CLINICAL TRIAL OF HEMATOCRIT STRATEGY IN HEART SURGERY

Summary

Principal Investigator: MICHAEL JOHN RIVKIN
Affiliation: Harvard University
Country: USA
Abstract: The optimal degree of hemodilution during profoundly hypothermic cardiopulmonary bypass (CPB) remain controversial, and widely disparate hemodilution protocols have evolved at centers undertaking infant cardiac surgery. Higher hematocrit (hct) exposes patients to the risks of microvascular occlusion, while lower hct may critically limit oxygen delivery to the brain and other organs. Preliminary data suggest that a higher hct provides superior brain and myocardial protection, but no randomized trials of outcome after use of higher vs. lower hct have been reported. In a single-center, prospective, randomized trial, hemodilution to a hct of 30 percent vs. 20 percent will be compared with respect to neurodevelopmental outcome and early postoperative course in a homogeneous population of infants with d-transposition of the great arteries undergoing the arterial switch operation. Specific Aim 1 will test the hypothesis that hemodilution to a hct of 30 percent, compared to 20 percent, will be associated with superior central nervous system protection. Our primary outcome variable will be developmental outcome at age 1 year, assessed with the Bayley Scales of Infant Development. Secondary outcome variables include 1) tissue release of S-100 protein as a measure of cerebral cellular injury; 2) cerebral hemodynamics and oxygenation, determined by near infrared spectroscopy (NIRS); 3) intrinsic cerebral vasoregulation, measured by NIRS and transcranial Doppler; and 4) at age 1 year, neurologic examination, the MacArthur inventory, and structural and volumetric findings on MRI. Specific Aim 2 will test the hypothesis that hemodilution to a hct of 30 percent, compared to 20 percent, will be associated with better early postoperative cardiovascular status. Our primary outcome measure will be the minimum cardiac index over the first postoperative 24 hours. Secondary outcome measures will include 1) the duration of postoperative endotracheal intubation, ICU stay, and hospital stay; 2) serum lactate levels; 3) the PaO2/FiO2 ratio; 4) levels of circulating pro-inflammatory cytokines; and 5) the percent change in total body water, estimated by bioelectrical impedance. The structure of the study will allow assessment of whether 1- year outcomes can be predicted by perioperative variable other than the hct strategies and, through the use of novel techniques such as NIRS and volumetric MRI, may provide insight into mechanisms by which hct and other perioperative variables affect the brain. The inferences reached in this study population should be broadly generalized to infants with other forms of congenital heart disease undergoing early repair and thus should have substantial impact on clinical practice.
Funding Period: 2000-07-05 - 2006-06-30
more information: NIH RePORT

Top Publications

  1. ncbi Randomized trial of hematocrit 25% versus 35% during hypothermic cardiopulmonary bypass in infant heart surgery
    Jane W Newburger
    Department of Cardiology, Children s Hospital Boston, Boston, Mass 02115, USA
    J Thorac Cardiovasc Surg 135:347-54, 354.e1-4. 2008
  2. ncbi Identification of pressure passive cerebral perfusion and its mediators after infant cardiac surgery
    Haim Bassan
    Department of Neurology, Children's Hospital, 300 Longwood Avenue, Boston MA 02115, USA
    Pediatr Res 57:35-41. 2005
  3. ncbi An evaluation of bilateral monitoring of cerebral oxygen saturation during pediatric cardiac surgery
    Barry D Kussman
    Department of Anesthesiology, Perioperative and Pain Medicine, Children s Hospital, 300 Longwood Ave, Boston, MA 02115, USA
    Anesth Analg 101:1294-300. 2005
  4. ncbi Postoperative hypothermia and blood loss after the neonatal arterial switch procedure
    Yusuke Iwata
    Department of Cardiovascular Surgery, Children s National Medical Center, Washington, DC 20010, USA
    Ann Thorac Surg 84:1627-32. 2007
  5. ncbi The effect of hematocrit during hypothermic cardiopulmonary bypass in infant heart surgery: results from the combined Boston hematocrit trials
    David Wypij
    Department of Cardiology, Children s Hospital Boston, Boston, Mass 02115, USA
    J Thorac Cardiovasc Surg 135:355-60. 2008
  6. ncbi Cerebral oximetry during infant cardiac surgery: evaluation and relationship to early postoperative outcome
    Barry D Kussman
    Department of Anesthesiology, Perioperative and Pain Medicine, Children s Hospital Boston, 300 Longwood Ave, Boston, MA 02115, USA
    Anesth Analg 108:1122-31. 2009
  7. ncbi Subtle hemorrhagic brain injury is associated with neurodevelopmental impairment in infants with repaired congenital heart disease
    Janet S Soul
    Department of Neurology, Children s Hospital Boston, Boston, MA 02115, USA
    J Thorac Cardiovasc Surg 138:374-81. 2009

Scientific Experts

  • Barry D Kussman
  • Jane W Newburger
  • JANET SUSAN SOUL
  • Richard A Jonas
  • David Wypij
  • Yusuke Iwata
  • Peter C Laussen
  • Haim Bassan
  • Emile A Bacha
  • Joseph M Forbess
  • John E Mayer
  • David C Bellinger
  • Frank Pigula
  • Pedro J del Nido
  • David Zurakowski
  • Gene Walter
  • Miles Tsuji
  • Kimberlee Gauvreau
  • Catherine Limperopoulos

Detail Information

Publications7

  1. ncbi Randomized trial of hematocrit 25% versus 35% during hypothermic cardiopulmonary bypass in infant heart surgery
    Jane W Newburger
    Department of Cardiology, Children s Hospital Boston, Boston, Mass 02115, USA
    J Thorac Cardiovasc Surg 135:347-54, 354.e1-4. 2008
    ..However, worse outcomes were concentrated in patients with hematocrit values of 20% or below, and the benefits of hematocrit values higher than 25% were uncertain...
  2. ncbi Identification of pressure passive cerebral perfusion and its mediators after infant cardiac surgery
    Haim Bassan
    Department of Neurology, Children's Hospital, 300 Longwood Avenue, Boston MA 02115, USA
    Pediatr Res 57:35-41. 2005
    ..001) of autoregulatory failure. This approach provides a means to identify and quantify disturbances of CPA. High CO(2) levels and fluctuating MAP are two important preventable factors associated with disturbed CPA...
  3. ncbi An evaluation of bilateral monitoring of cerebral oxygen saturation during pediatric cardiac surgery
    Barry D Kussman
    Department of Anesthesiology, Perioperative and Pain Medicine, Children s Hospital, 300 Longwood Ave, Boston, MA 02115, USA
    Anesth Analg 101:1294-300. 2005
    ..Further longitudinal neurological outcome studies are required to determine whether uni- or bi-hemispheric monitoring is required in this patient population...
  4. ncbi Postoperative hypothermia and blood loss after the neonatal arterial switch procedure
    Yusuke Iwata
    Department of Cardiovascular Surgery, Children s National Medical Center, Washington, DC 20010, USA
    Ann Thorac Surg 84:1627-32. 2007
    ..However, traditional intensive care practices emphasize aggressive rewarming, and the risk of excessive bleeding that may be related to hypothermia...
  5. ncbi The effect of hematocrit during hypothermic cardiopulmonary bypass in infant heart surgery: results from the combined Boston hematocrit trials
    David Wypij
    Department of Cardiology, Children s Hospital Boston, Boston, Mass 02115, USA
    J Thorac Cardiovasc Surg 135:355-60. 2008
    ..The form of the relationship between continuous hematocrit levels and outcomes requires further study...
  6. ncbi Cerebral oximetry during infant cardiac surgery: evaluation and relationship to early postoperative outcome
    Barry D Kussman
    Department of Anesthesiology, Perioperative and Pain Medicine, Children s Hospital Boston, 300 Longwood Ave, Boston, MA 02115, USA
    Anesth Analg 108:1122-31. 2009
    ..We examined changes in cerebral oxygen saturation during infant heart surgery and its relationship to anatomic diagnosis and early outcome...
  7. ncbi Subtle hemorrhagic brain injury is associated with neurodevelopmental impairment in infants with repaired congenital heart disease
    Janet S Soul
    Department of Neurology, Children s Hospital Boston, Boston, MA 02115, USA
    J Thorac Cardiovasc Surg 138:374-81. 2009
    ..We aimed to determine the incidence and type of brain injury in infants undergoing 2-ventricle repair in infancy and to determine risk factors associated with such injury...