Pulmonology

Intensive care unit admission for patients with pulmonary hypertension presenting to U.S. Emergency Departments

a b s t r a c t

Introduction: Pulmonary hypertension (PH) is an important contributor to morbidity and mortality in patients seeking emergency care, resulting in high acuity presentations and resource utilization. The objective was to characterize the rate of intensive care unit admission for PH among adult patients presenting to the emer- gency department (ED) along with other important clinical outcomes.

Methods: We analyzed data from the State Emergency Department Databases (SEDD) and State Inpatient Data- bases (SID) from two geographically separated U.S. states (New York and Nebraska). The primary outcome mea- sure was admission to an ICU. Other measures of interest included the Hospital admission rate, hospital length of stay , inpatient mortality, and rate of critical care procedures performed.

Results: From 2010 to 2014, in a sample of 34 million ED visits, patients with a diagnosis of PH accounted for 0.71% of all ED visits. Of the PH visits, 20.2% were admitted to the ICU, compared to 2.6% of all other visits (P < 0.001), with an aOR of 1.74 (95% CI 1. 72-1.76). The vast majority (94.6%) of PH patients were admitted to the hospital, compared to 20.5% for all other ED visits (P < 0.001). Hospital LOS and hospital-based mortality were higher in the PH group than for other ED patients. With the exception of invasive mechanical ventilation, a significantly higher percentage of patients with PH admitted to the ICU than other patients underwent all critical care proce- dures evaluated.

Conclusions: In this study, patients with PH who sought emergency care in U.S. EDs from 2010 to 2014 were sig- nificantly more likely to require ICU admission than all other patients. They were also significantly more likely to be admitted to the hospital than all other patients, had longer hospital LOS, increased risk of inpatient mortality, and underwent more critical care procedures. These findings indicate the high acuity of PH patients seeking emergency care and demonstrate the need for additional research into this population.

(C) 2021 Published by Elsevier Inc.

  1. Introduction

Pulmonary hypertension (PH) is a heterogeneous disorder, with five groups defined by the World Health Organization based upon the un- derlying etiology [1], all resulting in a mean pulmonary artery pressure over 25 mmHg [2]. Although clinicians have increasingly recognized the risks of PH and right ventricular failure over the last 30 years [3,4]. PH remains under-diagnosed [5-8]. Prior large epidemiologic studies have focused solely on Group 1 PH, or pulmonary Arterial hypertension (PAH), a rare disease with estimates of 5 to 15 cases per 1 million adults [9]. Recent reports indicate that PH, inclusive of all five groups, is

Abbreviations: ED, Emergency Department; PH, Pulmonary Hypertension; SEDD, State Emergency Department Databases; SID, State Inpatient Databases.

* Corresponding author at: 55 Fruit Street, Boston, MA 02114, United States of America.

E-mail addresses: [email protected] (S.R. Wilcox), [email protected] (M.K. Faridi), [email protected] (C.A. Camargo).

nonetheless relatively common in patients presenting to the Emergency Department (ED), with a prevalence of about 0.8% [10,11]. The manage- ment, both acutely and chronically, of patients with PH is challenging, as persistent elevations in pulmonary artery pressure can lead to acute de- compensation and right ventricular failure. Patients with PH require substantial economic resources, although most of the available data solely focus on patients Group 1 PH [12-14].

Improving the care of patients with PH requires understanding the burden of disease and the resources required to care for them. ICU ad- mission rates from the ED are a proxy for patient acuity and are associ- ated with increasED resource utilization and crowding [15]. The rate of ICU admission for PH patients has not been evaluated in a large, repre- sentative sample. A prior single-center study found that PH patients were admitted to the ICU at twice as often as all other ED visits [10]. While it may seem evident that patients with PH have higher acuity ED presentations and require ICU admission more frequently than other patients, the magnitude of this association is unknown.

https://doi.org/10.1016/j.ajem.2021.07.029 0735-6757/(C) 2021 Published by Elsevier Inc.

Quantifying the acuity and resource utilization of patients with PH pre- senting for emergency care is therefore integral to designing future studies of the management of PH.

Our objective was to characterize the rate of ICU admission among adult PH patients presenting to the ED along with other important clin- ical outcomes.

  1. Methods

We conducted a retrospective cohort study using data from the State Emergency Department Databases (SEDD) [16] and State Inpatient Da- tabases (SID) [17], developed for the Healthcare Cost and Utilization Project (HCUP) sponsored by the Agency for Healthcare Research and Quality (AHRQ. SEDD/SID collected data on all ED visits, regardless of disposition, from 2010 to 2014). The SEDD captures discharge informa- tion on all ED visits in a given state that do not result in an admission, while the SID includes inpatient data from short-term, acute-care, non- federal, general, and other specialty hospitals in participating states, in- cluding those hospitalized from the ED. The files include all patients, regardless of payer, providing a comprehensive view of inpatient care in a defined state over time. The SEDD and SID contain a core set of clin- ical and nonclinical information, including patient demographics, diag- noses, procedures, and hospital identifiers that permit linkage between SEDD and SID data. The SID encompass about 97% of all U.S. community hospital discharges. For the present analysis, data were used from New York and Nebraska SEDD and SID. These states were se- lected for their geographic distribution, large population, high Data quality, and chiefly because their databases contained unique encrypted patient-level identifiers that enable follow-up of specific patients over time. This study was declared exempt from review by the Institutional Review Board of MassGeneral Brigham (protocol # 2018P002337).

Patients included for analysis were those age 18 years and older, with any ED visit, with a diagnosis that met the 9th Revision of the Inter- national Classification of Diseases, Clinical Modification (ICD-9-CM) codes for PH, including Groups 1-5 of PH in the first through 10th diag- nosis field for an ED diagnosis or hospital diagnosis [1]. The list of in- cluded ICD-9-CM codes are provided in the Supplementary Material.

We presented the demographic characteristics of age, sex, and na- tional quartile for median Household income (as estimated by the pa- tient’s home ZIP code), as well as hospital urban or rural status. Primary Insurance types were categorized as public (Medicare and Medicaid), private, self-pay, and other. ED visit data were evaluated, in- cluding diagnoses, ED disposition, and hospital disposition. We selected comorbidities commonly associated with PH from Elixhauser comor- bidity list [18], including acquired immune deficiency syndrome, chronic pulmonary disease, congestive heart failure, diabetes with chronic complications, liver disease, metastatic cancer, renal failure, rheumatoid arthritis, and valvular disease.

The primary outcome measure was admission to an intensive care unit (ICU). Other measures of interest included hospital admission rate, Hospital length of stay , inpatient mortality, and rate of critical care procedures performed. Of note, data on ED LOS and ED observation unit admission are not available in the SEDD or SID.

    1. Statistical analysis

ED visits by patients with PH were compared to all other ED visits. Frequencies with proportions were reported for ED visit and hospital characteristics and chi-square test was used to test statistical signifi- cance (Table 1). ED and Hospital disposition variables were presented as proportions with corresponding 95% confidence intervals and were compared between PH and non-PH visits using chi-square test (Table 2). Similarly, bivariate analyses were run to explore associations of PH ED visit with Inpatient ICU Resource Utilization variables (Table 3). Multivariable logistic-regression model was run to test the re- lationship between pulmonary hypertension ED visits and ICU

admission (Table 4). Significance tests and confidence intervals for model estimates were based on robust standard errors to account for clustering within subjects. Variables were selected a priori for inclusion in the model including selected comorbidities commonly associated with PH from Elixhauser derived comorbidities. Additionally, the model was re-run after excluding deaths in the cohort. All analyses were conducted using SAS version 9.4 (SAS Institute, Cary, NC) software. A 2-sided P-value of <0.05 was considered statistically significant.

  1. Results
    1. Characteristics of study subjects

From 2010 to 2014, there were 248,692 ED visits for adults with PH, accounting for 0.71% of all ED visits studied (Table 1). Patients with PH were significantly older than non-PH patients, with a higher percentage of visits for patients in each age decile over age 61. The PH group was also comprised of more women (61.5% vs 57.3% P < 0.001) and were more likely to have Public insurance (86.5% vs 50.0%, P < 0.001). All assessed comorbidities were more common among patients with PH.

    1. Main results

Of the ED visits for patients with a diagnosis of PH, 94.6% were ad- mitted to the hospital, compared to 20.5% for all other ED visits (P < 0.001; Table 2). The ICU admission rate was also significantly higher for patients with PH, at 20.2% compared to 2.6% (95% CI: 20.0-20.4 vs. 2.6-2.6, P < 0.001). Hospital LOS was higher for the PH group than other admitted ED patient at 7.7 days vs. 5.7 days (P < 0.001). Mortality was higher for the PH group in every venue assessed, including in the ED (1.3% vs. 0.2%, P < 0.001), as an inpatient (5.7% vs 2.8%, P < 0.001), and in the ICU (13.2% vs 10.8%, P < 0.001).

Patients with PH had 74% increased odds of ICU admission compared to admitted non-PH patients (aOR: 1.74, 95% CI 1.72-1.76) (Table 4). The odds of ICU admission significantly increased for all age-groups compared to age group 18-30 years, whereas, female sex was associ- ated with decreased aOR of ICU admission. All comorbid conditions were also associated with a higher aOR of ICU admission. In sensitivity analysis excluding patients who died during the study period, the main results did not materially change (aOR: 1.78, 95% CI 1.76-1.80, P < 0.001).

For all critical care procedures evaluated, patients with PH admitted to the ICU were more likely to undergo procedures than other patients, apart from invasive mechanical ventilation (Table 4). Non-invasive ven- tilation was significantly more common, at 22.6% versus 8.4%, (95% CI: 22.3-23.0 and 8.4-8.5, P < 0.001).

  1. Discussion

In this large database study, ED visits by patients with ICD-9-CM codes corresponding to PH accounted for 0.71% of all ED visits, similar to the results of other recent studies [10,11]. A study at a tertiary care center found that 0.84% of patients had an existing diagnosis of PH, and a study of the Nationwide Emergency Department Sample (NEDS) database found that patients with PH account for 0.78% of visits. The de- mographics of the population in this current investigation were also similar to the existing PH literature [10,11,19,20], as most patients with PH were women, and PH patients were significantly older than the remaining ED patient population [11].

Patients with PH were more likely to be admitted to the hospital than all other patients, with 94.5% of PH patients admitted. This is higher than previous reports for all PH patients, which ranged from 56.6 to 86.9% [10,11] and Group 1 PH at 82% [19]. Of all PH patients presenting for emergency care, 20.2% were admitted to the ICU from the ED.

Notably, the rate of ICU admission for patients with PH in this study was significantly higher than the sole prior study (n = 1447

Table 1

Emergency Department visits for pulmonary hypertension in two U.S states (New York and Nebraska), 2010-2014

ED visit and Hospital Characteristics

Overall N (%)

PH Visits N (%)

All Other ED Visits N (%)

P-Value

Overall

34,858,625 (100)

248,692 (0.71)

34,609,933 (99.29)

<0.001

Age

18-30

9,424,218 (27.04)

3667 (1.47)

9,420,551 (27.22)

<0.001

31-40

5,680,022 (16.29)

6095 (2.45)

5,673,927 (16.39)

41-50

5,665,870 (16.25)

14,581 (5.86)

5,651,289 (16.33)

51-60

5,123,806 (14.70)

29,278 (11.77)

5,094,528 (14.72)

61-70

3,466,329 (9.94)

43,086 (17.33)

3,423,243 (9.89)

71-80

2,649,200 (7.60)

58,083 (23.36)

2,591,117 (7.49)

>80

2,849,180 (8.17)

93,902 (37.76)

2,755,278 (7.96)

Sex

<0.001

Male

15,231,600 (43.70)

95,673 (38.47)

15,135,927 (43.73)

Female

19,627,025 (56.30)

153,019 (61.53)

19,474,006 (56.27)

Primary Health Insurance Public

17,506,572 (50.22)

215,192 (86.53)

17,291,380 (49.96)

<0.001

Private

10,923,530 (31.34)

27,276 (10.97)

10,896,254 (31.48)

Self-pay

4,921,663 (14.12)

3383 (1.36)

4,918,280 (14.21)

Other

1,506,860 (4.32)

2841 (1.14)

1,504,019 (4.35)

Median household income by ZIP code 1 (lowest)

10,103,233 (28.98)

53,927 (21.68)

10,049,306 (29.04)

<0.001

2

8,142,426 (23.36)

52,813 (21.24)

8,089,613 (23.37)

3

6,894,009 (19.78)

52,125 (20.96)

6,841,884 (19.77)

4 (highest)

8,464,594 (24.28)

76,146 (30.62)

8,388,448 (24.24)

unknown

1,254,363 (3.60)

13,681 (5.50)

1,240,682 (3.58)

Selected Diagnoses

Acquired immune deficiency syndrome

70,859 (0.20)

1737 (0.70)

69,122 (0.20)

<0.001

Chronic pulmonary disease

2,664,734 (7.64)

88,423 (35.56)

2,576,311 (7.44)

Congestive heart failure

1,397,619 (4.01)

151,753 (61.02)

1,245,866 (3.60)

Diabetes with chronic complications

364,221 (1.04)

18,110 (7.28)

346,111 (1.00)

Liver disease

300,840 (0.86)

10,210 (4.11)

290,630 (0.84)

Metastatic cancer

235,734 (0.68)

4436 (1.78)

231,298 (0.67)

Renal failure

1,137,760 (3.26)

73,114 (29.40)

1,064,646 (3.08)

Rheumatoid arthritis

272,582 (0.78)

10,963 (4.41)

261,619 (0.76)

Valvular disease

367,261 (1.05)

44,343 (17.83)

322,918 (0.93)

Urban Location No

1,095,139 (3.19)

5960 (2.44)

1,089,179 (3.20)

<0.001

Yes

33,231,101 (96.81)

237,981 (97.56)

32,993,120 (96.80)

Abbreviations: ED, emergency department; PH, pulmonary hypertension.

PH patient visits) evaluating ICU admissions for PH patients in the ED [10]. While the rate of ICU admission for non-PH patients was similar between the two studies, at 2.7% vs 2.4% previously, in that single- center study, the rate of ICU admission for PH patients was 5.7% com- pared to 20.2% in the current investigation. In that study, the overall admission rate was also about half of the current admission rate.

Table 2

Major clinical outcomes for emergency department visits for patients with and without pulmonary hypertension

Outcome PH All Other ED Visits P-Value ED disposition, % (95% CI) <0.001

Discharged 4.46; (4.38, 4.54) 74.90; (74.89,

74.92)

This may indicate a difference in the patient population of that center or regional practice variations. Regardless, the rate of ICU admission for patients with PH is very high and is consistently higher than for non-PH patients presenting to the ED. Determining the illness severity of an ED population is challenging given the heterogeneity in presen- tations and variations in the demographics, resources, and practices, but ICU admission rates from the ED can serve as a surrogate for acu- ity [15]. These current findings indicate that patients with PH present- ing to the ED are a high acuity population and require substantial Healthcare resources.

Prior PH studies have varied regarding sex-related mortality differ- ences [19,21-23], but no study to our knowledge has assessed ICU ad- mission rates by sex. In the current study, while PH patients were more commonly women, men had a higher risk of ICU admission, con-

sistent with ED studies demonstrating higher acuity in male PH patients

Admitted to Hospital 94.57; (94.48,

94.66)

20.53; (20.52,

20.55)

[10,19]. The reason for the discrepancy in prior sex-based findings re-

Admitted to ICU 20.2 (20.0, 20.4) 2.59 (2.58, 2.59)

Death in ED 1.28 (1.09, 1.47) 0.208 (0.206,

0.210)

Inpatient outcomes <0.001

quires further study.

Older age was associated with increased ICU admission, with signif- icant increases associated with each decile of life, until a slight reversal of the pattern after age 80 years old. Prior studies have shown an in-

Hospital LOS, mean days (95% CI)

Inpatient mortality, % (95%

CI)

7.65; (7.62, 7.68) 5.72; (5.72, 5.73)

5.74; (5.64, 5.83) 2.83; (2.82, 2.84)

crease in mortality in the older PH population [11,21,24], and the ICU utilization likely reflects the expected higher acuity associated with age. The life-expectancy of patients with PH is increasing due to im-

ICU mortality, % (95% CI) 13.20 (12.91,

13.50)

10.76 (10.69,

10.82)

provED treatments [25]. Combined with the aging of the United States population [26], patients with PH represent another group that will con-

Abbreviations: CI, confidence interval; ED, emergency department; LOS, length of hospital stay; PH, pulmonary hypertension.

tinue to require additional resources. All comorbidities assessed were also associated with an increased rate of ICU admission, with the highest

Table 3

Association of pulmonary hypertension and other factors with intensive care unit admission from the emergency department

Variables

aOR, 95% CI

P-Value

Pulmonary Hypertension

No

1 (Reference)

Yes

1.74 (1.72-1.76)

<0.001

Age

18-30

1 (Reference)

31-40

1.35 (1.34-1.37)

<0.001

41-50

2.26 (2.23-2.28)

<0.001

51-60

3.49 (3.45-3.52)

<0.001

61-70

4.79 (4.75-4.84)

<0.001

71-80

5.30 (5.25-5.35)

<0.001

>80

5.14 (5.09-5.19)

<0.001

Sex

Male

1 (Reference)

Female

0.72 (0.71-0.72)

<0.001

Primary Health Insurance

Public

1 (Reference)

Private

0.87 (0.87-0.88)

<0.001

Self-pay

0.47 (0.47-0.48)

<0.001

Other

064 (0.63-0.65)

<0.001

Median household income by ZIP code

1 (lowest)

1 (Reference)

2

1.30 (1.29-1.31)

<0.001

3

1.30 (1.30-1.31)

<0.001

4 (highest)

1.47 (1.46-1.48)

<0.001

unknown

2.37 (2.35-2.40)

<0.001

Selected Diagnosis

Chronic pulmonary disease

1.99 (1.98-2.00)

<0.001

Congestive heart failure

2.74 (2.73-2.76)

<0.001

Diabetes with chronic complications

1.68 (1.68-1.70)

<0.001

Liver disease

2.86 (2.82-2.89)

<0.001

Metastatic cancer

2.87 (2.84-2.91)

<0.001

Renal failure

1.83 (1.82-1.84)

<0.001

Rheumatoid arthritis

1.76 (1.74-1.79)

0.002

Valvular disease

1.63 (1.62-1.65)

<0.001

Urban Location

No

1 (Reference)

Yes

1.04 (1.03-1.05)

<0.001

OR for patients with metastatic cancer, liver disease, and congestive heart failure, as would be anticipated.

With regard to secondar outcomes, the hospital LOS for PH patients at 7.7 days is also slightly longer than prior findings reporting 6.2 [11] to

6.67 days [27]. The inpatient mortality rate at 5.7% was significantly

higher for patients with PH than other patients admitted via the ED. These findings are concordant, however, with the previously published inpatient mortality rates for PH patients, 4.5 to 6.5% [11,19,21].

Once admitted to the ICU, patients with PH received more treat- ments and invasive procedures, especially hemodialysis and cardiac catheterizations. As renal failure and congestive heart failure were com- mon comorbidities in this population, at 29.4% and 61.0% respectively, these findings are not surprising, but the exact frequencies are helpful. Noninvasive mechanical ventilation was significantly more common,

possibly reflecting the comorbidities of congestive heart failure and chronic pulmonary disease. Additionally, given the physiologic risks of intubation in patients with PH [5], clinicians may have tried to avoid in- vasive mechanical ventilation. However, the rates of invasive mechani- cal ventilation were similar between the PH and all other ED patients admitted to the ICU, likely indicating the overall high acuity of the PH patients. The impact of the high rate of critical care procedures is ampli- fied by the fact that a far greater percentage of PH patients are admitted to the ICU. While this is still a minority of ED patient visits, the resource utilization in this subset of the population is substantial.

Historically, PH has been underappreciated in the ED [5] and throughout the rest of the healthcare system [8]. Yet, based upon this in- vestigation and a growing body of literature, PH is relatively common among patients seeking emergency care. As PH is consistently associ- ated with significantly increased hospital and ICU admission, hospital length of stay, mortality, and resource utilization, understanding the de- mographics and needs of this population is important for planning in emergency medicine and critical care alike.

    1. Limitations

The SEDD database relies on administrative rather than clinical data, and this study was not designed to reflect details of clinical care in the ED that may have affected mortality or admission rates. Second, studies based upon ICD-9-CM codes are always at risk of classification bias, and this is a particular issue with a previously under-reported condition such as PH [8]. PH can arise from numerous comorbidities associated with increased mortality, such as left-sided heart failure and chronic ob- structive pulmonary disease (COPD), these comorbidities may contrib- ute to the higher ICU admission rates in the PH cohort. However, patients with PH complicating heart failure [28] and pulmonary disease

[29] have higher mortality that patients with those conditions without PH, and as such, the needs of this population remain relevant. The SEDD database does not contain patient identifiers. We are therefore unable, with this database, to assess of the frequency of return visits, re- peat admissions, or long-term outcomes.

  1. Conclusions

In this large database study of patients who sought emergency care in New York and Nebraska EDs from 2010 to 2014, presentations by pa- tients with ICD-9-CM codes corresponding to PH were common, ac- counting for 0.71% of adult visits. Patients with PH were significantly more likely to be admitted to the ICU than all other patients. These pa- tients had longer hospital stays, increased risk of inpatient and ICU mor- tality, and received more invasive procedures compared to all other ED visits. Older age and comorbidities were associated with increased rates of ICU admission. These results demonstrate that patients with PH have high acuity and require substantial resources. Clinicians in the ED should be aware of the increased needs of this complex population. Fur- ther research is needed to prospectively recognize these patients in the ED and delineate the risk factors for poor outcomes and increased re- source utilization.

Table 4

Rate of Intensive Care Unit Procedures by pulmonary hypertension status

Intervention

PH Admitted to the ICU % (95% CI)

All Other ED Visits Admitted to the ICU % (95% CI)

P-Value

non-invasive ventilation

22.62; (22.25, 22.98)

8.40; (8.35, 8.46)

<0.001

Invasive mechanical ventilation

21.21; (20.86, 21.57)

21.04; (20.96, 21.13)

0.37

Arterial line

4.15; (3.98, 4.33)

3.56; (3.52, 3.59)

<0.001

Central line

14.58; (14.27, 14.89)

13.45; (13.38, 13.53)

<0.001

Dialysis

9.10; (8.85, 9.36)

6.38; (6.33, 6.43)

<0.001

Cardiac Catheterization

10.60; (10.33, 10.87)

6.94; (6.88, 6.99)

<0.001

Abbreviations: aOR, adjusted odds ratio; CI, confidence interval; PH, pulmonary hypertension.

Financial disclosure

This work was supported by an institutional grant, The Eleanor and Miles Shore Fellowship Program, through Harvard Medical School, hosted by the Department of Emergency Medicine at Massachusetts General Hospital.

Declaration of Competing Interest

The authors have no conflicts of interest to report.

Appendix A. Supplementary data

Supplementary data to this article can be found online at https://doi. org/10.1016/j.ajem.2021.07.029.

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