Risk factors for acute organ failure in intensive care unit patients who receive respiratory support in the absence of non-respiratory organ failure: an international prospective cohort study

Introduction: Many supposed low-risk intensive care unit (ICU) admissions develop acute organ failure (AOF). Identifying patients at high risk of developing AOF and targeting them with preventative strategies may be effective. Our study question was: in a population of ICU patients receiving positive pressure respiratory support (invasive or non-invasive) in the absence of non-respiratory AOF, what is the 14-day incidence of, risk factors for and time to acute organ failure?Methods: In an international prospective cohort study, patients receiving positive pressure respiratory support (invasive or non-invasive) in the absence of non-respiratory AOF were enrolled and followed for 14 days. The primary outcome measure was the incidence of any AOF (defined as SOFA 3 to 4) during follow-up.Results: A total of 123 of 766 screened patients (16.1%) were enrolled. Data are reported for 121 patients. In total, 45 out of 121 patients (37.2%) developed AOF. Mortality rates were higher in those with AOF: 17.8% versus 4.0% OR 5.11, P = 0.019) for ICU mortality; and 28.9% versus 11.8% (OR 2.80, P = 0.019) for hospital mortality. Median ICU length of stay was also longer in those with AOF (11 versus 3.0 days; P < 0.0001). Hypoxemic respiratory failure (P = 0.001) and cardiovascular dysfunction (that is, SOFA 1 to 2; P = 0.03) were associated with AOF. The median time to first AOF was two days.Conclusions: Patients receiving positive (invasive or non-invasive) pressure respiratory support in the absence of non-respiratory AOF are commonly admitted to ICU; AOF is frequent in these patients. Organ failure developed within a short period after admission. Hypoxemic respiratory failure and cardiovascular dysfunction were strongly associated with AOF

Effect of lower tidal volume ventilation facilitated by extracorporeal carbon dioxide removal vs standard care ventilation on 90-day mortality in patients with acute hypoxemic respiratory failure

Importance In patients who require mechanical ventilation for acute hypoxemic respiratory failure, further reduction in tidal volumes, compared with conventional low tidal volume ventilation, may improve outcomes. Objective To determine whether lower tidal volume mechanical ventilation using extracorporeal carbon dioxide removal improves outcomes in patients with acute hypoxemic respiratory failure. Design, Setting, and Participants This multicenter, randomized, allocation-concealed, open-label, pragmatic clinical trial enrolled 412 adult patients receiving mechanical ventilation for acute hypoxemic respiratory failure, of a planned sample size of 1120, between May 2016 and December 2019 from 51 intensive care units in the UK. Follow-up ended on March 11, 2020. Interventions Participants were randomized to receive lower tidal volume ventilation facilitated by extracorporeal carbon dioxide removal for at least 48 hours (n = 202) or standard care with conventional low tidal volume ventilation (n = 210). Main Outcomes and Measures The primary outcome was all-cause mortality 90 days after randomization. Prespecified secondary outcomes included ventilator-free days at day 28 and adverse event rates. Results Among 412 patients who were randomized (mean age, 59 years; 143 [35%] women), 405 (98%) completed the trial. The trial was stopped early because of futility and feasibility following recommendations from the data monitoring and ethics committee. The 90-day mortality rate was 41.5% in the lower tidal volume ventilation with extracorporeal carbon dioxide removal group vs 39.5% in the standard care group (risk ratio, 1.05 [95% CI, 0.83-1.33]; difference, 2.0% [95% CI, −7.6% to 11.5%]; P = .68). There were significantly fewer mean ventilator-free days in the extracorporeal carbon dioxide removal group compared with the standard care group (7.1 [95% CI, 5.9-8.3] vs 9.2 [95% CI, 7.9-10.4] days; mean difference, −2.1 [95% CI, −3.8 to −0.3]; P = .02). Serious adverse events were reported for 62 patients (31%) in the extracorporeal carbon dioxide removal group and 18 (9%) in the standard care group, including intracranial hemorrhage in 9 patients (4.5%) vs 0 (0%) and bleeding at other sites in 6 (3.0%) vs 1 (0.5%) in the extracorporeal carbon dioxide removal group vs the control group. Overall, 21 patients experienced 22 serious adverse events related to the study device. Conclusions and Relevance Among patients with acute hypoxemic respiratory failure, the use of extracorporeal carbon dioxide removal to facilitate lower tidal volume mechanical ventilation, compared with conventional low tidal volume mechanical ventilation, did not significantly reduce 90-day mortality. However, due to early termination, the study may have been underpowered to detect a clinically important difference