DOI QR코드

DOI QR Code

Fibrinolytic (Thrombolytic) Therapy for Post Intraventricular Hemorrhagic Hydrocephalus in Preterm Infants

  • Young Soo Park (Department of Neurosurgery and Children's Medical Center, Nara Medical University)
  • Received : 2022.11.25
  • Accepted : 2023.01.12
  • Published : 2023.05.01

Abstract

While the survival rate of preterm infants has increased dramatically over the last few decades, intraventricular hemorrhage and subsequent hydrocephalus remain major unsolved problems in neonatal intensive care. Once intraventricular hemorrhage occurs, severe neurological sequelae are inevitable. Treatment of this complicated pathology and achievement of favorable neurofunctional outcomes in fragile infants are crucial challenges for pediatric neurosurgeons. Fibrinolytic therapy, which chemically dissolves hematoma, is a promising and useful treatment method. In this paper, the historical background of fibrinolytic therapy for post-intraventricular hemorrhagic hydrocephalus in preterm infants is reviewed and a recent method of fibrinolytic therapy using urokinase is introduced.

Keywords

Acknowledgement

I would like to express my sincere gratitude to Andrew Whitelaw (Professor Emeritus, Bristol University) for his valuable advice, and to convey my deepest respect for his outstanding and excellent work over the years.

References

  1. Adams-Chapman I, Hansen NI, Stoll BJ, Higgins R; NICHD Research Network : Neurodevelopmental outcome of extremely low birth weight infants with posthemorrhagic hydrocephalus requiring shunt insertion. Pediatrics 121 : e1167-1177, 2008 https://doi.org/10.1542/peds.2007-0423
  2. Akdemir H, Selcuklu A, Pasaoglu A, Oktem IS, Kavuncu I : Treatment of severe intraventricular hemorrhage by intraventricular infusion of urokinase. Neurosurg Rev 18 : 95-100, 1995 https://doi.org/10.1007/BF00417665
  3. Behrens P, Tietze A, Walch E, Bittigau P, Buhrer C, Schulz M, et al. : Neurodevelopmental outcome at 2 years after neuroendoscopic lavage in neonates with posthemorrhagic hydrocephalus. J Neurosurg Pediatr 26 : 495-503, 2020 https://doi.org/10.3171/2020.5.PEDS20211
  4. Brouwer AJ, van Stam C, Uniken Venema M, Koopman C, Groenendaal F, de Vries LS : Cognitive and neurological outcome at the age of 5-8 years of preterm infants with post-hemorrhagic ventricular dilatation requiring neurosurgical intervention. Neonatology 101 : 210-216, 2012 https://doi.org/10.1159/000331797
  5. Chari A, Mallucci C, Whitelaw A, Aquilina K : Intraventricular haemorrhage and posthaemorrhagic ventricular dilatation: moving beyond CSF diversion. Childs Nerv Syst 37 : 3375-3383, 2021 https://doi.org/10.1007/s00381-021-05206-8
  6. Christian EA, Jin DL, Attenello F, Wen T, Cen S, Mack WJ, et al. : Trends in hospitalization of preterm infants with intraventricular hemorrhage and hydrocephalus in the United States, 2000-2010. J Neurosurg Pediatr 17 : 260-269, 2016 https://doi.org/10.3171/2015.7.PEDS15140
  7. Cizmeci MN, Groenendaal F, Liem KD, van Haastert IC, Benavente-Fernandez I, van Straaten HLM, et al. : Randomized controlled early versus late ventricular intervention study in posthemorrhagic ventricular dilatation: outcome at 2 years. J Pediatr 226 : 28-35.e3, 2020 https://doi.org/10.1016/j.jpeds.2020.08.014
  8. d'Arcangues C, Schulz M, Buhrer C, Thome U, Krause M, Thomale UW : Extended experience with neuroendoscopic lavage for posthemorrhagic hydrocephalus in neonates. World Neurosurg 116 : e217-e224, 2018 https://doi.org/10.1016/j.wneu.2018.04.169
  9. Dvalishvili A, Khinikadze M, Gegia G, Khutsishvili L : Neuroendoscopic lavage versus traditional surgical methods for the early management of posthemorrhagic hydrocephalus in neonates. Childs Nerv Syst 38 : 1897-1902, 2022 https://doi.org/10.1007/s00381-022-05606-4
  10. El-Dib M, Limbrick DD Jr, Inder T, Whitelaw A, Kulkarni AV, Warf B, et al. : Management of post-hemorrhagic ventricular dilatation in the infant born preterm. J Pediatr 226 : 16-27.e3, 2020 https://doi.org/10.1016/j.jpeds.2020.07.079
  11. Etus V, Kahilogullari G, Karabagli H, Unlu A : Early endoscopic ventricular irrigation for the treatment of neonatal posthemorrhagic hydrocephalus: a feasible treatment option or not? A multicenter study. Turk Neurosurg 28 : 137-141, 2018
  12. Gaberel T, Montagne A, Lesept F, Gauberti M, Lemarchand E, Orset C, et al. : Urokinase versus alteplase for intraventricular hemorrhage fibrinolysis. Neuropharmacology 85 : 158-165, 2014 https://doi.org/10.1016/j.neuropharm.2014.05.001
  13. Hansen A, Whitelaw A, Lapp C, Brugnara C : Cerebrospinal fluid plasminogen activator inhibitor-1: a prognostic factor in posthaemorrhagic hydrocephalus. Acta Paediatr 86 : 995-998, 1997 https://doi.org/10.1111/j.1651-2227.1997.tb15186.x
  14. Hansen AR, Volpe JJ, Goumnerova LC, Madsen JR : Intraventricular urokinase for the treatment of posthemorrhagic hydrocephalus. Pediatr Neurol 17 : 213-217, 1997 https://doi.org/10.1016/S0887-8994(97)00130-6
  15. Hirata K, Kimura T, Hirano S, Wada K, Kusuda S, Fujimura M, et al. : Outcomes of outborn very-low-birth-weight infants in Japan. Arch Dis Child Fetal Neonatal Ed 106 : 131-136, 2021 https://doi.org/10.1136/archdischild-2019-318594
  16. Honeyman SI, Boukas A, Jayamohan J, Magdum S : Neuroendoscopic lavage for the management of neonatal post-haemorrhagic hydrocephalus: a retrospective series. Childs Nerv Syst 38 : 115-121, 2022 https://doi.org/10.1007/s00381-021-05373-8
  17. Hudgins RJ, Boydston WR, Hudgins PA, Morris R, Adler SM, Gilreath CL : Intrathecal urokinase as a treatment for intraventricular hemorrhage in the preterm infant. Pediatr Neurosurg 26 : 281-187, 1997
  18. Jeon GW, Lee JH, Oh M, Chang YS : Serial long-term growth and neurodevelopment of very-low-birth-weight infants: 2022 update on the Korean neonatal network. J Korean Med Sci 37 : e263, 2022
  19. Kandula V, Mohammad LM, Thirunavu V, LoPresti M, Beestrum M, Lai GY, et al. : The role of blood product removal in intraventricular hemorrhage of prematurity: a meta-analysis of the clinical evidence. Childs Nerv Syst 38 : 239-252, 2022
  20. Kusuda S, Fujimura M, Sakuma I, Aotani H, Kabe K, Itani Y, et al. : Morbidity and mortality of infants with very low birth weight in Japan: center variation. Pediatrics 118 : e1130-1138, 2006 https://doi.org/10.1542/peds.2005-2724
  21. Luyt K, Jary SL, Lea CL, Young GJ, Odd DE, Miller HE, et al. : Drainage, irrigation and fibrinolytic therapy (DRIFT) for posthaemorrhagic ventricular dilatation: 10-year follow-up of a randomised controlled trial. Arch Dis Child Fetal Neonatal Ed 105 : 466-473, 2020 https://doi.org/10.1136/archdischild-2019-318231
  22. Mazzola CA, Choudhri AF, Auguste KI, Limbrick DD Jr, Rogido M, Mitchell L, et al. : Pediatric hydrocephalus: systematic literature review and evidence-based guidelines. Part 2: management of posthemorrhagic hydrocephalus in premature infants. J Neurosurg Pediatr 14 Suppl 1 : 8-23, 2014 https://doi.org/10.3171/2014.7.PEDS14322
  23. McClugage SG, Laskay NMB, Donahue BN, Arynchyna A, Zimmerman K, Aban IB, et al. : Functional outcomes at 2 years of age following treatment for posthemorrhagic hydrocephalus of prematurity: what do we know at the time of consult? J Neurosurg Pediatr 14 : 1-9, 2020 https://doi.org/10.3171/2019.12.PEDS19381
  24. Papile LA, Burstein J, Burstein R, Koffler H : Incidence and evolution of subependymal and intraventricular hemorrhage: a study of infants with birth weights less than 1,500 gm. J Pediatr 92 : 529-534, 1978 https://doi.org/10.1016/S0022-3476(78)80282-0
  25. Park YS : Intraventricular hemorrhage in the newborn, congenital and developmental cranial anomalies in Alexiou G, Prodromou N (eds) : Pediatric Neurosurgery for Clinicians. Cham : Springer, 2022, pp51-65
  26. Park YS : Treatment strategies and challenges to avoid cerebrospinal fluid shunting for pediatric hydrocephalus. Neurol Med Chir (Tokyo) 62 : 416-430, 2022 https://doi.org/10.2176/jns-nmc.2022-0100
  27. Park YS, Kotani Y, Kim TK, Yokota H, Sugimoto T, Nakagawa I, et al. : Efficacy and safety of intraventricular fibrinolytic therapy for post-intraventricular hemorrhagic hydrocephalus in extreme low birth weight infants: a preliminary clinical study. Childs Nerv Syst 37 : 69-79, 2021 https://doi.org/10.1007/s00381-020-04766-5
  28. Rainov NG, Burkert WL : Urokinase infusion for severe intraventricular haemorrhage. Acta Neurochir (Wien) 134 : 55-59, 1995 https://doi.org/10.1007/BF01428504
  29. Richard E, Cinalli G, Assis D, Pierre-Kahn A, Lacaze-Masmonteil T : Treatment of post-haemorrhage ventricular dilatation with an Ommaya's reservoir: management and outcome of 64 preterm infants. Childs Nerv Syst 17 : 334-340, 2001 https://doi.org/10.1007/s003810000418
  30. Savman K, Blennow M, Hagberg H, Tarkowski E, Thoresen M, Whitelaw A : Cytokine response in cerebrospinal fluid from preterm infants with posthaemorrhagic ventricular dilatation. Acta Paediatr 91 : 1357-1363, 2002 https://doi.org/10.1111/j.1651-2227.2002.tb02834.x
  31. Savman K, Nilsson UA, Blennow M, Kjellmer I, Whitelaw A : Non-protein-bound iron is elevated in cerebrospinal fluid from preterm infants with posthemorrhagic ventricular dilatation. Pediatr Res 49 : 208-212, 2001 https://doi.org/10.1203/00006450-200102000-00013
  32. Schulz M, Buhrer C, Pohl-Schickinger A, Haberl H, Thomale UW : Neuro-endoscopic lavage for the treatment of intraventricular hemorrhage and hydrocephalus in neonates. J Neurosurg Pediatr 13 : 626-635, 2014 https://doi.org/10.3171/2014.2.PEDS13397
  33. Stoll BJ, Hansen NI, Bell EF, Shankaran S, Laptook AR, Walsh MC, et al. : Neonatal outcomes of extremely preterm infants from the NICHD Neonatal Research Network. Pediatrics 126 : 443-456, 2010 https://doi.org/10.1542/peds.2009-2959
  34. Stoll BJ, Hansen NI, Bell EF, Walsh MC, Carlo WA, Shankaran S, et al. : Trends in care practices, morbidity, and mortality of extremely preterm neonates, 1993-2012. JAMA 314 : 1039-1051, 2015 https://doi.org/10.1001/jama.2015.10244
  35. Szpecht D, Wiak K, Braszak A, Szymankiewicz M, Gadzinowski J : Role of selected cytokines in the etiopathogenesis of intraventricular hemorrhage in preterm newborns. Childs Nerv Syst 32 : 2097-2103, 2016 https://doi.org/10.1007/s00381-016-3217-9
  36. Tirado-Caballero J, Rivero-Garvia M, Arteaga-Romero F, Herreria-Franco J, Lozano-Gonzalez A, Marquez-Rivas J : Neuroendoscopic lavage for the management of posthemorrhagic hydrocephalus in preterm infants: safety, effectivity, and lessons learned. J Neurosurg Pediatr 26 : 237-246, 2020 https://doi.org/10.3171/2020.2.PEDS2037
  37. Todo T, Usui M, Takakura K : Treatment of severe intraventricular hemorrhage by intraventricular infusion of urokinase. J Neurosurg 74 : 81-86, 1991 https://doi.org/10.3171/jns.1991.74.1.0081
  38. Volpe JJ : Intraventricular hemorrhage in the premature infant--current concepts. Part I. Ann Neurol 25 : 3-11, 1989 https://doi.org/10.1002/ana.410250103
  39. Volpe JJ : Intraventricular hemorrhage in the premature infant--current concepts. Part II. Ann Neurol 25 : 109-116, 1989 https://doi.org/10.1002/ana.410250202
  40. Whitelaw A, Aquilina K : Management of posthaemorrhagic ventricular dilatation. Arch Dis Child Fetal Neonatal Ed 97 : F229-F233, 2012 https://doi.org/10.1136/adc.2010.190173
  41. Whitelaw A, Evans D, Carter M, Thoresen M, Wroblewska J, Mandera M, et al. : Randomized clinical trial of prevention of hydrocephalus after intraventricular hemorrhage in preterm infants: brain-washing versus tapping fluid. Pediatrics 119 : e1071-e1078, 2007 https://doi.org/10.1542/peds.2006-2841
  42. Whitelaw A, Jary S, Kmita G, Wroblewska J, Musialik-Swietlinska E, Mandera M, et al. : Randomized trial of drainage, irrigation and fibrinolytic therapy for premature infants with posthemorrhagic ventricular dilatation: developmental outcome at 2 years. Pediatrics 125 : e852-e858, 2010 https://doi.org/10.1542/peds.2009-1960
  43. Whitelaw A, Mowinckel MC, Abildgaard U : Low levels of plasminogen in cerebrospinal fluid after intraventricular haemorrhage: a limiting factor for clot lysis? Acta Paediatr 84 : 933-936, 1995 https://doi.org/10.1111/j.1651-2227.1995.tb13795.x
  44. Whitelaw A, Mowinckel MC, Fellman V, Abildgaard U : Endogenous tissue plasminogen activator in neonatal cerebrospinal fluid. Eur J Pediatr 155 : 117-119, 1996 https://doi.org/10.1007/BF02075763
  45. Whitelaw A, Pople I, Cherian S, Evans D, Thoresen M : Phase 1 trial of prevention of hydrocephalus after intraventricular hemorrhage in newborn infants by drainage, irrigation, and fibrinolytic therapy. Pediatrics 111(4 Pt 1) : 759-765, 2003 https://doi.org/10.1542/peds.111.4.759
  46. Whitelaw A, Rivers RP, Creighton L, Gaffney P : Low dose intraventricular fibrinolytic treatment to prevent posthaemorrhagic hydrocephalus. Arch Dis Child 67(1 Spec No) : 12-14, 1992 https://doi.org/10.1136/adc.67.1_Spec_No.12
  47. Whitelaw A, Saliba E, Fellman V, Mowinckel MC, Acolet D, Marlow N : Phase I study of intraventricular recombinant tissue plasminogen activator for treatment of posthaemorrhagic hydrocephalus. Arch Dis Child Fetal Neonatal Ed 75 : F20-F26, 1996 https://doi.org/10.1136/fn.75.1.F20
  48. Wilson-Costello D, Friedman H, Minich N, Siner B, Taylor G, Schluchter M, et al. : Improved neurodevelopmental outcomes for extremely low birth weight infants in 2000-2002. Pediatrics 119 : 37-45, 2007 https://doi.org/10.1542/peds.2006-1416
  49. Yapicioglu H, Narli N, Satar M, Soyupak S, Altunbasak S : Intraventricular streptokinase for the treatment of posthaemorrhagic hydrocephalus of preterm. J Clin Neurosci 10 : 297-299, 2003 https://doi.org/10.1016/S0967-5868(03)00028-6
  50. Youn Y, Lee SM, Hwang JH, Cho SJ, Kim EK, Kim EA, et al. : Two-year outcomes of Korean very low birth weight infants born in 2013-2014. J Korean Med Sci 33 : e309, 2018