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Composite outcomes are commonly used in critical care trials to estimate the treatment effect of an intervention. A significant limitation of classical analytic approaches is that they assign equal statistical importance to each component in a composite, even if these do not have the same clinical importance (i.e., in a composite of death and organ failure, death is clearly more important). The win ratio (WR) method has been proposed as an alternative for trial outcomes evaluation, as it effectively assesses events based on their clinical relevance (i.e., hierarchical order) by comparing each patient in the intervention group with their counterparts in the control group. This statistical approach is increasingly used in cardiovascular outcome trials. However, WR may be useful to unveil treatment effects also in the critical care setting, because these trials are typically moderately sized, thus limiting the statistical power to detect small differences between groups, and often rely on composite outcomes that include several components of different clinical importance. Notably, the advantages of this approach may be offset by several drawbacks (such as ignoring ties and difficulties in selecting and ranking endpoints) and challenges in appropriate clinical interpretation (i.e., establishing clinical meaningfulness of the observed effect size). In this perspective article, we present some key elements to implementing WR statistics in critical care trials, providing an overview of strengths, drawbacks, and potential applications of this method. To illustrate, we conduct a reevaluation of the HYPO-ECMO (Hypothermia during Venoarterial Extracorporeal Membrane Oxygenation) trial using the WR framework as a case example.
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Cuidados Críticos , Avaliação de Resultados em Cuidados de Saúde , HumanosRESUMO
Extracorporeal Carbon Dioxide Removal (ECCO2R) is used in acute respiratory distress syndrome (ARDS) patients to facilitate lung-protective ventilatory strategies. Electrical Impedance Tomography (EIT) allows individual, non-invasive, real-time, bedside, radiation-free imaging of the lungs, providing global and regional dynamic lung analyses. To provide new insights for future ECCO2R research in ARDS, we propose a potential application of EIT to personalize End-Expiratory Pressure (PEEP) following each reduction in tidal volume (VT), as demonstrated in an illustrative case. A 72-year-old male with COVID-19 was admitted to the ICU for moderate ARDS. Monitoring with EIT was started to determine the optimal PEEP value (PEEPEIT), defined as the intersection of the collapse and overdistention curves, after each reduction in VT during ECCO2R. The identified PEEPEIT values were notably low (< 10 cmH2O). The decrease in VT associated with PEEPEIT levels resulted in improved lung compliance, reduced driving pressure and a more uniform ventilation pattern. Despite current Randomized Controlled Trials showing that ultra-protective ventilation with ECCO2R does not improve survival, the applicability of universal ultra-protective ventilation settings for all patients remains a subject of debate. Inappropriately set PEEP levels can lead to alveolar collapse or overdistension, potentially negating the benefits of VT reduction. EIT facilitates real-time monitoring of derecruitment associated with VT reduction, guiding physicians in determining the optimal PEEP value after each decrease in tidal volume. This original description of using EIT under ECCO2R to adjust PEEP at a level compromising between recruitability and overdistention could be a crucial element for future research on ECCO2R.
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Respiração com Pressão Positiva , Síndrome do Desconforto Respiratório , Masculino , Humanos , Idoso , Impedância Elétrica , Respiração com Pressão Positiva/métodos , Pulmão , Tomografia Computadorizada por Raios X , Síndrome do Desconforto Respiratório/terapia , Volume de Ventilação Pulmonar , Tomografia/métodosRESUMO
University students frequently resort to psychostimulants to enhance their physical and mental performance and manage academic pressures. However, these substances can lead to dependence and other undesired symptoms, and little empirical data are available for relevant stakeholders, raising significant concerns in health care. Therefore, this study aims to characterize neurostimulant use among university students in Rio Grande do Sul, Brazil. We collected from 880 students' data using anonymous self-administration. The questionnaire included consumption patterns of caffeine, nicotine, ecstasy, methamphetamine, "merla" (coca base), methylphenidate, cocaine, crack, and ketamine. Additionally, participants shared information on demographic and socioeconomic factors. Use of at least one neurostimulant was reported by89.2% of the participants. Among nonusers, the most frequently cited reason was "previous information about harmful effects of these drugs." Caffeine, followed by nicotine, ecstasy, and methylphenidate were the most consumed substances, with main reasons being "improving academic performance" and "recreation." Women more often consumed caffeine (72.7%), while other psychostimulants were more consumed by men (42.2%) and individuals of other genders (0.5%). Students who consumed other substances had higher family incomes than that of families of caffeine users. In addition, 60.4% of caffeine users resided with family members, whereas 63.3% of users of other substances did not. Our findings can offer essential data on the reasons and symptoms associated with the use of neurostimulants among university students. This information could aid in raising awareness among students, universities, and health-care agencies about this often-neglected subject.
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Pulmonary arterial hypertension (PAH) is characterized by a progressive increase in pulmonary vascular resistance (PVR) due to vascular remodeling of the small pulmonary arteries. In advanced RV failure or severe hypoxemia, extra corporeal life support (ECLS) is now to be considered, with the objective to bridge patients back to their baseline clinical state while waiting or right after lung transplantation, or bridge to pharmacological optimization of PAH (i.e., bridge to recovery). We describe herein a case of a 30-year-old woman (gravida 6, para 6) with an incident case of heritable PAH revealed by refractory hypoxemia. Despite the use of mechanical ventilation and fluid optimization, the patient remained profoundly hypoxemic. ECLS was then initiated to avoid tissue hypoxia. The mechanical option chosen was peripheral femoro-femoral venoarterial extracorporeal membrane oxygen (VA-ECMO), percutaneously implanted. Due to the absence of evidence of chronic respiratory disease or chronic thromboembolic pulmonary hypertension, this severe pre-capillary pulmonary hypertension was attributed to PAH. Therefore, epoprostenol infusion and an association of oral treatments (bosentan and tadalafil) were administered. A dramatic improvement was observed, allowing decannulation 7 days after the initiation of pharmacological treatment. After 29 days, the patient was discharged from the hospital with epoprostenol, bosentan, and tadalafil. The assessment has been completed by positive research on mutations (c.741C > G, p.Tyr247) corresponding to a loss of function of the bone morphogenetic protein receptor 2 (BMPR2) gene. The final diagnosis was heritable PAH. The use of ECLS has been well demonstrated in patients with PAH complicated by acute RV failure or refractory hypoxemia in the "bridge-to-transplantation" strategy. Only a few reports have described the use of ECLS as a "bridge-to-recovery" with PAH drugs in untreated or undertreated PAH patients, but none has described such a rapid improvement with resolution of refractory hypoxemia. More studies are needed to assess the benefits and limitations of the "bridge-to-recovery" strategy and to identify the patients most likely to benefit from it.
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Norepinephrine is the first-line vasopressor used in acute cardio-circulatory failure. At the bedside, its dose is critical as it serves to determine the severity of patients, to compare the patients between different studies, and to start specific interventions. Recently, several investigators underlined differences in the expression of norepinephrine doses according to countries and manufacturers. For various reasons, all norepinephrine products are processed to a salt formulation thereby generating a stable and soluble conjugated acid in a slightly acidic solution. Depending on the salt used, the total weight will differ, but the weight of pure norepinephrine base is the same. This results in at-risk situations with large variations in terms of practices, evaluation and treatment. In this technical note, we summarized the evidence and provided a few suggestions to improve the practices at different levels.
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Norepinefrina , Vasoconstritores , Humanos , Norepinefrina/administração & dosagem , Norepinefrina/uso terapêutico , Vasoconstritores/administração & dosagem , Vasoconstritores/uso terapêutico , FrançaRESUMO
BACKGROUND: Reliable predictors of outcomes in venoarterial extracorporeal membrane oxygenation (VA-ECMO) therapy are limited. While elevated lactate levels over time have been linked to outcomes in cardiogenic shock (CS), their significance in VA-ECMO-treated patients remains inconclusive. METHODS: We conducted a post hoc analysis of data from the HYPO-ECMO trial, which compared normothermia to moderate hypothermia in CS patients supported by VA-ECMO. We examined daily lactate levels collected over a week to assess their correlation with 30-day mortality. RESULTS: Among the 318 out of 334 patients (95%) with baseline lactate measurements, 66 had normal levels (< 2.2 mmol/l, 21%). No difference was found in lactate course between moderate hypothermia and normothermia groups. Lactate levels were consistently higher in non-survivors at each time point (p = 0.0002). Baseline hyperlactatemia was associated with an increased risk of death (Hazard Ratio [HR]: 1.85 (1.12-3.05), p = 0.016). When considering all time points, lactate levels during the ICU stay were significantly and gradually associated with a higher risk of death (p < 0.0001). In the overall population, a decrease in lactate levels was not linked to 30-day mortality. However, patients with baseline hyperlactatemia exhibited a more significant decrease in lactate levels from day one to seven (p < 0.0001). In this group, survivors had a significantly greater decrease in lactate levels at day 1 compared to non-survivors (63% (48-77) versus 57% (21-75), p = 0.026). Patients experiencing a secondary increase in lactate (24%) had a worse prognosis (Hazard Ratio: 1.78 (1.21-2.61), p = 0.004), regardless of both baseline lactate levels and the occurrence of severe ischemic adverse events (intestinal and/or limb ischemia). CONCLUSIONS: The consistent and significant association between lactate levels, whether assessed at baseline or during ICU treatment, and the risk of mortality underscores the pivotal prognostic relevance of lactate levels in patients with CS undergoing VA-ECMO therapy. The study findings provide some novel insights, regarding the trend profile and the relevance of a second peak during the 7 day period after ECMO start. Trial Registration identifier NCT02754193 registered on 2016-04-12.
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Background: new-onset atrial fibrillation remains a common complication in critical care settings, often necessitating treatment when the correction of triggers is insufficient to restore hemodynamics. The treatment strategy includes electric cardioversion in cases of hemodynamic instability and either rhythm control or rate control in the absence of instability. Landiolol, an ultrashort beta-blocker, effectively controls heart rate with the potential to regulate rhythm. Objectives This review aims to compare the efficacy of landiolol in controlling heart rate and converting to sinus rhythm in the critical care setting. Methods: We conducted a comprehensive review of the published literature from 2000 to 2022 describing the use of landiolol to treat atrial fibrillation in critical care settings, excluding both cardiac surgery and medical cardiac care settings. The primary outcome assessed was sinus conversion following landiolol treatment. Results: Our analysis identified 17 publications detailing the use of landiolol for the treatment of 324 critical care patients. While the quality of the data was generally low, primarily comprising non-comparative studies, landiolol consistently demonstrated similar efficacy in controlling heart rate and facilitating conversion to sinus rhythm in both non-surgical (75.7%) and surgical (70.1%) settings. The incidence of hypotension associated with landiolol use was 13%. Conclusions: The use of landiolol in critical care patients with new-onset atrial fibrillation exhibited comparable efficacy and tolerance in both non-surgical and surgical settings. Despite these promising results, further validation through randomized controlled trials is necessary.
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AIM: Venoarterial extracorporeal membrane oxygenation (VA-ECMO) has become a common intervention for patients with cardiogenic shock (CS), often complicated by cardiac arrest (CA). Moderate hypothermia (MH) has shown promise in mitigating ischemia-reperfusion injury following CA. The HYPO-ECMO trial aimed to compare the effect of MH versus normothermia in refractory CS rescued by VA-ECMO. The primary aim of this non-predefined post hoc study was to assess the treatment effect of MH in the subgroup of patients with cardiac arrest (CA) within the HYPO-ECMO trial. Additionally, we will evaluate the prognostic significance of CA in these patients. METHODS: This post hoc analysis utilized data from the randomized HYPO-ECMO trial conducted across 20 French cardiac shock care centers between October 2016 and July 2019. Participants included intubated patients receiving VA-ECMO for CS for less than 6 h, with 334 patients completing the trial. Patients were randomized to early MH (33-34 °C) or normothermia (36-37 °C) for 24 h. RESULTS: Of the 334 patients, 159 (48%) experienced preceding CA. Mortality in the CA group was 50.9% at 30 days and 59.1% at 180 days, compared to 42.3% and 51.4% in the no-CA group, respectively (adjusted risk difference [RD] at 30 days, 8.1% [-0.8 to 17.1%], p = 0.074 and RD at 180 days 7.0% [-3.0 to 16.9%], p = 0.17). MH was associated with a significant reduction in primary (RD -13.3% [-16.3 to -0.3%], p = 0.031) and secondary outcomes in the CA group only (p < 0.025 for all), with a significant interaction between MH and CA status for 180-day mortality [p = 0.03]. CONCLUSIONS: This post hoc analysis suggests that MH shows potential for reducing mortality and composite endpoints in patients with cardiac arrest and refractory CS treated with VA-ECMO without an increased risk of severe bleeding or infection. Further research is needed to validate these findings and elucidate underlying mechanisms.
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Oxigenação por Membrana Extracorpórea , Parada Cardíaca , Hipotermia Induzida , Choque Cardiogênico , Humanos , Oxigenação por Membrana Extracorpórea/métodos , Masculino , Feminino , Hipotermia Induzida/métodos , Pessoa de Meia-Idade , Parada Cardíaca/terapia , Parada Cardíaca/mortalidade , Parada Cardíaca/complicações , Choque Cardiogênico/terapia , Choque Cardiogênico/etiologia , Choque Cardiogênico/mortalidade , IdosoRESUMO
BACKGROUND: The incidence of heart failure and cardiogenic shock (CS) in older adults is continually increasing due to population aging. To date, prospective data detailing the specific characteristics, management and outcomes of CS in this population are scarce. METHODS: FRENSHOCK is a prospective registry including 772 CS patients from 49 centers. We studied 1-month and 1-year mortality among patients over 75-year-old, adjusted for independent predictors of 1-month and 1-year mortalities. RESULTS: Out of 772 patients included, 236 (30.6%) were 75 years old or more (mean age 81.9 ± 4.7 years, 63.6% male). Compared to patients <75 years old, older adults had a higher prevalence of comorbidities including hypertension, dyslipidemia, chronic kidney disease, and history of heart disease. Older adults were characterized by a lower blood pressure, as well as higher creatinine and lower haemoglobin levels at presentation. Yet, they were less likely to be treated with norepinephrine, epinephrine, invasive ventilation, and renal replacement therapy. They showed a higher 1-month (aHR: 2.5 [1.86-3.35], p < 0.01) and 1-year mortality (aHR: 2.01 [1.58-2.56], p < 0.01). Analysis of both 1-month and 1-year mortality stratified by age quartiles showed a gradual relationship between aging and mortality in CS patients. CONCLUSION: A third of patient with CS in critical care unit are older than 75 years and their risk of death at one month and one year is more than double compared to the younger ones. Further research is essential to identify best therapeutic strategy in this population. NCT02703038.
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Insuficiência Cardíaca , Choque Cardiogênico , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Insuficiência Cardíaca/complicações , Mortalidade Hospitalar , Unidades de Terapia Intensiva , Prognóstico , Sistema de Registros , Choque Cardiogênico/diagnóstico , Choque Cardiogênico/epidemiologia , Choque Cardiogênico/terapiaRESUMO
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 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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Insuficiência Cardíaca , Choque Cardiogênico , Humanos , Antagonistas Adrenérgicos beta/uso terapêutico , Antagonistas de Receptores de Angiotensina/uso terapêutico , Estudos Prospectivos , Sistema de Registros , Volume Sistólico , Função Ventricular Esquerda , Estudos Multicêntricos como Assunto , Estudos Observacionais como AssuntoRESUMO
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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Insuficiência Renal Crônica , Choque Cardiogênico , Humanos , Choque Cardiogênico/diagnóstico , Choque Cardiogênico/etiologia , Choque Cardiogênico/terapia , Insuficiência Renal Crônica/complicações , Insuficiência Renal Crônica/diagnóstico , Insuficiência Renal Crônica/epidemiologia , Comorbidade , Modelos de Riscos Proporcionais , Terapia de Substituição Renal/efeitos adversosRESUMO
BACKGROUND: Cardiogenic shock (CS) is the most severe form of acute heart failure. Discrepancies have been reported between sexes regarding delays, pathways and invasive strategies in CS complicating acute myocardial infarction. However, effect of sex on the prognosis of unselected CS remains controversial. OBJECTIVES: The aim was to analyze the impact of sex on aetiology, management and prognosis of CS. METHODS: The FRENSHOCK registry included all CS admitted in 49 French Intensive Care Units (ICU) and Intensive Cardiac Care Units (ICCU) between April and October 2016. RESULTS: Among the 772 CS patients included, 220 were women (28.5%). Women were older, less smokers, with less history of ischemic cardiac disease (20.5% vs 33.6%) than men. At admission, women presented less cardiac arrest (5.5 vs 12.2%), less mottling (32.5 vs 41.4%) and higher LVEF (30 ± 14 vs 25 ± 13%). Women were more often managed via emergency department while men were directly admitted at ICU/ICCU. Ischemia was the most frequent trigger irrespective of sex (36.4% in women vs 38.2%) but women had less coronary angiogram and PCI (45.9% vs 54% and 24.1 vs 31.3%, respectively). We found no major difference in medication and organ support. Thirty-day mortality (26.4 vs 26.5%), transplant or permanent assist device were similar in both sexes. CONCLUSION: Despite some more favorable parameters in initial presentation and no significant difference in medication and support, women shared similar poor prognosis than men. Further analysis is required to cover the lasting gap in knowledge regarding sex specificities to distinguish between differences and inequalities. NCT02703038.