title: Barbiturates impair cerebral metabolism during hypothermic circulatory arrest.
abstract: Barbiturates have been used as a method of cerebral protection in patients undergoing open heart operations. Phosphorus 31 nuclear magnetic resonance spectroscopy was used to assess barbiturate-induced alterations in the cerebral tissue energy state during cardiopulmonary bypass, hypothermic circulatory arrest, and subsequent reperfusion. Sheep were positioned in a 4.7-T magnet with a radiofrequency coil over the skull. Nuclear magnetic resonance spectra were obtained at 37 degrees C, during cardiopulmonary bypass before and after drug administration at 37 degrees C and 15 degrees C, throughout a 1-hour period of hypothermic circulatory arrest, and during a 2-hour reperfusion period. A group of animals (n = 8) was administered a bolus of sodium thiopental (40 mg/kg) during bypass at 37 degrees C followed by an infusion of 3.3 mg.kg-1 x min-1 until hypothermic arrest. A control group of animals (n = 8) received no barbiturate. The phosphocreatine/adenosine triphosphate ratio, reflecting tissue energy state, was lower during cardiopulmonary bypass at 15 degrees C in the treated animals compared with controls (1.06 +/- 0.08 versus 1.36 +/- 0.17; p < 0.001). Lower phosphocreatine/adenosine triphosphate ratios were observed throughout all periods of arrest and reperfusion in the barbiturate-treated animals compared with controls (p < or = 0.01). Thiopental prevented the increase in cerebral energy state normally observed with hypothermia and resulted in a decrease in the energy state of the brain during hypothermic circulatory arrest and subsequent reperfusion. These results suggest that thiopental administration before a period of hypothermic circulatory arrest may prove detrimental to the preservation of the energy state of the brain.
authors.affiliation: Surgery Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland.
authors.forename: M G
authors.initials: MG
authors.lastname: Siegman
authors.forename: R V
authors.initials: RV
authors.lastname: Anderson
authors.forename: R S
authors.initials: RS
authors.lastname: Balaban
authors.forename: T L
authors.initials: TL
authors.lastname: Ceckler
authors.forename: R E
authors.initials: RE
authors.lastname: Clark
authors.forename: J A
authors.initials: JA
authors.lastname: Swain
mesh_terms: D000255:Adenosine Triphosphate / Q000737:chemistry*; D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D001923:Brain Chemistry; D004734:Energy Metabolism; D005069:Evaluation Studies as Topic; D006324:Heart Arrest, Induced / Q000379:methods*; D007036:Hypothermia, Induced / Q000379:methods*; D009682:Magnetic Resonance Spectroscopy; D010725:Phosphocreatine / Q000737:chemistry*; D012756:Sheep; D013874:Thiopental / Q000008:administration & dosage / Q000009:adverse effects*
chemical_list: D010725:Phosphocreatine; D000255:Adenosine Triphosphate; D013874:Thiopental