Propofol: Relation between brain concentrations, electroencephalogram, middle cerebral artery blood flow velocity and cerebral oxygen extraction during induction of anesthesia

Department of Anaesthesia and Intensive Care, Royal Adelaide Hospital, Adelaide University, North Terrace, Adelaide, South Australia 5000, Australia.
Anesthesiology (Impact Factor: 5.88). 01/2003; 97(6):1363-70. DOI: 10.1097/00000542-200212000-00006
Source: PubMed


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.

8 Reads
    • "It is generally assumed that the rate of equilibration between the plasma and effect site of drug is independent of rate of drug administration, several studies suggest that this may not be the case for intravenous anesthetics. A complex interaction of rate, dosage and duration of anesthetic exposure as well as physiological factors might influence the plasma effect site concentration.[4] Various infusion rates of propofol have been used by different authors[5–7] to achieve a therapeutic blood concentration of propofol. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Clinically optimized focusing of drug administration to specific need of patient with bispectral index (BIS) monitoring results in reduced dose and faster recovery of consciousness. This study was planned with an aim to study and compare the conventional clinical end point or BIS on the requirement of dosage of propofol, hemodynamic effects, and BIS alterations following propofol induction. 70 patients, ASA I and II, 20-60 years undergoing elective surgical procedure under general anesthesia with endotracheal intubation were selected and divided into two groups. Group A received (inj.) fentanyl (2 μg/kg), followed 3 min later by inj. propofol at the rate of 30 mg/kg/hr infusion till the loss of response to verbal command while group B received inj. fentanyl (2 μg/kg), followed 3 min later by inj. propofol at the rate of 30 mg/kg/hr infusion. The end point of hypnosis was when the BIS value was sustained for 1 min at 48±2. The patients were intubated. Total induction dose of propofol was noted in each group. The value of BIS and hemodynamic parameters (heart rate, systolic/diastolic blood pressure) were noted at the time of loss of consciousness, at the time of intubation, and 1 min after intubation, thereafter every minute for first 10 min and thereafter every 10 min till end of surgery. Any involuntary muscle activity such as jerky movements, dystonic posturing, and opisthotonos were also recorded. The mean dose of propofol used in groups A and B were 1.85±0.48 mg/kg and 1.79±0.41 mg/kg, respectively. The dosage used in group B were less but not clinically significant (P=0.575). On comparing the dosage of propofol in males among the groups there was a significantly lower dosage of propofol required in group B (2.06±0.45 mg/kg and 1.83±0.32 mg/kg, respectively, P=0.016). This decrease however was not seen in female patients dosage being 1.65±0.44 mg/kg and 1.75±0.49 mg/kg, respectively (P=0.372). The hemodynamic variables including heart rate, systolic/diastolic blood pressure and BIS were comparable within the group at induction, post-induction, and intubation. However, there was a significant increase in all the parameters at postintubation readings (P<0.001). No significant difference in the induction dose of propofol was observed when assessed clinically (loss of verbal response) or by BIS monitoring. Traditional teaching to titrate the dose of propofol and depth of anesthesia during intubation by loss of verbal response is as good as BIS value monitoring.
    02/2013; 7(1):75-79. DOI:10.4103/1658-354X.109819
  • Source
    • "Due to the fast onset and recovery following administration, repeated neurologic examinations are easy to assess such as a child with sickle cell disease who comes in with altered mental status due to a stroke. Propofol also has anticonvulsant properties and reduces ICP which can be advantageous in sedating a patient with epilepsy or a patient with concerns for obstructive hydrocephalus due to a malfunctioning ventriculoperitoneal shunt to obtain diagnostic neuroradiologic imaging [44–46]. While there have been cases of propofol providing adequate sedation and successfully treating intracranial hypertension [47, 48], several pediatric traumatic brain injury case reports have reported metabolic acidosis and death in patients on prolonged (24 hrs) continuous infusion of propofol [49–53]. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Sedation and analgesia performed by the pediatrician and pediatric subspecialists are becoming increasingly common for diagnostic and therapeutic purposes in children with developmental disabilities and neurologic disorders (autism, epilepsy, stroke, obstructive hydrocephalus, traumatic brain injury, intracranial hemorrhage, and hypoxic-ischemic encephalopathy). The overall objectives of this paper are (1) to provide an overview on recent studies that highlight the increased risk for respiratory complications following sedation and analgesia in children with developmental disabilities and neurologic disorders, (2) to provide a better understanding of sedatives and analgesic medications which are commonly used in children with developmental disabilities and neurologic disorders on the central nervous system.
    International Journal of Pediatrics 07/2010; 2010. DOI:10.1155/2010/189142
  • Source
    • "Intravenous and inhalational anesthetics have differing effects on cerebral hemodynamics. Inhalational anesthetics cause some vasodilation, whereas intravenous anesthetics do not [1]–[5]. In addition, general anesthetics suppress the activity of brain glucose metabolism in animals and humans in a dose-dependent manner, and administration of a number of anesthetics suppress glucose utilization in the brain [6]–[8]. "
    [Show abstract] [Hide abstract]
    ABSTRACT: General anesthesia is routinely used as a surgical procedure and its safety has been endorsed by clinical outcomes; however, its effects at the molecular level have not been elucidated. General anesthetics influence glucose metabolism in the brain. However, the effects of anesthetics on brain metabolites other than those related to glucose have not been well characterized. We used a pattern recognition analysis of proton nuclear magnetic resonance spectra to visualize the changes in holistic brain metabolic phenotypes in response to the widely used intravenous anesthetic propofol and the volatile anesthetic isoflurane. Rats were randomized into five groups (n = 7 each group). Propofol and isoflurane were administered to two groups each, for 2 or 6 h. The control group received no anesthesia. Brains were removed directly after anesthesia. Hydrophilic compounds were extracted from excised whole brains and measured by proton nuclear magnetic resonance spectroscopy. All spectral data were processed and analyzed by principal component analysis for comparison of the metabolite profiles. Data were visualized by plotting principal component (PC) scores. In the plots, each point represents an individual sample. The propofol and isoflurane groups were clustered separately on the plots, and this separation was especially pronounced when comparing the 6-h groups. The PC scores of the propofol group were clearly distinct from those of the control group, particularly in the 6-h group, whereas the difference in PC scores was more subtle in the isoflurane group and control groups. The results of the present study showed that propofol and isoflurane exerted differential effects on holistic brain metabolism under anesthesia.
    PLoS ONE 06/2010; 5(6):e11172. DOI:10.1371/journal.pone.0011172 · 3.23 Impact Factor
Show more