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Anemia and Red Blood Cell Transfusion in Aneurysmal Subarachnoid Hemorrhage

  • Practice Guidance for the Critical Care Management of SAH
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Abstract

Anemia is very common in aneurysmal subarachnoid hemorrhage (aSAH), with approximately half of the aSAH patient population developing moderate anemia during their hospital stay. The available evidence (both physiologic and clinical) generally supports an association of anemia with unfavorable outcomes. Although aSAH shares a number of common mechanisms of secondary insult with other forms of acute brain injury, aSAH also has specific features that make it unique: an early phase (in which early brain injury predominates) and a delayed phase (in which delayed cerebral ischemia and vasospasm predominate). The effects of both anemia and transfusion are potentially variable between these phases, which may have unique considerations and possibly different risk–benefit profiles. Data on transfusion in this population are almost exclusively limited to observational studies, which suffer from significant heterogeneity and risk of bias. Overall, the results are conflicting, with the balance of the studies suggesting that transfusion is associated with unfavorable outcomes. The transfusion targets that are well established in other critically ill populations should not be automatically applied to patients with aSAH because of the unique disease characteristics of this population and the limited representation of aSAH in the clinical trials that established these targets. There are two upcoming clinical trials evaluating transfusion in aSAH that should help clarify specific transfusion targets. Until then, it is reasonable to base transfusion decisions on the current guidelines and use an individualized approach incorporating physiologic and clinical data when available.

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Fig. 1

Adapted from Okazaki T, Kuroda Y. Aneurysmal subarachnoid hemorrhage: intensive care for improving neurological outcome. J Intensive Care. 2018;6:28. https://doi.org/10.1186/s40560-018-0297-5 and from Dodd WS, Laurent D, Dumont AS, et al. Pathophysiology of delayed cerebral ischemia after subarachnoid hemorrhage: a review. J Am Heart Assoc. 2021;10:e021845.

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References

  1. Thomas J, Jensen L, Nahirniak S, Gibney RTN. Anemia and blood transfusion practices in the critically ill: a prospective cohort review. Heart Lung. 2010;39(3):217–25.

    Article  PubMed  Google Scholar 

  2. Hébert PC, Martin C, Yetisir E. A multicenter, randomized, controlled clinical trial of transfusion requirements in critical care. N Engl J Med. 1999;340:409–17.

    Article  PubMed  Google Scholar 

  3. Carson JL, Stanworth SJ, Dennis JA, et al. Transfusion thresholds for guiding red blood cell transfusion. Cochrane Database Syst Rev [internet]. 2021. https://doi.org/10.1002/14651858.CD002042.pub5.

    Article  PubMed  Google Scholar 

  4. Desjardins P, Turgeon AF, Tremblay M-H, et al. Hemoglobin levels and transfusions in neurocritically ill patients: a systematic review of comparative studies. Crit Care. 2012;16(2):R54.

    Article  PubMed  PubMed Central  Google Scholar 

  5. Kumar M. Anemia and blood transfusion in subarachnoid hemorrhage. JHN J [Internet]. 2009;4(4):6.

    Google Scholar 

  6. Wang Z, Ying Z, Bosy-Westphal A, et al. Specific metabolic rates of major organs and tissues across adulthood: evaluation by mechanistic model of resting energy expenditure. Am J Clin Nutr. 2010;92(6):1369–77.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Tameem A, Krovvidi H. Cerebral physiology. Contin Educ Anaesth Crit Care Pain. 2013;13(4):113–8.

    Article  Google Scholar 

  8. Williams LR, Leggett RW. Reference values for resting blood flow to organs of man. Clin Phys Physiol Meas. 1989;10(3):187–217.

    Article  CAS  PubMed  Google Scholar 

  9. Hoiland RL, Bain AR, Rieger MG, Bailey DM, Ainslie PN. Hypoxemia, oxygen content, and the regulation of cerebral blood flow. Am J Physiol Regul Integr Comp Physiol. 2016;310(5):R398-413.

    Article  PubMed  Google Scholar 

  10. Lassen NA. Normal average value of cerebral blood flow in younger adults is 50 ml/100 g/min. J Cereb Blood Flow Metab. 1985;5(3):347–9.

    Article  CAS  PubMed  Google Scholar 

  11. Cipolla M. The cerebral circulation. San Rafael: Morgan & Claypool Life Sciences; 2009.

    Book  Google Scholar 

  12. Fan AP, An H, Moradi F, et al. Quantification of brain oxygen extraction and metabolism with [15O]-gas PET: a technical review in the era of PET/MRI. Neuroimage. 2020;220:117136.

    Article  CAS  PubMed  Google Scholar 

  13. Brown MM, Wade JPH, Marshall J. Fundamental importance of arterial oxygen content in the regulation of cerebral blood flow in man. Brain. 1985;108(1):81–93.

    Article  PubMed  Google Scholar 

  14. Hino A, Ueda S, Mizukawa N, Imahori Y, Tenjin H. Effect of hemodilution on cerebral hemodynamics and oxygen metabolism. Stroke. 1992;23(3):423–6.

    Article  CAS  PubMed  Google Scholar 

  15. Mühling J, Dehne MG, Sablotzki A, Hempelmann G. Cerebral blood flow velocity during isovolemic hemodilution and subsequent autologous blood retransfusion. Can J Anesth/J Can Anesth. 1999;46(6):550–7.

    Article  Google Scholar 

  16. Carr JM, Ainslie PN, MacLeod DB, et al. Cerebral O2 and CO2 transport in isovolumic haemodilution: Compensation of cerebral delivery of O2 and maintenance of cerebrovascular reactivity to CO2. J Cereb Blood Flow Metab. 2023;43(1):99–114.

    Article  CAS  PubMed  Google Scholar 

  17. McLaren AT, David Mazer C, Zhang H, Liu E, Mok L, Hare GMT. A potential role for inducible nitric oxide synthase in the cerebral response to acute hemodilution. Can J Anesth/J Can Anesth. 2009;56(7):502–9.

    Article  Google Scholar 

  18. Hudetz AG, Shen H, Kampine JP. Nitric oxide from neuronal NOS plays critical role in cerebral capillary flow response to hypoxia. Am J Physiol Heart Circ Physiol. 1998;274(3):H982–9.

    Article  CAS  Google Scholar 

  19. Todd MM, Wu B, Maktabi M, Hindman BJ, Warner DS. Cerebral blood flow and oxygen delivery during hypoxemia and hemodilution: role of arterial oxygen content. Am J Physiol Heart Circ Physiol. 1994;267(5):H2025–31.

    Article  CAS  Google Scholar 

  20. Tomiyama Y, Jansen K, Brian JE, Todd MM. Hemodilution, cerebral O2 delivery, and cerebral blood flow: a study using hyperbaric oxygenation. Am J Physiol Heart Circ Physiol. 1999;276(4):H1190–6.

    Article  CAS  Google Scholar 

  21. Ekelund A, Reinstrup P, Ryding E, et al. Effects of iso- and hypervolemic hemodilution on regional cerebral blood flow and oxygen delivery for patients with vasospasm after aneurysmal subarachnoid hemorrhage. Acta Neurochir (Wien). 2002;144(7):703–13.

    Article  CAS  PubMed  Google Scholar 

  22. Tu Y-K, Liu H-M. Effects of isovolemic hemodilution on hemodynamics, cerebral perfusion, and cerebral vascular reactivity. Stroke. 1996;27(3):441–5.

    Article  CAS  PubMed  Google Scholar 

  23. Crystal GJ, Czinn EA, Salem MR. The mechanism of increased blood flow in the brain and spinal cord during hemodilution. Anesth Analg. 2014;118(3):637–43.

    Article  PubMed  Google Scholar 

  24. Willie CK, Tzeng Y-C, Fisher JA, Ainslie PN. Integrative regulation of human brain blood flow. J Physiol. 2014;592(5):841–59.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Fantini S, Sassaroli A, Tgavalekos KT, Kornbluth J. Cerebral blood flow and autoregulation: current measurement techniques and prospects for noninvasive optical methods. Neurophoton. 2016;3(3):031411.

    Article  Google Scholar 

  26. Czosnyka M, Smielewski P, Piechnik S, Steiner LA, Pickard JD. Cerebral autoregulation following head injury. J Neurosurg. 2001;95(5):756–63.

    Article  CAS  PubMed  Google Scholar 

  27. Czosnyka M, Smielewski P, Kirkpatrick P, Menon DK, Pickard JD. Monitoring of cerebral autoregulation in head-injured patients. Stroke. 1996;27(10):1829–34.

    Article  CAS  PubMed  Google Scholar 

  28. Brown MM, Marshall J. Effect of plasma exchange on blood viscosity and cerebral blood flow. BMJ. 1982;284(6331):1733–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Tu Y-K, Kuo M-F, Liu H-M. Cerebral oxygen transport and metabolism during graded isovolemic hemodilution in experimental global ischemia. J Neurol Sci. 1997;150(2):115–22.

    Article  CAS  PubMed  Google Scholar 

  30. Hare GMT, Mazer CD, Hutchison JS, et al. Severe hemodilutional anemia increases cerebral tissue injury following acute neurotrauma. J Appl Physiol. 2007;103:9.

    Article  Google Scholar 

  31. Dexter F, Hindman BJ. Effect of haemoglobin concentration on brain oxygenation in focal stroke: a mathematical modelling study. Br J Anaesth. 1997;79(3):346–51.

    Article  CAS  PubMed  Google Scholar 

  32. English SW, Chassé M, Turgeon AF, et al. Anemia prevalence and incidence and red blood cell transfusion practices in aneurysmal subarachnoid hemorrhage: results of a multicenter cohort study. Crit Care. 2018;22(1):169.

    Article  PubMed  PubMed Central  Google Scholar 

  33. Sampson TR, Dhar R, Diringer MN. Factors associated with the development of anemia after subarachnoid hemorrhage. Neurocrit Care. 2010;12(1):4–9.

    Article  PubMed  Google Scholar 

  34. Hayden SJ, Albert TJ, Watkins TR, Swenson ER. Anemia in critical illness: insights into etiology, consequences, and management. Am J Respir Crit Care Med. 2012;185(10):1049–57.

    Article  PubMed  PubMed Central  Google Scholar 

  35. Schmitt E, Meybohm P, Neef V, et al. Preoperative anaemia and red blood cell transfusion in patients with aneurysmal subarachnoid and intracerebral haemorrhage: a multicentre subanalysis of the German PBM network registry. Acta Neurochir (Wien). 2022;164(4):985–99.

    Article  PubMed  Google Scholar 

  36. Ayling OGS, Ibrahim GM, Alotaibi NM, Gooderham PA, Macdonald RL. Anemia after aneurysmal subarachnoid hemorrhage is associated with poor outcome and death. Stroke. 2018;49(8):1859–65.

    Article  PubMed  Google Scholar 

  37. Stein M, Brokmeier L, Herrmann J, et al. Mean hemoglobin concentration after acute subarachnoid hemorrhage and the relation to outcome, mortality, vasospasm, and brain infarction. J Clin Neurosci. 2015;22(3):530–4.

    Article  CAS  PubMed  Google Scholar 

  38. Kramer AH, Zygun DA, Bleck TP, Dumont AS, Kassell NF, Nathan B. Relationship between hemoglobin concentrations and outcomes across subgroups of patients with aneurysmal subarachnoid hemorrhage. Neurocrit Care. 2009;10(2):157–65.

    Article  CAS  PubMed  Google Scholar 

  39. Kramer AH, Gurka MJ, Nathan B, Dumont AS, Kassell NF, Bleck TP. Complications associated with anemia and blood transfusion in patients with aneurysmal subarachnoid hemorrhage. Crit Care Med. 2008;36(7):2070–5.

    Article  PubMed  Google Scholar 

  40. Naidech AM, Jovanovic B, Wartenberg KE, et al. Higher hemoglobin is associated with improved outcome after subarachnoid hemorrhage*. Crit Care Med. 2007;35(10):2383–9.

    Article  CAS  PubMed  Google Scholar 

  41. Castella A, Attanasio L, Schuind S, et al. Association of anemia and transfusions with outcome after subarachnoid hemorrhage. Clin Neurol Neurosurg. 2021;206:106676.

    Article  PubMed  Google Scholar 

  42. Oddo M, Milby A, Chen I, et al. Hemoglobin concentration and cerebral metabolism in patients with aneurysmal subarachnoid hemorrhage. Stroke. 2009;40(4):1275–81.

    Article  CAS  PubMed  Google Scholar 

  43. Kurtz P, Schmidt JM, Claassen J, et al. Anemia is associated with metabolic distress and brain tissue hypoxia after subarachnoid hemorrhage. Neurocrit Care. 2010;13(1):10–6.

    Article  CAS  PubMed  Google Scholar 

  44. Rowland MJ, Hadjipavlou G, Kelly M, Westbrook J, Pattinson KTS. Delayed cerebral ischaemia after subarachnoid haemorrhage: looking beyond vasospasm. Br J Anaesth. 2012;109(3):315–29.

    Article  CAS  PubMed  Google Scholar 

  45. Rass V, Helbok R. Early brain injury after poor-grade subarachnoid hemorrhage. Curr Neurol Neurosci Rep. 2019;19(10):78.

    Article  PubMed  PubMed Central  Google Scholar 

  46. Li R, Lin F, Chen Y, et al. Elevated blood hemoglobin on admission as an independent predictor of unfavorable outcomes in patients with aneurysmal subarachnoid hemorrhage. Neurosurg Rev [Internet]. 2022. https://doi.org/10.1007/s10143-022-01780-w.

    Article  PubMed  Google Scholar 

  47. Dhar R, Zazulia AR, Videen TO, Zipfel GJ, Derdeyn CP, Diringer MN. Red blood cell transfusion increases cerebral oxygen delivery in anemic patients with subarachnoid hemorrhage. Stroke. 2009;40(9):3039–44.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Dhar R, Scalfani MT, Zazulia AR, Videen TO, Derdeyn CP, Diringer MN. Comparison of induced hypertension, fluid bolus, and blood transfusion to augment cerebral oxygen delivery after subarachnoid hemorrhage: clinical article. JNS. 2012;116(3):648–56.

    Article  Google Scholar 

  49. Kurtz P, Helbok R, Claassen J, et al. The effect of packed red blood cell transfusion on cerebral oxygenation and metabolism after subarachnoid hemorrhage. Neurocrit Care. 2016;24(1):118–21.

    Article  CAS  PubMed  Google Scholar 

  50. Dhar R, Zazulia AR, Derdeyn CP, Diringer MN. RBC transfusion improves cerebral oxygen delivery in subarachnoid hemorrhage. Crit Care Med. 2017;45(4):653–9.

    Article  PubMed  PubMed Central  Google Scholar 

  51. Molyneux A. International Subarachnoid Aneurysm Trial (ISAT) of neurosurgical clipping versus endovascular coiling in 2143 patients with ruptured intracranial aneurysms: a randomised trial. The Lancet. 2002;360(9342):1267–74.

    Article  Google Scholar 

  52. Kramer AH, Diringer MN, Suarez JI, Naidech AM, Macdonald LR, Le Roux PD. Red blood cell transfusion in patients with subarachnoid hemorrhage: a multidisciplinary North American survey. Crit Care. 2011;15(1):R30.

    Article  PubMed  PubMed Central  Google Scholar 

  53. LeRoux P. Haemoglobin management in acute brain injury. Curr Opin Crit Care. 2013;19(2):83–91.

    Article  PubMed  Google Scholar 

  54. Mofor P, Oduguwa E, Tao J, et al. Postoperative transfusion guidelines in aneurysmal cerebral subarachnoid hemorrhage: a systematic review and critical summary of available evidence. World Neurosurg. 2021;S1878–8750(21):01850–7.

    Google Scholar 

  55. Naidech AM, Shaibani A, Garg RK, et al. Prospective, randomized trial of higher goal hemoglobin after subarachnoid hemorrhage. Neurocrit Care. 2010;13(3):313–20.

    Article  PubMed  Google Scholar 

  56. Retter A, Wyncoll D, Pearse R, et al. Guidelines on the management of anaemia and red cell transfusion in adult critically ill patients. Br J Haematol. 2013;160(4):445–64.

    Article  CAS  PubMed  Google Scholar 

  57. Diringer MN, Bleck TP, Claude Hemphill J, et al. Critical care management of patients following aneurysmal subarachnoid hemorrhage: recommendations from the Neurocritical Care Society’s multidisciplinary consensus conference. Neurocrit Care. 2011;15(2):211.

    Article  PubMed  Google Scholar 

  58. Connolly ES, Rabinstein AA, Carhuapoma JR, et al. Guidelines for the management of aneurysmal subarachnoid hemorrhage: a guideline for healthcare professionals from the American Heart Association/American Stroke Association. Stroke. 2012;43(6):1711–37.

    Article  PubMed  Google Scholar 

  59. Steiner T, Juvela S, Unterberg A, Jung C, Forsting M, Rinkel G. European stroke organization guidelines for the management of intracranial aneurysms and subarachnoid haemorrhage. Cerebrovasc Dis. 2013;35(2):93–112.

    Article  PubMed  Google Scholar 

  60. Committee for Guidelines for Management of Aneurysmal Subarachnoid Hemorrhage, Japanese Society on Surgery for Cerebral Stroke. Evidence-based guidelines for the management of aneurysmal subarachnoid hemorrhage. Neurol Med Chir (Tokyo). 2012;52(6):355–429.

    Article  Google Scholar 

  61. Treggiari MM, Rabinstein AA, Busl KM, et al. Guidelines for the neurocritical care management of aneurysmal subarachnoid hemorrhage. Neurocrit Care. 2023. https://doi.org/10.1007/s12028-023-01713-5.

    Article  PubMed  Google Scholar 

  62. Dong Y, Guo Z-N, Li Q, et al. Chinese Stroke Association guidelines for clinical management of cerebrovascular disorders: executive summary and 2019 update of clinical management of spontaneous subarachnoid haemorrhage. Stroke Vasc Neurol. 2019;4(4):176–81.

    Article  PubMed  PubMed Central  Google Scholar 

  63. English SW, McIntyre L. Is hemoglobin good for cerebral oxygenation and clinical outcome in acute brain injury? Curr Opin Crit Care. 2018;24(2):91–6.

    Article  PubMed  Google Scholar 

  64. Taccone F. Transfusion strategies in acute brain injured patients. A prospective multicenter randomized study. [Internet]. clinicaltrials.gov; 2021 [cited 2022 May 22]. https://clinicaltrials.gov/ct2/show/study/NCT02968654

  65. Cable CA, Razavi SA, Roback JD, Murphy DJ. RBC transfusion strategies in the ICU: a concise review. Crit Care Med. 2019;47(11):1637–44.

    Article  PubMed  PubMed Central  Google Scholar 

  66. Moman RN, Kor DJ, Chandran A, et al. Red blood cell transfusion in acute brain injury subtypes: an observational cohort study. J Crit Care. 2019;50:44–9.

    Article  PubMed  Google Scholar 

  67. Kumar MA, Levine J, Faerber J, et al. The effects of red blood cell transfusion on functional outcome after aneurysmal subarachnoid hemorrhage. World Neurosurg. 2017;108:807–16.

    Article  PubMed  Google Scholar 

  68. Pegoli M, Mandrekar J, Rabinstein AA, Lanzino G. Predictors of excellent functional outcome in aneurysmal subarachnoid hemorrhage. JNS. 2015;122(2):414–8.

    Article  Google Scholar 

  69. Kumar MA, Boland TA, Baiou M, et al. Red blood cell transfusion increases the risk of thrombotic events in patients with subarachnoid hemorrhage. Neurocrit Care. 2014;20(1):84–90.

    Article  PubMed  Google Scholar 

  70. Festic E, Rabinstein AA, Freeman WD, et al. Blood transfusion is an important predictor of hospital mortality among patients with aneurysmal subarachnoid hemorrhage. Neurocrit Care. 2013;18(2):209–15.

    Article  PubMed  Google Scholar 

  71. Broessner G, Lackner P, Hoefer C, et al. Influence of red blood cell transfusion on mortality and long-term functional outcome in 292 patients with spontaneous* subarachnoid hemorrhage. Crit Care Med. 2009;37(6):1886–92.

    Article  PubMed  Google Scholar 

  72. Springer MVMD, Schmidt JM, Wartenberg KEMD, Frontera JAMD, Badjatia NMD, Mayer SAMD. Predictors of global cognitive impairment 1 year after subarachnoid hemorrhage. Neurosurgery. 2009;65(6):1043–51.

    Article  PubMed  Google Scholar 

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Authors and Affiliations

  1. School of Epidemiology and Public Health, University of Ottawa, Ottawa, ON, Canada

    Luke A. Terrett

  2. College of Medicine, University of Saskatchewan, Saskatoon, SK, Canada

    Luke A. Terrett

  3. Department of Adult Critical Care, Saskatchewan Health Authority, Saskatoon, SK, Canada

    Luke A. Terrett

  4. Department of Medicine (Critical Care), University of Ottawa, Ottawa, ON, Canada

    Lauralyn McIntyre & Shane W. English

  5. Clinical Epidemiology Program (CEP), Ottawa Hospital Research Institute (OHRI), Civic Campus Room F202, 1053 Carling Avenue, Ottawa, ON, K1Y 4E9, Canada

    Lauralyn McIntyre & Shane W. English

  6. The Ottawa Hospital, Ottawa, ON, Canada

    Lauralyn McIntyre & Shane W. English

  7. Department of Anesthesiology and Critical Care Medicine, Université Laval, Quebec City, QC, Canada

    Alexis F. Turgeon

  8. Population Health and Optimal Health Practices Unit, Centre hospitalier universitaire de Québec-Université Laval Research Center, Quebec City, QC, Canada

    Alexis F. Turgeon

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LAT and SWE conceived and designed the manuscript. LAT performed the review of the literature and created the tables and figure. SWE, LM, and AFT reviewed each draft and provided critical feedback and content expertise. The final version was reviewed and approved by all authors.

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Correspondence to Shane W. English.

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S. English is the recipient of a National New Investigator Award from the Heart and Stroke Foundation. A. Turgeon holds a Canada Research Chair in Critical Care Neurology and Trauma.

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Terrett, L.A., McIntyre, L., Turgeon, A.F. et al. Anemia and Red Blood Cell Transfusion in Aneurysmal Subarachnoid Hemorrhage. Neurocrit Care 39, 91–103 (2023). https://doi.org/10.1007/s12028-023-01815-0

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