Purpose Long-term outcomes of critical illness may be affected by duration of critical illness and intensive care. We aimed to investigate differences in mortality and morbidity after short (<8 days) and prolonged (≥8 days) intensive care unit (ICU) stay.
Methods Former EPaNIC-trial patients were included in this preplanned prospective cohort, 5-year follow-up study. Mortality was assessed in all. For morbidity analyses, all long-stay and—for feasibility—a random sample (30%) of short-stay survivors were contacted. Primary outcomes were total and post-28-day 5-year mortality. Secondary outcomes comprised handgrip strength (HGF, %pred), 6-minute-walking distance (6MWD, %pred) and SF-36 Physical Function score (PF SF-36). One-to-one propensity-score matching of short-stay and long-stay patients was performed for nutritional strategy, demographics, comorbidities, illness severity and admission diagnosis. Multivariable regression analyses were performed to explore ICU factors possibly explaining any post-ICU observed outcome differences.
Results After matching, total and post-28-day 5-year mortality were higher for long-stayers (48.2% (95%CI: 43.9% to 52.6%) and 40.8% (95%CI: 36.4% to 45.1%)) versus short-stayers (36.2% (95%CI: 32.4% to 40.0%) and 29.7% (95%CI: 26.0% to 33.5%), p<0.001). ICU risk factors comprised hypoglycaemia, use of corticosteroids, neuromuscular blocking agents, benzodiazepines, mechanical ventilation, new dialysis and the occurrence of new infection, whereas clonidine could be protective. Among 276 long-stay and 398 short-stay 5-year survivors, HGF, 6MWD and PF SF-36 were significantly lower in long-stayers (matched subset HGF: 83% (95%CI: 60% to 100%) versus 87% (95%CI: 73% to 103%), p=0.020; 6MWD: 85% (95%CI: 69% to 101%) versus 94% (95%CI: 76% to 105%), p=0.005; PF SF-36: 65 (95%CI: 35 to 90) versus 75 (95%CI: 55 to 90), p=0.002).
Conclusion Longer duration of intensive care is associated with excess 5-year mortality and morbidity, partially explained by potentially modifiable ICU factors.
Trail registration number NCT00512122.
- critical illness
- long-term outcomes
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GH and NVA contributed equally.
Contributors Study concept and design: GH and GVdB. Acquisition of data: GH, HVM, PM, YD, AW, JG, JD and PW. Analysis and interpretation of data: GH, NVA and GVdB. Drafting of the manuscript: GH, NVA and GVdB. Critical revision of the manuscript for important intellectual content: GH, NVA, PM, HVM, YD, AW, JG, MPC, JD, RG, PW and GVdB. Statistical analysis: GH, NVA and GVdB. Obtained funding: GH, NVA and GVdB. Administrative, technical support: PW. Study supervision: GH, HVM, PW and GVdB.
Funding This work was supported by the Fund for Scientific Research, Flanders Belgium (grant G.0399.12 to GH; Fundamental Clinical Research fellowship to GH: 1805116N, MC: 1700111N; aspirant PhD fellowship to NVA: 1131618N), the clinical research fund (KOF) of the University Hospitals Leuven, Belgium (postdoctoral research fellowship to JG); the Methusalem program of the Flemish Government (METH/08/07 which has been renewed as METH/14/06 via KU Leuven) to GVdB; the European Research Council ERC Advanced grants (AdvG-2012-321670 from the Ideas Program of the EU FP7 and AdvG-2017-785809 from the Horizon 2020 Program of the EU) to GVdB. The authors have no conflict of interest with the sponsors of the study.
Competing interests None declared.
Patient consent for publication Not required.
Ethics approval The study protocol and informed consent forms were approved by the Leuven University Hospital Ethics Committee (ML4190). Patients gave separate informed consent for the five-year morbidity evaluations.
Provenance and peer review Not commissioned; externally peer reviewed.
Data availability statement Data sharing is offered under the format of collaborative projects. Proposals can be directed to the senior author (GVdB).