- Open Access
Blood transfusion and the lung: first do no harm?
Critical Care volume 15, Article number: 152 (2011)
Marked variability in transfusion practice exists in cardiac surgical patients, with consumption of approximately 20% of the worldwide allogeneic blood supply. Observational studies have reported an association between red blood cell transfusion and adverse outcome, including pulmonary complications, in cardiac surgery. Tuinman and colleagues report that transfusions were associated with activation of pulmonary inflammation and coagulation by measurement of biomarkers in bronchoalveolar lavage fluid, and suggest that transfusion may be a mediator of acute lung injury. This study provides interesting preliminary data, but is limited by multiple confounding variables (plasma transfusion, use of anticoagulants and heparin antagonists) and the small sample size. A large multicenter, prospective, randomized clinical trial regarding the safety (inclusive of pulmonary complications) and efficacy of red blood cell transfusion in cardiac surgery is needed.
Tuinman and colleagues report the results of a single-institution study in cardiac surgery patients (n = 45), documenting that bronchoalveolar lavage fluid cytokine and coagulation markers were significantly increased in a dose-dependent manner with transfusions . They conclude that transfusion was associated with activation of pulmonary inflammation/coagulation and systemic coagulation derangement.
The data are interesting and provocative, and provide a biologic basis for observational studies that reported an association between red blood cell (RBC) transfusions and increased pulmonary complications, including acute lung injury and acute respiratory distress syndrome [2, 3]. Translational research studies like this are needed to move this field forward.
Although increased inflammatory/coagulation markers were identified in the multiple transfusion cohort, no clinically relevant difference in pulmonary function (including the PaO2/FiO2 ratio) was identified . Duration of mechanical ventilation was longer in the multiple transfusion cohort, but all were of less than 1 day duration.
A major study limitation is that the three cohorts were not defined on the basis of RBC transfusions alone, as the multiple transfusion cohort received plasma/platelets in addition to RBC transfusions. This factor significantly confounds the issue, as plasma administration is associated with significantly increased risk for pulmonary complications [4–7]. In a systematic review/meta-analysis of 37 studies, plasma transfusion was associated with significantly increased acute lung injury risk (odds ratio, 2.92; 95% confidence interval, 1.99 to 4.29) .
Most importantly, the effects of anticoagulants, heparin antagonists (for example, protamine) or blood-saving strategies (for example, cell-saver technique) and the degree of intraoperative blood loss and hypoperfusion/shock were not considered. Additional study limitations include the small sample size, and increased EuroSCORE in the multiple transfusion cohort, and an inability to assess age of blood as a variable.
The fundamental question of whether RBC transfusion is safe/effective in cardiac surgery is important, and this current study highlights significant concerns particularly with regard to pulmonary complications. Significant variability in transfusion use in cardiac surgery persists, ranging from 7.8 to 92.8% for RBC transfusion . The Transfusion Requirements in Critical Care trial excluded cardiac surgical patients and patients who received trans-fusions before admission to the ICU . The recent Transfusion Requirements After Cardiac Surgery trial - a single-center prospective, randomized clinical trial with patients (n = 502) randomized to a liberal strategy (maintain hematocrit ≥30%) or to a restrictive strategy (maintain hematocrit ≥24%) - reported that for each transfused RBC unit, the risk of respiratory complications increased (odds ratio, 1.27; 95% confidence interval, 1.12 to 1.45; P <0.001) with no difference in 30-day all-cause mortality .
To resolve this issue regarding transfusion, a large multicenter, prospective, randomized clinical trial regarding the safety (including pulmonary complications) and efficacy of RBC transfusion in cardiac surgery is needed. The National Heart, Lung, and Blood Institute established a State-of-the-Science Symposium on Transfusion Medicine to identify important clinical trial research issues in this field, and a trial in cardiac surgery was strongly recommended .
fraction of inspired oxygen
intensive care unit
partial pressure of arterial oxygen
red blood cell.
Tuinman PR, Vlaar AP, Cornet AD, Hofstra JJ, Levi M, Meijers JC, Beishuizen A, Schultz MJ, Groeneveld JB, Juffermans NP: Blood transfusion during cardiac surgery is associated with inflammation and coagulation in the lung: a case control study. Crit Care 2011, 15: R59. 10.1186/cc10032
Marik PE, Corwin HL: Efficacy of red blood cell transfusion in the critically ill: a systematic review of the literature. Crit Care Med 2008, 36: 2667-2674. 10.1097/CCM.0b013e3181844677
Napolitano LM, Kurek S, Luchette FA, Corwin HL, Barie PS, Tisherman SA, Hebert PC, Anderson GL, Bard MR, Bromberg W, Chiu WC, Cipolle MD, Clancy KD, Diebel L, Hoff WS, Hughes KM, Munshi I, Nayduch D, Sandhu R, Yelon JA, American College of Critical Care Medicine of the Society of Critical Care Medicine; Eastern Association for the Surgery of Trauma Practice Management Workgroup: Clinical practice guideline: red blood cell transfusion in adult trauma and critical care. Crit Care Med 2009, 37: 3124-3157. erratum Crit Care Med 2010, 38: 1621 10.1097/CCM.0b013e3181b39f1b
Roback JD, Caldwell S, Carson J, Davenport R, Drew MJ, Eder A, Fung M, Hamilton M, Hess JR, Luban N, Perkins JG, Sachais BS, Shander A, Silverman T, Snyder E, Tormey C, Waters J, Djulbegovic B, American Association for the Study of Liver; American Academy of Pediatrics; United States Army; American Society of Anesthesiology; American Society of Hematology: Evidence-based practice guidelines for plasma transfusion. Transfusion 2010, 50: 1227-1239. 10.1111/j.1537-2995.2010.02632.x
Watson GA, Sperry JL, Rosengart M, Mineu JP, Harbrecth BG, Moore EE, Cuschieri J, Maier RV, Billiar TR, Peitzman AB, Inflammation and the Host Response to Injury Investigators: Fresh frozen plasma is independently associated with a higher risk of multiple organ failure and acute respiratory distress syndrome. J Trauma 2009, 67: 221-230. 10.1097/TA.0b013e3181ad5957
Inaba K, Branco BC, Rhee P, Blackbourne LH, Holcomb JB, Teixeiria PG, Shulman I, Nelson J, Demetriades D: Impact of plasma transfusion in trauma patients who do not require massive transfusion. J Am Coll Surg 2010, 210: 957-965. 10.1016/j.jamcollsurg.2010.01.031
Nascimento B, Callum J, Rubenfeld G, Neto JB, Lin Y, Rizoli S: Clinical review: fresh frozen plasma in massive bleedings - more questions than answers. Crit Care 2010, 14: 202. 10.1186/cc8205
Murad MH, Stubbs JR, Gandhi MJ, Wang AT, Paul A, Erwin PJ, Montori VM, Roback JD: The effect of plasma transfusion on morbidity and mortality: a systematic review and meta-analysis. Transfusion 2010, 50: 1370-1383. 10.1111/j.1537-2995.2010.02630.x
Bennett-Guerrero E, Zhao Y, O'Brien SM, Ferguson TB Jr, Peterson ED, Gammie JS, Song HK: Variation in use of blood transfusion in coronary artery bypass graft surgery. JAMA 2010, 304: 1568-1575. 10.1001/jama.2010.1406
Hébert 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.
Hajjar LA, Vincent JL, Galas FR, Nakamura RE, Silva CM, Santos MH, Fukushima J, Kalil Filho R, Sierra DB, Lopes NH, Mauad T, Roquim AC, Sundin MR, Leão WC, Almeida JP, Pomerantzeff PM, Dallan LO, Jatene FB, Stolf NA, Auler JO Jr: Transfusion requirements after cardiac surgery: the TRACS randomized controlled trial. JAMA 2010, 304: 1559-1567. 10.1001/jama.2010.1446
Blajchman MA, Glynn SA, Josephson CD, Kleinman SH, State-of-the Science Symposium Transfusion Medicine Committee: Clinical trial opportunities in transfusion medicine: proceedings of a National Heart, Lung, and Blood Institute State-of-the-Science Symposium. Transfus Med Rev 2010, 24: 259-285. 10.1016/j.tmrv.2010.05.002
The author declares that they have no competing interests.
About this article
Cite this article
Napolitano, L.M. Blood transfusion and the lung: first do no harm?. Crit Care 15, 152 (2011). https://doi.org/10.1186/cc10124
- Acute Lung Injury
- Pulmonary Complication
- Transfusion Requirement
- Bronchoalveolar Lavage Fluid