Abstracts

Rationale: Evaluating the role of status epilepticus in the pathophysiology of a swine model of severe traumatic brain injury requires anesthesia then sedation in an overnight intensive care unit. In vivo, 2-photon imaging to evaluate the ionic basis of epileptogenesis also requires anesthesia. However, GABA-acting anesthetics reduce the excitability of neurons, reduce frequency power spectra, alter network dynamics, and shorten or prevent seizures. A previously published sedation regimen in swine was not sufficient to sedate nor anesthetize in our model. Here, we describe the electrographic properties of a seizure-permissive anesthetic regimen (SPAR) that allows prolonged seizures.

Methods: We tested combinations of sedation protocols published for psychiatric patients, prisoners, end-of-life care, and an anesthetic protocol for cardiac surgery. We titrated intravenous dexmedetomidine, morphine, rocuronium, H1 agonists, and chlorpromazine until swine were not responsive to noxious stimuli as end-tidal isoflurane was reduced to zero. Yorkshire piglets (1 week = “infants”; 1 month = “toddlers”; N = 22) received multifactorial injuries including status epilepticus induced with kainic acid or a sham surgery and were sedated and mechanically ventilated overnight in an intensive care unit where EEG was recorded up to 22 hours with a 6-channel bipolar montage. Adult, Yucatan swine (N = 2) had radiotelemetric EEG implanted providing a 20-channel, bipolar montage and were recorded while awake and anesthetized.  

Results: A continuous infusion of dexmedetomidine (20 mcg/kg) and morphine (3.5 mg/kg) with boli of rocuronium every 30 minutes allowed for anesthesia followed by sedation via continuous infusions at reduced rates. H1 agonists provided no additional benefit. A bolus of morphine and rocuronium was given for movement during transition from isoflurane, and if not sufficient, then chlorpromazine (2 mg/kg) was administered. Following kainate administration under SPAR, electrographic status epilepticus lasted an average of 5.6 hours in “infants” and 8.4 hours in “toddlers” and then transitioned to an array of spike patterns lasting an additional 6-7 hours. The type of spike pattern was age-dependent. In “toddlers,” nitrous oxide was added to SPAR overnight in shams or if the seizure was short. The power spectra of a “toddler,” sham piglet while anesthetized with isoflurane resulted in low power across all frequencies, but delta waves appeared after transition to SPAR. 

Conclusions: Induction of unconsciousness and analgesia via agonism of alpha 2 adrenergic and opioid receptors and muscle relaxation via neuromuscular block enabled high-quality electrographic recordings of status epilepticus in anesthetized, immature piglets. We will continue to evaluate the power spectra among developmental stages of pigs during anesthesia with SPAR vs. isoflurane and while awake. 

Funding: NIH NICHD K01HD083759/ NIH R01 HD099397/ The Claflin Distinguished Scholar Award