Clinical Infectious Diseases MAJOR ARTICLE
Inpatient Mortality Among Solid Organ Transplant Recipients Hospitalized for Sepsis and Severe Sepsis John P. Donnelly,1,2,3 Jayme E. Locke,4,5 Paul A. MacLennan,4,5 Gerald McGwin Jr,3 Roslyn B. Mannon,4,5,6 Monika M. Safford,7,9 John W. Baddley,8 Paul Muntner,3 and Henry E. Wang1 1 Department of Emergency Medicine, School of Medicine, 2Department of Medicine, Division of Preventive Medicine, 3Department of Epidemiology, School of Public Health, 4Comprehensive Transplant Institute, 5Department of Surgery, Division of Transplantation, 6Department of Medicine, Division of Nephrology, 7Department of Medicine, and 8Department of Medicine, Division of Infectious Diseases, University of Alabama at Birmingham; and 9Department of Medicine, Weill Cornell Medical College, New York, New York
Background. Solid organ transplant (SOT) recipients are at elevated risk of sepsis. The impact of SOT on outcomes following sepsis is unclear. Methods. We performed a retrospective cohort study using data from University HealthSystem Consortium, a consortium of academic medical center affiliates. We examined the association between SOT and mortality among patients hospitalized with severe sepsis or explicitly coded sepsis in 2012–2014. We used International Classification of Diseases, Ninth Revision (ICD-9) codes to identify severe sepsis, explicitly coded sepsis, and SOT (kidney, liver, heart, lung, pancreas, or intestine transplants). We fit random-intercept logistic regression models to account for clustering by hospital. Results. There were 903 816 severe sepsis hospitalizations (39 618 [4.4%] with SOT) and 410 623 sepsis hospitalizations (14 526 [3.9%] with SOT) in 250 hospitals. SOT recipients were younger and more likely to be insured by Medicare than those without SOT. Among hospitalizations for severe sepsis and sepsis, in-hospital mortality was lower among those with vs those without SOT (5.5% vs 9.4% for severe sepsis; 8.7% vs 12.7% for sepsis). After adjustment, the odds ratio for mortality comparing SOT patients vs non-SOT was 0.83 (95% confidence interval [CI], .79–.87) for severe sepsis and 0.78 (95% CI, .73–.84) for sepsis. Compared to non-SOT patients, kidney, liver, and co-transplant (kidney-pancreas/kidney-liver) recipients demonstrated lower mortality. No association was present for heart transplant, and lung transplant was associated with higher mortality. Conclusions. Among patients hospitalized for severe sepsis or sepsis, those with SOT had lower inpatient mortality than those without SOT. Identifying the specific strategies employed for populations with improved mortality could inform best practices for sepsis among SOT and non-SOT populations. Keywords. sepsis; outcomes; transplant; infection; critical care.
In the United States, nearly 30 000 transplants were performed in 2014, and the number of solid organ transplant (SOT) recipients living with a functioning graft has been growing [1]. Although transplantation is a high-cost, intensive procedure, it is considered the best treatment for individuals experiencing organ failure, and has been shown to extend the life expectancy of recipients dramatically [2, 3]. For example, kidney transplant has been demonstrated to be the most cost-effective treatment for patients suffering from end-stage renal disease [4]. However, infection is the second leading cause of death for SOT recipients, a population that experiences increased risk of infectious complications posttransplant due to induced
Received 25 January 2016; accepted 23 April 2016; published online 23 May 2016. Presented in part: 16th Annual American Society of Transplant Surgeons Winter Symposium, Miami, Florida, 15 January 2016. Correspondence: H. E. Wang, Department of Emergency Medicine, University of Alabama at Birmingham, 619 19th St S, OHB 251, Birmingham, AL 35249 ([email protected]). Clinical Infectious Diseases® 2016;63(2):186–94 © The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail [email protected]. DOI: 10.1093/cid/ciw295
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immunosuppression, prolonged hospitalization, and intensive surgery [5–8]. Severe sepsis, or infection with systemic inflammation complicated by organ dysfunction, poses a substantial burden on the US healthcare system, leading to >750 000 hospitalizations and 200 000 deaths annually [9, 10]. Severe sepsis remains a leading cause of death in the United States, with in-hospital mortality ranging from 12% to 26% [11, 12]. Sepsis represents a common complication of transplant procedures, and SOT recipients have been shown to be at increased risk for sepsis compared with the general population [5, 13, 14]. However, several studies have shown that the syndrome of sepsis has a wider range of causative organisms and differing presentation among immunosuppressed individuals compared with immunocompetent individuals [15, 16]. In addition, traditional markers of systemic inflammatory response syndrome may not be present among the immunosuppressed, despite active overwhelming infection [17, 18]. Consistent with a reduced inflammatory response, a single-center study comparing bacteremic sepsis patients who were prior SOT recipients with non-SOT patients matched on age, sex, and location at the day of blood culture collection demonstrated
increased survival among those with prior SOT [19]. However, few national studies have been conducted to determine if these observations are consistent across the broader population of SOT recipients. Further study of sepsis outcomes among SOT recipients could help to inform future strategies for prevention and management, and also allow for optimization of posttransplant care among SOT recipients. Therefore, we examined the association between prior receipt of SOT and inpatient mortality following severe sepsis and sepsis in a national consortium of academic medical center–affiliated hospitals. METHODS Study Design
We conducted a retrospective cohort study using hospital discharge data from the University HealthSystem Consortium (UHC) clinical database (CDB). All data were submitted to UHC from individual institutions and provided for research purposes through the CDB. The study received approval from the Institutional Review Board of the University of Alabama at Birmingham for retrospective analysis of existing data. Data Source
The UHC is a consortium of academic medical centers and affiliated hospitals in the United States. With hospitals in 42 states, UHC aims to improve clinical, operational, and financial performance [20]. For quality improvement purposes, UHC maintains the CDB, which is a database that contains administrative data submitted by hospitals in the consortium. This data source captures the elements of the standard UB-04 reporting form and encompasses data pertaining to patient demographics, discharge diagnoses, procedures, and outcomes. We used available UHC CDB data for the period 1 January 2012 through 31 December 2014. Cohort Selection
The cohorts examined in this study consisted of patients hospitalized for severe sepsis and sepsis from UHC hospitals submitting data to the CDB. We excluded patients
Inpatient Mortality Among Solid Organ Transplant Recipients Hospitalized for Sepsis and Severe Sepsis John P. Donnelly,1,2,3 Jayme E. Locke,4,5 Paul A. MacLennan,4,5 Gerald McGwin Jr,3 Roslyn B. Mannon,4,5,6 Monika M. Safford,7,9 John W. Baddley,8 Paul Muntner,3 and Henry E. Wang1 1 Department of Emergency Medicine, School of Medicine, 2Department of Medicine, Division of Preventive Medicine, 3Department of Epidemiology, School of Public Health, 4Comprehensive Transplant Institute, 5Department of Surgery, Division of Transplantation, 6Department of Medicine, Division of Nephrology, 7Department of Medicine, and 8Department of Medicine, Division of Infectious Diseases, University of Alabama at Birmingham; and 9Department of Medicine, Weill Cornell Medical College, New York, New York
Background. Solid organ transplant (SOT) recipients are at elevated risk of sepsis. The impact of SOT on outcomes following sepsis is unclear. Methods. We performed a retrospective cohort study using data from University HealthSystem Consortium, a consortium of academic medical center affiliates. We examined the association between SOT and mortality among patients hospitalized with severe sepsis or explicitly coded sepsis in 2012–2014. We used International Classification of Diseases, Ninth Revision (ICD-9) codes to identify severe sepsis, explicitly coded sepsis, and SOT (kidney, liver, heart, lung, pancreas, or intestine transplants). We fit random-intercept logistic regression models to account for clustering by hospital. Results. There were 903 816 severe sepsis hospitalizations (39 618 [4.4%] with SOT) and 410 623 sepsis hospitalizations (14 526 [3.9%] with SOT) in 250 hospitals. SOT recipients were younger and more likely to be insured by Medicare than those without SOT. Among hospitalizations for severe sepsis and sepsis, in-hospital mortality was lower among those with vs those without SOT (5.5% vs 9.4% for severe sepsis; 8.7% vs 12.7% for sepsis). After adjustment, the odds ratio for mortality comparing SOT patients vs non-SOT was 0.83 (95% confidence interval [CI], .79–.87) for severe sepsis and 0.78 (95% CI, .73–.84) for sepsis. Compared to non-SOT patients, kidney, liver, and co-transplant (kidney-pancreas/kidney-liver) recipients demonstrated lower mortality. No association was present for heart transplant, and lung transplant was associated with higher mortality. Conclusions. Among patients hospitalized for severe sepsis or sepsis, those with SOT had lower inpatient mortality than those without SOT. Identifying the specific strategies employed for populations with improved mortality could inform best practices for sepsis among SOT and non-SOT populations. Keywords. sepsis; outcomes; transplant; infection; critical care.
In the United States, nearly 30 000 transplants were performed in 2014, and the number of solid organ transplant (SOT) recipients living with a functioning graft has been growing [1]. Although transplantation is a high-cost, intensive procedure, it is considered the best treatment for individuals experiencing organ failure, and has been shown to extend the life expectancy of recipients dramatically [2, 3]. For example, kidney transplant has been demonstrated to be the most cost-effective treatment for patients suffering from end-stage renal disease [4]. However, infection is the second leading cause of death for SOT recipients, a population that experiences increased risk of infectious complications posttransplant due to induced
Received 25 January 2016; accepted 23 April 2016; published online 23 May 2016. Presented in part: 16th Annual American Society of Transplant Surgeons Winter Symposium, Miami, Florida, 15 January 2016. Correspondence: H. E. Wang, Department of Emergency Medicine, University of Alabama at Birmingham, 619 19th St S, OHB 251, Birmingham, AL 35249 ([email protected]). Clinical Infectious Diseases® 2016;63(2):186–94 © The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail [email protected]. DOI: 10.1093/cid/ciw295
186
•
CID 2016:63 (15 July)
•
Donnelly et al
immunosuppression, prolonged hospitalization, and intensive surgery [5–8]. Severe sepsis, or infection with systemic inflammation complicated by organ dysfunction, poses a substantial burden on the US healthcare system, leading to >750 000 hospitalizations and 200 000 deaths annually [9, 10]. Severe sepsis remains a leading cause of death in the United States, with in-hospital mortality ranging from 12% to 26% [11, 12]. Sepsis represents a common complication of transplant procedures, and SOT recipients have been shown to be at increased risk for sepsis compared with the general population [5, 13, 14]. However, several studies have shown that the syndrome of sepsis has a wider range of causative organisms and differing presentation among immunosuppressed individuals compared with immunocompetent individuals [15, 16]. In addition, traditional markers of systemic inflammatory response syndrome may not be present among the immunosuppressed, despite active overwhelming infection [17, 18]. Consistent with a reduced inflammatory response, a single-center study comparing bacteremic sepsis patients who were prior SOT recipients with non-SOT patients matched on age, sex, and location at the day of blood culture collection demonstrated
increased survival among those with prior SOT [19]. However, few national studies have been conducted to determine if these observations are consistent across the broader population of SOT recipients. Further study of sepsis outcomes among SOT recipients could help to inform future strategies for prevention and management, and also allow for optimization of posttransplant care among SOT recipients. Therefore, we examined the association between prior receipt of SOT and inpatient mortality following severe sepsis and sepsis in a national consortium of academic medical center–affiliated hospitals. METHODS Study Design
We conducted a retrospective cohort study using hospital discharge data from the University HealthSystem Consortium (UHC) clinical database (CDB). All data were submitted to UHC from individual institutions and provided for research purposes through the CDB. The study received approval from the Institutional Review Board of the University of Alabama at Birmingham for retrospective analysis of existing data. Data Source
The UHC is a consortium of academic medical centers and affiliated hospitals in the United States. With hospitals in 42 states, UHC aims to improve clinical, operational, and financial performance [20]. For quality improvement purposes, UHC maintains the CDB, which is a database that contains administrative data submitted by hospitals in the consortium. This data source captures the elements of the standard UB-04 reporting form and encompasses data pertaining to patient demographics, discharge diagnoses, procedures, and outcomes. We used available UHC CDB data for the period 1 January 2012 through 31 December 2014. Cohort Selection
The cohorts examined in this study consisted of patients hospitalized for severe sepsis and sepsis from UHC hospitals submitting data to the CDB. We excluded patients
