Reversal of general anesthesia by administration of methylphenidate, amphetamine, modafinil, amantadine, and/or caffeine

• US 10,299,720 B2
• Filed: 02/10/2015
• Issued: 05/28/2019
• Est. Priority Date: 09/01/2010
• Status: Active Grant

• Current Assignee: The General Hospital Corporation (Mass General Brigham, Inc.)
• Original Assignee: The General Hospital Corporation (Mass General Brigham, Inc.)
• Inventors: Brown, Emery N., Purdon, Patrick L.
• Primary Examiner(s): Riggs, II, Larry D
• Application Number:
  US14/618,978
• Publication Number:
  US 20150196249A1
• Time in Patent Office: 1,568 Days
• Field of Search: None
• CPC Class Codes: A61B 5/316 Modalities, i.e. specific diagnostic methods
• CPC Class Codes: A61B 5/369 Electroencephalography [EEG] devices for psychotechnics A61B5/16
• CPC Class Codes: A61B 5/4821 Determining level or depth of anaesthesia A61B5/1106 takes precedence
• CPC Class Codes: A61K 31/13 Amines A61K31/04 takes precedence
• CPC Class Codes: A61K 31/137 Arylalkylamines, e.g. amphetamine, epinephrine, salbutamol, ephedrine or methadone
• CPC Class Codes: A61K 31/165 having aromatic rings, e.g. colchicine, atenolol, progabide
• CPC Class Codes: A61K 31/4458 only substituted in position 2, e.g. methylphenidate
• CPC Class Codes: A61K 31/522 having oxo groups directly attached to the heterocyclic ring, e.g. hypoxanthine, guanine, acyclovir
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61K 9/0019 Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner non-active ingredients are additionally classified in A61K47/00
• CPC Class Codes: A61P 23/00 Anaesthetics

Abstract

The present invention generally relates to compositions comprising anesthesia-reversing agents which facilitate or increase the time of awakening or reverse the effects of general anesthesia-induced unconsciousness. In some embodiments, the anesthesia reversing agent can be selected from any or a combination of methylphenidate (MPH), amphetamine, modafinil, amantadine, caffeine, or analogs or derivatives thereof. In some embodiments, compositions comprising at least one or more anesthesia-reversing agents can be used to facilitate awakening from anesthesia without or decreasing occurrence of delirium, and can be used in methods to treat or prevent the symptoms associated with emergence delirium, as well as treat a subject oversedated with general an esthesia. The invention also relates to methods for administering these compositions comprising anesthesia-reversing agents to subjects and for use.

Claims

1. An electronic method for determining a state of consciousness from electroencephalogram (“

EEG”

) signals acquired from a subject experiencing an administration of at least one anesthetic agent or at least one drug to facilitate emergence from anesthesia, the electronic method comprising;

acquiring EEG signals from EEG electrodes the EEG signals responsive to said state of consciousness of the subject experiencing said administration of said at least one anesthetic agent or said at least one drug to facilitate emergence from anesthesia;

electronically determining physiological data responsive to said EEG signals;

electronically processing said physiological data including applying at least one window to the physiological data;

for the at least one window, electronically calculating a multi-taper spectrum estimation; and

electronically generating a viewable spectrogram responsive to the multi-taper spectrum estimation, wherein the spectrogram is responsive of the state of consciousness of the subject.

2. The method of claim 1 further comprising electronically determining physiological effects on the state of consciousness of the subject of the at least one anesthetic agent or at let o one drug to facilitate emergence from anesthesia using the spectrogram.

3. The method of claim 2 wherein determining physiological effects includes electronically comparing the spectrogram to reference spectrograms.

4. The method of claim 1 further comprising electronically determining a therapeutically effective amount of the at least one anesthetic agent or at least one drug to facilitate emergence from anesthesia using the spectrogram.

5. The method of claim 4 wherein determining a therapeutically effective amount includes electronically comparing the spectrogram to reference spectrograms.

6. The method of claim 1 wherein electronically processing including applying at least one window includes applying a sliding window.

7. The method of claim 6 wherein applying a sliding window includes applying said sliding window stepped through a 0.05 second interval.

8. The method of claim 1 wherein calculating the multi-taper spectrum estimation includes calculating said multi-taper estimation using 5 tapers.

9. The method of claim 6, wherein electronically processing including applying at least one window includes applying said sliding window, said sliding window using a duration of 2 seconds.

10. The method of claim 1, further comprising electronically generating a report responsive said spectrogram.