Transfer hospitalizations for pediatric severe sepsis or septic shock: resource use and outcomes

Sepsis is a major contributor to child mortality and morbidity [1‐3], with significant in-hospital cost burden [1, 3]. The occurrence of organ dysfunction in the septic state, exemplified by severe sepsis or septic shock, is associated with elevated risk of adverse outcomes including death [4]. To ameliorate organ dysfunction, patients with severe sepsis and septic shock often require escalated care to provide artificial organ support such as continuous renal replacement therapy (CRRT) or extracorporeal membrane oxygenation (ECMO). Given the differential capacity of hospitals to provide such specialized resources, deployment of these advanced organ-supportive therapeutic modalities often requires transfer to hospitals with such resources [5, 6].

Given the time-sensitive nature of care for children with severe sepsis or septic shock, and the detrimental consequences of delayed definitive and resuscitative care, including lower survival and increased morbidity [7, 8], it is important to investigate for any association between transfer admission for the care of pediatric severe sepsis or septic shock and in-hospital patient survival and resource use. The research might elucidate opportunities to alleviate illness burden and the associated resource use burden and provide insight to approaches to improve healthcare delivery for children with sepsis.

The study was conducted to test the hypothesis that children with severe sepsis or septic shock who undergo interhospital transfer have higher in-hospital mortality, longer hospitalization, and higher overall hospital charges compared with those not transferred.

Some of the results of this study have been previously reported in the form of an abstract [9].

There were 8533 hospitalizations with severe sepsis or septic shock with transfer information in the database, representing an estimated 11,922 hospitalizations for pediatric severe sepsis or septic shock nationally in 2012. Of the 8533 hospitalizations, 2151 (25.4%) were associated with interhospital transfer, most often to urban teaching hospitals (Table 1). In the overall study cohort, extreme illness severity was observed in 77% of hospitalizations, comorbidities in 75% of children, and multiple (2 or more organ-system involvement) organ dysfunction in 26.4%. In-hospital mortality was 17%, average length of stay was 22 days, and the average charge per hospitalization was $314,950.

In bivariate analysis, patient and hospital characteristics varied by transfer status. In comparison with non-transferred children, transferred children were younger and had higher frequency of extreme illness severity (84% vs. 75%, p < .01) (Table 1). Multiple organ dysfunction also occurred in higher frequency among transferred than non-transferred children (32% vs. 24%, p < .01). There was no difference in the frequency of comorbidities by transfer status.

Transfer hospitalization was notably associated with higher use of invasive medical devices including arterial catheters, invasive mechanical ventilation, central venous catheters; and specialized technology, including CRRT and ECMO (Table 2). The occurrence of CPR did not differ by transfer status, occurring in 3.8% of transferred and 3.9% of non-transferred children (p = 0.84).

Unadjusted outcomes and resource use differed significantly between transferred and non-transferred children. Transferred children had longer hospitalization (30 vs. 22 days, p < .05) and accrued higher hospital charges ($385,275 vs. $290,882, p < .05). Crude mortality was also higher among transferred than non-transferred children (21.4% vs.15.0%, p < .01).

After multivariate adjustment for potential confounders, adjusted in-hospital mortality was not statistically different between transferred and non-transferred children (Odds Ratio:1.04, 95% Confidence interval [CI]:0.88–1.24). Similarly, adjusted length of hospital stay (1.1 days; 95% CI: − 1.2-3.4 days) and hospital charges (− 2814; 95% CI: − 31,656 – 26,028) for transferred versus non-transferred children were not statistically different.

One out of every four hospitalizations for children with severe sepsis or septic shock in the U.S. in 2012 was associated with interhospital transfer. While the exact indication for such transfer is unknown, the higher use of invasive medical devices and specialized medical technology such as ECMO and CRRT suggested these children were severely ill and in need of escalated care, likely prompting transfer.

Interhospital transfer is often indicative of a mismatch between a patient’s needs and the locally-available resources [14, 15], with the hope of salutary outcomes if such transfer was performed in a timely manner. Death from pediatric sepsis is often associated with multiple organ dysfunction the progression of which could be halted or reversed by timely institution of organ-supportive therapies [7, 16].

The study findings highlight significant variation in illness burden and resource-utilization by transfer status, with transfer hospitalizations more likely to involve children with extreme illness severity who were most often admitted to urban teaching hospitals. It was therefore not surprising that children who were transferred were more likely to undergo invasive medical device placement including arterial and central venous catheterization, tracheostomy, and invasive mechanical ventilation. This observation corroborates prior findings of higher resource utilization among critically ill patients who underwent inter-hospital transfer compared to those who did not [17]. Highly specialized and expensive technologies, including ECMO and CRRT, were similarly more likely to be deployed in the care of transferred children in comparison with non-transferred children. This finding of higher frequency of use of specialized technology among transferred versus non-transferred children, is likely indicative of greater illness severity among transferred children, corroborating prior report of an association between illness severity and deployment of invasive medical devices among the critically ill pediatric population [18]. The use of these technologies might have mitigated the impact of multiple organ dysfunction on patient death by limiting progression of organ dysfunction or enhancing resolution of organ dysfunction. Such assertion is supported by the observation that despite higher unadjusted mortality among transfer versus non-transfer hospitalizations, the mortality difference was no longer observed after multivariate adjustment for potential confounders including illness severity. This finding of similar severity-adjusted mortality also indicates the need to investigate processes of care and quality of care factors within the receiving urban hospitals that contributed to reduction in observed mortality.

Receiving hospitals bore a significant resource use burden reflected in their greater use of invasive medical technology along with the longer hospitalization and higher charges among transferred children in comparison to the non-transferred children. This disparate resource use burden was no longer evident after multivariate adjustment for potential factors that could confound the relationship between transfer status and resource use. The findings have implications for urban teaching hospitals that bear the brunt of these transfer hospitalizations. The first implication stems from the observation that higher charges and longer hospitalization among the transfer hospitalizations appeared commensurate to the severity of patient illness. Efforts to benchmark outcomes and resource use between hospitals that take care of critically ill children need to incorporate transfer admissions into algorithms for such inter-institutional assessments to avoid penalizing the receiving hospitals, as previously advocated for critically ill adults [19, 20]. Secondly, as an extension of this prior concept, the study findings highlight the need to routinely adjust in-hospital outcomes and resource use for illness severity and case mix [21, 22], without which hospitals that receive critically ill patients on interhospital transfer might be penalized for higher crude mortality and greater resource use.

The primary payer is an important variable that serves as a proxy for socioeconomic status. Public insurance coverage was associated with transfer status, a finding that corroborates recent work that noted significant variation in patient care processes, including transfer, by patients’ insurance coverage [23]. Given that such variation might impact patient outcomes [24], further work is warranted to investigate the reasons for such variation and the potential impact on outcomes and resource use in children with severe sepsis or septic shock.

The findings of the current study should be interpreted in light of certain limitations. It is vital to note that the reported hospital charges and LOS in the current study accrued from the care received at the hospital of definitive care thereby discounting the resource use expended at the referring hospital prior to interhospital transfer. As a result, the reported resource use burden accrued by the transferred children is likely an under-estimate of the actual burden. This limitation, imposed by the absence of linkable data for transferred children across hospitals in the data source for the study, highlights the need to conduct future longitudinal studies to provide a complete picture of the overall resource burden borne by children with pediatric sepsis who undergo transfer hospitalizations.

The KID is a database of administrative discharge data without clinical information beyond what can be captured in ICD-9-CM diagnosis and procedure codes. Therefore, it was not possible to study the clinical course for each patient, the need for and receipt of various therapeutic interventions, and how clinical care was coordinated at the patient and hospital level. An additional limitation is that the identification of cases of severe sepsis was ascertained via ICD-9-CM diagnosis codes, and is susceptible to inaccuracies of detection and attribution that may have biased our findings.

Also, while the care of patients with severe sepsis or septic shock might be improved by early resuscitation in the community prior to transfer to referral hospitals [7], determination of the characteristics of the referring hospitals and the circumstances surrounding transfer among the transfer hospitalizations, was not possible in the current study. This limited the ability to investigate any delay in resuscitative care, which might impact clinical outcomes and resource-utilization at the receiving hospital. Given the lack of clinical data, the characteristics and process of inter-hospital transport, and their potential impact on patient-level resource use and outcomes could not be ascertained. The KID contains non-clinical administrative data collected during patient hospitalizations and has no follow-up or longitudinal information on patients after hospital discharge. This limitation did not permit determination of long term patient morbidity and functional status.

One in four children with severe sepsis or septic shock required interhospital transfer for specialized care associated with greater use of invasive medical devices and specialized technology. Despite higher crude mortality and resource consumption among transferred children, adjusted mortality and resource use did not differ by transfer status. Further research should identify quality-of-care factors at the receiving hospitals that influenced clinical outcomes and resource use for critically ill children with severe sepsis or septic shock.