In this study, we found that longer hospital LOS before RRS activation was associated with worse clinical outcomes. Patients who stayed ≥ 5 days before RRS activation had higher 28-day and in-hospital mortality rates and were more likely to stay longer in the hospital after RRS activation compared with those who stayed < 5 days. This finding was robust after adjusting for variables reflecting the severity of illness at the time of RRS activation and even after propensity score-matched analysis.
The effectiveness of RRS has been studied extensively in the past two decades. Although early studies including cluster randomized trials failed to show significant reduction in mortality (13, 14), many other studies, such as before and after studies, have consistently shown positive results, as demonstrated in recent systematic review and meta-analysis studies (2, 15). However, in real-world practice, when implementing RRS, it is difficult to predict clinical outcomes of individual patients for whom RRS activated because a wide range of patients with various comorbidities are being reviewed by the RRS team.
Certain alarming vital signs or laboratory test abnormalities are usually used as screening tools for RRS activation (16). However, when two different patients with similar vital signs are reviewed by the RRS team, the expected outcomes may differ according to the patients’ current illness and comorbidities. As the volume of cases reviewed by the RRS team increases, it is important to be able to predict the clinical outcome to improve the cost-effectiveness and optimize resource use. This also relates to the decision about which patients should be admitted to the ICU when available beds and resources are limited. Patients who have a higher probability of recovery are usually given a higher priority for ICU admission (17). However, it is difficult for RRS staff members to review the functional status and detailed medical history of patients and assess the likelihood of recovery in a short time.
In this regard, attention has been focused on efforts to identify predictors of clinical outcomes for patients for whom RRS is activated. A prospective observational study reported that assessment of frailty would be helpful for predicting the clinical trajectory of patients (18). We hypothesized that hospital LOS before RRS activation may be a useful and simple predictor of clinical outcome after considering that severe frailty is usually associated with longer LOS (5). In two previous single-center studies that evaluated the effect of LOS before RRS activation on clinical outcomes, the late deterioration group (≥ 7 days) had more than twice the in-hospital mortality rate than the early deterioration group (< 2 days) (19, 20). However, those studies did not fully adjust for between-group differences in their analyses.
A study using the nationwide multicenter registry in the USA, which included about 280,000 patients, demonstrated that hours since admission before RRS activation was the second most important factor, after systolic blood pressure, in predicting in-hospital mortality (4). However, a limitation of that study was that patients’ underlying comorbidities were categorized too simply as either medical or surgical and either cardiac or noncardiac. A detailed history of underlying comorbidities is a critical factor affecting the outcome, as shown in a recent study that reported an in-hospital mortality rate of > 40% in patients with hematological malignancy for whom RRS was activated (21).
In this study, we found that time since admission before RRS activation was an independent significant predictor of clinical outcome. A longer LOS before RRS activation itself may suggest ineffectiveness of the initial treatment and reflect the severity of the illness that caused the patient to be admitted. Therefore, among the patients with long hospital LOS at the time of RRS activation, invasive treatment, such as mechanical ventilation, may be deemed as futile in a certain proportion of patients. This is reflected by our finding that more patients in the late deterioration group had discussion with RRS staff members regarding the DNR order. Although attending physicians have a principal role in communicating with patients and their family members, the intervention of a third party, the RRS team, may improve end-of-life care planning by avoiding unnecessary or futile invasive treatment (22, 23).
The association between longer hospital LOS and worse clinical outcomes may indicate that medical problems acquired in the hospital setting are usually more serious, particularly for infectious complications (24). This is also reflected in the previous finding that mortality rate associated with hospital-acquired pneumonia is much greater than that for community-acquired pneumonia (25). This is because patients with hospital-acquired pneumonia are at higher risk of infection with multidrug resistant pathogens. In our subgroup analysis, it was noted that the negative effects of longer hospital LOS on the clinical outcomes were more significant in patients who were admitted to surgical department or underwent a surgical operation. Given that postoperative wound infection or pneumonia are common problems leading to delay in discharge in surgical patients, these findings may be related to postoperative in-hospital infections due to difficult-to-treat pathogens (26).
Our study has several limitations. First, because of its retrospective observational design, we cannot exclude the possible effects of other unmeasured confounding factors. However, we found consistent results for the main analysis, propensity score-matched analysis, and several sensitivity analyses, which supports the robustness of our results. Second, we could not match every variable completely in our propensity score-matched analysis. Especially, the standardized difference between matched groups in the proportion of patients who underwent a surgical operation before RRS activation was 11.1%. Thus, we double adjusted the confounding variables to minimize the confounding effects (11). Furthermore, we performed a subgroup analysis according to whether the patient received a surgery. Third, a causal relationship cannot be inferred between hospital LOS before RRS activation and later clinical outcomes. Despite these limitations, we believe that hospital LOS at the time of RRS activation may provide a simple and reliable prognostic information on future outcomes.