This prospective, blinded, monocentric, observational study was conducted at the Kerckhoff-Hospital, Bad Nauheim, Germany. After gaining approval from the ethical committee of the Justus Liebig-University Giessen, Germany, and obtaining written informed consent, consecutive patients scheduled for elective open-chamber aortic or mitral valve reconstruction or replacement were included. Exclusion criteria were emergency surgery, lack of informed consent, pregnancy, pre-existing epilepsy, surgery in deep hypothermia or off-pump surgery. Patients were screened for pre-existing cognitive deficits using the mini-mental status examination (MMSE) the day before surgery. The anaesthetic, surgical and postoperative treatment was standardised and not influenced by the presented observation. Anaesthesia induction included propofol 2.5–3.0 mg/kg and sufentanil bolus 0.8–1.0 µg/kg. While propofol was applied continuously, remifentanil was added with 0.15–1.0 µg/kg*min as continuous analgesia. In addition to continuous remifentanil, sufentanil boli were applied before painful surgical procedures. The target of bispectral index (BIS) was between 40 and 60. To avoid air embolism while finishing cardiopulmonal bypasses, CO2 was inflated into the open heart and air was manually squeezed out. Patients were placed in a Trendelenburg position and the aortic root vent evacuated the air outside of the cavum and the aorta. Transoesophageal echocardiography was used to confirm that no air remained, then the aortal clamp was opened and the patient was positioned horizontally. After surgery, all patients were admitted to the ICU with analgo-sedative drugs (remifentanil and propofol) and invasive ventilation. After establishing the EEG monitoring, propofol and remifentanil were tapered with the target of early extubation. Piritramide and metamizole were used to obtain analgesia.
EEG monitoring started within the first hour after admission to the ICU (EEG-1100-system, NIHON KOHDEN Europe GmbH, Rosbach, Germany). An EEG was performed using 10 cup electrodes (Ag/AgCl) fixed at the scalp with electrode paste following abrasion of the skin surface. The electrodes were placed accordingly to the 10–20 system at Fp1, Fp2, C3, C4, P3, P4, T3, T4, Fz and Cz. EEG recording was continuously performed for up to 24 hours or stopped earlier if patients were discharged from the ICU or if more than 3 electrodes became dysfunctional. Afterwards, the EEG results were independently analysed with a focus on predominant background EEG frequencies, generalised or lateralised epileptic discharges (spikes, sharp waves, sharp-and-waves, spike-and-waves) and seizure-specific patterns (generalised or lateralised rhythmic epileptic discharges over a time of more than 10 seconds, long-lasting rhythmic slow waves and generalised rhythmic EEG activity different from the main EEG activity) by two EEG board-certified physicians (MT, PS) [7]. Both were blinded to patients’ treatment and outcome parameters. The EEG interpretation was performed after patients’ treatment, so the findings had no influence on the individual therapy. In the case of different interpretations, both investigators analysed the individual pattern together until a consensus was reached.
For secondary analysis, the incidence of delirium was assessed using the confusion assessment method for the intensive care unit (CAM-ICU), performed by nursing staff on the first and second postoperative day. Furthermore, length of stay in the ICU and postoperative strokes up to the end of inpatient rehabilitation were recorded. Doses of clorazepam for premedication, doses of tranexamic acid, time of extracorporeal bypass, aortic clamping time, lowest temperature during cardiopulmonary bypass, intraoperative BIS and mean arterial blood pressure (MAP) were recorded in the anaesthesia protocol and used to detect potentially uncontrollable influencing factors.
Statistical analysis
Due to the absence of preliminary data, a power analysis could not be performed. For this prevalence study, a sample size of 100 patients was targeted. The prevalence of seizures and epileptic discharges was analysed descriptively. For secondary analysis, a classification was performed for patients with/without epileptic discharges and for patients with/without seizure-specific EEG patterns. It was investigated whether the groups with/without epileptic discharges and with/without seizure-specific EEG patterns differed in patient characteristics (age, gender, BMI), preoperative mental state or intra-operative data. To verify whether the groups differed significantly in categorical variables, chi2-tests were calculated on the basis of a dichotomous scale level of the variable. For parametric continuous variables, a student’s t-tests were used. Continuous variables that did not meet the criteria of parametric testing were evaluated using Mann-Whitney U test. Normal distribution was proven with the Shapiro-Wilk test and variance homogeneity with the Levene test. For all metric variables, mean values and standard deviation (SD) were reported; for categorically scaled parameters, frequency and percentage were given. Statistical analyses were calculated using SPSS (version 24, IBM® SPSS® Statistics, USA). A significance level with p < 0.05 was considered to be statistically significant.