The association between the presence and burden of periodic discharges and outcome in septic patients: an observational prospective study

Abstract

Background Sepsis-associated encephalopathy (SAE) is frequent in septic patients. Electroencephalography (EEG) is very sensitive to detect early epileptic abnormalities, such as seizures and periodic discharges (PDs), and to quantify their duration (the so-called burden). However, the prevalence of these EEG abnormalities in septic patients, as well as their effect on morbidity and mortality, are still unclear. The aims of this study were to assess whether the presence of electrographic abnormalities (i.e. the absence of reactivity, the presence and burden of seizures and PDs) was associated with functional outcome and mortality in septic patients and whether these abnormalities were associated with sepsis-associated encephalopathy (SAE). Methods We prospectively included septic patients, without known chronic or acute intracranial disease or pre-existing acute encephalopathy, requiring ICU admission in a tertiary academic centre. Continuous EEG monitoring was started within 72 h after inclusion and performed for up to 7 days. A comprehensive assessment of consciousness and delirium was performed twice daily by a trained neuropsychologist. Primary endpoints were unfavourable functional outcome (UO, defined as a Glasgow Outcome Scale-Extended—GOSE—score < 5), and mortality collected at hospital discharge and secondary endpoint was the association of PDs with SAE. Mann–Whitney, Fisher’s exact and χ2 tests were used to assess differences in variables between groups, as appropriate. Multivariable logistic regression analysis with in-hospital mortality, functional outcome, SAE or PDs as the dependent variables were performed. Results We included 92 patients. No seizures were identified. Nearly 25% of patients had PDs. The presence of PDs and PDs burden was associated with UO in univariate (n = 15 [41%], p = 0.005 and p = 0.008, respectively) and, for PDs presence, also in multivariate analysis after correcting for disease severity (OR 3.82, IC 95% [1.27–11.49], p = 0.02). The PDs burden negatively correlated with GOSE (Spearman’s coefficient ρ = − 0.2, p = 0.047). The presence of PDs was also independently associated with SAE (OR 8.98 [1.11–72.8], p = 0.04). Reactivity was observed in the majority of patients and was associated with outcomes (p = 0.044 for both functional outcome and mortality). Conclusion Our findings suggest that PDs and PDs burden are associated with SAE and might affect outcome in septic patients.

The spectrum of sepsis-associated encephalopathy: a clinical perspective

“…1 ) [ 28 , 30 – 33 ]. Amplitude and continuity can also be affected, from low voltage and discontinuous background (10–60% of cases) to burst suppression or suppression (3–8% of cases) [ 31 , 32 , 34 ]. The more severe EEG patterns are mostly observed in sedated patients, and thus the proportion of EEG abnormalities related to sedation versus SAE is not easy to assess.…”

“…Most ESz are non-convulsive, highlighting the interest of continuous EEG recording [ 35 ]. ESz are observed in 0–30% of cases [ 31 , 32 , 34 , 36 ].…”

“…Some EEG patterns are associated with delirium, including slow delta rhythm, absence of EEG reactivity, discontinuity, and presence/burden periodic discharges (PDs) [ 31 , 34 , 37 ]. PDs may contribute to brain hypoxia and might be considered as a cause of secondary brain injury [ 34 ]. Conversely, rapid beta activity is associated with a reduced risk of delirium [ 38 ].…”

“…A recent prospective study highlighted that triphasic waves, slow delta background and suppressed EEG were the most frequent patterns observed within 24h prior to death [ 32 ]. The score on the Synek scale, which was developed in anoxic and trauma patients, is also associated with mortality in septic patients, similarly to PDs presence/burden [ 31 , 34 ]. In a general population of medical ICU patients remaining unresponsive after sedation interruption, a pattern consisting of a reactive standard electroencephalography with a background frequency greater than 4 Hz was associated with reduced mortality [ 24 ].…”

“…> 12.5µg/L) in sepsis varies between 28 and 53% [ 45 , 46 ]. Previous studies showed a modest increase in NSE concentrations during sepsis, with median serum levels of 6.6 [IQR 4.1–13.8] µg/L [ 45 ], 18.8 [IQR 13.9 –30.5] µg/L [ 34 ], and 30.33 [IQR 19.6–46.5] µg/L [ 47 ].…”