Вы находитесь на странице: 1из 8

Volume of emergency department admissions for sepsis is related

to inpatient mortality: Results of a nationwide cross-sectional


analysis
Emilie S. Powell, MD, MBA; Rahul K. Khare, MD; D. Mark Courtney, MD; Joe Feinglass, PhD

Objectives: Emergency department resuscitation plays a sig- odds ratios of mortality were 0.73 (95% confidence interval, 0.64 –
nificant role in sepsis care, and it is unknown if patient outcomes 0.83; p < .001) in quartile 4 (highest volume), 0.83 in quartile 3 (95%
vary by institution based on the level of sepsis experience of the confidence interval, 0.74 – 0.93; p ⴝ .001), and 0.90 in quartile 2 (95%
emergency department. This study examines whether there is an confidence interval, 0.82– 0.99; p < .05) when compared to quartile
association between the annual volume of patients admitted via 1 (lowest volume). Adjusted results were similar for early mortality:
the emergency department with sepsis and inpatient mortality. 0.69 (95% confidence interval, 0.61– 0.76; p < .001) in quartile 4, 0.83
Design: Cross-sectional analysis of the 2007 Nationwide Inpa- in quartile 3 (95% confidence interval, 0.74 – 0.93; p < .05), and 0.85
tient Sample. in quartile 2 (95% confidence interval, 0.77– 0.94; p < .05) when
Setting and Patients: We included 87,166 adult emergency compared to quartile 1.
department sepsis admissions from 551 hospitals. Conclusions: After adjustment for comorbidity and hospital-
Measurements: Hospitals were categorized into quartiles by 2007 level factors, there was a significant relationship between emer-
emergency department sepsis volume. Univariate associations of patient gency department sepsis case volume and overall and early
characteristics, hospital characteristics, and inpatient mortality with inpatient mortality among patients admitted through the emer-
sepsis volume level were evaluated by chi-square test. A population- gency department with sepsis. Patients admitted to hospitals in
averaged logistic regression model of inpatient mortality was used to the highest-volume quartile had 27% lower odds of inpatient
estimate the effects of age, gender, comorbid conditions, payer status, mortality in this large heterogeneous sample. (Crit Care Med 2010;
median zip code income, hospital bed size, teaching status, and emer- 38:2161–2168)
gency department sepsis volume. KEY WORDS: sepsis; outcome assessment; mortality; health ser-
Main Results: Overall inpatient sepsis mortality was 18.0% and vices research
early mortality (2 days after admission) was 6.9%. The risk-adjusted

S epsis is a growing problem in tance of ED sepsis care has resulted in ac- EDs with greater experience in sepsis re-
the United States, with mortality cepted, validated approaches to immediate suscitation actually perform better and
rates that reach 50%– 60% once and aggressive resuscitation that have been have improved patient outcomes.
the disease progresses to septic adopted in many hospitals in quality im- One method of assessing the potential
shock (1–3). Although not all sepsis pa- provement efforts and as a standard of care contribution of ED experience in sepsis re-
tients are admitted through, or initially re- (10 –12). These approaches can be time and suscitation is to examine if there is a rela-
suscitated in, the emergency department resource intensive, and successful imple- tionship between annual case volume and
(ED), care in this setting plays a significant mentation and patient outcome could be inpatient mortality among patients admit-
role in the treatment of sepsis nationwide, dependent on the level of experience at ted to the hospital via the ED with sepsis.
and care delivered in the ED can signifi- both the clinician and institution levels. The volume– outcome relationship has
cantly reduce mortality (4 –9). The impor- However, little is known about whether been explored extensively in the surgical
literature. Higher case volume, reflecting
experience, has been demonstrated to cor-
relate with superior quality of care (13, 14).
From the Department of Emergency Medicine Dr. Khare received a year-long fellowship training
(ESP, RKK, MC), Feinberg School of Medicine, North- grant from Agency for Healthcare. The remaining au-
It is possible that higher annual ED sepsis
western University, Chicago, IL; Institute for Healthcare thors have not disclosed any potential conflicts of case volume may reflect greater depart-
Studies and Division of General Internal Medicine (ESP, interest. ment-level experience in treating sepsis
RKK, JF), Northwestern University, Feinberg School of Supplemental digital content is available for this ar- and superior quality of care. If experience
Medicine, Chicago, IL. ticle. Direct URL citations appear in the printed text and
Dr. Powell and Dr. Khare are supported by National are provided in the HTML and .pdf versions of this article
and case volume are related to superior
Research Service Award postdoctoral fellowship grant on the journal’s Web site (www.ccmjournal.com). quality of care, as has been shown in the
through the Institute for Healthcare Studies at North- For information regarding this article, surgical literature, then we would expect to
western University under institutional awards from E-mail: emilie-powell@md.northwestern.edu see lower early inpatient mortality (within
Agency for Healthcare Research and Quality (T-32 HS Copyright © 2010 by the Society of Critical Care
000078 and F-32 HS 17876-01). Dr. Courtney was Medicine and Lippincott Williams & Wilkins
the first 2 days of admission), as well as
supported by grant 5K23HL077404-04 from the Na- lower overall inpatient mortality at higher-
DOI: 10.1097/CCM.0b013e3181f3e09c
tional Heart, Lung, and Blood Institute. volume institutions.

Crit Care Med 2010 Vol. 38, No. 11 2161


The primary goal of this investigation fined by Martin et al (3) to detect patients with erally and state-funded program providing med-
was to use population-based national hos- sepsis from hospital discharge data: 038 (septi- ical care for those with low incomes) or self-pay
pital discharge data to examine whether cemia), 020.2 (septicemic plague), 790.7 (bacte- (uninsured) into a single category.
there is an association between inpatient remia), 117.9 (disseminated fungal infection), To account for confounding attributable to
mortality and the annual volume of pa- 112.5 (disseminated Candida infection), or comorbid conditions present on admission that
tients admitted to the hospital via the ED 112.81 (disseminated fungal endocarditis). may have influenced mortality, we used the Elix-
with a principal diagnosis of sepsis. We ex- Of 134,824 NIS adult sepsis admissions in hauser International Classification of Diseases
amined this question before and after con- 2007, 42,212 (31.3%) were admitted through a ninth revision secondary diagnosis codes to
source other than the ED and were therefore identify conditions likely to have been present on
trolling for other key patient and hospital
excluded from this analysis. To ensure that admission. These conditions often have been
characteristics. We hypothesized that hos-
hospitals with extremely low frequencies of used in mortality models to adjust for the sever-
pitals with higher ED sepsis case volume
sepsis admissions did not bias the analysis, we ity of preexisting illness (15). Patients were clas-
would have superior outcomes as defined excluded admissions from hospitals with ⬍25 sified as having or not having each of 30 Elix-
by lower early inpatient (within 2 days pos- sepsis admissions in 2007. This applied to hauser chronic comorbid conditions. We first
tadmission) and overall inpatient mortality. 2,468 admissions (2.7% of the ED sepsis pa- tested the univariate association of each Elix-
tient sample) from 287 hospitals. This exclu- hauser comorbid condition with inpatient mor-
METHODS sion allowed comparison of the remaining in- tality and included conditions found to have
stitutions to more likely reflect process rather significant associations in the final multivariate
Study Design than purely structural quality of care. Finally, models of inpatient mortality.
patients transferred to another acute care hos- Hospital-level data available in the NIS in-
We performed a cross-sectional analysis of pital after admission through the ED (3.5% of cluded bed size (categorized by NIS as small,
the 2007 Healthcare Cost and Utilization Project all ED admissions) were also excluded because medium, or large; based on the number of
Nationwide Inpatient Sample (NIS). The NIS is their survival could not be attributed to the short-term acute beds in the hospital and spe-
the largest publicly available all-payer inpatient admitting hospital (Figure 1). cific to the hospital region, location, and
database in the United States and is provided by
teaching status), teaching status (member of
the U.S. Agency for Healthcare Research and
the Council of Teaching Hospitals or not), and
Quality. Data are weighted to result in a sample Data Synthesis: Patient and
location (rural vs. urban). To assess whether
that is representative of all admissions to non- Hospital Variables ED sepsis case volume was an independent
federal U.S. hospitals on an annual basis. Addi-
NIS data included admission source, dis- predictor of mortality, these hospital charac-
tional details of the NIS can be found on the
charge status (alive or dead), gender, age (di- teristics were also included in multivariate
Healthcare Cost and Utilization Project Web site
vided into quintiles), and race/ethnicity (black, models of inpatient mortality.
(http://www.hcup-us.ahrq.gov/). The Northwest-
ern University Institutional Review Board found Hispanic, white, other, or missing). Race and
this study of deidentified data exempt. ethnicity data were missing for 28.1% of study
ED Sepsis Case Volume
patients from states where this information was
Sample Selection not mandated; therefore, this demographic in- The primary predictor variable of interest,
formation was not included in the multivariate hospital ED sepsis case volume, was defined as
The 2007 NIS contains 8,043,415 discharge analysis. NIS data also included length of stay, the number of admissions originating in the ED
records from 1,044 hospitals in 40 states. Dis- primary payer source, and patients’ zip code me- to a given hospital with a principal diagnosis of
charge data include International Classification dian incomes (divided into quartiles). As an ad- sepsis in 2007. In addition to testing the signif-
of Diseases ninth revision coded diagnoses. Ad- ditional proxy for lower socioeconomic status in icance of annual ED sepsis volume as a contin-
missions for sepsis were identified based on the the analyses, because individual income level is uous measure, ED sepsis admissions to each
principal diagnosis International Classification not available from the NIS, we coded patients
hospital were empirically divided equally into
of Diseases ninth revision codes previously de- with a primary payer status of Medicaid (a fed-
four volume-level quartiles to improve interpre-
tation of multivariate model odds ratios (ORs).

Key Outcome Measures

The key outcome measures in this study


were overall inpatient mortality (death at any
time during hospital admission) and early inpa-
tient mortality (death within the first 2 days of
admission). We chose to evaluate early mortality
in addition to overall inpatient mortality to more
directly examine the impact of ED sepsis care
while minimizing possible delayed confounding
events that may affect mortality independent of
ED or early resuscitation events (e.g., ventilator-
associated pneumonia, establishment of do-not-
resuscitate status, procedure complications).
Evaluating early inpatient mortality at a fixed
interval from admission also avoids the potential
Figure 1. Study population sample selection. NIS, nationwide inpatient sample; ED, emergency pitfall of higher overall inpatient mortality re-
department. lated to longer lengths of stay.

2162 Crit Care Med 2010 Vol. 38, No. 11


Statistical Analysis tality of 6.9%. This represents approxi- tween patients in each of the sepsis case
mately 428,000 estimated admissions to volume quartiles. All admissions had a
Analyses were conducted with SPSS version
all U.S. nonfederal hospitals and ap- mean patient age of 69.9 yrs (95% CI,
17.0 (SPSS, Chicago, IL) and STATA version
proximately 77,000 deaths nationwide. 69.8 –70.1). There was a slight trend to-
10.0 (STATA, College Station, TX). Patient and
The median annual ED sepsis case vol- ward older age in the highest-volume
hospital characteristic data were evaluated
across sepsis case volume quartiles with chi-
ume per hospital was 249 sepsis admis- quartile hospitals as compared to the low-
square tests for categorical variables and analysis sions (range, 25–1251). The four annual est-volume quartile (p ⬍ .001). Just more
of variance for continuous measures. The unad- hospital volume quartiles ranged from 25 than half (52.9%) of the sample was fe-
justed univariate association of ED sepsis case to 145, from 146 to 248, from 249 to 371, male. For states with available data on
volume with mortality was evaluated continu- and ⬎371 admissions per year. Figure 2 race and ethnicity (71.8% of the sample
ously with a t test and by quartiles with the displays the distribution of hospital inpa- population), we found a heterogeneous
chi-square test. A population-averaged logistic tient mortality rates for the 551 hospitals distribution of race and ethnicity, with
regression model with an exchangeable working in our sample. 48.1% of the patient sample being black,
correlation matrix was used to analyze the si- On preliminary analysis, 96% of the Hispanic, or of other nonwhite races or
multaneous effects of age, gender, comorbid patients in our study population had a ethnicities. Patients admitted through
conditions, payer status, hospital size, location, principal diagnosis of septicemia (038). the higher-volume EDs had a relatively
and ED sepsis case volume (measured either We found that 13 of the 30 Elixhauser greater number of coded comorbidities
continuously or as quartile levels) on mortality. comorbid conditions were significantly (p ⬍ .05). Patients admitted through EDs
This approach accounts for nesting of admis- associated with higher mortality (p ⬍ in the highest quartile had a greater pro-
sions within hospitals (16). Forward censoring .05). These conditions included alcohol portion of patients with chronic heart
was not used in developing this regression abuse, congestive heart failure, chronic failure, cancer, coagulopathy, fluid and
model. National population estimates were made pulmonary disease, coagulopathy, cancer electrolyte disorders, pulmonary circula-
using the discharge-level weights provided with (combination of patients with lymphoma, tion disorders, peripheral vascular dis-
the NIS. Results are reported as ORs and 95%
solid tumor without metastasis, or meta- ease, and renal failure as compared with
confidence intervals (95% CIs). Significant asso-
static cancer), fluid and electrolyte disor- patients admitted through EDs in the
ciations were interpreted as p ⬍ .05. We used the
discharge-level weights and the postestimation ad-
ders, liver disease, peripheral vascular lowest sepsis case volume quartile (p ⬍
justment command in STATA to simulate the es-
disorders, pulmonary circulation disor- .05). Admissions to the lowest sepsis case
timated number of lives saved had all hospitals ders, renal failure, and weight loss (see volume hospitals had a higher proportion
performed at the level of the highest ED volume Supplemental Table 1 [Supplemental of the lowest income quartile patients
quartile. The resulting difference between pre- Digital Content 1, http://links.lww.com/ (p ⬍ .05). Each of the sepsis case volume
dicted and actual 2007 mortality was used to esti- CCM/A167]). We included indicators for quartiles had a similar percentage of pa-
mate potential lives saved across all U.S. nonfederal these 11 (after the three oncologic co- tients with Medicaid or without insur-
hospital ED admissions for sepsis in 2007. morbidities were combined) conditions ance as compared with patients with an-
in the final analysis. other form of insurance, including
RESULTS patients age 65 or older insured by Medi-
Patient and Hospital care (p ⫽ .53).
ED Sepsis Patient Sample Characteristics Across the ED The sample was primarily from urban
Sepsis Case Volume Quartiles hospitals (88.2%); 36.7% of admissions
The final study population included were from small or medium hospitals.
87,166 patients from 551 hospitals, Table 1 displays patient and hospital More than half of ED admissions for sep-
with an overall inpatient mortality rate characteristic data for the 2007 ED sepsis sis were to nonteaching hospitals
of 18.0% and an early inpatient mor- patient sample, including differences be- (58.5%). Hospitals in the highest-volume
quartile were nearly all located in urban
areas (98.2%). Only 70.6% of the lowest-
volume quartile hospitals were urban.
The highest-volume quartile also in-
cluded a significantly higher percentage
of hospitals with large bed size (80.1% vs.
39.3% in the lowest quartile; p ⬍ .05).
Last, the highest-volume quartile hospi-
tals were also more likely to be teaching
hospitals (60.8% vs. 23.1% in the lowest
quartile; p ⬍ .05).

Univariate Association of ED
Sepsis Case Volume and
Mortality

There was a significant inverse asso-


Figure 2. Inpatient sepsis mortality. Distribution of hospital inpatient mortality rates for patients ciation between ED sepsis case volume
admitted through the emergency department with a principal diagnosis of sepsis. and both early and overall inpatient

Crit Care Med 2010 Vol. 38, No. 11 2163


Table 1. Unadjusted analyses

ED Sepsis Case Volume (Quartiles)

Quartile 1: 25–145 Quartile 2: 146–248 Quartile 3: 249–371 Quartile 4: ⬎371


Sample % Cases/yr Cases/yr Cases/yr Cases/yr
(n ⫽ 87,166) (n ⫽ 21,566) (n ⫽ 21,774) (n ⫽ 21,695) (n ⫽ 22,131) p

Patient characteristics
Age (yr) ⬍.001
18–50 13.7 13.5 14.2 13.2 14.0
51–65 21.0 21.3 21.4 21.3 20.2
66–74 17.8 18.0 18.5 17.8 17.0
75–84 27.3 27.4 26.4 27.3 28.2
⬎84 20.1 19.9 19.4 20.4 20.6
Female 52.9 52.9 53.2 52.7 52.9 .74
Race/ethnicitya ⬍.001
White 51.9 54.8 51.6 54.5 46.6
Black 10.1 7.9 10.5 9.7 12.0
Hispanic 7.3 4.1 8.6 9.5 7.0
Other 2.6 1.8 1.8 3.6 3.2
Mean comorbid conditions (SD) 3.5 (⫾1.86) 3.3 (⫾1.74) 3.5 (⫾1.83) 3.6 (⫾1.89) 3.7 (⫾1.94) ⬍.001
Selected comorbid conditions
Alcohol abuse 3.4 3.3 3.6 3.4 3.1 .05
Cancerb 10.7 9.7 11.3 10.8 11.0 ⬍.001
Chronic heart failure 25.7 24.6 25.2 26.4 26.6 ⬍.001
Chronic pulmonary disease 25.8 25.8 26.0 25.8 25.4 .54
Coagulopathy 11.3 10.0 11.8 12.1 11.2 ⬍.001
Fluid and electrolyte disorder 57.0 55.0 56.3 59.4 57.4 ⬍.001
Liver failure 4.6 4.1 5.2 4.7 4.3 ⬍.001
Peripheral vascular disease 7.1 6.4 6.5 7.3 8.3 ⬍.001
Pulmonary circulation disorder 3.1 2.6 3.1 3.2 3.3 ⬍.001
Renal failure 23.9 21.6 24.5 25.3 24.3 ⬍.001
Weight loss 11.7 9.8 10.6 13.2 13.1 ⬍.001
Zip code median income quartilea ⬍.001
1 (lowest) 28.4 34.4 29.2 26.7 23.6
2 27.1 27.4 27.6 25.8 27.5
3 24.0 21.2 22.7 24.9 27.0
4 (highest) 20.5 16.9 20.4 22.7 21.9
Primary insurance .53
Medicaid/self-pay 11.5 11.3 11.7 11.5 11.4
Other insurance 88.5 88.7 88.3 88.5 88.6
Hospital characteristics
Location ⬍.001
Rural 11.8 29.4 13.7 2.6 1.8
Urban 88.2 70.6 86.3 97.4 98.2
Bed size ⬍.001
Small 11.5 20.9 10.4 5.2 9.5
Medium 25.2 39.8 24.5 26.5 10.4
Large 63.3 39.3 65.1 68.2 80.1
Teaching status ⬍.001
Teaching 41.5 23.1 36.1 45.3 60.8
Nonteaching 58.5 76.9 63.9 54.7 39.2
Inpatient mortality
1-day early mortality 4.9 5.6 5.1 5.0 4.1 ⬍.001
2-day early mortality 6.9 7.8 7.1 7.1 5.8 ⬍.001
3-day early mortality 8.3 9.2 8.6 8.5 7.0 ⬍.001
Overall mortality 18.0 18.2 18.9 18.7 16.4 ⬍.001

Unadjusted univariate associations of patient and hospital characteristics of patients admitted through the emergency department with a principal
diagnosis of sepsis across sepsis case volume quartiles. Unadjusted univariate associations of inpatient mortality across the emergency department sepsis
case volume quartiles.
a
All variables had ⬍1% missing data with the exception of race and ethnicity (28.1% missing) and median household income by zip code quartile (2.5%
missing); bcancer is a combination of three Elixhauser comorbid conditions: lymphoma, metastatic cancer, or solid tumor without metastasis.

mortality when ED sepsis case volume significantly lower across ED sepsis vol- mortality as compared to the lowest-
was evaluated continuously (p ⬍ .001; ume quartiles; case volume increased volume quartile (quartile 1; p ⫽ .03),
data not shown). Table 1 presents 1 day, for up to 3 days after admission. How- admissions in quartiles 2 and 3 with the
2 days (early inpatient mortality), and 3 ever, when examining overall inpatient highest inpatient mortality rates had
days after admission, as well as overall mortality, we found that although the higher overall inpatient mortality than
inpatient mortality rates by volume highest ED sepsis volume quartile patients in both quartile 1 and quartile
quartiles. Early inpatient mortality was (quartile 4) had significantly lower 4 (both comparisons: p ⬍ .001).

2164 Crit Care Med 2010 Vol. 38, No. 11


Table 2. Multivariate logistic regression Multivariate Analyses: ED
Sepsis Case Volume and
Early Inpatient Mortality Overall Inpatient Mortality
Odds Ratio Odds Ratio Mortality
(95% Confidence Interval) (95% Confidence Interval)
There was a highly significant associ-
Patient characteristics ation between both early and overall in-
Age (yr) patient mortality and ED sepsis case vol-
18–50 Reference Reference ume when included in the model as a
51–65 1.41 (1.26–1.58)a 1.41 (1.31–1.51)a continuous variable (p ⬍ .001; data not
66–74 1.75 (1.55–1.98)a 1.71 (1.59–1.85)a
75–84 2.36 (2.10–2.64)a 2.21 (2.05–2.37)a
shown). Patients admitted via the ED to
⬎84 3.30 (2.93–3.70)a 2.90 (2.68–3.13)a hospitals in the highest annual ED sepsis
Female 1.05 (0.99–1.11) 0.99 (0.96–1.03) case volume quartile had 27% lower odds
Selected comorbid conditions of inpatient death (OR, 0.73; 95% CI,
Alcohol abuse 1.42 (1.23–1.64)a 1.42 (1.29–1.56)a 0.64 – 0.83; p ⬍ .001) and 31% lower odds
Cancer 1.74 (1.61–1.87)a 1.99 (1.89–2.10)a
Chronic heart failure 0.94 (0.88–1.00)b 1.38 (1.33–1.44)a of early inpatient death (OR, 0.69; 95%
Chronic pulmonary disease 0.85 (0.79–0.90)a 0.99 (0.95–1.03) CI, 0.61– 0.80; p ⬍ .001) when compared
Coagulopathy 1.20 (1.11–1.30)a 1.92 (1.82–2.01)a to patients admitted to hospitals in the
Fluid and electrolyte disorder 1.20 (1.14–1.27)a 1.39 (1.34–1.44)a lowest ED sepsis case volume quartile.
Liver failure 1.78 (1.58–2.00)a 1.88 (1.73–2.03)a
Peripheral vascular disease 1.31 (1.19–1.44)a 1.19 (1.11–1.27)a
Unlike the unadjusted results presented
Pulmonary circulation disorder 0.97 (0.83–1.14) 1.26 (1.15–1.39)a in Table 1, the multivariate model results
Renal failure 0.97 (0.91–1.03) 1.19 (1.14–1.24)a indicated that patients admitted to the
Weight loss 0.48 (0.43–0.54)a 1.20 (1.14–1.27)a second highest ED sepsis case volume
Zip code median income quartile quartile (quartile 3) also had 17% lower
Quartile 1 (lowest) Reference Reference
Quartile 2 0.96 (0.89–1.04) 0.98 (0.93–1.03) odds of inpatient mortality (OR, 0.83;
Quartile 3 0.96 (0.89–1.04) 0.97 (0.92–1.03) 95% CI, 0.74 – 0.93; p ⫽ .001) and 17%
Quartile 4 (highest) 1.00 (0.92–1.09) 0.96 (0.90–1.02) lower odds of early mortality (OR, 0.83;
Medicaid/self–pay 1.21 (1.09–1.34)a 1.09 (1.02–1.16)b 95% CI, 0.74 – 0.93; p ⬍ .05) when com-
Hospital characteristics
Rural location 0.91 (0.81–1.02) 0.75 (0.67–0.84)a
pared to patients admitted to the lowest
Bed size quartile hospitals. The ED volume–
Small Reference Reference outcome relationship continued to hold
Medium 1.00 (0.89–1.14) 1.09 (0.97–1.22) for early mortality and overall inpatient
Large 1.07 (0.94–1.20) 1.20 (1.07–1.35) b mortality in quartile 2 (OR, 0.85; 95% CI,
Teaching hospital 1.05 (0.97–1.14) 1.21 (1.12–1.31)a
Emergency department sepsis 0.77– 0.95; p ⬍ .05 and OR, 0.90; 95% CI,
case volume/yr (quartile) 0.82– 0.99; p ⬍ .05, respectively). Ad-
25–145 (1) Reference Reference justed mortality results based on the
146–248 (2) 0.85 (0.77–0.95)b 0.90 (0.82–0.99)b multivariate model translate to an esti-
249–371 (3) 0.83 (0.74–0.93)b 0.83 (0.74–0.93)b mated overall inpatient mortality of
⬎371 (4) 0.69 (0.61–0.80)a 0.73 (0.64–0.83)a
17.2% and estimated early inpatient mor-
Multivariate logistic regression (adjusted) analyses of the likelihood of overall and early (within 2 tality of 6.4%.
days of hospital admission) inpatient mortality in 87,166 admissions from the emergency department The model of overall inpatient mortal-
with a principal diagnosis of sepsis to 551 hospitals in 2007. ity had a C-statistic of 0.64 (95% CI,
a
p ⬍ .001; bp ⬍ .05. 0.63– 0.64), whereas the model of early
mortality had a C-statistic of 0.61 (95%
CI, 0.61– 0.62). Results were virtually
Multivariate Analyses: Patient Medicaid or self-pay patients (OR, 1.09; identical when the analyses were per-
and Hospital Factors and 95% CI, 1.02–1.16; p ⬍ .05 and OR, formed including hospitals with ⬍25 ad-
1.21; 95% CI, 1.09 –1.34; p ⬍ .001, re- missions included (data not shown).
Mortality
spectively).
Many hospital and patient factors Patients admitted to teaching hospi- DISCUSSION
were significantly associated with mor- tals had 21% greater odds of inpatient
tality when simultaneously controlling This is the first work to our knowledge
death when compared to nonteaching
for other risk factors (Table 2). The risk to demonstrate a relationship between
hospitals (OR, 1.21; 95% CI, 1.12–1.31;
of inpatient mortality and early inpa- ED sepsis volume and hospital mortality
tient mortality increased with age. Most p ⬍ .001) and patients admitted to larger and is one of the few analyses of the
of the comorbid conditions included in hospitals had a similar 20% increased association between ED case volume and
the adjusted model were associated odds of inpatient mortality (OR, 1.20; outcome (17, 18). We first demonstrate
with an increased risk of mortality. Af- 95% CI, 1.07–1.35; p ⬍ .05). These rela- interhospital variability in mortality
ter adjustment for other factors, there tionships held for early mortality, but the among patients admitted to the hospital
was no significant association between differences were smaller and nonsignifi- via the ED with sepsis. Even after exclud-
zip code median income level and mor- cant (OR, 1.05; 95% CI, 0.97–1.14; p ⫽ ing extreme outlier hospital EDs with ex-
tality, but there was an increased odds .238 and OR, 1.07; 95% CI, 0.94 –1.20; tremely low sepsis volumes of ⬍25 cases
of both overall and early mortality for p ⫽ .302, respectively). per year, our results demonstrate a wide

Crit Care Med 2010 Vol. 38, No. 11 2165


variation in mortality rates across a nor- mortality as compared with patients in hospital teaching status. Thus, although
mal distribution (Fig. 2). This variation in the two middle quartiles, this difference selective referral patterns could play a
outcome alone could support that there disappears in the fully adjusted analysis small role, it is likely that greater experi-
are likely significant quality-of-care dif- after adjustment for these comorbid con- ence in sepsis resuscitation confers a
ferences in sepsis treatment across hos- ditions and other patient and hospital fac- quality-of-care advantage.
pitals and EDs in this nationwide sample. tors. Using the NIS nationally representa-
However, our findings further demon- tive discharge weights and extrapolating
strate a significant association between Large Hospitals vs. High- to all U.S. hospital ED admissions for
an ED-specific factor, ED sepsis case vol- Volume Sepsis Centers sepsis, if all hospitals were to perform at
ume, and both overall and early inpatient the level of the highest sepsis volume
mortality after adjustment for comorbid The adjusted results demonstrate that quartile hospitals, then we would achieve
conditions and hospital factors such as although patients admitted through hos- a reduction in the baseline adjusted mor-
bed size and teaching status. Patients ad- pitals with a high volume of ED sepsis tality rate from 17.2% to 15.0%, and this
mitted through hospital EDs in the high- admissions have lower mortality, patients would result in approximately 9,400 lives
est sepsis volume quartile had 27% lower admitted through hospitals with large saved annually.
risk-adjusted odds of inpatient mortality. bed size have significantly higher overall This study provides support for the
These findings were robust with respect mortality. There were 38 hospitals in the potential role of studying the operations
to early inpatient mortality: there was a highest ED sepsis volume quartile: 37 of of high-volume institutions to discover
31% lower risk-adjusted odds of early in- these are unsurprisingly also classified by sepsis resuscitation delivery best prac-
patient mortality. Early mortality would the NIS as large-bed-size hospitals. There tices, ultimately to be disseminated to all
presumably be more closely related to the are 275 total large-bed-size hospitals, and types of EDs, regardless of experience and
ED resuscitation of a septic patient. This a significant proportion of large-bed-size volume. The solution may lie in targeted
early mortality reduction gives even hospitals have EDs in the second and efforts toward EDs with low sepsis vol-
greater support to the potential positive third sepsis volume quartiles (43.9% of umes to increase education of care pro-
effects of ED experience and quality of large-bed-size hospitals). The overall un- viders with respect to early recognition,
care. We believe that these differences in adjusted mortality rates at large-bed-size diagnosis, resuscitation, and technical as-
mortality across institutions, after adjust- hospitals in ED volume quartiles 2 and 3 pects of sepsis care. Implementation of
ment for comorbid conditions and hospi- were 19.3% and 19.0%, respectively, as sepsis best practices is likely to be differ-
tal factors, likely reflect improved ED compared to 16.9% at the 37 large-bed- ent and require alterations in smaller
quality of care in higher sepsis volume size hospitals with EDs in the highest ED low-volume institutions as compared to
EDs with more experience in sepsis re- sepsis volume quartile. higher-volume institutions. Future
suscitation. This higher quality of care work should examine the success
can lead to potentially important conse- Volume–Outcome Relationship achieved at higher-volume institutions
quences for patient survival. and Quality of Care to identify best operational practices in
sepsis care delivery and then translate
Differences Between the ED The relationship between volume and and adapt these best practices to lower-
Sepsis Volume Quartiles outcome has been explored extensively in volume institutions through methodol-
other disciplines, particularly elective ogies in translational and dissemina-
Although the four sepsis case volume surgery (13). There are two major hy- tion research (20).
quartiles are quite clinically similar with potheses that have been presented to ex-
respect to patients’ age distribution and plain the volume– outcome relationship Limitations
gender, patients in the highest sepsis case and its relationship to quality of care:
volume quartile have a significantly selective referral patterns (patients dis- There are several limitations to this
greater number of comorbid conditions proportionately seek care at, and physi- study, many of which are inherent to
recorded when compared to the lowest cians refer to, hospitals known for high secondary data analysis of population-
sepsis volume quartile. There are also sig- quality) and the practice-makes-perfect based hospital discharge datasets. The
nificant differences between patients seen theory (experience through higher vol- principal diagnosis is widely accepted as
at hospitals in the highest vs. the lowest ume improves quality of care) (19). In the diagnosis chiefly responsible for ad-
quartiles with respect to the incidence of high-acuity emergent conditions, such as mission to the hospital (21). We were
specific comorbid conditions, such as sepsis, the practice-makes-perfect ratio- unable, in this deidentified dataset, to go
cancer, chronic heart failure, peripheral nale is much more likely to be the dom- back to source medical records to con-
vascular disease, and renal failure. We inant reason for better quality of care firm this for each case. In an effort to
hypothesize that other significant differ- (19). Septic patients are acutely and se- increase the specificity of our patient co-
ences, such as fluid and electrolyte disor- verely ill and often do not have the luxury hort search strategy, we excluded all pa-
ders and coagulopathy, indicate higher of choosing to which ED they present. tients with a secondary diagnosis of sepsis
sepsis severity at higher-volume centers However, in our sample population, high and therefore likely missed some patients
(Table 1). sepsis volume centers were more likely to admitted through the ED with sepsis but
This could occur if secondary diagno- be associated with academic institutions were admitted for other significant con-
sis codes were assigned in relation to the (60.8% in highest-volume quartile vs. ditions. Ideally, we would have performed
primary sepsis disease process. Although 23.1% in the lowest-volume quartile; p ⬍ further analyses on patients with varying
patients in the lowest sepsis case volume .001), the volume– outcome relationship severity of illness, i.e., sepsis, severe sep-
quartile have lower unadjusted overall remained significant after adjustment for sis, and septic shock. However, we were

2166 Crit Care Med 2010 Vol. 38, No. 11


also unable to define the population of The logistic regression model discrim- may result in a significant mortality re-
patients admitted via the ED with severe ination is relatively low, as indicated by duction nationwide.
sepsis because the diagnosis of organ fail- the C-statistics. This is a function in part
ure as a secondary diagnosis could have of the high sepsis mortality rate that pre-
been based on a subsequent in-hospital cludes high accuracy for a model predict- REFERENCES
complication that might not have been ing that all patients survive. Models of
present at ED evaluation. For this reason, lower-death-rate conditions (⬍5%) gen- 1. Angus DC, Linde-Zwirble WT, Lidicker J, et
the reported mortality rate of 18.0% for erally achieve C-statistics between 0.7 al: Epidemiology of severe sepsis in the
sepsis admissions is lower than that com- and 0.8. Model C-statistics are also lower United States: Analysis of incidence, out-
monly reported for patients with severe because we lacked access to detailed clin- come, and associated costs of care. Crit Care
sepsis or septic shock (1, 2). ical information to better adjust for the Med 2001; 29:1303–1310
It is also important to recognize that severity of illness. The inclusion of more 2. Dombrovskiy VY, Martin AA, Sunderram J, et
hospitals may have varying tendencies to detailed information on admission sever- al: Rapid increase in hospitalization and
diagnose sepsis at different stages of the ity of illness, such as Acute Physiology mortality rates for severe sepsis in the United
States: A trend analysis from 1993 to 2003.
disease process. For example, hospitals and Chronic Health Evaluation scores,
Crit Care Med 2007; 35:1244 –1250
with a greater number of sepsis patients would add to the calibration and discrim- 3. Martin GS, Mannino DM, Eaton S, et al: The
may be more likely to diagnose and treat ination of the mortality models that nev- epidemiology of sepsis in the United States
sepsis early in the disease process and ertheless will have large remaining un- from 1979 through 2000. N Engl J Med 2003;
therefore maintain patients at a lower measured elements of chance. 348:1546 –1554
severity of illness overall and subse- Finally, the results of this study are lim- 4. Gao F, Melody T, Daniels DF, et al: The
quently have lower mortality rates. Lower ited to demonstrating that there was an impact of compliance with 6-hour and 24-
sepsis volume centers could be more con- association between ED sepsis case volume hour sepsis bundles on hospital mortality in
servative in their approach to diagnosing and mortality and a variation in sepsis in- patients with severe sepsis: A prospective ob-
sepsis and therefore care for a population patient mortality and early mortality across servational study. Crit Care 2005;
9:R764 –R770
with higher severity of illness. Further hospitals based on annual ED sepsis case
5. Jones AE, Focht A, Horton JM, et al: Prospec-
research is needed to better understand volume. We are unable to comment with
tive external validation of the clinical effec-
this potential confounder. Alternatively, certainty on why EDs with higher sepsis tiveness of an emergency department-based
as discussed, we hypothesize that patients case volumes performed better than other early goal-directed therapy protocol for se-
in the highest sepsis volume quartile hospital EDs, but we postulate that it is less vere sepsis and septic shock. Chest 2007;
might have a higher severity of illness. If likely a patient selection effect and more 132:425– 432
we were to have limited our analysis to likely to be related to better sepsis resusci- 6. Nguyen HB, Corbett SW, Steele R, et al:
only patients with severe sepsis or septic tation experience and quality of care. Fu- Implementation of a bundle of quality indi-
shock, then we hypothesize that this ture research should examine processes-of- cators for the early management of severe
would reduce this potential confounder care differences between EDs with varying sepsis and septic shock is associated with
and we would see a more pronounced experience levels to determine whether decreased mortality. Crit Care Med 2007; 35:
1105–1112
relationship between ED sepsis volume specific factors in sepsis resuscitation pro-
7. Puskarich MA, Marchick MR, Kline JA, et al:
and mortality. cess are associated with improved out- One year mortality of patients treated with
Use of administrative hospital data comes. an emergency department based early goal
also guided the information that we are directed therapy protocol for severe sepsis
able to analyze and study. We are limited CONCLUSION and septic shock: A before and after study.
to the comorbid conditions and severity Crit Care 2009; 13:R167
of illness classification methods provided The results of this model demonstrate 8. Sands KE, Bates DW, Lanken PN, et al: Epi-
by International Classification of Diseases a wide variation in mortality rates among demiology of sepsis syndrome in 8 academic
ninth revision codes. We hypothesize that patients admitted to hospitals across the medical centers. JAMA 1997; 278:234 –240
some of the differences in association be- United States via the ED with sepsis and 9. Wang HE, Shapiro NI, Angus DC, et al: Na-
tional estimates of severe sepsis in United
tween certain comorbid conditions and support a significant association between
States emergency departments. Crit Care
early mortality vs. overall mortality are ED sepsis experience and mortality. After Med 2007; 35:1928 –1936
secondary to coding bias. For example, adjustment for comorbid conditions and 10. Dellinger RP, Levy MM, Carlet JM, et al:
weight loss is protective in the adjusted hospital-level factors, there was a signif- Surviving Sepsis Campaign: international
model of early inpatient mortality but icant relationship between ED sepsis case guidelines for management of severe sepsis
hazardous in the model of overall mor- volume and individual overall and early and septic shock: 2008. Crit Care Med 2008;
tality. We hypothesize that this is because inpatient mortality in patients admitted 36:296 –327
of more intensive coding of acute com- through the ED with sepsis. When com- 11. The Surviving Sepsis Campaign and Institute
plications for patients with early hospital pared with hospitals with the lowest an- for Healthcare Improvement Sepsis Bundles:
death, as opposed to coding of more nual ED volume of sepsis cases, patients 1009 [cited October 25, 2009]. Available at:
http://www.ihi.org/IHI/topics/CriticalCare/
chronic conditions for patients who re- cared for in the highest quartile hospitals
Sepsis. Accessed August 26, 2010
mained in the hospital longer and then had 27% lower odds of overall inpatient
12. Townsend SR, Schorr C, Levy MM, et al:
died. We did not have access to more mortality in this large heterogeneous Reducing mortality in severe sepsis: The Sur-
refined severity measures such as detailed sample. Efforts to optimize sepsis resus- viving Sepsis Campaign. Clin Chest Med
admission laboratory or imaging data to citation experience and translate sepsis 2008; 29:721–733, x
confirm the presence or absence of severe resuscitation best practices to lower- 13. Birkmeyer JD, Siewers AE, Finlayson EV, et
sepsis on admission to the hospital. volume EDs should be considered and al: Hospital volume and surgical mortality in

Crit Care Med 2010 Vol. 38, No. 11 2167


the United States. N Engl J Med 2002; 346: ysis for discrete and continuous outcomes. outcome relationship: Practice-makes-
1128 –1137 Biometrics 1986; 42:121–130 perfect or selective-referral patterns? Health
14. Elixhauser A, Steiner C, Fraser I: Volume 17. Chase M, Hollander JE: Volume and out- Serv Res 1987; 22:26
thresholds and hospital characteristics in the come: The more patients the better? Ann 20. Westfall JM, Mold J, Fagnan L: Practice-
United States. Health Aff (Millwood) 2003; Emerg Med 2006; 48:657– 659 based research–“Blue Highways” on the NIH
22:167–177 18. Schull MJ, Vermeulen MJ, Stukel TA: The roadmap. JAMA 2007; 297:403– 406
15. Elixhauser A, Steiner C, Harris DR, et al: risk of missed diagnosis of acute myocardial 21. International Classification of Diseases-9-CM
Comorbidity measures for use with adm- infarction associated with emergency depart- Official Guidelines for Coding and Reporting
inistrative data. Med Care; 1998: ment volume. Ann Emerg Med 2006; 48: 2005. [cited December 1, 2009]. Available at:
8 –27 647– 655 http://www.cdc.gov/nchs/data/icd9/icdguide09.
16. Zeger SL, Liang KY: Longitudinal data anal- 19. Luft HS, Hunt SS, Maerki SC: The volume- pdf. Accessed August 26, 2010

2168 Crit Care Med 2010 Vol. 38, No. 11