Guidelines on human factors in critical situations 2023.

OBJECTIVE: To provide guidelines to define the place of human factors in the management of critical situations in anaesthesia and critical care. DESIGN: A committee of nineteen experts from the SFAR and GFHS learned societies was set up. A policy of declaration of links of interest was applied and respected throughout the guideline-producing process. Likewise, the committee did not benefit from any funding from a company marketing a health product (drug or medical device). The committee followed the GRADE® method (Grading of Recommendations Assessment, Development and Evaluation) to assess the quality of the evidence on which the recommendations were based. METHODS: We aimed to formulate recommendations according to the GRADE® methodology for four different fields: 1/ communication, 2/ organisation, 3/ working environment and 4/ training. Each question was formulated according to the PICO format (Patients, Intervention, Comparison, Outcome). The literature review and recommendations were formulated according to the GRADE® methodology. RESULTS: The experts' synthesis work and application of the GRADE® method resulted in 21 recommendations. Since the GRADE® method could not be applied in its entirety to all the questions, the guidelines used the SFAR "Recommendations for Professional Practice" A means of secured communication (RPP) format and the recommendations were formulated as expert opinions. CONCLUSION: Based on strong agreement between experts, we were able to produce 21 recommendations to guide human factors in critical situations.

Association between in-ICU red blood cells transfusion and 1-year mortality in ICU survivors.

BACKGROUND: Impact of in-ICU transfusion on long-term outcomes remains unknown. The purpose of this study was to assess in critical-care survivors the association between in-ICU red blood cells transfusion and 1-year mortality. METHODS: FROG-ICU, a multicenter European study enrolling all-comers critical care patients was analyzed (n = 1551). Association between red blood cells transfusion administered in intensive care unit and 1-year mortality in critical care survivors was analyzed using an augmented inverse probability of treatment weighting-augmented inverse probability of censoring weighting method to control confounders. RESULTS: Among the 1551 ICU-survivors, 42% received at least one unit of red blood cells while in intensive care unit. Patients in the transfusion group had greater severity scores than those in the no-transfusion group. According to unweighted analysis, 1-year post-critical care mortality was greater in the transfusion group compared to the no-transfusion group (hazard ratio (HR) 1.78, 95% CI 1.45-2.16). Weighted analyses including 40 confounders, showed that transfusion remained associated with a higher risk of long-term mortality (HR 1.21, 95% CI 1.06-1.46). CONCLUSIONS: Our results suggest a high incidence of in-ICU RBC transfusion and that in-ICU transfusion is associated with a higher 1-year mortality among in-ICU survivors. Trial registration ( NCT01367093 ; Registered 6 June 2011).

Features of Inflammatory Heart Reactions Following mRNA COVID-19 Vaccination at a Global Level.

Myocarditis and pericarditis may constitute adverse reactions of mRNA coronavirus disease 2019 (COVID-19) vaccines. This study aimed to document these reactions and to assess the association with patient sex and age. This is as an observational retrospective study using a case-non-case design (also called disproportionality study) on inflammatory heart reactions reported with mRNA COVID-19 vaccines within the World Health Organization (WHO) global safety database (VigiBase), up to June 30, 2021. Results are expressed using reporting odds ratios (RORs) and their 95% confidence interval (95% CI). Of 716,576 reports related to mRNA COVID-19 vaccines, 2,277 were cases of inflammatory heart reactions, including 1241 (55%) myocarditis and 851 (37%) pericarditis. The main age group was 18-29 years (704, 31%), and mostly male patients (1,555, 68%). Pericarditis onset was delayed compared with myocarditis with a median time to onset of 8 (3-21) vs. 3 (2-6) days, respectively (P = 0.001). Regarding myocarditis, an important disproportionate reporting was observed in adolescents (ROR, 22.3, 95% CI 19.2-25.9) and in 18-29 years old (ROR, 6.6, 95% CI 5.9-7.5) compared with older patients, as well as in male patients (ROR, 9.4, 95% CI 8.3-10.6). Reporting rate of myocarditis was increased in young adults and adolescents. Inflammatory heart reactions may rarely occur shortly following mRNA COVID-19 vaccination. Although an important disproportionate reporting of myocarditis was observed among adolescents and young adults, particularly in male patients, reporting rates support a very rare risk, that does not seem to compromise the largely positive benefit-risk balance of these vaccines. Furthermore, this study confirmed the value of disproportionality analyses for estimation of relative risks among subgroups of patients.

Activity of the adrenomedullin system to personalise post-discharge diuretic treatment in acute heart failure.

BACKGROUND: Quantifying the activity of the adrenomedullin system might help to monitor and guide treatment in acute heart failure (AHF) patients. The aims were to (1) identify AHF patients with marked benefit or harm from specific treatments at hospital discharge and (2) predict mortality by quantifying the adrenomedullin system activity. METHODS: This was a prospective multicentre study. AHF diagnosis and phenotype were centrally adjudicated by two independent cardiologists among patients presenting to the emergency department with acute dyspnoea. Adrenomedullin system activity was quantified using the biologically active component, bioactive adrenomedullin (bio-ADM), and a prohormone fragment, midregional proadrenomedullin (MR-proADM). Bio-ADM and MR-proADM concentrations were measured in a blinded fashion at presentation and at discharge. Interaction with specific treatments at discharge and the utility of these biomarkers on predicting outcomes during 365-day follow-up were assessed. RESULTS: Among 1886 patients with adjudicated AHF, 514 patients (27.3%) died during 365-day follow-up. After adjusting for age, creatinine, and treatment at discharge, patients with bio-ADM plasma concentrations above the median (> 44.6 pg/mL) derived disproportional benefit if treated with diuretics (interaction p values < 0.001). These findings were confirmed when quantifying adrenomedullin system activity using MR-proADM (n = 764) (interaction p values < 0.001). Patients with bio-ADM plasma concentrations above the median were at increased risk of death (hazard ratio 1.87, 95% CI 1.57-2.24; p < 0.001). For predicting 365-day all-cause mortality, both biomarkers performed well, with MR-proADM presenting an even higher predictive accuracy compared to bio-ADM (p < 0.001). CONCLUSIONS: Quantifying the adrenomedullin's system activity may help to personalise post-discharge diuretic treatment and enable accurate risk-prediction in AHF.

Inotropes and vasopressors are associated with increased short-term mortality but not long-term survival in critically ill patients.

OBJECTIVE: Limited information is currently available on the impact of vasoactive medications in intensive care (ICU) and long-term outcomes. The main objective of our study was to describe the association between the use of inotropes and/or vasopressors and ICU mortality. Secondary objectives were to evaluate the association between the use of vasoactive drugs and in-hospital as well as 1-year all-cause mortality in ICU survivors. METHODS: FROG-ICU was a prospective, observational, multi-centre cohort designed to investigate long-term mortality of critically ill adult patients. Cox proportional hazards models were used to evaluate the association between the use of inotropes and/or vasopressors and ICU mortality, as well as in-hospital and 1-year all-cause mortality in a propensity-score matched cohort. RESULTS: The study included 2087 patients, 939 of whom received inotropes and/or vasopressors during the initial ICU stay. Patients treated with vasoactive medications were older and had a more severe clinical presentation. In a propensity score-matched cohort of 1201 patients, ICU mortality was higher in patients who received vasoactive medications (HR of 1.40 [1.10-1.78], p = 0.007). One thousand six hundred thirty-five patients survived the index ICU hospitalisation. There was no significant difference according to the use of inotropes and/or vasopressors in the propensity-score matched cohort on in-hospital mortality (HR of 0.94 [0.60-1.49], p = 0.808) as well as one-year all-cause mortality (HR 0.94 [0.71-1.24], p = 0.643). CONCLUSION: Inotropic and/or vasopressor therapy is a strong predictor of in-ICU death. However, the use of inotropes and/or vasopressors during ICU admission was not associated with a worse prognosis after ICU discharge.

The association of biological sex and long-term outcomes in patients with acute dyspnea at the emergency department.

BACKGROUND AND IMPORTANCE: Marked differences have been described between women and men in disease prevalence, clinical presentation, response to treatment and outcomes. However, such data are scarce in the acutely ill. An awareness of differences related to biological sex is essential for the success of clinical care and outcomes in patients presenting with acute dyspnea, the most frequent cause of emergency department (ED) admission. OBJECTIVES: The aim of the present study was to assess the effect of biological sex on 1-year all-cause mortality in patients presenting with acute dyspnea to the ED. DESIGN, SETTINGS AND PARTICIPANTS: Consecutive adult patients presenting with acute dyspnea in two Lithuanian EDs were included. Clinical characteristics, laboratory data and medication use at discharge were collected. Follow-up at 1 year was performed via national data registries. OUTCOMES MEASURE AND ANALYSIS: The primary outcome of the study was 1-year all-cause mortality. Hazard ratios (HRs) for 1-year mortality according to biological sex were calculated using a Cox proportional hazards regression model, with and without adjustment for the following confounders: age, systolic blood pressure, creatinine, sodium and hemoglobin. MAIN RESULTS: A total of 1455 patients were included. Women represented 43% of the study population. Compared to men, women were older [median (interquartile range [IQR]) age 74 (65-80) vs. 68 (59-77) years, P < 0.0001]. The duration of clinical signs before admission was shorter for women [median (IQR) duration 4 (1-14) vs. 7(2-14) days, P = 0.006]. Unadjusted 1-year all-cause mortality was significantly lower in women (21 vs. 28%, P = 0.001). Adjusted HR of 1-year all-cause mortality was lower in women when compared to men [HR 0.68 (0.53-0.88), P = 0.0028]. Additional sensitivity analyses confirmed the survival benefit for women in subgroups including age greater and lower than 75 years, the presence of comorbidities and causes of dyspnea (cardiac or noncardiac). CONCLUSION: Women have better 1-year survival than men after the initial ED presentation for acute dyspnea. Understanding the biological sex-related differences should lead toward precision medicine, and improve clinical decision-making to promote gender equality in health.

Elevated Plasma Bioactive Adrenomedullin and Mortality in Cardiogenic Shock: Results from the OptimaCC Trial.

AIMS: Bioactive adrenomedullin (bio-ADM) was recently shown to be a prognostic marker in patients with acute circulatory failure. We investigate the association of bio-ADM with organ injury, functional impairment, and survival in cardiogenic shock (CS). METHODS: OptimaCC was a multicenter and randomized trial in 57 patients with CS. In this post-hoc analysis, the primary endpoint was to assess the association between bio-ADM and 30-day all-cause mortality. Secondary endpoints included adverse events and parameters of organ injury or functional impairment. RESULTS: Bio-ADM values were higher in 30-day non-survivors than 30-day survivors at inclusion (median (interquartile range) 67.0 (54.6-142.9) pg/mL vs. 38.7 (23.8-63.6) pg/mL, p = 0.010), at 24 h (p = 0.012), and up to 48 h (p = 0.027). Using a bio-ADM cutoff of 53.8 pg/mL, patients with increased bio-ADM had a HR of 3.90 (95% confidence interval 1.43-10.68, p = 0.008) for 30-day all-cause mortality, and similar results were observed even after adjustment for severity scores. Patients with the occurrence of refractory CS had higher bio-ADM value at inclusion (90.7 (59.9-147.7) pg/mL vs. 40.7 (23.0-64.7) pg/mL p = 0.005). Bio-ADM values at inclusion were correlated with pulmonary vascular resistance index, estimated glomerular filtration rate, and N-terminal pro-B-type natriuretic peptide (r = 0.49, r = -0.47, and r = 0.64, respectively; p < 0.001). CONCLUSIONS: In CS patients, the values of bio-ADM are associated with some parameters of organ injury and functional impairment and are prognostic for the occurrence of refractory CS and 30-day mortality.

The Physiological Deep Learner: First application of multitask deep learning to predict hypotension in critically ill patients.

Critical care clinicians are trained to analyze simultaneously multiple physiological parameters to predict critical conditions such as hemodynamic instability. We developed the Multi-task Learning Physiological Deep Learner (MTL-PDL), a deep learning algorithm that predicts simultaneously the mean arterial pressure (MAP) and the heart rate (HR). In an external validation dataset, our model exhibited very good calibration: R2 of 0.747 (95% confidence interval, 0.692 to 0.794) and 0.850 (0.815 to 0.879) for respectively, MAP and HR prediction 60-minutes ahead of time. For acute hypotensive episodes defined as a MAP below 65 mmHg for 5 min, our MTL-PDL reached a predictive value of 90% for patients at very high risk (predicted MAP ≤ 60 mmHg) and 2‰ for patients at low risk (predicted MAP >70 mmHg). Based on its excellent prediction performance, the Physiological Deep Learner has the potential to help the clinician proactively adjust the treatment in order to avoid hypotensive episodes and end-organ hypoperfusion.

SARS-CoV-2 vaccination efficacy on hospitalisation and variants.

We report data regarding three countries with similar healthcare systems which had three different vaccinal strategies between 1st of January and 10th of April 2021: rapid full vaccination (Israel), rapid first-dose vaccination (United Kingdom) and a delayed vaccination strategy (France).

Monitoring circulating dipeptidyl peptidase 3 (DPP3) predicts improvement of organ failure and survival in sepsis: a prospective observational multinational study.

BACKGROUND: Dipeptidyl peptidase 3 (DPP3) is a cytosolic enzyme involved in the degradation of various cardiovascular and endorphin mediators. High levels of circulating DPP3 (cDPP3) indicate a high risk of organ dysfunction and mortality in cardiogenic shock patients. METHODS: The aim was to assess relationships between cDPP3 during the initial intensive care unit (ICU) stay and short-term outcome in the AdrenOSS-1, a prospective observational multinational study in twenty-four ICU centers in five countries. AdrenOSS-1 included 585 patients admitted to the ICU with severe sepsis or septic shock. The primary outcome was 28-day mortality. Secondary outcomes included organ failure as defined by the Sequential Organ Failure Assessment (SOFA) score, organ support with focus on vasopressor/inotropic use and need for renal replacement therapy. cDPP3 levels were measured upon admission and 24 h later. RESULTS: Median [IQR] cDPP3 concentration upon admission was 26.5 [16.2-40.4] ng/mL. Initial SOFA score was 7 [5-10], and 28-day mortality was 22%. We found marked associations between cDPP3 upon ICU admission and 28-day mortality (unadjusted standardized HR 1.8 [CI 1.6-2.1]; adjusted HR 1.5 [CI 1.3-1.8]) and between cDPP3 levels and change in renal and liver SOFA score (p = 0.0077 and 0.0009, respectively). The higher the initial cDPP3 was, the greater the need for organ support and vasopressors upon admission; the longer the need for vasopressor(s), mechanical ventilation or RRT and the higher the need for fluid load (all p < 0.005). In patients with cDPP3 > 40.4 ng/mL upon admission, a decrease in cDPP3 below 40.4 ng/mL after 24 h was associated with an improvement of organ function at 48 h and better 28-day outcome. By contrast, persistently elevated cDPP3 at 24 h was associated with worsening organ function and high 28-day mortality. CONCLUSIONS: Admission levels and rapid changes in cDPP3 predict outcome during sepsis. Trial Registration ClinicalTrials.gov, NCT02393781. Registered on March 19, 2015.