Cerebrospinal fluid concentrations of propofol during anaesthesia in humans

Abstract

The concentration of propofol in and surrounding the human brain during propofol anaesthesia is unknown. We measured simultaneously the concentration of propofol in cerebrospinal fluid (CSF) from an indwelling intraventricular catheter and the concentration in arterial blood in five neurosurgical patients before, during induction (at 2.5 and 5 min) and during a maintenance propofol infusion (at 15 and 30 min). After induction of anaesthesia with propofol 2 mg kg-1, anaesthesia was maintained with an infusion of 8 mg kg-1 h-1 for 15 min and then reduced to 6 mg kg-1 h-1. The plasma concentration of propofol increased rapidly during induction and reached a plateau concentration of mean 2.24 (SD 0.66) micrograms ml-1 after 5 min. The concentration of propofol in CSF showed a slower increase during induction and remained almost constant at 35.5 (19.6) ng ml-1 at 15-30 min after induction. The CSF concentration of propofol that we measured was 1.6% of the plasma concentration and consistent with the high protein binding of the drug in plasma.

HCN1 Channels as Targets for Anesthetic and Nonanesthetic Propofol Analogs in the Amelioration of Mechanical and Thermal Hyperalgesia in a Mouse Model of Neuropathic Pain

“…Using the same pharmacokinetic model as the Diprofusor software (Dawidowicz et al, 2002), total effect site propofol concentration in Engdahl et al (1998) is estimated to be 2.75-2.80 mg/ml and 3.25-3.30 mg/ml by , both of which are in good agreement with the observed values. Our modeling is based on a 30-year-old man, with height of 178 cm and weight of 75 kg.…”

“…2,6-DTBP does not potentiate GABA A -Rs nor is it a general anesthetic at concentrations equivalent to those that are hypnotic for propofol (James and Glen, 1980;Engdahl et al, 1998;Krasowski et al, 2001;Dawidowicz et al, 2002Dawidowicz and Kalitynski, 2003). Thus, if potentiation of GABA A -Rs represents a critical aspect of propofol's efficacy as a neuropathic pain-selective analgesic, then 2,6-DTBP would be expected to be ineffective.…”

“…a The fixed-rate dosing regimens in Engdahl et al (1998) and yield comparable total propofol plasma levels as the target controlled infusion regimens utilized in Dawidowicz et al (2002) and Dawidowicz and Kalitynski (2003). Using the same pharmacokinetic model as the Diprofusor software (Dawidowicz et al, 2002), total effect site propofol concentration in Engdahl et al (1998) is estimated to be 2.75-2.80 mg/ml and 3.25-3.30 mg/ml by , both of which are in good agreement with the observed values.…”

Application of integrative thermodynamic-hemodynamic-pharmacokinetic model to propofol anesthesia for hypothermic decompression

“…Especially, in neurosurgical patients, the propofol concentration in CSF was 50-to 100-fold lower than in blood [13]. The simulation result (1.4%) agrees well with the clinical knowledge.…”

“…Various propofol infusion rates are assumed to the pharmacokinetic model, and then the simulation results of transient behavior of the model are compared with the published clinical data or theoretical results. Figure 2 shows an example of the agreement of the simulated propofol concentration in the arterial blood and that in the CSF with the data measured by Engdahl and colleagues [13], where a general anesthesia was induced into neurosurgical patients with propofol 2 mg kg -1 intravenously within 2 min and maintained with a continuous infusion of propofol commenced 5 min after the start of induction at an initial infusion rate of 8 mg kg -1 h -1 for 15 min and then reduced to 6 mg kg -1 h -1 . Concerning the simulation results, plasma propofol concentrations of the model at 2.5, 5, 15 and 30 min are 5.0, 1.8, 2.7 and 2.8 µg ml -1 , respectively, as shown in Fig.…”