Between-trial heterogeneity in ARDS research

Juschten, Jenny; Tuinman, P. R.; Guo, Tingjie; Juffermans, Nicole P.; Schultz, Marcus J.; Loer, Stephan A.; Girbes, Armand R.J.; Grooth, Harm-Jan de

doi:10.1007/s00134-021-06370-w

Cited by 18 publications

(18 citation statements)

References 96 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The most critical factor in managing ARDS patients is the initiation of lung-protective ventilation instantaneously after endotracheal intubation. However, the development of therapeutic strategies for ARDS is complicated because ARDS is not a disease but a very heterogeneous syndrome ( Juschten et al, 2021 ). The optimal ventilation strategy for ARDS still remains to be refined.…”

Section: Future Trial Design: Personalized Mechanical Ventilationmentioning

confidence: 99%

Unsuccessful and Successful Clinical Trials in Acute Respiratory Distress Syndrome: Addressing Physiology-Based Gaps

et al. 2021

View full text Add to dashboard Cite

The acute respiratory distress syndrome (ARDS) is a severe form of acute hypoxemic respiratory failure caused by an insult to the alveolar-capillary membrane, resulting in a marked reduction of aerated alveoli, increased vascular permeability and subsequent interstitial and alveolar pulmonary edema, reduced lung compliance, increase of physiological dead space, and hypoxemia. Most ARDS patients improve their systemic oxygenation, as assessed by the ratio between arterial partial pressure of oxygen and inspired oxygen fraction, with conventional intensive care and the application of moderate-to-high levels of positive end-expiratory pressure. However, in some patients hypoxemia persisted because the lungs are markedly injured, remaining unresponsive to increasing the inspiratory fraction of oxygen and positive end-expiratory pressure. For decades, mechanical ventilation was the only standard support technique to provide acceptable oxygenation and carbon dioxide removal. Mechanical ventilation provides time for the specific therapy to reverse the disease-causing lung injury and for the recovery of the respiratory function. The adverse effects of mechanical ventilation are direct consequences of the changes in pulmonary airway pressures and intrathoracic volume changes induced by the repetitive mechanical cycles in a diseased lung. In this article, we review 14 major successful and unsuccessful randomized controlled trials conducted in patients with ARDS on a series of techniques to improve oxygenation and ventilation published since 2010. Those trials tested the effects of adjunctive therapies (neuromuscular blocking agents, prone positioning), methods for selecting the optimum positive end-expiratory pressure (after recruitment maneuvers, or guided by esophageal pressure), high-frequency oscillatory ventilation, extracorporeal oxygenation, and pharmacologic immune modulators of the pulmonary and systemic inflammatory responses in patients affected by ARDS. We will briefly comment physiology-based gaps of negative trials and highlight the possible needs to address in future clinical trials in ARDS.

show abstract

Section: Future Trial Design: Personalized Mechanical Ventilationmentioning

confidence: 99%

Unsuccessful and Successful Clinical Trials in Acute Respiratory Distress Syndrome: Addressing Physiology-Based Gaps

et al. 2021

View full text Add to dashboard Cite

show abstract

“…Although numerous interventions, for example, low tidal volume ventilation [ 2 ] and conservative fluid strategies [ 3 ], have been employed in the management of ARDS, whose hospital mortality remained significantly high in critical illness patients in intensive care unit (ICU), especially that of invasive ventilation [ 4 ]. In addition, the large variability in mortality exists in ARDS, which was thought to contribute to indeterminate or conflicting study results in most randomized clinical trials in patients with ARDS [ 5 ].…”

Section: Introductionmentioning

confidence: 99%

Development and validation of a clinical risk model to predict the hospital mortality in ventilated patients with acute respiratory distress syndrome: a population-based study

Liang

et al. 2022

BMC Pulm Med

View full text Add to dashboard Cite

Background Large variability in mortality exists in patients of acute respiratory distress syndrome (ARDS), especially those with invasive ventilation. The aim of this study was to develop a model to predict risk of in-hospital death in ventilated ARDS patients. Methods Ventilated patients with ARDS from two public databases (MIMIC-III and eICU-CRD) were randomly divided as training cohort and internal validation cohort. Least absolute shrinkage and selection operator (LASSO) and then Logistic regression was used to construct a predictive model with demographic, clinical, laboratory, comorbidities and ventilation variables ascertained at first 24 h of ICU admission and invasive ventilation. Our model was externally validated using data from another database (MIMIC-IV). Results A total of 1075 adult patients from MIMIC-III and eICU were randomly divided into training cohort (70%, n = 752) and internal validation cohort (30%, n = 323). 521 patients were included from MIMIC-IV. From 176 potential predictors, 9 independent predictive factors were included in the final model. Five variables were ascertained within the first 24 h of ICU admission, including age (OR, 1.02; 95% CI: 1.01–1.03), mean of respiratory rate (OR, 1.04; 95% CI: 1.01–1.08), the maximum of INR (OR, 1.14; 95% CI: 1.03–1.31) and alveolo-arterial oxygen difference (OR, 1.002; 95% CI: 1.001–1.003) and the minimum of RDW (OR, 1.17; 95% CI: 1.09–1.27). And four variables were collected within the first 24 h of invasive ventilation: mean of temperature (OR, 0.70; 95% CI: 0.57–0.86), the maximum of lactate (OR, 1.15; 95% CI: 1.09–1.22), the minimum of blood urea nitrogen (OR, 1.02; 95% CI: 1.01–1.03) and white blood cell counts (OR, 1.03; 95% CI: 1.01–1.06). Our model achieved good discrimination (AUC: 0.77, 95% CI: 0.73–0.80) in training cohort but the performance declined in internal (AUC: 0.75, 95% CI: 0.69–0.80) and external validation cohort (0.70, 95% CI: 0.65–0.74) and showed modest calibration. Conclusions A risk score based on routinely collected variables at the start of admission to ICU and invasive ventilation can predict mortality of ventilated ARDS patients, with a moderate performance.

show abstract

“…We (and others) previously showed that prediction of CER in ARDS RCTs is challenging because of the differences between RCTs being explained only partly by differences in inclusion criteria and baseline population characteristics. 18,128 Because a priori specification of CER is susceptible to random error and deviations from predicted control-arm mortality will impact on detectable ATE, trialists should consider the use of adaptive RCT designs that can account for this during the conduct of the trial. In addition, this approach could be supplemented by simulation of different scenarios during RCT planning.…”

Section: Discussionmentioning

confidence: 99%