P < .001) and remained unchanged after propensity score adjustment (adjusted odds ratio 1.31 [95% CI 1.16-1.49], P < .001). CONCLUSIONS: Age was an independent and unchangeable risk factor for death in mechanically ventilated subjects. However, survival rates of very elderly subjects were > 50%. Denial of critical care based solely on age is not justified. (ClinicalTrials.gov registration NCT02731898.).

Metagenome of a Bronchoalveolar Lavage Fluid Sample from a Confirmed COVID-19 Case in Quito, Ecuador, Obtained Using Oxford Nanopore MinION Technology.

We report the metagenome analysis of a bronchoalveolar lavage (BAL) fluid sample from a confirmed coronavirus disease 2019 (COVID-19) case in Quito, Ecuador. Sequencing was performed using MinION technology.

Genome sequencing of the first SARS-CoV-2 reported from patients with COVID-19 in Ecuador.

SARS-CoV-2, the etiological agent of COVID-19 was first described in Wuhan in December 2019 and has now spread globally. Ecuador was the second country in South America to report confirmed cases. The first case reported in Quito, the capital city of Ecuador, was a tourist who came from the Netherlands and presented symptoms on March 10th, 2020 (index case). In this work we used the MinION platform (Oxford Nanopore Technologies) to sequence the metagenome of the bronchoalveolar lavage (BAL) from this case reported, and subsequently we sequenced the whole genome of the index case and other three patients using the ARTIC network protocols. Our data from the metagenomic approach confirmed the presence of SARS-CoV-2 coexisting with pathogenic bacteria suggesting coinfection. Relevant bacteria found in the BAL metagenome were Streptococcus pneumoniae, Mycobacterium tuberculosis, Staphylococcus aureus and Chlamydia spp. Lineage assignment of the four whole genomes revealed three different origins. The variant HEE-01 was imported from the Netherlands and was assigned to B lineage, HGSQ-USFQ-018, belongs to the B.1 lineage showing nine nucleotide differences with the reference strain and grouped with sequences from the United Kingdom, and HGSQ-USFQ-007 and HGSQ-USFQ-010 belong to the B lineage and grouped with sequences from Scotland. All genomes show mutations in their genomes compared to the reference strain, which could be important to understand the virulence, severity and transmissibility of the virus. Our findings also suggest that there were at least three independent introductions of SARS-CoV-2 to Ecuador.

Hospital Mortality and Effect of Adjusting PaO2/FiO2 According to Altitude Above the Sea Level in Acclimatized Patients Undergoing Invasive Mechanical Ventilation. A Multicenter Study / Mortalidad hospitalaria y efecto de ajustar el cociente PaO2/FiO2 de acuerdo con la altitud por encima del nivel del mar en pacientes aclimatados que se someten a ventilación mecánica invasiva. Un estudio multicéntrico

OBJECTIVE: (I) Analyze the effect of altitude above the sea level on the mortality rate in patients undergoing invasive mechanical ventilation. (II) Validate the traditional equation for adjusting PaO2/FiO2 according to the altitude. DESIGN: A prospective, observational, multicenter and international study conducted during August 2016. PATIENTS: Inclusion criteria: (I) age between 18 and 90 years old, (II) admitted to intensive care unit (ICU) situated at the same altitude above the sea level (AASL) in which the patients has stayed, at least, during the previous 40 days and (III) received invasive MV for at least 12 h. MATERIAL AND METHODS: All variables were registered the day of intubation (day 0). Patients were followed until death, ICU discharge or day 28. PaO2/FiO2 ratio was adjusted by the AASL according to: PaO2/FiO2 * (barometric pressure/760). Categorical variables were compared with χ2 and Cochran-Mantel-Haenszel test. Continuous variables with Mann-Whitney. Correlation between continuous variables was analyzed graphically and analytically. Logistic regression model was constructed to identify factors associated to mortality. Kapplan-Meier method was used to estimate the probability of survival according to the altitude. A 2-side p value < 0.05 was consider significant. RESULTS: 249 patients (< 1500 m n = 55; 1500 to < 2500 m n = 20; 2500 to < 3500 m n=155 and ≥ 3500 m n=19) were included. Adjusted and non-adjusted PaO2/FiO2 were correlated with several respiratory and non respiratory variables. None discordances between non adjusted and adjusted PaO2/FiO2 were identified. However, several correlations were appreciated only in patients situated < 1500 m or in > 1500 m. Seventy-nine patients died during the ICU stayed (32%). The mortality curve was not affected by the altitude above the sea level. Variables independently associated to mortality are: PEEP, age, systolic arterial blood pressure, and platelet count. AUROC: 0.72. CONCLUSION: In acclimatized patients undergoing invasive mechanical ventilation, the traditional equation for adjusting PaO2/FiO2 according the elevation above the sea level seems to be inaccurate and the altitude above the sea level does not affect the mortality risk

OBJETIVO: 1) Analizar el efecto de la altitud por encima del nivel del mar en la tasa de mortalidad de pacientes sometidos a ventilación mecánica invasiva, y 2) Validar la ecuación tradicional de ajuste de PaO2/FiO2, de acuerdo con la altitud. DISEÑO: Estudio internacional prospectivo, observacional y multicéntrico realizado durante agosto de 2016. PACIENTES: Criterios de inclusión: 1 Edad comprendida entre 18 y 90 años, 2 Haber sido ingresado en una unidad de cuidados intensivos (UCI) situada a la misma altitud por encima del nivel del mar (AASL) en la cual el paciente haya estado durante al menos los 40 días previos al estudio, y 3) Haber recibido ventilación mecánica (VM) durante al menos 12 h. MATERIALES Y MÉTODOS: Todas las variables se registraron el día de la intubación (día 0). El seguimiento se realizó hasta la muerte del paciente, el alta de la UCI o el día 28. El cociente PaO2/FiO2 se ajustó según los criterios de la AASL de acuerdo con: PaO2/FiO2 * (presión barométrica/760). Las variables categóricas se compararon mediante la prueba de χ2 y el test Cochran-Mantel-Haenszel, y las variables continuas con el test de Mann-Whitney. La correlación entre las variables continuas se analizó de forma gráfica y analítica. Para identificar los factores asociados a la mortalidad se elaboró un modelo de regresión logística. Se utilizó el método de Kaplan-Meier para estimar la probabilidad de supervivencia de acuerdo con la altitud. Un valor de p < 0,05 en la prueba bilateral se consideró como significativo. RESULTADOS: Se incluyeron 249 pacientes (< 1.500 m, n = 55; 1.500 a < 2.500 m, n = 20; 2.500 a < 3.500 m, n = 155 y ≥ 3.500 m, n = 19). El cociente PaO2/FiO2 mostró correlación con las variables graves tanto respiratorias como no respiratorias. No se registraron discordancias entre el cociente PaO2/FiO2 ajustado y sin ajustar. Únicamente se observaron diversas correlaciones entre los pacientes situados a < 1.500 m o a > 1.500 m. Setenta y nueve pacientes (32%) murieron durante la estancia en la UCI. La altitud sobre el nivel del mar no afectó a la curva de mortalidad. Las variables asociadas de forma independiente con la mortalidad fueron la presión positiva al final de la espiración (PEEP), la edad, la presión arterial sistólica y el recuento de plaquetas. El área bajo la curva ROC (AUROC) fue de 0,72. CONCLUSIÓN: En pacientes aclimatados sometidos a ventilación mecánica invasiva la ecuación tradicional para ajustar el cociente PaO2/FiO2, de acuerdo con la elevación sobre el nivel del mar parece inexacta. Por otro lado, la altitud por encima del nivel del mar no afecta al riego de mortalidad

Inter-country variability over time in the mortality of mechanically ventilated patients.

PURPOSE: Variations in clinical characteristics and management and in the mortality of mechanically ventilated patients have not been sufficiently evaluated. We hypothesized that mortality shows a variability associated with country after adjustment for clinical characteristics and management. METHODS: Analysis of four studies carried out at 6-year intervals over an 18-year period. The studies included 26,024 patients (5183 in 1998, 4968 in 2004, 8108 in 2010, and 7765 in 2016) admitted to 1253 units from 38 countries. The primary outcome was 28-day mortality. We performed analyses using multilevel logistic modeling with mixed-random effects, including country as a random variable. To evaluate the effect of management strategies on mortality, a mediation analysis was performed. RESULTS: Adjusted 28-day mortality decreased significantly over time (first study as reference): 2004: odds ratio 0.82 (95% confidence interval [CI] 0.72-0.93); 2010: 0.63 (95% CI 0.53-0.75); 2016: 0.49 (95% CI 0.39-0.61). A protective ventilatory strategy and the use of continuous sedation mediated a moderate fraction of the effect of time on mortality in patients with moderate hypoxemia and without hypoxemia, respectively. Logistic multilevel modeling showed a significant effect of country on mortality: median odds ratio (MOR) in 1998: 2.02 (95% CI 1.57-2.48); in 2004: 1.76 (95% CI 1.47-2.06); in 2010: 1.55 (95% CI 1.37-1.74), and in 2016: 1.39 (95% CI 1.25-1.54). CONCLUSIONS: These findings suggest that country could contribute, independently of confounder variables, to outcome. The magnitude of the effect of country decreased over time. Clinical trials registered with http://www.clinicaltrials.gov (NCT02731898).

Hospital Mortality and Effect of Adjusting PaO2/FiO2 According to Altitude Above the Sea Level in Acclimatized Patients Undergoing Invasive Mechanical Ventilation. A Multicenter Study.

OBJECTIVE: (i) Analyze the effect of altitude above the sea level on the mortality rate in patients undergoing invasive mechanical ventilation. (ii) Validate the traditional equation for adjusting PaO2/FiO2 according to the altitude. DESIGN: A prospective, observational, multicenter and international study conducted during August 2016. PATIENTS: Inclusion criteria: (i) age between 18 and 90 years old, (ii) admitted to intensive care unit (ICU) situated at the same altitude above the sea level (AASL) in which the patients has stayed, at least, during the previous 40 days and (iii) received invasive MV for at least 12h. MATERIAL AND METHODS: All variables were registered the day of intubation (day 0). Patients were followed until death, ICU discharge or day 28. PaO2/FiO2 ratio was adjusted by the AASL according to: PaO2/FiO2*(barometric pressure/760). Categorical variables were compared with χ2 and Cochran-Mantel-Haenszel test. Continuous variables with Mann-Whitney. Correlation between continuous variables was analyzed graphically and analytically. Logistic regression model was constructed to identify factors associated to mortality. Kapplan-Meier method was used to estimate the probability of survival according to the altitude. A 2-side p value <0.05 was consider significant. RESULTS: 249 patients (<1500m n=55; 1500 to <2500m n=20; 2500 to <3500m n=155 and ≥3500m n=19) were included. Adjusted and non-adjusted PaO2/FiO2 were correlated with several respiratory and non respiratory variables. None discordances between non adjusted and adjusted PaO2/FiO2 were identified. However, several correlations were appreciated only in patients situated <1500m or in >1500m. Seventy-nine patients died during the ICU stayed (32%). The mortality curve was not affected by the altitude above the sea level. Variables independently associated to mortality are: PEEP, age, systolic arterial blood pressure, and platelet count. AUROC: 0.72. CONCLUSION: In acclimatized patients undergoing invasive mechanical ventilation, the traditional equation for adjusting PaO2/FiO2 according the elevation above the sea level seems to be inaccurate and the altitude above the sea level does not affect the mortality risk.

Early rise in central venous pressure during a spontaneous breathing trial: A promising test to identify patients at high risk of weaning failure?

BACKGROUND: The spontaneous breathing trial (SBT) assesses the risk of weaning failure by evaluating some physiological responses to the massive venous return increase imposed by discontinuing positive pressure ventilation. This trial can be very demanding for some critically ill patients, inducing excessive physical and cardiovascular stress, including muscle fatigue, heart ischemia and eventually cardiac dysfunction. Extubation failure with emergency reintubation is a serious adverse consequence of a failed weaning process. Some data suggest that as many as 50% of patients that fail weaning do so because of cardiac dysfunction. Unfortunately, monitoring cardiovascular function at the time of the SBT is complex. The aim of our study was to explore if central venous pressure (CVP) changes were related to weaning failure after starting an SBT. We hypothesized that an early rise on CVP could signal a cardiac failure when handling a massive increase on venous return following a discontinuation of positive pressure ventilation. This CVP rise could identify a subset of patients at high risk for extubation failure. METHODS: Two-hundred and four mechanically ventilated patients in whom an SBT was decided were subjected to a monitoring protocol that included blinded assessment of CVP at baseline, and at 2 minutes after starting the trial (CVP-test). Weaning failure was defined as reintubation within 48-hours following extubation. Comparisons between two parametric or non-parametric variables were performed with student T test or Mann Whitney U test, respectively. A logistic multivariate regression was performed to determine the predictive value on extubation failure of usual clinical variables and CVP at 2-min after starting the SBT. RESULTS: One-hundred and sixty-five patients were extubated after the SBT, 11 of whom were reintubated within 48h. Absolute CVP values at 2-minutes, and the change from baseline (dCVP) were significantly higher in patients with extubation failure as compared to those successfully weaned. dCVP was an early predictor for reintubation (OR: 1.70 [1.31,2.19], p<0.001). CONCLUSIONS: An early rise in CVP after starting an SBT was associated with an increased risk of extubation failure. This might represent a warning signal not captured by usual SBT monitoring and could have relevant clinical implications.