Skip to main content

Advertisement

SpringerLink
Log in

Targeting Hemoglobin to Reduce Delayed Cerebral Ischemia After Subarachnoid Hemorrhage

  • Review Article
  • Published:
Translational Stroke Research Aims and scope Submit manuscript

Abstract

Delayed cerebral ischemia (DCI) continues to be a sequela of aneurysmal subarachnoid hemorrhage (aSAH) that carries significant morbidity and mortality. Aside from nimodipine, no therapeutic agents are available to reduce the incidence of DCI. Pathophysiologic mechanisms contributing to DCI are poorly understood, but accumulating evidence over the years implicates several factors. Those have included microvessel vasoconstriction, microthrombosis, oxidative tissue damage, and cortical spreading depolarization as well as large vessel vasospasm. Common to these processes is red blood cell leakage into the cerebrospinal fluids (CSF) and subsequent lysis which releases hemoglobin, a central instigator in these events. This has led to the hypothesis that early blood removal may improve clinical outcome and reduce DCI. This paper will provide a narrative review of the evidence of hemoglobin as an instigator of DCI. It will also elaborate on available human data that discuss blood clearance and CSF drainage as a treatment of DCI. Finally, we will address a recent novel device that is currently being tested, the Neurapheresis CSF Management System™. This is an automated dual-lumen lumbar drainage system that has an option to filter CSF and return it to the patient.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

Data Availability

Data sharing not applicable to this article as no datasets were generated or analyzed during the current study.

References

  1. Dodd WS, Laurent D, Dumont AS, Hasan DM, Jabbour PM, Starke RM, et al. Pathophysiology of delayed cerebral ischemia after subarachnoid hemorrhage: a review. J Am Heart Assoc. 2021;10:e021845.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Geraghty JR, Testai FD. Delayed cerebral ischemia after subarachnoid hemorrhage: beyond vasospasm and towards a multifactorial pathophysiology. Curr Atheroscler Rep. 2017;19:50.

    Article  PubMed  CAS  Google Scholar 

  3. Macdonald RL. Delayed neurological deterioration after subarachnoid haemorrhage. Nat Rev Neurol. 2014;10:44–58.

    Article  CAS  PubMed  Google Scholar 

  4. Connolly ES Jr, Rabinstein AA, Carhuapoma JR, Derdeyn CP, Dion J, Higashida RT, 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;43:1711–37.

    Article  PubMed  Google Scholar 

  5. Pool JL. Cerebral vasospasm. N Engl J Med. 1958;259:1259–64.

    Article  CAS  PubMed  Google Scholar 

  6. Rothenberg SF, Corday E. Etiology of the transient cerebral stroke. J Am Med Assoc. 1957;164:2005–8.

    Article  CAS  PubMed  Google Scholar 

  7. Pool JL, Jacobson S, Fletcher TA. Cerebral vasospasm; clinical and experimental evidence. J Am Med Assoc. 1958;167:1599–601.

    Article  CAS  PubMed  Google Scholar 

  8. Robertson EG. Cerebral lesions due to intracranial aneurysms. Brain. 1949;72:150–85.

    Article  CAS  PubMed  Google Scholar 

  9. Frontera JA, Fernandez A, Schmidt JM, Claassen J, Wartenberg KE, Badjatia N, et al. Defining vasospasm after subarachnoid hemorrhage: what is the most clinically relevant definition? Stroke. 2009;40:1963–8.

    Article  PubMed  Google Scholar 

  10. Dhar R, Scalfani MT, Blackburn S, Zazulia AR, Videen T, Diringer M. Relationship between angiographic vasospasm and regional hypoperfusion in aneurysmal subarachnoid hemorrhage. Stroke. 2012;43:1788–94.

    Article  PubMed  PubMed Central  Google Scholar 

  11. Blackburn SL, Kumar PT, McBride D, Zeineddine HA, Leclerc J, Choi HA, et al. Unique contribution of haptoglobin and haptoglobin genotype in aneurysmal subarachnoid hemorrhage. Front Physiol. 2018;9:592.

    Article  PubMed  PubMed Central  Google Scholar 

  12. Peeyush Kumar T, McBride DW, Dash PK, Matsumura K, Rubi A, Blackburn SL. Endothelial cell dysfunction and injury in subarachnoid hemorrhage. Mol Neurobiol. 2019;56:1992–2006.

    Article  CAS  PubMed  Google Scholar 

  13. Crowley RW, Medel R, Dumont AS, Ilodigwe D, Kassell NF, Mayer SA, et al. Angiographic vasospasm is strongly correlated with cerebral infarction after subarachnoid hemorrhage. Stroke. 2011;42:919–23.

    Article  PubMed  Google Scholar 

  14. van der Steen WE, Zijlstra IA, Verbaan D, Boers AMM, Gathier CS, van den Berg R, et al. Association of quantified location-specific blood volumes with delayed cerebral ischemia after aneurysmal subarachnoid hemorrhage. AJNR Am J Neuroradiol. 2018;39:1059–64.

    Article  PubMed  PubMed Central  Google Scholar 

  15. Findlay JM, Macdonald RL, Weir BK. Current concepts of pathophysiology and management of cerebral vasospasm following aneurysmal subarachnoid hemorrhage. Cerebrovasc Brain Metab Rev. 1991;3:336–61.

    CAS  PubMed  Google Scholar 

  16. Macdonald RL, Weir BK. A review of hemoglobin and the pathogenesis of cerebral vasospasm. Stroke. 1991;22:971–82.

    Article  CAS  PubMed  Google Scholar 

  17. Horky LL, Pluta RM, Boock RJ, Oldfield EH. Role of ferrous iron chelator 2,2’-dipyridyl in preventing delayed vasospasm in a primate model of subarachnoid hemorrhage. J Neurosurg. 1998;88:298–303.

    Article  CAS  PubMed  Google Scholar 

  18. Borsody M, Burke A, Coplin W, Miller-Lotan R, Levy A. Haptoglobin and the development of cerebral artery vasospasm after subarachnoid hemorrhage. Neurology. 2006;66:634–40.

    Article  CAS  PubMed  Google Scholar 

  19. Clark JF, Sharp FR. Bilirubin oxidation products (BOXes) and their role in cerebral vasospasm after subarachnoid hemorrhage. J Cereb Blood Flow Metab. 2006;26:1223–33.

    Article  CAS  PubMed  Google Scholar 

  20. Keyrouz SG, Diringer MN. Clinical review: prevention and therapy of vasospasm in subarachnoid hemorrhage. Crit Care. 2007;11:220.

    Article  PubMed  PubMed Central  Google Scholar 

  21. Pluta RM, Hansen-Schwartz J, Dreier J, Vajkoczy P, Macdonald RL, Nishizawa S, et al. Cerebral vasospasm following subarachnoid hemorrhage: time for a new world of thought. Neurol Res. 2009;31:151–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Lee JY, Keep RF, He Y, Sagher O, Hua Y, Xi G. Hemoglobin and iron handling in brain after subarachnoid hemorrhage and the effect of deferoxamine on early brain injury. J Cereb Blood Flow Metab. 2010;30:1793–803.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Clark JF, Harm A, Saffire A, Biehle SJ, Lu A, Pyne-Geithman GJ. Bilirubin oxidation products seen post subarachnoid hemorrhage have greater effects on aged rat brain compared to young. Acta Neurochir Suppl. 2011;110:157–62.

    PubMed  Google Scholar 

  24. Pyne-Geithman GJ, Nair SG, Stamper DN, Clark JF. Role of bilirubin oxidation products in the pathophysiology of DIND following SAH. Acta Neurochir Suppl. 2013;115:267–73.

    PubMed  Google Scholar 

  25. Leclerc JL, Blackburn S, Neal D, Mendez NV, Wharton JA, Waters MF, et al. Haptoglobin phenotype predicts the development of focal and global cerebral vasospasm and may influence outcomes after aneurysmal subarachnoid hemorrhage. Proc Natl Acad Sci U S A. 2015;112:1155–60.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Tso MK, Macdonald RL. Subarachnoid hemorrhage: a review of experimental studies on the microcirculation and the neurovascular unit. Transl Stroke Res. 2014;5:174–89.

    Article  PubMed  Google Scholar 

  27. Akeret K, Buzzi RM, Schaer CA, Thomson BR, Vallelian F, Wang S, et al. Cerebrospinal fluid hemoglobin drives subarachnoid hemorrhage-related secondary brain injury. J Cereb Blood Flow Metab. 2021:271678X211020629.

  28. Helms C, Kim-Shapiro DB. Hemoglobin-mediated nitric oxide signaling. Free Radic Biol Med. 2013;61:464–72.

    Article  CAS  PubMed  Google Scholar 

  29. Wu F, Liu Z, Li G, Zhou L, Huang K, Wu Z, et al. Inflammation and oxidative stress: potential targets for improving prognosis after subarachnoid hemorrhage. Front Cell Neurosci. 2021;15:739506.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Sabri M, Ai J, Lakovic K, D’Abbondanza J, Ilodigwe D, Macdonald RL. Mechanisms of microthrombi formation after experimental subarachnoid hemorrhage. Neuroscience. 2012;224:26–37.

    Article  CAS  PubMed  Google Scholar 

  31. Pluta RM, Dejam A, Grimes G, Gladwin MT, Oldfield EH. Nitrite infusions to prevent delayed cerebral vasospasm in a primate model of subarachnoid hemorrhage. JAMA. 2005;293:1477–84.

    Article  CAS  PubMed  Google Scholar 

  32. Pyne-Geithman GJ, Morgan CJ, Wagner K, Dulaney EM, Carrozzella J, Kanter DS, et al. Bilirubin production and oxidation in CSF of patients with cerebral vasospasm after subarachnoid hemorrhage. J Cereb Blood Flow Metab. 2005;25:1070–7.

    Article  CAS  PubMed  Google Scholar 

  33. Siasios I, Kapsalaki EZ, Fountas KN. Cerebral vasospasm pharmacological treatment: an update. Neurol Res Int. 2013;2013:571328.

    Article  PubMed  PubMed Central  Google Scholar 

  34. Lin G, Macdonald RL, Marton LS, Kowalczuk A, Solenski NJ, Weir BK. Hemoglobin increases endothelin-1 in endothelial cells by decreasing nitric oxide. Biochem Biophys Res Commun. 2001;280:824–30.

    Article  CAS  PubMed  Google Scholar 

  35. Ayer RE, Zhang JH. Oxidative stress in subarachnoid haemorrhage: significance in acute brain injury and vasospasm. Acta Neurochir Suppl. 2008;104:33–41.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Cheng YW, Li WJ, Dou XJ, Jia R, Yang H, Liu XG, et al. Role of endothelin1 and its receptors in cerebral vasospasm following subarachnoid hemorrhage. Mol Med Rep. 2018;18:5229–36.

    CAS  PubMed  Google Scholar 

  37. Fassbender K, Hodapp B, Rossol S, Bertsch T, Schmeck J, Schutt S, et al. Endothelin-1 in subarachnoid hemorrhage: an acute-phase reactant produced by cerebrospinal fluid leukocytes. Stroke. 2000;31:2971–5.

    Article  CAS  PubMed  Google Scholar 

  38. Mayer SA, Aldrich EF, Bruder N, Hmissi A, Macdonald RL, Viarasilpa T, et al. Thick and diffuse subarachnoid blood as a treatment effect modifier of clazosentan after subarachnoid hemorrhage. Stroke. 2019;50:2738–44.

    Article  CAS  PubMed  Google Scholar 

  39. Macdonald RL, Kassell NF, Mayer S, Ruefenacht D, Schmiedek P, Weidauer S, et al. Clazosentan to overcome neurological ischemia and infarction occurring after subarachnoid hemorrhage (CONSCIOUS-1): randomized, double-blind, placebo-controlled phase 2 dose-finding trial. Stroke. 2008;39:3015–21.

    Article  CAS  PubMed  Google Scholar 

  40. Macdonald RL, Higashida RT, Keller E, Mayer SA, Molyneux A, Raabe A, et al. Clazosentan, an endothelin receptor antagonist, in patients with aneurysmal subarachnoid haemorrhage undergoing surgical clipping: a randomised, double-blind, placebo-controlled phase 3 trial (CONSCIOUS-2). Lancet Neurol. 2011;10:618–25.

    Article  CAS  PubMed  Google Scholar 

  41. Macdonald RL, Higashida RT, Keller E, Mayer SA, Molyneux A, Raabe A, et al. Randomized trial of clazosentan in patients with aneurysmal subarachnoid hemorrhage undergoing endovascular coiling. Stroke. 2012;43:1463–9.

    Article  CAS  PubMed  Google Scholar 

  42. Zheng VZ, Wong GKC. Neuroinflammation responses after subarachnoid hemorrhage: a review. J Clin Neurosci. 2017;42:7–11.

    Article  PubMed  Google Scholar 

  43. Vecchione C, Frati A, Di Pardo A, Cifelli G, Carnevale D, Gentile MT, et al. Tumor necrosis factor-alpha mediates hemolysis-induced vasoconstriction and the cerebral vasospasm evoked by subarachnoid hemorrhage. Hypertension. 2009;54:150–6.

    Article  CAS  PubMed  Google Scholar 

  44. Suzuki H, Fujimoto M, Kawakita F, Liu L, Nakano F, Nishikawa H, et al. Toll-like receptor 4 and tenascin-C signaling in cerebral vasospasm and brain injuries after subarachnoid hemorrhage. Acta Neurochir Suppl. 2020;127:91–6.

    Article  PubMed  Google Scholar 

  45. Okada T, Suzuki H. Toll-like receptor 4 as a possible therapeutic target for delayed brain injuries after aneurysmal subarachnoid hemorrhage. Neural Regen Res. 2017;12:193–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Akamatsu Y, Pagan VA, Hanafy KA. The role of TLR4 and HO-1 in neuroinflammation after subarachnoid hemorrhage. J Neurosci Res. 2020;98:549–56.

    Article  CAS  PubMed  Google Scholar 

  47. Griffiths S, Clark J, Adamides AA, Ziogas J. The role of haptoglobin and hemopexin in the prevention of delayed cerebral ischaemia after aneurysmal subarachnoid haemorrhage: a review of current literature. Neurosurg Rev. 2020;43:1273–88.

    Article  PubMed  Google Scholar 

  48. Chou SH, Feske SK, Simmons SL, Konigsberg RG, Orzell SC, Marckmann A, et al. Elevated peripheral neutrophils and matrix metalloproteinase 9 as biomarkers of functional outcome following subarachnoid hemorrhage. Transl Stroke Res. 2011;2:600–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Provencio JJ, Altay T, Smithason S, Moore SK, Ransohoff RM. Depletion of Ly6G/C(+) cells ameliorates delayed cerebral vasospasm in subarachnoid hemorrhage. J Neuroimmunol. 2011;232:94–100.

    Article  CAS  PubMed  Google Scholar 

  50. Pradilla G, Wang PP, Legnani FG, Ogata L, Dietsch GN, Tamargo RJ. Prevention of vasospasm by anti-CD11/CD18 monoclonal antibody therapy following subarachnoid hemorrhage in rabbits. J Neurosurg. 2004;101:88–92.

    Article  CAS  PubMed  Google Scholar 

  51. Provencio JJ, Swank V, Lu H, Brunet S, Baltan S, Khapre RV, et al. Neutrophil depletion after subarachnoid hemorrhage improves memory via NMDA receptors. Brain Behav Immun. 2016;54:233–42.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. McBride DW, Blackburn SL, Peeyush KT, Matsumura K, Zhang JH. The role of thromboinflammation in delayed cerebral ischemia after subarachnoid hemorrhage. Front Neurol. 2017;8:555.

    Article  PubMed  PubMed Central  Google Scholar 

  53. Suzuki S, Suzuki M, Iwabuchi T, Kamata Y. Role of multiple cerebral microthrombosis in symptomatic cerebral vasospasm: with a case report. Neurosurgery. 1983;13:199–203.

    Article  CAS  PubMed  Google Scholar 

  54. Vergouwen MD, Vermeulen M, Coert BA, Stroes ES, Roos YB. Microthrombosis after aneurysmal subarachnoid hemorrhage: an additional explanation for delayed cerebral ischemia. J Cereb Blood Flow Metab. 2008;28:1761–70.

    Article  PubMed  Google Scholar 

  55. Dienel A, Kumar TP, Blackburn SL, McBride DW. Role of platelets in the pathogenesis of delayed injury after subarachnoid hemorrhage. J Cereb Blood Flow Metab. 2021:271678X211020865.

  56. Dienel A, Ammassam Veettil R, Hong SH, Matsumura K, Kumar TP, Yan Y, et al. Microthrombi correlates with infarction and delayed neurological deficits after subarachnoid hemorrhage in mice. Stroke. 2020;51:2249–54.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. James RF, Khattar NK, Aljuboori ZS, Page PS, Shao EY, Carter LM, et al. Continuous infusion of low-dose unfractionated heparin after aneurysmal subarachnoid hemorrhage: a preliminary study of cognitive outcomes. J Neurosurg. 2018:1–8.

  58. Dorhout Mees SM, van den Bergh WM, Algra A, Rinkel GJ. Antiplatelet therapy for aneurysmal subarachnoid haemorrhage. Cochrane Database Syst Rev. 2007:CD006184.

  59. Kole MJ, Wessell AP, Ugiliweneza B, Cannarsa GJ, Fortuny E, Stokum JA, et al. Low-dose intravenous heparin infusion after aneurysmal subarachnoid hemorrhage is associated with decreased risk of delayed neurological deficit and cerebral infarction. Neurosurgery. 2021;88:523–30.

    Article  PubMed  Google Scholar 

  60. Zanaty M, Allan L, Samaniego EA, Piscopo A, Ryan E, Torner JC, et al. Phase 1/2a trial of ISPASM. Stroke. 2021;52:3750–8.

    Article  CAS  PubMed  Google Scholar 

  61. Buehler PW, Abraham B, Vallelian F, Linnemayr C, Pereira CP, Cipollo JF, et al. Haptoglobin preserves the CD163 hemoglobin scavenger pathway by shielding hemoglobin from peroxidative modification. Blood. 2009;113:2578–86.

    Article  CAS  PubMed  Google Scholar 

  62. Macdonald RL, Katan M. Haptoglobin and hemoglobin in subarachnoid hemorrhage: a tale of 2 globins. Neurology. 2019;92:831–2.

    Article  PubMed  Google Scholar 

  63. Hugelshofer M, Buzzi RM, Schaer CA, Richter H, Akeret K, Anagnostakou V, et al. Haptoglobin administration into the subarachnoid space prevents hemoglobin-induced cerebral vasospasm. J Clin Invest. 2019;129:5219–35.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  64. Zhao X, Song S, Sun G, Strong R, Zhang J, Grotta JC, et al. Neuroprotective role of haptoglobin after intracerebral hemorrhage. J Neurosci. 2009;29:15819–27.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  65. Leclerc JL, Li C, Jean S, Lampert AS, Amador CL, Diller MA, et al. Temporal and age-dependent effects of haptoglobin deletion on intracerebral hemorrhage-induced brain damage and neurobehavioral outcomes. Exp Neurol. 2019;317:22–33.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  66. Garland P, Morton MJ, Haskins W, Zolnourian A, Durnford A, Gaastra B, et al. Haemoglobin causes neuronal damage in vivo which is preventable by haptoglobin. Brain Commun. 2020;2:fcz053.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  67. Yu Y, Lin Z, Yin Y, Zhao J. The ferric iron chelator 2,2’-dipyridyl attenuates basilar artery vasospasm and improves neurological function after subarachnoid hemorrhage in rabbits. Neurol Sci. 2014;35:1413–9.

    Article  PubMed  Google Scholar 

  68. Lee JY, Keep RF, Hua Y, Ernestus RI, Xi G. Deferoxamine reduces early brain injury following subarachnoid hemorrhage. Acta Neurochir Suppl. 2011;112:101–6.

    Article  PubMed  Google Scholar 

  69. Li Y, Yang H, Ni W, Gu Y. Effects of deferoxamine on blood-brain barrier disruption after subarachnoid hemorrhage. PLoS One. 2017;12:e0172784.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  70. Vollmer DG, Hongo K, Ogawa H, Tsukahara T, Kassell NF. A study of the effectiveness of the iron-chelating agent deferoxamine as vasospasm prophylaxis in a rabbit model of subarachnoid hemorrhage. Neurosurgery. 1991;28:27–32.

    Article  CAS  PubMed  Google Scholar 

  71. Komotar RJ, Hahn DK, Kim GH, Starke RM, Garrett MC, Merkow MB, et al. Efficacy of lamina terminalis fenestration in reducing shunt-dependent hydrocephalus following aneurysmal subarachnoid hemorrhage: a systematic review. Clinical article. J Neurosurg. 2009;111:147–54.

    Article  PubMed  Google Scholar 

  72. Mizukami M, Kawase T, Usami T, Tazawa T. Prevention of vasospasm by early operation with removal of subarachnoid blood. Neurosurgery. 1982;10:301–7.

    Article  CAS  PubMed  Google Scholar 

  73. Takahashi S, Sonobe M, Nagamine Y. Early operations for ruptured intracranial aneurysms. Comparative study with computed tomography. Acta Neurochir (Wien). 1981;57:23–31.

    Article  CAS  PubMed  Google Scholar 

  74. Rabinstein AA, Pichelmann MA, Friedman JA, Piepgras DG, Nichols DA, McIver JI, et al. Symptomatic vasospasm and outcomes following aneurysmal subarachnoid hemorrhage: a comparison between surgical repair and endovascular coil occlusion. J Neurosurg. 2003;98:319–25.

    Article  PubMed  Google Scholar 

  75. Inagawa T, Yamamoto M, Kamiya K. Effect of clot removal on cerebral vasospasm. J Neurosurg. 1990;72:224–30.

    Article  CAS  PubMed  Google Scholar 

  76. Yoshimoto Y, Wakai S, Satoh A, Tejima T, Hamano M. A prospective study on the effects of early surgery on vasospasm after subarachnoid hemorrhage. Surg Neurol. 1999;51:392–7 (discussion 7-8).

    Article  CAS  PubMed  Google Scholar 

  77. Shirao S, Yoneda H, Ishihara H, Harada K, Ueda K, Sano Y, et al. Fate of clots in patients with subarachnoid hemorrhage after different surgical treatment modality: a comparison between surgical clipping and Guglielmi detachable coil embolization. Neurosurgery. 2011;68:966–73 (discussion 73).

    Article  PubMed  Google Scholar 

  78. Kasuya H, Shimizu T, Kagawa M. The effect of continuous drainage of cerebrospinal fluid in patients with subarachnoid hemorrhage: a retrospective analysis of 108 patients. Neurosurgery. 1991;28:56–9.

    Article  CAS  PubMed  Google Scholar 

  79. Klimo P Jr, Kestle JR, MacDonald JD, Schmidt RH. Marked reduction of cerebral vasospasm with lumbar drainage of cerebrospinal fluid after subarachnoid hemorrhage. J Neurosurg. 2004;100:215–24.

    Article  PubMed  Google Scholar 

  80. Otawara Y, Ogasawara K, Kubo Y, Sasoh M, Ogawa A. Effect of continuous cisternal cerebrospinal fluid drainage for patients with thin subarachnoid hemorrhage. Vasc Health Risk Manag. 2007;3:401–4.

    PubMed  PubMed Central  Google Scholar 

  81. Maeda Y, Shirao S, Yoneda H, Ishihara H, Shinoyama M, Oka F, et al. Comparison of lumbar drainage and external ventricular drainage for clearance of subarachnoid clots after Guglielmi detachable coil embolization for aneurysmal subarachnoid hemorrhage. Clin Neurol Neurosurg. 2013;115:965–70.

    Article  PubMed  Google Scholar 

  82. Chung DY, Leslie-Mazwi TM, Patel AB, Rordorf GA. Management of external ventricular drains after subarachnoid hemorrhage: a multi-institutional survey. Neurocrit Care. 2017;26:356–61.

    Article  PubMed  PubMed Central  Google Scholar 

  83. Kwon OY, Kim YJ, Kim YJ, Cho CS, Lee SK, Cho MK. The utility and benefits of external lumbar CSF drainage after endovascular coiling on aneurysmal subarachnoid hemorrhage. J Korean Neurosurg Soc. 2008;43:281–7.

    Article  PubMed  PubMed Central  Google Scholar 

  84. Hoekema D, Schmidt RH, Ross I. Lumbar drainage for subarachnoid hemorrhage: technical considerations and safety analysis. Neurocrit Care. 2007;7:3–9.

    Article  PubMed  Google Scholar 

  85. Panni P, Donofrio CA, Barzaghi LR, Giudice L, Albano L, Righi C, et al. Safety and feasibility of lumbar drainage in the management of poor grade aneurysmal subarachnoid hemorrhage. J Clin Neurosci. 2019;64:64–70.

    Article  PubMed  Google Scholar 

  86. Hanggi D, Liersch J, Turowski B, Yong M, Steiger HJ. The effect of lumboventricular lavage and simultaneous low-frequency head-motion therapy after severe subarachnoid hemorrhage: results of a single center prospective Phase II trial. J Neurosurg. 2008;108:1192–9.

    Article  PubMed  Google Scholar 

  87. Al-Tamimi YZ, Bhargava D, Feltbower RG, Hall G, Goddard AJ, Quinn AC, et al. Lumbar drainage of cerebrospinal fluid after aneurysmal subarachnoid hemorrhage: a prospective, randomized, controlled trial (LUMAS). Stroke. 2012;43:677–82.

    Article  PubMed  Google Scholar 

  88. Park S, Yang N, Seo E. The effectiveness of lumbar cerebrospinal fluid drainage to reduce the cerebral vasospasm after surgical clipping for aneurysmal subarachnoid hemorrhage. J Korean Neurosurg Soc. 2015;57:167–73.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  89. Borkar SA, Singh M, Kale SS, Suri A, Chandra PS, Kumar R, et al. Spinal cerebrospinal fluid drainage for prevention of vasospasm in aneurysmal subarachnoid hemorrhage: a prospective, randomized controlled study. Asian J Neurosurg. 2018;13:238–46.

    Article  PubMed  PubMed Central  Google Scholar 

  90. Fang Y, Shao Y, Lu J, Dong X, Zhao X, Zhang J, et al. The effectiveness of lumbar cerebrospinal fluid drainage in aneurysmal subarachnoid hemorrhage with different bleeding amounts. Neurosurg Rev. 2020;43:739–47.

    Article  PubMed  Google Scholar 

  91. Alcala-Cerra G, Paternina-Caicedo A, Diaz-Becerra C, Moscote-Salazar LR, Gutierrez-Paternina JJ, Nino-Hernandez LM, et al. External lumbar cerebrospinal fluid drainage in patients with aneurysmal subarachnoid hemorrhage: a systematic review and meta-analysis of controlled trials. Neurologia. 2016;31:431–44.

    Article  CAS  PubMed  Google Scholar 

  92. Kreiter KT, Mayer SA, Howard G, Knappertz V, Ilodigwe D, Sloan MA, et al. Sample size estimates for clinical trials of vasospasm in subarachnoid hemorrhage. Stroke. 2009;40:2362–7.

    Article  PubMed  Google Scholar 

  93. Lu X, Ji C, Wu J, You W, Wang W, Wang Z, et al. Intrathecal fibrinolysis for aneurysmal subarachnoid hemorrhage: evidence from randomized controlled trials and cohort studies. Front Neurol. 2019;10:885.

    Article  PubMed  PubMed Central  Google Scholar 

  94. Eicker SO, Beseoglu K, Etminan N, Perrin J, Taskin A, Steiger HJ, et al. The effect of intraventricular thrombolysis in combination with low-frequency head motion after severe subarachnoid hemorrhage: interim analysis of safety, clot clearance rate and delayed cerebral ischemia. Acta Neurochir Suppl. 2012;114:323–8.

    Article  PubMed  Google Scholar 

  95. Shi L, Xu L, Shi L, Brandon D, Chen S, Zhang J. Intraventricular recombinant tissue plasminogen activator in treatment of aneurysmal intraventricular hemorrhage: a meta-analysis. Curr Drug Targets. 2017;18:1399–407.

    Article  CAS  PubMed  Google Scholar 

  96. Jang KM, Choi HH, Nam TK, Park YS, Kwon JT, Byun JS, et al. The effect of locally administered fibrinolytic drugs following aneurysmal subarachnoid hemorrhage : a meta-analysis with eight randomized controlled studies. J Korean Neurosurg Soc. 2021;64:207–16.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  97. Amin-Hanjani S, Ogilvy CS, Barker FG 2nd. Does intracisternal thrombolysis prevent vasospasm after aneurysmal subarachnoid hemorrhage? A meta-analysis. Neurosurgery. 2004;54:326–34 (discussion 34-5).

    Article  PubMed  Google Scholar 

  98. Gaberel T, Gakuba C, Fournel F, Le Blanc E, Gaillard C, Peyro-Saint-Paul L, et al. FIVHeMA: Intraventricular fibrinolysis versus external ventricular drainage alone in aneurysmal subarachnoid hemorrhage: a randomized controlled trial. Neurochirurgie. 2019;65:14–9.

    Article  CAS  PubMed  Google Scholar 

  99. Roelz R, Schubach F, Coenen VA, Jenkner C, Scheiwe C, Grauvogel J, et al. Stereotactic cisternal lavage in patients with aneurysmal subarachnoid hemorrhage with urokinase and nimodipine for the prevention of secondary brain injury (SPLASH): study protocol for a randomized controlled trial. Trials. 2021;22:285.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  100. Bardutzky J, Witsch J, Juttler E, Schwab S, Vajkoczy P, Wolf S. EARLYDRAIN- outcome after early lumbar CSF-drainage in aneurysmal subarachnoid hemorrhage: study protocol for a randomized controlled trial. Trials. 2011;12:203.

    Article  PubMed  PubMed Central  Google Scholar 

  101. Blackburn SL, Grande AW, Swisher CB, Hauck EF, Jagadeesan B, Provencio JJ. Prospective trial of cerebrospinal fluid filtration after aneurysmal subarachnoid hemorrhage via lumbar catheter (PILLAR). Stroke. 2019;50:2558–61.

    Article  PubMed  PubMed Central  Google Scholar 

  102. Blackburn SL, Swisher CB, Grande AW, Rubi A, Verbick LZ, McCabe A, et al. Novel dual lumen catheter and filtration device for removal of subarachnoid hemorrhage: first case report. Oper Neurosurg (Hagerstown). 2019;16:E148–53.

    Article  PubMed  Google Scholar 

  103. Khani M, Sass LR, Sharp MK, McCabe AR, Zitella Verbick LM, Lad SP, et al. In vitro and numerical simulation of blood removal from cerebrospinal fluid: comparison of lumbar drain to Neurapheresis therapy. Fluids Barriers CNS. 2020;17:23.

    Article  PubMed  PubMed Central  Google Scholar 

  104. Qureshi AI, Lobanova I, Huang W, Ishfaq MF, Broderick JP, Cassarly CN, et al. Lessons learned from phase II and phase III trials investigating therapeutic agents for cerebral ischemia associated with aneurysmal subarachnoid hemorrhage. Neurocrit Care. 2021.

  105. Roos YB, de Haan RJ, Beenen LF, Groen RJ, Albrecht KW, Vermeulen M. Complications and outcome in patients with aneurysmal subarachnoid haemorrhage: a prospective hospital based cohort study in the Netherlands. J Neurol Neurosurg Psychiatry. 2000;68:337–41.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

We would like to thank Toan Dongchau for the help in writing the manuscript. The figures in this manuscript were reproduced from Stroke journal from Prospective Trial of Cerebrospinal Fluid Filtration After Aneurysmal Subarachnoid Hemorrhage via Lumbar Catheter (PILLAR) by Blackburn et al.

Author information

Authors and Affiliations

  1. Department of Neurosurgery, The University of Texas Health Science Center at Houston, 6400 Fannin Street, Suite 2800, Houston, TX, 77030, USA

    Hussein A. Zeineddine, Pedram Honarpisheh, Devin McBride, Peeyush Kumar Thankamani Pandit, Ari Dienel, Sung-Ha Hong & Spiros Blackburn

  2. Clinical Innovation and Research Institute, Memorial Hermann Hospital-Texas Medical Center, Houston, TX, USA

    James Grotta

Authors
  1. Hussein A. Zeineddine
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Pedram Honarpisheh
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Devin McBride
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Peeyush Kumar Thankamani Pandit
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Ari Dienel
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Sung-Ha Hong
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. James Grotta
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Spiros Blackburn
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Spiros Blackburn.

Ethics declarations

Conflict of Interest

Spiros Blackburn is supported by 4R44NS110247, K23NS106054, and the Brain Aneurysm Foundation. Spiros Blackburn is Site PI for PILLAR and PILLAR-XT. Devin McBride is supported by NIH1R01NS115887 and the Brain Aneurysm Foundation. Peeyush Thankamani is supported by NIH R01NS121339. James Grotta is supported by research grants from the Patient Centered Outcomes Research institute R-1511–33024, NIH 1U01NS100699, R01 NS110779, 1U01NS110772, and CSL Behring.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Zeineddine, H.A., Honarpisheh, P., McBride, D. et al. Targeting Hemoglobin to Reduce Delayed Cerebral Ischemia After Subarachnoid Hemorrhage. Transl. Stroke Res. 13, 725–735 (2022). https://doi.org/10.1007/s12975-022-00995-9

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12975-022-00995-9

Keywords

Search

Navigation