Variability in pharmacologically-induced coma for treatment of refractory status epilepticus

Abstract

ObjectiveTo characterize the amount of EEG suppression achieved in refractory status epilepticus (RSE) patients treated with pharmacologically-induced coma (PIC).MethodsWe analyzed EEG recordings from 35 RSE patients between 21–84 years-old who received PIC that target burst suppression and quantified the amount of EEG suppression using the burst suppression probability (BSP). Then we measured the variability of BSPs with respect to a reference level of BSP 0.8 ± 0.15. Finally, we also measured the variability of BSPs with respect to the amount of intravenous anesthetic drugs (IVADs) received by the patients.ResultsPatients remained in the reference BSP range for only 8% (median, interquartile range IQR [0, 29] %) of the total time under treatment. The median time with BSP below the reference range was 84% (IQR [37, 100] %). BSPs in some patients drifted significantly over time despite constant infusion rates of IVADs. Similar weight-normalized infusion rates of IVADs in different patients nearly always resulted in distinct BSPs (probability 0.93 (IQR [0.82, 1.0]).ConclusionThis study quantitatively identified high variability in the amount of EEG suppression achieved in clinical practice when treating RSE patients. While some of this variability may arise from clinicians purposefully deviating from clinical practice guidelines, our results show that the high variability also arises in part from significant inter- and intra- individual pharmacokinetic/pharmacodynamic variation. Our results indicate that the delicate balance between maintaining sufficient EEG suppression in RSE patients and minimizing IVAD exposure in clinical practice is challenging to achieve. This may affect patient outcomes and confound studies seeking to determine an optimal amount of EEG suppression for treatment of RSE. Therefore, our analysis points to the need for developing an alternative paradigm, such as vigilant anesthetic management as happens in operating rooms, or closed-loop anesthesia delivery, for investigating and providing induced-coma therapy to RSE patients.

New-onset super refractory status epilepticus: A case-series

“…Some reports have not found an association between specific comainducing agents or the extent of BS on outcome [3], while others have raised concerns about the higher morbidity and mortality in BS group, mostly due to prolonged ITU stay and anaesthetic exposure [29]. The amount of BS achieved in clinical practice is also variable, partly due to inter-and intra-individual pharmacokinetic/pharmacodynamic variability [17], making it even more challenging to address the above issues.…”

“…Indeed, IVAT for the treatment of the pathological EEG features during RSE is far from standardised and relies mostly on pragmatic approaches [15] and weak recommendations supported by low quality evidence [1]. The endpoint against which an IVAT should be titrated [16,17] and the management of inter-ictal patterns remain controversial [18,19], yet it highlights the necessity for advanced monitoring in the form of continuous critical care EEG (cCCEEG) [20,21] to avoid IVAT-related sideeffects [22].…”

To Wean or Not to Wean: Machine Learning to the Rescue

“…A study evaluated the variability of the BS pattern in 35 RSE patients in TC, with the reference BS ratio being 0.8 + 0.15. 21 Only 8% (median, IQR 0%-29%) of total time was spent at the reference BS range. This study highlighted the remarkable variability of the amount of BS within patients.…”

Etiology of Burst Suppression EEG Patterns

“…Clinical trials are needed to determine how efficacious this treatment is (Rossetti and Lowenstein, 2011). Other recent studies have indicated that burst suppression is inconsistently maintained during such treatment (An et al, 2018).…”