Physostigmine and Methylphenidate Induce Distinct Arousal States During Isoflurane General Anesthesia in Rats.

Background: Although emergence from general anesthesia is clinically treated as a passive process driven by the pharmacokinetics of drug clearance, agents that hasten recovery from general anesthesia may be useful for treating delayed emergence, emergence delirium, and postoperative cognitive dysfunction. Activation of central monoaminergic neurotransmission with methylphenidate has been shown to induce reanimation (active emergence) from general anesthesia. Cholinergic neurons in the brainstem and basal forebrain are also known to promote arousal.

Electrical stimulation of the ventral tegmental area induces reanimation from general anesthesia.

Background: Methylphenidate or a D1 dopamine receptor agonist induces reanimation (active emergence) from general anesthesia. The authors tested whether electrical stimulation of dopaminergic nuclei also induces reanimation from general anesthesia.

Methods: In adult rats, a bipolar insulated stainless steel electrode was placed in the ventral tegmental area (VTA, n = 5) or substantia nigra (n = 5).

A brain-machine interface for control of medically-induced coma.

Medically-induced coma is a drug-induced state of profound brain inactivation and unconsciousness used to treat refractory intracranial hypertension and to manage treatment-resistant epilepsy. The state of coma is achieved by continually monitoring the patient's brain activity with an electroencephalogram (EEG) and manually titrating the anesthetic infusion rate to maintain a specified level of burst suppression, an EEG marker of profound brain inactivation in which bursts of electrical activity alternate with periods of quiescence or suppression. The medical coma is often required for several days.

A brain-machine interface for control of burst suppression in medical coma.

Burst suppression is an electroencephalogram (EEG) marker of profound brain inactivation and unconsciousness and consists of bursts of electrical activity alternating with periods of isoelectricity called suppression. Burst suppression is the EEG pattern targeted in medical coma, a drug-induced brain state used to help recovery after brain injuries and to treat epilepsy that is refractory to conventional drug therapies. The state of coma is maintained manually by administering an intravenous infusion of an anesthetic, such as propofol, to target a pattern of burst suppression on the EEG.

Real-time segmentation of burst suppression patterns in critical care EEG monitoring.

Objective: Develop a real-time algorithm to automatically discriminate suppressions from non-suppressions (bursts) in electroencephalograms of critically ill adult patients.

Methods: A real-time method for segmenting adult ICU EEG data into bursts and suppressions is presented based on thresholding local voltage variance. Results are validated against manual segmentations by two experienced human electroencephalographers.

Real-time closed-loop control in a rodent model of medically induced coma using burst suppression.

Background: A medically induced coma is an anesthetic state of profound brain inactivation created to treat status epilepticus and to provide cerebral protection after traumatic brain injuries. The authors hypothesized that a closed-loop anesthetic delivery system could automatically and precisely control the electroencephalogram state of burst suppression and efficiently maintain a medically induced coma.

Methods: In six rats, the authors implemented a closed-loop anesthetic delivery system for propofol consisting of: a computer-controlled pump infusion, a two-compartment pharmacokinetics model defining propofol's electroencephalogram effects, the burst-suppression probability algorithm to compute in real time from the electroencephalogram the brain's burst-suppression state, an online parameter-estimation procedure and a proportional-integral controller.

Activation of D1 dopamine receptors induces emergence from isoflurane general anesthesia.

Background: A recent study showed that methylphenidate induces emergence from isoflurane anesthesia. Methylphenidate inhibits dopamine and norepinephrine reuptake transporters. The objective of this study was to test the hypothesis that selective dopamine receptor activation induces emergence from isoflurane anesthesia.

Active emergence from propofol general anesthesia is induced by methylphenidate.

Background: A recent study showed that methylphenidate induces emergence from isoflurane general anesthesia. Isoflurane and propofol are general anesthetics that may have distinct molecular mechanisms of action. The objective of this study was to test the hypothesis that methylphenidate actively induces emergence from propofol general anesthesia.

A state-space model of the burst suppression ratio.

Burst suppression is an electroencephalogram pattern observed in states of severely reduced brain activity, such as general anesthesia, hypothermia and anoxic brain injuries. The burst suppression ratio (BSR), defined as the fraction of EEG spent in suppression per epoch, is the standard quantitative measure used to characterize burst suppression. We present a state space model to compute a dynamic estimate of the BSR as the instantaneous probability of suppression.

Methylphenidate actively induces emergence from general anesthesia.

Background: Although accumulating evidence suggests that arousal pathways in the brain play important roles in emergence from general anesthesia, the roles of monoaminergic arousal circuits are unclear. In this study, the authors tested the hypothesis that methylphenidate (an inhibitor of dopamine and norepinephrine transporters) induces emergence from isoflurane general anesthesia.

Methods: Using adult rats, the authors tested the effect of intravenous methylphenidate on time to emergence from isoflurane general anesthesia.