Application of the Berlin definition in children with acute respiratory distress syndrome

Soo Yeon Kim; Yoon Hee Kim; In Suk Sol; Min Jung Kim; Seo Hee Yoon; Kyung Won Kim; Myung Hyun Sohn; Kyu-Earn Kim

doi:10.4168/aard.2016.4.4.257

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Kim, Kim, Sol, Kim, Yoon, Kim, Sohn, and Kim: Application of the Berlin definition in children with acute respiratory distress syndrome

Original Article

Allergy, Asthma & Respiratory Disease 2016; 4(4): 257-263.

Published online: 31 July 2016

DOI: https://doi.org/10.4168/aard.2016.4.4.257

Application of the Berlin definition in children with acute respiratory distress syndrome

Soo Yeon Kim, Yoon Hee Kim, In Suk Sol, Min Jung Kim, Seo Hee Yoon, Kyung Won Kim, Myung Hyun Sohn

, Kyu-Earn Kim

Department of Pediatrics, Severance Hospital, Institute of Allergy, Brain Korea 21 PLUS Project for Medical Science, Yonsei University College of Medicine, Seoul, Korea.

Correspondence to: Myung Hyun Sohn, Department of Pediatrics, Severance Hospital, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul 03722, Korea. Tel: +82-2-2228-2050, Fax: +82-2-393-9118, mhsohn@yuhs.ac

Received 13 October 2015 Revised 19 October 2015 Accepted 29 October 2015

(open-access):

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/).

Abstract

Purpose

The revised Berlin definition (BD) showed better predictive validity for mortality in adults with acute respiratory distress syndrome (ARDS). We examined the validity of BD for pediatric ARDS as compared to the American–European Consensus Conference definition (AECCD).

Methods

This single-center, retrospective study included 127 patients aged 1 month to 19 years who were admitted to the medical intensive care unit due to acute lung injury (ALI, n=31) or ARDS (n=96) using the AECCD. All patient characteristics and mortality rates were compared between the individual severity groups according to the BD and AECCD.

Results

Sixty-four patients (50%) died. Mortality rates increased across the severity groups according to both definitions (26% in mild, 42% in moderate, and 75% in severe by the BD [P<0.001]; 26% in ALI non-ARDS and 58% in ARDS by the AECCD [P=0.002]). The mortality risk increased only for 'severe ARDS' (hazard radio for mortality, 2.56; 95% confidence intervals [CI], 1.14–5.78; P=0.023) after adjusting for confounding factors. The BD better predicted mortality, with an integrated area under the receiver operating characteristic curve (iAUC) of 0.651 (95% CI, 0.571–0.725), than the AECCD, with an iAUC of 0.584 (95% CI, 0.523–0.637). The pediatric risk of mortality (PRISM) III and pediatric index of mortality 3 scores were significantly different across BD severity groups, whereas only PRISM III scores were different according to the AECCD.

Conclusion

The BD applied to children with ARDS. It could be adopted to severity classifications and predict pediatric ARDS mortality better than the AECCD.

Keywords: Acute respiratory distress syndrome, Child, Mortality, Validity

Figures and Tables

Fig. 1

Kaplan-Meier curves for mortality according American-European Consensus Conference (AECC) and Berlin definition severity classes. Survival according to the AECC (A) and Berlin (B) definition. (A) Solid and dashed lines represent acute lung injury (ALI) non-ARDS and acute respiratory distress syndrome (ARDS) classes, respectively. (B) Solid, dashed, and dotted lines represent mild, moderate, and severe ARDS, respectively. Significant differences are shown in both definitions (P= 0.004 and P< 0.001, respectively by Log-rank test).

Fig. 2

Predictive accuracy for mortality: integrated area under the curve (iAUC) by follow-up time. Solid and dotted lines represent the American-European Consensus Conference (AECC) definition and Berlin definition, respectively. The Berlin definition had better mortality predictions, with an iAUC of 0.651 (95% confidence interval [CI], 0.571–0.725), than the AECC definition, which had an iAUC of 0.584 (95% CI, 0.523–0.637).

Table 1

Patient demographics (n= 127)

Demographic	Value
Age (yr)	4.1 (1.7–10.5)
Male sex	79 (62)
PRISM III	9 (5–15)
PIM 3	11.3 (5.3–28.2)
PaO₂/FiO₂ at the diagnosis	131.7 (82–199.5)
Predisposing risk factors of ARDS
Pneumonia	69 (54)
Sepsis	29 (23)
Aspiration	18 (14)
Bronchiolitis	4 (3)
Others	5 (4)
Major comorbidities
Neurologic disease	52 (41)
Pediatric cancer	34 (27)
Outcomes
Mortality	64 (50)
ECMO/mortality^*	65 (51)
In survivors (n=63)
ICU length of stay (day)	11 (8–22)
Ventilator care duration (day)	9 (6–20)

Values are presented as median (interquartile range) or number (%).

PRISM III, pediatric risk of mortality III; PIM 3, pediatric index of mortality 3; PaO₂, arterial partial pressure of oxygen; FiO₂, fraction of inspired oxygen; ARDS, acute respiratory distress syndrome; ECMO, extracorporeal membrane oxygenation; ICU, intensive care unit.

^*ECMO/mortality, composite variable including both mortality cases and ECMO insertion cases.

Table 2

Clinical characteristics and physiological variables of patients across severity categories using the AECC definition and the Berlin definition

Variable	AECC definition		Berlin definition
Variable	ALI non-ARDS (n=31)	ARDS (n=96)	Mild ARDS (n = 31)	Moderate ARDS (n = 48)	Severe ARDS (n = 48)
Age (yr)	4.4 (1.3–9.7)	4.1 (1.8–10.8)	4.4 (1.3–9.7)	4.1 (1.6–11.8)	4.1 (2.0–10.5)
Male sex	15 (48)	64 (67)	15 (48)	35 (73)	29 (60)
PRISM III	8 (4–13)	10 (6–17)	8 (4–13)	7 (3–13)	12 (8–19)^‡,§
PIM 3	6.3 (4.5–12.7)	15.3 (6.0–30.4)^*	6.3 (4.5–12.7)	7.2 (4.8–21.5)	27.5 (9.8–41.0)^‡,§
Ventilatory parameter
PaO₂/FiO₂	236.7 (212.0–270.3)	100.1 (73.0–144.9)^*	236.7 (212.0–270.3)	143.8 (128.3–167.1)^†	73.0 (58.2–86.8)^‡,§
FiO₂	0.4 (0.4–0.5)	0.7 (0.6–1.0)^*	0.4 (0.4–0.5)	0.6 (0.5–0.6)^†	1.0 (0.9–1.0)^‡,§
TV/BWt (mL/kg)	6.3 (5.3–6.9)	6.8 (6.1–7.7)^*	6.3 (5.3–6.9)	6.5 (6.0–7.2)	7.2 (6.3–8.2)^‡
Ppeak	21 (15–25)	25 (20–29)^*	21 (15–25)	22 (19–25)	29 (20–32)^‡,§
PEEP	5 (5–5)	7 (5–8)^*	5 (5–5)	5 (5–7)^†	8 (6–10)^‡,§
Primary outcomes
Mortality	8 (26)	56 (58)^*	8 (26)	20 (42)	36 (75)^‡,§
ECMO/mortality	8 (26)	57 (59)^*	8 (26)	20 (42)	37 (77)^‡,§
Secondary outcomes (in survivors)
ICU length of stay (day)	11 (8–25)	12 (8–22)	11 (8–25)	10.5 (8–20.8)	20 (8.3–29.5)
Ventilator care duration (day)	9 (5–24)	9.5 (6–19.8)	9 (5–24)	9 (6–17)	18 (5.3–26.3)

Values are presented as median (interquartile range) or number (%).

AECC, American-European Consensus Conference; ALI, acute lung injury; ARDS, acute respiratory distress syndrome; PRISM III, pediatric risk of mortality III; PIM 3, pediatric index of mortality 3; PaO₂, arterial partial pressure of oxygen; FiO₂, fraction of inspired oxygen; TV, tidal volume; BWt, body weight; Ppeak, peak pressure; PEEP, positive end-expiratory pressure; ECMO, extracorporeal membrane oxygenation; ICU, intensive care unit.

^*ALI non-ARDS vs. ARDS: P< 0.01. ^†Mild ARDS vs. moderate ARDS: P< 0.01. ^‡Mild ARDS vs. severe ARDS: P< 0.01. ^§Moderate ARDS vs. severe ARDS: P< 0.01.

Table 3

Multivariate analysis using the Cox model for mortality

Variable	Hazard ratio	95% Confidence interval	P-value
Age	0.98	0.93–1.03	0.419
Male sex	1.02	0.59–1.74	0.957
PRISM III	1.01	0.97–1.06	0.553
PIM 3	1.02	1.00–1.03	0.008
Underlying disease
Pneumonia	0.91	0.49–1.68	0.753
Sepsis	2.56	1.42–4.60	0.002
Neurologic disease	1.02	0.53–1.97	0.954
Pediatric cancer	2.43	1.16–5.08	0.018
AECC definition
ALI non-ARDS (reference)
ARDS	1.73	0.80–3.76	0.166
Berlin definition
Mild ARDS (reference)
Moderate ARDS	1.17	0.50–2.72	0.725
Severe ARDS	2.56	1.14–5.78	0.023

PRISM III, pediatric risk of mortality III; PIM 3, pediatric index of mortality 3; AECC, American-European Consensus Conference; ALI, acute lung injury; ARDS, acute respiratory distress syndrome.

Notes

This research was supported by Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education (2007-0056092 and 2011-0024036).

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ORCID iDs: Myung Hyun Sohn
https://orcid.org/http://orcid.org/0000-0002-2478-487X
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