Pharmacodynamic Effects of Ketamine on Epileptiform Activity and Continuous Electroencephalography (cEEG) Frequency Spectra
Abstract number :
1.299
Submission category :
7. Anti-seizure Medications / 7C. Cohort Studies
Year :
2021
Submission ID :
1826518
Source :
www.aesnet.org
Presentation date :
12/4/2021 12:00:00 PM
Published date :
Nov 22, 2021, 06:54 AM
Authors :
Megan Barra, PharmD, BCPS, BCCCP - Massachusetts General Hospital; Lisa Coles, PhD - Department of Experimental and Clinical Pharmacology - College of Pharmacy and Center for Orphan Drug Research, University of Minnesota; Can Ozan Tan, PhD - Department of Physical Medicine and Rehabilitation - Spaulding Rehabilitation Hospital; Jaideep Kapur, MBBS, PhD - Department of Neurology - University of Virginia; James Chamberlain, MD - Division of Emergency Medicine - Children’s National Medical Center; Robert Silbergleit, MD - Department of Emergency Medicine - University of Michigan; Thomas Bleck, MD - Feinberg School of Medicine, Northwestern University and Rush Medical College; Andrew Cole, MD - Department of Neurology - Massachusetts General Hospital; Shlomo Shinnar, MD, PhD - Montefiore Medical Center, Albert Einstein College of Medicine; James Cloyd, PharmD - Department of Experimental and Clinical Pharmacology - College of Pharmacy and Center for Orphan Drug Research, University of Minnesota; Eric Rosenthal, MD - Department of Neurology - Massachusetts General Hospital
Rationale: Ketamine is an emerging therapy for refractory status epilepticus (RSE) associated with GABA-mediated pharmacoresistance. We evaluated pharmacodynamic signatures of ketamine on epileptiform activity and EEG frequency spectra to infer the peak and duration of expected effect and recovery.
Methods: We evaluated frequency spectral power and epileptiform abnormality burden as pharmacodynamic responses in consecutive patients bolused with ketamine during cEEG monitoring for RSE (04/2016-02/2021). Frequency-specific power (z-scores standardized to a 15-minute pre-administration baseline) and global spike count burden were measured (Persyst, Inc.) at baseline and 5-minute post-administration windows. An Emax pharmacodynamic model examined the association between EEG changes and estimated blood concentration.
Results: 18 patients were treated with bolus ketamine (1.3 mg/kg [IQR 0.9, 1.6] median dose; 5 [4,7] median baseline antiseizure or anesthetic medications). The baseline spike count (median 25 [6, 216] spikes/300 second) decreased by -10 [-81, 3] at 30 minutes and -15 [-69, -5] at 60 minutes. Ketamine ≥ 1.5mg/kg was associated with decreased power in the 1-4-Hz, 4-8-Hz, 8-13-Hz, 13-20-Hz, 25-30-Hz bands in 89%, 78%, 67%, 56%, 0% of patients at 30 minutes and 89%, 78%, 56%, 56%, 0% at 60 minutes, respectively. The median differences from the baseline spike count for ketamine >1.5mg/kg (median 89 [18, 273]) spikes were -20 [-106, -20] at 30 minutes and -32 [-106, -32] at 60 minutes. Effects of ketamine < 1.5mg/kg were less for both spike count and spectral power. EEG spectral changes commonly peaked at 30 minutes and recovered by 60 minutes. Pharmacodynamic modeling (Emax model) demonstrated tight temporal correlation of estimated blood concentrations with EEG spectral changes.
Anti-seizure Medications