Lung Injury Prediction Score in Hospitalized Patients at Risk of Acute Respiratory Distress Syndrome

Graciela J. Soto, MD, MS; Daryl J. Kor, MD, MSc; Pauline K. Park, MD; Peter C. Hou, MD; David A. Kaufman, MD; Mimi Kim, ScD; Hemang Yadav, MBBS; Nicholas Teman, MD; Michael C. Hsu, MS; Tatyana Shvilkina, DO; Yekaterina Grewal, MD; Manuel De Aguirre, MD; Sampath Gunda, MD; Ognjen Gajic, MD; Michelle Ng Gong, MD, MS

Disclosures

Crit Care Med. 2016;44(12):2182-2191.

Abstract and Introduction

Abstract

Objective: The Lung Injury Prediction Score identifies patients at risk for acute respiratory distress syndrome in the emergency department, but it has not been validated in non-emergency department hospitalized patients. We aimed to evaluate whether Lung Injury Prediction Score identifies non-emergency department hospitalized patients at risk of developing acute respiratory distress syndrome at the time of critical care contact.

Design: Retrospective study.

Setting: Five academic medical centers.

Patients: Nine hundred consecutive patients (≥ 18 yr old) with at least one acute respiratory distress syndrome risk factor at the time of critical care contact.

Interventions: None.

Measurements and Main Results: Lung Injury Prediction Score was calculated using the worst values within the 12 hours before initial critical care contact. Patients with acute respiratory distress syndrome at the time of initial contact were excluded. Acute respiratory distress syndrome developed in 124 patients (13.7%) a median of 2 days (interquartile range, 2–3) after critical care contact. Hospital mortality was 22% and was significantly higher in acute respiratory distress syndrome than non-acute respiratory distress syndrome patients (48% vs 18%; p < 0.001). Increasing Lung Injury Prediction Score was significantly associated with development of acute respiratory distress syndrome (odds ratio, 1.31; 95% CI, 1.21–1.42) and the composite outcome of acute respiratory distress syndrome or death (odds ratio, 1.26; 95% CI, 1.18–1.34). A Lung Injury Prediction Score greater than or equal to 4 was associated with the development of acute respiratory distress syndrome (odds ratio, 4.17; 95% CI, 2.26–7.72), composite outcome of acute respiratory distress syndrome or death (odds ratio, 2.43; 95% CI, 1.68–3.49), and acute respiratory distress syndrome after accounting for the competing risk of death (hazard ratio, 3.71; 95% CI, 2.05–6.72). For acute respiratory distress syndrome development, the Lung Injury Prediction Score has an area under the receiver operating characteristic curve of 0.70 and a Lung Injury Prediction Score greater than or equal to 4 has 90% sensitivity (misses only 10% of acute respiratory distress syndrome cases), 31% specificity, 17% positive predictive value, and 95% negative predictive value.

Conclusions: In a cohort of non-emergency department hospitalized patients, the Lung Injury Prediction Score and Lung Injury Prediction Score greater than or equal to 4 can identify patients at increased risk of acute respiratory distress syndrome and/or death at the time of critical care contact but it does not perform as well as in the original emergency department cohort.

Introduction

The acute respiratory distress syndrome (ARDS) is associated with high morbidity and mortality worldwide.^[1,2] Lung protective ventilation is the only treatment available to lower the risk of death with ARDS.^[3] Given the lack of effective treatments, the focus of the scientific and clinical communities has shifted to ARDS prevention with the goal of delivering interventions in the pre-ARDS state to halt the progression to ARDS in patients at risk.^[4,5] This is the objective of the National Heart, Lung, and Blood Institute (NHLBI)-funded Prevention and Early Treatment of Acute Lung Injury (PETAL) network that focuses on clinical trials aimed at the prevention and early treatment of ARDS.^[5] ARDS does not develop in the majority of patients with established predisposing conditions.^[6,7] To minimize harm from exposure to therapeutic strategies, we need tools for early identification of patients at higher risk of ARDS for whom preventive interventions have a favorable risk-to-benefit ratio. The Lung Injury Prediction Score (LIPS) is a validated prediction model that uses clinical data at the time of presentation to the emergency department (ED) to identify patients at high risk for ARDS.^[6,8,9] A LIPS greater than or equal to 4 is currently used to enroll high-risk patients in clinical trials on ARDS prevention.^[10–12]

Although the LIPS successfully stratifies patients at higher risk for ARDS at the time of ED presentation, it is not validated for patients at risk of ARDS in the hospital wards. Half of the patients with an ARDS-predisposing condition on hospital admission are not admitted to an ICU^[13,14] and over half of the patients with sepsis or pneumonia are initially treated in the hospital wards.^[15–17] Because the LIPS uses criteria "at the time of hospital admission," it is not clear how well it performs in patients who develop predisposing conditions after the initial ED presentation or who deteriorate clinically after hospital admission requiring critical care evaluation or ICU transfer. Such validation is important to use the LIPS in prevention trials to identify ward patients at higher risk of ARDS.

Therefore, the purpose of this study is to validate the LIPS in non-ED hospitalized patients at higher risk of ARDS when they require critical care evaluation from areas of the hospital other than the ED.

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Next Section

Table 1. Baseline Demographics, Clinical Characteristics, and Outcomes
Characteristic	Cohort (n = 900)	No ARDS (n = 776)	ARDS (n = 124)	p ^a
Demographics
Age (median, IQR)	65 (53–76)	65 (53–76.5)	64.5 (53.5–75.5)	0.98
Gender
Female	451 (50)	391 (50)	60 (48)	0.68
Male	449 (50)	385 (50)	64 (52)
Race
White	587 (66)	517 (67)	70 (57)	0.02
Non-White	308 (34)	255 (33)	53 (43)
Ethnicity
Non-Hispanic	535 (60)	469 (61)	66 (53)	0.006
Hispanic	115 (13)	88 (11)	27 (22)
Unknown/unavailable	243 (27)	212 (28)	31 (25)
Smoking
None	420 (46)	359 (46)	61 (49)	0.80
Former	352 (39)	306 (39)	46 (37)
Current	113 (13)	97 (12)	16 (13)
Unknown/unavailable	15 (2)	14 (2)	1 (1)
Initial critical care contact
No. of days from hospital admission to initial contact	2.36 (1–6)	2.27 (1–6)	3 (1–7.5)	0.02
Type of contact
Critical care evaluation	627 (70)	527 (68)	100 (81)	0.004
Direct ICU admission	273 (30)	249 (32)	24 (19)
ICU admission after critical care evaluation (n = 627)^b	480 (76)	391 (74)	89 (89)	0.001
Time to ICU admission (hr) (n = 479)^c	1 (1–2.5)	1 (1–1.75)	1.6 (1–5)	< 0.001
Prior critical care evaluation	49 (5)	33 (4)	16 (13)	< 0.001
Acute physiology and chronic health evaluation II (median, IQR)	15 (11–20)	15 (11–19.7)	18 (15–22)	< 0.001
Location of contact
Floor/wards	650 (72)	553 (71)	97 (78)	0.02
Step-down-unit	92 (10)	76 (10)	16 (13)
OR/recovery room	147 (16)	138 (17)	9 (7)
Other (endoscopy, dialysis)	11 (1)	9 (1)	2 (2)
ARDS predisposing conditions
Pneumonia	352 (39)	284 (37)	68 (55)	< 0.001
Sepsis	494 (55)	415 (53)	79 (64)	0.03
Pancreatitis	51 (6)	48 (6)	3 (2)	0.09
Aspiration	117 (13)	87 (11)	30 (24)	< 0.001
Shock	258 (29)	214 (28)	44 (35)	0.07
High-risk surgery
Cardiac	8 (0.8)	8 (1)	0 (0)	0.25
Thoracic	4 (0.4)	3 (0.4)	1 (0.8)	0.51
Acute abdomen	69 (8)	64 (8)	5 (4)	0.10
Orthopedic spine	11 (1)	11 (1)	0 (0)	0.18
Risk modifiers
Alcohol abuse	159 (18)	133 (17)	26 (21)	0.29
Obesity (body mass index, > 30)	315 (35)	272 (35)	43 (35)	0.93
Chemotherapy	115 (13)	93 (12)	22 (18)	0.07
Diabetes mellitus	345 (38)	295 (38)	50 (40)	0.62
Emergency surgery	104 (12)	99 (13)	5 (4)	0.005
Respiratory rate (beats/min)	23 (20–30)	22 (20–28)	27 (20–33)	< 0.001
Tachypnea (respiratory rate, > 30)	208 (23)	167 (22)	41 (33)	0.005
Spo₂ (%) (n = 881)	94 (91–97)	94 (91–97)	92 (88–96)	< 0.001
Low Spo₂ (< 95%)	477 (53)	399 (51)	78 (63)	0.01
F_IO2 (%) (n = 768)	32 (24–60)	30 (21–50)	55 (30–100)	< 0.001
High F_IO2 (> 35% or > 4 L/min)	455 (51)	370 (48)	85 (68)	< 0.001
Albumin (g/dL) (n = 305)	2.9 (2.4–3.4)	2.9 (2.5–3.4)	2.6 (2.2–3.3)	0.02
Hypoalbuminemia (< 3.5 g/dL)	233 (26)	188 (24)	45 (36)	0.004
Acidosis (pH, < 7.35)	190 (21)	151 (19)	39 (31)	0.002
Arterial pH (n = 422)	7.37 (7.28–7.43)	7.37 (7.29–7.43)	7.38 (7.21–7.44)	0.39
Lung Injury Prediction Score (median, IQR)	5 (3.5–7)	5 (3.5–6.5)	6.5 (5.5–8)	< 0.001
Mechanical ventilation
Invasive MV after initial contact	158 (18)	103 (13)	55 (44)	< 0.001
Invasive MV anytime within 7 d	366 (41)	251 (33)	115 (93)	< 0.001
Invasive MV at any time after initial contact	369 (41)	253 (33)	116 (94)	< 0.001
Time to intubation	1 (1)	1 (1)	1 (1–2)	0.01
Duration of invasive ventilation (d)	3.5 (2–7.82)	2.89 (1.17–6.85)	5.11 (2.6–11.5)	< 0.001
Noninvasive ventilation after initial contact	63 (7)	54 (7)	9 (7)	0.90
Noninvasive ventilation at any time after contact	114 (21)	71 (17)	43 (35)	< 0.001
Ventilator parameters on initial intubation
TV (mL)	450 (400–500)	450 (400–500)	450 (400–500)	0.35
TV (mL/Kg by predicted body weight)	7.31 (6.5–8.44)	7.31 (6.50–8.37)	7.07 (6.49–8.59)	0.88
Peak inspiratory pressure	23 (18–28)	22 (18–27)	25 (20–32)	< 0.001
Plateau pressure	18 (14–23)	18 (14–22.5)	18 (14–25)	0.51
Positive end-expiratory pressure	5 (5–6)	5 (5)	5 (5–8)	0.14
Outcomes
Hospital mortality	200 (22)	140 (18)	60 (48)	< 0.001
Death within 7 d of contact	101 (11)	77 (10)	24 (19)	0.002
Time to death (d)	7 (3–18)	6.5 (3–16)	10.5 (5–20)	0.01
ICU LOS	3 (1.75–6.4)	2.83 (1.5–5.29)	7 (4–13)	< 0.001
Hospital LOS	14 (8.2–24)	13.6 (8–22)	21 (12.4–36)	< 0.001
Death location (n = 200)
ICU	111 (55)	77 (55)	34 (56)
Floor	88 (44)	63 (45)	25 (42)	0.29
Step-down unit/intermediate care	1 (1)	0 (0)	1 (2)
Disposition (n = 700)
Home	341 (49)	320 (50)	21 (33)
Nursing home	34 (5)	32 (5)	2 (3)
Skilled nursing facility	236 (34)	209 (33)	27 (42)
Rehabilitation center	60 (8)	49 (8)	11 (17)	0.05
Transferred to another hospital	14 (2)	13 (2)	1 (2)
Hospice	2 (0.2)	2 (0.3)	0 (0)
Other (against medical advice)	13 (2)	11 (2)	2 (3)

ARDS = acute respiratory distress syndrome, IQR = interquartile range, LOS = length of stay, MV = mechanical ventilation, OR = odds ratio, TV = tidal volume.
^a p values compare patients with and without acute respiratory distress syndrome (ARDS).
^bThe denominators are 527 for the non-ARDS group and 100 for the ARDS group.
^cThe data represent 390 patients in the non-ARDS group and 89 in the ARDS group.

Table 2. Lung Injury Prediction Score Performance and Association of Lung Injury Prediction Score With Acute Respiratory Distress Syndrome or the Composite Outcome (Acute Respiratory Distress Syndrome or death) in the Full Cohort, Excluding all Deaths, and in the Competing Risk Analysis
LIPS Performance	ARDS (Full Cohort)	Composite (Full Cohort)	ARDS (Excluding Deaths)
LIPS, OR (95% CI)	1.31 (1.21–1.42)	1.26 (1.18–1.34)	1.31 (1.18–1.45)
LIPS ≥ 4, OR (95% CI)	4.17 (2.26–7.72)	2.43 (1.68–3.49)	3.40 (1.59–7.26)
Sensitivity (95% CI)	90.3 (83.7–94.9)	83.3 (78.2–87.6)	87.5 (76.8–94.4)
Specificity (95% CI)	30.9 (27.6–34.3)	32.7 (29–36.5)	32.7 (29–36.5)
Positive predictive value (95% CI)	17.3 (14.4–20.4)	33.9 (30.3–37.7)	11.5 (8.86–14.7)
Negative predictive value (95% CI)	95.2 (91.8–97.5)	82.5 (77.2–87)	96.3 (92.8–98.3)

ARDS = acute respiratory distress syndrome, LIPS = Lung Injury Prediction Score, OR = odds ratio.

Authors and Disclosures

Graciela J. Soto, MD, MS¹, Daryl J. Kor, MD, MSc², Pauline K. Park, MD³, Peter C. Hou, MD⁴, David A. Kaufman, MD⁵, Mimi Kim, ScD⁶, Hemang Yadav, MBBS⁷, Nicholas Teman, MD³, Michael C. Hsu, MS⁸, Tatyana Shvilkina, DO⁸, Yekaterina Grewal, MD⁵, Manuel De Aguirre, MD⁵, Sampath Gunda, MD¹, Ognjen Gajic, MD⁹ and Michelle Ng Gong, MD, MS¹

¹Department of Medicine, Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, NY.
²Division of Anesthesiology, Mayo Clinic, Rochester, MN.
³Department of Surgery, University of Michigan Health System, Ann Arbor, MI.
⁴Section of Emergency Medicine and Critical Care, Department of Emergency Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA.
⁵Section of Pulmonary, Critical Care, and Sleep Medicine, Bridgeport Hospital, Yale New Haven Health System, Bridgeport, CT.
⁶Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, NY.
⁷Division of Pulmonary and Critical Care Medicine, Department of Medicine, Mayo Clinic, Rochester, MN.
⁸Department of Emergency Medicine, Brigham and Women's Hospital, Boston, MA.
⁹Department of Medicine, Mayo Clinic, Rochester, MN.

Address requests for reprints to
Graciela J, Soto, MD, MS, Associate Professor of Medicine, Division of Critical Care Medicine, Jay B. Langner Critical Care Service, Department of Medicine, Montefiore Medical Center, 111 East 210th Street, Gold Zone (Main Floor), Bronx, New York 10467. E-mail: gsoto@montefiore.org

Dr. Soto received support for article research from the National Institutes of Health (NIH). Dr. Kor received support for article research from the NIH and received funding till date. His institution received funding from the NIH. Dr. Kaufman received funding from the Critical Care Roundtable. His institution received funding from the NIH-National Heart, Lung, and Blood Institute (NHLBI). Dr. Kim's institution received funding from the NIH and the Lupus foundation. Dr. Hsu disclosed other support (As a research graduate trainee, he did not receive any payment, nor did he ask for a professional letter of recommendation from the more experienced partner[s]). Dr. Gajic received support for article research from the NIH. Dr. Gong received support for article research from the NIH. Her institution received funding from the NHLBI and Center for Medicare and Medicaid Services. The remaining authors have disclosed that they do not have any potential conflicts of interest.

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