title: Combination of alpha-stat strategy and hemodilution exacerbates neurologic injury in a survival piglet model with deep hypothermic circulatory arrest.
abstract: BACKGROUND
  The optimal pH strategy and hematocrit during cardiopulmonary bypass with deep hypothermic circulatory arrest (DHCA) remain controversial. We studied the interaction of pH strategy and hematocrit and their combined impact on cerebral oxygenation and neurological outcome in a survival piglet model including monitoring by near-infrared spectroscopy (NIRS).
  
  
  METHODS
  Thirty-six piglets (9.2+/-1.1 kg) underwent DHCA under varying conditions with continuous monitoring by NIRS (pH-stat or alpha-stat strategy, hematocrit 20% or 30%, DHCA time 60, 80, or 100 minutes). Neurological recovery was evaluated daily. The brain was fixed in situ on postoperative day 4 and a histological score (HS) for neurological injury was assessed.
  
  
  RESULTS
  Oxygenated hemoglobin (HbO2) and total hemoglobin signals detected by NIRS were significantly lower with alpha-stat strategy during cooling (p < 0.001), suggesting insufficient cerebral blood supply and oxygenation. HbO2 declined to a plateau (nadir) during DHCA. Time to nadir was significantly shorter in lower hematocrit groups (p < 0.01). Significantly delayed neurologic recovery was seen with alpha-stat strategy compared with pH-stat (p < 0.05). The alpha-stat group had a worse histological score compared with those assigned to pH-stat (p < 0.001). Neurologic impairment was estimated to be over 10 times more likely for animals randomized to alpha-stat compared with pH-stat strategy (odds ratio = 10.7, 95% confidence interval = 3.8 to 25.2).
  
  
  CONCLUSIONS
  Combination of alpha-stat strategy and lower hematocrit exacerbates neurological injury after DHCA. The mechanism of injury is inadequate cerebral oxygenation during cooling and a longer plateau period of minimal O2 extraction during DHCA.
authors.affiliation: Department of Cardiac Surgery, Children's Hospital and Harvard Medical School, Boston, Massachusetts 02115, USA.
authors.forename: Takahiko
authors.initials: T
authors.lastname: Sakamoto
authors.forename: David
authors.initials: D
authors.lastname: Zurakowski
authors.forename: Lennart F
authors.initials: LF
authors.lastname: Duebener
authors.forename: Shinichi
authors.initials: S
authors.lastname: Hatsuoka
authors.forename: Hart G W
authors.initials: HG
authors.lastname: Lidov
authors.forename: Gregory L
authors.initials: GL
authors.lastname: Holmes
authors.forename: Ulrich A
authors.initials: UA
authors.lastname: Stock
authors.forename: Peter C
authors.initials: PC
authors.lastname: Laussen
authors.forename: Richard A
authors.initials: RA
authors.lastname: Jonas
mesh_terms: D000818:Animals; D001835:Body Weight; D001921:Brain / Q000098:blood supply; D002545:Brain Ischemia / Q000209:etiology*; D002315:Cardiopulmonary Bypass; D006324:Heart Arrest, Induced; D006400:Hematocrit; D006438:Hemodilution / Q000009:adverse effects*; D006863:Hydrogen-Ion Concentration; D007036:Hypothermia, Induced / Q000009:adverse effects / Q000379:methods*; D023421:Models, Animal; D009994:Osmolar Concentration; D012039:Regional Blood Flow; D019265:Spectroscopy, Near-Infrared; D013552:Swine