The influence of fentanyl upon cerebral high-energy metabolites, lactate, and glucose during severe hypoxia in the rat

Abstract

The effects of intravenous administration of high-dose fentanyl (100 μg·kg-1, loading dose followed by an infusion of 200 μg·kg-1·h-1) were compared with those of a barbiturate (pentobarbital sodium 25 mg·kg-1, intraperitoneal) or hypothermia (rectal temperature 32°C) on changes in cerebral cortical tissue levels of adenosine triphosphate (ATP), phosphocreatine (PCr), lactate, and glucose in severely hypoxemic rats (Pa(O2) 13-23 mmHg for 20 min) with unilateral (left side) carotid ligation (10-12 animals in each group). Ligation of the carotid artery alone produced no change in brain high-energy metabolites, lactate, or glucose. The control values on the ligated side (nitrous oxide, 70%, + normoxia group) for cortical ATP, PCr, lactate, and glucose were 2.86 ± 0.09 (μmol·g-1 wet weight, mean ± 1 SE), 3.83 ± 0.11, 1.68 ± 0.21, and 3.29 ± 0.47, respectively. Hypoxia (nitrous oxide, 70%, + hypoxia group) produced a significant (P < 0.05) decrease in ATP (1.83 ± 0.37) and PCr (1.93 ± 0.48) and an increase in lactate (15.8 ± 1.77) compared with the normoxic group, whereas brain glucose was not significantly changed (1.97 ± 0.65). Fentanyl (fentanyl + hypoxia group) did not prevent the deleterious effects of hypoxia on cortical high energy metabolites (ATP, 2.0 ± 0.27; PCr, 2.24 ± 0.3) or lactate (19.33 ± 3.16); however, fentanyl caused no alteration in high-energy cerebral metabolite concentrations in normoxic rats, nor did fentanyl produce a significant difference in brain tissue glucose or lactate. In contrast to the effects of fentanyl, pentobarbital (barbiturate + hypoxia group) or hypothermia (nitrous oxide + hypothermia + hypoxia group) prevented the significant decrease in ATP or PCr and attenuated, but did not eliminate, the increase in lactate. Though hypoxia produced changes on the unligated (right) side these tended to be similar to the ligated side though typically less severe. Blood glucose concentrations were determined on samples obtained before and after the experimental insult. The concentrations of glucose were variable, but there appeared to be no relationship between treatment or changes in brain metabolites and blood glucose. In summary, fentanyl in doses that have previously been shown to reduce cerebral oxygen metabolism by 35% did not prevent or retard the loss of cerebral high-energy metabolites or the production of lactate during 20 min of severe hypoxia. This was in distinct contrast to the effects of mild hypothermia or an anesthetic dose of pentobarbital.