We investigated the association between frailty and clinical characteristics and outcomes among patients with suspected infection in ICUs. Approximately one third of patients in this study population were classified as frail according to their CFS scores. Vulnerable and frail patients appeared to have poor outcomes after the acute disease phase compared with fit patients, although there were no differences between the groups in terms of short-term in-hospital mortality.
Some of the results of our study differed from those of previous studies. The proportion of elderly patients in our study was higher than that in previous studies; the median age of patients in our study was 72 years; in other studies, the median age was 6211 and 64 years12. However, the percentage of frail patients in our study was equivalent or lower than that in previous studies (31.4% vs. 29.5%11 and 43.0%12). The higher proportion of elderly patients in our study may be explained by the fact that Japan has one of the world's oldest populations.19 Another explanation may be that our cohort included a large proportion of patients with sepsis.20 Regarding the prevalence of frailty, there may have been less frail patients in this study because our study institutions were tertiary emergency care centers and only patients admitted to ICUs were included. Alternatively, it may have been due to the difference between the trajectory of sepsis and the trajectory of chronic diseases such as heart failure21 and respiratory failure.22
We confirmed that frail and vulnerable patients had more comorbidities compared with fit patients. Comorbidities included congestive heart failure, cerebrovascular diseases, and COPD as well as those described in previous studies.23,24 Our results were very similar to previous reports that included heterogeneous diseases, although we selected patients with suspected infection only. There exists a controversy regarding the relationship between individual comorbidities and frailty.25 The combination of individual comorbidities and frailty may not be related to the primary disease, although it is natural that more comorbidities lead to greater frailty.
Our findings with regard to body temperature and C-reactive protein levels suggest that frailty may be associated with a poor acute inflammatory response. Some studies have reported that frailty was associated with chronic changes in the immune response, including the imbalance of decline in immune function and increased inflammation.26,27 Other studies have reported that aging was related to changes in the acute immune response,28,29 due to dysfunction of immune cells or decreased cytokines working as a part of innate and adaptive immunity.28 Both frailty and aging may be involved in weakening the acute inflammatory response. Further studies are needed to clarify the relationship between frailty, aging, and poor inflammatory responses.
Regarding mortality, we found that more vulnerable and frail patients died after the acute disease phase, although this difference was not statistically significant. This tendency was consistent with previous reports.1,11 In the acute disease phase, disease severity may have had a greater impact on mortality than frailty. In the late disease phase, we did not observe the patients' status after discharge, and frail patients who transferred to other institutions in the early disease phase may have subsequently died. Further studies are needed to assess the association between frailty and long-term mortality in patients admitted to ICUs with suspected infection.
Moreover, our study showed that mortality rates in vulnerable and frail patients were similar, whereas previous studies in ICUs demonstrated that the severity of frailty was associated with mortality.8,14 We may have provided a greater level of clinical care for very frail patients because the Japanese national health insurance system is universal. This may have contributed to the reduction of mortality among frail patients. Alternatively, the relationship between the severity of frailty and mortality may not have been linear among patients with sepsis. Mortality from septic shock is very high.15 Vulnerable and frail patients may have already been at risk of death. Further studies are needed to assess the association between the severity of frailty and mortality in patients with sepsis.
This study had some limitations. First, fewer patients had CFS scores of 5 in our study compared with those in previous studies.8,11,14 There is a possibility that some CSF scores were misclassified. The CFS score is not widely used to assess frailty in Japan. Education in the use of the CFS score may have been necessary although the CSF has been found to be a reliable tool even if the assessor is different.30 Second, we did not follow up the patients' outcomes after hospital discharge. We used the last observation carried forward. Third, we did not have information about treatments that may have been related to the patients' outcomes in this database. However, most patients should have received appropriate treatments according to guidelines such as the Surviving Sepsis Campaign Guideline, which is used in national certified ICUs.31