Immediate Transfusion in African Children with Uncomplicated Severe Anemia.
Anemia
/ complications
Blood Transfusion
/ economics
Child
Child, Preschool
Cost-Benefit Analysis
Female
Follow-Up Studies
Health Care Costs
Hemoglobins
/ analysis
Humans
Infant
Length of Stay
/ economics
Malaria
/ complications
Malawi
/ epidemiology
Male
Patient Readmission
/ statistics & numerical data
Time-to-Treatment
Transfusion Reaction
/ epidemiology
Uganda
/ epidemiology
Journal
The New England journal of medicine
ISSN: 1533-4406
Titre abrégé: N Engl J Med
Pays: United States
ID NLM: 0255562
Informations de publication
Date de publication:
01 08 2019
01 08 2019
Historique:
entrez:
1
8
2019
pubmed:
1
8
2019
medline:
8
8
2019
Statut:
ppublish
Résumé
The World Health Organization recommends not performing transfusions in African children hospitalized for uncomplicated severe anemia (hemoglobin level of 4 to 6 g per deciliter and no signs of clinical severity). However, high mortality and readmission rates suggest that less restrictive transfusion strategies might improve outcomes. In this factorial, open-label, randomized, controlled trial, we assigned Ugandan and Malawian children 2 months to 12 years of age with uncomplicated severe anemia to immediate transfusion with 20 ml or 30 ml of whole-blood equivalent per kilogram of body weight, as determined in a second simultaneous randomization, or no immediate transfusion (control group), in which transfusion with 20 ml of whole-blood equivalent per kilogram was triggered by new signs of clinical severity or a drop in hemoglobin to below 4 g per deciliter. The primary outcome was 28-day mortality. Three other randomizations investigated transfusion volume, postdischarge supplementation with micronutrients, and postdischarge prophylaxis with trimethoprim-sulfamethoxazole. A total of 1565 children (median age, 26 months) underwent randomization, with 778 assigned to the immediate-transfusion group and 787 to the control group; 984 children (62.9%) had malaria. The children were followed for 180 days, and 71 (4.5%) were lost to follow-up. During the primary hospitalization, transfusion was performed in all the children in the immediate-transfusion group and in 386 (49.0%) in the control group (median time to transfusion, 1.3 hours vs. 24.9 hours after randomization). The mean (±SD) total blood volume transfused per child was 314±228 ml in the immediate-transfusion group and 142±224 ml in the control group. Death had occurred by 28 days in 7 children (0.9%) in the immediate-transfusion group and in 13 (1.7%) in the control group (hazard ratio, 0.54; 95% confidence interval [CI], 0.22 to 1.36; P = 0.19) and by 180 days in 35 (4.5%) and 47 (6.0%), respectively (hazard ratio, 0.75; 95% CI, 0.48 to 1.15), without evidence of interaction with other randomizations (P>0.20) or evidence of between-group differences in readmissions, serious adverse events, or hemoglobin recovery at 180 days. The mean length of hospital stay was 0.9 days longer in the control group. There was no evidence of differences in clinical outcomes over 6 months between the children who received immediate transfusion and those who did not. The triggered-transfusion strategy in the control group resulted in lower blood use; however, the length of hospital stay was longer, and this strategy required clinical and hemoglobin monitoring. (Funded by the Medical Research Council and Department for International Development; TRACT Current Controlled Trials number, ISRCTN84086586.).
Sections du résumé
BACKGROUND
The World Health Organization recommends not performing transfusions in African children hospitalized for uncomplicated severe anemia (hemoglobin level of 4 to 6 g per deciliter and no signs of clinical severity). However, high mortality and readmission rates suggest that less restrictive transfusion strategies might improve outcomes.
METHODS
In this factorial, open-label, randomized, controlled trial, we assigned Ugandan and Malawian children 2 months to 12 years of age with uncomplicated severe anemia to immediate transfusion with 20 ml or 30 ml of whole-blood equivalent per kilogram of body weight, as determined in a second simultaneous randomization, or no immediate transfusion (control group), in which transfusion with 20 ml of whole-blood equivalent per kilogram was triggered by new signs of clinical severity or a drop in hemoglobin to below 4 g per deciliter. The primary outcome was 28-day mortality. Three other randomizations investigated transfusion volume, postdischarge supplementation with micronutrients, and postdischarge prophylaxis with trimethoprim-sulfamethoxazole.
RESULTS
A total of 1565 children (median age, 26 months) underwent randomization, with 778 assigned to the immediate-transfusion group and 787 to the control group; 984 children (62.9%) had malaria. The children were followed for 180 days, and 71 (4.5%) were lost to follow-up. During the primary hospitalization, transfusion was performed in all the children in the immediate-transfusion group and in 386 (49.0%) in the control group (median time to transfusion, 1.3 hours vs. 24.9 hours after randomization). The mean (±SD) total blood volume transfused per child was 314±228 ml in the immediate-transfusion group and 142±224 ml in the control group. Death had occurred by 28 days in 7 children (0.9%) in the immediate-transfusion group and in 13 (1.7%) in the control group (hazard ratio, 0.54; 95% confidence interval [CI], 0.22 to 1.36; P = 0.19) and by 180 days in 35 (4.5%) and 47 (6.0%), respectively (hazard ratio, 0.75; 95% CI, 0.48 to 1.15), without evidence of interaction with other randomizations (P>0.20) or evidence of between-group differences in readmissions, serious adverse events, or hemoglobin recovery at 180 days. The mean length of hospital stay was 0.9 days longer in the control group.
CONCLUSIONS
There was no evidence of differences in clinical outcomes over 6 months between the children who received immediate transfusion and those who did not. The triggered-transfusion strategy in the control group resulted in lower blood use; however, the length of hospital stay was longer, and this strategy required clinical and hemoglobin monitoring. (Funded by the Medical Research Council and Department for International Development; TRACT Current Controlled Trials number, ISRCTN84086586.).
Identifiants
pubmed: 31365799
doi: 10.1056/NEJMoa1900105
pmc: PMC7611152
mid: EMS127442
doi:
Substances chimiques
Hemoglobins
0
Banques de données
ISRCTN
['ISRCTN84086586']
Types de publication
Journal Article
Multicenter Study
Randomized Controlled Trial
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
407-419Subventions
Organisme : Medical Research Council
ID : MC_UU_12023/17
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC_PC_MR/R019258/1
Pays : United Kingdom
Organisme : University Hospital Southampton NHS Foundation Trust
ID : MR/J012483
Pays : International
Organisme : Wellcome Trust
ID : 202800/Z/16/Z
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC_UU_12023/26
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/J012483/1
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC_U122886353
Pays : United Kingdom
Investigateurs
S Kiguli
(S)
R O Opoka
(RO)
E Nabawanuka
(E)
J Kayaga
(J)
C Williams Musika
(C)
E Kadama
(E)
I Mbwali
(I)
L Nuwabaine
(L)
R Nakikwaku
(R)
J Nsubuga
(J)
K Mpande
(K)
R Adoo
(R)
O Ouma
(O)
N K Adia
(NK)
P Olupot-Olupot
(P)
J Nteziyaremye
(J)
C Namanyanja
(C)
G Passi
(G)
T Sennyondo
(T)
R Adong
(R)
C B Okalebo
(CB)
E Atimango
(E)
S Mwamula
(S)
J Kapsindet
(J)
G Kiluli
(G)
R Muhindo
(R)
G Masifa
(G)
N Thembo
(N)
G Odong
(G)
C Engoru
(C)
F Alaroker
(F)
M Nakuya
(M)
D Aromut
(D)
M Ariima
(M)
M Itipe
(M)
M G Atim
(MG)
M Abeno
(M)
B Amede
(B)
M Olupot
(M)
S Okwi
(S)
M G Kulume
(MG)
G Among
(G)
P Onyas
(P)
E D Achipa
(ED)
K Maitland
(K)
A Mpoya
(A)
P Maitha
(P)
S Uyoga
(S)
T N Williams
(TN)
A Macharia
(A)
M Mallewa
(M)
Y Chimalizeni
(Y)
N Kennedy
(N)
F Kumwenda
(F)
G Chagaluka
(G)
E Nkosi
(E)
T Sochera
(T)
A Malenga
(A)
B Gushu
(B)
T Phiri
(T)
A Chisale
(A)
N Mitole
(N)
E Chokani
(E)
A Munthali
(A)
D Kyeyune Byabazaire
(D)
B Wabwire
(B)
B M'baya
(B)
G Frost
(G)
K Walsh
(K)
D M Gibb
(DM)
E C George
(EC)
M Thomason
(M)
D Baptiste
(D)
L McCabe
(L)
A S Walker
(AS)
A Ali
(A)
K Khamis
(K)
M Madula
(M)
G Abongo
(G)
P Saramago Goncalves
(P)
P Revill
(P)
S Walker
(S)
A Fox
(A)
R Heydermann
(R)
I Bates
(I)
B Urban
(B)
M Boele von Hensbroek
(M)
F Kyomuhendo
(F)
S Nakalanzi
(S)
J Chabuka
(J)
N Mkandawire
(N)
J Evans
(J)
F Fitzgerald
(F)
E Molyneux
(E)
I Lubega
(I)
M Murphy
(M)
P Kazembe
(P)
J Crawley
(J)
T Peto
(T)
P Musoke
(P)
J Todd
(J)
G Mirembe
(G)
F Tenu
(F)
Commentaires et corrections
Type : CommentIn
Type : CommentIn
Type : CommentIn
Type : CommentIn
Informations de copyright
Copyright © 2019 Massachusetts Medical Society.
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