Chanu Rhee

Regulatory Mandates for Sepsis Care — Reasons for Caution

The attention and resources being dedicated to improving sepsis care are welcome. The policy response to this apparent epidemic, however, ought to be tempered by recognition that we do not yet have reliable tools for measuring sepsis incidence.

Incidence and Trends of Sepsis in US Hospitals Using Clinical vs Claims Data, 2009-2014

Importance Estimates from claims-based analyses suggest that the incidence of sepsis is increasing and mortality rates from sepsis are decreasing. However, estimates from claims data may lack clinical fidelity and can be affected by changing diagnosis and coding practices over time. Objective To estimate the US national incidence of sepsis and trends using detailed clinical data from the electronic health record (EHR) systems of diverse hospitals. Design, Setting, and Population Retrospective cohort study of adult patients admitted to 409 academic, community, and federal hospitals from 2009-2014. Exposures Sepsis was identified using clinical indicators of presumed infection and concurrent acute organ dysfunction, adapting Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3) criteria for objective and consistent EHR-based surveillance. Main Outcomes and Measures Sepsis incidence, outcomes, and trends from 2009-2014 were calculated using regression models and compared with claims-based estimates using International Classification of Diseases, Ninth Revision, Clinical Modification codes for severe sepsis or septic shock. Case-finding criteria were validated against Sepsis-3 criteria using medical record reviews. Results A total of 173 690 sepsis cases (mean age, 66.5 [SD, 15.5] y; 77 660 [42.4%] women) were identified using clinical criteria among 2 901 019 adults admitted to study hospitals in 2014 (6.0% incidence). Of these, 26 061 (15.0%) died in the hospital and 10 731 (6.2%) were discharged to hospice. From 2009-2014, sepsis incidence using clinical criteria was stable (+0.6% relative change/y [95% CI, −2.3% to 3.5%], P = .67) whereas incidence per claims increased (+10.3%/y [95% CI, 7.2% to 13.3%], P < .001). In-hospital mortality using clinical criteria declined (−3.3%/y [95% CI, −5.6% to −1.0%], P = .004), but there was no significant change in the combined outcome of death or discharge to hospice (−1.3%/y [95% CI, −3.2% to 0.6%], P = .19). In contrast, mortality using claims declined significantly (−7.0%/y [95% CI, −8.8% to −5.2%], P < .001), as did death or discharge to hospice (−4.5%/y [95% CI, −6.1% to −2.8%], P < .001). Clinical criteria were more sensitive in identifying sepsis than claims (69.7% [95% CI, 52.9% to 92.0%] vs 32.3% [95% CI, 24.4% to 43.0%], P < .001), with comparable positive predictive value (70.4% [95% CI, 64.0% to 76.8%] vs 75.2% [95% CI, 69.8% to 80.6%], P = .23). Conclusions and Relevance In clinical data from 409 hospitals, sepsis was present in 6% of adult hospitalizations, and in contrast to claims-based analyses, neither the incidence of sepsis nor the combined outcome of death or discharge to hospice changed significantly between 2009-2014. The findings also suggest that EHR-based clinical data provide more objective estimates than claims-based data for sepsis surveillance.

West Nile virus encephalitis acquired via liver transplantation and clinical response to intravenous immunoglobulin: case report and review of the literature

C. Rhee, E.F. Eaton, W. Concepcion, B.G. Blackburn. West Nile virus encephalitis acquired via liver transplantation and clinical response to intravenous immunoglobulin: case report and review of the literature.
Transpl Infect Dis 2011: 13: 312–317. All rights reserved

Comparison of Trends in Sepsis Incidence and Coding Using Administrative Claims Versus Objective Clinical Data

BACKGROUND National reports of a dramatic rise in sepsis incidence are largely based on analyses of administrative databases. It is unclear if these estimates are biased by changes in coding practices over time. METHODS We calculated linear trends in the annual incidence of septicemia, sepsis, and severe sepsis at 2 academic hospitals from 2003 to 2012 using 5 different claims methods and compared case identification rates to selected objective clinical markers, including positive blood cultures, vasopressors, and/or lactic acid levels. RESULTS The annual incidence of hospitalizations with sepsis claims increased over the decade, ranging from a 54% increase for the method combining septicemia, bacteremia, and fungemia codes (P < .001 for linear trend) to a 706% increase for explicit severe sepsis/septic shock codes (P = .001). In contrast, the incidence of hospitalizations with positive blood cultures decreased by 17% (P = .006), and hospitalizations with positive blood cultures with concurrent vasopressors and/or lactic acidosis remained stable (P = .098). The sensitivity of sepsis claims for capturing hospitalizations with positive blood cultures with concurrent vasopressors and/or lactic acidosis increased (P < .001 for all methods), whereas the proportion of septicemia hospitalizations with positive blood cultures decreased from 50% to 30% (P < .001). CONCLUSIONS The incidence of hospitalizations with sepsis codes rose dramatically while hospitalizations with corresponding objective clinical markers remained stable or decreased. Coding for sepsis has become more inclusive, and septicemia diagnoses are increasingly being applied to patients without positive blood cultures. These changes likely explain some of the apparent rise in sepsis incidence and underscore the need for more reliable surveillance methods.

A Framework for the Development and Interpretation of Different Sepsis Definitions and Clinical Criteria

Although sepsis was described more than 2,000 years ago, and clinicians still struggle to define it, there is no “gold standard,” and multiple competing approaches and terms exist. Challenges include the ever-changing knowledge base that informs our understanding of sepsis, competing views on which aspects of any potential definition are most important, and the tendency of most potential criteria to be distributed in at-risk populations in such a way as to hinder separation into discrete sets of patients. We propose that the development and evaluation of any definition or diagnostic criteria should follow four steps: 1) define the epistemologic underpinning, 2) agree on all relevant terms used to frame the exercise, 3) state the intended purpose for any proposed set of criteria, and 4) adopt a scientific approach to inform on their usefulness with regard to the intended purpose. Usefulness can be measured across six domains: 1) reliability (stability of criteria during retesting, between raters, over time, and across settings), 2) content validity (similar to face validity), 3) construct validity (whether criteria measure what they purport to measure), 4) criterion validity (how new criteria fare compared to standards), 5) measurement burden (cost, safety, and complexity), and 6) timeliness (whether criteria are available concurrent with care decisions). The relative importance of these domains of usefulness depends on the intended purpose, of which there are four broad categories: 1) clinical care, 2) research, 3) surveillance, and 4) quality improvement and audit. This proposed methodologic framework is intended to aid understanding of the strengths and weaknesses of different approaches, provide a mechanism for explaining differences in epidemiologic estimates generated by different approaches, and guide the development of future definitions and diagnostic criteria.

Application of a Framework to Assess the Usefulness of Alternative Sepsis Criteria

The current definition of sepsis is life-threatening, acute organ dysfunction secondary to a dysregulated host response to infection. Criteria to operationalize this definition can be judged by six domains of usefulness (reliability, content, construct and criterion validity, measurement burden, and timeliness). The relative importance of these six domains depends on the intended purpose for the criteria (clinical care, basic and clinical research, surveillance, or quality improvement [QI] and audit). For example, criteria for clinical care should have high content and construct validity, timeliness, and low measurement burden to facilitate prompt care. Criteria for surveillance or QI/audit place greater emphasis on reliability across individuals and sites and lower emphasis on timeliness. Criteria for clinical trials require timeliness to ensure prompt enrollment and reasonable reliability but can tolerate high measurement burden. Basic research also tolerates high measurement burden and may not need stability over time. In an illustrative case study, we compared examples of criteria designed for clinical care, surveillance and QI/audit among 396,241 patients admitted to 12 academic and community hospitals in an integrated health system. Case rates differed four-fold and mortality three-fold. Predictably, clinical care criteria, which emphasized timeliness and low burden and therefore used vital signs and routine laboratory tests, had the greater case identification with lowest mortality. QI/audit criteria, which emphasized reliability and criterion validity, used discharge information and had the lowest case identification with highest mortality. Using this framework to identify the purpose and apply domains of usefulness can help with the evaluation of existing sepsis diagnostic criteria and provide a roadmap for future work.

Estimating Ten-Year Trends in Septic Shock Incidence and Mortality in United States Academic Medical Centers Using Clinical Data

Background: Reports that septic shock incidence is rising and mortality rates declining may be confounded by improving recognition of sepsis and changing coding practices. We compared trends in septic shock incidence and mortality in academic hospitals using clinical vs claims data. Methods: We identified all patients with concurrent blood cultures, antibiotics, and vasopressors for ≥ two consecutive days, and all patients with International Classification of Diseases, 9th edition (ICD‐9) codes for septic shock, at 27 academic hospitals from 2005 to 2014. We compared annual incidence and mortality trends. We reviewed 967 records from three hospitals to estimate the accuracy of each method. Results: Of 6.5 million adult hospitalizations, 99,312 (1.5%) were flagged by clinical criteria, 82,350 (1.3%) by ICD‐9 codes, and 44,651 (0.7%) by both. Sensitivity for clinical criteria was higher than claims (74.8% vs 48.3%; P < .01), whereas positive predictive value was comparable (83% vs 89%; P = .23). Septic shock incidence, based on clinical criteria, rose from 12.8 to 18.6 cases per 1,000 hospitalizations (average, 4.9% increase/y; 95% CI, 4.0%‐5.9%), while mortality declined from 54.9% to 50.7% (average, 0.6% decline/y; 95% CI, 0.4%‐0.8%). In contrast, septic shock incidence, based on ICD‐9 codes, increased from 6.7 to 19.3 per 1,000 hospitalizations (19.8% increase/y; 95% CI, 16.6%‐20.9%), while mortality decreased from 48.3% to 39.3% (1.2% decline/y; 95% CI, 0.9%‐1.6%). Conclusions: A clinical surveillance definition based on concurrent vasopressors, blood cultures, and antibiotics accurately identifies septic shock hospitalizations and suggests that the incidence of patients receiving treatment for septic shock has risen and mortality rates have fallen, but less dramatically than estimated on the basis of ICD‐9 codes.

Improving documentation and coding for acute organ dysfunction biases estimates of changing sepsis severity and burden: a retrospective study

IntroductionClaims-based analyses report that the incidence of sepsis-associated organ dysfunction is increasing. We examined whether coding practices for acute organ dysfunction are changing over time and if so, whether this is biasing estimates of rising severe sepsis incidence and severity.MethodsWe assessed trends from 2005 to 2013 in the annual sensitivity and incidence of discharge ICD-9-CM codes for organ dysfunction (shock, respiratory failure, acute kidney failure, acidosis, hepatitis, coagulopathy, and thrombocytopenia) relative to standardized clinical criteria (use of vasopressors/inotropes, mechanical ventilation for ≥2 consecutive days, rise in baseline creatinine, low pH, elevated transaminases or bilirubin, abnormal international normalized ratio or low fibrinogen, and decline in platelets). We studied all adult patients with suspected infection (defined by ≥1 blood culture order) at two US academic hospitals.ResultsAcute organ dysfunction codes were present in 57,273 of 191,695 (29.9 %) hospitalizations with suspected infection, most commonly acute kidney failure (60.2 % of cases) and respiratory failure (28.9 %). The sensitivity of all organ dysfunction codes except thrombocytopenia increased significantly over time. This was most pronounced for acute kidney failure codes, which increased in sensitivity from 59.3 % in 2005 to 87.5 % in 2013 relative to a fixed definition for changes in creatinine (p = 0.019 for linear trend). Acute kidney failure codes were increasingly assigned to patients with smaller creatinine changes: the average peak creatinine change associated with a code was 1.99 mg/dL in 2005 versus 1.49 mg/dL in 2013 (p <0.001 for linear decline). The mean number of dysfunctional organs in patients with suspected infection increased from 0.32 to 0.59 using discharge codes versus 0.69 to 0.79 using clinical criteria (p <0.001 for both trends and comparison of the two trends). The annual incidence of hospitalizations with suspected infection and any dysfunctional organ rose an average of 5.9 % per year (95 % CI 4.3, 7.4 %) using discharge codes versus only 1.1 % (95 % CI 0.1, 2.0 %) using clinical criteria.ConclusionsCoding for acute organ dysfunction is becoming increasingly sensitive and the clinical threshold to code patients for certain kinds of organ dysfunction is decreasing. This accounts for much of the apparent rise in severe sepsis incidence and severity imputed from claims.

Objective Sepsis Surveillance Using Electronic Clinical Data

OBJECTIVE To compare the accuracy of surveillance of severe sepsis using electronic health record clinical data vs claims and to compare incidence and mortality trends using both methods. DESIGN We created an electronic health record-based surveillance definition for severe sepsis using clinical indicators of infection (blood culture and antibiotic orders) and concurrent organ dysfunction (vasopressors, mechanical ventilation, and/or abnormal laboratory values). We reviewed 1,000 randomly selected medical charts to characterize the definitions accuracy and stability over time compared with a claims-based definition requiring infection and organ dysfunction codes. We compared incidence and mortality trends from 2003-2012 using both methods. SETTING Two US academic hospitals. PATIENTS Adult inpatients. RESULTS The electronic health record-based clinical surveillance definition had stable and high sensitivity over time (77% in 2003-2009 vs 80% in 2012, P=.58) whereas the sensitivity of claims increased (52% in 2003-2009 vs 67% in 2012, P=.02). Positive predictive values for claims and clinical surveillance definitions were comparable (55% vs 53%, P=.65) and stable over time. From 2003 to 2012, severe sepsis incidence imputed from claims rose by 72% (95% CI, 57%-88%) and absolute mortality declined by 5.4% (95% CI, 4.6%-6.7%). In contrast, incidence using the clinical surveillance definition increased by 7.7% (95% CI, -1.1% to 17%) and mortality declined by 1.7% (95% CI, 1.1%-2.3%). CONCLUSIONS Sepsis surveillance using clinical data is more sensitive and more stable over time compared with claims and can be done electronically. This may enable more reliable estimates of sepsis burden and trends.

Impact of Intravenous Immunoglobulin on Survival in Necrotizing Fasciitis With Vasopressor-Dependent Shock: A Propensity Score–Matched Analysis From 130 US Hospitals

Background Shock frequently complicates necrotizing fasciitis (NF) caused by group A Streptococcus (GAS) or Staphylococcus aureus. Intravenous immunoglobulin (IVIG) is sometimes administered for presumptive toxic shock syndrome (TSS), but its frequency of use and efficacy are unclear. Methods Adult patients with NF and vasopressor-dependent shock undergoing surgical debridement from 2010 to 2014 were identified at 130 US hospitals. IVIG cases were propensity-matched and risk-adjusted. The primary outcome was in-hospital mortality and the secondary outcome was median length of stay (LOS). Results Of 4127 cases of debrided NF with shock at 121 centers, only 164 patients (4%) at 61 centers received IVIG. IVIG subjects were younger with lower comorbidity indices, but higher illness severity. Clindamycin and vasopressor intensity were higher among IVIG cases, as was coding for TSS and GAS. In-hospital mortality did not differ between matched IVIG and non-IVIG groups (crude mortality, 27.3% vs 23.6%; adjusted odds ratio, 1.00 [95% confidence interval, .55-1.83]; P = .99). Early IVIG (≤2 days) did not alter this effect (P = .99). Among patients coded for TSS, GAS, and/or S. aureus, IVIG use was still unusual (59/868 [6.8%]) and lacked benefit (P = .63). Median LOS was similar between IVIG and non-IVIG groups (26 [13-49] vs 26 [11-43]; P = .84). Positive predictive values for identifying true NF and debridement among IVIG cases using our algorithms were 97% and 89%, respectively, based on records review at 4 hospitals. Conclusions Adjunctive IVIG was administered infrequently in NF with shock and had no apparent impact on mortality or hospital LOS beyond that achieved with debridement and antibiotics.