Outcomes Associated With Early RBC Transfusion in Pediatric Severe Sepsis: A Propensity-Adjusted Multicenter Cohort Study.
Journal
Shock (Augusta, Ga.)
ISSN: 1540-0514
Titre abrégé: Shock
Pays: United States
ID NLM: 9421564
Informations de publication
Date de publication:
01 01 2022
01 01 2022
Historique:
pubmed:
11
10
2021
medline:
3
3
2022
entrez:
10
10
2021
Statut:
ppublish
Résumé
Little is known about the epidemiology of and outcomes related to red blood cell (RBC) transfusion in septic children across multiple centers. We performed propensity-adjusted secondary analyses of the Biomarker Phenotyping of Pediatric Sepsis and Multiple Organ Failure (PHENOMS) study to test the hypothesis that early RBC transfusion is associated with fewer organ failure-free days in pediatric severe sepsis. Four hundred one children were enrolled in the parent study. Children were excluded from these analyses if they received extracorporeal membrane oxygenation (n = 22) or died (n = 1) before sepsis day 2. Propensity-adjusted analyses compared children who received RBC transfusion on or before sepsis day 2 (early RBC transfusion) with those who did not. Logistic regression was used to model the propensity to receive early RBC transfusion. A weighted cohort was constructed using stabilized inverse probability of treatment weights. Variables in the weighted cohort with absolute standardized differences >0.15 were added to final multivariable models. Fifty percent of children received at least one RBC transfusion. The majority (68%) of first transfusions were on or before sepsis day 2. Early RBC transfusion was not independently associated with organ failure-free (-0.34 [95%CI: -2, 1.3] days) or PICU-free days (-0.63 [-2.3, 1.1]), but was associated with the secondary outcome of higher mortality (aOR 2.9 [1.1, 7.9]). RBC transfusion is common in pediatric severe sepsis and may be associated with adverse outcomes. Future studies are needed to clarify these associations, to understand patient-specific transfusion risks, and to develop more precise transfusion strategies.
Sections du résumé
BACKGROUND
Little is known about the epidemiology of and outcomes related to red blood cell (RBC) transfusion in septic children across multiple centers. We performed propensity-adjusted secondary analyses of the Biomarker Phenotyping of Pediatric Sepsis and Multiple Organ Failure (PHENOMS) study to test the hypothesis that early RBC transfusion is associated with fewer organ failure-free days in pediatric severe sepsis.
METHODS
Four hundred one children were enrolled in the parent study. Children were excluded from these analyses if they received extracorporeal membrane oxygenation (n = 22) or died (n = 1) before sepsis day 2. Propensity-adjusted analyses compared children who received RBC transfusion on or before sepsis day 2 (early RBC transfusion) with those who did not. Logistic regression was used to model the propensity to receive early RBC transfusion. A weighted cohort was constructed using stabilized inverse probability of treatment weights. Variables in the weighted cohort with absolute standardized differences >0.15 were added to final multivariable models.
RESULTS
Fifty percent of children received at least one RBC transfusion. The majority (68%) of first transfusions were on or before sepsis day 2. Early RBC transfusion was not independently associated with organ failure-free (-0.34 [95%CI: -2, 1.3] days) or PICU-free days (-0.63 [-2.3, 1.1]), but was associated with the secondary outcome of higher mortality (aOR 2.9 [1.1, 7.9]).
CONCLUSIONS
RBC transfusion is common in pediatric severe sepsis and may be associated with adverse outcomes. Future studies are needed to clarify these associations, to understand patient-specific transfusion risks, and to develop more precise transfusion strategies.
Identifiants
pubmed: 34628452
doi: 10.1097/SHK.0000000000001863
pii: 00024382-202201000-00012
pmc: PMC8678199
mid: NIHMS1740671
doi:
Types de publication
Journal Article
Multicenter Study
Observational Study
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
88-94Subventions
Organisme : NICHD NIH HHS
ID : RL1 HD107777
Pays : United States
Organisme : NICHD NIH HHS
ID : U10 HD050012
Pays : United States
Organisme : NICHD NIH HHS
ID : UG1 HD049983
Pays : United States
Organisme : NICHD NIH HHS
ID : U10 HD049981
Pays : United States
Organisme : NICHD NIH HHS
ID : U10 HD049983
Pays : United States
Organisme : NICHD NIH HHS
ID : U10 HD063106
Pays : United States
Organisme : NICHD NIH HHS
ID : U10 HD063114
Pays : United States
Organisme : NICHD NIH HHS
ID : U01 HD049934
Pays : United States
Organisme : NIGMS NIH HHS
ID : R01 GM108618
Pays : United States
Organisme : NICHD NIH HHS
ID : U10 HD063108
Pays : United States
Organisme : NHLBI NIH HHS
ID : K08 HL123925
Pays : United States
Organisme : NICHD NIH HHS
ID : RL1 HD107779
Pays : United States
Organisme : NICHD NIH HHS
ID : U10 HD050096
Pays : United States
Informations de copyright
Copyright © 2021 by the Shock Society.
Déclaration de conflit d'intérêts
The authors report no conflicts of interests.
Références
Lin JC, Spinella PC, Fitzgerald JC, Tucci M, Bush JL, Nadkarni VM, Thomas NJ, Weiss SL. New or progressive multiple organ dysfunction syndrome in pediatric severe sepsis: a sepsis phenotype with higher morbidity and mortality. Pediatr Crit Care Med 2017; 18 (1):8–16.
Typpo K, Watson RS, Bennett TD, Farris RWD, Spaeder MC, Petersen NJ. Pediatric Existing Data Analysis (PEDAL) Investigators and Pediatric Acute Lung Injury and Sepsis Investigators (PALISI) Network. Outcomes of day 1 multiple organ dysfunction syndrome in the PICU. Pediatr Crit Care Med 2019; 20 (10):914–922.
Ceneviva G, Paschall JA, Maffei F, Carcillo JA. Hemodynamic support in fluid-refractory pediatric septic shock. Pediatr 1998; 102 (2):e19.
Weiss SL, Peters MJ, Alhazzani W, Agus MSD, Flori HR, Inwald DP, Nadel S, Schlapbach LJ, Tasker RC, Argent AC, et al. Surviving sepsis campaign international guidelines for the management of septic shock and sepsis-associated organ dysfunction in children. Intensive Care Med 2020; 46: (Suppl 1): 10–67.
Srouji LS, Moore-Clingenpeel M, Hensley J, Steele L, Greathouse K, Anglim L, Hanson-Huber L, Nateri J, Nicol K, Hall MW, et al. Shock severity modifies associations between RBC transfusion in the first 48 hours of sepsis onset and the duration of organ dysfunction in critically ill septic children. Pediatr Crit Care Med 2020; 21 (8):e475–e484.
Weiss SL, Fitzgerald JC, Pappachan J, Wheeler D, Jaramillo-Bustamante JC, Salloo A, Singhi SC, Erickson S, Roy JA, Bush JL, et al. Global epidemiology of pediatric severe sepsis: the sepsis prevalence, outcomes, and therapies study. Am J Respir Crit Care Med 2015; 191 (10):1147–1157.
Villanueva C, Colomo A, Bosch A, Concepcion M, Hernandez-Gea V, Aracil C, Graupera I, Poca M, Alvarez-Urturi C, Gordillo J, et al. Transfusion strategies for acute upper gastrointestinal bleeding. N Engl J Med 2013; 368 (1):11–21.
Demaret P, Tucci M, Karam O, Trottier H, Ducruet T, Lacroix J. Clinical outcomes associated with RBC transfusions in critically ill children: a 1-year prospective study. Pediatr Crit Care Med 2015; 16 (6):505–514.
Rohde JM, Dimcheff DE, Blumberg N, Saint S, Langa KM, Kuhn L, Hickner A, Rogers MAM. Health care-associated infection after red blood cell transfusion: a systematic review and meta-analysis. JAMA 2014; 311 (13):1317–1326.
Loor G, Rajeswaran J, Li L, Sabik JF 3rd, Blackstone EH, McCrae KR, Koch CG. The least of 3 evils: exposure to red blood cell transfusion, anemia, or both? J Thorac Cardiovasc Surg 2013; 146 (6):1480–1487. e6.
Murphy GJ, Reeves BC, Rogers CA, Rizvi SI, Culliford L, Angelini GD. Increased mortality, postoperative morbidity, and cost after red blood cell transfusion in patients having cardiac surgery. Circulation 2007; 116 (22):2544–2552.
Lacroix J, Hebert PC, Hutchison JS, Hume HA, Tucci M, Ducruet T, Gauvin F, Collet JP, Toledano BJ, Robillard P, et al. Transfusion strategies for patients in pediatric intensive care units. N Engl J Med 2007; 356 (16):1609–1619.
Muszynski JA, Guzzetta NA, Hall MW, Macrae D, Valentine SL, Bateman ST, Spinella PC. Pedaitric Critical Care Transfusion and Anemia Expertise Initiative (TAXI); Pediatric Critical Care Blood Research Network (Blood Net), and the Pediatric Acute Lung Injury and Sepsis Investigators (PALISI) Network. Recommendations on RBC transfusions for critically ill children with nonhemorrhagic shock from the pediatric critical care transfusion and anemia expertise initiative. Pediatr Crit Care Med 2018; 19: (9S Suppl 1): S121–S126.
Carcillo JA, Berg RA, Wessel D, Pollack M, Meert K, Hall M, Newth C, Lin JC, Shanley T, Cornell T, et al. A multicenter network assessment of three inflammation phenotypes in pediatric sepsis-induced multiple organ failure. Pediatr Crit Care Med 2019; 20 (12):1137–1146.
Goldstein B, Giroir B, Randolph A. International pediatric sepsis consensus conference: definitions for sepsis and organ dysfunction in pediatrics. Pediatr Crit Care Med 2005; 6 (1):2–8.
Doughty LA, Kaplan SS, Carcillo JA. Inflammatory cytokine and nitric oxide responses in pediatric sepsis and organ failure. Crit Care Med 1996; 24 (7):1137–1143.
Barbaro RP, Boonstra PS, Kuo KW, Selewski DT, Bailly DK, Stone CL, Chow CY, Annich GM, Moler FW, Paden ML. Evaluating mortality risk adjustment among children receiving extracorporeal support for respiratory failure. ASAIO J 2019; 65 (3):277–284.
Muszynski JA, Reeder RW, Hall MW, Berg RA, Shanley TP, Newth CJL, Pollack MM, Wessel D, Carcillo J, Harrison R, et al. RBC transfusion practice in pediatric extracorporeal membrane oxygenation support. Crit Care Med 2018; 46 (6):e552–e559.
Du Pont-Thibodeau G, Tucci M, Ducruet T, Lacroix J. Survey on stated transfusion practices in PICUs. Pediatr Crit Care Med 2014; 15 (5):409–416.
Pollack MM, Patel KM, Ruttimann UE. PRISM III: an updated Pediatric Risk of Mortality score. Crit Care Med 1996; 24 (5):743–752.
Feudtner C, Christakis DA, Connell FA. Pediatric deaths attributable to complex chronic conditions: a population-based study of Washington State, 1980–1997. Pediatr 2000; 106 (1 Pt 2):205–209.
Muszynski JA, Nofziger R, Moore-Clingenpeel M, Greathouse K, Anglim L, Steele L, Hensley J, Hanson-Huber L, Nateri J, Ramilo O, et al. Early immune function and duration of organ dysfunction in critically III children with sepsis. Am J Respir Crit Care Med 2018; 198 (3):361–369.
Weiss SL, Fitzgerald JC, Balamuth F, Alpern ER, Lavelle J, Chilutti M, Grundmeier R, Nadkarni VM, Thomas NJ. Delayed antimicrobial therapy increases mortality and organ dysfunction duration in pediatric sepsis. Crit Care Med 2014; 42 (11):2409–2417.
Graw JA, Mayeur C, Rosales I, Liu Y, Sabbisetti VS, Riley FE, Rechester O, Malhotra R, Warren HS, Colvin RB, et al. Haptoglobin or hemopexin therapy prevents acute adverse effects of resuscitation after prolonged storage of red cells. Circulation 2016; 134 (13):945–960.
Janz DR, Ware LB. The role of red blood cells and cell-free hemoglobin in the pathogenesis of ARDS. J Intensive Care 2015; 3:20.
Muszynski JA, Spinella PC, Cholette JM, Acker JP, Hall MW, Juffermans NP, Kelly DP, Blumberg N, Nicol K, Liedel J, et al. Transfusion-related immunomodulation: review of the literature and implications for pediatric critical illness. Transfusion 2017; 57 (1):195–206.
Qing DY, Conegliano D, Shashaty MG, Seo J, Reilly JP, Worthen GS, Huh D, Meyer NJ, Mangalmurti NS. Red blood cells induce necroptosis of lung endothelial cells and increase susceptibility to lung inflammation. Am J Respir Crit Care Med 2014; 190 (11):1243–1254.
Remy KE, Hall MW, Cholette J, Juffermans NP, Nicol K, Doctor A, Blumberg N, Spinella PC, Norris PJ, Dahmer MK, et al. Mechanisms of red blood cell transfusion-related immunomodulation. Transfusion 2018; 58 (3):804–815.
Seo J, Conegliano D, Farrell M, Cho M, Ding X, Seykora T, Qing D, Mangalmurti NS, Huh D. A microengineered model of RBC transfusion-induced pulmonary vascular injury. Sci Rep 2017; 7 (1):3413.
Silliman CC, Kelher MR, Khan SY, West FB, McLaughlin NJD, Elzi DJ, England K, Bjornsen J, Kuldanek SA, Banerjee A. Supernatants and lipids from stored red blood cells activate pulmonary microvascular endothelium through the BLT2 receptor and protein kinase C activation. Transfusion 2017; 57 (11):2690–2700.
Straat M, van Hezel ME, Boing A, Tuip-De Boer A, Weber N, Nieuwland R, van Bruggen R, Juffermans NP. Monocyte-mediated activation of endothelial cells occurs only after binding to extracellular vesicles from red blood cell products, a process mediated by beta-integrin. Transfusion 2016; 56 (12):3012–3020.
Carson JL, Guyatt G, Heddle NM, Grossman BJ, Cohn CS, Fung MK, Gernsheimer T, Holcomb JB, Kaplan LJ, Katz LM, et al. Clinical practice guidelines from the AABB: red blood cell transfusion thresholds and storage. JAMA 2016; 316 (19):2025–2035.
Valentine SLBS, Bembea MM, Muszynski JA, Doctor A, Spinella PC, Steiner ME, Tucci M, Hassan NE, Parker RI, Lacroix J, et al. Consensus recommendations for red blood cell transfusion practice in critically ill children from the Pediatric Critical Care Transfusion and Anemia Expertise Initiative (TAXI). Pediatr Crit Care Med 2018; 19 (9):884–898.
Holst LB, Haase N, Wetterslev J, Wernerman J, Guttormsen AB, Karlsson S, Johansson PI, Aneman A, Vang ML, Winding R, et al. Lower versus higher hemoglobin threshold for transfusion in septic shock. N Engl J Med 2014; 371 (15):1381–1391.
Hassan NE, Reischman DE, Fitzgerald RK, Faustino EVS. Prophylaxis against thrombosis practice study investigators, the pediatric acute lung injury and Sepsis Investigators/BloodNet Investigators. Hemoglobin levels across the pediatric critical care spectrum: a point prevalence study. Pediatr Crit Care Med 2018; 19 (5):e227–e234.
Leteurtre S, Duhamel A, Salleron J, Grandbastien B, Lacroix J, Leclerc F. PELOD-2: an update of the PEdiatric logistic organ dysfunction score. Crit Care Med 2013; 41 (7):1761–1773.
Zimmerman JJ, Banks R, Berg RA, Zuppa A, Newth CJ, Wessel D, Pollack MM, Meert KL, Hall MW, Quasney M, et al. Trajectory of mortality and health-related quality of life morbidity following community-acquired pediatric septic shock. Crit Care Med 2020; 48 (3):329–337.
Zimmerman JJ, Banks R, Berg RA, Zuppa A, Newth CJ, Wessel D, Pollack MM, Meert KL, Hall MW, Quasney M, et al. Critical illness factors associated with long-term mortality and health-related quality of life morbidity following community-acquired pediatric septic shock. Crit Care Med 2020; 48 (3):319–328.
Almizraq RJ, Norris PJ, Inglis H, Menocha S, Wirtz MR, Juffermans N, Pandey S, Spinella PC, Acker JP, Muszynski JA. Blood manufacturing methods affect red blood cell product characteristics and immunomodulatory activity. Blood Adv 2018; 2 (18):2296–2306.
Muszynski J, Nateri J, Nicol K, Greathouse K, Hanson L, Hall M. Immunosuppressive effects of red blood cells on monocytes are related to both storage time and storage solution. Transfusion 2012; 52 (4):794–802.