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BACKGROUND: Whether proton-pump inhibitors are beneficial or harmful for stress ulcer prophylaxis in critically ill patients undergoing invasive ventilation is unclear. METHODS: In this international, randomized trial, we assigned critically ill adults who were undergoing invasive ventilation to receive intravenous pantoprazole (at a dose of 40 mg daily) or matching placebo. The primary efficacy outcome was clinically important upper gastrointestinal bleeding in the intensive care unit (ICU) at 90 days, and the primary safety outcome was death from any cause at 90 days. Multiplicity-adjusted secondary outcomes included ventilator-associated pneumonia, Clostridioides difficile infection, and patient-important bleeding. RESULTS: A total of 4821 patients underwent randomization in 68 ICUs. Clinically important upper gastrointestinal bleeding occurred in 25 of 2385 patients (1.0%) receiving pantoprazole and in 84 of 2377 patients (3.5%) receiving placebo (hazard ratio, 0.30; 95% confidence interval [CI], 0.19 to 0.47; P<0.001). At 90 days, death was reported in 696 of 2390 patients (29.1%) in the pantoprazole group and in 734 of 2379 patients (30.9%) in the placebo group (hazard ratio, 0.94; 95% CI, 0.85 to 1.04; P = 0.25). Patient-important bleeding was reduced with pantoprazole; all other secondary outcomes were similar in the two groups. CONCLUSIONS: Among patients undergoing invasive ventilation, pantoprazole resulted in a significantly lower risk of clinically important upper gastrointestinal bleeding than placebo, with no significant effect on mortality. (Funded by the Canadian Institutes of Health Research and others; REVISE ClinicalTrials.gov number, NCT03374800.).
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Enfermedad Crítica , Pantoprazol , Inhibidores de la Bomba de Protones , Respiración Artificial , Humanos , Pantoprazol/uso terapéutico , Pantoprazol/efectos adversos , Pantoprazol/administración & dosificación , Respiración Artificial/efectos adversos , Masculino , Persona de Mediana Edad , Femenino , Inhibidores de la Bomba de Protones/uso terapéutico , Inhibidores de la Bomba de Protones/efectos adversos , Inhibidores de la Bomba de Protones/administración & dosificación , Anciano , Hemorragia Gastrointestinal/prevención & control , 2-Piridinilmetilsulfinilbencimidazoles/uso terapéutico , 2-Piridinilmetilsulfinilbencimidazoles/efectos adversos , 2-Piridinilmetilsulfinilbencimidazoles/administración & dosificación , Úlcera Péptica/prevención & control , Unidades de Cuidados Intensivos , Neumonía Asociada al Ventilador/prevención & control , Método Doble Ciego , Estrés Fisiológico , AdultoRESUMEN
Critical care uses syndromic definitions to describe patient groups for clinical practice and research. There is growing recognition that a "precision medicine" approach is required and that integrated biologic and physiologic data identify reproducible subpopulations that may respond differently to treatment. This article reviews the current state of the field and considers how to successfully transition to a precision medicine approach. To impact clinical care, identification of subpopulations must do more than differentiate prognosis. It must differentiate response to treatment, ideally by defining subgroups with distinct functional or pathobiological mechanisms (endotypes). There are now multiple examples of reproducible subpopulations of sepsis, acute respiratory distress syndrome, and acute kidney or brain injury described using clinical, physiological, and/or biological data. Many of these subpopulations have demonstrated the potential to define differential treatment response, largely in retrospective studies, and that the same treatment-responsive subpopulations may cross multiple clinical syndromes (treatable traits). To bring about a change in clinical practice, a precision medicine approach must be evaluated in prospective clinical studies requiring novel adaptive trial designs. Several such studies are underway, but there are multiple challenges to be tackled. Such subpopulations must be readily identifiable and be applicable to all critically ill populations around the world. Subdividing clinical syndromes into subpopulations will require large patient numbers. Global collaboration of investigators, clinicians, industry, and patients over many years will therefore be required to transition to a precision medicine approach and ultimately realize treatment advances seen in other medical fields.
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Cuidados Críticos , Unidades de Cuidados Intensivos , Medicina de Precisión , Humanos , Medicina de Precisión/métodos , Cuidados Críticos/métodos , Cuidados Críticos/normas , Consenso , Síndrome , Enfermedad Crítica/terapia , Fenotipo , Síndrome de Dificultad Respiratoria/terapia , Síndrome de Dificultad Respiratoria/diagnóstico , Síndrome de Dificultad Respiratoria/clasificaciónRESUMEN
Patients with cirrhosis are prone to developing acute kidney injury (AKI), a complication associated with a markedly increased in-hospital morbidity and mortality, along with a risk of progression to chronic kidney disease. Whereas patients with cirrhosis are at increased risk of developing any phenotype of AKI, hepatorenal syndrome (HRS), a specific form of AKI (HRS-AKI) in patients with advanced cirrhosis and ascites, carries an especially high mortality risk. Early recognition of HRS-AKI is crucial since administration of splanchnic vasoconstrictors may reverse the AKI and serve as a bridge to liver transplantation, the only curative option. In 2023, a joint meeting of the International Club of Ascites (ICA) and the Acute Disease Quality Initiative (ADQI) was convened to develop new diagnostic criteria for HRS-AKI, to provide graded recommendations for the work-up, management and post-discharge follow-up of patients with cirrhosis and AKI, and to highlight priorities for further research.
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Lesión Renal Aguda , Síndrome Hepatorrenal , Cirrosis Hepática , Humanos , Lesión Renal Aguda/etiología , Lesión Renal Aguda/diagnóstico , Lesión Renal Aguda/terapia , Cirrosis Hepática/complicaciones , Síndrome Hepatorrenal/etiología , Síndrome Hepatorrenal/terapia , Síndrome Hepatorrenal/diagnóstico , Ascitis/etiología , Ascitis/terapia , Ascitis/diagnóstico , ConsensoRESUMEN
OBJECTIVES: Acute kidney injury (AKI) is a common form of organ dysfunction in the ICU. AKI is associated with adverse short- and long-term outcomes, including high mortality rates, which have not measurably improved over the past decade. This review summarizes the available literature examining the evidence of the need for precision medicine in AKI in critical illness, highlights the current evidence for heterogeneity in the field of AKI, discusses the progress made in advancing precision in AKI, and provides a roadmap for studying precision-guided care in AKI. DATA SOURCES: Medical literature regarding topics relevant to precision medicine in AKI, including AKI definitions, epidemiology, and outcomes, novel AKI biomarkers, studies of electronic health records (EHRs), clinical trial design, and observational studies of kidney biopsies in patients with AKI. STUDY SELECTION: English language observational studies, randomized clinical trials, reviews, professional society recommendations, and guidelines on areas related to precision medicine in AKI. DATA EXTRACTION: Relevant study results, statements, and guidelines were qualitatively assessed and narratively synthesized. DATA SYNTHESIS: We synthesized relevant study results, professional society recommendations, and guidelines in this discussion. CONCLUSIONS: AKI is a syndrome that encompasses a wide range of underlying pathologies, and this heterogeneity has hindered the development of novel therapeutics for AKI. Wide-ranging efforts to improve precision in AKI have included the validation of novel biomarkers of AKI, leveraging EHRs for disease classification, and phenotyping of tubular secretory clearance. Ongoing efforts such as the Kidney Precision Medicine Project, identifying subphenotypes in AKI, and optimizing clinical trials and endpoints all have great promise in advancing precision medicine in AKI.
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Lesión Renal Aguda , Biomarcadores , Medicina de Precisión , Lesión Renal Aguda/terapia , Humanos , Medicina de Precisión/métodos , Enfermedad Crítica/terapia , Registros Electrónicos de SaludRESUMEN
OBJECTIVES: To identify research priorities in the management, epidemiology, outcome, and pathophysiology of sepsis and septic shock. DESIGN: Shortly after publication of the most recent Surviving Sepsis Campaign Guidelines, the Surviving Sepsis Research Committee, a multiprofessional group of 16 international experts representing the European Society of Intensive Care Medicine and the Society of Critical Care Medicine, convened virtually and iteratively developed the article and recommendations, which represents an update from the 2018 Surviving Sepsis Campaign Research Priorities. METHODS: Each task force member submitted five research questions on any sepsis-related subject. Committee members then independently ranked their top three priorities from the list generated. The highest rated clinical and basic science questions were developed into the current article. RESULTS: A total of 81 questions were submitted. After merging similar questions, there were 34 clinical and ten basic science research questions submitted for voting. The five top clinical priorities were as follows: 1) what is the best strategy for screening and identification of patients with sepsis, and can predictive modeling assist in real-time recognition of sepsis? 2) what causes organ injury and dysfunction in sepsis, how should it be defined, and how can it be detected? 3) how should fluid resuscitation be individualized initially and beyond? 4) what is the best vasopressor approach for treating the different phases of septic shock? and 5) can a personalized/precision medicine approach identify optimal therapies to improve patient outcomes? The five top basic science priorities were as follows: 1) How can we improve animal models so that they more closely resemble sepsis in humans? 2) What outcome variables maximize correlations between human sepsis and animal models and are therefore most appropriate to use in both? 3) How does sepsis affect the brain, and how do sepsis-induced brain alterations contribute to organ dysfunction? How does sepsis affect interactions between neural, endocrine, and immune systems? 4) How does the microbiome affect sepsis pathobiology? 5) How do genetics and epigenetics influence the development of sepsis, the course of sepsis and the response to treatments for sepsis? CONCLUSIONS: Knowledge advances in multiple clinical domains have been incorporated in progressive iterations of the Surviving Sepsis Campaign guidelines, allowing for evidence-based recommendations for short- and long-term management of sepsis. However, the strength of existing evidence is modest with significant knowledge gaps and mortality from sepsis remains high. The priorities identified represent a roadmap for research in sepsis and septic shock.
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Sepsis , Choque Séptico , Humanos , Choque Séptico/terapia , Choque Séptico/diagnóstico , Sepsis/diagnóstico , Resucitación , Respiración Artificial , Cuidados CríticosRESUMEN
Adsorption-based extracorporeal therapies have been subject to technical developments and clinical application for close to five decades. More recently, new technological developments in membrane and sorbent manipulation have made it possible to deliver more biocompatible extracorporeal adsorption therapies to patients with a variety of conditions. There are several key rationales based on physicochemical principles and clinical considerations that justify the application and investigation of such therapies as evidenced by multiple ex-vivo, experimental, and clinical observations. Accordingly, unspecific adsorptive extracorporeal therapies have now been applied to the treatment of a wide array of conditions from poisoning to drug overdoses, to inflammatory states and sepsis, and acute or chronic liver and kidney failure. In response to the rapidly expanding knowledge base and increased clinical evidence, we convened an Acute Disease Quality Initiative (ADQI) consensus conference dedicated to such treatment. The data show that hemoadsorption has clinically acceptable short-term biocompatibility and safety, technical feasibility, and experimental demonstration of specified target molecule removal. Pilot studies demonstrate potentially beneficial effects on physiology and larger studies of endotoxin-based hemoadsorption have identified possible target phenotypes for larger randomized controlled trials (RCTs). Moreover, in a variety of endogenous and exogenous intoxications, removal of target molecules has been confirmed in vivo. However, some studies have raised concerns about harm or failed to deliver benefits. Thus, despite many achievements, modern hemoadsorption remains a novel and experimental intervention with limited data, and a large research agenda.
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PURPOSE OF REVIEW: Acute kidney injury (AKI) in critical illness is common, and survivors are faced with a host of adverse outcomes. In this article, we review the current landscape of outcomes and care in survivors of AKI and critical illness. RECENT FINDINGS: Follow-up care of survivors of AKI and critical illness is prudent to monitor for and mitigate the risk of adverse outcomes. Observational data have suggested improvement in outcomes with nephrology-based follow-up care, and recent interventional studies demonstrate similar findings. However, current post-AKI care is suboptimal with various challenges, such as breakdowns in the transition of care during hospital episodes and into the community, barriers for patients in follow-up, and lack of identification of high-risk patients for nephrology-based follow-up. Tools predictive of renal nonrecovery and long-term outcomes may help to identify high-risk patients who may benefit the most from nephrology-based care post-AKI. SUMMARY: Follow-up care of survivors of AKI and critical illness may improve outcomes and there is a need to prioritize transitions of care into the community. Further research is needed to elucidate the best ways to risk-stratify and manage post-AKI survivors to improve outcomes.
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BACKGROUND: During the COVID-19 pandemic, many intensive care units (ICUs) halted research to focus on COVID-19-specific studies. OBJECTIVE: To describe the conduct of an international randomized trial of stress ulcer prophylaxis (Re-Evaluating the Inhibition of Stress Erosions in the ICU [REVISE]) during the pandemic, addressing enrolment patterns, center engagement, informed consent processes, data collection, a COVID-specific substudy, patient transfers, and data monitoring. METHODS: REVISE is a randomized trial among mechanically ventilated patients, comparing pantoprazole 40 mg IV to placebo on the primary efficacy outcome of clinically important upper gastrointestinal bleeding and the primary safety outcome of 90-day mortality. We documented protocol implementation status from March 11th 2020-August 30th 2022. RESULTS: The Steering Committee did not change the scientific protocol. From the first enrolment on July 9th 2019 to March 10th 2020 (8 months preceding the pandemic), 267 patients were enrolled in 18 centers. From March 11th 2020-August 30th 2022 (30 months thereafter), 41 new centers joined; 59 were participating by August 30th 2022 which enrolled 2961 patients. During a total of 1235 enrolment-months in the pandemic phase, enrolment paused for 106 (8.6%) months in aggregate (median 3 months, interquartile range 2;6). Protocol implementation involved a shift from the a priori consent model pre-pandemic (188, 58.8%) to the consent to continue model (1615, 54.1%, p < 0.01). In one new center, an opt-out model was approved. The informed consent rate increased slightly (80.7% to 85.0%, p = 0.05). Telephone consent encounters increased (16.6% to 68.2%, p < 0.001). Surge capacity necessitated intra-institutional transfers; receiving centers continued protocol implementation whenever possible. We developed a nested COVID-19 substudy. The Methods Centers continued central statistical monitoring of trial metrics. Site monitoring was initially remote, then in-person when restrictions lifted. CONCLUSION: Protocol implementation adaptations during the pandemic included a shift in the consent model, a sustained high consent rate, and launch of a COVID-19 substudy. Recruitment increased as new centers joined, patient transfers were optimized, and monitoring methods were adapted.
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COVID-19 , Humanos , COVID-19/prevención & control , COVID-19/epidemiología , Pantoprazol/uso terapéutico , SARS-CoV-2 , Unidades de Cuidados Intensivos/estadística & datos numéricos , Pandemias/prevención & control , Femenino , Respiración Artificial/estadística & datos numéricos , Masculino , Protocolos Clínicos , Persona de Mediana Edad , Hemorragia Gastrointestinal/prevención & control , Antiulcerosos/uso terapéutico , Antiulcerosos/administración & dosificaciónRESUMEN
BACKGROUND: Vitamin D deficiency in critically ill patients is associated with poor outcomes, and vitamin D supplementation is recommended for patients with chronic kidney disease. Whether acute kidney injury (AKI) is associated with altered Vitamin D metabolism is unknown. We aimed to compare the longitudinal profiles of serum 25(OH)D and 1,25(OH)2D concentrations in critically ill patients with and without moderate to severe AKI and explore the impact of renal recovery and parathyroid hormone (PTH). METHODS: In this prospective, observational study in two centres in the UK, critically ill patients with and without AKI underwent serial measurement of serum 25(OH)D and 1,25(OH)2D and plasma PTH concentrations for 5 days. Linear mixed model analysis and sensitivity analyses were performed. RESULTS: Serial data of 137 patients were analysed. Seventy-one patients had AKI stage II/III of whom 23 recovered kidney function during the 5-day study period; 66 patients did not have AKI at enrolment of whom 14 developed new AKI. On day of enrolment, patients' serum 25(OH)D concentrations were low (median 18 nmol/L) but there was no significant difference between patients with and without AKI. Median serum 1,25(OH)2D levels were significantly lower in patients with AKI II/III (41 pmol/L [IQR 26, 58]) compared to similarly unwell patients without AKI (54 pmol/L [IQR 33, 69]) during the 5-day period. Recovery of kidney function in patients with AKI was associated with a rise in 1,25(OH)2D concentrations. Plasma PTH results were impacted by serum calcium and magnesium levels but not associated with 1,25(OH)2D levels. CONCLUSIONS: Critically ill patients with moderate-to-severe AKI have significantly lower serum 1,25(OH)2D concentrations than similarly sick patients without AKI but there was no difference in serum 25(OH)D concentrations. Recovery of AKI was associated with a rise in serum 1,25(OH)2D concentrations. More research is needed to investigate the health benefits and safety of supplementation with active vitamin D in critically ill patients with moderate-to-severe AKI. Trial registration Clinicaltrials.gov (NCT02869919), registered on 16 May 2016.
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Lesión Renal Aguda , Deficiencia de Vitamina D , Humanos , Estudios Prospectivos , Enfermedad Crítica , Vitamina D , Deficiencia de Vitamina D/complicaciones , Hormona ParatiroideaRESUMEN
BACKGROUND: Angiotensin-converting enzyme inhibitor (ACEi) and angiotensin receptor blockers (ARB) medications are widely prescribed. We sought to assess how pre-admission use of these medications might impact the response to angiotensin-II treatment during vasodilatory shock. METHODS: In a post-hoc subgroup analysis of the randomized, placebo-controlled, Angiotensin Therapy for High Output Shock (ATHOS-3) trial, we compared patients with chronic angiotensin-converting enzyme inhibitor (ACEi) use, and patients with angiotensin receptor blocker (ARB) use, to patients without exposure to either ACEi or ARB. The primary outcome was mean arterial pressure after 1-h of treatment. Additional clinical outcomes included mean arterial pressure and norepinephrine equivalent dose requirements over time, and study-drug dose over time. Biological outcomes included baseline RAS biomarkers (renin, angiotensin-I, angiotensin-II, and angiotensin-I/angiotensin-II ratio), and the change in renin from 0 to 3 h. RESULTS: We included n = 321 patients, of whom, 270 were ACEi and ARB-unexposed, 29 were ACEi-exposed and 22 ARB-exposed. In ACEi/ARB-unexposed patients, angiotensin-treated patients, compared to placebo, had higher hour-1 mean arterial pressure (9.1 mmHg [95% CI 7.6-10.1], p < 0.0001), lower norepinephrine equivalent dose over 48-h (p = 0.0037), and lower study-drug dose over 48-h (p < 0.0001). ACEi-exposed patients treated with angiotensin-II showed similarly higher hour-1 mean arterial pressure compared to ACEi/ARB-unexposed (difference in treatment-effect: - 2.2 mmHg [95% CI - 7.0-2.6], pinteraction = 0.38), but a greater reduction in norepinephrine equivalent dose (pinteraction = 0.0031) and study-drug dose (pinteraction < 0.0001) over 48-h. In contrast, ARB-exposed patients showed an attenuated effect of angiotensin-II on hour-1 mean arterial pressure versus ACEi/ARB-unexposed (difference in treatment-effect: - 6.0 mmHg [95% CI - 11.5 to - 0.6], pinteraction = 0.0299), norepinephrine equivalent dose (pinteraction < 0.0001), and study-drug dose (pinteraction = 0.0008). Baseline renin levels and angiotensin-I/angiotensin-II ratios were highest in ACEi-exposed patients. Finally, angiotensin-II treatment reduced hour-3 renin in ACEi/ARB-unexposed and ACEi-exposed patients but not in ARB-exposed patients. CONCLUSIONS: In vasodilatory shock patients, the cardiovascular and biological RAS response to angiotensin-II differed based upon prior exposure to ACEi and ARB medications. ACEi-exposure was associated with increased angiotensin II responsiveness, whereas ARB-exposure was associated with decreased responsiveness. These findings have clinical implications for patient selection and dosage of angiotensin II in vasodilatory shock. Trial Registration ClinicalTrials.Gov Identifier: NCT02338843 (Registered January 14th 2015).
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Inhibidores de la Enzima Convertidora de Angiotensina , Choque , Humanos , Inhibidores de la Enzima Convertidora de Angiotensina/efectos adversos , Angiotensina II/uso terapéutico , Renina , Antagonistas de Receptores de Angiotensina/efectos adversos , Choque/tratamiento farmacológico , Norepinefrina/uso terapéuticoRESUMEN
Acute kidney injury (AKI) often complicates sepsis and is associated with high morbidity and mortality. In recent years, several important clinical trials have improved our understanding of sepsis-associated AKI (SA-AKI) and impacted clinical care. Advances in sub-phenotyping of sepsis and AKI and clinical trial design offer unprecedented opportunities to fill gaps in knowledge and generate better evidence for improving the outcome of critically ill patients with SA-AKI. In this manuscript, we review the recent literature of clinical trials in sepsis with focus on studies that explore SA-AKI as a primary or secondary outcome. We discuss lessons learned and potential opportunities to improve the design of clinical trials and generate actionable evidence in future research. We specifically discuss the role of enrichment strategies to target populations that are most likely to derive benefit and the importance of patient-centered clinical trial endpoints and appropriate trial designs with the aim to provide guidance in designing future trials.
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Lesión Renal Aguda , Sepsis , Humanos , Lesión Renal Aguda/terapia , Lesión Renal Aguda/complicaciones , Enfermedad Crítica/terapia , Sepsis/complicaciones , Sepsis/terapia , Ensayos Clínicos como AsuntoRESUMEN
BACKGROUND: Variation in usual practice in fluid trials assessing lower versus higher volumes may affect overall comparisons. To address this, we will evaluate the effects of heterogeneity in treatment intensity in the Conservative versus Liberal Approach to Fluid Therapy of Septic Shock in Intensive Care trial. This will reflect the effects of differences in site-specific intensities of standard fluid treatment due to local practice preferences while considering participant characteristics. METHODS: We will assess the effects of heterogeneity in treatment intensity across one primary (all-cause mortality) and three secondary outcomes (serious adverse events or reactions, days alive without life support and days alive out of hospital) after 90 days. We will classify sites based on the site-specific intensity of standard fluid treatment, defined as the mean differences in observed versus predicted intravenous fluid volumes in the first 24 h in the standard-fluid group while accounting for differences in participant characteristics. Predictions will be made using a machine learning model including 22 baseline predictors using the extreme gradient boosting algorithm. Subsequently, sites will be grouped into fluid treatment intensity subgroups containing at least 100 participants each. Subgroups differences will be assessed using hierarchical Bayesian regression models with weakly informative priors. We will present the full posterior distributions of relative (risk ratios and ratios of means) and absolute differences (risk differences and mean differences) in each subgroup. DISCUSSION: This study will provide data on the effects of heterogeneity in treatment intensity while accounting for patient characteristics in critically ill adult patients with septic shock. REGISTRATIONS: The European Clinical Trials Database (EudraCT): 2018-000404-42, ClinicalTrials. gov: NCT03668236.
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Fluidoterapia , Choque Séptico , Humanos , Fluidoterapia/métodos , Choque Séptico/terapia , Cuidados Críticos/métodos , Teorema de Bayes , Aprendizaje AutomáticoRESUMEN
INTRODUCTION: In critically ill patients undergoing continuous renal replacement therapy (CRRT), a positive fluid balance (FB) is associated with adverse outcomes. However, current FB management practices in CRRT patients are poorly understood. We aimed to study FB and its components in British and Australian CRRT patients to inform future trials. METHODS: We obtained detailed electronic health record data on all fluid-related variables during CRRT and hourly FB for the first 7 days of treatment. RESULTS: We studied 1,616 patients from three tertiary intensive care units (ICUs) in two countries. After the start of CRRT, the mean cumulative FB became negative at 31 h and remained negative over 7 days to a mean nadir of -4.1 L (95% confidence interval (CI) of -4.6 to -3.5). The net ultrafiltration (NUF) rate was the dominant fluid variable (-67.7 mL/h; standard deviation (SD): 75.7); however, residual urine output (-34.7 mL/h; SD: 54.5), crystalloid administration (48.1 mL/h; SD: 44.6), and nutritional input (36.4 mL/h; SD: 29.7) significantly contributed to FB. Patients with a positive FB after 72 h of CRRT were more severely ill, required high-dose vasopressors, and had high lactate concentrations (5.0 mmol/L; interquartile range: 2.3-10.5). A positive FB was independently associated with increased hospital mortality (odds ratio: 1.70; 95% CI; p = 0.004). CONCLUSION: In the study ICUs, most CRRT patients achieved a predominantly NUF-dependent negative FB. Patients with a positive FB at 72 h had greater illness severity and haemodynamic instability. Achieving equipoise for conducting trials that target a negative early FB in such patients may be difficult.
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Terapia de Reemplazo Renal Continuo , Enfermedad Crítica , Fluidoterapia , Humanos , Terapia de Reemplazo Renal Continuo/métodos , Enfermedad Crítica/terapia , Masculino , Femenino , Persona de Mediana Edad , Anciano , Fluidoterapia/métodos , Unidades de Cuidados Intensivos , Equilibrio Hidroelectrolítico , Australia , Lesión Renal Aguda/terapia , Lesión Renal Aguda/mortalidad , AdultoRESUMEN
BACKGROUND: Rhabdomyolysis describes a syndrome characterized by muscle necrosis and the subsequent release of creatine kinase and myoglobin into the circulation. Myoglobin elimination with extracorporeal hemoadsorption has been shown to effectively remove myoglobin from the circulation. Our aim was to provide best practice consensus statements developed by the Hemoadsorption in Rhabdomyolysis Task Force (HRTF) regarding the use of hemadsorption for myoglobin elimination. METHODS: A systematic literature search was performed until 11th of January 2023, after which the Rhabdomyolysis RTF was assembled comprising international experts from 6 European countries. Online conferences were held between 18th April - 4th September 2023, during which 37 consensus questions were formulated and using the Delphi process, HRTF members voted online on an anonymised platform. In cases of 75 to 90% agreement a second round of voting was performed. RESULTS: Using the Delphi process on the 37 questions, strong consensus (> 90% agreement) was achieved in 12, consensus (75 to 90% agreement) in 10, majority (50 to 74%) agreement in 13 and no consensus (< 50% agreement) in 2 cases. The HRTF formulated the following recommendations: (1) Myoglobin contributes to the development of acute kidney injury; (2) Patients with myoglobin levels of > 10,000 ng/ml should be considered for extracorporeal myoglobin removal by hemoadsorption; (3) Hemoadsorption should ideally be started within 24 h of admission; (4) If myoglobin cannot be measured then hemoadsorption may be indicated based on clinical picture and creatinine kinase levels; (5) Cartridges should be replaced every 8-12 h until myoglobin levels < 10,000 ng/ml; (6) In patients with acute kidney injury, hemoadsorption can be discontinued before dialysis is terminated and should be maintained until the myoglobin concentration values are consistently < 5000 ng/ml. CONCLUSIONS: The current consensus of the HRTF support that adjuvant hemoadsorption therapy in severe rhabdomyolysis is both feasible and safe and may be an effective method to reduce elevated circulating levels of myoglobin.
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Mioglobina , Rabdomiólisis , Humanos , Rabdomiólisis/terapia , Mioglobina/sangre , Hemabsorción , Técnica Delphi , ConsensoRESUMEN
BACKGROUND: Urinary Chemokine (C-C motif) ligand 14 (CCL14) is a biomarker associated with persistent severe acute kidney injury (AKI). There is limited data to support the implementation of this AKI biomarker to guide therapeutic actions. METHODS: Sixteen AKI experts with clinical CCL14 experience participated in a Delphi-based method to reach consensus on when and how to potentially use CCL14. Consensus was defined as ≥ 80% agreement (participants answered with 'Yes', or three to four points on a five-point Likert Scale). RESULTS: Key consensus areas for CCL14 test implementation were: identifying challenges and mitigations, developing a comprehensive protocol and pairing it with a treatment plan, and defining the target population. The majority agreed that CCL14 results can help to prioritize AKI management decisions. CCL14 levels above the high cutoff (> 13 ng/mL) significantly changed the level of concern for modifying the AKI treatment plan (p < 0.001). The highest level of concern to modify the treatment plan was for discussions on renal replacement therapy (RRT) initiation for CCL14 levels > 13 ng/mL. The level of concern for discussion on RRT initiation between High and Low, and between Medium and Low CCL14 levels, showed significant differences. CONCLUSION: Real world urinary CCL14 use appears to provide improved care options to patients at risk for persistent severe AKI. Experts believe there is a role for CCL14 in AKI management and it may potentially reduce AKI-disease burden. There is, however, an urgent need for evidence on treatment decisions and adjustments based on CCL14 results.
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Lesión Renal Aguda , Biomarcadores , Técnica Delphi , Terapia de Reemplazo Renal , Lesión Renal Aguda/orina , Lesión Renal Aguda/terapia , Lesión Renal Aguda/diagnóstico , Humanos , Biomarcadores/orina , Consenso , Quimiocinas CC/orina , Europa (Continente)Asunto(s)
Lesión Renal Aguda , Aminoácidos , Procedimientos Quirúrgicos Cardíacos , Puente Cardiopulmonar , Complicaciones Posoperatorias , Humanos , Lesión Renal Aguda/diagnóstico , Lesión Renal Aguda/epidemiología , Lesión Renal Aguda/etiología , Lesión Renal Aguda/prevención & control , Aminoácidos/administración & dosificación , Aminoácidos/efectos adversos , Procedimientos Quirúrgicos Cardíacos/efectos adversos , Puente Cardiopulmonar/efectos adversos , Creatinina/sangre , Infusiones Intravenosas , Riñón/efectos de los fármacos , Complicaciones Posoperatorias/diagnóstico , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/etiología , Complicaciones Posoperatorias/prevención & control , Estudios Multicéntricos como Asunto , Ensayos Clínicos Controlados Aleatorios como AsuntoRESUMEN
Critical illness is a continuum with different phases and trajectories. The "Intensive Care Unit (ICU) without walls" concept refers to a model whereby care is adjusted in response to the patient's needs, priorities, and preferences at each stage from detection, escalation, early decision making, treatment and organ support, followed by recovery and rehabilitation, within which all healthcare staff, and the patient are equal partners. The rapid response system incorporates monitoring and alerting tools, a multidisciplinary critical care outreach team and care bundles, supported with education and training, analytical and governance functions, which combine to optimise outcomes of critically ill patients, independent of location.
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Cuidados Críticos , Enfermedad Crítica , Unidades de Cuidados Intensivos , Humanos , Unidades de Cuidados Intensivos/organización & administración , Enfermedad Crítica/rehabilitación , Enfermedad Crítica/terapia , Cuidados Críticos/métodos , Cuidados Críticos/organización & administraciónRESUMEN
INTRODUCTION: Acute kidney injury (AKI) is a common complication of septic shock and together these conditions carry a high mortality risk. In septic patients who develop severe AKI, renal cortical perfusion is deficient despite normal macrovascular organ blood flow. This intra-renal perfusion abnormality may be amenable to pharmacological manipulation, which may offer mechanistic insight into the pathophysiology of septic AKI. The aim of the current study is to investigate the effects of vasopressin and angiotensin II on renal microcirculatory perfusion in a cohort of patients with septic shock. METHODS AND ANALYSIS: In this single centre, mechanistically focussed, randomised controlled study, 45 patients with septic shock will be randomly allocated to either of the study vasopressors (vasopressin or angiotensin II) or standard therapy (norepinephrine). Infusions will be titrated to maintain a mean arterial pressure (MAP) target set by the attending clinician. Renal microcirculatory assessment will be performed for the cortex and medulla using contrast-enhanced ultrasound (CEUS) and urinary oxygen tension (pO2), respectively. Renal macrovascular flow will be assessed via renal artery ultrasound. Measurement of systemic macrovascular flow will be performed through transthoracic echocardiography (TTE) and microvascular flow via sublingual incident dark field (IDF) video microscopy. Measures will be taken at baseline, +1 and +24hrs following infusion of the study drug commencing. Blood and urine samples will also be collected at the measurement time points. Longitudinal data will be compared between groups and over time. DISCUSSION: Vasopressors are integral to the management of patients with septic shock. This study aims to further understanding of the relationship between this therapy, renal perfusion and the development of AKI. In addition, using CEUS and urinary pO2, we hope to build a more complete picture of renal perfusion in septic shock by interrogation of the constituent parts of the kidney. Results will be published in peer-reviewed journals and presented at academic meetings. TRIAL REGISTRATION: The REPERFUSE study was registered on Clinical Trials.gov (NCT06234592) on the 30th Jan 24.
Asunto(s)
Lesión Renal Aguda , Microcirculación , Choque Séptico , Vasoconstrictores , Humanos , Choque Séptico/tratamiento farmacológico , Choque Séptico/fisiopatología , Vasoconstrictores/uso terapéutico , Vasoconstrictores/administración & dosificación , Microcirculación/efectos de los fármacos , Lesión Renal Aguda/tratamiento farmacológico , Lesión Renal Aguda/etiología , Riñón/efectos de los fármacos , Riñón/fisiopatología , Riñón/irrigación sanguínea , Vasopresinas/administración & dosificación , Vasopresinas/uso terapéutico , Angiotensina II/administración & dosificación , Masculino , Femenino , Norepinefrina/administración & dosificación , Norepinefrina/uso terapéutico , Circulación Renal/efectos de los fármacos , Persona de Mediana Edad , AdultoRESUMEN
PURPOSE: A positive fluid balance (FB) is associated with harm in intensive care unit (ICU) patients with acute kidney injury (AKI). We aimed to understand how a positive balance develops in such patients. METHODS: Multinational, retrospective cohort study of critically ill patients with AKI not requiring renal replacement therapy. RESULTS: AKI occurred at a median of two days after admission in 7894 (17.3%) patients. Cumulative FB became progressively positive, peaking on day three despite only 848 (10.7%) patients receiving fluid resuscitation in the ICU. In those three days, persistent crystalloid use (median:60.0 mL/h; IQR 28.9-89.2), nutritional intake (median:18.2 mL/h; IQR 0.0-45.9) and limited urine output (UO) (median:70.8 mL/h; IQR 49.0-96.7) contributed to a positive FB. Although UO increased each day, it failed to match input, with only 797 (10.1%) patients receiving diuretics in ICU. After adjustment, a positive FB four days after AKI diagnosis was associated with an increased risk of hospital mortality (OR 1.12;95% confidence intervals 1.05-1.19;p-value <0.001). CONCLUSION: Among ICU patients with AKI, cumulative FB increased after diagnosis and was associated with an increased risk of mortality. Continued crystalloid administration, increased nutritional intake, limited UO, and minimal use of diuretics all contributed to positive FB. KEY POINTS: Question How does a positive fluid balance develop in critically ill patients with acute kidney injury? Findings Cumulative FB increased after AKI diagnosis and was secondary to persistent crystalloid fluid administration, increasing nutritional fluid intake, and insufficient urine output. Despite the absence of resuscitation fluid and an increasing cumulative FB, there was persistently low diuretics use, ongoing crystalloid use, and a progressive escalation of nutritional fluid therapy. Meaning Current management results in fluid accumulation after diagnosis of AKI, as a result of ongoing crystalloid administration, increasing nutritional fluid, limited urine output and minimal diuretic use.