Using the Japanese nationwide medical claims database, this study demonstrated that a high hospital volume significantly contributed to decreasing the in-hospital mortality in sepsis cases. Moreover, higher volume hospitals were associated with higher daily medical costs per person in sepsis.
Several studies have investigated the relationship between the hospital volume and mortality in sepsis patients. While some studies revealed a beneficial effect of the hospital volume on mortality in sepsis 15,16, other investigations showed contradictory results 17,18. The disparities among the studies could be attributed to the differences in the study design, number of enrolled patients, adjusted variables, and medical systems in each country. An insufficient number of study participants and an arbitrary threshold of high-volume hospitals would lead to underpowered studies to detect valid results. Our study clearly demonstrated that high-volume hospitals and the number of hospitalized patients significantly correlated with reduced in-hospital mortality in sepsis patients. The strength of our study is its large cohort data of 1,781,014 patients, which outnumbered that of the previous studies. Additionally, we used various statistical methods to enhance the robustness of our analysis. While the investigations using quartile groups of hospital volume presented plausible results, application of fractional polynomials and restricted cubic splines with the hospital volume as a continuous variable compensated for the limitation of the arbitrary categorization.
The mechanism of the beneficial effect of high-volume hospitals on mortality is potentially explained by several components, including abundant medical resources, more experienced medical staff, and higher capability of implementing evidence-based practices 25–27. In general, high-volume hospitals have more ICU staff, beds, and medical equipment, such as mechanical ventilators and blood purification devices. It seems reasonable that the availability of abundant medical resources with more experienced staff contributes to improving the clinical outcomes of sepsis patients. On the other hand, considering that patients subjected to mechanical ventilation, RRT, or ICU admission comprised less than 20% of the cohort, these components may not substantially affect the benefits of high-volume hospitals. The consistent benefit of high-volume hospitals despite the confounder adjustment for ICU admission and organ dysfunctions implies that the other elements contributed to the advantages. As the intensity of physician staffing and compliance with implementing guidelines-based treatment were not investigated in our study, detailed mechanisms of the effect of hospital volume on mortality should be clarified in future investigations.
Although we demonstrated higher daily medical costs per person and shorter length of stay in association with higher sepsis case volume, no associations were reported in a previous publication 16. Besides sepsis, overall cancer surgery costs were inversely associated with the hospital volume as well as surgeon volume through a shorter length of stay 19,20. In these reports, abundant experience of the staff was suggested as the possible reason for the shorter length of hospitalization in high-volume hospitals than in the low-volume ones. Similarly, Endo et al. showed better survival and lower total cost per admission in high-volume hospitals for severe trauma patients using an administrative database 22. In contrast, a previous study enrolling burn injury patients demonstrated a positive correlation between the hospital volume and medical costs during hospitalization 21. The plausible reason for the increased medical costs was the high proportion of intensive treatments performed in high-volume hospitals, such as mechanical ventilation and cultured skin grafts. This study demonstrated that not only daily medical costs per person but also medical costs per hospitalization increased according to the number of annual sepsis patients, despite a shorter length of stay. As the proportion of patients on artificial organ support is greater in high-volume hospitals than in low-volume hospitals, the proportional association between the hospital volume and medical costs would be conceivable.
Hospital volume was shown to be a crucial factor in improving in-hospital mortality in this study; however, centralization of sepsis patients requires deep consideration and meticulous debate prior to policy implementation. While the acceleration of the centralization improved the survival rate after pancreatic cancer surgery 28, it might not be appropriate to apply such a policy to sepsis management without careful deliberation. Since sepsis patients require a time-sensitive approach with early recognition and immediate initiation of treatment, transportation of sepsis patients could reduce the treatment effect due to delayed antibiotic administration and the introduction of sepsis management bundles 29,30. Therefore, investigation of the detailed mechanisms responsible for better clinical outcomes in high-volume hospitals should be conducted rather than encouraging the transportation of sepsis patients to high-volume hospitals.
This study has several limitations that must be addressed prior to drawing conclusions. First, the administrative database did not include laboratory data to calculate the severity scores. Second, treatment policy such as withholding or withdrawal of life-sustaining treatment was not collected from the database, which could be a confounding factor affecting the results. Third, categorization into quartiles might lead to a bias in determining the effect of hospital volume on outcomes. However, in our study, the complementary analysis using hospital volume as a continuous variable potentially increased the robustness. Fourth, the detailed proportions of the medical costs were not described in this study. Fifth, long-term mortality rate and quality of life were not investigated in the cohort. Sixth, plausible reasons for the association between the hospital volume and the mortality or medical costs were not sufficiently explained. In conclusion, this study, using a Japanese nationwide medical claims database, suggests that higher volume hospitals are likely to have better survival and higher daily medical costs per person in sepsis cases as compared to the lower volume hospitals. Further research is warranted to validate these results and clarify the mechanisms underlying these associations.