
==== Front
Crit Care Explor
Crit Care Explor
CC9
Critical Care Explorations
2639-8028
Lippincott Williams & Wilkins Hagerstown, MD

39254656
CCE-D-24-00056
00006
10.1097/CCE.0000000000001150
3
Observational Study
Outcomes of Extracorporeal Membrane Oxygenation in Acute Respiratory Distress Syndrome in Pediatric Trauma Patients
Ahmed Nasim MBBS, MBA, FACS 12
Kuo Yen-Hong PhD 23
1 Division of Trauma & Surgical Critical Care, Jersey Shore University Medical Center, Neptune, NJ.
2 Hackensack Meridian School of Medicine, Nutley, NJ.
3 Hackensack Meridian Health Research Institute, Nutley, NJ.
For information regarding this article, E-mail: Nasim.Ahmed@hmhn.org
10 9 2024
9 2024
6 9 e1150Copyright © 2024 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of the Society of Critical Care Medicine.
2024
https://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal.

IMPORTANCE:

Acute respiratory distress syndrome (ARDS) is associated with high mortality and morbidity. Extracorporeal membrane oxygenation (ECMO) is one of the interventions that have been in practice for ARDS for decades.

OBJECTIVES:

The purpose of the study was to investigate the outcomes of ECMO in pediatric trauma patients who suffered from ARDS.

DESIGN:

Observational cohort study.

SETTING AND PARTICIPANTS:

The Trauma Quality Improvement Program database for years 2017 to 2019 and 2021 through 2022 was accessed for the study. All children younger than 18 years old who were admitted to the hospital after trauma and suffered from ARDS were included in the study. Other variables included in the study were patients’ demographics, clinical characteristics, Injury Severity Score (ISS), Glasgow Coma Scale (GCS) score, comorbidities, and outcomes.

MAIN OUTCOMES AND MEASURES:

ECMO is the exposure, and the outcomes are in-hospital mortality and hospital complications (acute kidney injury [AKI], pneumonia and deep vein thrombosis [DVT]).

RESULTS:

Of 453 patients who qualified for the study, propensity score matching found 50 pairs of patients. There were no significant differences identified between the groups, ECMO+ vs. ECMO– on patients’ age in years (16 yr; interquartile range [IQR], 13.25–17 yr vs. 16 yr [14.25–17 yr]), race (White; 62.0% vs. 66.0%), sex (male; 78% vs. 76%), ISS (23 [IQR, 9.25–34] vs. 22 [9.25–32]), and GCS (15 [IQR, 3–15] vs. 13.5 [3–15]), mechanism of injury; and comorbidities. There was no difference between the groups, ECMO+ vs. ECMO–, in-hospital mortality (10.0% vs. 20.0%; p = 0.302), hospital complications (AKI 12.0% vs. 2.0%; p = 0.131), pneumonia (10.0% vs. 20.0%; p = 0.182 > ), and DVT (16% vs. 6%; p = 0.228).

CONCLUSIONS AND RELEVANCE:

No difference in mortality was observed in injured children who suffered from the ARDS and were placed on ECMO when compared with patients who were not placed on ECMO. Patients with trauma and ARDS who require ECMO have comparable outcomes to those who do not receive ECMO. A larger sample size study is needed to find the exact benefit of ECMO in this patients’ cohort.

acute respiratory distress syndrome
extracorporeal membrane oxygenation
outcomes
pediatric trauma
OPEN-ACCESSTRUE
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pmcKEY POINTS

Question: Does extracorporeal membrane oxygenation (ECMO) intervention in pediatric trauma patients who suffer ARDS cause worse mortality?

Findings: Our study did not show any difference between the groups, ECMO+ vs. ECMO– and in-hospital mortality (10.0% vs. 20.0%; p = 0.302).

Meaning: The mortality in ECMO patients was lower than the conventional mode of ventilation in ARDS patients; however, there was no statistical difference found between the groups. A larger sample size study is needed to answer the benefit of ECMO.

Extracorporeal membrane oxygenation (ECMO) is one of the supportive interventions used to manage severe acute respiratory distress syndrome (ARDS). Venovenous ECMO is used exclusively for respiratory failure, including ARDS, whereas venoarterial ECMO is used if additional cardiac support is needed. Worldwide, the use of ECMO in children has been increasing for the last 5 decades due to reported favorable outcomes, technological improvements, and increased availability of specialized ECMO centers (1, 2). A recent population-based study evaluated the ECMO outcomes in children younger than 18 years old including approximately 30% of patients who were neonates (0–30 d). The average age of the cohort was 2.9 years old (3). Approximately 50% of patients suffered from cardiac abnormality and approximately 20% of them suffered from respiratory failure. Their study showed 56.4% survival at hospital discharge and 51.5% survival after 1 year.

Prior studies evaluated the role of ECMO in adult patients with severe ARDS following trauma yielded conflicting results (4–7). Randomized trials on ECMO for the ARDS also consisted of adult patients with variable mortality outcomes (8, 9). However, there is a gap in information regarding the outcomes of ECMO in pediatric trauma patients who suffer from severe ARDS. Barbaro et al (10) performed a comparative study of ECMO vs. no ECMO in children who suffered from ARDS and found no significant difference in outcomes, including mortality, length of stay, or functional outcomes. This study included medical illnesses (pneumonia, aspiration, sepsis, etc.) and did not mention the inclusion of trauma patients. Therefore, we designed a study to determine whether ECMO is associated with improved outcomes in injured children with severe ARDS. We hypothesized that ECMO would be associated with a lower in-hospital mortality rate.

METHODS

The Trauma Quality Improvement Program (TQIP) database of 2017 through 2019 and 2021 and 2022 was accessed for the study. The TQIP database is considered a benchmark of outcomes of trauma patients. Currently, more than 900 institutions across the United States deposit trauma patients’ data in the TQIP on a voluntary basis. The TQIP is owned and maintained by the American College of Surgeons and shares the data on outcomes of the patients with an individual institution (11). All pediatric patients (< 18 yr old) who were admitted to the hospital after sustaining traumatic mechanisms (blunt or penetrating) of injury and who fulfilled the criteria for ARDS were included in the study. Variables reviewed included sex, race, injury type, mechanism of injury, Injury Severity Score (ISS), severe Abbreviated Injury Scale (AIS ≥ 3) score of body regions, Glasgow Coma Scale (GCS) score, and certain comorbidities including attention deficit disorder, history of congenital anomalies, prematurity, bleeding disorder, mental and personality disorder, and substance abuse. Based on the data dictionary of the TQIP database, ARDS was defined as a respiratory failure with associated bilateral opacification on a chest radiograph, and the condition could not be explained by other medical conditions, such as, cardiogenic shock, fluid overload, etc (12). Patients were then categorized into two groups: ECMO+ (International Classification of Diseases, 10th Edition procedure codes; venovenous [5A15223, 5A1522F, and 5A1522H] and venoarterial [5A1522G]) and ECMO–. The patients who died in the emergency department were excluded from the study. Due to unavailability of 2020 data, we have not used the 2020 data in this study.

The primary outcome of the study was overall in-hospital mortality. The secondary outcomes were hospital complications and discharge disposition.

First, summary statistic was presented as the median and interquartile range (IQR) (first quartile–third quartile) for continuous variables, and the percentage was used for categorical variables. The patients who were placed on ECMO+ vs. patients who were not placed on ECMO– were compared on univariate analysis using Wilcoxon rank-sum test and chi-square test or fisher exact test for continuous and categorical variables, respectively. The propensity score for “group” (ECMO+ or ECMO–) was calculated for each subject. Then the one-to-one matching was performed using the “nearest neighbor” approach with a caliper of 0.25 sd. The propensity score matching was performed using the R package “MatchIt” (Version 4.5.5) (13). The variables used for calculating the propensity score (age, race [White], sex, ISS, GCS, and severe chest injury [AIS ≥ 3]). The matching was assessed based on the improvement of the standardized mean difference. The continuous variable of the matched group was analyzed using the Wilcoxon signed-rank test. McNemar test was used to compare the categorical variables between matched groups. The two-sided p values were reported for each test. A p value of less than 0.05 was considered an indication of statistical significance. Statistical analysis was performed using the R language (Version 4.3.2, Viennna, Austria) (14).

All procedures followed were in accordance with the ethical standards of the Institutional Review Board (IRB) of Hackensack Meridian Health (HMH) and with the Helsinki Declaration of 1975, as revised in 2008. Since the data of National Trauma Data Bank (NTDB) are de-identified patient’s information available to the researchers, the study was exempted from HMH IRB review. Informed consent, given this retrospective study, was performed from the de-identified National database from the American College of Surgeons that is available to all researchers, this study was exempted from the IRB review as per policy, and no informed consent was required.

RESULTS

Patients’ Characteristics and Univariate Analysis

Of 453 children who qualified for the study, 50 children (11.04%) were placed on ECMO. The remaining 403 patients (88.96%) were managed on conventional ventilators without ECMO. Approximately 12% of patients were placed on venoarterial ECMO, and approximately 88% of patients were placed on venovenous ECMO. Of 50 patients, 49 patients’ data on the timing of the ECMO procedure was available; the median time of placement of ECMO from the time of admission was 2 days (IQR, 2–6 d). The ECMO patients were a little older compared with non-ECMO patients (16 yr [IQR, 13.25–17 yr] vs. 14 yr [7.5–16 yr]; p = 0.012). A higher proportion of patients who were placed on ECMO sustained injury due to being hit by a vehicle (14.0% vs. 8.2%; p = 0.008), sustained a higher proportion of severe lower extremity injury (AIS ≥ 3; 36.0% vs. 21.1%; p = 0.028), and severe neck injury (8.0% vs. 2.0%; p = 0.033) when compared with patients who were not placed on ECMO (Table 1).

TABLE 1. Univariate Analysis Between Extracorporeal Membrane Oxygenation Versus No Extracorporeal Membrane Oxygenation

Variable	All (n = 453)	No ECMO (n = 403)	ECMO (n = 50)	p	
Age (yr), median (Q1–Q3)	15 (8–16)	14 (7.5–16)	16 (13.25–17)	0.012	
Race, n (%)					
 American Indian	3 (0.7)	2 (0.5)	1 (2)	0.297	
 Asian	5 (1.1)	3 (0.7)	2 (4)	0.096	
 Black	98 (21.6)	89 (22.1)	9 (18)	0.632	
 Pacific Islander	1 (0.2)	0 (0)	1 (2)	0.110	
 Race other	62 (13.7)	57 (14.1)	5 (10)	0.558	
 White	265 (58.5)	234 (58.1)	31 (62)	0.704	
Sex, n (%)				0.107	
 Female	150 (33.1)	139 (34.5)	11 (22)		
 Male	303 (66.9)	264 (65.5)	39 (78)		
Injury Severity Score, median (Q1–Q3)	24 (9–34)	25 (9–35)	23 (9.25–34)	0.886	
Glasgow Coma Scale, median (Q1–Q3)	10 (3–15)	8 (3–15)	15 (3–15)	0.043	
Trauma type, n (%)				0.611	
 Blunt	383 (84.5)	339 (84.1)	44 (88)		
 Penetrating	70 (15.5)	64 (15.9)	6 (12)		
Mechanism, n (%)				0.008	
 All others	85 (18.8)	69 (17.1)	16 (32)		
 Fall	84 (18.5)	81 (20.1)	3 (6)		
 Gun Shot Wound	62 (13.7)	56 (13.9)	6 (12)		
 Motor Vehicle Trauma	182 (40.2)	164 (40.7)	18 (36)		
 Pedestrian hit by	40 (8.8)	33 (8.2)	7 (14)		
Comorbidities, n (%)					
 Attention deficit disorder	1 (0.2)	1 (0.2)	0 (0)	> 0.99	
 Congenital disorder	6 (1.3)	6 (1.5)	0 (0)	> 0.99	
 Prematurity	3 (0.7)	2 (0.5)	1 (2)	0.297	
 Mental personality disorder	19 (4.2)	16 (4)	3 (6)	0.454	
 Substance abuse	14 (3.1)	12 (3)	2 (4)	0.660	
 Bleeding	13 (2.9)	13 (3.2)	0 (0)	0.378	
Abbreviated Injury Scale (≥ 3) severe injury, n (%)					
 Brain	208 (45.9)	191 (47.4)	17 (34)	0.101	
 Neck	12 (2.6)	8 (2)	4 (8)	0.033	
 Face	4 (0.9)	4 (1)	0 (0)	> 0.99	
 Spine	33 (7.3)	29 (7.2)	4 (8)	0.774	
 Chest	188 (41.5)	165 (40.9)	23 (46)	0.594	
 Abdomen	106 (23.4)	90 (22.3)	16 (32)	0.178	
 Upper extremity	4 (0.9)	3 (0.7)	1 (2)	0.375	
 Lower extremity	103 (22.7)	85 (21.1)	18 (36)	0.028	
ECMO = extracorporeal membrane oxygenation.

Propensity Matching Analysis

After propensity score matching, there was a substantial improvement in the standardized mean differences among matching variables. The matching methodology created 50 pairs of patients. There were no differences found between the groups, ECMO+ vs. ECMO– on patients’ age in years (16 yr [IQR, 13.25–17 yr vs. 16 yr [14.25–17 yr]; p = 0.431), race (White; 62.0% vs. 66.0%; p = 0.845), sex (male; 78.0% vs. 76.0%; p ≥ 0.99), ISS (23 [IQR, 9.25–34] vs. 22 [9.25–32]; p = 0.582, and GCS (15 [IQR, 3–15] vs. 13.5 [3–15]; p = 0.353); mechanism of injury; and comorbidities (Table 2).

TABLE 2. Propensity Matched Analysis Between Extracorporeal Membrane Oxygenation Versus No Extracorporeal Membrane Oxygenation

Variable	All (n = 100)	No ECMO (n = 50)	ECMO (n = 50)	p	
Age (yr), median (Q1–Q3)	16 (14–17)	16 (14.25–17)	16 (13.25–17)	0.431	
Race, n (%)					
 American Indian	1 (1)	0 (0)	1 (2)	NA	
 Asian	2 (2)	0 (0)	2 (4)	NA	
 Black	17 (17)	8 (16)	9 (18)	> 0.99	
 Pacific Islander	1 (1)	0 (0)	1 (2)	NA	
 Race other	12 (12)	7 (14)	5 (10)	0.773	
 White	64 (64)	33 (66)	31 (62)	0.845	
Sex, n (%)				> 0.99	
 Female	23 (23)	12 (24)	11 (22)		
 Male	77 (77)	38 (76)	39 (78)		
Injury Severity Score, median (Q1–Q3)	22 (9–34)	22 (9.25–32)	23 (9.25–34)	0.582	
Glasgow Coma Scale, median (Q1–Q3)	14 (3–15)	13.5 (3–15)	15 (3–15)	0.353	
Trauma type, n (%)				0.579	
 Blunt	85 (85)	41 (82)	44 (88)		
 penetrating	15 (15)	9 (18)	6 (12)		
Mechanism, n (%)				NA	
 All others	26 (26)	10 (20)	16 (32)		
 Fall	10 (10)	7 (14)	3 (6)		
 Gun Shot Wound	15 (15)	9 (18)	6 (12)		
 Motor Vehicle Trauma	37 (37)	19 (38)	18 (36)		
 Pedestrian hit by	12 (12)	5 (10)	7 (14)		
Comorbidities, n (%)					
 Prematurity	1 (1)	0 (0)	1 (2)	NA	
 Mental personality disorder	6 (6)	3 (6)	3 (6)	> 0.99	
 Substance abuse	4 (4)	2 (4)	2 (4)	> 0.99	
 Bleeding	1 (1)	1 (2)	0 (0)	NA	
Abbreviated Injury Scale (≥ 3) severe injury, n (%)					
 Brain	38 (38)	21 (42)	17 (34)	0.540	
 Neck	6 (6)	2 (4)	4 (8)	NA	
 Spine	7 (7)	3 (6)	4 (8)	NA	
 Chest	46 (46)	23 (46)	23 (46)	> 0.99	
 Abdomen	27 (27)	11 (22)	16 (32)	0.302	
 Upper extremity	1 (1)	0 (0)	1 (2)	NA	
 Lower extremity	33 (33)	15 (30)	18 (36)	0.646	
ECMO = extracorporeal membrane oxygenation, NA = not applicable.

Outcomes

There was no difference between the groups, ECMO+ vs. ECMO– and in-hospital mortality in pair analysis (10.0% vs. 20.0%; p = 0.302). There were no differences found between the groups, in-hospital complications (acute kidney injury: 12.0% vs. 2.0%; p = 0.131), pneumonia (10.0% vs. 20.0%; p = 0.182), deep vein thrombosis (16% vs. 6%; p = 0.228), pulmonary embolism (2% vs. 2%; p = 1.000), and stroke (2% vs. 2%; p = 1.000). Patients who survived at the time of discharge did not show any difference regardless of whether the patients were placed on ECMO or not on ECMO (discharge to home without additional care, 48.9% vs. 52.9%; p = 0.949; Table 3)

TABLE 3. Outcomes of Patients, Extracorporeal Membrane Oxygenation Versus No Extracorporeal Membrane Oxygenation in Post-Matched Analysis

Variable	No ECMO (n = 50)	ECMO (n = 50)	OR (95% CI)	Absolute Risk Difference (95% CI)	p	
Mortality, n (%)	10 (20)	5 (10)	0.5 (0.065–1.533)	–0.1 (–0.269 to 0.069)	0.302	
Hospital (length of stay), d	21 (12–32)	22 (14–39)			0.762	
Complications, n (%)						
 Acute kidney injury	1 (2)	6 (12)	6 (1.112 to –6.325)	0.1 (–0.02 to 0.22)	0.131	
 Respiratory complications	35 (70)	30 (60)	0 (–0.091 to 0.111)	–0.1 (–0.203 to 0.003)	0.074	
 Sepsis	2 (4)	0 (0)	NA	–0.04 (–0.094 to 0.014)	NA	
 Ventilator-associated pneumonia	10 (20)	5 (10)	0.286 (–0.095 to 1.219)	–0.1 (–0.234 to 0.034)	0.182	
ECMO = extracorporeal membrane oxygenation, NA = not applicable, OR = odds ratio.

Hospital length of stay; median (95% CI), Kaplan-Meier procedure, and ICU and ventilator days; and median (first quartile–third quartile).

DISCUSSION

Our study showed that approximately 11% of children (age < 18) who developed ARDS were placed on ECMO. In-hospital mortality of children on ECMO in post-matched analysis was (10.0% vs. 20.0%; p = 0.302) compared with children who were not placed on ECMO; however, no statistically significant difference was identified. Similarly, no differences were found between the ECMO+ vs. ECMO– patients regarding the in-hospital complications and discharge to home.

Our study showed ECMO intervention in children with ARDS after trauma had a lower mortality rate compared with ECMO intervention in ARDS in adult trauma patients (4–7). The reported mortality of ECMO intervention after an ARDS in adult trauma patients ranged between 13% and 56%. Our study showed 10% mortality rate among children (< 18 yr old) who were placed on ECMO with ARDS after trauma, which is relatively lower than the adult population. It is unsurprising to see a lower mortality rate in our study because previous studies have shown age as an independent factor of overall mortality and younger age is a favorable factor (15, 16). A study from the NTDB analyzed the data from 2007 to 2011 and included 36 pediatric patients on ECMO, showing a mortality rate of 42% (17), which was much higher than our analysis of the recent (2017–2019 & 2021 and 2022) TQIP database study that included 50 patients in the matched sample, which showed mortality at 10.0%. The reason for discrepancies in the mortality outcome may be due to more inclination to use ECMO in ARDS now compared with a decade ago when the ECMO might have been used as a last resort (18). Another reason for the higher mortality in the above study perhaps due to the inclusion of all mechanisms of patients including drowning 11%, burn 16.7%, and poisoning 6.8%, etc. One of the case series of eight patients, five children and three adults, with ARDS after trauma showed four of five pediatric patients (80%) survived after ECMO intervention (19). Another relatively recent review study on ECMO in pediatric trauma patients showed the survival rate ranged from 50% to 100% (20). In their study, approximately 50% of patients were discharged to home, and approximately 64% of patients had good neurologic recovery. Our study result showed a lower mortality rate in patients who were placed on ECMO; however, there was no significant association in overall in-hospital mortality between the groups, ECMO+ vs. ECMO– (10.0% vs. 20.0%; p = 0.302) and the result was consistent with the previous study (17).

Although our study on ECMO in injured children (< 18 yr) is one of the two largest sample size studies, the study has several limitations. First, it is still a small sample size study. Second, the study data was accessed from the TQIP database, which lacks important information regarding the actual values of the Pao2 and Fio2 and its ratios. A recent meta-analysis showed higher Pao2 before ECMO placement was associated with survival benefit (21). Third, we performed propensity score matching to compare the two groups to reduce the selection bias; however, the lack of information may not have eliminated the selection bias.

CONCLUSIONS

Among children who suffer from ARDS complications following trauma, the use of ECMO failed to show any association with mortality benefit. More studies on injured children are needed to find the exact benefit of ECMO utilization.

ACKNOWLEDGMENTS

We thank Elli Gourna Paleoudis, MS, PhD, performed the critical reading and final editing of the article.

Dr. Ahmed conceived and designed the study. Dr. Ahmed was responsible for retrieving the study data, while Dr. Kuo performed the data analysis. Drs. Ahmed and Kuo both contributed to article writing.

The authors have disclosed that they do not have any potential conflicts of interest.
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