In August 2009, our hospital added 22-channel digital continuous EEG recordings for the first 48 h after resuscitation from cardiac arrest as standard monitoring for all comatose post-cardiac arrest patients, as part of an ongoing quality improvement process [6
]. A minority of subjects had video cEEG recordings obtained. For consecutive patients hospitalized after in-hospital or out-of-hospital cardiac arrest presumed because of cardiac etiology, demographic data, survival, and functional outcome were prospectively recorded in a quality improvement database. Analyses of these quality improvement data were deemed an exempt activity by the University of Pittsburgh Institutional Review Board. The Cerebral Performance Category (CPC) and Modified Rankin Score (mRS) were used as outcome measures. The five categories of the CPC are: CPC 1, conscious and alert with good cerebral performance; CPC 2, conscious and alert with moderate cerebral performance; CPC 3, conscious with severe cerebral disability; CPC 4, comatose or in persistent vegetative state; and CPC 5, brain dead, circulation preserved. The mRS was also used to evaluate disability. The mRS is a 7-point scale that ranges from 0 (no symptoms at all) to 6 (death). A good outcome was defined as a CPC of 1 or 2 or a mRS of ≤3. Both the measures are reported because they measure different aspects of the subject's outcome [15
]. Additionally, time intervals from arrest to cEEG placement, from cEEG placement to seizure development, and from arrest to seizure development were recorded.
Convulsive seizures, including myoclonic, were defined as correlated clinical (motor) seizures and EEG seizure patterns. Myoclonic status epilepticus (MSE) was defined as a more than 30 min period of myoclonic jerks time locked with bursts in a burst-suppression pattern or associated with generalized periodic epileptiform discharges (GPEDs) [16
]. Seizures were considered nonconvulsive (electrographic) if an EEG seizure pattern had no prominent motor clinical correlate on simultaneous video or on clinical examination.
Diagnostic criteria for NCSE are controversial and there are no agreed upon criteria to diagnose NCSE in obtunded or comatose patients [17
]. We defined an electrographic seizure as repetitive generalized or focal spikes, sharp waves, spike-and-wave or sharp-slow wave complexes at ≥3 Hz or sequential rhythmic, periodic, or quasi-periodic waves at ≥1 Hz with unequivocal evolution in frequency, morphology, or location lasting at least 10 s [18
]. Electrographic status epilepticus or NCSE was defined as a state of impaired consciousness with: (1) a continuous electrographic seizure lasting 30 min or greater or recurrent electrographic seizures for over 30 min; (2) the presence of GPEDs lasting at least 30 min at a rate of ≥2.5 Hz; and (3) presence of GPEDs lasting at least 30 min at a rate of ≥1 Hz that evolved as described above. GPEDs at a rate of <2.5 Hz not satisfying criteria 3 above were classified as interictal GPEDs (, ; ). Our criteria represent a slight modification of several other published criteria [18
a The start of a 3 min electrographic seizure in an 80-year-old woman in NCSE. b The evolving discharge 40 s later. c The discharge ends, followed by suppression
Generalized periodic polyspikes in a 52-year-old woman
EEGs were interpreted during patient care by board certified neurologists, and all files with malignant cEEG patterns were subsequently analyzed by two clinical neurophysiologists with expertise in electroencephalography (AP, RB).
Seizures were treated according to local protocol. TH (goal temperature 33°C for 24 h) is provided to the majority of comatose post-cardiac arrest patients in our facility and all subjects in this study. Induction is accomplished by rapid infusion of 30 cc/kg of 4°C saline along with surface cooling. Neuromuscular paralysis is used during induction but rarely employed during the maintenance and rewarming phases of TH. During TH, sedation is titrated for ventilator asynchrony or shivering. The rate of rewarming is 0.2–0.3°C/h. Once the temperature is >36°C, sedation is titrated for a Ramsay Sedation Scale of 3. Most subjects receiving TH treatment after cardiac arrest receive a propofol infusion titrated to suppress shivering, or midazolam infusion if hypotensive. Those experiencing NCSE or MSE are initially treated with a bolus of lorazepam followed by loading with phenytoin. Levetiracetam and valproic acid are employed next, followed by either a continuous infusion of midazolam or pentobarbital for refractory cases.
Initial neurologic examination within the first 6 h of resuscitation and without sedation or paralytic was recorded using the Full Outline of Unresponsiveness (FOUR) score by one of the physician authors (JCR, FXG, and CWC) [21
]. This 16-point score is designed to evaluate the comatose patient with greater texture than the Glasgow Coma Scale, which is one subscale in the SOFA. The FOUR score is composed of a 0–4 score for Motor, Brainstem, Respiratory, and Eye responses. A lower score signifies greater impairment. Organ system dysfunction was determined using the individual organ dysfunction subscales of the Serial Organ Function Assessment (SOFA) scale [22
]. The SOFA score ranges from 0 to 4 in each of the following organ systems: cardiovascular, respiratory, nervous, liver, coagulation, and renal. A higher score signifies greater impairment. Four categories of post-cardiac arrest illness severity were defined by neurological examination and SOFA score on presentation [2
] (). In prior work, category of illness severity is associated with survival, neurologic outcome, and development of multiple organ failure (MOF) 2]. MOF was defined as a score ≥3 on three or more subscales during the first 72 h of hospitalization.
Categories of initial post-arrest illness severity
Fisher's exact test and the Mann–Whitney test were used to explore differences in demographic and outcome data based on electrographic seizure development. Fisher's exact test was also used to determine associations between electrographic seizure development and: (1) category of post-arrest illness severity, (2) initial rhythm of arrest, and (3) location of arrest (in-or out-of hospital cardiac arrest). These variables were chosen as they are known predictors of outcome. Data were analyzed using STATA v. 11.0 (STATA Corporation, College Station, TX).