IMPORTANCEIn 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 MEASURESThe 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.

Acute kidney injury (AKI) affects up to 60% of intensive care unit (ICU) patients and is associated with mortality rates of between 15 and 60%. Up to two-thirds of patients with AKI go on to require renal replacement therapy (RRT). 1 Without the ability to replace native renal function, mortality from the complications of fluid overload, refractory hyperkalaemia, and metabolic derangement would be far higher. From the 1960s, hollow-fibre dialysers became available as a form of RRT and were able to be mass produced, with Scribner starting the first outpatient dialysis centres in the USA. Haemofiltration, as a form of RRT, began in the 1970s and is now an indispensable tool used as part of modern critical care management. Despite improvements in technologies, there has been only slow improvement in mortality since the 1980s. The reasons postulated for this include the lack of diagnostic tools available to detect early AKI, delayed initiation of RRT, inadequate delivery of RRT, and the inability to replace kidney function fully with current RRT modalities. Little information exists on trends in the epidemiology of AKI; however, there are several reasons to suspect that its incidence is on the rise: the increasing age and comorbidities of the hospitalized population; an increase in the prevalence of risk factors for AKI such as chronic kidney disease and diabetes; and more widespread use of i.v. contrast for cardiovascular and other radiological procedures. Mechanisms of RRT Worldwide, RRT can be provided as peritoneal dialysis, intermittent haemodialysis (IHD), and continuous renal replacement therapy (CRRT), which includes continuous veno-venous haemofiltration (CVVH), continuous veno-venous haemodialysis (CVVHD) and continuous veno-venous haemodiafiltration (CVVHDF). The majority of UK critical care units use either CVVHF or CVVHDF. 2 Some units use hybrid therapies that combine IHD and CRRT; this technique is commonly known as slow low-efficiency daily dialysis. Slow continuous ultrafiltration (SCUF) is an alternative mode of RRT used to control fluid balance particularly in patients with diuretic-unresponsive cardiorenal syndrome. The aims of RRT are solute and water removal, correction of electrolyte abnormalities, and normalization of acid-base disturbances. This is achieved via diffusion or convection which is, respectively, referred to as haemodialysis or haemofiltration. The system comprises an extracorporeal circuit filled by blood arising from a wide-bore double-lumen central venous catheter Key points • Despite improvements in renal replacement therapy (RRT) technology, the mortality associated with acute kidney injury remains high.

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Large randomised controlled trials show no benefit of high intensity renal replacement therapy compared to lower intensity regimens. Previous data suggest large variation in practice. This audit evaluated practices in relation to intensity of replacement therapy in critical care units across the Scottish National Health Service over a 28-day period. The mean delivered weight-adjusted effluent flow rates for continuous veno-venous haemofiltration were 29.1 (8.1 SD) ml kg À1 h À1which was 89% of that prescribed. For continuous veno-venous haemodiafiltration, the mean delivered dose was 41.3 (7.9) ml kg À1 h À1 which was 88.4% of that prescribed. Of the eight patients undergoing intermittent haemodialysis, seven had daily treatments, whilst the eighth had four treatments in five days. The prescription and delivery of renal replacement therapy within Scottish critical care units are routinely performed at an intensity that is higher than necessary. Avoidance of excessive dose could provide important cost savings.