Propofol: relation between brain concentrations, electroencephalogram, middle cerebral artery blood flow velocity, and cerebral oxygen extraction during induction of anesthesia.
ABSTRACT The potential benefit of propofol dose regimens that use physiologic pharmacokinetic modeling to target the brain has been demonstrated in animals, but no data are available on the rate of propofol distribution to the brain in humans. This study measured the brain uptake of propofol in humans and the simultaneous effects on electroencephalography, cerebral blood flow velocity (V(mca)), and cerebral oxygen extraction.
Seven subjects had arterial and jugular bulb catheters placed before induction. Electroencephalography and V(mca) were recorded during induction with propofol while blood samples were taken from both catheters for later propofol analysis. Brain uptake of propofol was calculated using mass balance principles, with effect compartment modeling used to quantitate the rate of uptake.
Bispectral index (electroencephalogram) values decreased to a minimum value of approximately 4 at around 7 min from the onset of propofol administration and then slowly recovered. This was accompanied by decreases in V(mca), reaching a minimum value of approximately 40% of baseline. Cerebral oxygen extraction did not change, suggesting parallel changes in cerebral metabolism. There was slow equilibrium of propofol between the blood and the brain (t(1/2keo) of 6.5 min), with a close relation between brain concentrations and bispectral index, although with considerable interpatient variability. The majority of the decreases in V(mca), and presumably cerebral metabolism, corresponded with bispectral index values reaching 40-50 and the onset of burst suppression.
Description of brain distribution of propofol will allow development of physiologic pharmacokinetic models for propofol and evaluation of dose regimens that target the brain.
SourceAvailable from: Zeljko Bosnjak[Show abstract] [Hide abstract]
ABSTRACT: Recent studies in various animal models have suggested that anesthetics such as propofol, when administered early in life, can lead to neurotoxicity. These studies have raised significant safety concerns regarding the use of anesthetics in the pediatric population and highlight the need for a better model to study anesthetic-induced neurotoxicity in humans. Human embryonic stem cells are capable of differentiating into any cell type and represent a promising model to study mechanisms governing anesthetic-induced neurotoxicity.Anesthesiology 06/2014; DOI:10.1097/ALN.0000000000000345 · 6.17 Impact Factor
[Show abstract] [Hide abstract]
ABSTRACT: Comparative study between fast and slow induction of propofol given by target-controlled infusion: expected propofol concentration at the effect site. Randomized controlled trialRevista Brasileira de Anestesiologia 11/2014; 65(2):99. DOI:10.1016/j.bjane.2013.07.015 · 0.42 Impact Factor
[Show abstract] [Hide abstract]
ABSTRACT: Propofol and remifentanil alter intracellular Ca(2+) concentration ([Ca(2+)]i) in neural stem/progenitor cells by activating γ-aminobutyric acid type A receptors and by reducing testosterone levels. However, whether this process affects neural stem/progenitor cell proliferation and differentiation remains unknown. In the present study, we applied propofol and remifentanil, alone or in combination, at low, moderate or high concentrations (1, 2-2.5 and 4-5 times the clinically effective blood drug concentration), to neural stem/progenitor cells from the hippocampi of newborn rat pups. Low concentrations of propofol, remifentanil or both had no noticeable effect on cell proliferation or differentiation; however, moderate and high concentrations of propofol and/or remifentanil markedly suppressed neural stem/progenitor cell proliferation and differentiation, and induced a decrease in [Ca(2+)]i during the initial stage of neural stem/progenitor cell differentiation. We therefore propose that propofol and remifentanil interfere with the proliferation and differentiation of neural stem/progenitor cells by altering [Ca(2+)]i. Our findings suggest that propofol and/or remifentanil should be used with caution in pediatric anesthesia.Neural Regeneration Research 11/2014; 9(22):2002-7. DOI:10.4103/1673-5374.145384 · 0.23 Impact Factor