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. 2024 Sep 1;52(9):e463-e472.
doi: 10.1097/CCM.0000000000006315. Epub 2024 Apr 25.

Exploring the Impact of Age, Frailty, and Multimorbidity on the Effect of ICU Interventions: A Systematic Review of Randomized Controlled Trials

Andrew Perrella  1 , Olivia Geen  2 , Manan Ahuja  3 , Stephanie Scott  4 , Ramya Kaushik  5 , Lauren E Ferrante  6 , Nathan E Brummel  7 , John Muscedere  8 , Bram Rochwerg  3   9
Affiliations

Exploring the Impact of Age, Frailty, and Multimorbidity on the Effect of ICU Interventions: A Systematic Review of Randomized Controlled Trials

Andrew Perrella et al. Crit Care Med. .

Abstract

Objectives: To date, age, frailty, and multimorbidity have been used primarily to inform prognosis in older adults. It remains uncertain, however, whether these patient factors may also predict response to critical care interventions or treatment outcomes.

Data sources: We conducted a systematic search of top general medicine and critical care journals for randomized controlled trials (RCTs) examining critical care interventions published between January 1, 2011, and December 31, 2021.

Study selection: We included RCTs of critical care interventions that examined any one of three subgroups-age, frailty, or multimorbidity. We excluded cluster RCTs, studies that did not report interventions in an ICU, and studies that did not report data examining subgroups of age, frailty, or multimorbidity.

Data extraction: We collected study characteristics (single vs. multicountry enrollment, single vs. multicenter enrollment, funding, sample size, intervention, comparator, primary outcome and secondary outcomes, length of follow-up), study population (inclusion and exclusion criteria, average age in intervention and comparator groups), and subgroup data. We used the Instrument for assessing the Credibility of Effect Modification Analyses instrument to evaluate the credibility of subgroup findings.

Data synthesis: Of 2037 unique citations, we included 48 RCTs comprising 50,779 total participants. Seven (14.6%) RCTs found evidence of statistically significant effect modification based on age, whereas none of the multimorbidity or frailty subgroups found evidence of statistically significant subgroup effect. Subgroup credibility ranged from very low to moderate.

Conclusions: Most critical care RCTs do not examine for subgroup effects by frailty or multimorbidity. Although age is more commonly considered, the cut-point is variable, and relative effect modification is rare. Although interventional effects are likely similar across age groups, shared decision-making based on individual patient preferences must remain a priority. RCTs focused specifically on critically ill older adults or those living with frailty and/or multimorbidity are crucial to further address this research question.

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Conflict of interest statement

Dr. Geen received funding from Outro Health. Dr. Ferrante’s institution received funding from the National Institutes of Health (NIH). Dr. Ferrante is supported by a Paul B. Beeson Emerging Leaders in Aging Career Development Award from the National Institute on Aging (K76 AG057203) and the Yale Claude D. Pepper Older Americans Independence Center (P30 AG021342). Drs. Ferrante and Brummel received support for article research from the NIH. Dr. Brummel’s institution received funding from the National Institute on Aging. Dr. Muscedere is the Scientific Director of the Canadian Frailty Network, which is funded by the Government of Canada. Dr. Brummel is supported by the National Institutes of Health under awards R01HD107103 and R01AG077644. The remaining authors have disclosed that they do not have any potential conflicts of interest.

Figures

Figure 1:
Figure 1:
Hypothetical effect on 30-day mortality if older adults respond differently to ICU interventions.
See this image and copyright information in PMC

References

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