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Background Acute hypoxaemic respiratory failure requiring mechanical ventilation is a major cause of morbidity and mortality and has significant resource implications in terms of intensive care unit and hospital stay. Objective To assess the cost-effectiveness of extracorporeal carbon dioxide removal compared to ventilation alone in patients with acute hypoxaemic respiratory failure. Design A cost-utility analysis embedded within a pragmatic, multicentre, allocation-concealed, open-label, randomised controlled trial. Participants Four hundred and twelve (of a planned sample size of 1120) adult patients receiving mechanical ventilation for acute hypoxaemic respiratory failure, were recruited between May 2016 and December 2019 from 51 intensive care units in the UK. Interventions Participants were randomised (1 : 1) to receive extracorporeal carbon dioxide removal for at least 48 hours (n = 202) or standard care with ventilation alone (n = 210). Outcomes Health-related quality of life via the EuroQol-5 Dimensions, five-level version, health resource use and associated costs were measured over the study period. The cost per quality-adjusted life-year was estimated at 12 months post randomisation. Results Mean EuroQol-5 Dimensions, five-level version utility scores were low and similar for each group. Quality-adjusted life-years were calculated for those patients with complete EuroQol-5 Dimensions, five-level version data (extracorporeal carbon dioxide removal n = 140, ventilation alone n = 143) and there was no discernible difference in quality-adjusted life-years at 12 months (mean difference –0.01; 95% confidence interval –0.06 to 0.05; 140). Total 12-month health resource use cost (including intervention costs) was calculated for those patients with complete cost data (extracorporeal carbon dioxide removal n = 125, ventilation alone n = 126) and costs were statistically significantly higher in the extracorporeal carbon dioxide removal group (mean difference £7668.76, 95% confidence interval 159.75, 15,177.77). Multiple imputation was used for missing total cost and quality-adjusted life-year data in the cost-utility analysis. Ventilation alone dominated extracorporeal carbon dioxide removal and there was 0% probability of extracorporeal carbon dioxide removal being cost-effective compared to ventilation alone for all willingness to pay thresholds per quality-adjusted life-year considered (£0–50,000). Conclusions Extracorporeal carbon dioxide removal was associated with significantly higher costs, but no benefit in health-related quality of life. Given the data, extracorporeal carbon dioxide removal is not considered to be a cost-effective approach to treating patients with acute hypoxaemic respiratory failure. Limitations These included the absence of a baseline healthy utility score, minor data loss related to not obtaining complete intensive care unit readmission data for Scottish participants, and not estimating long-term cost-effectiveness due to the study closing early. Future work Measuring baseline health-related quality of life in critical care studies is difficult; future economic evaluations in this setting should consider measuring health-related quality of life as soon as possible after the patients regain capacity. Trial registration This trial is registered as NCT02654327 and ISRCTN 31262122. Funding This article presents independent research funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme as award number 13/143/02.

Background: Recovery following critical illness is complex due to the many challenges patients face which influence their long-term outcomes. We explored patients' views about facilitators of recovery after critical illness which could be used to inform the components and timing of specific rehabilitation interventions. Aims: To explore the views of patients after discharge from an intensive care unit (ICU) about their recovery and factors that facilitated recovery, and to determine additional services that patients felt were missing during their recovery. Methods: Qualitative study involving individual face-to-face semi-structured interviews at six months (n = 11) and twelve months (n = 10). Written, informed consent was obtained. [Ethics approval 17/NI/0115]. Interviews were audiotaped, transcribed and analysed using template analysis. Findings: Template analysis revealed four core themes: (1) Physical activity and function; (2) Recovery of cognitive and emotional function; (3) Facilitators to recovery; and (4) Gaps in healthcare services. Conclusion: Patient reported facilitators to recovery include support and guidance from others and self-motivation and goal setting, equipment for mobility and use of technology. Barriers include a lack of follow up services, exercise rehabilitation, peer support and personal feedback. Patients perceived that access to specific healthcare services was fragmented and where services were unavailable this contributed to slower or poorer quality of recovery. ICU patient recover could be facilitated by a comprehensive rehabilitation intervention that includes patient-directed strategies and health care services. [ABSTRACT FROM AUTHOR]

The article focuses on assessing the heterogeneous treatment effects of extracorporeal CO2 removal (ECCO2R) in acute hypoxemic respiratory failure. Topics include the evaluation of patient subgroups with differing treatment effects, the use of machine learning to predict treatment outcomes, and the identification of patients who may benefit from ECCO2R.

Background: Dead space and respiratory system elastance (Ers) may influence the clinical benefit of a ventilation strategy combining very low tidal volume (VT) with extracorporeal carbon dioxide removal (ECCO2R) in patients with acute hypoxemic respiratory failure. We sought to evaluate whether the effect of ECCO2R on mortality varies according to ventilatory ratio (VR; a composite variable reflective of dead space and shunt) and Ers. Methods: Secondary analysis of a trial of a strategy combining very low VT and low-flow ECCO2R planned before the availability of trial results. Bayesian logistic regression was used to estimate the posterior probability of effect moderation by VR, Ers, and severity of hypoxemia (ratio of arterial partial pressure of oxygen to fraction of inspired oxygen [PaO2:FiO2]) on 90-day mortality. Credibility of effect moderation was appraised according to the Instrument for Assessing the Credibility of Effect Modification Analyses criteria. Results: A total of 405 patients were available for analysis. The effect of the intervention on mortality varied substantially with VR (posterior probability of interaction, 94%; high credibility). Benefit was more probable than harm in patients with VR 3 or higher. In patients with VR less than 3, the probability of increased mortality with intervention was high (>90%). The effect of the intervention also varied with PaO2:FiO2 (posterior probability of interaction, >99%; low credibility). Benefit was more probable than harm in patients with PaO2:FiO2 110 mm Hg or higher. The effect of the intervention did not vary substantially with Ers (posterior probability of interaction, 68%; low credibility). Conclusions: VR has a highly credible influence on the effect of a strategy combining very low VT and low-flow ECCO2R on mortality. This intervention may reduce mortality in patients with high VR. (Funded by an Early Career Investigator Award from the Canadian Institutes of Health Research to Dr. Goligher.) [ABSTRACT FROM AUTHOR]

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.Trial Registration: ClinicalTrials.gov Identifier: NCT02654327. [ABSTRACT FROM AUTHOR]

Importance: For hospitalized critically ill adults with suspected sepsis, procalcitonin (PCT) and C-reactive protein (CRP) monitoring protocols can guide the duration of antibiotic therapy, but the evidence of the effect and safety of these protocols remains uncertain., Objective: To determine whether decisions based on assessment of CRP or PCT safely results in a reduction in the duration of antibiotic therapy., Design, Setting, and Participants: A multicenter, intervention-concealed randomized clinical trial, involving 2760 adults (≥18 years), in 41 UK National Health Service (NHS) intensive care units, requiring critical care within 24 hours of initiating intravenous antibiotics for suspected sepsis and likely to continue antibiotics for at least 72 hours., Intervention: From January 1, 2018, to June 5, 2024, 918 patients were assigned to the daily PCT-guided protocol, 924 to the daily CRP-guided protocol, and 918 assigned to standard care., Main Outcomes and Measures: The primary outcomes were total duration of antibiotics (effectiveness) and all-cause mortality (safety) to 28 days. Secondary outcomes included critical care unit data and hospital stay data. Ninety-day all-cause mortality was also collected., Results: Among the randomized patients (mean age 60.2 [SD, 15.4] years; 60.3% males), there was a significant reduction in antibiotic duration from randomization to 28 days for those in the daily PCT-guided protocol compared with standard care (mean duration, 10.7 [SD, 7.6] days for standard care and 9.8 [SD, 7.2] days for PCT; mean difference, 0.88 days; 95% CI, 0.19 to 1.58, P = .01). For all-cause mortality up to 28 days, the daily PCT-guided protocol was noninferior to standard care, where the noninferiority margin was set at 5.4% (19.4% [170 of 878] of patients receiving standard care; 20.9% [184 of 879], PCT; absolute difference, 1.57; 95% CI, -2.18 to 5.32; P = .02). No difference was found in antibiotic duration for standard care vs daily CRP-guided protocol (mean duration, 10.6 [7.7] days for CRP; mean difference, 0.09; 95% CI, -0.60 to 0.79; P = .79). For all-cause mortality, the daily CRP-guided protocol was inconclusive compared with standard care (21.1% [184 of 874] for CRP; absolute difference, 1.69; 95% CI, -2.07 to 5.45; P = .03)., Conclusions and Relevance: Care guided by measurement of PCT reduces antibiotic duration safely compared with standard care, but CRP does not. All-cause mortality for CRP was inconclusive., Trial Registration: isrctn.org Identifier: ISRCTN47473244.