Early IL-1 receptor blockade in severe inflammatory respiratory failure complicating COVID-19.

Around the tenth day after diagnosis, ∼20% of patients with coronavirus disease 2019 (COVID-19)-associated pneumonia evolve toward severe oxygen dependence (stage 2b) and acute respiratory distress syndrome (stage 3) associated with systemic inflammation often termed a "cytokine storm." Because interleukin-1 (IL-1) blocks the production of IL-6 and other proinflammatory cytokines, we treated COVID-19 patients early in the disease with the IL-1 receptor antagonist, anakinra. We retrospectively compared 22 patients from three different centers in France with stages 2b and 3 COVID-19-associated pneumonia presenting with acute severe respiratory failure and systemic inflammation who received either standard-of-care treatment alone (10 patients) or combined with intravenous anakinra (12 patients). Treatment started at 300 mg⋅d-1 for 5 d, then tapered with lower dosing over 3 d. Both populations were comparable for age, comorbidities, clinical stage, and elevated biomarkers of systemic inflammation. All of the patients treated with anakinra improved clinically (P < 0.01), with no deaths, significant decreases in oxygen requirements (P < 0.05), and more days without invasive mechanical ventilation (P < 0.06), compared with the control group. The effect of anakinra was rapid, as judged by significant decrease of fever and C-reactive protein at day 3. A mean total dose of 1,950 mg was infused with no adverse side effects or bacterial infection. We conclude that early blockade of the IL-1 receptor is therapeutic in acute hyperinflammatory respiratory failure in COVID-19 patients.

Delayed intensive care unit admission is associated with increased mortality in patients with cancer with acute respiratory failure.

Acute respiratory failure (ARF) is the leading reason for intensive care unit (ICU) admission in patients with cancer. The aim of this study was to identify early predictors of death in patients with cancer admitted to the ICU for ARF who were not intubated at admission. We conducted analysis of a prospective randomized controlled trial including 219 patients with cancer with ARF in which day-28 mortality was a secondary endpoint. Mortality at day 28 was 31.1%. By multivariate analysis, independent predictors of day-28 mortality were: age (odds ratio [OR] 1.30/10 years, 95% confidence interval [CI] [1.01-1.68], p = 0.04), more than one line of chemotherapy (OR 2.14, 95% CI [1.08-4.21], p = 0.03), time between respiratory symptoms onset and ICU admission > 2 days (OR 2.50, 95% CI [1.25-5.02], p = 0.01), oxygen flow at admission (OR 1.07/L, 95% CI [1.00-1.14], p = 0.04) and extra-respiratory symptoms (OR 2.84, 95%CI [1.30-6.21], p = 0.01). After adjustment for the logistic organ dysfunction (LOD) score at admission, only time between respiratory symptoms onset and ICU admission > 2 days and LOD score were independently associated with day-28 mortality. Determinants of death include both factors non-amenable to change, and delay in ARF management. These results suggest that early intensive care management of patients with cancer with ARF may translate to better survival.

Prognosis of acute respiratory distress syndrome in neutropenic cancer patients.

To date, no study has been specifically designed to identify determinants of death in neutropenic cancer patients presenting with acute respiratory distress syndrome (ARDS). The aim of this study was to identify early predictive factors of 28-day mortality in these patients. Factors associated with 28-day mortality during intensive care unit (ICU) stay were also described. 70 consecutive cancer patients with ARDS and neutropenia were prospectively analysed over a 6-yr period. Mortality at 28 days was 63%. Factors independently associated with good prognosis were: lobar ARDS (OR 0.10, 95% CI 0.02-0.48), use of initial antibiotic treatment active on difficult to treat bacteria (ticarcillin-resistant Pseudomonas aeruginosa, Stenotrophomonas maltophilia or extended-spectrum ß-lactamase-producing strains) (OR 0.08, 95% CI 0.02-0.33) and first-line chemotherapy (OR 0.08, 95% CI 0.02-0.37). During the ICU stay, mortality was associated with the markers of organ dysfunctions, the absence of neutropenia recovery and the use of vasopressors. During the first 3 weeks, the conditional probability of discharge alive from ICU did not decrease. At ICU admission, first-line chemotherapy, lobar ARDS and antibiotic treatment active on difficult-to-treat bacteria were associated with survival. During ICU stay, mortality was associated with organ dysfunctions and use of vasopressors. Most survivors have an ICU stay of >3 weeks.

High central venous oxygen saturation in the latter stages of septic shock is associated with increased mortality.

INTRODUCTION: Current guidelines recommend maintaining central venous oxygen saturation (ScvO2) higher than 70% in patients with severe sepsis and septic shock. As high levels of ScvO2 may reflect an inadequate use of oxygen, our aim was to evaluate the relation between maximal ScvO2 levels (ScvO2max) and survival among intensive care unit (ICU) patients with septic shock. METHODS: We retrospectively analyzed data from all admissions to our ICU between January 2008 and December 2009. All septic shock patients in whom the ScvO2 was measured were included. The measures of ScvO2max within the first 72 hours after the onset of shock were collected. RESULTS: A total of 1,976 patients were screened and 152 (7.7%) patients met the inclusion criteria. The level of ScvO2max was 85% (78 to 89) in the non-survivors, compared with 79% (72 to 87) in the survivors (P = 0.009). CONCLUSIONS: Our findings raise concerns about high levels of ScvO2 in patients with septic shock. This may reflect the severity of the shock with an impaired oxygen use. Future strategies may target an optimization of tissue perfusion in this specific subgroup of patients.