Supraspinal anesthesia: behavioral and electroencephalographic effects of intracerebroventricularly infused pentobarbital, propofol, fentanyl, and midazolam.
BACKGROUND
Anesthetic endpoints of unconsciousness and immobility result from agent effects on both brain and spinal cord that are difficult to separate during systemic administration. To investigate cerebral mechanism of anesthetic-induced unconsciousness, the authors studied behavioral and electrophysiologic effects of four anesthetics infused intracerebroventricularly to conscious rats. The authors aimed to produce progressively increasing anesthetic depths, indicated by electro-encephalographic synchronization and behavioral change.


METHODS
During anesthesia, rats were equipped with intracerebroventricular infusion catheters, hind-paw stimulation, and epidural electrodes to record the electroencephalogram from the somatosensory cortex. Silicone bolus was injected into the fourth ventricle to minimize drug distribution to the spinal cord. 60 min later, 50-min infusion of pentobarbital (6.0 mg/h), fentanyl (0.75 microg/h), propofol (3.0 mg/h), or midazolam (0.24 mg/h) was initiated. Vibrissal, olfactory, corneal, and tail-pinch responses were tested every 10 min.


RESULTS
All agents depressed vibrissal, olfactory, and corneal responses; propofol and pentobarbital produced the strongest effect. All agents except propofol depressed tail-pinch response; fentanyl and pentobarbital produced the strongest effect. All agents except midazolam increased delta power. Pentobarbital enhanced theta power. All agents except fentanyl enhanced alpha and beta power. Pentobarbital and midazolam slightly increased, whereas fentanyl decreased, gamma power. Pentobarbital increased and midazolam decreased somatosensory evoked potential; these changes were small and apparently unrelated to behavior.


CONCLUSIONS
Alpha and beta power increase may reflect sedative component of anesthesia. Simultaneous delta, alpha, and beta power increase may correlate with loss of consciousness. Theta and delta power increase may reflect surgical anesthesia. Opioid-induced gamma power decrease may reflect suppression of pain perception. Pentobarbital-, fentanyl-, and midazolam-induced immobility to noxious stimulation may be mediated supraspinally.
Jugovac
Izabela
I
Department of Anesthesiology, Medical College of Wisconsin, 8701 Watertown Plank Road, Milwaukee, WI 53226, USA.
Imas
Olga
O
Hudetz
Anthony G
AG
D018686:Anesthetics, Intravenous / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D001921:Brain / Q000473:pathology; D003243:Consciousness / Q000187:drug effects; D003627:Data Interpretation, Statistical; D004558:Electric Stimulation; D004567:Electrodes, Implanted; D004569:Electroencephalography / Q000187:drug effects*; D004827:Epilepsy / Q000139:chemically induced / Q000503:physiopathology; D005283:Fentanyl / Q000008:administration & dosage / Q000494:pharmacology*; D006993:Hypnotics and Sedatives / Q000008:administration & dosage / Q000494:pharmacology*; D007276:Injections, Intraventricular; D007427:Intracranial Pressure / Q000187:drug effects; D008297:Male; D008874:Midazolam / Q000008:administration & dosage / Q000494:pharmacology*; D010424:Pentobarbital / Q000008:administration & dosage / Q000494:pharmacology*; D015742:Propofol / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013116:Spinal Cord / Q000473:pathology
D018686:Anesthetics, Intravenous; D006993:Hypnotics and Sedatives; D010424:Pentobarbital; D008874:Midazolam; D005283:Fentanyl; D015742:Propofol