Propofol Pharmacodynamics and Bispectral Index During Key Moments of Awake Craniotomy.
BACKGROUND
During awake craniotomy, the patient's language centers are identified by neurological testing requiring a fully awake and cooperative patient. Hence, anesthesia aims for an unconscious patient at the beginning and end of surgery but an awake and responsive patient in between. We investigated the plasma (Cplasma) and effect-site (Ceffect-site) propofol concentration as well as the related Bispectral Index (BIS) required for intraoperative return of consciousness and begin of neurological testing.


METHODS
In 13 patients, arterial Cplasma were measured by high-pressure liquid chromatography and Ceffect-site was estimated based on the Marsh and Schnider pharmacokinetic/dynamic (pk/pd) models. The BIS, Cplasma and Ceffect-site were compared during the intraoperative awakening period at designated time points such as return of consciousness and start of the Boston Naming Test (neurological test).


RESULTS
Return of consciousness occurred at a BIS of 77±7 (mean±SD) and a measured Cplasma of 1.2±0.4 μg/mL. The Marsh model predicted a significantly (P<0.001) higher Cplasma of 1.9±0.4 µg/mL as compared with the Schnider model (Cplasma=1.4±0.4 µg/mL) at return of consciousness. Neurological testing was possible as soon as the BIS had increased to 92±6 and measured Cplasma had decreased to 0.8±0.3 µg/mL. This translated into a time delay of 23±12 minutes between return of consciousness and begin of neurological testing. At begin of neurological testing, Cplasma according to Marsh (Cplasma=1.3±0.5 µg/mL) was significantly (P=0.002) higher as compared with the Schnider model (Cplasma=1.0±0.4 µg/mL).


CONCLUSIONS
To perform intraoperative neurological testing, patients are required to be fully awake with plasma propofol concentrations as low as 0.8 µg/mL. Following our clinical setup, the Schnider pk/pd model estimates propofol concentrations significantly more accurate as compared with the Marsh model at this neurologically crucial time point.
Departments of Anesthesiology and Intensive Care Medicine.
Martin
M
Soehle
Department of Anesthesiology and Intensive Care Medicine, Sana Clinic Berlin-Lichtenberg, Berlin.
Christina F
CF
Wolf
C3P Analysis, Pharmacy Department, Plymouth Hospitals NHS Trust, Plymouth, UK.
Melanie J
MJ
Priston
Department of Neurosurgery, University of Aachen, Aachen.
Georg
G
Neuloh
Epileptology, University of Bonn, Bonn.|Epilepsy Centre Bethel, Mara Hospital, Bielefeld, Germany.
Christian G
CG
Bien
Departments of Anesthesiology and Intensive Care Medicine.
Andreas
A
Hoeft
Departments of Anesthesiology and Intensive Care Medicine.
Richard K
RK
Ellerkmann
D000328:Adult; D000368:Aged; D000465:Algorithms; D000758:Anesthesia; D018686:Anesthetics, Intravenous / Q000097:blood / Q000493:pharmacokinetics*; D003243:Consciousness; D056805:Consciousness Monitors; D003399:Craniotomy / Q000379:methods*; D004569:Electroencephalography; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D008875:Middle Aged; D009483:Neuropsychological Tests; D015742:Propofol / Q000097:blood / Q000493:pharmacokinetics*; D014851:Wakefulness
D018686:Anesthetics, Intravenous; D015742:Propofol