Acute kidney injury (AKI) is a frequent and severe complication of both COVID-19-related acute respiratory distress syndrome (ARDS) and non-COVID-19-related ARDS. The COVID-19 Critical Care ...Consortium (CCCC) has generated a global data set on the demographics, management and outcomes of critically ill COVID-19 patients. The LUNG-SAFE study was an international prospective cohort study of patients with severe respiratory failure, including ARDS, which pre-dated the pandemic.
The incidence, demographic profile, management and outcomes of early AKI in patients undergoing invasive mechanical ventilation for COVID-19-related ARDS were described and compared with AKI in a non-COVID-19-related ARDS cohort.
Of 18,964 patients in the CCCC data set, 1699 patients with COVID-19-related ARDS required invasive ventilation and had relevant outcome data. Of these, 110 (6.5%) had stage 1, 94 (5.5%) had stage 2, 151 (8.9%) had stage 3 AKI, while 1214 (79.1%) had no AKI within 48 h of initiating invasive mechanical ventilation. Patients developing AKI were older and more likely to have hypertension or chronic cardiac disease. There were geo-economic differences in the incidence of AKI, with lower incidence of stage 3 AKI in European high-income countries and a higher incidence in patients from middle-income countries. Both 28-day and 90-day mortality risk was increased for patients with stage 2 (HR 2.00, p < 0.001) and stage 3 AKI (HR 1.95, p < 0.001). Compared to non-COVID-19 ARDS, the incidence of shock was reduced with lower cardiovascular SOFA score across all patient groups, while hospital mortality was worse in all groups no AKI (30 vs 50%), Stage 1 (38 vs 58%), Stage 2 (56 vs 74%), and Stage 3 (52 vs 72%), p < 0.001. The time profile of onset of AKI also differed, with 56% of all AKI occurring in the first 48 h in patients with COVID-19 ARDS compared to 89% in the non-COVID-19 ARDS population.
AKI is a common and serious complication of COVID-19, with a high mortality rate, which differs by geo-economic location. Important differences exist in the profile of AKI in COVID-19 versus non-COVID-19 ARDS in terms of their haemodynamic profile, time of onset and clinical outcomes.
Recent advances in our understanding of the epidemiology of ARDS has generated key insights into the incidence, risk factors, demographics, management and outcomes from this devastating clinical ...syndrome.
ARDS occurs in 10% of all ICU patients, in 23% of all mechanically ventilated patients, with 5.5 cases per ICU bed each year. Although some regional variation exists regarding ARDS incidence, this may be less than previously thought. Subphenotypes are increasingly identified within the ARDS cohort, with studies identifying a 'hyperinflammatory' or 'reactive' subgroup that has a higher mortality, and may respond differently to therapeutic interventions. Demographic factors, such as race, may also affect the therapeutic response. Although mortality in ARDS is decreasing in clinical trials, it remains unchanged at approximately 40% in major observational studies. Modifiable ventilatory management factors, including PEEP, airway pressures, and respiratory rate are associated with mortality in ARDS. Hospital and ICU organizational factors play a role in outcome, whereas socioeconomic status is independently associated with survival in patients with ARDS. The Kigali adaptation of the Berlin ARDS definition may provide useful insights into the burden of ARDS in the developing world.
ARDS exerts a substantial disease burden, with 40% of patients dying in hospital. Diverse factors, including patient-related factors such as age and illness severity, country level socioeconomic status, and ventilator management and ICU organizational factors each contribute to outcome from ARDS. Addressing these issues provides opportunities to improve outcome in patients with ARDS.
BACKGROUNDConsiderable variability exists regarding CO2 management in early ARDS, with the impact of arterial CO2 tension on management and outcomes poorly understood. RESEARCH QUESTIONTo determine ...the prevalence and impact of hypocapnia and hypercapnia on the management and outcomes of patients with early ARDS enrolled in the Large Observational Study to Understand the Global Impact of Severe Acute Respiratory Failure (LUNG SAFE) study, an international multicenter observational study. STUDY DESIGN AND METHODSOur primary objective was to examine the prevalence of day 1 and sustained (day 1 and 2) hypocapnia (Paco2 < 35 mm Hg), normocapnia (Paco2 35-45 mm Hg), and hypercapnia (Paco2 > 45 mm Hg) in patients with ARDS. Secondary objectives included elucidating the effect of CO2 tension on ventilatory management and examining the relationship with ARDS outcome. RESULTSOf 2,813 patients analyzed, 551 (19.6%; 95%CI, 18.1-21.1) were hypocapnic, 1,018 (36.2%; 95% CI, 34.4-38.0) were normocapnic, and 1,214 (43.2%; 95% CI, 41.3-45.0) were hypercapnic, on day 1. Sustained hypocapnia was seen in 252 (9.3%; 95% CI, 8.2-10.4), sustained normocapnia in 544 (19.3%; 95% CI, 17.9-20.8), and sustained hypercapnia in 654 (24.1%; 95% CI, 22.5-25.7) patients. Hypocapnia was more frequent and severe in patients receiving noninvasive ventilation but also was observed in patients on controlled mechanical ventilation. Sustained hypocapnia was more frequent in middle-income countries, whereas sustained hypercapnia was more frequent in Europe. ARDS severity profile was highest in sustained hypercapnia, and these patients received more protective ventilation. No independent association was seen between arterial CO2 and outcome. In propensity-matched analyses, the hospital mortality rate was 36% in both sustained normocapnic and hypercapnic patients (P = 1.0). ICU mortality was higher in patients with mild to moderate ARDS receiving sustained hypocapnia (38.1%) compared with normocapnia (27.1%). INTERPRETATIONNo evidence was found for benefit or harm with hypercapnia. Of concern, ICU mortality was higher with sustained hypocapnia in mild to moderate ARDS.
We wished to determine the influence of sex on the management and outcomes in acute respiratory distress syndrome (ARDS) patients in the Large Observational Study to Understand the Global Impact of ...Severe Acute Respiratory Failure (LUNG SAFE).
We assessed the effect of sex on mortality, intensive care unit and hospital length of stay, and duration of invasive mechanical ventilation (IMV) in patients with ARDS who underwent IMV, adjusting for plausible clinical and geographic confounders.
Of 2377 patients with ARDS, 905 (38%) were female and 1472 (62%) were male. There were no sex differences in clinician recognition of ARDS or critical illness severity profile. Females received higher tidal volumes (8.2±2.1
7.2±1.6 mL·kg
; p<0.0001) and higher plateau and driving pressures compared with males. Lower tidal volume ventilation was received by 50% of females compared with 74% of males (p<0.0001). In shorter patients (height ≤1.69 m), females were significantly less likely to receive lower tidal volumes. Surviving females had a shorter duration of IMV and reduced length of stay compared with males. Overall hospital mortality was similar in females (40.2%)
males (40.2%). However, female sex was associated with higher mortality in patients with severe confirmed ARDS (OR for sex (male
female) 0.35, 95% CI 0.14-0.83).
Shorter females with ARDS are less likely to receive lower tidal volume ventilation, while females with severe confirmed ARDS have a higher mortality risk. These data highlight the need for better ventilatory management in females to improve their outcomes from ARDS.
ARDS, first described in 1967, is the commonest form of acute severe hypoxemic respiratory failure. Despite considerable advances in our knowledge regarding the pathophysiology of ARDS, insights into ...the biologic mechanisms of lung injury and repair, and advances in supportive care, particularly ventilatory management, there remains no effective pharmacological therapy for this syndrome. Hospital mortality at 40% remains unacceptably high underlining the need to continue to develop and test therapies for this devastating clinical condition. The purpose of the review is to critically appraise the current status of promising emerging pharmacological therapies for patients with ARDS and potential impact of these and other emerging therapies for COVID-19-induced ARDS. We focus on drugs that: (1) modulate the immune response, both via pleiotropic mechanisms and via specific pathway blockade effects, (2) modify epithelial and channel function, (3) target endothelial and vascular dysfunction, (4) have anticoagulant effects, and (5) enhance ARDS resolution. We also critically assess drugs that demonstrate potential in emerging reports from clinical studies in patients with COVID-19-induced ARDS. Several therapies show promise in earlier and later phase clinical testing, while a growing pipeline of therapies is in preclinical testing. The history of unsuccessful clinical trials of promising therapies underlines the challenges to successful translation. Given this, attention has been focused on the potential to identify biologically homogenous subtypes within ARDS, to enable us to target more specific therapies ‘precision medicines.’ It is hoped that the substantial number of studies globally investigating potential therapies for COVID-19 will lead to the rapid identification of effective therapies to reduce the mortality and morbidity of this devastating form of ARDS.
Adjunctive strategies are an important part of the management of ARDS. However, their application in clinical practice remains inconsistent.
We wished to determine the frequency and patterns of use ...of adjunctive strategies in patients with moderate to severe ARDS (Pao
/Fio
P/F ratio < 150) enrolled into the Large observational study to UNderstand the Global impact of Severe Acute respiratory FailurE (LUNG SAFE) study.
The LUNG SAFE study was an international, multicenter, prospective cohort study of patients with severe respiratory failure, conducted in 2014 in 459 ICUs from 50 countries. The primary objective of this substudy was to determine the frequency of use of widely available (neuromuscular blockade, prone position) adjuncts vs adjuncts requiring specialized equipment (extracorporeal membrane oxygenation, inhaled vasodilators, high-frequency ventilation) in patients in the first 48 h of moderate to severe ARDS (P/F ratio < 150).
Of 1,146 patients on invasive ventilation with moderate to severe ARDS, 811 patients (71%) received no adjunct within 48 h of ARDS onset. Of 335 (29%) that received adjunctive strategies, 252 (75%) received a single strategy, and 83 (25%) receiving more than one adjunct. Of ARDS nonsurvivors, 67% did not receive any adjunctive strategy in the first 48 h. Most patients (67%) receiving specialized adjuncts did not receive prone positioning or neuromuscular blockade. Patients that received adjuncts were more likely to have their ARDS recognized, be younger and sicker, have pneumonia, be more difficult to ventilate, and be in a European high-income country than those that did not receive adjuncts.
Three in 10 patients with moderate to severe ARDS, and only one-third of nonsurvivors, received adjunctive strategies over the first 48 h of ARDS. A more consistent and evidence-driven approach to adjunct use may reduce costs and improve outcomes in patients with moderate to severe ARDS.
ClinicalTrials.gov; No.: NCT02010073; URL: www.clinicaltrials.gov.
PDF
