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BACKGROUND: ARDS is a heterogeneous condition with two subphenotypes identified by different methodologies. Our group similarly identified two ARDS subphenotypes using nine routinely available clinical variables. However, whether these are associated with differential response to treatment has yet to be explored. RESEARCH QUESTION: Are there differential responses to positive end-expiratory pressure (PEEP) strategies on 28-day mortality according to subphenotypes in adult patients with ARDS? STUDY DESIGN AND METHODS: We evaluated data from two prior ARDS trials (Higher vs Lower Positive End-Expiratory Pressures in Patients With the ARDS [ALVEOLI] and the Alveolar Recruitment in ARDS Trial [ART]) that compared different PEEP strategies. We classified patients into one of two subphenotypes as described previously. We assessed the differential effect of PEEP with a Bayesian hierarchical logistic model for the primary outcome of 28-day mortality. RESULTS: We analyzed data from 1,559 patients with ARDS. Compared with lower PEEP, a higher PEEP strategy resulted in higher 28-day mortality in patients with subphenotype A disease in the ALVEOLI study (OR, 1.61; 95% credible interval [CrI], 0.90-2.94) and ART (OR, 1.73; 95% CrI, 1.01-2.98), with a probability of harm resulting from higher PEEP in this subphenotype of 94.3% and 97.7% in the ALVEOLI and ART studies, respectively. Higher PEEP was not associated with mortality in patients with subphenotype B disease in each trial (OR, 0.95 [95% CrI, 0.51-1.73] and 1.00 [95% CrI, 0.63-1.55], respectively), with probability of benefit of 56.4% and 50.7% in the ALVEOLI and ART studies, respectively. These effects were not modified by Pao2 to Fio2 ratio, driving pressure, or the severity of illness for the cohorts. INTERPRETATION: We found evidence of differential response to PEEP strategies across two ARDS subphenotypes, suggesting possible harm with a higher PEEP strategy in one subphenotype. These observations may assist with predictive enrichment in future clinical trials.
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Background: Right ventricular dysfunction (RVD) is a complication following congenital cardiac surgery in children and can lead to systemic venous congestion, low cardiac output, and organ dysfunction. Venous congestion can be transmitted backwards and adversely affect encapsulated organs such as the kidneys. Primary objective: To investigate the association between systemic venous congestion, as estimated by Venous Excess Ultrasound (VExUS), and the occurrence of acute kidney injury (AKI) in children with RVD following congenital heart surgery. Secondary objectives included comparing changes in VExUS scores after initiating treatment for RVD and venous congestion. Methods and results: This was a prospective observational study in children with RVD. The VExUS study was performed on day 1, day 2, and day 3 and categorized as VExUS-1, VExUS-2, and VExUS-3. Among 43 patients with RVD and dilated inferior vena cava, 19/43 (44%), 10/43 (23%), and 12/43 (28%) were VExUS-2 and VExUS-3, respectively. There was an association between severe RVD and elevated pulmonary artery systolic pressures and a VExUS score >2. A significant association was observed between central venous pressure (CVP) measurements and VExUS. Among 31 patients with a high VExUS score >2, 18 (58%) had AKI. Additionally, improvement in CVP and fluid balance was associated with improving VExUS scores following targeted treatment for RVD. Conclusion: VExUS serves as a valuable bedside tool for diagnosing and grading venous congestion through ultrasound Doppler. An elevated VExUS score was associated with the occurrence of AKI, and among the components of VExUS, portal vein pulsatility may be useful as a predictor of AKI. How to cite this article: Natraj R, Bhaskaran AK, Rola P, Haycock K, Siuba MTT, Ranjit S. Venous Congestion Assessed by Venous Excess Ultrasound (VExUS) and Acute Kidney Injury in Children with Right Ventricular Dysfunction. Indian J Crit Care Med 2024;28(5):447-452.
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BACKGROUND: A non-tunneled dialysis catheter (nTDC) is often the vascular access of choice to initiate dialysis in an intensive care unit (ICU). In the absence of contraindications, if a patient remains dialysis dependent beyond 2-weeks, the options are either to replace the nTDC with another nTDC or convert to a tunneled dialysis catheter (TDC). As a standard of care, TDCs are placed under fluoroscopic guidance. OBJECTIVES: To determine if TDCs and other tunneled central venous catheters (tCVC) can be placed safely using anatomical landmark techniques without the use of fluoroscopy. RESEARCH DESIGN: Subjects that met a predetermined selection criteria underwent placement of tunneled catheters with the use of the anatomical landmark technique. We looked at various outcomes to determine the safety and effectiveness of this technique. SUBJECTS: One hundred eleven TDCs and other tCVCs were placed using the anatomical landmark technique in the intensive care unit. RESULTS: All but one (110/111) of the catheters placed had recommended tip placement confirmed by at least one blinded physician. Major complications encountered were bleeding (two cases), pneumothorax (one case), and line associated blood stream infection (one case). We did find a higher-than-expected rate of "unnecessary procedures" with 18/111 lines placed in patients who did not survive beyond 7 days after placement of the catheter. CONCLUSIONS: Using the anatomical landmark technique for bedside tunneled catheter placement can be an effective approach in the right population.
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OBJECTIVE: Conventional prediction models fail to integrate the constantly evolving nature of critical illness. Alternative modelling approaches to study dynamic changes in critical illness progression are needed. We compare static risk prediction models to dynamic probabilistic models in early critical illness. DESIGN: We developed models to simulate disease trajectories of critically ill COVID-19 patients across different disease states. Eighty per cent of cases were randomly assigned to a training and 20% of the cases were used as a validation cohort. Conventional risk prediction models were developed to analyse different disease states for critically ill patients for the first 7 days of intensive care unit (ICU) stay. Daily disease state transitions were modelled using a series of multivariable, multinomial logistic regression models. A probabilistic dynamic systems modelling approach was used to predict disease trajectory over the first 7 days of an ICU admission. Forecast accuracy was assessed and simulated patient clinical trajectories were developed through our algorithm. SETTING AND PARTICIPANTS: We retrospectively studied patients admitted to a Cleveland Clinic Healthcare System in Ohio, for the treatment of COVID-19 from March 2020 to December 2022. RESULTS: 5241 patients were included in the analysis. For ICU days 2-7, the static (conventional) modelling approach, the accuracy of the models steadily decreased as a function of time, with area under the curve (AUC) for each health state below 0.8. But the dynamic forecasting approach improved its ability to predict as a function of time. AUC for the dynamic forecasting approach were all above 0.90 for ICU days 4-7 for all states. CONCLUSION: We demonstrated that modelling critical care outcomes as a dynamic system improved the forecasting accuracy of the disease state. Our model accurately identified different disease conditions and trajectories, with a <10% misclassification rate over the first week of critical illness.
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COVID-19 , Estado Terminal , Humanos , Estado Terminal/terapia , Estudos Retrospectivos , Unidades de Terapia Intensiva , Hospitalização , COVID-19/epidemiologia , Cuidados CríticosRESUMO
Background: This document updates previously published Clinical Practice Guidelines for the management of patients with acute respiratory distress syndrome (ARDS), incorporating new evidence addressing the use of corticosteroids, venovenous extracorporeal membrane oxygenation, neuromuscular blocking agents, and positive end-expiratory pressure (PEEP). Methods: We summarized evidence addressing four "PICO questions" (patient, intervention, comparison, and outcome). A multidisciplinary panel with expertise in ARDS used the Grading of Recommendations, Assessment, Development, and Evaluation framework to develop clinical recommendations. Results: We suggest the use of: 1) corticosteroids for patients with ARDS (conditional recommendation, moderate certainty of evidence), 2) venovenous extracorporeal membrane oxygenation in selected patients with severe ARDS (conditional recommendation, low certainty of evidence), 3) neuromuscular blockers in patients with early severe ARDS (conditional recommendation, low certainty of evidence), and 4) higher PEEP without lung recruitment maneuvers as opposed to lower PEEP in patients with moderate to severe ARDS (conditional recommendation, low to moderate certainty), and 5) we recommend against using prolonged lung recruitment maneuvers in patients with moderate to severe ARDS (strong recommendation, moderate certainty). Conclusions: We provide updated evidence-based recommendations for the management of ARDS. Individual patient and illness characteristics should be factored into clinical decision making and implementation of these recommendations while additional evidence is generated from much-needed clinical trials.
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Bloqueadores Neuromusculares , Síndrome do Desconforto Respiratório , Adulto , Humanos , Corticosteroides/uso terapêutico , Pulmão , Bloqueadores Neuromusculares/uso terapêutico , Respiração com Pressão Positiva , Síndrome do Desconforto Respiratório/tratamento farmacológicoRESUMO
Background: Over one-third of patients with septic shock have adjunctive vasopressors added to first-line vasopressors. However, no randomized trial has detected improved mortality with adjunctive vasopressors. Published systematic reviews and meta-analysis have sought to inform the use of adjunctive vasopressors, yet each published review has limitations that hinder its interpretation. This review aims to overcome the limitations of previous reviews by systematically synthesizing the direct evidence for adjunctive vasopressor therapy use in adult patients with septic shock. Methods: We will conduct a systematic review and meta-analysis of randomized controlled trials evaluating adjunctive vasopressors (vasopressin analogues, angiotensin II, hydroxocobalamin, methylene blue, and catecholamine analogues) in adult patients with septic shock. Relevant studies will be identified through comprehensive searches of MEDLINE, Embase, CENTRAL, and reference lists of previous systematic reviews. Only randomized trials comparing adjunctive vasopressors (>75% of subjects on vasopressors at enrollment) to standard care vasopressors in adults with septic shock (>75% of subjects having septic shock) will be included. Titles and abstracts will be screened, full-text articles assessed for eligibility, and data extracted from included studies. Outcomes of interest include short-term mortality, intermediate-term mortality, kidney replacement therapy, digital/peripheral ischemia, and venous thromboembolism. Pairwise meta-analysis using a random-effects model will be utilized to estimate the risk ratio for the outcomes. Risk of bias will be adjudicated with the Cochrane Risk of Bias 2 tool, and GRADE will be used to rate the certainty of the body of evidence. Discussion: Although adjunctive vasopressors are commonly used in patients with septic shock their effect on patient-important outcomes is unclear. This study is planned to use rigorous systematic review methodology, including strict adhere to established guidelines, in order to overcome limitations of previously-published reviews and inform clinical practice and treatment guidelines for the use of adjunctive vasopressors in adults with septic shock. Systematic review registration: PROSPERO CRD4202327984.
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Rationale: Guidelines recommend using end-expiration pulmonary pressure measurements to determine the hemodynamic subgroups in pulmonary hypertension. Pulmonary artery wedge pressure (PAWP) determinations averaged across the respiratory cycle (PAWPav) instead of PAWP at end-expiration (PAWPee) and cardiac output (CO) measured by Fick (COFick) instead of thermodilution (COTD) may affect the hemodynamic classification of pulmonary hypertension. Objectives: To assess the impact on the pulmonary hypertension hemodynamic classification of the use of PAWPee versus PAWPav as well as COFick versus COTD. Methods: This was a single-center retrospective study of consecutive patients (n = 151) who underwent right heart catheterization with COTD, COFick, PAWPee, and PAWPav. A secondary cohort consisted of consecutive patients (n = 71) who had mean pulmonary artery pressure at end-expiration (mPAPee) and mPAP averaged across the respiratory cycle (mPAPav) measured, as well as PAWPee and PAWPav. Results: The PAWPee and PAWPav were 16.8 ± 6.4 and 15.1 ± 6.8 mm Hg, respectively, with a mean difference of 1.7 ± 2.1 mm Hg. The COTD and COFick determinations were 5.0 ± 2.4 and 5.3 ± 2.5 L/min, respectively, with a mean difference of -0.4 ± 1.3 L/min. The hemodynamic group distribution was significantly different when using PAWPee versus PAWPav, when using either COTD or COFick (P < 0.001 for both comparisons), and these results were consistent in our secondary cohort. The pulmonary hypertension hemodynamic group distribution was not significantly different between COTD and COFick when using either PAWPee or PAWPav. Conclusions: The methodology used to measure PAWP, either at end-expiration or averaged across the respiratory cycle, significantly impacts the hemodynamic classification of pulmonary hypertension.
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Hipertensão Pulmonar , Humanos , Pressão Propulsora Pulmonar , Hipertensão Pulmonar/diagnóstico , Estudos Retrospectivos , Débito Cardíaco , Hemodinâmica , Cateterismo Cardíaco , Artéria PulmonarRESUMO
Despite its significant limitations, the PaO2 /FIO2 remains the standard tool to classify disease severity in ARDS. Treatment decisions and research enrollment have depended on this parameter for over 50 years. In addition, several variables have been studied over the past few decades, incorporating other physiologic considerations such as ventilation efficiency, lung mechanics, and right-ventricular performance. This review describes the strengths and limitations of all relevant parameters, with the goal of helping us better understand disease severity and possible future treatment targets.
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Síndrome do Desconforto Respiratório , Humanos , Síndrome do Desconforto Respiratório/terapia , Pulmão , Gravidade do Paciente , Índice de Gravidade de Doença , Fenômenos Fisiológicos RespiratóriosRESUMO
PURPOSE: Vasopressin, used as a catecholamine adjunct, is a vasoconstrictor that may be detrimental in some hemodynamic profiles, particularly left ventricular (LV) systolic dysfunction. This study tested the hypothesis that echocardiographic parameters differ between patients with a hemodynamic response after vasopressin initiation and those without a response. METHODS: This retrospective, single-center, cross-sectional study included adults with septic shock receiving catecholamines and vasopressin with an echocardiogram performed after shock onset but before vasopressin initiation. Patients were grouped by hemodynamic response, defined as decreased catecholamine dosage with mean arterial pressure ≥ 65 mmHg six hours after vasopressin initiation, with echocardiographic parameters compared. LV systolic dysfunction was defined as LV ejection fraction (LVEF) <45%. RESULTS: Of 129 included patients, 72 (56%) were hemodynamic responders. Hemodynamic responders, versus non-responders, had higher LVEF (61% [55%,68%] vs. 55% [40%,65%]; p = 0.02) and less-frequent LV systolic dysfunction (absolute difference -16%; 95% CI -30%,-2%). Higher LVEF was associated with higher odds of hemodynamic response (for each LVEF 10%, response OR 1.32; 95% CI 1.04-1.68). Patients with LV systolic dysfunction, versus without LV systolic dysfunction, had higher mortality risk (HR(t) = e[0.81-0.1*t]; at t = 0, HR 2.24; 95% CI 1.08-4.64). CONCLUSIONS: Pre-drug echocardiographic profiles differed in hemodynamic responders after vasopressin initiation versus non-responders.
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Choque Séptico , Disfunção Ventricular Esquerda , Adulto , Humanos , Catecolaminas , Estudos Transversais , Ecocardiografia , Hemodinâmica , Estudos Retrospectivos , Vasoconstritores , VasopressinasRESUMO
The clinical spectrum of severe acute respiratory syndrome coronavirus-2 infection ranges from asymptomatic infection or mild respiratory symptoms to pneumonia, with severe cases leading to acute respiratory distress syndrome with multiorgan involvement. The clinical management of patients with coronavirus disease 2019 (COVID-19) acute respiratory distress syndrome (ARDS) changed over the course of the pandemic, being adjusted as more evidence became available. This article will review how the ventilatory management of COVID-19 ARDS evolved and will conclude with current evidence-based recommendations.
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COVID-19 , Síndrome do Desconforto Respiratório , Humanos , COVID-19/terapia , Respiração Artificial , SARS-CoV-2 , Oxigênio , Síndrome do Desconforto Respiratório/terapiaRESUMO
OBJECTIVE: To summarize knowledge and identify gaps in evidence regarding treatment of right ventricular dysfunction (RVD) in acute respiratory distress syndrome (ARDS). DATA SOURCES: We conducted a comprehensive search of MEDLINE, Embase, CINAHL, Web of Science, and the Cochrane Central Register of Controlled Trials. STUDY SELECTION: Studies were included if they reported effects of treatments on right ventricular function, whether or not the intent was to modify right ventricular function. DATA EXTRACTION: Data extraction was performed independently and in duplicate by two authors. Data items included the study design, patient population, type of intervention, comparison group, and RV-specific outcomes. DATA SYNTHESIS: Of 1,430 studies screened, 51 studies reporting on 1,526 patients were included. By frequency, the included studies examined the following interventions: ventilator settings (29.4%), inhaled medications (33.3%), extracorporeal life support (13.7%), intravenous or oral medications (13.7%), and prone positioning (9.8%). The majority of the studies were non-randomized experimental studies (53%), with the next most common being case reports (16%). Only 5.9% of studies were RCTs. In total, 27% of studies were conducted with the goal of modifying RV function. CONCLUSIONS: Given the prevalence of RVD in ARDS and its association with mortality, the dearth of research on this topic is concerning. This review highlights the need for prospective trials aimed at treating RV dysfunction in ARDS.
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Ventrículos do Coração , Síndrome do Desconforto Respiratório , Humanos , Estudos Prospectivos , Síndrome do Desconforto Respiratório/terapia , Respiração Artificial , Posicionamento do PacienteRESUMO
BACKGROUND: In septic shock, vasopressors aim to improve tissue perfusion and prevent persistent organ dysfunction, a characteristic of chronic critical illness (CCI). Adjunctive vasopressin is often used to decrease catecholamine dosage, but the association of vasopressin response with subsequent patient outcomes is unclear. We hypothesized vasopressin response is associated with favorable clinical trajectory. METHODS: We included patients with septic shock receiving vasopressin as a catecholamine adjunct in this retrospective cohort study. We defined vasopressin response as a lowering of the catecholamine dose required to maintain mean arterial pressure ≥65 mm Hg, 6â h after vasopressin initiation. Clinical trajectories were adjudicated as early death (ED; death before day 14), CCI (ICU stay ≥14 days with persistent organ dysfunction), or rapid recovery (RR; not meeting ED or CCI criteria). Trajectories were placed on an ordinal scale with ED the worst outcome, CCI next, and RR the best outcome. The association of vasopressin response with clinical trajectory was assessed with multivariable ordinal logistic regression. RESULTS: In total 938 patients were included; 426 (45.4%) were vasopressin responders. The most frequent trajectory was ED (49.8%), 29.7% developed CCI, and 20.5% had rapid recovery. In survivors to ICU day 14 (those without ED), 59.2% had CCI and 40.8% experienced RR. Compared with vasopressin non-responders, vasopressin responders less frequently experienced ED (42.5% vs. 55.9%) and more frequently experienced RR (24.6% vs. 17.0%; P < 0.01). After controlling for confounders, vasopressin response was independently associated with higher odds of developing a better clinical trajectory (OR 1.63; 95% CI 1.26-2.10). Medical patients most frequently developed ED and survivors more commonly developed CCI than RR; surgical patients developed the three trajectories with similar frequency (P < 0.01). CONCLUSIONS: Vasopressin responsive status was associated with improved clinical trajectory in septic shock patients. Early vasopressin response is a potential novel prognostic marker for short-term clinical trajectory.
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Choque Séptico , Humanos , Choque Séptico/tratamento farmacológico , Estudos Retrospectivos , Insuficiência de Múltiplos Órgãos , Vasopressinas/uso terapêutico , Vasoconstritores/uso terapêutico , Catecolaminas , Estado TerminalRESUMO
AIMS: Pulmonary hypertension (PH) management is dependent on cardiac output (CO) assessment. The gold standard Fick method for CO and cardiac index (CI) measurement is not widely available. An accessible and reliable method for CO/CI estimation is needed not only in catheterization labs but also in other environments such as the intensive care unit, where pulmonary artery catheters are less likely to be used. We hypothesized that veno-arterial carbon dioxide gradient (PvaCO2) is a reliable surrogate for Fick CI in patients with PH. METHODS AND RESULTS: A single-centre retrospective analysis of patients with PH who underwent direct Fick CI (DFCI) measurement during right heart catheterization. The primary outcome was correlation between PvaCO2 and DFCI. To assess the agreement between central and mixed venous CO2 values, a separate prospective cohort of patients was analysed. Data from 186 patients with all haemodynamic types of PH were analysed. PvaCO2 moderately correlated with Fick CI, R = -0.51 [95% confidence interval (CI): -0.61, -0.39]. A higher PvaCO2 was associated with an increased risk of CI < 2.5 L/min/m2 (odds ratio: 1.88, 95% CI: 1.55, 2.35). Low thermodilution CI with normal veno-arterial carbon dioxide gradient values was associated with a thermodilution underestimation of Fick CI. In the prospective analysis of 32 patients, central venous CO2 overestimated mixed venous values (mean difference 3.3, 95% CI: 2.5, 4.0) and there was poor agreement overall (limits of agreement -1.10, 7.59). CONCLUSION: Veno-arterial carbon dioxide gradient moderately correlates with Fick CI and may be useful to identify patients with low CI. Central and mixed venous CO2 values should not be used interchangeably in PH.
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Hipertensão Pulmonar , Humanos , Hipertensão Pulmonar/diagnóstico , Dióxido de Carbono , Estudos Retrospectivos , Débito Cardíaco , HemodinâmicaRESUMO
ABSTRACT: Objective: Several studies have shown septic shock developing later during the hospital stay is associated with higher mortality. However, the precise point at which time from hospital admission to the onset of septic shock (admission-shock-onset-time) becomes an independent prognostic marker of mortality remains unknown. This study evaluated the association between admission-shock-onset-time and in-hospital mortality among patients with septic shock and the optimal cutoff period to categorize early- and late-onset septic shock. Method: We conducted a single-center retrospective, observational cohort study at a quaternary academic hospital comprising adult patients with septic shock admitted to a medical intensive care unit (ICU) from January 2011 to December 2020. A multivariable additive logistic regression model was developed to assess if log-transformed admission-shock-onset-time was associated with in-hospital mortality. The thin plate spline function was used to describe the nonlinear relationship between the log-transformed admission-shock-onset-time and in-hospital mortality. The primary outcome was in-hospital mortality, and the secondary outcome was ICU mortality. Results: Two thousand five hundred twenty patients met the inclusion criteria with an overall in-hospital mortality of 37.3%. The log-transformed admission-shock-onset-time was associated with higher in-hospital and ICU mortality even after adjusting for clinical variables. The odds ratio for in-hospital mortality continued to increase throughout the observation period. The adjusted odds ratio exceeded 2 in between 20.1 and 54.6 h, and it surpassed 3 in between 54.6 and 148.4 h of the time from the hospital admission to shock onset. Conclusion: In-hospital mortality continued to rise as admission-shock-onset-time increased in patients with septic shock. No clear dichotomization between early and late septic shock could be ascertained, and this categorization may limit our understanding of the temporal relationship of shock onset to mortality.
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Choque Séptico , Adulto , Mortalidade Hospitalar , Hospitais , Humanos , Unidades de Terapia Intensiva , Estudos RetrospectivosRESUMO
Acute respiratory distress syndrome (ARDS) occurs in up to 10% of patients with respiratory failure admitted through the emergency department. Use of noninvasive respiratory support has proliferated in recent years; clinicians must understand the relative merits and risks of these technologies and know how to recognize signs of failure. The cornerstone of ARDS care of the mechanically ventilated patient is low-tidal volume ventilation based on ideal body weight. Adjunctive therapies, such as prone positioning and neuromuscular blockade, may have a role in the emergency department management of ARDS depending on patient and department characteristics.