In this study, we demonstrated that sepsis patients treated in the ICU exhibited decreased in-hospital mortality compared with those out of the ICU using a propensity score matching analysis. Lower mortality among sepsis patients admitted to the ICU was also presented in the age subgroup analyses and other confounding adjustment analyses, suggesting that the results were robust, regardless of differences in patient backgrounds and treatment intensity.
The advantages of ICU admission over hospitalization in general wards for critically ill patients were consistent with previous reports ([8–13]). In a comparative observational study, mechanically ventilated patients hospitalized in the ICU exhibited a higher in-hospital survival rate than those in medical wards with fewer endotracheal tube-related complications [12]. Another study comparing critically ill patients on ventilator support treated in the ICU and high-dependency care units demonstrated decreased in-hospital mortality [13]. Although a superior survival rate attributable to ICU management has been demonstrated in critically ill patients, few studies have focused on sepsis patients with regard to the efficacy of ICU management on clinical outcomes. To the best of our knowledge, this study is the first to demonstrate the advantages of ICU admission in patients with sepsis using confounding adjustment analyses. Although we performed a propensity score matching analysis to adjust for baseline imbalances, there might be other confounding factors that could affect the results. A potential confounder could be the treatment policy, such as withholding or withdrawing from intensive therapies. In the subgroup analyses concerning age, the significant advantage in ICU settings over general wards was consistent among all age subgroups. Intriguingly, the mortality differences in the subgroup analyses were greater in the old and oldest old groups than in the overall value but not in adults. This result implied that confounding factors were not adjusted in the main analysis in the old and oldest old groups, whereas the subgroup analysis in adults strengthened the robustness that ICU treatment contributed to decreasing mortality. Likewise, the consistency of the decreased mortality among cancer patients admitted to the ICU supports the plausibility of our hypothesis. Future studies should address detailed information about treatment policies in the database.
The exact mechanisms of the advantages in ICU management can be attributed to several factors, including sufficient medical resources and artificial organ support [3, 4]. Mechanical ventilation could be performed in general wards; however, close monitoring might be difficult owing to the lack of adequate resources, leading to mechanical complications such as accidental extubation and delayed recognition of equipment failures [12]. These errors may worsen clinical outcomes in critically ill patients. In the present study, the differences in mortality between the two groups were greater among patients on mechanical ventilation than among those without artificial support. In contrast, patients on RRT exhibited smaller mortality differences than those without RRT. However, the reason for this discrepancy remains to be determined.
To provide an appropriate environment where mechanical organ support is performed without iatrogenic complications, consistent ICU services by intensivists and sufficient nurse staffing are warranted. Regarding their optimal allocation, the lack of intensivists in the ICU or lower patient-to-intensivist ratios reportedly increase the mortality of critically ill patients [27, 28]. Although a high-intensity ICU model or closed-ICU, where intensivists are responsible for day-to-day management, is recommended, the benefit of a 24-hour service of intensivists remains controversial [3]. Furthermore, nurse staffing also contributes to altering patient outcomes [29, 30]. In Japan, the nurse-to-patient ratio in general wards is 1:7 or higher, whereas the ICU allocates one nurse to two patients. While an appropriate nurse-to-patient ratio is lacking owing to scarce evidence, inadequate nursing staffing increases the in-hospital risk of death through insufficient delivery of basic care [31]. Accordingly, ICU settings with a sufficient number of intensivists and nurses for patients would be preferable for sepsis management, particularly for patients receiving mechanical organ support.
While the abundance of staffing and medical resources in the ICU depends on governmental policies and medical systems in different countries, the number of ICU beds per capita by country also varies widely. Compared with other developed countries, Japan has fewer ICU beds (five beds per 100,000 people). In western countries, the number of ICU beds varies: 3.5 beds per 100,000 population in the U.K., 9.3 beds per 100,000 population in France, 13.5 beds per 100,000 population in Canada, and 20 beds per 100,000 population in the U.S. [15, 32, 33]. In addition to variations in the number of ICU beds, the indications for ICU admission and critical care services vary among these countries. In a demographic study comparing critical care delivery between Japan and the U.S., the details of ICU utilization differed by age population, proportion of postoperative ICU admissions, and severity of the critical illness. In terms of severity, the mean APACHE III score among Japanese patients was higher than that among American patients. These differences might be attributable to medical policies, demographic characteristics, and cultural norms [14]. In this context, our results should be interpreted cautiously in accordance with the characteristics of the healthcare system.
This study, however, has several limitations. First, the medical claims database lacks laboratory data. As a calculation of severity scores, such as the SOFA score, was unavailable, we used the number of organ dysfunctions and organ supports to adjust imbalances. Second, confounding by indication for ICU admission was not adjusted. Discrete decisions by responsible physicians potentially cause biased perceptions of disease severity and prognosis among medical personnel. Third, long-term outcomes were not assessed in this study. Fourth, the primary diagnosis for hospitalization in some patients was not sepsis. Fifth, treatment policies, such as withholding or withdrawal of life-sustaining interventions, were not recorded due to the study design, which could have affected the mortality of non-ICU patients. As a result, we performed a subgroup analysis by age to scrutinize the results among younger populations who are unlikely to be withheld or withdrawn from intensive care. Future investigations are warranted to collect detailed patient information, including treatment policy, and to elucidate the mechanisms that favor ICU admission for clinical outcomes.