Early Initiation of Continuous Renal Replacement Therapy Improves Clinical Outcomes in Patients With Acute Respiratory Distress Syndrome

doi:10.1097/MAJ.0000000000000379

The American Journal of the Medical Sciences

Volume 349, Issue 3, March 2015, Pages 199-205

https://doi.org/10.1097/MAJ.0000000000000379 Get rights and content

Abstract

Background

The acute respiratory distress syndrome (ARDS) is a common devastating syndrome in intensive care unit in critically ill patients. Continuous renal replacement therapy (CRRT) has been shown beneficial effects on oxygenation and survival in patients with ARDS. However, it is still controversial about the timing of initiation of CRRT.

Methods

Fifty-three patients with ARDS admitted to intensive care unit in Zhejiang Provincial People’s Hospital, China from 2009 to 2013 were enrolled in the study. The authors compared ventilation parameter, including PaO₂/FIO₂, A-a gradient, positive end-expiratory pressure, plateau pressure, dynamic compliance and hemodynamic parameters, including central venous pressure, mean arterial pressure, cardiac index, extravascular lung water index, fluid balance between early initiation (within 12 hours after ARDS onset) and late initiation of CRRT (48 hours after ARDS onset) groups. The authors further investigated transforming growth factor (TGF)-β1 level changes in serum and bronchoalveolar lavage fluid (BALF) by enzyme-linked immunosorbent assay during 7 days of follow-up.

Results

Significant improvement of oxygenation and shorter duration of mechanical ventilation were observed in early CRRT group during 7-day followup. In addition, TGF-β1 concentrations in serum and BALF were significantly decreased in patients with early initiation of CRRT compared to those with late initiation of CRRT on day 2 and day 7. Furthermore, patients who died of ARDS had higher levels of TGF-β1 in BALF than survivors.

Conclusions

Our findings showed that early initiation of CRRT is associated with favorable clinical outcomes in ARDS patients, which might be due to the reduced serum and BALF TGF-β1 levels through CRRT. However, large multi-center studies are needed to make further recommendations as to the optimal use of CRRT in ARDS patient populations.

Section snippets

Study Patients Selection

Fifty-three patients aged between 25 and 65 years admitted to the ICU at Zhejiang Provincial People’s Hospital, China from March 2009 to March 2013 and who met the 1994 American-European Consensus definition for ARDS²⁶ were enrolled in the study. Informed consent was obtained from patients or surrogates. The protocol was approved by the institutional review board of the hospital. Patients were excluded if they had immunodeficiency, autoimmune disease or cancer or were under any form of

Patient Characteristics

In the present study, the baseline patient characteristics are shown in Table 1. We analyzed a total number of 53 patients with ARDS who fulfilled the diagnostic criteria. All patients were treated according to the low-tidal-volume strategy previously reported.²⁷ The mean age in patients with early CRRT was 50.36 years and 70.4% (19/27) was male while the mean age in patients with late CRRT was 53.12 years and 65.4% (17/26) was male. The mean age in healthy control group was 46.79 years and 70%

DISCUSSION

In the current study, we have showed that early initiation of CRRT improves clinical outcomes in patients with ARDS, including improvement of oxygenation and decreased ventilator duration. Furthermore, our data suggested that it maybe associated with removal of lung water and inflammatory cytokine TGF-β1 in serum and BALF.

In ARDS, the fluid clearance process is defective with compromised alveolar-capillary barrier function.³⁰ It is widely believed that edema fluid must be cleared for patients

CONCLUSIONS

Taken together, our findings suggested that early initiation of CRRT is associated with favorable clinical outcomes in patients with ARDS, which might be due to the reduced serum and BALF TGFβ1 levels through CRRT. However, large multicenter studies are needed to make further recommendations as to the optimal use of CRRT in ARDS patient populations.

ACKNOWLEDGMENTS

The authors thank Dr. Ziqiang Zhu at the National Institutes of Health for the critical review of the manuscript.

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There are several methods of restrictive fluid management such as reduced infusion and use of diuretics, and an appropriate decision should be made according to the patient's condition. As a result of restrictive fluid management, mortality (6 RCTs [331–336]: N = 1,214) decreased by 28/1,000 patients (95% CI: 74 fewer–23 more patients), and VFD (1 RCT [336]: N = 1,000) was extended by an average of 2.5 days (95% CI: 1.12 days longer–3.88 days longer). The number of days where hemodynamic events assumed to be harmful did not occur (1 RCT [336]: N = 1,000) was shortened by an average of 0.3 days (95% CI: 0.57 days shorter–0.03 days shorter) as a result of restrictive infusion management, so the predicted desirable effect was judged to be “small.”
The joint committee of the Japanese Society of Intensive Care Medicine/Japanese Respiratory Society/Japanese Society of Respiratory Care Medicine on ARDS Clinical Practice Guideline has created and released the ARDS Clinical Practice Guideline 2021.
The 2016 edition of the Clinical Practice Guideline covered clinical questions (CQs) that targeted only adults, but the present guideline includes 15 CQs for children in addition to 46 CQs for adults. As with the previous edition, we used a systematic review method with the Grading of Recommendations Assessment Development and Evaluation (GRADE) system as well as a degree of recommendation determination method. We also conducted systematic reviews that used meta-analyses of diagnostic accuracy and network meta-analyses as a new method.
Recommendations for adult patients with ARDS are described: we suggest against using serum C-reactive protein and procalcitonin levels to identify bacterial pneumonia as the underlying disease (GRADE 2D); we recommend limiting tidal volume to 4–8 mL/kg for mechanical ventilation (GRADE 1D); we recommend against managements targeting an excessively low SpO₂ (PaO₂) (GRADE 2D); we suggest against using transpulmonary pressure as a routine basis in positive end-expiratory pressure settings (GRADE 2B); we suggest implementing extracorporeal membrane oxygenation for those with severe ARDS (GRADE 2B); we suggest against using high-dose steroids (GRADE 2C); and we recommend using low-dose steroids (GRADE 1B). The recommendations for pediatric patients with ARDS are as follows: we suggest against using non-invasive respiratory support (non-invasive positive pressure ventilation/high-flow nasal cannula oxygen therapy) (GRADE 2D); we suggest placing pediatric patients with moderate ARDS in the prone position (GRADE 2D); we suggest against routinely implementing NO inhalation therapy (GRADE 2C); and we suggest against implementing daily sedation interruption for pediatric patients with respiratory failure (GRADE 2D).
This article is a translated summary of the full version of the ARDS Clinical Practice Guideline 2021 published in Japanese (URL: https://www.jrs.or.jp/publication/jrs_guidelines/). The original text, which was written for Japanese healthcare professionals, may include different perspectives from healthcare professionals of other countries.
Continuous Renal Replacement Therapies for Acute Kidney Injury
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Acute kidney injury (AKI) is a clinical syndrome characterized by an abrupt decrease in kidney function. It leads to the inability of the kidney to excrete waste products, manage electrolytes, regulate fluid balance, and maintain acid-base status. Based on the Kidney Disease: Improving Global Outcomes (KDIGO) definition, the most recent epidemiological studies estimate that AKI occurs in 21% of hospital admissions, and overall, 11% of patients with AKI will require dialysis. AKI is associated with an increased risk of mortality, reaching greater than 50% in severe AKI and up to 80% when renal replacement therapy (RRT) is required in intensive care unit (ICU). Continuous RRT (CRRT) has been increasingly used, especially in the intensive care settings. This chapter reviews the basic techniques of CRRT and its applications, dosing, and outcomes in AKI.
Outcomes of renal replacement therapy in the critically ill with COVID-19
2021, Medicina Intensiva
Citation Excerpt :
While there has been a focus on the scarcity of ventilators and ICU bed availability,5,9 the dialysis machines and nursing expertise are typically scarcer, and the required resources are not available at all institutions. While older studies have suggested that RRT may potentially have beneficial effects in disease processes such as sepsis and Acute Respiratory Distress Syndrome (ARDS),10,11 other studies have called this into question12–14 and the use of CRRT was correlated with a higher mortality in during the Middle East Respiratory Coronavirus (MERS-CoV) outbreak.15 A recent meta-analysis showed that 20% of COVID-19 patients may need CRRT (rates varying from 5 to 60%), and so its effect on outcomes is of particular interest.16
To describe outcomes of critically ill patients with COVID-19, particularly the association of renal replacement therapy to mortality.
A single-center prospective observational study was carried out.
ICU of a tertiary care center.
Consecutive adults with COVID-19 admitted to the ICU.
Renal replacement therapy.
Demographic data, medical history, illness severity, type of oxygen therapy, laboratory data and use of renal replacement therapy to generate a logistic regression model describing independent risk factors for mortality.
Of the total of 166 patients, 51% were mechanically ventilated and 26% required renal replacement therapy. The overall hospital mortality rate was 36%, versus 56% for those requiring renal replacement therapy, and 68% for those with both mechanical ventilation and renal replacement therapy. The logistic regression model identified four independent risk factors for mortality: age (adjusted OR 2.8 [95% CI 1.8–4.4] for every 10-year increase), mechanical ventilation (4.2 [1.7–10.6]), need for continuous venovenous hemofiltration (2.3 [1.3–4.0]) and C-reactive protein (1.1 [1.0–1.2] for every 10 mg/L increase).
In our cohort, acute kidney injury requiring renal replacement therapy was associated to a high mortality rate similar to that associated to the need for mechanical ventilation, while multiorgan failure necessitating both techniques implied an extremely high mortality risk.
Describir los resultados de pacientes críticamente enfermos con COVID-19, especialmente la asociación de la terapia de reemplazo renal con la mortalidad.
Estudio observacional, prospectivo y unicéntrico.
En la unidad de cuidados intensivos (UCI) de un centro de atención terciaria.
Pacientes adultos con COVID-19 ingresados de forma consecutiva en la UCI.
Administración de terapia de reemplazo renal.
Datos demográficos, antecedentes médicos, gravedad de la enfermedad, tipo de oxigenoterapia, datos analíticos y uso de terapia de reemplazo renal para generar un modelo de regresión logística que describa factores de riesgo independientes de la mortalidad.
De los 166 pacientes, el 51% recibieron ventilación mecánica (VM) y el 26% requirió terapia de reemplazo renal (TRR). La mortalidad hospitalaria global fue del 36%, frente al 56% en el caso de los pacientes que requirieron TRR y el 68% en el subconjunto de pacientes que necesitó tanto VM como RTT. Un modelo de regresión logística señala cuatro factores de riesgo independientes de la mortalidad: edad (OR ajustada: 2,8 [IC del 95%: 1,8-4,4] por cada incremento de 10 años), ventilación mecánica (4,2 [1,7-10,6]), necesidad de hemofiltración venovenosa continua (HVVC) (2,3 [1,3-4,0]), y proteína C reactiva (1,1 [1,0-1,2] por cada incremento de 10 mg/L).
En nuestra cohorte, la lesión renal aguda que necesita TRR se asocia con una mortalidad similarmente elevada a la de los pacientes que requieren VM, y la insuficiencia multiorgánica que hace necesarias ambas intervenciones se asocia con un riesgo de mortalidad extremadamente alta.
The novel biomarkers for assessing clinical benefits of continuous renal replacement therapy in pediatric sepsis: a pilot study
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The role of early blood purification for miliary tuberculosis presenting as acute respiratory distress syndrome in pregnancy: A case report
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View all citing articles on Scopus

Supported by the Grants from Science and Technology Department of Zhejiang Province, China (2011R50018-14) and Zhejiang Provincial Health Department, China (2012KYB021 and 2013RCA004).

The authors have no conflicts of interest to disclose.

View full text

Clinical InvestigationEarly Initiation of Continuous Renal Replacement Therapy Improves Clinical Outcomes in Patients With Acute Respiratory Distress Syndrome

Abstract

Background

Methods

Results

Conclusions

Section snippets

Study Patients Selection

Patient Characteristics

DISCUSSION

CONCLUSIONS

ACKNOWLEDGMENTS

Chest

Eur J Intern Med

J Am Coll Cardiol

Kidney Int Suppl

J Crit Care

Am J Kidney Dis

Chest

Acute respiratory distress syndrome: the Berlin Definition

JAMA

The acute respiratory distress syndrome

N Engl J Med

Tumor necrosis factor-alpha and angiostatin are mediators of endothelial cytotoxicity in bronchoalveolar lavages of patients with acute respiratory distress syndrome

Am J Respir Crit Care Med

TGF-beta is a critical mediator of acute lung injury

J Clin Invest

Ligation of protease-activated receptor 1 enhances alpha(v)beta6 integrin-dependent TGF-beta activation and promotes acute lung injury

J Clin Invest

Active transforming growth factor-beta1 activates the procollagen I promoter in patients with acute lung injury

Intensive Care Med

Transforming growth factorbeta induces human T lymphocyte migration in vitro

J Immunol

The acute respiratory distress syndrome: a role for transforming growth factor-beta 1

Am J Respir Cell Mol Biol

TGF-beta1 inhibits surfactant component expression and epithelial cell maturation in cultured human fetal lung

Am J Physiol

Transforming growth factorbeta: a mediator of cell regulation in acute respiratory distress syndrome

Crit Care Med

Anti-transforming growth factor-beta monoclonal antibodies prevent lung injury in hemorrhaged mice

Am J Respir Cell Mol Biol

Effect of antibody to transforming growth factor beta on bleomycin induced accumulation of lung collagen in mice

Thorax

Extracorporeal blood treatment (EBT) methods in SIRS/Sepsis

Int J ArtifOrgans

Continuous renal replacement therapy in the adult intensive care unit: history and current trends

Crit Care Nurse

Extracorporeal therapies in non-renal disease: treatment of sepsis and the peak concentration hypothesis

Blood Purif

Clinical Investigation
Early Initiation of Continuous Renal Replacement Therapy Improves Clinical Outcomes in Patients With Acute Respiratory Distress Syndrome