Lower versus higher hemoglobin threshold for transfusion in ARDS patients with and without ECMO
O Hunsicker, L Materne, V Bünger, A Krannich, F Balzer, C Spies, R C Francis, S Weber-Carstens, M Menk, J A Graw, O Hunsicker, L Materne, V Bünger, A Krannich, F Balzer, C Spies, R C Francis, S Weber-Carstens, M Menk, J A Graw
Abstract
Background: Efficacy and safety of different hemoglobin thresholds for transfusion of red blood cells (RBCs) in adults with an acute respiratory distress syndrome (ARDS) are unknown. We therefore assessed the effect of two transfusion thresholds on short-term outcome in patients with ARDS.
Methods: Patients who received transfusions of RBCs were identified from a cohort of 1044 ARDS patients. After propensity score matching, patients transfused at a hemoglobin concentration of 8 g/dl or less (lower-threshold) were compared to patients transfused at a hemoglobin concentration of 10 g/dl or less (higher-threshold). The primary endpoint was 28-day mortality. Secondary endpoints included ECMO-free, ventilator-free, sedation-free, and organ dysfunction-free composites.
Measurements and main results: One hundred ninety-two patients were eligible for analysis of the matched cohort. Patients in the lower-threshold group had similar baseline characteristics and hemoglobin levels at ARDS onset but received fewer RBC units and had lower hemoglobin levels compared with the higher-threshold group during the course on the ICU (9.1 [IQR, 8.7-9.7] vs. 10.4 [10-11] g/dl, P < 0.001). There was no difference in 28-day mortality between the lower-threshold group compared with the higher-threshold group (hazard ratio, 0.94 [95%-CI, 0.59-1.48], P = 0.78). Within 28 days, 36.5% (95%-CI, 27.0-46.9) of the patients in the lower-threshold group compared with 39.5% (29.9-50.1) of the patients in the higher-threshold group had died. While there were no differences in ECMO-free, sedation-free, and organ dysfunction-free composites, the chance for successful weaning from mechanical ventilation within 28 days after ARDS onset was lower in the lower-threshold group (subdistribution hazard ratio, 0.36 [95%-CI, 0.15-0.86], P = 0.02).
Conclusions: Transfusion at a hemoglobin concentration of 8 g/dl, as compared with a hemoglobin concentration of 10 g/dl, was not associated with an increase in 28-day mortality in adults with ARDS. However, a transfusion at a hemoglobin concentration of 8 g/dl was associated with a lower chance for successful weaning from the ventilator during the first 28 days after ARDS onset.
Trial registration: ClinicalTrials.gov NCT03871166.
Keywords: ARDS; Red blood cells; Transfusion.
Conflict of interest statement
The authors have no competing of interest in relation to this manuscript.
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References
- Bellani G, Laffey JG, Pham T, Fan E, Brochard L, Esteban A, Gattinoni L, van Haren F, Larsson A, McAuley DF, Ranieri M, Rubenfeld G, Thompson BT, Wrigge H, Slutsky AS, Pesenti A, Investigators LS, Group ET. Epidemiology, patterns of care, and mortality for patients with acute respiratory distress syndrome in intensive care units in 50 countries. JAMA. 2016;315:788–800. doi: 10.1001/jama.2016.0291.
- Pham T, Rubenfeld GD. Fifty years of research in ARDS. The epidemiology of acute respiratory distress syndrome. A 50th birthday review. Am J Respir Crit Care Med. 2017;195:860–870. doi: 10.1164/rccm.201609-1773CP.
- Thompson BT, Chambers RC, Liu KD. Acute respiratory distress syndrome. N Engl J Med. 2017;377:562–572. doi: 10.1056/NEJMra1608077.
- Carson JL, Guyatt G, Heddle NM, Grossman BJ, Cohn CS, Fung MK, Gernsheimer T, Holcomb JB, Kaplan LJ, Katz LM, Peterson N, Ramsey G, Rao SV, Roback JD, Shander A, Tobian AA. Clinical practice guidelines from the AABB: red blood cell transfusion thresholds and storage. JAMA. 2016;316:2025–2035. doi: 10.1001/jama.2016.9185.
- Vincent JL, Jaschinski U, Wittebole X, Lefrant JY, Jakob SM, Almekhlafi GA, Pellis T, Tripathy S, Rubatto Birri PN, Sakr Y, Investigators I. Worldwide audit of blood transfusion practice in critically ill patients. Crit Care. 2018;22:102. doi: 10.1186/s13054-018-2018-9.
- Vlaar AP, Oczkowski S, de Bruin S, Wijnberge M, Antonelli M, Aubron C, Aries P, Duranteau J, Juffermans NP, Meier J, Murphy GJ, Abbasciano R, Muller M, Shah A, Perner A, Rygaard S, Walsh TS, Guyatt G, Dionne JC, Cecconi M. Transfusion strategies in non-bleeding critically ill adults: a clinical practice guideline from the European Society of Intensive Care Medicine. Intensive Care Med. 2020;46:673–696. doi: 10.1007/s00134-019-05884-8.
- Fan E, Del Sorbo L, Goligher EC, Hodgson CL, Munshi L, Walkey AJ, Adhikari NKJ, Amato MBP, Branson R, Brower RG, Ferguson ND, Gajic O, Gattinoni L, Hess D, Mancebo J, Meade MO, McAuley DF, Pesenti A, Ranieri VM, Rubenfeld GD, Rubin E, Seckel M, Slutsky AS, Talmor D, Thompson BT, Wunsch H, Uleryk E, Brozek J, Brochard LJ, American Thoracic Society ESoICM, Society of Critical Care M An Official American Thoracic Society/European Society of Intensive Care Medicine/Society of critical care medicine clinical practice guideline: mechanical ventilation in adult patients with acute respiratory distress syndrome. Am J Respir Crit Care Med. 2017;195:1253–1263. doi: 10.1164/rccm.201703-0548ST.
- Griffiths MJD, McAuley DF, Perkins GD, Barrett N, Blackwood B, Boyle A, Chee N, Connolly B, Dark P, Finney S, Salam A, Silversides J, Tarmey N, Wise MP, Baudouin SV. Guidelines on the management of acute respiratory distress syndrome. BMJ Open Respir Res. 2019;6:e000420. doi: 10.1136/bmjresp-2019-000420.
- Fichtner F, Moerer O, Weber-Carstens S, Nothacker M, Kaisers U, Laudi S, Guideline G. Clinical guideline for treating acute respiratory insufficiency with invasive ventilation and extracorporeal membrane oxygenation: evidence-based recommendations for choosing modes and setting parameters of mechanical ventilation. Respiration. 2019;98:357–372. doi: 10.1159/000502157.
- Martucci G, Grasselli G, Tanaka K, Tuzzolino F, Panarello G, Schmidt M, Bellani G, Arcadipane A. Hemoglobin trigger and approach to red blood cell transfusions during veno-venous extracorporeal membrane oxygenation: the international TRAIN-ECMO survey. Perfusion. 2019;34:39–48. doi: 10.1177/0267659119830526.
- Voelker MT, Busch T, Bercker S, Fichtner F, Kaisers UX, Laudi S. Restrictive transfusion practice during extracorporeal membrane oxygenation therapy for severe acute respiratory distress syndrome. Artif Organs. 2015;39:374–378. doi: 10.1111/aor.12385.
- Weingart C, Lubnow M, Philipp A, Bein T, Camboni D, Muller T. Comparison of coagulation parameters, anticoagulation, and need for transfusion in patients on interventional lung assist or veno-venous extracorporeal membrane oxygenation. Artif Organs. 2015;39:765–773. doi: 10.1111/aor.12464.
- Agerstrand CL, Burkart KM, Abrams DC, Bacchetta MD, Brodie D. Blood conservation in extracorporeal membrane oxygenation for acute respiratory distress syndrome. Ann Thorac Surg. 2015;99:590–595. doi: 10.1016/j.athoracsur.2014.08.039.
- Force ADT, Ranieri VM, Rubenfeld GD, Thompson BT, Ferguson ND, Caldwell E, Fan E, Camporota L, Slutsky AS. Acute respiratory distress syndrome: the Berlin Definition. JAMA. 2012;307:2526–2533.
- Yehya N, Harhay MO, Curley MAQ, Schoenfeld DA, Reeder RW. Re-appraisal of ventilator-free days in critical care research. Am J Respir Crit Care Med. 2019;200:828–836. doi: 10.1164/rccm.201810-2050CP.
- Azoulay E, Lemiale V, Mourvillier B, Garrouste-Orgeas M, Schwebel C, Ruckly S, Argaud L, Cohen Y, Souweine B, Papazian L, Reignier J, Marcotte G, Siami S, Kallel H, Darmon M, Timsit JF, Group OS. Management and outcomes of acute respiratory distress syndrome patients with and without comorbid conditions. Intensive Care Med. 2018;44:1050–1060. doi: 10.1007/s00134-018-5209-6.
- Brunner E, Domhof S, Langer F. Nonparametric analysis of longitudinal data in factorial experiments. Hoboken: Wiley; 2002.
- Austin PC. A comparison of 12 algorithms for matching on the propensity score. Stat Med. 2014;33:1057–1069. doi: 10.1002/sim.6004.
- Hoenig JM, Heisey DM. The abuse of power: the pervasive fallacy of power calculations for data analysis. Am Stat. 2001;55:19–24. doi: 10.1198/000313001300339897.
- Mueller MM, Van Remoortel H, Meybohm P, Aranko K, Aubron C, Burger R, Carson JL, Cichutek K, De Buck E, Devine D, Fergusson D, Follea G, French C, Frey KP, Gammon R, Levy JH, Murphy MF, Ozier Y, Pavenski K, So-Osman C, Tiberghien P, Volmink J, Waters JH, Wood EM, Seifried E, Group IPF. Patient blood management: recommendations from the 2018 Frankfurt consensus conference. JAMA. 2019;321:983–997. doi: 10.1001/jama.2019.0554.
- Bergamin FS, Almeida JP, Landoni G, Galas F, Fukushima JT, Fominskiy E, Park CHL, Osawa EA, Diz MPE, Oliveira GQ, Franco RA, Nakamura RE, Almeida EM, Abdala E, Freire MP, Filho RK, Auler JOC, Jr, Hajjar LA. Liberal versus restrictive transfusion strategy in critically ill oncologic patients: the transfusion requirements in critically ill oncologic patients randomized controlled trial. Crit Care Med. 2017;45:766–773. doi: 10.1097/CCM.0000000000002283.
- Hebert PC, Wells G, Blajchman MA, Marshall J, Martin C, Pagliarello G, Tweeddale M, Schweitzer I, Yetisir E. A multicenter, randomized, controlled clinical trial of transfusion requirements in critical care. Transfusion requirements in critical care investigators, Canadian Critical Care Trials Group. N Engl J Med. 1999;340:409–417. doi: 10.1056/NEJM199902113400601.
- Hebert PC, Wells G, Marshall J, Martin C, Tweeddale M, Pagliarello G, Blajchman M. Transfusion requirements in critical care. A pilot study. Canadian critical care trials group. JAMA. 1995;273:1439–1444. doi: 10.1001/jama.1995.03520420055038.
- Holst LB, Haase N, Wetterslev J, Wernerman J, Guttormsen AB, Karlsson S, Johansson PI, Aneman A, Vang ML, Winding R, Nebrich L, Nibro HL, Rasmussen BS, Lauridsen JR, Nielsen JS, Oldner A, Pettila V, Cronhjort MB, Andersen LH, Pedersen UG, Reiter N, Wiis J, White JO, Russell L, Thornberg KJ, Hjortrup PB, Muller RG, Moller MH, Steensen M, Tjader I, Kilsand K, Odeberg-Wernerman S, Sjobo B, Bundgaard H, Thyo MA, Lodahl D, Maerkedahl R, Albeck C, Illum D, Kruse M, Winkel P, Perner A, Group TT, Scandinavian Critical Care Trials G Lower versus higher hemoglobin threshold for transfusion in septic shock. N Engl J Med. 2014;371:1381–1391. doi: 10.1056/NEJMoa1406617.
- Palmieri TL, Holmes JHT, Arnoldo B, Peck M, Potenza B, Cochran A, King BT, Dominic W, Cartotto R, Bhavsar D, Kemalyan N, Tredget E, Stapelberg F, Mozingo D, Friedman B, Greenhalgh DG, Taylor SL, Pollock BH. Transfusion requirement in burn care evaluation (TRIBE): a multicenter randomized prospective trial of blood transfusion in major burn injury. Ann Surg. 2017;266:595–602. doi: 10.1097/SLA.0000000000002408.
- Walsh TS, Boyd JA, Watson D, Hope D, Lewis S, Krishan A, Forbes JF, Ramsay P, Pearse R, Wallis C, Cairns C, Cole S, Wyncoll D, Investigators R. Restrictive versus liberal transfusion strategies for older mechanically ventilated critically ill patients: a randomized pilot trial. Crit Care Med. 2013;41:2354–2363. doi: 10.1097/CCM.0b013e318291cce4.
- Amato MB, Meade MO, Slutsky AS, Brochard L, Costa EL, Schoenfeld DA, Stewart TE, Briel M, Talmor D, Mercat A, Richard JC, Carvalho CR, Brower RG. Driving pressure and survival in the acute respiratory distress syndrome. N Engl J Med. 2015;372:747–755. doi: 10.1056/NEJMsa1410639.
- Combes A, Hajage D, Capellier G, Demoule A, Lavoue S, Guervilly C, Da Silva D, Zafrani L, Tirot P, Veber B, Maury E, Levy B, Cohen Y, Richard C, Kalfon P, Bouadma L, Mehdaoui H, Beduneau G, Lebreton G, Brochard L, Ferguson ND, Fan E, Slutsky AS, Brodie D, Mercat A, Eolia Trial Group R, Ecmonet Extracorporeal membrane oxygenation for severe acute respiratory distress syndrome. N Engl J Med. 2018;378:1965–1975. doi: 10.1056/NEJMoa1800385.
- Acute Respiratory Distress Syndrome N. Brower RG, Matthay MA, Morris A, Schoenfeld D, Thompson BT, Wheeler A. Ventilation with lower tidal volumes as compared with traditional tidal volumes for acute lung injury and the acute respiratory distress syndrome. N Engl J Med. 2000;342:1301–1308. doi: 10.1056/NEJM200005043421801.
- Carson JL, Stanworth SJ, Roubinian N, Fergusson DA, Triulzi D, Doree C, Hebert PC. Transfusion thresholds and other strategies for guiding allogeneic red blood cell transfusion. Cochrane Database Syst Rev. 2016;10:CD002042.
- Schonhofer B, Wenzel M, Geibel M, Kohler D. Blood transfusion and lung function in chronically anemic patients with severe chronic obstructive pulmonary disease. Crit Care Med. 1998;26:1824–1828. doi: 10.1097/00003246-199811000-00022.
- Silver MR. Anemia in the long-term ventilator-dependent patient with respiratory failure. Chest. 2005;128:568S–575S. doi: 10.1378/chest.128.5_suppl_2.568S.
- Lai YC, Ruan SY, Huang CT, Kuo PH, Yu CJ. Hemoglobin levels and weaning outcome of mechanical ventilation in difficult-to-wean patients: a retrospective cohort study. PLoS ONE. 2013;8:e73743. doi: 10.1371/journal.pone.0073743.
- Roubinian NH, Plimier C, Woo JP, Lee C, Bruhn R, Liu VX, Escobar GJ, Kleinman SH, Triulzi DJ, Murphy EL, Busch MP. Effect of donor, component, and recipient characteristics on hemoglobin increments following red blood cell transfusion. Blood. 2019;134:1003–1013. doi: 10.1182/blood.2019000773.
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