Prognostic Value of Variations in Serum Biomarkers and Prognostic Scores Values Between Admission and Second Day in Intensive Care Unit Septic Patients.

Objective To determinate the prognostic value of procalcitonin (PCT) and C-reactive protein (CRP) changes during the first two days of admission to the ICU with sepsis and/or septic shock, and to compare it with changes in Acute Physiology And Chronic Health Evaluation II (APACHE-II) and Sepsis-related Organ Failure Assessment (SOFA) prognostic scores. Methods A single-center prospective observational study was performed. Fifty consecutive patients admitted to the ICU, diagnosed of severe sepsis/septic shock were included. We considered risk factors for infection: diabetes mellitus, chronic obstructive pulmonary disease (COPD), previous antibiotic treatment, central intravascular catheter, bladder catheter, active neoplasia. Results Median aged 67(52-75) years with median APACHE-II 19(14-25) points and SOFA scores 7(5-11) points on admission, and 28-day mortality of 42%. When we studied the relationship between mortality and the changes between the day of admission and the second day of the variables studied, we found that APACHE-II (p = 0.001) and SOFA (p = 0.002) between admission and second day raised significantly in no survivors, with no significant changes in CRP and PCT. Multivariate analysis showed that mortality was significantly associated to changes in SOFA score (odds ratio [OR], 2.13; 95% confidence interval [CI], 1.18-3.86) and to the presence of one or more risk factors for infection (OR, 6.01; 95% CI, 1.01-35.78) but not with PCT changes. Mortality was also related to the variations between the day of admission and the fifth day on APACHE-II (p = 0.002), SOFA (p < 0.001) and PCT (p = 0.012). Conclusions Changes in SOFA and APACHE-II scores between admission and second day in ICU septic patients are more sensitive mortality predictors than the observed changes in CRP and PCT values. Changes in PCT levels between the day of ICU admission and the fifth day are significantly related to mortality and may be useful as an additional marker in patient outcome.

Efficacy and safety of early treatment with sarilumab in hospitalised adults with COVID-19 presenting cytokine release syndrome (SARICOR STUDY): protocol of a phase II, open-label, randomised, multicentre, controlled clinical trial.

INTRODUCTION: About 25% of patients with COVID-19 develop acute respiratory distress syndrome (ARDS) associated with a high release of pro-inflammatory cytokines such as interleukin-6 (IL-6). The aim of the SARICOR study is to demonstrate that early administration of sarilumab (an IL-6 receptor inhibitor) in hospitalised patients with COVID-19, pulmonary infiltrates and a high IL-6 or D-dimer serum level could reduce the progression of ARDS requiring high-flow nasal oxygen or mechanical ventilation (non-invasive or invasive). METHODS AND ANALYSIS: Phase II, open-label, randomised, multicentre, controlled clinical trial to study the efficacy and safety of the administration of two doses of sarilumab (200 and 400 mg) plus best available therapy (BAT) in hospitalised adults with COVID-19 presenting cytokine release syndrome. This strategy will be compared with a BAT control group. The efficacy and safety will be monitored up to 28 days postadministration. A total of 120 patients will be recruited (40 patients in each arm). ETHICS AND DISSEMINATION: The clinical trial has been approved by the Research Ethics Committee of the coordinating centre and authorised by the Spanish Agency of Medicines and Medical Products. If the hypothesis is verified, the dissemination of the results could change clinical practice by increasing early administration of sarilumab in adult patients with COVID-19 presenting cytokine release syndrome, thus reducing intensive care unit admissions. TRIAL REGISTRATION NUMBER: NCT04357860.

Validation of the ICH score in patients with spontaneous intracerebral haemorrhage admitted to the intensive care unit in Southern Spain.

OBJECTIVE: Validation of the intracerebral haemorrhage (ICH) score in patients with a diagnosis of spontaneous ICH admitted to the intensive care unit (ICU). METHODS: A multicentre cohort study was conducted in all consecutive patients with ICH admitted to the ICUs of three hospitals with a neurosurgery department between 2009 and 2012 in Andalusia, Spain. Data collected included ICH, Glasgow Coma Scale (GCS) and Acute Physiology and Chronic Health Evaluation II (APACHE-II) scores. Demographic data, location and volume of haematoma and 30-day mortality rate were also collated. RESULTS: A total of 336 patients were included. 105 of whom underwent surgery. Median (IQR) age: 62 (50-70) years. APACHE-II: 21(15-26) points, GCS: 7 (4-11) points, ICH score: 2 (2-3) points. 11.1% presented with bilateral mydriasis on admission (mortality rate=100%). Intraventricular haemorrhage was observed in 58.9% of patients. In-hospital mortality was 54.17% while the APACHE-II predicted mortality was 57.22% with a standardised mortality ratio (SMR) of 0.95 (95% CI 0.81 to 1.09) and a Hosmer-Lemenshow test value (H) of 3.62 (no significant statistical difference, n.s.). 30-day mortality was 52.38% compared with the ICH score predicted mortality of 48.79%, SMR: 1.07 (95% CI 0.91 to 1.23), n.s. Mortality was higher than predicted at the lowest scores and lower than predicted in the more severe patients, (H=55.89, p<0.001), Gruppo Italiano per la Valutazione degli Interventi in Terapia Intensiva calibration belt (p<0.001). The area under a receiver operating characteristic (ROC) curve was 0.74 (95% CI 0.69 to 0.79). CONCLUSIONS: ICH score shows an acceptable discrimination as a tool to predict mortality rates in patients with spontaneous ICH admitted to the ICU, but its calibration is suboptimal.

Prolonged Mechanical Ventilation as a Predictor of Mortality After Cardiac Surgery.

BACKGROUND: Mortality among the small percentage of cardiac surgery patients receiving prolonged mechanical ventilation is high, but this issue appears to be inadequately addressed in guidelines. METHODS: This study is a retrospective analysis of prospective, multi-center, and observational study in Spain including all adults undergoing cardiac surgery in 3 Andalusian hospitals between June 2008 and December 2012. RESULTS: The study included 3,588 adults with mean ± SD age of 63.5 ± 12.8 y and with median (interquartile range) EuroSCORE of 5 (3-7) points. Prolonged mechanical ventilation (> 24 h) was required by 415 subjects (11.6%), with ICU mortality of 44.3% (184 subjects), and was not required by 3,173 subjects (88.4%), with ICU mortality of 3.1% (99 subjects, P < .001). Prolonged mechanical ventilation was associated with more complications and was required by 4.5% of subjects with a EuroSCORE <5, 11.2% with a score of 5-7, 27.2% with a score of 8-10, and 32.2% with a score > 10. In the multivariable analysis, ICU mortality was associated with illness severity, duration of bypass surgery, surgery type, and prolonged mechanical ventilation (odds ratio 15.19, 95% CI 11.56-22.09). The main cause of death was multiple organ failure and sepsis in subjects who required prolonged mechanical ventilation (50.3%) and cardiogenic shock in those who did not (59.2%). CONCLUSION: Prolonged postoperative mechanical ventilation was required by 10-20% of cardiac surgery subjects, who constitute a specific group that represents most of the postoperative mortality, which is associated with multiple organ failure and sepsis.

Intratracheal dopamine attenuates pulmonary edema and improves survival after ventilator-induced lung injury in rats.

INTRODUCTION: Clearance of alveolar oedema depends on active transport of sodium across the alveolar-epithelial barrier. beta-Adrenergic agonists increase clearance of pulmonary oedema, but it has not been established whether beta-agonist stimulation achieves sufficient oedema clearance to improve survival in animals. The objective of this study was to determine whether the increased pulmonary oedema clearance produced by intratracheal dopamine improves the survival of rats after mechanical ventilation with high tidal volume (HVT). METHODS: This was a randomized, controlled, experimental study. One hundred and thirty-two Wistar-Kyoto rats, weighing 250 to 300 g, were anaesthetized and cannulated via endotracheal tube. Pulmonary oedema was induced by endotracheal instillation of saline solution and mechanical ventilation with HVT. Two types of experiment were carried out. The first was an analysis of pulmonary oedema conducted in six groups of 10 rats ventilated with low (8 ml/kg) or high (25 ml/kg) tidal volume for 30 or 60 minutes with or without intratracheally instilled dopamine. At the end of the experiment the animals were exsanguinated and pulmonary oedema analysis performed. The second experiment was a survival analysis, which was conducted in two groups of 36 animals ventilated with HVT for 60 minutes with or without intratracheal dopamine; survival of the animals was monitored for up to 7 days after extubation. RESULTS: In animals ventilated at HVT with or without intratracheal dopamine, oxygen saturation deteriorated over time and was significantly higher at 30 minutes than at 60 minutes. After 60 minutes, a lower wet weight/dry weight ratio was observed in rats ventilated with HVT and instilled with dopamine than in rats ventilated with HVT without dopamine (3.9 +/- 0.27 versus 4.9 +/- 0.29; P = 0.014). Survival was significantly (P = 0.013) higher in animals receiving intratracheal dopamine and ventilated with HVT, especially at 15 minutes after extubation, when 11 of the 36 animals in the HVT group had died as compared with only one out of the 36 animals in the HVT plus dopamine group. CONCLUSION: Intratracheal dopamine instillation increased pulmonary oedema clearance in rats ventilated with HVT, and this greater clearance was associated with improved survival.