Introduction
Upper gastrointestinal bleeding is a common gastrointestinal emergency. Despite advances
in risk factor modification and preventive strategies, upper gastrointestinal bleeding
remains common, affecting up to 100 to 170 per 100,000 adults annually, with an associated
mortality of 5 % to 14 % [1]. The hospitalization rate for upper gastrointestinal bleeding is estimated to be
six-fold higher than that of lower gastrointestinal bleeding [2]. Multiple risk factors have been described for upper gastrointestinal bleeding,
including Helicobacter pylori infection, nonsteroidal anti-inflammatory medication use, chronic liver disease,
and antiplatelet/anticoagulant medication use [3]. The most common causes of upper gastrointestinal bleeding include (in approximate
descending order of frequency): gastric and duodenal ulcers, esophago-gastric varices,
erosive esophagitis, erosive gastritis, portal gastropathy, vascular ectasia, mass
lesions and Mallory-Weiss syndrome [4]
[5]. In approximately 10 % of cases, no source of bleeding can be identified.
Esophagogastroduodenoscopy (EGD) has invaluable diagnostic and therapeutic utility
in upper gastrointestinal bleeding. It is the modality of choice for identifying the
etiology of upper gastrointestinal bleeding given its high sensitivity and specificity,
along with the ability to achieve therapeutic hemostasis and prevent rebleeding in
most patients [6]
[7]
[8]. However, the benefit of early endoscopy (EGD within 24 hours) remains unclear,
with studies showing variable results. A retrospective study of a community-based
practice of 909 hospitalized patients found a reduction in length of stay in all patients
who underwent early endoscopy, and a reduction in the risk for recurrent bleeding
and surgery in high-risk patients (those with ulcers or tears with active bleeding,
arterial spurting, or a visible vessel, and a history of bleeding esophageal or gastric
varices) [9]. Another observational cohort study of 3800 patients admitted with upper gastrointestinal
bleeding showed similar benefits, while another population-based study found a reduction
in length of stay and need for surgery [10]. One previous analysis of national inpatient data found that early EGD was associated
with lower risk of mortality [11]. However, other studies did not show improved outcomes. In a retrospective analysis
of 502 patients in Canada, for example, patients who underwent endoscopy within 24
hours had higher rates of mortality and need for surgery than those who underwent
endoscopy > 24 hours after presentation [12]. Another national study of over 4000 patients in the UK found no improvement in
mortality or need for surgery in patients who underwent early (< 12 hours) endoscopy,
however, they did have shorter length of stay and there was a trend toward lower rebleeding
rates in high-risk patients [13].
Multiple guidelines currently recommend endoscopy within 24 hours of presentation
for non-variceal upper gastrointestinal bleeding [14]
[15]
[16] Use of early endoscopy has increased in a previous national database analysis, along
with a reduction in mortality for patients hospitalized with upper gastrointestinal
bleeding, however, this study did not investigate the association between early endoscopy
and mortality [17]. In addition, this analysis found that despite increased rates of endoscopy over
time, only 54 % of patients underwent endoscopy within 24 hours in 2009. Other studies
have also found that a significant proportion of patients fail to undergo endoscopy
within 24 hours [18]
[19]. Hence, utilizing a nationwide database, we aimed to: 1) compare mortality during
hospitalizations in those who received early EGD (< 24 hours) or delayed EGD (> 24hours)
for upper gastrointestinal bleeding, as well as those who did not undergo EGD; 2)
compare the length of hospitalization, need for blood transfusion, and incidence of
acute renal failure and other complications among the 3 groups; and 3) Compare the
impact of early vs delayed EGD on the total costs of hospital stay in patients with
upper gastrointestinal bleeding
Patients and methods
Study design and data source
This was a retrospective longitudinal study of admissions to acute care hospitals
for upper gastrointestinal bleeding. Data on hospital admissions of all adult patients
(18 years or older) were extracted from the National Inpatient Sample (NIS) from 2007
to 2013. The NIS is the largest publicly available all-payer inpatient discharge database
in the United States. Developed and maintained by the Agency for Healthcare Research
and Quality, it comprises a 20 % sample of all inpatient discharges from US hospitals
meant to be representative of nationwide acute care hospitalizations. The database
contains de-identified information regarding each hospitalization, including demographic
characteristics, admission status, comorbidities, discharge diagnoses, procedures,
outcomes, and costs of hospitalization. Patients admitted under observation status
and patients admitted to short-term rehabilitation hospitals, long-term non – acute
care hospitals, psychiatric hospitals, and alcoholism or chemical dependency units
are not included.
Study population
We used International Classification of Diseases, Ninth Revision, Clinical Modification
(ICD-9-CM) codes to identify all hospitalized adults aged at least 18 years who were
discharged with a diagnosis of upper gastrointestinal bleeding, during 2007 through
2013.
The patients have listed a primary discharge diagnosis and up to 24 secondary discharge
diagnoses. The patients can also have up to 15 procedure codes associated with the
discharges. This database also describes the day the procedure was conducted.
Patients were classified as having upper gastrointestinal bleeding by querying all
diagnostic codes for the ICD-9-CM codes corresponding to upper gastrointestinal bleeding.
For these patients, performance of EGD during admission was determined by querying
all procedural codes for the ICD-9-CM codes corresponding to EGD; early EGD was defined
as having EGD performed within 24 hours of admission and late EGD was defined as having
EGD performed after 24 hours of admission. Patients with multiple EGDs during the
same admission were classified based on when the first procedure was done. All diagnostic
and procedural codes used for classifications are found in Appendix 1.
Definition of Variables, comorbidities, and other covariates
The NIS contains demographic information on all hospitalizations, including age, gender,
race and, primary and secondary insurance. Patient’s comorbidity was adjusted. The
Healthcare Cost and Utilization Project (HCUP) Comorbidity Software was used to generate
Elixhauser comorbidities from ICD-9 CM diagnosis codes (https://www.hcup-us.ahrq.gov/toolssoftware/comorbidity/comorbidity.jsp). A modified Charlson Comorbidity Index (CCI) was calculated using the NIS Disease
Severity Measure files. Several modifications were performed because not all 22 comorbidities
are coded into the NIS database: 1) history of myocardial infarction was omitted and
2) liver disease was given an adjusted weight of 2 points rather than 1 for mild disease
and 3 points for moderate to severe disease.
Apart from the comorbidities scored by the CCI, we also identified the presence of
specific comorbidities that may play an important role in the severity of bleeding.
Indicators of severity of bleeding such as hypovolemia/shock, acute renal failure
and need for dialysis, respiratory failure, as well as the frequency of various supportive
interventions as surrogate indicators of hemodynamic status, such as endotracheal
intubation, were also noted and used as covariates in multivariate analysis of the
outcomes by using the ICD-9-CM codes.
Outcomes
We analyzed the following outcomes: 1) prevalence of upper gastrointestinal bleeding
in hospitalizations, 2) timing of endoscopy in admissions associated with upper gastrointestinal
bleeding, 3) in-hospital mortality in admissions with upper gastrointestinal bleeding
in respect to timing of endoscopy; and 4) Length of stay and hospitalization charges
associated with upper gastrointestinal bleeding in respect to timing of endoscopy.
Statistical analysis
Data are presented as mean ± standard deviation for continuous variables or weighted
frequency (%) for categorical factors. A univariate analysis was performed to assess
differences between the 3 groups (no EGD, early EGD and late EGD); continuous variables
were compared using t-tests and categorical variables were compared using Rao-Scott chi-square tests. In
addition, multivariable analysis was performed to assess differences between the groups
in terms of the outcomes of interest while adjusting for patient and hospital characteristics.
Logistic regression analysis was used to model mortality and linear regression analysis
was used for length of stay and total costs. NIS is based on a complex sampling design
that includes stratification, clustering and weighting; SAS Survey procedures facilitate
the unbiased assessment of population estimates. A P < 0.001 was considered statistically significant because of the large sample size;
this significance criterion has been used by previous NIS studies. All analyses were
performed using SAS (version 9.4, The SAS Institute, Cary, NC).
Results
From the NIS database dated 2007 to 2013, a total of 2,066,707 adult patients (older
than 18 years of age) were identified as having the primary discharge diagnosis of
upper gastrointestinal bleeding. Among these patients, 1,735,116 (83.96 %) had undergone
EGD during the admission, while 331,591 (16 %) did not have an EGD. Of the patients
who underwent EGD, 1,020,744 were noted to have had an early EGD (within the first
24 hours), while 714,372 had delayed EGD ( > 24 hours).
[Table 1] presents the various etiologies of upper gastrointestinal bleeding among the hospital
admissions. Bleeding peptic ulcer was the by far the most common cause of upper gastrointestinal
bleeding making up almost 50 % of the patient population. Much less common causes
of upper gastrointestinal bleeding, such as Dieulafoy lesions, comprised 1.9 % of
the studied subjects.
Table 1
Etiology of upper gastrointestinal hemorrhage.
|
Upper gastrointestinal hemorrhage
|
n (%)
|
|
Bleeding esophageal varices
|
222,148 (12.4)
|
|
Bleeding peptic ulcer
|
876,320 (49.0)
|
|
Mallory-Weiss
|
186,634 (10.4)
|
|
Gastritis with hemorrhage
|
423,450 (23.7)
|
|
Dieulafoy’s lesion of stomach or duodenum
|
32,790 (1.8)
|
|
Angiodysplasia of stomach or duodenum with hemorrhage
|
155,594 (8.7)
|
[Table 2] shows the basic characteristics and demographics of the 3 studied groups (early
EGD, delayed EGD, no EGD). Patients in the delayed EGD group were older with a mean
age of 67.6 ± 0.11 years, compared to 64.0 ± 0.09 years in the early EGD group and
63.9 ± 0.13 years in the no EGD group (P < 0.001). Patients in all groups were more likely to be men and to have Medicare.
Patients who underwent delayed EGD had a higher CCI than the other two groups (P < 0.001). The proportion of patients with a CCI of 3 or more in the delayed group
was 76 % as compared to 61.4 % in the early EGD group and 69.1 % in the no EGD group
(P < 0.001).
Table 2
Patient and hospital characteristics.
|
Factor
|
Early EGD
n = 870,159
|
Late EGD
n = 631,412
|
No EGD
n = 287,961
|
P value
|
|
Age (years), mean ±SD
|
64.0 ± 0.10
|
67.6 ± 0.12
|
64.1 ± 0.15
|
< 0.001
|
|
Age (years)
|
|
|
|
< 0.001
|
|
18 – 35
|
49,577 (5.7)
|
24,095 (3.8)
|
24,620 (8.5)
|
|
|
36 – 50
|
135,750 (15.6)
|
71,031 (11.2)
|
43,509 (15.1)
|
|
|
51 – 65
|
261,147 (30.0)
|
161,303 (25.5)
|
73,123 (25.4)
|
|
|
> 65
|
423,686 (48.7)
|
374,983 (59.4)
|
146,709 (50.9)
|
|
|
Gender
|
|
|
|
< 0.001
|
|
Male
|
503,200 (57.8)
|
326,560 (51.7)
|
151,710 (52.7)
|
|
|
Female
|
366,816 (42.2)
|
304,828 (48.3)
|
136,167 (47.3)
|
|
|
Race
|
|
|
|
< 0.001
|
|
White
|
564,485 (64.9)
|
345,664 (54.7)
|
170,051 (59.1)
|
|
|
Black
|
92,057 (10.6)
|
72,628 (11.5)
|
36,626 (12.7)
|
|
|
Hispanic
|
82,140 (9.4)
|
46,547 (7.4)
|
22,135 (7.7)
|
|
|
Other
|
54,097 (6.2)
|
30,317 (4.8)
|
14,699 (5.1)
|
|
|
Unknown
|
77,380 (8.9)
|
136,256 (21.6)
|
44,450 (15.4)
|
|
|
Insurance
|
|
|
|
< 0.001
|
|
Medicare
|
457,208 (52.7)
|
405,556 (64.3)
|
165,366 (57.6)
|
|
|
Medicaid
|
85,399 (9.8)
|
58,067 (9.2)
|
35,398 (12.3)
|
|
|
Private Insurance
|
218,286 (25.1)
|
115,434 (18.3)
|
55,025 (19.2)
|
|
|
Other
|
107,152 (12.3)
|
51,319 (8.1)
|
31,362 (10.9)
|
|
|
CCI, mean ± SD
|
3.5 ±0.01
|
4.2 ±0.02
|
3.9 ±0.02
|
< 0.001
|
|
CCI
|
|
|
|
< 0.001
|
|
0
|
98,254 (11.3)
|
40,975 (6.5)
|
31,234 (10.8)
|
|
|
1
|
97,742 (11.2)
|
46,192 (7.3)
|
25,215 (8.8)
|
|
|
2
|
117,390 (13.5)
|
65,663 (10.4)
|
32,524 (11.3)
|
|
|
3
|
136,029 (15.6)
|
87,965 (13.9)
|
37,447 (13.0)
|
|
|
4 +
|
420,744 (48.4)
|
390,617 (61.9)
|
161,542 (56.1)
|
|
|
Weekend admission
|
|
|
|
< 0.001
|
|
Weekday
|
684,462 (78.7)
|
463,964 (73.5)
|
220,873 (76.7)
|
|
|
Weekend
|
185,698 (21.3)
|
167,448 (26.5)
|
67,088 (23.3)
|
|
|
Hospital location
|
|
|
|
< 0.001
|
|
Rural
|
91,210 (10.6)
|
75,349 (12.0)
|
46,290 (16.2)
|
|
|
Urban
|
771,664 (89.4)
|
552,410 (88.0)
|
239,666 (83.8)
|
|
|
Hospital teaching status
|
|
|
|
0.066
|
|
Non-teaching
|
506,008 (58.6)
|
357,462 (56.9)
|
162,213 (56.7)
|
|
|
Teaching
|
356,865 (41.4)
|
270,297 (43.1)
|
123,743 (43.3)
|
|
|
Bed size of hospital
|
|
|
|
< 0.001
|
|
Small
|
94,952 (11.0)
|
71,213 (11.3)
|
40,098 (14.0)
|
|
|
Medium
|
225,847 (26.2)
|
149,910 (23.9)
|
69,256 (24.2)
|
|
|
Large
|
542,074 (62.8)
|
406,636 (64.8)
|
176,602 (61.8)
|
|
|
Region of hospital
|
|
|
|
< 0.001
|
|
Northeast
|
156,660 (18.0)
|
106,811 (16.9)
|
54,506 (18.9)
|
|
|
Midwest
|
169,273 (19.5)
|
174,267 (27.6)
|
62,823 (21.8)
|
|
|
South
|
345,145 (39.7)
|
244,930 (38.8)
|
113,465 (39.4)
|
|
|
West
|
199,081 (22.9)
|
105,404 (16.7)
|
57,166 (19.9)
|
|
|
Median household income
|
|
|
|
< 0.001
|
|
1
|
234,860 (27.6)
|
189,671 (30.8)
|
90,823 (32.4)
|
|
|
2
|
225,128 (26.5)
|
165,045 (26.8)
|
74,592 (26.6)
|
|
|
3
|
206,899 (24.3)
|
145,666 (23.6)
|
63,398 (22.6)
|
|
|
4
|
182,937 (21.5)
|
115,635 (18.8)
|
51,602 (18.4)
|
|
Data presented as Weighted Frequency (%) unless otherwise stated
The rates of adverse events (AEs) also varied among the groups as shown in [Table 3]. Endoscopic therapy was found to be more common in patients who underwent early
EGD (43.8 %) compared to the delayed EGD group (31.6 %) (P < 0.001). Patients who did not undergo EGD were less likely to get blood transfusions
(33.7 %) as compared to those who underwent early EGD (55.0 %) and delayed EGD (51.6 %).
Patients who underwent early EGD were less likely to have hypovolemia and shock than
the other groups (13.7 % in the early EGD group, with 14.2 % and 14.9 % in the delayed
and no-EGD groups respectively). Acute respiratory failure was more likely in the
no-EGD group at 10.9 %, than 8.3 % in the delayed EGD group and 5.2 % in the early
EGD group (P < 0.001). Patients in the delayed EGD group were more likely to develop acute renal
failure (27.0 %) as compared with the no-EGD group (24.5 %) and the early EGD group
(16.7 %) (P < 0.001).
Table 3
Adverse events and outcomes.
|
Factor
|
Early EGD
n = 870,159
|
Late EGD
n = 631,412
|
No EGD
n = 287,961
|
P value
|
|
Blood transfusion
|
477,264 (54.8)
|
323,938 (51.3)
|
97,391 (33.8)
|
< 0.001
|
|
Hypovolemia/shock
|
116,826 (13.4)
|
88,880 (14.1)
|
42,538 (14.8)
|
< 0.001
|
|
Acute renal failure
|
139,094 (16.0)
|
164,278 (26.0)
|
68,726 (23.9)
|
< 0.001
|
|
Acute respiratory failure
|
43,479 (5.0)
|
51,071 (8.1)
|
30,886 (10.7)
|
< 0.001
|
|
Endoscopic therapy
|
375,649 (43.2)
|
195,296 (30.9)
|
---
|
< 0.001
|
|
LOS (days)
|
4.6 ± 0.02
|
8.5 ± 0.08
|
7.7 ± 0.09
|
< 0.001
|
|
Total charges ($)
|
38313.6 ± 529.8
|
64412.2 ± 1267.2
|
62266.7 ± 1737.1
|
< 0.001
|
|
Inflation-adjusted charges (2013 $)
|
36347.6 ± 502.3
|
60915.2 ± 1202.6
|
58987.4 ± 1653.7
|
< 0.001
|
|
Died during hospitalization
|
26,181 (3.0)
|
26,457 (4.2)
|
24,491 (8.5)
|
< 0.001
|
Data presented as mean ± standard error or Weighted Frequency (%)
Outcomes
Mortality
The primary outcome of the study was in-hospital mortality. Mortality was found to
be significantly higher in the delayed EGD group as compared to the early EGD group
(4.2 % vs 3.0 % P < 0.001) ([Table 3]). Mortality was much higher in the no-EGD group (8.5 %) compared to the early and
late EGD groups (P < 0.001).
On multivariate analysis, patients who did not undergo EGD were 3 times likely to
die compared to those who underwent early EGD (OR 3.0; 99.9 % CI 2.8 – 3.2; P < 0.001) ([Table 4]). Also, those who had a delayed EGD were 1.4 times more likely to die compared with
early EGD patients (OR 1.4; 99.9 % CI 1.3 – 1.5; P < 0.001). Patients with a CCI of 4 or more had an over 4-fold chance of mortality
compared to those with a CCI of 0 (OR 4.4; 99.9 % CI 3.7 – 5.1; P < 0.001). Other risk factors associated with a higher in-hospital mortality for upper
gastrointestinal bleeding on multivariate analysis included male sex (OR 1.4; 99.9 %
CI 1.3 – 1.5; P < 0.001), Hispanic ethnicity (OR 1.1; 99.9 % CI 1.0 – 1.2; P < 0.001), insurance other than Medicare (OR 1.4; 99.9 % CI 1.2 – 1.6; P < 0.001), weekend admission (OR 1.1; 99.9 % CI 1.0 – 1.2; P < 0.001), and admission to a large (OR 1.3; 99.9 % CI 1.2 – 1.5; p < 0.001), urban
(OR 1.3; 99.9 % CI 1.1 – 1.5; P < 0.001) teaching hospital (OR 1.4; 99.9 % CI 1.2 – 1.4; P < 0.001). Interestingly, black race was associated with a lower risk for in-hospital
mortality (OR 0.9; 99.9 % CI 0.8 – 0.9; P < 0.001).
Table 4
Multivariable analysis for predictors of in-hospital mortality in patients with upper
gastrointestinal hemorrhage.
|
Factor
|
OR (99.9 % CI)
|
P value
|
|
EGD
|
|
|
|
No vs. early
|
3.0 (2.8, 3.2)
|
< 0.001
|
|
Late vs. early
|
1.4 (1.3, 1.5)
|
< 0.001
|
|
Age (5 yr. increase)
|
0.99 (0.97, 1.00)
|
0.010
|
|
Male vs. female
|
1.4 (1.3, 1.5)
|
< 0.001
|
|
Race
|
|
|
|
Black vs. white
|
0.86 (0.78, 0.95)
|
< 0.001
|
|
Hispanic vs. white
|
1.1 (1.00, 1.2)
|
< 0.001
|
|
Other vs. white
|
1.02 (0.89, 1.2)
|
0.24
|
|
Unknown vs. white
|
0.93 (0.82, 1.05)
|
0.070
|
|
Insurance
|
|
|
|
Medicaid vs. medicare
|
1.7 (1.5, 1.9)
|
< 0.001
|
|
Private Insurance vs. medicare
|
1.1 (1.04, 1.2)
|
< 0.001
|
|
Other vs. medicare
|
1.4 (1.2, 1.6)
|
< 0.001
|
|
CCI
|
|
|
|
1 vs. 0
|
1.6 (1.4, 1.9)
|
< 0.001
|
|
2 vs. 0
|
2.4 (2.0, 2.8)
|
< 0.001
|
|
3 vs. 0
|
3.0 (2.5, 3.6)
|
< 0.001
|
|
4 + vs. 0
|
4.2 (3.6, 5.0)
|
< 0.001
|
|
Weekend vs. weekday
|
1.08 (1.01, 1.2)
|
< 0.001
|
|
Urban vs. rural hospital
|
1.3 (1.1, 1.5)
|
< 0.001
|
|
Teaching vs. non-teaching hospital
|
1.3 (1.2, 1.4)
|
< 0.001
|
|
Bed size of hospital
|
|
|
|
Medium vs. small
|
1.1 (1.00, 1.3)
|
0.93
|
|
Large vs. small
|
1.3 (1.2, 1.5)
|
< 0.001
|
|
Region of hospital
|
|
|
|
Midwest vs. northeast
|
0.83 (0.73, 0.95)
|
< 0.001
|
|
South vs. northeast
|
0.93 (0.83, 1.04)
|
0.68
|
|
West vs. northeast
|
0.99 (0.87, 1.1)
|
0.009
|
|
Median household income
|
|
|
|
2 vs. 1
|
0.95 (0.88, 1.03)
|
0.73
|
|
3 vs. 1
|
0.93 (0.85, 1.01)
|
0.27
|
|
4 vs. 1
|
0.90 (0.82, 1.00)
|
0.018
|
|
OR, odds ratio; CI, confidence interval
|
Length of hospital stay
Length of hospital stay was found to vary among the three groups as well. Patients
who underwent early EGD had a shorter length of stay compared to the delayed EGD and
no-EGD groups (4.6 vs 8.5 vs 7.6 days, respectively; P < 0.001) ([Table 3]) On multivariate analysis, hospital stay was 2.9 days longer for patients who did
not undergo EGD compared to patients who underwent early EGD (99.9 % CI 2.7 – 3.2;
P < 0.001). Patients who underwent delayed EGD were in the hospital for 3.7 days longer
compared to early EGD patients (99.9 % CI 3.5 – 4.0; P < 0.001). Severity of upper gastrointestinal bleeding as determined by the CCI score
was found to be a predictor of length of stay. A CCI score of 1 was associated with
1.3-day increase in length of stay (99.9 % CI 1.08 – 1.5 P < 0.001). Additional CCI points were associated with a gradual increase in length
of hospital stay. Reaching a CCI of 4 was an associated 3.8-day increase in length
of stay (99.9 % CI 3.5 – 4.1; P < 0.001) as compared to a CCI of 0 ([Table 5]).
Table 5
Multivariable analysis for predictors of length of stay in patients with upper gastrointestinal
hemorrhage.
|
Factor
|
Estimate (99.9 % CI)
|
P value
|
|
EGD
|
|
|
|
No vs. early
|
3.0 (2.7, 3.3)
|
< 0.001
|
|
Late vs. early
|
3.7 (3.5, 4.0)
|
< 0.001
|
|
Age (5 yr. increase)
|
– 0.18 (– 0.22, – 0.14)
|
< 0.001
|
|
Male vs. female
|
0.36 (0.27, 0.46)
|
< 0.001
|
|
Race
|
|
|
|
Black vs. white
|
0.30 (0.05, 0.55)
|
< 0.001
|
|
Hispanic vs. white
|
– 0.03 (– 0.32, 0.27)
|
0.77
|
|
Other vs. white
|
0.42 (0.12, 0.73)
|
< 0.001
|
|
Unknown vs. white
|
– 0.78 (– 1.2, – 0.41)
|
< 0.001
|
|
Insurance
|
|
|
|
Medicaid vs. medicare
|
0.92 (0.65, 1.2)
|
< 0.001
|
|
Private Insurance vs. medicare
|
– 0.28 (– 0.45, – 0.11)
|
< 0.001
|
|
Other vs. medicare
|
– 0.63 (– 0.84, – 0.41)
|
< 0.001
|
|
CCI
|
|
|
|
1 vs. 0
|
1.2 (1.02, 1.5)
|
< 0.001
|
|
2 vs. 0
|
2.0 (1.8, 2.3)
|
< 0.001
|
|
3 vs. 0
|
2.7 (2.4, 3.0)
|
< 0.001
|
|
4 + vs. 0
|
3.8 (3.4, 4.1)
|
< 0.001
|
|
Weekend vs. weekday
|
– 0.26 (– 0.37, – 0.15)
|
< 0.001
|
|
Urban vs. rural hospital
|
1.4 (1.1, 1.6)
|
< 0.001
|
|
Teaching vs. non-teaching hospital
|
0.97 (0.68, 1.3)
|
< 0.001
|
|
Bed size of hospital
|
|
|
|
Medium vs. small
|
0.17 (– 0.18, 0.52)
|
0.11
|
|
Large vs. small
|
0.92 (0.55, 1.3)
|
< 0.001
|
|
Region of hospital
|
|
|
|
Midwest vs. northeast
|
– 1.1 (– 1.5, – 0.68)
|
< 0.001
|
|
South vs. northeast
|
– 0.49 (– 0.85, – 0.13)
|
< 0.001
|
|
West vs. Northeast
|
– 0.86 (– 1.3, – 0.43)
|
< 0.001
|
|
Median household income
|
|
|
|
2 vs. 1
|
– 0.00 (– 0.17, 0.16)
|
0.94
|
|
3 vs. 1
|
– 0.12 (– 0.32, 0.08)
|
0.044
|
|
4 vs. 1
|
– 0.11 (– 0.36, 0.13)
|
0.12
|
|
CI, confidence interval
|
Hospital cost
The increase in mean hospital costs correlated with increasing disease severity as
measured by the CCI, as well as delayed EGD compared to early EGD. Total charges were
significantly higher in the delayed EGD group and no-EGD group compared to the early
EGD group ($ 66775.5 ± 1143.8 vs $ 64023.9 ± 1561.8 vs $ 39608.2 ± 464.2 P < 0.001) ([Table 3]). In multivariate analysis, cost of hospital stay (inflation-adjusted hospital charges)
was found to be $ 28,024.62 higher for delayed EGD (99.9 % CI 25,077.42 – 30,971.81
P < 0.001) and $ 24,780.18 higher for the no-EGD group (99.9 % CI 20,725.18 – 28,835.17 p < 0.001)
when compared with the early EGD group ([Table 6]). Cost of stay was also impacted by the severity of upper gastrointestinal bleeding.
A CCI score of 1 was associated with a $14801.58 increase in the cost of hospital
stay as compared to a CCI score of 0 (99 % CI 12465.57 – 17137.58 P < 0.001), while a CCI score of 4 was associated with a $ 41,782.41 increase in cost
of hospitalization compared to a CCI score of 0. (CI 37,252.13 – 46,312.69 P < 0.001)
Table 6
Multivariable analysis for predictors of inflation-adjusted hospital charges in patients
with upper gastrointestinal hemorrhage.
|
Factor
|
Estimate (99.9 % CI)
|
P value
|
|
EGD
|
|
|
|
No vs. early
|
24,378.86 (19,943.49, 28,814.23)
|
< 0.001
|
|
Late vs. early
|
26,852.55 (23,601.21, 30,103.90)
|
< 0.001
|
|
Age (5 yr. increase)
|
– 3,022.01 (– 3,613.88, – 2,430.14)
|
< 0.001
|
|
Male vs. female
|
5,513.55 (4,457.10, 6,570.00)
|
< 0.001
|
|
Race
|
|
|
|
Black vs. white
|
1,631.11 (– 2,274.41, 5,536.62)
|
0.17
|
|
Hispanic vs. white
|
6,284.29 (1,389.01, 11,179.57)
|
< 0.001
|
|
Other vs. white
|
6,413.02 (2,175.14, 10,650.90)
|
< 0.001
|
|
Unknown vs. white
|
– 12,386.24 (– 16,988.51, – 7,783.97)
|
< 0.001
|
|
Insurance
|
|
|
|
Medicaid vs. medicare
|
6,987.58 (3,962.04, 10,013.12)
|
< 0.001
|
|
Private insurance vs. medicare
|
– 8.59 (– 2,079.90, 2,062.73)
|
0.99
|
|
Other vs. medicare
|
– 6,357.65 (– 9,166.05, – 3,549.26)
|
< 0.001
|
|
CCI
|
|
|
|
1 vs. 0
|
13,534.73 (11,216.53, 15,852.93)
|
< 0.001
|
|
2 vs. 0
|
23,681.27 (20,222.78, 27,139.77)
|
< 0.001
|
|
3 vs. 0
|
31,516.04 (27,386.09, 35,646.00)
|
< 0.001
|
|
4 + vs. 0
|
39,525.91 (34,474.41, 44,577.41)
|
< 0.001
|
|
Weekend vs. weekday
|
– 1,469.50 (– 2,663.68, – 275.31)
|
< 0.001
|
|
Urban vs. rural hospital
|
18– 682.78 (15,062.53, 22,303.03)
|
< 0.001
|
|
Teaching vs. non-teaching hospital
|
11,516.06 (6,135.51, 16,896.61)
|
< 0.001
|
|
Bed size of hospital
|
|
|
|
Medium vs. small
|
4,670.46 (– 323.05, 9,663.97)
|
0.002
|
|
Large vs. small
|
15,343.59 (9,701.29, 20,985.88)
|
< 0.001
|
|
Region of hospital
|
|
|
|
Midwest vs. northeast
|
– 12,299.10 (– 22,791.04, – 1,807.16)
|
< 0.001
|
|
South vs. northeast
|
– 8,473.23 (– 18,701.45, 1,754.99)
|
0.006
|
|
West vs. northeast
|
10,772.76 (– 274.86, 21,820.39)
|
0.001
|
|
Median household income
|
|
|
|
2 vs. 1
|
387.45 (– 2,043.14, 2,818.05)
|
0.60
|
|
3 vs. 1
|
1,774.22 (– 1,751.15, 5,299.58)
|
0.098
|
|
4 vs. 1
|
2,724.03 (– 2,612.88, 8,060.93)
|
0.093
|
|
CI confidence interval
|
Discussion
This nationwide inpatient database study shows that early EGD was associated with
lower morbidity and mortality as compared to delayed EGD or no EGD. Patients who underwent
early EGD had lower incidence of acute renal and respiratory failure. In addition,
the overall costs, including the costs of the procedure, and length of hospital stay
were much higher in patients who did not undergo early EGD.
Acute upper gastrointestinal bleeding is a true gastrointestinal emergency [20]. Previous data found mortality associated with upper gastrointestinal bleeding ranging
from 3.5 % to 10 % [15]. However, analysis of more recent nationwide data found the mortality associated
with upper gastrointestinal bleeding has been decreasing over the past 2 decades,
down to 2.1 % in 2009 [17]. Multiple guidelines recommend endoscopy within 24 hours for patients with upper
gastrointestinal bleeding [14]
[15]
[16]. Endoscopic intervention in patients with upper gastrointestinal bleeding is associated
with a reduction in blood transfusion requirements, length of intensive care unit
stay, and total hospital stay [15]. A nationwide database analysis found that rates of early EGD have been increasing
over the past 20 years [17].
Our study found a significant reduction in mortality associated with early EGD as
compared to delayed or no EGD. A previous nationwide analysis found reduction in mortality
in concordance with an increase in early EGD in upper gastrointestinal bleeding over
the past 20 years leading up until 2009 [17]. In addition, another analysis of nationwide data prior to 2007 also found a reduction
in mortality with early EGD [11]. Our study adds to these results by including more recent inpatient data, and controlling
for other risk factors using logistic regression to detect the association of lower
mortality with early EGD, as compared to delayed EGD or no EGD. Performing early EGD
may be associated with lower mortality rates for multiple reasons, including earlier
time to endoscopic therapies to control active bleeding and subsequently reduce need
for transfusions and other supportive therapies, such as vasopressors, and risk stratification
of high-risk and low-risk lesions, which may triage patients to either more aggressive
interventions in high-risk lesions or earlier discharge in low-risk lesions.
Our study also found a lower rate of complications, such as renal failure and respiratory
failure, in patients who underwent early EGD. Early EGD has been previously found
to reduce the risk of recurrent bleeding, transfusion requirements [21] and the need for emergent surgery especially in patients with high-risk stigmata
for upper gastrointestinal bleeding [9]. Cooper et al have also shown that early endoscopy is associated with a clinically
significant, although not statistically significant, lower risk of recurrent bleeding
after adjusting for confounding factors [9].
Early EGD also has benefits in reducing length of stay and hospital costs. In our
analysis, early EGD was associated with a reduction by over 3 days of hospitalization
compared to both delayed and no EGD. This may be for several reasons, however likely
bleeding lesions may be effectively treated and stopped sooner, leading to faster
recovery and low-risk lesions may be identified sooner, leading to earlier discharge.
This in turn can lead to an overall reduction in costs of the associated hospitalization.
This is consistent with previous studies that have found a reduction in length of
stay with early EGD [21]
[22].
Previous studies have found that EGD can help in deciding if the patient has low-risk
stigmata for recurrent bleeding and thus helps in deciding if we can safely discharge
a patient home with follow up as an outpatient [15]. In a study by Cipolletta et al [23], 464 patients who had acute upper gastrointestinal bleeding underwent EGD within
12 hours of hospital admission, of whom 95 patients were randomized to outpatient
versus inpatient management. No difference in the clinical outcome was noted between
the 2 groups. Thus, this study helps delineate the role of early EGD in deciding outpatient
versus inpatient management. In addition, in this study, the median cost was $ 340
in the outpatient group versus $ 3940 in the inpatient group [23]. Lai et al have also shown this in their retrospective study in which patients with
clean base ulcer were stable for discharge on the day of procedure, without an increased
risk for rebleeding [24]. Based on these results, early EGD seems to help in reducing the substantial burden
imposed on health care resources without adversely affecting the patient outcome.
In addition to reducing inpatient costs, early EGD also reduces costs in the outpatient
arena. This has been also been reported by Lee et al, where they showed that a patient
population who underwent early endoscopy had lesser post discharge unplanned physician
visits [25].
Although diagnostic endoscopies and endoscopic therapies have become more frequently
utilized in patients who present with upper gastrointestinal bleeding, the timing
of EGD varies significantly. Previous studies have found improved rates of early endoscopy,
however, al bare majority of patients receive EGD within 24 hours [17]
[18]
[19]. In our study, only 59 % of patients who received an EGD had it within the first
24 hours. Considering the benefits of early EGD, protocols should be set regarding
the timing of EGD in patients with acute non-variceal upper gastrointestinal bleeding,
as many a times, timing alone often dictates clinical success. Early EGD provides
the benefit of achieving early hemostasis in high-risk patients whereas low-risk patients
benefit by avoiding prolonged hospitalization. Similarly, it has been shown that late
EGD offers no additional benefit over standard medical management [21]. Various reasons exist for why patients may not receive EGD within 24 hours, especially
in a large database analysis such as our study, including weekend admissions, incorrect
diagnoses, and patients who may have been classified as low enough risk to not require
EGD. There may also be patient-related factors that could delay EGD, specifically
certain co-morbidities, such as severe cardiopulmonary instability or coagulopathy,
which may be unavoidable and require correction prior to EGD. Lastly, certain disease
factors in upper gastrointestinal bleeding may necessitate radiographic or surgical
intervention preferentially to EGD. Overall, a protocol-based approach for upper gastrointestinal
bleeding stressing early EGD, with establishment of a gastrointestinal rapid response
team available after hours and on weekends, may not only be cost-effective but also
better for patient safety and outcomes.
Our study has several strengths, in that it included a large sample size of representative
hospital admissions for the United States over a recent period of time (2007 – 2013),
and thus should largely reflect current practice. However, in interpreting the findings
of our study, several potential limitations should be kept in mind. First, the study
wasbased on ICD-9 CM discharge diagnoses, so there is a possibility of incorrect classification.
Second, the study was based on discharge diagnosis, and information on the endoscopic
findings was not available. Hence, we could not separate the patients into low-risk
and high-risk categories based on stigmata of recent hemorrhage. Third, our study
was based on hospitalized patients. It did not reflect patients who underwent outpatient
endoscopy for upper gastrointestinal bleeding that might have prevented hospitalization.
Lastly, a significant potential limitation is the retrospective nature of the study,
and given that, we can only report the association of early EGD with improved outcomes
and we cannot infer causality. Specifically, there exists the potential for confounding
factors in the delayed and no-EGD groups that led them to have either delayed or no
EGD. As mentioned above, these patients could have had underlying co-morbidities,
such as severe cardiopulmonary instability or coagulopathy, preventing them from undergoing
EGD in a timely manner, or they might have had severe or complicated disease requiring
alternative therapies be performed such as angiography, TIPS or surgery. In that case,
poor outcomes may have been related to the underlying severity of illness, as opposed
to lack of intervention. Alternatively, patients could have had very mild upper gastrointestinal
bleeding that did not warrant an EGD. We were unable to adjudicate whether these 2
groups balanced each other out given the retrospective nature of our analysis, thus
the possibility exists that the higher rate of AEs in the delayed EGD group were not
in fact related to a lack of intervention, but to a patient’s underlying disease or
comorbidities. Due to these limitations, further large-scale retrospective and, more
importantly, prospective studies should be undertaken in order to assess outcomes
based on timing of EGD, ideally in similarly matched patient groups based on clinical
status, underlying comorbidities, and whether their gastrointestinal bleeding was
severe or complicated such that it may have required radiographic or surgical intervention.
Conclusions
Early EGD (within 24 hours) is associated with lower in-hospital mortality and morbidity
as compared to delayed EGD or no EGD in-hospital admissions for upper gastrointestinal
bleeding. In addition, early EGD is associated with shorter length of stay and lower
total hospital costs. Despite multiple guidelines recommending early EGD, the rate
of early EGD remains inadequate. Future protocols should be developed to incorporate
early EGD in order to improve patient, hospital, and economic outcomes. Given this
study is retrospective, we cannot determine that early EGD was the causal driver of
improved outcomes, thus future prospective studies will be required to confirm this
finding.
Appendix 1
ICD-9-CM Diagnostic and Procedure Codes.
|
Description
|
ICD-9-CM Code
|
|
UGIH
|
|
|
Bleeding esophageal varices
|
456.0, 456.2, 456.20
|
|
Bleeding peptic ulcer (gastric or duodenal)
|
531.0x, 531.2x, 531.4x, 531.6x,
532.0x, 532.2x, 532.4x, 532.6x,
533.0x, 533.2x, 533.4x, 533.6x,
534.0x, 534.2x, 534.4x, 534.6x
|
|
Mallory – Weiss
|
530.7
|
|
Gastritis with hemorrhage
|
535.01, 535.11, 535.21, 535.41, 535.51, 535.61
|
|
Dieulafoy's lesion of stomach or duodenum
|
537.84
|
|
Angiodysplasia of stomach or duodenum with hemorrhage
|
537.83
|
|
Other diagnoses
|
|
|
Acute renal failure (including dialysis)
|
584.5, 584.6, 584.7, 584.8, 584.9, V45.1, V56.0, V56.1
|
|
Hypovolemia including shock
|
276.5, 276.50, 276.51, 276.52, 785.59
|
|
Acute respiratory failure
|
518.81
|
|
Procedures
|
|
|
Blood transfusion
|
99.03, 99.04
|
|
Dialysis (for acute renal failure definition)
|
39.95
|
|
EGD
|
45.13, 45.14, 45.16, 42.23, 44.13, 42.33, 44.43
|
|
Endoscopic therapy at EGD
|
42.33, 44.43
|
UGIH, upper gastrointestinal hemorrhage; EGD, esophagogastroduodenoscopy
