Anesthesiology
-
Cerebral blood flow (CBF) is rigorously regulated by various powerful mechanisms to safeguard the match between cerebral metabolic demand and supply. The question of how a change in cardiac output (CO) affects CBF is fundamental, because CBF is dependent on constantly receiving a significant proportion of CO. The authors reviewed the studies that investigated the association between CO and CBF in healthy volunteers and patients with chronic heart failure. ⋯ Given that CBF regulation is multifactorial but the various processes must exert their effects on the cerebral circulation simultaneously, the authors propose a conceptual framework that integrates the various CBF-regulating processes at the level of cerebral arteries/arterioles while still maintaining autoregulation. The clinical implications pertinent to the effect of CO on CBF are discussed. Outcome research relating to the management of CO and CBF in high-risk patients or during high-risk surgeries is needed.
-
The optimal oxygen administration strategy during resuscitation from hemorrhagic shock (HS) is still controversial. Improving oxygenation and mitigating oxidative stress simultaneously seem to be contradictory goals. To maximize oxygen delivery while minimizing oxidative damage, the authors proposed the notion of gradually increased oxygen administration (GIOA), which entails making the arterial blood hypoxemic early in resuscitation and subsequently gradually increasing to hyperoxic, and compared its effects with normoxic resuscitation, hyperoxic resuscitation, and hypoxemic resuscitation in severe HS. ⋯ GIOA improved systemic/tissue oxygenation and mitigated oxidative stress simultaneously after resuscitation from severe HS. GIOA may be a promising strategy to improve resuscitation from HS and deserves further investigation.
-
Clinical Trial
Methadone Pharmacogenetics: CYP2B6 Polymorphisms Determine Plasma Concentrations, Clearance, and Metabolism.
Interindividual variability in methadone disposition remains unexplained, and methadone accidental overdose in pain therapy is a significant public health problem. Cytochrome P4502B6 (CYP2B6) is the principle determinant of clinical methadone elimination. The CYP2B6 gene is highly polymorphic, with several variant alleles. CYP2B6.6, the protein encoded by the CYP2B6*6 polymorphism, deficiently catalyzes methadone metabolism in vitro. This investigation determined the influence of CYP2B6*6, and other allelic variants encountered, on methadone concentrations, clearance, and metabolism. ⋯ CYP2B6 polymorphisms influence methadone plasma concentrations, because of altered methadone metabolism and thus clearance. Genetic influence is greater for oral than IV methadone and S- than R-methadone. CYP2B6 pharmacogenetics explains, in part, interindividual variability in methadone elimination. CYP2B6 genetic effects on methadone metabolism and clearance may identify subjects at risk for methadone toxicity and drug interactions.