Background
Anti‐SARS‐CoV‐2 S antibodies prevent viral replication. Critically ill COVID‐19 patients show viral material in plasma, associated with a dysregulated host response. If these antibodies ...influence survival and viral dissemination in ICU‐COVID patients is unknown.
Patients/Methods
We studied the impact of anti‐SARS‐CoV‐2 S antibodies levels on survival, viral RNA‐load in plasma, and N‐antigenaemia in 92 COVID‐19 patients over ICU admission.
Results
Frequency of N‐antigenaemia was >2.5‐fold higher in absence of antibodies. Antibodies correlated inversely with viral RNA‐load in plasma, representing a protective factor against mortality (adjusted HR CI 95%, p): (S IgM AUC ≥ 60: 0.44 0.22; 0.88, 0.020); (S IgG AUC ≥ 237: 0.31 0.16; 0.61, <0.001). Viral RNA‐load in plasma and N‐antigenaemia predicted increased mortality: (N1‐viral load ≥2.156 copies/ml: 2.25 1.16; 4.36, 0.016); (N‐antigenaemia: 2.45 1.27; 4.69, 0.007).
Conclusions
Low anti‐SARS‐CoV‐2 S antibody levels predict mortality in critical COVID‐19. Our findings support that these antibodies contribute to prevent systemic dissemination of SARS‐CoV‐2.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Sepsis is a common cause of acute respiratory distress syndrome (ARDS) associated with a high mortality. A panel of biomarkers (BMs) to identify septic patients at risk for developing ARDS, or at ...high risk of death, would be of interest for selecting patients for therapeutic trials, which could improve ARDS diagnosis and treatment, and survival chances in sepsis and ARDS. We measured nine protein BMs by ELISA in serum from 232 adult septic patients at diagnosis (152 required invasive mechanical ventilation and 72 had ARDS). A panel including the BMs RAGE, CXCL16 and Ang-2, plus PaO
/FiO
, was good in predicting ARDS (area under the curve = 0.88 in total septic patients). Best performing panels for ICU death are related to the presence of ARDS, need for invasive mechanical ventilation, and pulmonary/extrapulmonary origin of sepsis. In all cases, the use of BMs improved the prediction by clinical markers. Our study confirms the relevance of RAGE, Ang-2, IL-1RA and SP-D, and is novel supporting the inclusion of CXCL16, in BMs panels for predicting ARDS diagnosis and ARDS and sepsis outcome.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Purpose:
To determine the epidemiology and outcome of severe sepsis and septic shock after 9 years of the implementation of the Surviving Sepsis Campaign (SSC) and to build a mortality prediction ...model.
Methods:
This is a prospective, multicenter, observational study performed during a 5-month period in 2011 in a network of 11 intensive care units (ICUs). We compared our findings with those obtained in the same ICUs in a study conducted in 2002.
Results:
The current cohort included 262 episodes of severe sepsis and/or septic shock, and the 2002 cohort included 324. The prevalence was 14% (95% confidence interval: 12.5-15.7) with no differences to 2002. The population-based incidence was 31 cases/100 000 inhabitants/year. Patients in 2011 had a significantly lower Acute Physiology and Chronic Health Evaluation II (APACHE II; 21.9 ± 6.6 vs 25.5 ± 7.07), Logistic Organ Dysfunction Score (5.6 ± 3.2 vs 6.3 ± 3.6), and Sequential Organ Failure Assessment (SOFA) scores on day 1 (8 ± 3.5 vs 9.6 ± 3.7; P < .01). The main source of infection was intraabdominal (32.5%) although microbiologic isolation was possible in 56.7% of cases. The 2011 cohort had a marked reduction in 48-hour (7% vs 14.8%), ICU (27.2% vs 48.2%), and in-hospital (36.7% vs 54.3%) mortalities. Most relevant factors associated with death were APACHE II score, age, previous immunosuppression and liver insufficiency, alcoholism, nosocomial infection, and Delta SOFA score.
Conclusion:
Although the incidence of sepsis/septic shock remained unchanged during a 10-year period, the implementation of the SSC guidelines resulted in a marked decrease in the overall mortality. The lower severity of patients on ICU admission and the reduced early mortality suggest an improvement in early diagnosis, better initial management, and earlier antibiotic treatment.
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NUK, OILJ, SAZU, UKNU, UL, UM, UPUK
ABSTRACT Background Injury patterns may differ in trauma patients when age is considered. This information is relevant in the management of trauma patients and for planning preventive measures. ...Methods We included in the study all patients admitted for traumatic disease in the participating ICUs from November 23rd , 2012 to July 31st , 2015 with complete records. Data on epidemiology, injury patterns, severity scores, acute management, resources utilisation and outcome were recorded and compared in the following groups of age: ≤ 55 years (young adults), 56–65 years (adults), 66–75 years (elderly), > 75 years (very elderly). Quantitative data were reported as median (Interquartile Range (IQR) 25–75) and categorical data as number and percentage. Comparison between groups of age with quantitative variables was performed using the analysis of variance (ANOVA) test. Differences between groups with categorical variables were compared using the chi-square test. A value of p < 0.05 was considered significant. Results We included 2700 patients (78.9% male). Median age was 46 (31–62) years. Blunt trauma was present in 93.7% of the patients. Median RTS was 7.55 (5.97–7.84). Median ISS was 20 (13–26). High-energy trauma secondary to motor-vehicle accident with rhabdomyolysis and drugs abuse showed an inverse linear association with ageing, whilst pedestrian falls with isolated brain injury, being run-over and pre-injury antiplatelets or anticoagulant treatment increased with age (in all cases p < 0.001). Multiple injuries were more common in young adults ( p < 0.001). Acute kidney injury prevalence was higher in elderly and very elderly patients ( p < 0.001). ICU Mortality increased with age in spite of similar severity scores in all groups ( p < 0.001). The main cause of death in all groups was intracranial hypertension. Conclusions Different injury patterns exist in relation with ageing in trauma ICU patients. Adult patients were more likely to present high-energy trauma with significant injuries in different areas whilst elderly patients were prone to low-energy falls, complicated by antiplatelets or anticoagulants use, resulting in severe brain injury and increased mortality.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
Purpose
To evaluate the effect of the intravenous (i.v.)
l
-alanyl-
l
-glutamine dipeptide supplementation during 5 days on clinical outcome in trauma patients admitted to the intensive care unit ...(ICU).
Methods
This was a prospective, randomized, double-blind, multicenter trial. Glutamine was not given as a component of nutrition but as an extra infusion. The primary outcome variable was the number of new infections within the first 14 days.
Results
We included 142 patients. There were no differences between groups in baseline characteristics. Up to 62 % of the patients in the placebo group and 63 % in the treatment group presented confirmed infections (
p
= 0.86). ICU length of stay was 14 days in both groups (
p
= 0.54). Hospital length of stay was 27 days in the placebo group and 29 in the treatment group (
p
= 0.88). ICU mortality was 4.2 % in both groups (
p
= 1). Sixty percent of the patients presented low glutamine levels before randomization. At the end of the treatment (6th day), 48 % of the patients maintained low glutamine levels (39 % of treated patients vs. 57 % in the placebo group). Patients with low glutamine levels at day 6 had more number of infections (58.8 vs. 80.9 %;
p
= 0.032) and longer ICU (9 vs. 20 days;
p
< 0.01) and hospital length of stay (24 vs. 41 days;
p
= 0.01).
Conclusions
There was no benefit with i.v.
l
-alanyl-
l
-glutamine dipeptide supplementation (0.5 g/kg body weight/day of the dipeptide) during 5 days in trauma patients admitted to the ICU. The i.v. glutamine supplementation was not enough to normalize the plasma glutamine levels in all patients. Low plasma glutamine levels at day 6 were associated with a worse outcome.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OBVAL, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
PURPOSE:To determine the long-term degree of compliance with the Surviving Sepsis Campaign (SSC) bundles and related outcomes after an educational program in septic patients admitted to a network of ...intensive care units (ICU).
METHODS:Prospective, observational, multicenter study in several ICUs during a 5-month period for evaluating the degree of compliance with the SSC bundles of resuscitation in the first 6 h (B6H) and management in the following 24 h (B24H). We compared the findings with those from a historical cohort at the same ICUs after an educational program (EDUSEPSIS) 5 years earlier.
RESULTS:The study cohort comprised 231 episodes of severe sepsis and the historical cohort included 217. In the current cohort, we found a better compliance with B6H compared with the historical cohort (27.7% vs. 9.7%, P < 0.001), and lower compliance with B24H (4.3% vs. 12.9%, P < 0.001). ICU and in-hospital mortalities were reduced from 37.3% to 27.1% (P = 0.02) and from 45.3% to 36.7% (P = 0.06), respectively. This reduction occurred linearly with the number of B6H items completed (P for trend <0.001). All B6H measures were individually associated with lower ICU mortality. Measurement of plasma lactate, blood cultures, and administration of broad-spectrum antibiotics were associated with lower in-hospital mortality. No benefit was observed regarding B24H.
CONCLUSIONS:Our study confirmed that an educational campaign aimed at early recognition and management of patients with severe sepsis improves compliance with management recommendations and hospital survival in the long term.
COVID-19 can course with respiratory and extrapulmonary disease. SARS-CoV-2 RNA is detected in respiratory samples but also in blood, stool and urine. Severe COVID-19 is characterized by a ...dysregulated host response to this virus. We studied whether viral RNAemia or viral RNA load in plasma is associated with severe COVID-19 and also to this dysregulated response.
A total of 250 patients with COVID-19 were recruited (50 outpatients, 100 hospitalized ward patients and 100 critically ill). Viral RNA detection and quantification in plasma was performed using droplet digital PCR, targeting the N1 and N2 regions of the SARS-CoV-2 nucleoprotein gene. The association between SARS-CoV-2 RNAemia and viral RNA load in plasma with severity was evaluated by multivariate logistic regression. Correlations between viral RNA load and biomarkers evidencing dysregulation of host response were evaluated by calculating the Spearman correlation coefficients.
The frequency of viral RNAemia was higher in the critically ill patients (78%) compared to ward patients (27%) and outpatients (2%) (p < 0.001). Critical patients had higher viral RNA loads in plasma than non-critically ill patients, with non-survivors showing the highest values. When outpatients and ward patients were compared, viral RNAemia did not show significant associations in the multivariate analysis. In contrast, when ward patients were compared with ICU patients, both viral RNAemia and viral RNA load in plasma were associated with critical illness (OR CI 95%, p): RNAemia (3.92 1.183-12.968, 0.025), viral RNA load (N1) (1.962 1.244-3.096, 0.004); viral RNA load (N2) (2.229 1.382-3.595, 0.001). Viral RNA load in plasma correlated with higher levels of chemokines (CXCL10, CCL2), biomarkers indicative of a systemic inflammatory response (IL-6, CRP, ferritin), activation of NK cells (IL-15), endothelial dysfunction (VCAM-1, angiopoietin-2, ICAM-1), coagulation activation (D-Dimer and INR), tissue damage (LDH, GPT), neutrophil response (neutrophils counts, myeloperoxidase, GM-CSF) and immunodepression (PD-L1, IL-10, lymphopenia and monocytopenia).
SARS-CoV-2 RNAemia and viral RNA load in plasma are associated with critical illness in COVID-19. Viral RNA load in plasma correlates with key signatures of dysregulated host responses, suggesting a major role of uncontrolled viral replication in the pathogenesis of this disease.
Background
Pre-evaluation of endogenous immunoglobulin levels is a potential strategy to improve the results of intravenous immunoglobulins in sepsis, but more work has to be done to identify those ...patients who could benefit the most from this treatment. The objective of this study was to evaluate the impact of endogenous immunoglobulins on the mortality risk in sepsis depending on disease severity.
Methods
This was a retrospective observational study including 278 patients admitted to the ICU with sepsis fulfilling the SEPSIS-3 criteria, coming from the Spanish GRECIA and ABISS-EDUSEPSIS cohorts. Patients were distributed into two groups depending on their Sequential Organ Failure Assessment score at ICU admission (SOFA < 8,
n
= 122 and SOFA ≥ 8,
n
= 156), and the association between immunoglobulin levels at ICU admission with mortality was studied in each group by Kaplan–Meier and multivariate logistic regression analysis.
Results
ICU/hospital mortality in the SOFA < 8 group was 14.8/23.0%, compared to 30.1/35.3% in the SOFA ≥ 8 group. In the group with SOFA < 8, the simultaneous presence of total IgG < 407 mg/dl, IgM < 43 mg/dl and IgA < 219 mg/dl was associated with a reduction in the survival mean time of 6.6 days in the first 28 days and was a robust predictor of mortality risk either during the acute or during the post-acute phase of the disease (OR for ICU mortality: 13.79; OR for hospital mortality: 7.98). This predictive ability remained in the absence of prior immunosuppression (OR for ICU mortality: 17.53; OR for hospital mortality: 5.63). Total IgG < 407 mg/dl or IgG1 < 332 mg/dl was also an independent predictor of ICU mortality in this group. In contrast, in the SOFA ≥ 8 group, we found no immunoglobulin thresholds associated with neither ICU nor hospital mortality.
Conclusions
Endogenous immunoglobulin levels may have a different impact on the mortality risk of sepsis patients based on their severity. In patients with moderate organ failure, the simultaneous presence of low levels of IgG, IgA and IgM was a consistent predictor of both acute and post-acute mortalities.
To analyze the impact of positive end-expiratory pressure (PEEP) changes on intracranial pressure (ICP) dynamics in patients with acute brain injury (ABI).
Observational, prospective and multicenter ...study (PEEP-PIC study).
Seventeen intensive care units in Spain.
Neurocritically ill patients who underwent invasive neuromonitorization from November 2017 to June 2018.
Baseline ventilatory, hemodynamic and neuromonitoring variables were collected immediately before PEEP changes and during the following 30 min.
PEEP and ICP changes.
One-hundred and nine patients were included. Mean age was 52.68 (15.34) years, male 71 (65.13%). Traumatic brain injury was the cause of ABI in 54 (49.54%) patients. Length of mechanical ventilation was 16.52 (9.23) days. In-hospital mortality was 21.1%. PEEP increases (mean 6.24–9.10 cmH2O) resulted in ICP increase from 10.4 to 11.39 mmHg, P < .001, without changes in cerebral perfusion pressure (CPP) (P = .548). PEEP decreases (mean 8.96 to 6.53 cmH2O) resulted in ICP decrease from 10.5 to 9.62 mmHg (P = .052), without changes in CPP (P = .762). Significant correlations were established between the increase of ICP and the delta PEEP (R = 0.28, P < .001), delta driving pressure (R = 0.15, P = .038) and delta compliance (R = −0.14, P = .052). ICP increment was higher in patients with lower baseline ICP.
PEEP changes were not associated with clinically relevant modifications in ICP values in ABI patients. The magnitude of the change in ICP after PEEP increase was correlated with the delta of PEEP, the delta driving pressure and the delta compliance.
Analizar el impacto de los cambios en la Presión positiva al final de la espiración (PEEP) sobre la Presión Intracraneal (PIC) en pacientes con lesión cerebral aguda (ABI).
Estudio prospectivo, observacional y multicéntrico (PEEP-PIC).
Diecisiete Unidades de Cuidados Intensivos en España.
Pacientes neurocríticos que recibieron monitorización invasiva de la PIC desde Noviembre 2017 hasta Junio 2018.
Se recogieron los parámetros ventilatorios, hemodinámicos y variables de neuromonitorización inmediatamente antes de las modificaciones de la PEEP y durante los 30 minutos posteriores.
PEEP y cambios en la PIC.
Se incluyeron 109 pacientes. Edad media 52,68 (15,34) años, hombres 71 (65,13%). La causa de lesión cerebral fue traumática en 54 pacientes (49,54%). La estancia media fue de 16,52 (9,23) días. La mortalidad hospitalaria fue del 21,1%. Los aumentos de PEEP (media 6,24 a 9,10 cmH2O) resultaron en un aumento de la PIC de 10,4 a 11,39 mmHg, P < .001, sin cambios en la PPC (P = ,548). Los descensos de la PEEP (media 8,96 a 6,53 cmH2O) resultaron en un descenso de la PIC de 10,5 a 9,62 mmHg (P = ,052), sin cambios en la PPC (P = ,762). Se establecieron correlaciones significativas entre el aumento de PIC y el delta de PEEP (R = 0,28, P < ,001), el delta driving pressure (R = 0,15, P = ,038) y el delta de complianza (R = −0,14, P = ,052). El aumento de PIC fue mayor en pacientes con PIC basal baja.
Los cambios en la PEEP no se asociaron a cambios clínicamente relevantes en la PIC de los pacientes con lesion cerebral aguda. La magnitud del aumento de la PIC tras el aumento de PEEP se correlacionó con el delta PEEP, delta driving pressure y el delta complianza.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
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