Frailty as a Prognostic Indicator in Intensive Care

Background: The percentage of patients in intensive care who are 80 years old or older is continually increasing. Such patients already made up more than 20% of all patients in intensive care in Germany in the years 2007–2011. Meanwhile, effective treatments that support the organs of the body and keep severely ill patients alive are also being continually developed and refined. Frailty is a key prognostic parameter. The scientifically based assessment of frailty can be highly useful in intensive care medicine with regard to consented decision-making, individualized prognostication, treatment planning, and aftercare.

Methods: Pertinent publications were retrieved by a selective search in the PubMed database. On the basis of the literature assessment, a variety of screening instruments were used to assess frailty and its significance for very old, critically ill patients in German intensive care units.

Results: Only a small number of screening instruments are suitable for routine use in German intensive care units. The scores vary in diagnostic precision. The Clinical Frailty Scale (CFS) enables highly accurate prognostication; it considers the patient in relation to his or her social environment, and to the reference population. Categorization is achieved by means of pictograms that are supplemented with brief written descriptions. The CFS can be used prospectively and is easy to learn. Its interrater reliability is high (weighted Cohen’s κ: 0.85 [0.84; 0.87]), and it has been validated for routine use in intensive care units in Germany.

Conclusion: None of the available scores enable perfect prognostication. In Germany, frailty in intensive-care patients is currently best assessed on a simple visual scale (CFS).

The very old (aged 80 years and over) and the old (65 and over) constitute a growing subgroup of intensive care patients. It is estimated that by the year 2030, more than 25% of the population of western Europe will be in the 65+ age group (1). In Austria, the proportion of very old intensive care patients rose from 11.5% in 1998 to 15.3% in 2008 (2). Another study found that more than 20% of German intensive care patients were aged 80 or over in the period 2007 to 2011 (3). Comparable increases have been observed in Denmark, the Netherlands, and Australia (e1, e2, e3). In Scandinavia, the proportion of very old patients in intensive care is expected to rise to 36% by 2025 (e4).

An estimated 25 to 50% of patients aged ≥ 80 years are classified as frail (e5). The WHO defines frailty as a clinically discernible state in which the ability of older persons to cope with both routine and acute stressors is reduced. Advanced age is not, however, synonymous with frailty; rather, many different factors are involved (e6). The cumulative molecular and cellular damage caused by genetic, epigenetic, and environmental factors results in a reduced physiological reserve, potentially affecting all organ systems (Figure). These aging processes vary in pace of progress and take place over a period of decades. This leads to considerable biological and functional heterogeneity among very old patients (e7). It is not always easy to distinguish frailty from multimorbidity. Large clinical studies have shown that multimorbidity—measured using a comorbidity and polypharmacy score (CPS) (e8)—alone has no predictive value for 30-day mortality in acutely critically ill elderly patients (4).

Figure

Pathophysiological processes in connection with the development and consequences of frailty. (modified from Clegg et al. [e5])

Frail patients have a much greater degree of functional impairment than non-frail patients following critical illness and are more likely to have to be admitted to a care home (5, e9). Overall, frail patients run a much higher risk of morbidity and mortality than non-frail patients of the same age (5). Intensive care personnel have a particular responsibility to assess the prognosis of elderly critically ill patients. A subgroup analysis of the ELDICUS study showed that the relative benefit—that is, the difference in mortality between patients with and without intensive care treatment—is greatest in the very old (2.3% in the age group 18 to 44 years versus 17% in those over 84 years) (1). This relative advantage existed despite initially comparable results on the intensive care scores used to measure severity of illness (SOFA, APACHE, SAPS II). This finding underlines the fact that these established instruments do not capture all relevant dimensions, in that they do not take sufficient account of the functional heterogeneity of this age group (6).

Alongside documentation of the acute illness that has led to intensive care admission and its specific prognosis, assessment of frailty can help to evaluate the overall prognosis and assist in planning individual patient-specific treatment measures at various times: it can make a contribution to the assessment of the patient’s status prior to the acute illness that resulted in hospital admission. Thus, from the time of admission to intensive care onward, the evaluation of frailty can help to estimate the long-term prognosis, assess the patient’s capacity for rehabilitation after intensive care, and (re)evaluate the utility of continued intensive care treatment (e10). The focal point should be agreement with the patient and their family members about the course of action to be pursued. In common with every other medical decision, this evaluation should follow the principles of doing good (“bonum facere”), doing no harm (“non nocere”), and acting according to the patient’s wishes (“voluntas aegroti suprema lex” [“the will of the patient is paramount”]). Numerous instruments have been designed to this end, differing with regard to the underlying concepts, the information needed for scoring purposes, and clinical validation. No randomized controlled trial has yet demonstrated that development of a score is associated with a survival benefit. Nevertheless, frailty is, independently of the specific acute illness, a predictor for survival, complication rate, and quality of life after intensive care treatment (8).

This review follows on from the articles on frailty published in Deutsches Ärzteblatt International by Mende et al. and Olotu et al. (9, 10). While Mende et al. (9) provided an excellent overview of the many different screening instruments available, Olotu et al. (10) elucidated the role of frailty in perioperative medicine. In this review article we explore the significance of frailty for the prognosis and for treatment planning in critically ill patients of advanced age and discuss the suitability of various established screening methods for use in German intensive care units. Since documentation and administrative tasks already take up much of the working time of intensivists, one important aspect is whether swift and reliable assessment of frailty can feasibly be integrated into the daily intensive care routine in Germany.

Method

For the purposes of this review we conducted a selective search of the PubMed database, including original articles, national and international guidelines, meta-analyses, and selective reviews. Analysis was restricted to records published between January 2000 and 28 March 2020. The search criteria and search terms are presented in eBox 1.

eBox 1

Literature search

eBox 2

Modified frailty index (mFI)

Results

Screening methods

The concepts behind the various operationalized measurements for quantification of frailty differ from one another, in some cases widely (e11, 11). For this reason, a large number of different instruments have been developed for qualitative and quantitative classification of individual frailty. A overview of the instruments discussed herein is provided in Table 1. A more detailed synopsis can be found in the article by Mende et al. (9). The scores differ—from study to study—in their diagnostic accuracy. None of the scores enables prediction of the prognosis with absolute certainty. The diagnostic characteristics of the screening methods discussed herein, as depicted in selected studies with the emphasis on intensive care, are presented in Table 2 and the eTable.

Table 1

Techniques for screening of frailty

Table 2

Selected studies on instruments for frailty screening that are relevant for German intensive care units*

eTable

Diagnostic characteristics of the individual instrument in further selected studies with no immediate relevance for German intensive care units*

Fried’s phenotype

Fried’s phenotype of frailty (FP) is based on five criteria of individual functional capacity (12):

• Unintentional loss of weight
• General exhaustion
• Lack of muscle strength
• Slow walking speed
• Reduced physical activity

One point is assigned for each criterion fulfilled. A patient who scores 0 points is classified as robust, 1–2 points as prefrail, and ≥ 3 points as frail. The FP was recently validated prospectively in old (≥ 70 years) intensive care patients (5): long-term follow-up showed that among all patients who left the intensive care unit alive, those who were frail had a significantly higher incidence of both lasting dependence of care and mortality. A limitation of the FP is the necessity for active participation by the patient, which is not possible for the critically ill.

FRAIL scale

The FRAIL scale is based on Fried’s phenotype and, like the FP, asks about the following:

• Fatigue
• Resistance (muscle strength, ability to walk up one flight of stairs)
• Ambulation (ability to walk 100 m)
• Illnesses (more than five)
• Loss of weight (> 5 % or 5 kg in previous 6 months)

The score is evaluated as for the FP. The difference from the FP is that the items are verifiable (13). This score has been validated in various studies (all in the USA) (e12, 14). A study on intensive care patients ≥  65 years of age revealed that—with comparable SOFA scores—mortality at 1 month and at 6 months was higher in patients classified as frail using the FRAIL scale (15). The FRAIL scale has not yet been validated for German intensive care units.

Frailty index, modified frailty index, and electronic frailty index

Frailty indexes (FI) are models for measuring cumulative deficits. They are based on symptoms, clinical signs, illnesses, and laboratory test results that have been identified as deficits for the frail patient. Originally, 70 to 92 variables were defined (16). Each variable must be biologically plausible, must increase with age, and must not be fulfilled by all patients at too young an age (17). The difference between FI and the derivative electronic frailty index (eFI) is that FI require the patients themselves to complete an exhaustive questionnaire, while the eFI evaluates routinely available digital data (18). Subsequent studies succeeded in reducing the variables to 11 items (modified frailty index, mFI) (Table 2) with no loss of accuracy (19). A modified FI with 52 criteria was used in patients ≥ 65 years in Chinese intensive care units. Depending on the cut-off, this FI predicted 30-day mortality with high accuracy (e13). These findings were replicated in another study (e14). However, the results are very difficult to transfer to the situation in Germany. One problem is that many studies use different FI. Both FI and the eFI are time-consuming and require data that are generally not available at the time of admission to the intensive care unit. There is currently no validation for German intensive care units.

Hospital Frailty Risk Score

The Hospital Frailty Risk Score (HFRS), derived from the eFI, uses ICD-10 codes to estimate frailty (20). By means of a cluster analysis in older patients who displayed higher mortality and morbidity than others of the same age, Gilbert et al. identified 109 ICD-10 codes that were overrepresented in this cohort. Every individual ICD code was weighted differently. A score of >5 equated to intermediate risk of frailty, and >15 to high risk. The studies that investigated the HFRS were predominantly retrospective analyses (20). In most cases the admitting physician in Germany has no access to a list of the patient’s ICD-10 codes. Studies have shown that the HFRS yields no additional benefit for the estimation of mortality (21, 22). Overall, the data indicate that the HFRS is neither practicable nor of prognostic utility in Germany.

Clinical Frailty Scale

The Clinical Frailty Scale (CFS) is based on the FI, correlates well with it, and is a greatly simplified instrument (23). Moreover, the CFS has been modified specifically for use in intensive care units (24). The CFS looks at the patient’s social environment (“needs help with washing”) and compares them to the reference population (“much fitter than others in their age group”). This distinguishes the CFS from the FP, which, for its part, looks more closely at sarcopenia—a syndrome complementary to frailty with many features in common (25). Different levels of frailty are represented in pictograms (1 = very fit, ≥ 5 = frail, 9 = terminally ill). The pictograms have been translated into German with the involvement of the German Society of Geriatrics (Deutsche Gesellschaft für Geriatrie; DGG) and are available free of charge (www.uniklinik-duesseldorf.de/cfs).

The CFS integrates both physical and cognitive elements and also delivers brief written descriptions. A statement (secondary medical history) from a family member or care provider is generally necessary for classification, although assessment also functions reliably without the involvement of relatives (26). The CFS has been successfully validated for patients above 50 years of age (8). In intensive care patients, the CFS with a cut-off of ≥ 5 is equivalent to the SAPS 3 intensive care score for prediction of 30-day survival (27). Even after adjustment for SAPS 3, CFS remained a strong independent predictor of 30-day mortality. In intensive care patients over 65 with initially identical SOFA and SAPS II scores, CFS (cut-off ≥ 5) is superior to both FP and conventional intensive care scores (SOFA, SAPS II) in prediction of 6-month mortality (25). In a subgroup analysis from an international multicenter prospective study, the CFS in German intensive care units was also independently associated with the prognosis (28). An exhaustive meta-analysis confirmed both the practicability and the informative value of the CFS in the field of intensive care (29). The CFS possesses “almost perfect” inter-rater reliability when evaluated by several different persons (weighted Cohen’s κ 0.85; 95% confidence interval [0.84; 0.87]) (4). The assessment of the intensive care team does not differ significantly from that of the geriatric consultant (30). In emergency patients, too, the CFS has high predictive power for 30-day mortality and hospitalization as well as good inter-rater reliability (weighted Cohen’s κ 0.74; [0.64; 0.85]) (31). The CFS can also be used in patients with dementia syndrome. It has not been validated, however, in patients with stable permanent disabilities, such as infantile brain damage. This must be taken into account when assigning patients with dementia syndrome to levels 1 to 9. The extent to which the patient needs assistance with activities of daily life is crucial. Assessment by means of FP is more complex than with CFS, but the predictive power of the latter is equivalent or inferior (25, 32). The two scores show high correlation.

In summary, the CFS—used prospectively or retrospectively—has been validated for the intensive care setting, is simple to use, and assesses a patient’s frailty with high reliability despite the low consumption of resources (classification by means of pictograms). Use of the CFS has been recommended by the National Institute for Health and Care Excellence (e15). In Germany, the DGG and the German Interdisciplinary Association for Intensive Care and Emergency Medicine (Deutsche Interdisziplinäre Vereinigung für Intensiv- und Notfallmedizin; DIVI) have translated and annotated the CFS. The suitability of the CFS for prediction of the prognosis in COVID-19 in the intensive care setting is currently being assessed in a multicenter prospective study (NCT04321265).

Other scores

Large prospective multicenter studies have shown that the use of other scores ascertaining cognitive performance (IQCODE) and the extent of independence in performing daily tasks (Katz Index of Independence for Activities of Daily Living) in more detail yield no additional benefit relative to the CFS (4). Attempts have been made to identify suitable biomarkers for frailty (“frailty troponin”) (33). The decisive processes that have to be elucidated for this purpose in laboratory tests are inflammation, mitochondrial function, calcium homeostasis, markers of fibrosis, neuronal damage, and markers of the cytoskeleton. To date, no single marker for the degree of frailty has been pinpointed (e16). With the exception of clinical studies, these approaches are not currently being pursued in intensive care.

Summary

Frailty is a powerful independent predictor of the short-term and long-term prognosis of very old patients in the intensive care setting. A number of instruments are available for assessment of frailty, but the bulk of them are of limited applicability, if at all, in German intensive care units (eTable) (15, 22, 30, 31, 32, 35, 36, 37, 38, e9, e13, e14). The CFS, with its superior practicability and good prediction of the prognosis, has proved useful for routine application in intensive care units.

Conflict of interest statement
The authors declare that no conflict of interest exists.

Manuscript received on 31 March 2020, revised version accepted on
9 June 2020

Translated from the original German by David Roseveare

Corresponding author
Prof. Dr. Dr. med. Christian Jung
Klinik für Kardiologie, Pulmonologie und Angiologie
Medizinische Fakultät
Universitätsklinikum der Heinrich-Heine-Universität Düsseldorf
Moorenstr. 5, 40225 Düsseldorf, Germany

Cite this as
Jung C, Bruno RR, Wernly B, Wolff G, Beil M, Kelm M: Frailty as a prognostic indicator in intensive care. Dtsch Arztebl Int 2020; 117: 668–73. DOI: 10.3238/arztebl.2020.0668

►Supplementary material

For eReferences please refer to:
www.aerzteblatt-international.de/ref4020

eBoxes, eTable:
www.aerzteblatt-international.de/20m0668

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This article has been certified by the North Rhine Academy for Continuing Medical Education. The questions on this article can be found at http://daebl.de/RY95. The deadline for submission is 1 October 2021

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