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IMPORTANCE: Ventilator-associated pneumonia (VAP) frequently occurs in patients with cardiac arrest. Diagnosis of VAP after cardiac arrest remains challenging, while the use of current biomarkers such as C-reactive protein (CRP) or procalcitonin (PCT) is debated. OBJECTIVES: To evaluate biomarkers' impact in helping VAP diagnosis after cardiac arrest. DESIGN SETTING AND PARTICIPANTS: This is a prospective ancillary study of the randomized, multicenter, double-blind placebo-controlled ANtibiotherapy during Therapeutic HypothermiA to pRevenT Infectious Complications (ANTHARTIC) trial evaluating the impact of antibiotic prophylaxis to prevent VAP in out-of-hospital patients with cardiac arrest secondary to shockable rhythm and treated with therapeutic hypothermia. An adjudication committee blindly evaluated VAP according to predefined clinical, radiologic, and microbiological criteria. All patients with available biomarker(s), sample(s), and consent approval were included. MAIN OUTCOMES AND MEASURES: The main endpoint was to evaluate the ability of biomarkers to correctly diagnose and predict VAP within 48 hours after sampling. The secondary endpoint was to study the combination of two biomarkers in discriminating VAP. Blood samples were collected at baseline on day 3. Routine and exploratory panel of inflammatory biomarkers measurements were blindly performed. Analyses were adjusted on the randomization group. RESULTS: Among 161 patients of the ANTHARTIC trial with available biological sample(s), patients with VAP (n = 33) had higher body mass index and Acute Physiology and Chronic Health Evaluation II score, more unwitnessed cardiac arrest, more catecholamines, and experienced more prolonged therapeutic hypothermia duration than patients without VAP (n = 121). In univariate analyses, biomarkers significantly associated with VAP and showing an area under the curve (AUC) greater than 0.70 were CRP (AUC = 0.76), interleukin (IL) 17A and 17C (IL17C) (0.74), macrophage colony-stimulating factor 1 (0.73), PCT (0.72), and vascular endothelial growth factor A (VEGF-A) (0.71). Multivariate analysis combining novel biomarkers revealed several pairs with p value of less than 0.001 and odds ratio greater than 1: VEGF-A + IL12 subunit beta (IL12B), Fms-related tyrosine kinase 3 ligands (Flt3L) + C-C chemokine 20 (CCL20), Flt3L + IL17A, Flt3L + IL6, STAM-binding protein (STAMBP) + CCL20, STAMBP + IL6, CCL20 + 4EBP1, CCL20 + caspase-8 (CASP8), IL6 + 4EBP1, and IL6 + CASP8. Best AUCs were observed for CRP + IL6 (0.79), CRP + CCL20 (0.78), CRP + IL17A, and CRP + IL17C. CONCLUSIONS AND RELEVANCE: Our exploratory study shows that specific biomarkers, especially CRP combined with IL6, could help to better diagnose or predict early VAP occurrence in cardiac arrest patients.
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Biomarcadores , Hipotermia Inducida , Neumonía Asociada al Ventilador , Polipéptido alfa Relacionado con Calcitonina , Humanos , Biomarcadores/sangre , Neumonía Asociada al Ventilador/diagnóstico , Neumonía Asociada al Ventilador/sangre , Neumonía Asociada al Ventilador/tratamiento farmacológico , Masculino , Femenino , Hipotermia Inducida/métodos , Persona de Mediana Edad , Anciano , Estudios Prospectivos , Polipéptido alfa Relacionado con Calcitonina/sangre , Método Doble Ciego , Antibacterianos/uso terapéutico , Proteína C-Reactiva/análisis , Proteína C-Reactiva/metabolismo , Paro Cardíaco/sangre , Valor Predictivo de las PruebasRESUMEN
BACKGROUND: Cardiogenic shock and sepsis are severe haemodynamic states that are frequently present concomitantly, leading to substantial mortality. Despite its frequency and clinical significance, there is a striking lack of literature on the outcomes of combined sepsis and cardiogenic shock. METHODS: FRENSHOCK was a prospective registry including 772 patients with cardiogenic shock from 49 centres. The primary endpoint was 1-month all-cause mortality. Secondary endpoints included heart transplantation, ventricular assistance device and all-cause death rate at 1year. RESULTS: Among the 772 patients with cardiogenic shock included, 92 cases were triggered by sepsis (11.9%), displaying more frequent renal and hepatic acute injuries, with lower mean arterial pressure. Patients in the sepsis group required broader use of dobutamine (90.1% vs. 81.2%; P=0.16), norepinephrine (72.5% vs. 50.8%; P<0.01), renal replacement therapy (29.7% vs. 14%; P<0.01), non-invasive ventilation (36.3% vs. 24.4%; P=0.09) and invasive ventilation (52.7% vs. 35.9%; P=0.02). Sepsis-triggered cardiogenic shock resulted in higher 1-month (41.3% vs. 24.0%; adjusted hazard ratio: 1.94, 95% confidence interval: 1.36-2.76; P<0.01) and 1-year (62.0% vs. 42.9%; adjusted hazard ratio 1.75, 95% confidence interval 1.32-2.33; P<0.01) all-cause death rates. No significant difference was found at 1year for heart transplantation or ventricular assistance device (8.7% vs. 10.3%; adjusted odds ratio 0.72, 95% confidence interval 0.32-1.64; P=0.43). In patients with sepsis-triggered cardiogenic shock, neither the presence of a preexisting cardiomyopathy nor the co-occurrence of other cardiogenic shock triggers had any additional impact on death. CONCLUSIONS: The association between sepsis and cardiogenic shock represents a common high-risk scenario, leading to higher short- and long-term death rates, regardless of the association with other cardiogenic shock triggers or the presence of preexisting cardiomyopathy.
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BACKGROUND: The Sequential Organ Failure Assessment (SOFA) score is an important tool in diagnosing sepsis and quantifying organ dysfunction. However, despite emerging evidence of differences in sepsis pathophysiology between women and men, sex is currently not being considered in the SOFA score. We aimed to investigate potential sex-specific differences in organ dysfunction, as measured by the SOFA score, in patients with sepsis or septic shock and explore outcome associations. METHODS: Retrospective analysis of sex-specific differences in the SOFA score of prospectively enrolled ICU patients with sepsis or septic shock admitted to one of 85 certified Swiss ICUs between 01/2021 and 12/2022. RESULTS: Of 125,782 patients, 5947 (5%) were admitted with a clinical diagnosis of sepsis (2244, 38%) or septic shock (3703, 62%). Of these, 5078 (37% women) were eligible for analysis. A statistically significant difference of the total SOFA score on admission was found between women (mean 7.5 ± SD 3.6 points) and men (7.8 ± 3.6 points, Wilcoxon rank-sum p < 0.001). This was driven by differences in the coagulation (p = 0.008), liver (p < 0.001) and renal (p < 0.001) SOFA components. Differences between sexes were more prominent in younger patients < 52 years of age (women 7.1 ± 4.0 points vs men 8.1 ± 4.2 points, p = 0.004). No sex-specific differences were found in ICU length of stay (women median 2.6 days (IQR 1.3-5.3) vs men 2.7 days (IQR 1.2-6.0), p = 0.13) and ICU mortality (women 14% vs men 15%, p = 0.17). CONCLUSION: Sex-specific differences exist in the SOFA score of patients admitted to a Swiss ICU with sepsis or septic shock, particularly in laboratory-based components. Although the clinical meaningfulness of these differences is unclear, a reevaluation of sex-specific thresholds for SOFA score components is warranted in an attempt to make more accurate and individualised classifications.
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Unidades de Cuidados Intensivos , Puntuaciones en la Disfunción de Órganos , Sepsis , Choque Séptico , Humanos , Femenino , Masculino , Unidades de Cuidados Intensivos/organización & administración , Unidades de Cuidados Intensivos/estadística & datos numéricos , Persona de Mediana Edad , Anciano , Estudios Retrospectivos , Sepsis/clasificación , Sepsis/fisiopatología , Sepsis/diagnóstico , Sepsis/mortalidad , Choque Séptico/fisiopatología , Choque Séptico/mortalidad , Choque Séptico/clasificación , Choque Séptico/diagnóstico , Suiza/epidemiología , Factores Sexuales , Estudios Prospectivos , AdultoRESUMEN
BACKGROUND: Chronic kidney disease (CKD) is one of the leading causes of death worldwide, closely interrelated with cardiovascular diseases, ultimately leading to the failure of both organs - the so-called "cardiorenal syndrome". Despite this burden, data related to cardiogenic shock outcomes in CKD patients are scarce. METHODS: FRENSHOCK (NCT02703038) was a prospective registry involving 772 patients with cardiogenic shock from 49 centres. One-year outcomes (rehospitalization, death, heart transplantation, ventricular assist device) were analysed according to history of CKD at admission and were adjusted on independent predictive factors. RESULTS: CKD was present in 164 of 771 patients (21.3%) with cardiogenic shock; these patients were older (72.7 vs. 63.9years) and had more comorbidities than those without CKD. CKD was associated with a higher rate of all-cause mortality at 1month (36.6% vs. 23.2%; hazard ratio 1.39, 95% confidence interval 1.01-1.9; P=0.04) and 1year (62.8% vs. 40.5%, hazard ratio 1.39, 95% confidence interval 1.09-1.77; P<0.01). Patients with CKD were less likely to be treated with norepinephrine/epinephrine or undergo invasive ventilation or receive mechanical circulatory support, but were more likely to receive renal replacement therapy (RRT). RRT was associated with a higher risk of all-cause death at 1month and 1year regardless of baseline CKD status. CONCLUSIONS: Cardiogenic shock and CKD are frequent "cross-talking" conditions with limited therapeutic options, resulting in higher rates of death at 1month and 1year. RRT is a strong predictor of death, regardless of preexisting CKD. Multidisciplinary teams involving cardiac and kidney physicians are required to provide integrated care for patients with failure of both organs.
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Insuficiencia Renal Crónica , Choque Cardiogénico , Humanos , Choque Cardiogénico/diagnóstico , Choque Cardiogénico/etiología , Choque Cardiogénico/terapia , Insuficiencia Renal Crónica/complicaciones , Insuficiencia Renal Crónica/diagnóstico , Insuficiencia Renal Crónica/epidemiología , Comorbilidad , Modelos de Riesgos Proporcionales , Terapia de Reemplazo Renal/efectos adversosRESUMEN
To create robust and adaptable methods for lung pneumonia diagnosis and the assessment of its severity using chest X-rays (CXR), access to well-curated, extensive datasets is crucial. Many current severity quantification approaches require resource-intensive training for optimal results. Healthcare practitioners require efficient computational tools to swiftly identify COVID-19 cases and predict the severity of the condition. In this research, we introduce a novel image augmentation scheme as well as a neural network model founded on Vision Transformers (ViT) with a small number of trainable parameters for quantifying COVID-19 severity and other lung diseases. Our method, named Vision Transformer Regressor Infection Prediction (ViTReg-IP), leverages a ViT architecture and a regression head. To assess the model's adaptability, we evaluate its performance on diverse chest radiograph datasets from various open sources. We conduct a comparative analysis against several competing deep learning methods. Our results achieved a minimum Mean Absolute Error (MAE) of 0.569 and 0.512 and a maximum Pearson Correlation Coefficient (PC) of 0.923 and 0.855 for the geographic extent score and the lung opacity score, respectively, when the CXRs from the RALO dataset were used in training. The experimental results reveal that our model delivers exceptional performance in severity quantification while maintaining robust generalizability, all with relatively modest computational requirements. The source codes used in our work are publicly available at https://github.com/bouthainas/ViTReg-IP .
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COVID-19 , Pulmón , Neumonía , Índice de Severidad de la Enfermedad , Humanos , COVID-19/diagnóstico por imagen , Neumonía/diagnóstico por imagen , Pulmón/diagnóstico por imagen , Radiografía Torácica/métodos , Aprendizaje Profundo , SARS-CoV-2 , Redes Neurales de la ComputaciónRESUMEN
INTRODUCTION: Toll-like receptors play crucial roles in the sepsis-induced systemic inflammatory response. Septic shock mortality correlates with overexpression of neutrophilic TLR2 and TLR9, while the role of TLR4 overexpression remains a debate. In addition, TLRs are involved in the pathogenesis of viral infections such as COVID-19, where the single-stranded RNA of SARS-CoV-2 is recognized by TLR7 and TLR8, and the spike protein activates TLR4. METHODS: In this study, we conducted a comprehensive analysis of TLRs 1-10 expressions in white blood cells from 71 patients with bacterial and viral infections. Patients were divided into 4 groups based on disease type and severity (sepsis, septic shock, moderate, and severe COVID-19) and compared to 7 healthy volunteers. RESULTS: We observed a significant reduction in the expression of TLR4 and its co-receptor CD14 in septic shock neutrophils compared to the control group (p < 0.001). Severe COVID-19 patients exhibited a significant increase in TLR3 and TLR7 levels in neutrophils compared to controls (p < 0.05). Septic shock patients also showed a similar increase in TLR7 in neutrophils along with elevated intermediate monocytes (CD14+CD16+) compared to the control group (p < 0.005 and p < 0.001, respectively). However, TLR expression remained unchanged in lymphocytes. CONCLUSION: This study provides further insights into the mechanisms of TLR activation in various infectious conditions. Additional analysis is needed to assess their correlation with patient outcome and to evaluate the impact of TLR-pathway modulation during septic shock and severe COVID-19.
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COVID-19 , SARS-CoV-2 , Receptor Toll-Like 10 , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Infecciones Bacterianas/inmunología , COVID-19/inmunología , COVID-19/sangre , Leucocitos/inmunología , Leucocitos/metabolismo , Receptores de Lipopolisacáridos/metabolismo , Neutrófilos/inmunología , SARS-CoV-2/inmunología , Sepsis/inmunología , Choque Séptico/inmunología , Choque Séptico/sangre , Receptor Toll-Like 1/metabolismo , Receptor Toll-Like 1/genética , Receptor Toll-Like 7/metabolismo , Receptor Toll-Like 7/genética , Receptores Toll-Like/metabolismo , Anciano de 80 o más AñosRESUMEN
BACKGROUND: Extracorporeal membrane oxygenation (ECMO) is associated with a high risk of bleeding complications. The specific impact of ECMO on fibrinolysis remains unexplored. The objective of the current pilot observational prospective study was to investigate the longitudinal dynamics of fibrinolytic markers-i.e., changes over time-in the context of bleeding events in patients on ECMO. METHODS: Longitudinal dynamics of contact phase components (kininogen and bradykinin) and fibrinolysis markers (tissue plasminogen activator [tPA], plasminogen activator inhibitor-1 [PAI-1], their complexes [tPAâ¢PAI-1], plasmin-antiplasmin complexes, plasminogen, and D-dimer) were measured in patients undergoing venovenous and venoarterial ECMO, before implantation, at 0, 6, and 12 h after implantation, and daily thereafter. RESULTS: The cohort consisted of 30 patients (214 ECMO days). The concentrations of tPA, D-dimer, plasmin-antiplasmin complexes, PAI-1, and tPAâ¢PAI-1 complexes were increased, whereas plasminogen decreased compared to normal values. A noteworthy divergence was observed between hemorrhagic and nonhemorrhagic patients: in bleeding patients, D-dimer, plasmin-antiplasmin, tPA, PAI-1, and tPAâ¢PAI-1 followed an increasing kinetics before hemorrhage and then decreased to their baseline level; conversely, nonbleeding patients showed a decreasing kinetics in these markers. Also, D-dimer and tPA followed an increasing kinetics in bleeding patients compared to nonbleeding patients (median values for D-dimer dynamics: 1,080 vs. -440 ng/ml, P = 0.05; tPA dynamics: 0.130 vs. 0.100 nM, P = 0.038), and both markers significantly increased the day before hemorrhage. A tPA concentration above 0.304 nM was associated with bleeding events (odds ratio, 4.92; 95% CI, 1.01 to 24.08; P = 0.049). CONCLUSIONS: Contact activation induces fibrinolysis in ECMO patients, especially in patients experiencing bleeding. This finding supports the role of this mechanism as a possible causal factor for hemorrhages during ECMO and open new avenues for novel therapeutic perspectives.
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Oxigenación por Membrana Extracorpórea , Fibrinólisis , Humanos , Oxigenación por Membrana Extracorpórea/efectos adversos , Oxigenación por Membrana Extracorpórea/métodos , Proyectos Piloto , Fibrinólisis/fisiología , Estudios Prospectivos , Masculino , Femenino , Persona de Mediana Edad , Adulto , Hemorragia/etiología , Hemorragia/sangre , Hemorragia/terapia , Activador de Tejido Plasminógeno/sangre , Biomarcadores/sangre , Inhibidor 1 de Activador Plasminogénico/sangre , Anciano , Productos de Degradación de Fibrina-Fibrinógeno/análisis , Productos de Degradación de Fibrina-Fibrinógeno/metabolismo , Estudios de CohortesRESUMEN
BACKGROUND: The effects of pharmacological therapy on cardiogenic shock (CS) survivors have not been extensively studied. Thus, this study investigated the association between guideline-directed heart failure (HF) medical therapy (GDMT) and one-year survival rate in patients who are post-CS. METHODS AND RESULTS: FRENSHOCK (French Observatory on the Management of Cardiogenic Shock in 2016) registry was a prospective multicenter observational survey, conducted in metropolitan French intensive care units and intensive cardiac care units. Of 772 patients, 535 patients were enrolled in the present analysis following the exclusion of 217 in-hospital deaths and 20 patients with missing medical records. Patients with triple GDMT (beta-blockers, renin-angiotensin system inhibitors, and mineralocorticoid receptor antagonists) at discharge (n=112) were likely to have lower left ventricular ejection fraction on admission and at discharge compared with those without triple GDMT (n=423) (22% versus 28%, P<0.001 and 29% versus 37%, P<0.001, respectively). In the overall cohort, the one-year mortality rate was 23%. Triple GDMT prescription was significantly associated with a lower one-year all-cause mortality compared with non-triple GDMT (adjusted hazard ratio 0.44 [95% CI, 0.19-0.80]; P=0.007). Similarly, 2:1 propensity score matching and inverse probability treatment weighting based on the propensity score demonstrated a lower incidence of one-year mortality in the triple GDMT group. As the number of HF drugs increased, a stepwise decrease in mortality was observed (log rank; P<0.001). CONCLUSIONS: In survivors of CS, the one-year mortality rate was significantly lower in those with triple GDMT. Therefore, this study suggests that intensive HF therapy should be considered in patients following CS.
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Insuficiencia Cardíaca , Choque Cardiogénico , Humanos , Antagonistas Adrenérgicos beta/uso terapéutico , Antagonistas de Receptores de Angiotensina/uso terapéutico , Estudios Prospectivos , Sistema de Registros , Volumen Sistólico , Función Ventricular Izquierda , Estudios Multicéntricos como Asunto , Estudios Observacionales como AsuntoRESUMEN
Importance: International guidelines recommend body temperature control below 37.8 °C in unconscious patients with out-of-hospital cardiac arrest (OHCA); however, a target temperature of 33 °C might lead to better outcomes when the initial rhythm is nonshockable. Objective: To assess whether hypothermia at 33 °C increases survival and improves function when compared with controlled normothermia in unconscious adults resuscitated from OHCA with initial nonshockable rhythm. Data Sources: Individual patient data meta-analysis of 2 multicenter, randomized clinical trials (Targeted Normothermia after Out-of-Hospital Cardiac Arrest [TTM2; NCT02908308] and HYPERION [NCT01994772]) with blinded outcome assessors. Unconscious patients with OHCA and an initial nonshockable rhythm were eligible for the final analysis. Study Selection: The study cohorts had similar inclusion and exclusion criteria. Patients were randomized to hypothermia (target temperature 33 °C) or normothermia (target temperature 36.5 to 37.7 °C), according to different study protocols, for at least 24 hours. Additional analyses of mortality and unfavorable functional outcome were performed according to age, sex, initial rhythm, presence or absence of shock on admission, time to return of spontaneous circulation, lactate levels on admission, and the cardiac arrest hospital prognosis score. Data Extraction and Synthesis: Only patients who experienced OHCA and had a nonshockable rhythm with all causes of cardiac arrest were included. Variables from the 2 studies were available from the original data sets and pooled into a unique database and analyzed. Clinical outcomes were harmonized into a single file, which was checked for accuracy of numbers, distributions, and categories. The last day of follow-up from arrest was recorded for each patient. Adjustment for primary outcome and functional outcome was performed using age, gender, time to return of spontaneous circulation, and bystander cardiopulmonary resuscitation. Main Outcomes and Measures: The primary outcome was mortality at 3 months; secondary outcomes included unfavorable functional outcome at 3 to 6 months, defined as a Cerebral Performance Category score of 3 to 5. Results: A total of 912 patients were included, 490 from the TTM2 trial and 422 from the HYPERION trial. Of those, 442 had been assigned to hypothermia (48.4%; mean age, 65.5 years; 287 males [64.9%]) and 470 to normothermia (51.6%; mean age, 65.6 years; 327 males [69.6%]); 571 patients had a first monitored rhythm of asystole (62.6%) and 503 a presumed noncardiac cause of arrest (55.2%). At 3 months, 354 of 442 patients in the hypothermia group (80.1%) and 386 of 470 patients in the normothermia group (82.1%) had died (relative risk [RR] with hypothermia, 1.04; 95% CI, 0.89-1.20; P = .63). On the last day of follow-up, 386 of 429 in the hypothermia group (90.0%) and 413 of 463 in the normothermia group (89.2%) had an unfavorable functional outcome (RR with hypothermia, 0.99; 95% CI, 0.87-1.15; P = .97). The association of hypothermia with death and functional outcome was consistent across the prespecified subgroups. Conclusions and Relevance: In this individual patient data meta-analysis, including unconscious survivors from OHCA with an initial nonshockable rhythm, hypothermia at 33 °C did not significantly improve survival or functional outcome.
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Reanimación Cardiopulmonar , Hipotermia Inducida , Hipotermia , Paro Cardíaco Extrahospitalario , Masculino , Adulto , Humanos , Anciano , Paro Cardíaco Extrahospitalario/terapia , Hipotermia Inducida/métodos , Pronóstico , InconscienciaRESUMEN
BACKGROUND: Disseminated intravascular coagulation (DIC) worsens the prognosis of septic shock and contributes to multiple organ failure. To date, no data linking DIC and acute kidney injury (AKI) occurrence, severity, and evolution in this setting are available. We aimed at analyzing the association between AKI occurrence, severity and evolution in patients with septic shock-induced DIC. In a prospective monocentric cohort study, consecutive patients, 18 years and older, admitted in the ICU of Strasbourg University Hospital in the setting of systemic hypotension requiring vasopressor related to an infection, without history of terminal chronic kidney disease were eligible. AKI was defined according to the KDIGO classification. DIC diagnosis was based on the International Society on Thrombosis and Haemostasis (ISTH) score. Evolution of AKI was evaluated through the composite endpoint of major adverse kidney events. Only patients with DIC that occurred before or at the time of AKI diagnosis were considered. Univariate and multivariate analysis were performed to determine factors associated with renal outcomes. RESULTS: 350 patients were included, of whom 129 experienced DIC. Patients with DIC were more seriously ill (median SAPS II 64 vs. 56, p < 0.001), and had higher 28-day mortality (43.3% vs. 26.2%, p < 0.001). AKI was more frequent in patients with DIC (86.8% vs. 74.2%, p < 0.005), particularly for the more severe stage of AKI [KDIGO 3 in 58.1% of patients with DIC vs. 30.8% of patients without DIC, p < 0.001, AKI requiring renal replacement therapy (RRT) in 47.3% of patients with DIC vs. 21.3% of patients without DIC, p < 0.001]. After adjustment for confounding factors, DIC occurrence remained associated with the risk of having the more severe stage of AKI with an odds ratio (OR) of 2.74 [IC 95% (1.53-4.91), p < 0.001], and with the risk of requiring RRT during the ICU stay [OR 2.82 (1.53-5.2), p < 0.001]. CONCLUSION: DIC appears to be strongly associated with the risk of developing the more severe form of AKI (stage 3 of the KDIGO classification, RRT requirement), even after adjustment for severity and other relevant factors.
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BACKGROUND: Whether preventive inhaled antibiotics may reduce the incidence of ventilator-associated pneumonia is unclear. METHODS: In this investigator-initiated, multicenter, double-blind, randomized, controlled, superiority trial, we assigned critically ill adults who had been undergoing invasive mechanical ventilation for at least 72 hours to receive inhaled amikacin at a dose of 20 mg per kilogram of ideal body weight once daily or to receive placebo for 3 days. The primary outcome was a first episode of ventilator-associated pneumonia during 28 days of follow-up. Safety was assessed. RESULTS: A total of 850 patients underwent randomization, and 847 were included in the analyses (417 assigned to the amikacin group and 430 to the placebo group). All three daily nebulizations were received by 337 patients (81%) in the amikacin group and 355 patients (83%) in the placebo group. At 28 days, ventilator-associated pneumonia had developed in 62 patients (15%) in the amikacin group and in 95 patients (22%) in the placebo group (difference in restricted mean survival time to ventilator-associated pneumonia, 1.5 days; 95% confidence interval [CI], 0.6 to 2.5; P = 0.004). An infection-related ventilator-associated complication occurred in 74 patients (18%) in the amikacin group and in 111 patients (26%) in the placebo group (hazard ratio, 0.66; 95% CI, 0.50 to 0.89). Trial-related serious adverse effects were seen in 7 patients (1.7%) in the amikacin group and in 4 patients (0.9%) in the placebo group. CONCLUSIONS: Among patients who had undergone mechanical ventilation for at least 3 days, a subsequent 3-day course of inhaled amikacin reduced the burden of ventilator-associated pneumonia during 28 days of follow-up. (Funded by the French Ministry of Health; AMIKINHAL ClinicalTrials.gov number, NCT03149640; EUDRA Clinical Trials number, 2016-001054-17.).
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Amicacina , Antibacterianos , Neumonía Asociada al Ventilador , Adulto , Humanos , Amicacina/administración & dosificación , Amicacina/efectos adversos , Amicacina/uso terapéutico , Método Doble Ciego , Neumonía Asociada al Ventilador/etiología , Neumonía Asociada al Ventilador/prevención & control , Respiración Artificial/efectos adversos , Resultado del Tratamiento , Administración por Inhalación , Antibacterianos/administración & dosificación , Antibacterianos/efectos adversos , Antibacterianos/uso terapéutico , Enfermedad CríticaRESUMEN
Background: Cardiac arrest is the most life-threatening complication of attempted suicide by hanging. However, data are scarce on its characteristics and outcome predictors. Methods: This retrospective observational multicentre study in 31 hospitals included consecutive adults admitted after cardiac arrest induced by suicidal hanging. Factors associated with in-hospital mortality were identified by multivariate logistic regression with multiple imputations for missing data and adjusted to the temporal trends over the study period. Results: Of 450 patients (350 men, median age, 43 [34-52] years), 305 (68%) had a psychiatric history, and 31 (6.9%) attempted hanging while hospitalized. The median time from unhanging to cardiopulmonary resuscitation was 0 [0-5] min, and the median time to return of spontaneous circulation (ROSC) was 20 [10-30] min. Seventy-nine (18%) patients survived to hospital discharge. Three variables were independently associated with higher in-hospital mortality: time from collapse or unhanging to ROSC>20 min (odds ratio [OR], 4.71; 95% confidence intervals [95%CIs], 2.02-10.96; p = 0.0004); glycaemia >1.4 g/L at admission (OR, 6.38; 95%CI, 2.60-15.66; p < 0.0001); and lactate >3.5 mmol/L at admission (OR, 6.08; 95%CI, 1.71-21.06; p = 0.005). A Glasgow Coma Scale (GCS) score of >5 at admission was associated with lower in-hospital mortality (OR, 0.009; 95%CI, 0.02-0.37; p = 0.0009). Conclusion: In patients with hanging-induced cardiac arrest, time from collapse or unhanging to return of spontaneous circulation, glycaemia, arterial lactate, and coma depth at admission were independently associated with survival to hospital discharge. Knowledge of these risk factors may help guide treatment decisions in these patients at high risk of hospital mortality.
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AIMS: Impact of skin mottling has been poorly studied in patients admitted for cardiogenic shock. This study aimed to address this issue and identify determinants of 30-day and 1-year mortality in a large cardiogenic shock cohort of all etiologies. METHODS AND RESULTS: FRENSHOCK is a prospective multicenter observational registry conducted in French critical care units between April and October, 2016. Among the 772 enrolled patients (mean age 65.7 ± 14.9 years; 71.5% male), 660 had skin mottling assessed at admission (85.5%) with almost 39% of patients in cardiogenic shock presenting mottling. The need for invasive respiratory support was significantly higher in patients with mottling (50.2% vs. 30.1%, p < 0.001) and likewise for the need for renal replacement therapy (19.9% vs. 12.4%, p = 0.09). However, the need for mechanical circulatory support was similar in both groups. Patients with mottling at admission presented a higher length of stay (19 vs. 16 days, p = 0.033), a higher 30-day mortality rate (31% vs. 23.3%, p = 0.031), and also showed significantly higher mortality at 1-year (54% vs. 42%, p = 0.003). The subgroup of patients in whom mottling appeared during the first 24 h after admission had the worst prognosis at 30 days. CONCLUSION: Skin mottling at admission in patients with cardiogenic shock was statistically associated with prolonged length of stay and poor outcomes. As a perfusion-targeted resuscitation parameter, mottling is a simple, clinical-based approach and may thus help to improve and guide immediate goal-directed therapy to improve cardiogenic shock patients' outcomes.
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Despite significant advancements in critical care medicine, limited attention has been given to sex and gender disparities in management and outcomes of patients admitted to the intensive care unit (ICU). While "sex" pertains to biological and physiological characteristics, such as reproductive organs, chromosomes and sex hormones, "gender" refers more to sociocultural roles and human behavior. Unfortunately, data on gender-related topics in the ICU are lacking. Consequently, data on sex and gender-related differences in admission to the ICU, clinical course, length of stay, mortality, and post-ICU burdens, are often inconsistent. Moreover, when examining specific diagnoses in the ICU, variations can be observed in epidemiology, pathophysiology, presentation, severity, and treatment response due to the distinct impact of sex hormones on the immune and cardiovascular systems. In this narrative review, we highlight the influence of sex and gender on the clinical course, management, and outcomes of the most encountered intensive care conditions, in addition to the potential co-existence of unconscious biases which may also impact critical illness. Diagnoses with a known sex predilection will be discussed within the context of underlying sex differences in physiology, anatomy, and pharmacology with the goal of identifying areas where clinical improvement is needed. To optimize patient care and outcomes, it is crucial to comprehend and address sex and gender differences in the ICU setting and personalize management accordingly to ensure equitable, patient-centered care. Future research should focus on elucidating the underlying mechanisms driving sex and gender disparities, as well as exploring targeted interventions to mitigate these disparities and improve outcomes for all critically ill patients.
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BACKGROUND: Respiratory mechanics is a key element to monitor mechanically ventilated patients and guide ventilator settings. Besides the usual basic assessments, some more complex explorations may allow to better characterize patients' respiratory mechanics and individualize ventilation strategies. These advanced respiratory mechanics assessments including esophageal pressure measurements and complete airway closure detection may be particularly relevant in critically ill obese patients. This study aimed to comprehensively assess respiratory mechanics in obese and non-obese ICU patients with or without ARDS and evaluate the contribution of advanced respiratory mechanics assessments compared to basic assessments in these patients. METHODS: All intubated patients admitted in two ICUs for any cause were prospectively included. Gas exchange and respiratory mechanics including esophageal pressure and end-expiratory lung volume (EELV) measurements and low-flow insufflation to detect complete airway closure were assessed in standardized conditions (tidal volume of 6 mL kg-1 predicted body weight (PBW), positive end-expiratory pressure (PEEP) of 5 cmH2O) within 24 h after intubation. RESULTS: Among the 149 analyzed patients, 52 (34.9%) were obese and 90 (60.4%) had ARDS (65.4% and 57.8% of obese and non-obese patients, respectively, p = 0.385). A complete airway closure was found in 23.5% of the patients. It was more frequent in obese than in non-obese patients (40.4% vs 14.4%, p < 0.001) and in ARDS than in non-ARDS patients (30% vs. 13.6%, p = 0.029). Respiratory system and lung compliances and EELV/PBW were similarly decreased in obese patients without ARDS and obese or non-obese patients with ARDS. Chest wall compliance was not impacted by obesity or ARDS, but end-expiratory esophageal pressure was higher in obese than in non-obese patients. Chest wall contribution to respiratory system compliance differed widely between patients but was not predictable by their general characteristics. CONCLUSIONS: Most respiratory mechanics features are similar in obese non-ARDS and non-obese ARDS patients, but end-expiratory esophageal pressure is higher in obese patients. A complete airway closure can be found in around 25% of critically ill patients ventilated with a PEEP of 5 cmH2O. Advanced explorations may allow to better characterize individual respiratory mechanics and adjust ventilation strategies in some patients. Trial registration NCT03420417 ClinicalTrials.gov (February 5, 2018).
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Enfermedad Crítica , Síndrome de Dificultad Respiratoria , Humanos , Peso Corporal , Obesidad/complicaciones , Respiración Artificial , Síndrome de Dificultad Respiratoria/complicaciones , Síndrome de Dificultad Respiratoria/terapia , Mecánica RespiratoriaRESUMEN
BACKGROUND & AIMS: After a prolonged intensive care unit (ICU) stay patients experience increased mortality and morbidity. The primary aim of this study was to assess the prognostic value of nutritional status, body mass composition and muscle strength, as assessed by body mass index (BMI), bioelectrical impedance analysis (BIA), handgrip (HG) test, and that of the biological features to predict one-year survival at the end of a prolonged ICU stay. METHODS: This was a multicenter prospective observational study. Survivor patients older than 18 years with ICU length of stay >72 h were eligible for inclusion. BIA and HG were performed at the end of the ICU stay. Malnutrition was defined by BMI and fat-free mass index (FFMI). The primary endpoint was one-year mortality. Multivariable logistic regression was performed to determine parameters associated with mortality. RESULTS: 572 patients were included with a median age of 63 years [53.5; 71.1], BMI of 26.6 kg/m2 [22.8; 31.3], SAPS II score of 43 [31; 58], and ICU length of stay of 9 days [6; 15]. Malnutrition was observed in 142 (24.9%) patients. During the 1-year follow-up after discharge, 96 (18.5%) patients died. After adjustment, a low HG test score (aOR = 1.44 [1.11; 1.89], p = 0.01) was associated with 1-year mortality. Patients with low HG score, malnutrition, and Albuminemia <30 g/L had a one-year death rate of 41.4%. Conversely, patients with none of these parameters had a 1-year death rate of 4.1%. CONCLUSION: BIA to assess FFMI, HG and albuminemia at the end of ICU stay could be used to predict 1-year mortality. Their ability to identify patients eligible for a structured recovery program could be studied.
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Fuerza de la Mano , Desnutrición , Humanos , Persona de Mediana Edad , Estudios Prospectivos , Desnutrición/diagnóstico , Desnutrición/complicaciones , Fuerza Muscular , Composición Corporal , Unidades de Cuidados IntensivosRESUMEN
OBJECTIVES: Staphylococcus epidermidis (SE) is a supposedly low-virulence agent, which may cause proven bloodstream infections (BSIs), with little-known consequences on intensive care unit (ICU) patients. We aimed at studying ICU patients diagnosed with BSIs caused by SE (SE-BSIs). METHODS: We constituted a retrospective cohort in two medical ICUs. SE-BSIs were defined by two or more independent SE-positive blood cultures of the same strain, within 48 hours, without concurrent infection. RESULTS: We included 59 patients; 58% were men (n = 34), with median age of 67 (interquartile range 60-74) years and a simplified acute physiology score II of 59 (36-74) points, and 56% were immunocompromised (n = 33). Among the 37 (63%) patients requiring norepinephrine initiation or increase at the onset of SE-BSI versus patients not requiring vasopressors (37%; n = 22), concomitant arterial lactate levels reached 2.8 (1.9-5.8) versus 1.5 (1.3-2.2) mmol/l (P <0.01), whereas the mean blood pressure was 49 (42-54) versus 61 (56-65) mm Hg (P = 0.01) and the mortality was 46% (n = 17) vs 14% (n = 3) at day 28 (P = 0.01), respectively. Regarding antibiotics, the susceptibility rates toward linezolid and vancomycin were 71% (n = 41/58) and 100% (n = 54/54), respectively. At the time of SE-BSI, all but one patient had a central venous access device. CONCLUSION: This work highlights SE-BSIs as a cause of septic shock, mostly in immunocompromised ICU patients, with increasing concerns about resistance to antibiotics and central line management.
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Choque Séptico , Masculino , Humanos , Persona de Mediana Edad , Anciano , Femenino , Choque Séptico/tratamiento farmacológico , Staphylococcus epidermidis , Estudios Retrospectivos , Unidades de Cuidados Intensivos , Antibacterianos/uso terapéuticoRESUMEN
AIMS: Characteristics, management, and outcomes of patients with active cancer admitted for cardiogenic shock remain largely unknown. This study aimed to address this issue and identify the determinants of 30-day and 1-year mortality in a large cardiogenic shock cohort of all aetiologies. METHODS AND RESULTS: FRENSHOCK is a prospective multicenter observational registry conducted in French critical care units between April and October 2016. 'Active cancer' was defined as a malignancy diagnosed within the previous weeks with planned or ongoing anticancer therapy. Among the 772 enrolled patients (mean age 65.7 ± 14.9 years; 71.5% male), 51 (6.6%) had active cancer. Among them, the main cancer types were solid cancers (60.8%), and hematological malignancies (27.5%). Solid cancers were mainly urogenital (21.6%), gastrointestinal (15.7%), and lung cancer (9.8%). Medical history, clinical presentation, and baseline echocardiography were almost the same between groups. In-hospital management significantly differed: patients with cancers received more catecholamines or inotropes (norepinephrine 72% vs. 52%, P = 0.005 and norepinephrine-dobutamine combination 64.7% vs. 44.5%, P = 0.005), but had less mechanical circulatory support (5.9% vs. 19.5%, P = 0.016). They presented a similar 30-day mortality rate (29% vs. 26%) but a significantly higher mortality at 1-year (70.6% vs. 45.2%, P < 0.001). In multivariable analysis, active cancer was not associated with 30-day mortality but was significantly associated with 1-year mortality in 30-day survivors [HR 3.61 (1.29-10.11), P = 0.015]. CONCLUSION: Active cancer patients accounted for almost 7% of all cases of cardiogenic shock. Early mortality was the same regardless of active cancer or not, whereas long-term mortality was significantly increased in patients with active cancer.
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Neoplasias , Choque Cardiogénico , Humanos , Masculino , Persona de Mediana Edad , Anciano , Anciano de 80 o más Años , Femenino , Choque Cardiogénico/epidemiología , Choque Cardiogénico/etiología , Choque Cardiogénico/terapia , Estudios Prospectivos , Dobutamina/uso terapéutico , Norepinefrina/uso terapéutico , Neoplasias/complicaciones , Neoplasias/epidemiologíaRESUMEN
Biological rhythms are important regulators of immune functions. In intensive care unit (ICU), sepsis is known to be associated with rhythm disruption. Our objectives were to determine factors associated with rhythm disruption of the body temperature and to assess the relationship between temperature and mortality in septic shock patients; In a cohort of septic shock, we recorded body temperature over a 24-h period on day 2 after ICU admission. For each patient, the temperature rhythmicity was assessed by defining period and amplitude, and the adjusted average (mesor) of the temperature by sinusoidal regression and cosinor analysis. Analyses were performed to assess factors associated with the three temperature parameters (period, amplitude, and mesor) and mortality. 162 septic shocks were enrolled. The multivariate analysis demonstrates that the period of temperature was associated with gender (women, coefficient -2.2 h, p = 0.031) and acetaminophen use (coefficient -4.3 h, p = 0.002). The mesor was associated with SOFA score (coefficient -0.05 °C per SOFA point, p = 0.046), procalcitonin (coefficient 0.001 °C per ng/mL, p = 0.005), and hydrocortisone use (coefficient -0.5 °C, p = 0.002). The amplitude was associated with the dialysis (coefficient -0.5 °C, p = 0.002). Mortality at day 28 was associated with lower mesor (adjusted hazard ratio 0.50, 95% CI 0.28 to 0.90; p = 0.02), and higher amplitude (adjusted hazard ratio 5.48, 95% CI 1.66 to 18.12; p = 0.005) of temperature. Many factors, such as therapeutics, influence the body temperature during septic shock. Lower mesor and higher amplitude were associated with mortality and could be considered prognostic markers in ICU. In the age of artificial intelligence, the incorporation of such data in an automated scoring alert could compete with physicians to identify high-risk patients during septic shock.