Impact of renin-angiotensin-aldosterone system inhibition on mortality in critically ill COVID-19 patients with pre-existing hypertension: a prospective cohort study.

BACKGROUND: The influence of renin-angiotensin-aldosterone system (RAAS) inhibitors on the critically ill COVID-19 patients with pre-existing hypertension remains uncertain. This study examined the impact of previous use of angiotensin-converting enzyme inhibitors (ACEi) and angiotensin receptor blockers (ARB) on the critically ill COVID-19 patients. METHODS: Data from an international, prospective, observational cohort study involving 354 hospitals spanning 54 countries were included. A cohort of 737 COVID-19 patients with pre-existing hypertension admitted to intensive care units (ICUs) in 2020 were targeted. Multi-state survival analysis was performed to evaluate in-hospital mortality and hospital length of stay up to 90 days following ICU admission. RESULTS: A total of 737 patients were included-538 (73%) with pre-existing hypertension had received ACEi/ARBs before ICU admission, while 199 (27%) had not. Cox proportional hazards model showed that previous ACEi/ARB use was associated with a decreased hazard of in-hospital death (HR, 0.74, 95% CI 0.58-0.94). Sensitivity analysis adjusted for propensity scores showed similar results for hazards of death. The average length of hospital stay was longer in ACEi/ARB group with 21.2 days (95% CI 19.7-22.8 days) in ICU and 6.7 days (5.9-7.6 days) in general ward compared to non-ACEi/ARB group with 16.2 days (14.1-18.6 days) and 6.4 days (5.1-7.9 days), respectively. When analysed separately, results for ACEi or ARB patient groups were similar for both death and discharge. CONCLUSIONS: In critically ill COVID-19 patients with comorbid hypertension, use of ACEi/ARBs prior to ICU admission was associated with a reduced risk of in-hospital mortality following adjustment for baseline characteristics although patients with ACEi/ARB showed longer length of hospital stay. Clinical trial registration The registration number: ACTRN12620000421932; The date of registration: 30, March 2020; The URL of the registration: https://www.australianclinicaltrials.gov.au/anzctr/trial/ACTRN12620000421932 .

Haematological Trends and Transfusion during Adult Extracorporeal Membrane Oxygenation: A Single Centre Study.

The temporal trends in haematological parameters and their associations with blood product transfusion requirements in patients supported with extracorporeal membrane oxygenation (ECMO) are poorly understood. We performed a retrospective data analysis to better understand the behaviour of haematological and coagulation parameters and their associations with transfusion requirements during ECMO. METHODS: Patient demographics, haematological and coagulation parameters, plasma haemoglobin and fibrinogen concentrations, platelet count, the international normalised ratio (INR), the activated partial thromboplastin time (APTT), and blood product transfusion data from 138 patients who received ECMO in a single high-volume centre were analysed. RESULTS: Ninety-two patients received venoarterial (VA) ECMO and 46 patients received venovenous (VV) ECMO. The median (IQR) duration of VA, and VV ECMO was 8 (5-13) days and 13 (8-23) days, respectively. There were significant reductions in haemoglobin, the platelet count, and the fibrinogen concentration upon initiation of ECMO. On average, over time, patients on VV ECMO had platelet counts 44 × 109/L higher than those on VA ECMO (p ≤ 0.001). Fibrinogen and APTT did not vary significantly based on the mode of ECMO (p = 0.55 and p = 0.072, respectively). A platelet count < 50 × 109/L or a fibrinogen level < 1.8 g/L was associated with 50% chance of PRBC transfusion, regardless of the ECMO type, and packed red blood cell (PRBC) transfusion was more common with VA ECMO. APTT was predictive of the transfusion requirement, and the decrement in APTT was discriminatory between VVECMO survivors and nonsurvivors. CONCLUSION: ECMO support is associated with reductions in haemoglobin, platelet count, and fibrinogen. Patients supported with VA ECMO are more likely to receive a PRBC transfusion compared to those on VV ECMO. Thrombocytopaenia, hypofibrinogenaemia, and anticoagulation effect the likelihood of requiring PRBC transfusion. Further research is needed to define optimal blood management during ECMO, including appropriate transfusion triggers and the anticoagulation intensity.

The impact of reduction in intensity of mechanical ventilation upon venovenous ECMO initiation on radiographically assessed lung edema scores: A retrospective observational study.

Background: Patients with severe acute respiratory distress syndrome (ARDS) typically receive ultra-protective ventilation after extracorporeal membrane oxygenation (ECMO) is initiated. While the benefit of ECMO appears to derive from supporting "lung rest", reductions in the intensity of mechanical ventilation, principally tidal volume limitation, may manifest radiologically. This study evaluated the relative changes in radiographic assessment of lung edema (RALE) score upon venovenous ECMO initiation in patients with severe ARDS. Methods: Digital chest x-rays (CXR) performed at baseline immediately before initiation of ECMO, and at intervals post (median 1.1, 2.1, and 9.6 days) were reviewed in 39 Adult ARDS patients. One hundred fifty-six digital images were scored by two independent, blinded radiologists according to the RALE (Radiographic Assessment of Lung Edema) scoring criteria. Ventilatory data, ECMO parameters and fluid balance were recorded at corresponding time points. Multivariable analysis was performed analyzing the change in RALE score over time relative to baseline. Results: The RALE score demonstrated excellent inter-rater agreement in this novel application in an ECMO cohort. Mean RALE scores increased from 28 (22-37) at baseline to 35 (26-42) (p < 0.001) on D1 of ECMO; increasing RALE was associated with higher baseline APACHE III scores [ß value +0.19 (0.08, 0.30) p = 0.001], and greater reductions in tidal volume [ß value -2.08 (-3.07, -1.10) p < 0.001] after ECMO initiation. Duration of mechanical ventilation, and ECMO support did not differ between survivors and non-survivors. Conclusions: The magnitude of reductions in delivered tidal volumes correlated with increasing RALE scores (radiographic worsening) in ARDS patients receiving ECMO. Implications for patient centered outcomes remain unclear. There is a need to define appropriate ventilator settings on venovenous ECMO, counterbalancing the risks vs. benefits of optimal "lung rest" against potential atelectrauma.