Early impairment of intracranial conduction time predicts mortality in deeply sedated critically ill patients: a prospective observational pilot study

Abstract

Background: Somatosensory (SSEP) and brainstem auditory (BAEP) evoked potentials are neurophysiological tools which, respectively, explore the intracranial conduction time (ICCT) and the intrapontine conduction time (IPCT). The prognostic values of prolonged cerebral conduction times in deeply sedated patients have never been assessed. Sedated patients are at risk of developing new neurological complications, undetected. In this prospective observational bi-center pilot study, we investigated whether early impairment of SSEP's ICCT and/or BAEP's IPCT could predict in-ICU mortality or altered mental status (AMS), in deeply sedated critically ill patients.

Methods: SSEP by stimulation of the median nerve and BAEP were assessed in critically ill patients receiving deep sedation on day 3 following ICU admission. Deep sedation was defined by a Richmond Assessment sedation Scale (RASS) <-3. Mean left- and right-side ICCT and IPCT were measured for each patient. Primary and secondary outcomes were, respectively, in-ICU mortality and AMS defined as the occurrence of delirium and/or delayed awakening after discontinuation of sedation.

Results: Eighty-six patients were studied of which 49 (57%) were non-brain-injured and 37 (43%) were brain-injured. Impaired ICCT was a predictor of in-ICU mortality after adjustment on the global Sequential Organ Failure Assessment score (SOFA) [OR (95% CI) = 2.69 (1.05-6.85); p = 0.039] and on the non-neurological SOFA components [2.67 (1.05-6.81); p = 0.040]. IPCT was more frequently delayed in the subgroup of patients who developed post-sedation AMS (24%) compared those without AMS (0%). However, this difference did not reach statistical significance (p = 0.053). Impairment rates of ICCT and IPCT were not found to be significantly different between non-brain- and brain-injured subgroups of patients.

Conclusion: In critically ill patients receiving deep sedation, early ICCT impairment was associated with mortality. Somatosensory and brainstem auditory evoked potentials may be useful early warning indicators of brain dysfunction as well as prognostic markers in deeply sedated critically ill patients.

Keywords: Altered mental status; Brain dysfunction; Deep sedation; Delirium; Evoked potentials; ICU; Neurophysiological assessment; Outcome; Prognostic.

Fig. 1

Flowchart. *Brain-injured patient was defined by admission to the ICU for acute brain injury

Fig. 2

Schematic representation of median nerve’s somatosensory evoked potentials (SSEP) responses localizations on brain MRI (a) and typical examples of their normal wave forms as well as recording electrodes montages (b). SSEP elicited by electric stimulation (15 mA) of median nerve at the wrist: N9, N13 and P14, respectively, the brachial plexus, cervical spinal cord, and cervico-medullary (subcortical) responses. N20 and P25 are responses of the primary sensory cortex. N9–N13 inter-peak latencies (IPL) represent a proximal peripheral nerve conduction time, and P14–N20 IPL the intracranial conduction time (ICCT). Recording and reference electrodes were placed at Cv7 (7th cervical vertebra)—Fz: for the N13 cervical spinal cord response and Cz-cSh (contralateral shoulder): for the subcortical far-field potential: P14. The cortical components, N20 and P25 were recorded at the contralateral C3′ or C4′ positions (2 cm behind C3 or C4) according to the international 10–20 system. Two sets of 500 sweeps were averaged

Fig. 3

Schematic representation of brainstem auditory evoked potentials (BAEP) responses localizations on a brain MRI (a) and typical examples of their normal wave forms as well as recording montage (b). BAEP elicited by auditory click (100-µs 80-dB) applied to one ear, with a (−20 dB) masking of the contralateral ear by “white noise.” The recurrence frequency was 19.3 Hz (bandpass, 150–1500 Hz; sweep time, 10 ms). BAEP were picked up in Fz. with the reference electrode placed at the earlobe ipsilateral to the stimulated ear (Fz—A1 or A2). Two sets of 2000 sweeps were averaged. The I–III IPL represents the peripheral conduction time of the auditory pathway, when the III–V IPL represents the intrapontine conduction time (IPCT)