The timing of renal-replacement therapy in critically ill patients who have acute kidney injury but no potentially life-threatening complication directly related to renal failure is a subject of ...debate.
In this multicenter randomized trial, we assigned patients with severe acute kidney injury (Kidney Disease: Improving Global Outcomes KDIGO classification, stage 3 stages range from 1 to 3, with higher stages indicating more severe kidney injury) who required mechanical ventilation, catecholamine infusion, or both and did not have a potentially life-threatening complication directly related to renal failure to either an early or a delayed strategy of renal-replacement therapy. With the early strategy, renal-replacement therapy was started immediately after randomization. With the delayed strategy, renal-replacement therapy was initiated if at least one of the following criteria was met: severe hyperkalemia, metabolic acidosis, pulmonary edema, blood urea nitrogen level higher than 112 mg per deciliter, or oliguria for more than 72 hours after randomization. The primary outcome was overall survival at day 60.
A total of 620 patients underwent randomization. The Kaplan-Meier estimates of mortality at day 60 did not differ significantly between the early and delayed strategies; 150 deaths occurred among 311 patients in the early-strategy group (48.5%; 95% confidence interval CI, 42.6 to 53.8), and 153 deaths occurred among 308 patients in the delayed-strategy group (49.7%, 95% CI, 43.8 to 55.0; P=0.79). A total of 151 patients (49%) in the delayed-strategy group did not receive renal-replacement therapy. The rate of catheter-related bloodstream infections was higher in the early-strategy group than in the delayed-strategy group (10% vs. 5%, P=0.03). Diuresis, a marker of improved kidney function, occurred earlier in the delayed-strategy group (P<0.001).
In a trial involving critically ill patients with severe acute kidney injury, we found no significant difference with regard to mortality between an early and a delayed strategy for the initiation of renal-replacement therapy. A delayed strategy averted the need for renal-replacement therapy in an appreciable number of patients. (Funded by the French Ministry of Health; ClinicalTrials.gov number, NCT01932190.).
The role of extracorporeal membrane oxygenation (ECMO) remains ill defined in pulmonary embolism (PE). We investigated outcomes in patients with high-risk PE undergoing ECMO according to initial ...therapeutic strategy.
From 01 January 2014 to 31 December 2015, 180 patients from 13 Departments in nine centres with high-risk PE were retrospectively included. Among those undergoing ECMO, we compared characteristics and outcomes according to adjunctive treatment strategy (systemic thrombolysis, surgical embolectomy, or no reperfusion therapy). Primary outcome was all-cause 30-day mortality. Secondary outcome was 90-day major bleeding. One hundred and twenty-eight patients were treated without ECMO; 52 (mean age 47.6 years) underwent ECMO. Overall 30-day mortality was 48.3% 95% confidence interval (CI) 41-56 (87/180); 43% (95% CI 34-52) (55/128) in those treated without ECMO vs. 61.5% (95% CI 52-78) (32/52) in those with ECMO (P = 0.008). In patients undergoing ECMO, 30-day mortality was 76.5% (95% CI 57-97) (13/17) for ECMO + fibrinolysis, 29.4% (95% CI 51-89) (5/17) for ECMO + surgical embolectomy, and 77.7% (95% CI 59-97) (14/18) for ECMO alone (P = 0.004). Among patients with ECMO, 20 (38.5%, 95% CI 25-52) had a major bleeding event in-hospital; without significant difference across groups.
In patients with high-risk PE, those with ECMO have a more severe presentation and worse prognosis. Extracorporeal membrane oxygenation in patients with failed fibrinolysis and in those with no reperfusion seems to be associated with particularly unfavourable prognosis compared with ECMO performed in addition to surgical embolectomy. Our findings suggest that ECMO does not appear justified as a stand-alone treatment strategy in PE patients, but shows promise as a complement to surgical embolectomy.
Purpose
To report four cases of life-threatening COVID-19 pneumonia in patients with high blood concentrations of neutralizing autoantibodies against type I interferons (IFNs), who were treated with ...plasma exchange (PE) as a rescue therapy.
Methods
Prospective case series, which included patients, diagnosed with RT-PCR-confirmed SARS-CoV-2 infection and positive autoantibodies against type I IFNs in two French intensive care units (ICUs) between October 8 and November 14, 2020. Six critically ill COVID-19 patients with no anti-IFN antibodies were used as controls. Anti-IFN autoantibodies and IFN concentrations, together with the levels of anti-SARS-CoV-2 antibodies, were measured sequentially in serum. Viral load was determined in the upper and lower respiratory tract. Patients were followed during hospital stay.
Results
Three men and one woman were included. Three of the patients had four PE sessions each, while another had three PE sessions. PE decreased the concentrations of autoantibodies against type I IFN in all four patients, whereas anti-SARS-CoV-2 antibody levels remained stable. Autoantibodies against type I IFN levels were high in tracheal aspirates of one patient and decreased after three PE sessions. By contrast, anti-IFN autoantibodies were not detected in tracheal aspirates from five control patients without detectable anti-IFN autoantibodies in serum. During PE, serum IFN-α levels slightly increased in three out of four patients, and upper respiratory tract viral load decreased in all patients. All patients were alive at day 28 of ICU admission. Two patients eventually died in the ICU, while the two survivors were discharged from the ICU at days 50 and 66.
Conclusions
PE efficiently removes autoantibodies against type I IFNs, including those detected in tracheal aspirates, without affecting anti-SARS-CoV-2 antibody levels, in patients with life-threatening COVID-19 pneumonia. The clinical benefit of PE in patients with autoantibodies against type I IFNs should be tested in a larger study.
Background
Growing evidence associates organ dysfunction(s) with impaired metabolism in sepsis. Recent research has increased our understanding of the role of substrate utilization and mitochondrial ...dysfunction in the pathophysiology of sepsis-related organ dysfunction. The purpose of this review is to present this evidence as a coherent whole and to highlight future research directions.
Main text
Sepsis is characterized by systemic and organ-specific changes in metabolism. Alterations of oxygen consumption, increased levels of circulating substrates, impaired glucose and lipid oxidation, and mitochondrial dysfunction are all associated with organ dysfunction and poor outcomes in both animal models and patients. The pathophysiological relevance of bioenergetics and metabolism in the specific examples of sepsis-related immunodeficiency, cerebral dysfunction, cardiomyopathy, acute kidney injury and diaphragmatic failure is also described.
Conclusions
Recent understandings in substrate utilization and mitochondrial dysfunction may pave the way for new diagnostic and therapeutic approaches. These findings could help physicians to identify distinct subgroups of sepsis and to develop personalized treatment strategies. Implications for their use as bioenergetic targets to identify metabolism- and mitochondria-targeted treatments need to be evaluated in future studies.
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