No correlation between remifentanil blood, cerebrospinal fluid and cerebral extracellular fluid levels and TCI prediction: a pharmacokinetic study

Minerva Anestesiol. 2015 Mar;81(3):305-11. Epub 2014 Jul 24.

Abstract

Background: The aims of this paper were to elucidate the difference in concentration among remifentanil blood, cerebrospinal fluid and cerebral extracellular fluid levels, and to verify the presumable existence of a correlation between arterial and cerebral remifentanil. We used brain microdialysis to shed light on this aspect of the pharmacokinetic and to correlate these findings with Minto's model.

Methods: The study population was formed by 9 patients scheduled for elective intracranial surgery for cerebral supratentorial neoplasia. All patients received general anaesthetic; 100 microliters of dialysate were collected. Furthermore, arterial blood samples of 3 mL each were collected, respectively one at the beginning and one at the end of the sampling period. We determined the concentration of remifentanil and its main metabolite, remifentanil acid, in the blood and in the brain. The predictive performance of the Minto pharmacokinetic parameter set was evaluated by examining the performance error.

Results: The mean Performance Error was -45.13% (min -21.80, max -88.75) for the first series of arterial samples, -38.29% (min -6.57, max -79.17) for the second one and 67.73% (min 7, max -93.12) for the extra cellular fluid sample. The concentration of remifentanil set pumps was correlated with blood concentration for both series of samples. Neither the set concentration, nor the arterial samples were correlated with extra cellular fluid values.

Conclusion: There was a wide interindividual variability with regard both to blood and cerebral remifentanil concentration. Moreover, the ratio between arterial blood and cerebral remifentanil was not consistent among our patients in spite of a stable infusion rate of remifentanil; at the end we found a trend of over prediction in the ratio between the various compartments examined.

MeSH terms

  • Adult
  • Anesthesia, Intravenous / methods*
  • Anesthetics, Intravenous / blood
  • Anesthetics, Intravenous / cerebrospinal fluid
  • Anesthetics, Intravenous / pharmacokinetics*
  • Brain Neoplasms / surgery
  • Extracellular Fluid / metabolism*
  • Female
  • Humans
  • Infusions, Intravenous
  • Male
  • Middle Aged
  • Neurosurgical Procedures
  • Piperidines / blood
  • Piperidines / cerebrospinal fluid
  • Piperidines / pharmacokinetics*
  • Predictive Value of Tests
  • Remifentanil

Substances

  • Anesthetics, Intravenous
  • Piperidines
  • Remifentanil