1. • Medical admissions comprised nearly half of the admissions of pediatric patients
with systolic HF during the 5 year study period. Of these, 65% needed ICU care
during the admission.
• In a medical admission of a pediatric patient with systolic HF, RBC transfusion was
independently associated with higher risk of hospital mortality and greater
resource utilization, even in the setting of multiple other comorbidities.
• A majority of the patients receiving RBC transfusion during a medical admission
did not have a documented indication for the transfusion, and were neither
anemic nor having a bleeding/hemorrhagic complication.
• RBC remain a precious resource and were not found to be helpful for patient
outcomes in this study. Our findings suggest a need for closer examination of RBC
transfusion practice as a modifiable risk factor in this population.
BLOOD TRANSFUSIONS ARE ASSOCIATED WITH MORTALITY IN PEDIATRIC PATIENTS WITH SYSTOLIC HEART FAILURE –
A MULTI-INSTITUTIONAL ANALYSIS
BACKGROUND
K Puri1
, RD Morales Demori1
, PA Checchia1
, Y Wang2
, MM Anders1
1 – Section of Critical Care Medicine, Department of Pediatrics, Baylor College of Medicine, Texas Children’s Hospital;
2 – Cardiovascular Research Core, Section of Cardiology, Department of Pediatrics, Baylor College of Medicine, Texas Children’s Hospital
CONCLUSIONS
• Restrictive thresholds for red blood cell (RBC) transfusion have not
been shown to be inferior to liberal transfusion thresholds after
cardiac surgery in pediatric or adult patients.1,2
• RBC transfusions are associated with readmission due to heart failure
(HF) in adults after aortic valve replacements, and with increased risk
of right ventricle-pulmonary artery conduit failure in pediatric
patients.3,4
• Data are limited about RBC transfusions in pediatric patients with HF.
METHODS
• Retrospective cohort study querying the Pediatric Health Information
System (PHIS) database, comprised of 50 free-standing children’s
hospitals from 01/01/2012 to 12/31/2017.
• Inclusion Criteria: Admissions of patients aged < 21 years (yr) with ICD-
9/10 codes for systolic HF.
• Exclusion Criteria for Primary Analysis: Patients undergoing any
invasive surgical procedure which may necessitate blood transfusion,
including extracorporeal membrane oxygenation (ECMO), RACHS-1
surgery, ventricular assist device (VAD), heart transplantation (HTx), or
other surgeries (Others).
• Demographic and clinical features and procedures during admission
reviewed using ICD-9/10 coding.
• Outcomes: Primary outcome was mortality and secondary outcomes
were hospital length of stay (LOS) and billed charges.
• Univariate and multivariable analyses performed using generalized
estimating equations (GEE) for categorical outcomes and mixed
modeling (with logarithmic transformation due to non-normal
distribution) for continuous outcomes, to account for clustering by
hospitals - factors with p<0.2 on univariate analysis included in the
initial multivariable model, and factors with p<0.05 retained in
successive models.
RESULTS
AIMS AND HYPOTHESIS
• AIMS: (i) To assess the burden of RBC transfusions during medical
admissions of pediatric patients with HF, and (ii) to assess the
association of RBC transfusions with admission outcomes in these
patients.
• HYPOTHESIS: RBC transfusion is associated with hospital mortality in
medical admissions of pediatric patients with HF.
• 10,798 patients met initial inclusion criteria - 726 underwent HTx, 504 underwent VAD (without HTx), 1781 underwent RACHS-1 surgery (without VAD or
HTx), 188 underwent ECMO (without HTx or VAD or RACHS-1 surgery), and 3036 underwent other surgical procedures (excluding cardiac or ECMO) were
excluded
• 4,563 medical admissions included in the primary analysis.
• Separate exploratory analysis performed for the groups with surgical interventions. This was limited by inability to differentiate if they received RBC
transfusion during perioperative period/cardiopulmonary bypass or at other times during the admission.
• Demographics: Median age: 3 yr (IQR 0 – 13 yr), Sex: 54% (2,473) male; Race/Ethnicity: 45% (2,042)non-Hispanic white, 26% (1,162) Hispanic, 15% (683) non-
Hispanic Black, 13% (585) Others, 2% (91) unknown.
• Clinical Characteristics: overall hospital mortality 5% (244). Congenital heart disease present in 60% (2,756).
• RBC transfusion administered in 11% (481). Of these, 41% (198/481) were anemic and 10% (49/481) had bleeding complications during the admission.
• Reason for RBC transfusion uncertain for the remaining cases (surgical indications already excluded in initial selection criteria).
TABLE 1. COMPARISON OF DEMOGRAPHIC AND CLINICAL FEATURES BETWEEN
TRANSFUSED AND NON-TRANSFUSED GROUPS
CLINICAL FEATURES
TRANSFUSED
(n=554)
NON-TRANSFUSED
(n=4417)
p-value
Age in years, median (IQR) 0 (0 – 8) 3 (0 – 13) <0.001
Male Sex, n (%) 260 (47) 2213 (50) 0.947
Anemia, n (%) 198 (36) 546 (12) <0.001
Bleeding, n (%) 49 (9) 435 (10) 0.752
Congenital Heart Disease, n (%) 303 (55) 2453 (56) 0.219
Concomitant Diastolic HF, n (%) 233 (42) 1829 (41) 0.130
Kidney Failure, n (%) 137 (25) 691 (16) <0.001
Liver Failure, n (%) 22 (4) 71 (2) <0.001
Mechanical Ventilation, n (%) 323 (58) 1025 (23) <0.001
ICU Admission, n (%) 427 (77) 2527 (57) <0.001
Length of Stay in ICU in days,
median (IQR)
7 (2 – 14) 2 (0 – 6) <0.001
Risk of Mortality Score, n (%) <0.001
Major or Severe 423 (88) 2591 (66)
Minor or Moderate 58 (12) 1491 (34)
OUTCOMES
Mortality, n (%) 68 (12) 176 (4) <0.001
Length of Stay in days, median
(IQR)
16 (8 – 29) 7 (3 – 13) <0.001
Billed Charges (US Dollars), median
(IQR)
358,215 (154,020 –
773,283)
90,857 (37,092 –
234,170)
<0.001
TABLE 2. UNIVARIATE AND MULTIVARIABLE ANALYSIS FOR PRIMARY OUTCOME
CHARACTERISTIC
DEATH
(N=244)
SURVIVED
(N=4319)
p-value
uni
p-value
multi#
OR (95% CI)
Age in years, median (IQR) 2 (0 – 13.0) 3 (0 – 13.0) 0.967
Male Sex, n (%) 124 (51) 2349 (54) 0.280
Race/Ethnicity, n (%)@
Non-Hispanic White 92 (38) 1950 (45) Ref Ref
Hispanic 78 (32) 1084 (25) 0.008 0.010
1.57 (1.12 –
2.20)
Non-Hispanic Black 33 (14) 650 (15) 0.726 0.219
Others 41 (17) 635 (15) 0.533 0.686
RBC transfusion, n (%) 68 (28) 413 (10) <0.001 0.014
1.55 (1.09 –
2.19)
Anemia, n (%) 57 (23) 687 (16) 0.002
Bleeding Complications, n (%) 33 (14) 451 (10) 0.127
Congenital Heart Disease, n
(%)
145 (59) 2611 (60) 0.749
Concomitant Diastolic HF, n
(%)
112 (46) 1950 (45) 0.814
Kidney Failure, n (%) 118 (48) 710 (16) <0.001 <0.001
3.05 (2.28 –
4.07)
Liver Failure, n (%) 22 (9) 71 (2) <0.001 <0.001
2.83 (1.67 –
4.80)
Mechanical Ventilation, n (%) 199 (82) 1149 (27) <0.001 <0.001
10.68 (7.43 –
15.35)
SECONDARY OUTCOMES:
•LENGTH OF STAY - Transfused cohort had longer LOS (median 16 days (IQR 8 – 29
days) vs 7 days (IQR 3 – 13 days) in non-transfused, p < 0.001) on univariate and
multivariable analysis.
• Other factors significant on multivariable analysis – age at admission
(p=0.027), anemia (p<0.001), concomitant diastolic HF (p = 0.039),
mechanical ventilation (p<0.001), and kidney failure (p<0.001).
•BILLED CHARGES - Transfused cohort had greater billed charges (median $ 358,215
(IQR $ 154,020 – $ 773,283) vs $ 90,857 ($ 37,092 – $ 234,170) in non-transfused,
p<0.001) on univariate and multivariable analysis.
• Other factors remaining significant on multivariable analysis – age at
admission (p<0.001), race/ethnicity (p<0.001), congenital heart disease
(p<0.001), anemia (p<0.001), mechanical ventilation (p<0.001), and kidney
failure (p<0.001).
PRIMARY OUTCOME ANALYSIS - TABLE 2:
•RBC transfusion was associated with hospital mortality (28% vs 10%,
p<0.001) on univariate and multivariable regression analysis.
•Other factors remaining significant on multivariable analysis - kidney failure
(p<0.001), liver failure (p<0.001) and mechanical ventilation (p<0.001).
RESULTS
REFERENCES: 1 – Shehata N et al. Restrictive compared with liberal red cell transfusion strategies in cardiac surgery: a meta-analysis. Eur Heart J. 2018 Aug 10; 2 - Cholette J et al. Recommendations on RBC Transfusion in Infants and Children With Acquired and Congenital Heart Disease From the Pediatric Critical Care Transfusion and Anemia Expertise Initiative. Pediatr Crit Care Med. 2018 Sep;19(9S Suppl
1):S137-S148; 3 - Durand E et al. Incidence, Prognostic Impact, and Predictive Factors of Readmission for Heart Failure After Transcatheter Aortic Valve Replacement. JACC Cardiovasc Interv. 2017 Dec 11;10(23):2426-2436; 4 - Therrien J et al. Repeated blood transfusions: Identification of a novel culprit of early graft failure in children. Int J Cardiol. 2018 Mar 1;254:90-95.
Ref: reference
Factors included in initial regression model – all with p<0.2; Factors in final regression model: race/ethnicity,
kidney failure, liver failure, RBC transfusion, mechanical ventilation
EXPLORATORY ANALYSIS FOR PEDIATRIC HF ADMISSIONS WITH SURGERY:
•HTx group (n = 726) – RBC transfusion was not associated with hospital mortality
(4% in transfused, vs 2.8% in non-transfused, p = 0.388).
•VAD without HTx group (n = 188) – RBC transfusion was not associated with hospital
mortality (38% in transfused vs 31% in non-transfused, p = 0.287).
•RACHS-1 surgery without VAD or HTx group (n = 1781) – RBC transfusion was
associated with mortality on univariate and multivariable analysis (6.2% vs 3.1%, p =
0.003, OR 2.33, 95% CI 1.34 – 4.06).
•ECMO without VAD or HTx or RACHS-1 surgery group (n = 504) - RBC transfusion
was not associated with hospital mortality (42% in transfused vs 39% in non-
transfused, p = 0.569).
•Other surgical procedures group (n = 3036) – RBC transfusion was associated with
hospital mortality on univariate but NOT on multivariable regression analysis (6.2%
vs 3.2%, p = 0.083 on multivariable analysis, OR 1.41, 95% CI 0.96 – 2.07).
COMPARISON OF DEMOGRAPHIC AND CLINICAL FEATURES BETWEEN
TRANSFUSED AND NOT-TRANSFUSED COHORTS – TABLE 1:
•Compared to the non-transfused group, the transfused group was younger
(p < 0.001), and more likely to have clinical comorbidities - including anemia
(p<0.001), kidney failure (p<0.001), liver failure (p<0.001), and mechanical
ventilation (p<0.001).