Frailty as a predictor of adverse outcomes in burn patients: a systematic review

Background The identification of new prognostic tools for the prediction of burn patients’ morbidity outcomes is necessary. Considering the feasibility of frailty assessment in the clinical setting, we aim to systematically review the literature on the associations between frailty and adverse outcomes in burn patients. Methods Studies were retrieved from MEDLINE (through PubMed), Web of Science, Scopus, and Embase from their inception up to 8 September 2022. Included studies were those that used frailty indices to predict adverse outcomes in burn patients. The quality assessment was done using the National, Heart, Lung, and Blood Institute (NHLBI) checklist. The results were synthesized narratively. Results We included 18 studies. The sample size among the included studies varied between 42–1615 patients. There were 12 research articles and 6 conference abstracts. Most of the studies were recently published in 2021 and 2022. Seven different frailty measures were evaluated. The following frailty measures were used: Canadian Study for Health and Ageing (CSHA) Clinical Frailty score (CFS), Modified frailty index-11 (mFI-11), Hospital frailty index, FRAIL scale, Emergency General Surgery Frailty Index (EGSFI), and Burn frailty index (BFI). There was only one report regarding a specific frailty index designed for the burn population (BFI). Except for one study (which used mFI-11), all included studies have shown a significant effect between assessing frailty and predicting worse outcomes. The CFS was an independent predictor of mortality among the burn population with high certainty of evidence. We found a significant association for other frailty indices as a predictor of mortality, however, the certainty of evidence regarding those was not high. Eight studies found a positive association between assessing frailty and unfavorable discharge location. There was no association between frailty and increased length of stay. Conclusion In conclusion, the postadmission assessment of frailty can be a reliable tool for predicting unfavorable outcomes and mortalities among patients with burn injuries. In addition, future studies with various populations from other countries are required to evaluate the efficacy of frailty indices measurement in order to strengthen the available evidence. Supplementary Information The online version contains supplementary material available at 10.1186/s12877-023-04302-5.


Introduction
Burn injuries usually lead to morbidities, reduced quality of life, and fiscal burdens on the patients and their families.Burns also raises the cost of healthcare services, as their treatment requires extensive follow-ups, accompanied by prolonged hospital stays and potential surgical interventions [1].Prognostic risk factors of burn are stated by older age, wider total body surface area burn (TBSA), inhalational injury, mechanical ventilation, presence of tracheotomy, and time from of burn injury to BICU admission and initial centre of first emergency treatment [2].Understanding the prognosis of a burn patient can help us determine their treatment protocols and patient care facilities.Numerous injury scoring systems are already at our disposal regarding burn patients, including but not limited to age, total body surface area burned, inhalation injury, size and depth of burn, and serum creatine kinase [3].A study by Silva et al. [4] reported that elderly burn patients' comorbidities have a prevalence of 53-68%.The patients are at greater risk of premature death as a consequence of injuries, including burn injuries [1,5,6].In the study by Pham and colleagues [7] which was conducted using data from burn centers in the United States and Canada, the in-hospital mortality rate for 55-64, 65-74, and ≥ 75 years old of age was 8.7%, 16.2%, and 24.4%, respectively.The major limitation of age consideration is the fact that it does not predict the physiological or psychological status of the elderly population.Therefore, a practical tool must consider different aspects of an elder patient.In fact, frailty, which is a state of vulnerability of an individual, has increased due to age-related decline in the function of the body [8].Previous studies from single centers with small sample sizes have demonstrated the effects of frailty on burn mortality and showed that frailty is associated with an increased risk of mortality [9][10][11][12].
Frailty, usually defined as conditions with excessive vulnerability in response to endogenous and exogenous stressors, has also been proposed as a valid tool for predicting adverse outcomes among burn patients, and there have been some articles recently published on this subject [9,[13][14][15].There is no universal definition for frailty, although definitions have been described in some studies [16][17][18][19].However, frailty is best defined as a balance between assets and deficits, where if the deficits outweigh the assets, the person is deemed frail [20].These factors can be measured, and in turn, frailty itself can be measured by pooling the overall results of these measures.Frailty indices such as The Canadian Study of Health and Aging frailty index and The Modified Frailty index (MFI) are derived by this method.The Canadian Study of Health and Aging clinical frailty scale (CSHA-CFS) is a 7-point clinical opinion scale created in order to be used as a clinical alternative to The Canadian Study of Health and Aging frailty index [21].The CFS is a validated measure for assessing one's physical frailty [21].This scale does not evaluate psychological or social domains.The scoring system starts with 1 (very fit) and ends with 9 (terminally ill).One can be frail if the overall score becomes 5 or higher.Like CFS, the mFI-11 only assess physical domains and there have been critiques on its low responsiveness to change [22,23].
Systematic reviews have been conducted on prognostic factors regarding burn patients [3,24].However, no study has reviewed and examined the prognostic value of frailty in burn patients.Considering the feasibility of frailty assessment in the clinical setting, we aim to systematically review the literature on the associations between frailty and adverse outcomes in burn patients..

Methodology
The present systematic review was conducted based on Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and guideline retrieved from the Cochrane Handbook for Systematic Reviews of Interventions [25,26].The protocol of this review was prospectively registered on PROSPERO with the following registration code: CRD42022353197.

Search strategy
We performed a comprehensive database search in international databases, including Medline (via PubMed), Embase, Scopus, and Web of science up to 8 September 2022.No limitation was implemented on our search results.Furthermore, by screening the reference section of the potentially included articles, eligible studies were identified.A combination of the following keywords and Boolean operators were used to design the strategy of our systematic search: Burns, Burning, Frailty, Frailness, Debility, and Frail.The detailed search strategy of each database with exact results and time of the performance is available in Supplementary material Table 1.

Eligibility criteria
The inclusion criteria based on PICOT definition were: 1) Population: adult burn patients; 2) Index: evaluated frailty as a predictor of post admission outcomes using a well-established and validated frailty scale; 3) Comparison: not applicable; 4) Outcome: reported relevant outcomes including but not limited to mortality, length of stay, high level of care discharge, and etc.; 5) Type of Study: all types of original studies.The was no limitation on date and the language of the published report.Conference abstracts were also included but their quality was not assessed due to limited data available regarding their methodology.Review studies, case report studies, meta-analyses, commentary studies, and letter to editor articles without any relevant data were excluded.

Screening and data extraction
Screening the articles were performed in 2 steps: 1) Initial screening by title/abstracts; and 2) Full texts screening.Disagreements were resolved through discussion.Data were extracted on an Excel spreadsheet.The extracted data included Author, Year, Country, Registry/ Duration, Population, Total patients, Frailty index used, Cut-offs, and Main Findings.A third reviewer checked both screening and data extraction parts.

Quality assessment
The quality assessment was evaluated by two reviewers (S.R. and M.A.) using a checklist derived from National, Heart, Lung, and Blood Institute (NHLBI) tools for cohort and cross-sectional studies [27] 2. The overall quality of a study was based on the overall judgment of authors who answered and evaluated each study.Any discrepancies in quality assessment were resolved by the third reviewer.

Synthesis and certainty of evidence
Since there were a lot of heterogeneity in the ways of reporting the findings of each article, we decided not to perform a meta-analysis.To rate the evidence, we used the GRADE-pro website and its definitions for each domain.Further detail about the system of rating has been provided in our previous work and on the GRADEpro website [28][29][30].Briefly, to report the pooled results of the studies and evaluating the certainty of evidence available for each frailty index, we used the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system developed for systematic reviews by assessing different domains which includes: 1) Risk of bias: the overall results of the quality assessment of each study was used to determine if it is necessary to rate down the evidence.The results derived from conference abstracts was considered to have serious risk of bias; 2) Inconsistency: in cases where different results were available from different studies (for example one study reports favorable use of frailty index and the other study not), the evidence was decreased one level; 3) Indirectness: defined exactly as defined by the GRADE team; 4) Imprecision: having few number of studies reporting the relevant outcome would decrease the level of evidence; 5) Publication bias: defined exactly as defined by the GRADE team.The certainty of evidence starts from high and ends on very low.Issues in each domain will decrease the evidence one or two levels [31,32].

Summary of frailty indices used
Among the included studies, there were 7 different frailty measures used for assessing the prognostic value of them among burn population.The most used frailty measure was the one developed by the Canadian Study for Health and Ageing (CSHA) Clinical Frailty score (CFS) (64%) [9-15, 33-35, 37, 38, 41].Among the included studies, only 2 reported their outcomes among different frail groups [14,15]

Frailty and postadmission outcomes
Except for one study [42], all included studies have shown a significant effect between assessing frailty and predicting worse outcomes following the admission of burn patients.Fifteen of the included studies, assessed the use of frailty as an independent predictor of mortality [9-15, 33, 36, 38, 39, 41-44].Only two studies by Wallace [42] and Romanowski [38] reported a non-significant association.Based on our synthesis, the CFS was an independent predictor of mortality among burn population with high certainty of evidence (Table 3).Each of the following measures was assessed once with regard to predicting the odds of mortality: positive association of Hospital frailty index, FRAIL scale, EGSFI, and BFI.Regarding mFI-11 and mFI-5, there were heterogeneous results regarding their positive association [39,42].Considering other outcomes, unfavorable discharge location and length of stay were among the most reported, respectively.All eight studies found a positive association between assessing frailty and unfavorable discharge location [10,11,13,35,36,40,41,44]. Regarding length of stay, only BFI and FRAIL scale showed significant increase in length of stay among prefrail/frail group by assessing frailty using FRAIL scale [40,44].Maxwell et al. found a decrease in length of stay among those whose were assessed as frail by BFI index [44].All other studies did not find any association regarding frailty and increased length of stay.The detailed results of other outcomes are available in Tables 1 and 2.

Quality of the included studies
Among the journal articles assessed regarding their quality, one rated Poor, five rated Fair, and six rated Good.The detailed results of our quality assessment are available in Table 3.

Discussion
In the present systematic review, we evaluated different frailty indices among burn patients.Also, we conducted a comprehensive assessment in the published articles regarding this topic.Seven different frailty indices were used in the included studies, including CFS, mFI-11, mFI-5, hospital frailty index, EGSFI, FRAIL scale, and BFI.The mostly used frailty indices were the CFS and mFIs, respectively.However, data regarding the association between frailty measurement as a prognostic tool among burn patients is limited.Most of the included studies showed that there is a positive correlation between    measurement of frailty and the prediction of severe and comorbid outcomes among burn patients during their hospitalization.Although there is only one developed index to assess frailty among burn patients (BFI), based on our assessments, results obtained from the CFS index had a higher certainty of evidence score compared with other frailty indices, suggesting that it can be used as a reasonably reliable index than other indices.Our results yielded that measuring CFS as among admitted burn patients was able to predict mortality and poor discharge location.Furthermore, there were no significant association between measuring CFS and the length of hospital stay.It is worth mentioning that BFI was designed based on a previous validated frailty scale (EGSFI).Most of the included studies assessed the frailty scales for their patients at the time of admission because of the importance to predict burn outcome and status as soon as possible.Based on our results showing prognostic property of frailty assessment, it seems to be important to use standardized frailty scales (such as CFS and mFIs as common scales) for all burn patients at time of admission to predict their mortality, unfavorable discharge location, and length of stay.
During the initial period of admission with the busy and complicated condition of initial treatment of burn patients, the Frailty Score is simple to assess, understand, and communicate with clear criteria based on determined levels of patient function.Assessment of the risk of mortality and any worse outcome allows burn care teams to evaluate the impact of the primary hospital care and follow-up on burn outcomes.
In a study by Maxwell et al. [44], the association between burn-related complications and frailty was assessed using burn frailty index (BFI).It is worth mentioning that BFI was designed based on a previous validated frailty scale (EGSFI) which was previously validated for the burn patients as a useful tool for predicting morbidity and mortality [36].However, using BFI was associated with better sensitivity and specify for predicting all cause mortality (0.923 and 0.771 vs. 0.846 and 0.736).A major concern regarding the burn frailty index is the fact that it can only be completed by patients who are able to fill the questionnaire, due to some questions such as questions about personal feelings.The CFS has an advantage over the burn frailty index because it can also be assessed using medical records or from the family members.Rockwood et al. [21] described a cumulative deficit model which is a model encompassing social, comorbidities, and cognitive factors.These factors increase the frailty index when combined.It has been reported in a systematic literature review by Shamliyan and colleagues [47] that frailty is associated with poor life expectancy.However, Sepehripour et al. [37] showed that clinical frailty scale was not correlated with higher or lower life expectancy in elder burn trauma survivors.Moreover, they saw a positive correlation between complications and frailty status.
Previous studies have been conducted in order to assess the predictors of mortality and other severe outcomes among burn patients [48-50].However, there is no study which comprehensively assess the available evidence regarding the association of frailty and outcomes following burn injury.Age, %TBSA, % full thickness burn, female gender, inhalation injury, surgery including escharotomy, and the depth of burn were among the factors that has been reported to predict the length of stay among these patients [48].In our study, however, the evidence suggests there were no association between frailty as a predictor of length of stay.Only one study which used BFI was reported a significant increase in the length of stay among frail patients [44].Regarding health-related quality of life, a systematic review by Spronk et al. reported several factors including but not limited to severity of injury, depression, and post-traumatic stress symptoms as an independent predictor [50].There were no studies reporting the predictive value of frailty on qualityof life following burn injury.A recent systematic review and meta-analysis have evaluated the available risk models for predicating mortality among burn patients [49].They found the classic Baux; the revised Baux; and the Fatality by Longevity, APACHE II score, Measured Extent of burn, and Sex (FLAMES) among the best predictors of mortality.It is worth noting there was no discussion regarding measurement of frailty as a potential predictor of mortality in their systematic review [49].
There are several strengths regarding the present study.We performed a comprehensive bibliometric database search in order to identify all published articles in any language evaluating frailty indices on burn injury patients.We have also included conference abstracts to maximize the validity of our results.Also, there is no other systematic review or a meta-analysis on elderly burn patients.We fully screened the included studies and reported their data as several individual outcomes.Furthermore, we assessed the certainty of evidence in both outcomes and frailty indices used.Our study has some limitations.On one hand, a meta-analysis could not be performed in this systematic review, mainly due to the heterogeneity of the studies and low available data.On the other hand, most of our data were regarding the CFS index and there is low certainty of evidence about other frailty indices.Finally, the subjectiveness of our methodology using the GRADE system to synthesis our results may cause bias to our findings.Therefore, we suggest performing additional studies specifically on the frailty masseurs which have low or very low certainty of evidence regarding their use in burn patients.

Conclusion
In conclusion, based on the results of the present systematic review, assessment of frailty can be developed and be used as a predictive tool for mortalities among the patients with burn injuries.In addition, more studies with various populations from other countries are also required to evaluate the efficacy of frailty measurement.Although there are considerable evidence indicating CFS as a great tool regarding this goal, future studies are needed to assess other frailty indices which were explained in details in this systematic review.
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• support for research data, including large and complex data types • gold Open Access which fosters wider collaboration and increased citations maximum visibility for your research: over 100M website views per year . The second most used (11%) frailty index was the Modified frailty index-11 (mFI-11) [46].Both studies which have used mFI-11 were conference abstracts [39, 42].Each of the mentioned measures was used once within the reviewed studies: the Modified frailty index-5 (mFI-5) [39].Hospital frailty index [43], FRAIL scale [40], Emergency General Surgery Frailty Index (EGSFI) [36], and Burn frailty index (BFI) [44].The burn frailty index was developed based on the previous validated tool EGSFI.

Table 1
Characteristics of the included articles

Table 2
Summary results of synthesis and certainty of evidence a Poor or unfavorable discharge is the discharge to skilled nursing facility b Not Serious: no downgrade in the certainty of evidence; Serious: one downgrade in the certainty of evidence; Very Serious: two downgrades in the certainty of evidence; NA: not applicable