Clinical observation: Rhythmic and periodic EEG patterns in postanoxic coma can possibly be related to propofol discontinuation.

OBJECTIVES: To investigate whether rhythmic/periodic EEG patterns (RPP) appearing after propofol discontinuation are more likely to be related to the elimination phase of propofol, or are an expression of severe brain damage. METHODS: In a retrospective cohort of comatose postanoxic patients, EEG was assessed one hour before (baseline) and on hour after discontinuation of propofol. Presence and duration of RPP were related to (changes in) EEG background pattern and duration of sedation. RESULTS: In eleven (of 36 eligible) patients RPP appeared after propofol discontinuation and disappeared in seven of these patients within one hour. A continuous background pattern at baseline and shorter duration of propofol infusion seemed associated with (earlier) spontaneous disappearance of RPP. In ten patients with RPP at baseline, the EEG did not change, and in one patient it changed into burst-suppression. CONCLUSION: Our findings suggest that RPP after propofol discontinuation could be propofol-related. DISCUSSION: RPP might be related to propofol discontinuation rather than an expression of severe brain damage, especially in case of, and congruent with, a continuous pattern at the time of propofol discontinuation. This opens a new insight in this phenomenon and its transient nature. In clinical practice, we suggest to consider the timing of propofol discontinuation when assessing the EEG signal in postanoxic patients.

EEG in a four-electrode frontotemporal montage reliably predicts outcome after cardiac arrest.

AIM: To increase efficiency of continuous EEG monitoring for prognostication of neurological outcome in patients after cardiac arrest, we investigated the reliability of EEG in a four-electrode frontotemporal (4-FT) montage, compared to our standard nine-electrode (9-EL) montage. METHODS: EEG recorded with Ag/AgCl cup-electrodes at 12 and/or 24 h after cardiac arrest of 153 patients was available from a previous study. 220 EEG epochs of 5 minutes were reexamined in a 4-FT montage according to the ACNS criteria. Background classification was compared to the available 9-EL classification using Cohens kappa. Reliability for prognostication was assessed in 151 EEG epochs at 24 h after CA using sensitivity and specificity for prediction of poor (cerebral performance categories (CPC) 3-5) and good (CPC 1-2) neurological outcome. RESULTS: Agreement for EEG background classification between the two montages was substantial with a kappa of 0.85 (95%-CI 0.81-0.90). Specificity for prediction of poor outcome was 100% (95%-CI 95-100) for both montages, sensitivity was 31% (95%-CI 21-43) for the 4-FT montage and 35% (95%-CI 24-47) for the 9-EL montage. Good outcome was predicted with 65% specificity (95%-CI 53-76) and 81% sensitivity (95%-CI 71-89) for the 4-FT montage, similar to the 9-EL montage. CONCLUSION: In this cohort, EEG background patterns determined in a four-electrode frontotemporal montage predict both poor and good outcome after CA with similar reliability. Our results may contribute to decreasing the workload of EEG monitoring in patients after CA without compromising reliability of outcome prediction. However, validation in a larger cohort is necessary, as is a multimodal approach.

Treating Rhythmic and Periodic EEG Patterns in Comatose Survivors of Cardiac Arrest.

BACKGROUND: Whether the treatment of rhythmic and periodic electroencephalographic (EEG) patterns in comatose survivors of cardiac arrest improves outcomes is uncertain. METHODS: We conducted an open-label trial of suppressing rhythmic and periodic EEG patterns detected on continuous EEG monitoring in comatose survivors of cardiac arrest. Patients were randomly assigned in a 1:1 ratio to a stepwise strategy of antiseizure medications to suppress this activity for at least 48 consecutive hours plus standard care (antiseizure-treatment group) or to standard care alone (control group); standard care included targeted temperature management in both groups. The primary outcome was neurologic outcome according to the score on the Cerebral Performance Category (CPC) scale at 3 months, dichotomized as a good outcome (CPC score indicating no, mild, or moderate disability) or a poor outcome (CPC score indicating severe disability, coma, or death). Secondary outcomes were mortality, length of stay in the intensive care unit (ICU), and duration of mechanical ventilation. RESULTS: We enrolled 172 patients, with 88 assigned to the antiseizure-treatment group and 84 to the control group. Rhythmic or periodic EEG activity was detected a median of 35 hours after cardiac arrest; 98 of 157 patients (62%) with available data had myoclonus. Complete suppression of rhythmic and periodic EEG activity for 48 consecutive hours occurred in 49 of 88 patients (56%) in the antiseizure-treatment group and in 2 of 83 patients (2%) in the control group. At 3 months, 79 of 88 patients (90%) in the antiseizure-treatment group and 77 of 84 patients (92%) in the control group had a poor outcome (difference, 2 percentage points; 95% confidence interval, -7 to 11; P = 0.68). Mortality at 3 months was 80% in the antiseizure-treatment group and 82% in the control group. The mean length of stay in the ICU and mean duration of mechanical ventilation were slightly longer in the antiseizure-treatment group than in the control group. CONCLUSIONS: In comatose survivors of cardiac arrest, the incidence of a poor neurologic outcome at 3 months did not differ significantly between a strategy of suppressing rhythmic and periodic EEG activity with the use of antiseizure medication for at least 48 hours plus standard care and standard care alone. (Funded by the Dutch Epilepsy Foundation; TELSTAR ClinicalTrials.gov number, NCT02056236.).

SSEP amplitudes add information for prognostication in postanoxic coma.

OBJECTIVE: To investigate whether somatosensory evoked potential (SSEP) amplitude adds information for prediction of poor outcome in postanoxic coma. METHODS: In this retrospective cohort study we included adult patients admitted after cardiac arrest between January 2010 and June 2018 who remained in coma and had SSEP recorded for prognostication. Outcome was dichotomized in poor (Cerebral Performance Category (CPC) 4-5) and good (CPC 1-3) at ICU discharge. Sensitivity of bilaterally absent N20 potential was calculated. In case the N20 potential was not bilaterally absent, the amplitude contralateral to stimulation side (baseline-N20, N20-P25, and maximum) was determined. At a specificity of 100%, SEPP amplitude sensitivities were determined for poor outcome. RESULTS: SSEP recordings were performed in 197 patients of whom 57 had bilaterally absent N20 potentials. From 140 patients, 16 (11%) had a good outcome. The sensitivity for poor outcome of bilaterally absent N20 was 31%. At a specificity of 100%, contralateral amplitude thresholds were 0.34 µV (baseline-N20), 0.99 µV (N20-P25) and 1.0 µV (maximum), corresponding to a sensitivity for poor outcome of 38%, 44% and 40%. Combination of bilaterally absent N20 and a N20-P25 threshold below 0.99 µV yielded a sensitivity of 62%. CONCLUSIONS: Our results confirm that very low cortical SSEP amplitudes are highly predictive of poor outcome in patients with postanoxic coma. Adding 'N20-P25 threshold amplitude' to the 'bilaterally absent N20' criterion, increased sensitivity substantially.

Autonomic nervous system activity and the risk of nosocomial infection in critically ill patients with brain injury.

PURPOSE: Nosocomial infection contributes to adverse outcome after brain injury. This study investigates whether autonomic nervous system activity is associated with a decreased host immune response in patients following stroke or traumatic brain injury (TBI). METHODS: A prospective study was performed in adult patients with TBI or stroke who were admitted to the Intensive Care Unit of our tertiary university hospital between 2013 and 2016. Heart rate variability (HRV) was recorded daily and assessed for autonomic nervous system activity. Outcomes were nosocomial infections and immunosuppression, which was assessed ex vivo using whole blood stimulations with plasma of patients with infections, matched non-infected patients and healthy controls. RESULTS: Out of 64 brain injured patients, 23 (36%) developed an infection during their hospital stay. The ability of brain injured patients to generate a host response to the bacterial endotoxin lipopolysaccharides (LPS) was diminished compared to healthy controls (p < 0.001). Patients who developed an infection yielded significantly lower TNF-α values (86 vs 192 pg/mL, p = 0.030) and a trend towards higher IL-10 values (122 vs 84 pg/mL, p = 0.071) following ex vivo whole blood stimulations when compared to patients not developing an infection. This decreased host immune response was associated with altered admission HRV values. Brain injured patients who developed an infection showed increased normalized high-frequency power compared to patients not developing an infection (0.54 vs 0.36, p = 0.033), whereas normalized low-frequency power was lower in infected patients (0.46 vs 0.64, p = 0.033). CONCLUSION: Brain injured patients developing a nosocomial infection show parasympathetic predominance in the acute phase following brain injury, reflected by alterations in HRV, which parallels a decreased ability to generate an immune response to stimulation with LPS.

Awakening after a sleeping pill: Restoring functional brain networks after severe brain injury.

Some patients with severe brain injury show short-term neurological improvements, such as recovery of consciousness, motor function, or speech after administering zolpidem, a GABA receptor agonist. The working mechanism of this paradoxical phenomenon remains unknown. In this study, we used electroencephalography and magnetoencephalography to investigate a spectacular zolpidem-induced awakening, including the recovery of functional communication and the ability to walk in a patient with severe hypoxic-ischemic brain injury. We show that cognitive deficits, speech loss, and motor impairments after severe brain injury are associated with stronger beta band connectivity throughout the brain and suggest that neurological recovery after zolpidem occurs with the restoration of beta band connectivity. This exploratory work proposes an essential role for beta rhythms in goal-directed behavior and cognition. It advocates further fundamental and clinical research on the role of increased beta band connectivity in the development of neurological deficits after severe brain injury.

EEG reactivity testing for prediction of good outcome in patients after cardiac arrest.

OBJECTIVE: To determine the additional value of EEG reactivity (EEG-R) testing to EEG background pattern for prediction of good outcome in adult patients after cardiac arrest (CA). METHODS: In this post hoc analysis of a prospective cohort study, EEG-R was tested twice a day, using a strict protocol. Good outcome was defined as a Cerebral Performance Category score of 1-2 within 6 months. The additional value of EEG-R per EEG background pattern was evaluated using the diagnostic odds ratio (DOR). Prognostic value (sensitivity and specificity) of EEG-R was investigated in relation to time after CA, sedative medication, different stimuli, and repeated testing. RESULTS: Between 12 and 24 hours after CA, data of 108 patients were available. Patients with a continuous (n = 64) or discontinuous (n = 19) normal voltage background pattern with reactivity were 3 and 8 times more likely to have a good outcome than without reactivity (continuous: DOR, 3.4; 95% confidence interval [CI], 0.97-12.0; p = 0.06; discontinuous: DOR, 8.0; 95% CI, 1.0-63.97; p = 0.0499). EEG-R was not observed in other background patterns within 24 hours after CA. In 119 patients with a normal voltage EEG background pattern, continuous or discontinuous, any time after CA, prognostic value was highest in sedated patients (sensitivity 81.3%, specificity 59.5%), irrespective of time after CA. EEG-R induced by handclapping and sternal rubbing, especially when combined, had highest prognostic value. Repeated EEG-R testing increased prognostic value. CONCLUSION: EEG-R has additional value for prediction of good outcome in patients with discontinuous normal voltage EEG background pattern and possibly with continuous normal voltage. The best stimuli were clapping and sternal rubbing.

Electroencephalographic reactivity as predictor of neurological outcome in postanoxic coma: A multicenter prospective cohort study.

OBJECTIVE: Outcome prediction in patients after cardiac arrest (CA) is challenging. Electroencephalographic reactivity (EEG-R) might be a reliable predictor. We aimed to determine the prognostic value of EEG-R using a standardized assessment. METHODS: In a prospective cohort study, a strictly defined EEG-R assessment protocol was executed twice per day in adult patients after CA. EEG-R was classified as present or absent by 3 EEG readers, blinded to patient characteristics. Uncertain reactivity was classified as present. Primary outcome was best Cerebral Performance Category score (CPC) in 6 months after CA, dichotomized as good (CPC = 1-2) or poor (CPC = 3-5). EEG-R was considered reliable for predicting poor outcome if specificity was ≥95%. For good outcome prediction, a specificity of ≥80% was used. Added value of EEG-R was the increase in specificity when combined with EEG background, neurological examination, and somatosensory evoked potentials (SSEPs). RESULTS: Of 160 patients enrolled, 149 were available for analyses. Absence of EEG-R for poor outcome prediction had a specificity of 82% and a sensitivity of 73%. For good outcome prediction, specificity was 73% and sensitivity 82%. Specificity for poor outcome prediction increased from 98% to 99% when EEG-R was added to a multimodal model. For good outcome prediction, specificity increased from 70% to 89%. INTERPRETATION: EEG-R testing in itself is not sufficiently reliable for outcome prediction in patients after CA. For poor outcome prediction, it has no substantial added value to EEG background, neurological examination, and SSEPs. For prediction of good outcome, EEG-R seems to have added value. ANN NEUROL 2019.

Disruption of Brain-Heart Coupling in Sepsis.

PURPOSE: To investigate heart rate and EEG variability and their coupling in patients with sepsis and determine their relationship to sepsis severity and severity of sepsis-associated brain dysfunction. METHODS: Fifty-two patients with sepsis were prospectively identified, categorized as comatose (N = 30) and noncomatose (N = 22), and compared with 11 control subjects. In a 30-minute EEG and electrocardiogram recording, heart rate variability and EEG variability (measured by the variability of relative power in a modified alpha band = RAP) and their coupled oscillations were quantified using linear (least-square periodogram and magnitude square coherence) and nonlinear (Shannon entropy and mutual information) measures. These measures were compared between the three groups and correlated with outcome, adjusting for severity of sepsis. RESULTS: Several measures of heart rate variability and EEG variability and of their coupled oscillations were significantly lower in patients with sepsis compared with controls and correlated with outcome. This correlation was not independent when adjusting for severity of sepsis. CONCLUSIONS: Sepsis is associated with lower variability of both heart rate and RAP on EEG and reduction of their coupled oscillations. This uncoupling is associated with the severity of encephalopathy. Combined EEG and electrocardiogram monitoring may be used to gain insight in underlying mechanisms of sepsis and quantify brainstem or thalamic dysfunction.