Diagnostic value of mismatch-negativity and P3a event-related potentials for sepsis-associated encephalopathy in non-sedated patients: a pilot study

doi:10.5847/wjem.j.1920-8642.2026.034

Abstract

Abstract:

BACKGROUND: Although the Confusion Assessment Methods for the Intensive Care Unit (CAM-ICU) is a recommended tool for diagnosing sepsis-associated encephalopathy (SAE), it has several limitations. Mismatch-negativity (MMN) and P3a are components of event-related potentials (ERPs) used with electroencephalography (EEG) and are associated with cerebral function changes in critically ill patients. This study aimed to provide a quantitative, non-invasive method to guide SAE diagnosis in non-sedated patients.

METHODS: From January 2022 to March 2023, sepsis patients without sedation were enrolled and assessed via the CAM-ICU, Glasgow Coma Scale (GCS), and ERP under standard procedures. Both MMN and P3a data were collected. The diagnostic value of MMN and P3a was assessed with processed ERP data.

RESULTS: Thirty-six patients were included in this study, comprising 19 patients with SAE and 17 patients without SAE (NSAE). MMN and P3a amplitudes decreased, and only FzMMN amplitude significantly decreased in SAE patients (2.03 [1.08, 2.93] mV vs. 3.21 [1.92, 4.34] mV, P=0.040). After median dichotomization, low F3P3a and FzP3a amplitudes were associated with higher CAM-ICU positivity rates and APACHE II scores. Both amplitude in F3P3a (AUC=0.710, 95%CI: 0.527-0.893, P=0.034) and FzP3a (AUC=0.700, 95%CI: 0.519-0.881, P=0.041) exhibited moderate diagnostic efficacy for SAE, while FzMMN amplitude lacks effective diagnostic value.

CONCLUSION: In this pilot study, ERP components F3P3a and FzP3a amplitudes demonstrated moderate diagnostic value for SAE. These exploratory findings require confirmation in larger and powered cohorts.

Key words: Sepsis-associated encephalopathy, Event-related potentials, Mismatch-negativity, Electroencephalography, Diagnostic value

Zengzheng Ge, Xin Lu, Shiyuan Yu, Mubing Qin, Chao Gong, Qun Xu, Yanxia Gao, Joseph Harold Walline, Huadong Zhu, Yi Li. Diagnostic value of mismatch-negativity and P3a event-related potentials for sepsis-associated encephalopathy in non-sedated patients: a pilot study[J]. World Journal of Emergency Medicine, 2026, 17(2): 172-178.

Figures/Tables 4

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Variables	SAE (n=19)	NSAE (n=17)	P-value
Male, n (%)	9 (47%)	8 (47%)	0.515
Age, years	62.1±12.7	65.4±11.4	0.433
SOFA score	9.1±3.9	6.5±2.8	0.048*
APACHE II score	21.5±4.6	17.6±5.1	0.030*
GCS score	11.2±4.4	15.0±0.0	0.012*
Mean arterial pressure, mmHg	66 (59, 112)	68 (61,113)	0.654
Heart rate, beats/min	101±17	99±14	0.332
SpO₂, %	95.6 (91.1, 98.5)	95.2 (93.2, 98.8)	0.129
Temperature, ℃	37.6±1.9	37.5±1.8	0.113
Underlying disease, n (%)
Hypertension	6 (32%)	7 (41%)	0.089
Diabetes	7 (37%)	7 (41%)	0.286
Coronary artery disease	5 (27%)	5 (29%)	0.781
Chronic renal dysfunction	3 (16%)	1 (6%)	0.069
COPD	2 (11%)	1 (6%)	0.112
Cancer	2 (11%)	2 (12%)	0.557
Clinical measurements
pH	7.37±0.12	7.39±0.15	0.278
PaO₂, mmHg	77.2±10.5	81.5±8.2	0.129
PaCO₂, mmHg	28.3±4.5	27.1±3.4	0.490
Lactate, mmol/L	6.1±4.2	4.6±2.3	0.249
White blood cells, ×10⁹/L	15.1±12.7	16.5±11.2	0.314
Neutrophils, ×10⁹/L	13.1±10.5	13.7±8.9	0.428
Lymphocytes, ×10⁹/L	0.71 (0.42, 0.91)	0.69 (0.38, 0.87)	0.297
Creatinine, μmol/L	109.2±27.1	111.0±19.8	0.343
ALT, U/L	32.3±8.5	33.5±10.1	0.299
Biliary, μmol/L	17.1±7.1	16.9±8.9	0.314
Interventions, n (%)
Needs vasopressor	6 (32%)	5 (29%)	0.115
Needs CRRT	2 (11%)	1 (6%)	0.112
Outcomes
ICU stay, d	2.9±1.3	3.3±1.4	0.087
Hospital stay, d	10.1±2.7	7.9±3.5	0.145
Mortality, n (%)	3 (16%)	1 (6%)	0.091

ERP variables	SAE (n=19)	NSAE (n=17)	P-value
P3a
F3 Amp (mV)	3.31 (1.11, 4.06)	4.25 (3.55, 5.74)	0.222
F3 Lat (mS)	312.5 (267.75, 337.5)	330 (301, 355)	0.601
Fz Amp (mV)	2.40 (1.28, 4.37)	4.52 (2.60, 5.91)	0.128
Fz Lat (mS)	305.5 (279.25, 343.5)	337 (305, 358)	0.301
F4 Amp (mV)	3.11 (1.51, 4.48)	4.22 (3.23, 5.81)	0.149
F4 Lat (mS)	321.5 (283.75, 349.25)	338 (321, 361)	0.436
Cz Amp (mV)	1.89 (1.21, 4.07)	3.74 (1.47, 5.94)	0.605
Cz Lat (mS)	286 (262.25, 333)	340 (309, 362)	0.161
MMN
F3 Amp (mV)	2.34 (1.42, 2.61)	2.38 (1.6, 3.06)	0.153
F3 Lat (mS)	151.5 (118.5, 176)	142 (104, 174)	0.078
Fz Amp (mV)	2.03 (1.08, 2.93)	3.21 (1.92, 4.34)	0.040*
Fz Lat (mS)	141 (123, 186)	134 (118.75, 166.25)	0.169
F4 Amp (mV)	2.14 (1.41, 3.12)	2.18 (1.37, 3.04)	0.598
F4 Lat (mS)	158 (125.5, 189.25)	142 (122, 183)	0.086
Cz Amp (mV)	2.22 (1.1, 2.78)	2.33 (1.4, 3.52)	0.090
Cz Lat (mS)	151 (124.75, 187.75)	148 (120, 183)	0.127

Outcomes	High level (n=18)	Low level (n=18)	P-value
FzMMN Amp
GCS	13 (12, 15)	13 (11, 15)	0.694
SOFA	7 (5, 12)	9 (5.5, 9.25)	0.651
APACHE II	20 (17, 24)	19 (16.75, 22.25)	0.731
CAM-ICU (n, %)	6 (33.3)	13 (72.2)	0.032*
Mortality (n, %)	1 (5.6)	3 (16.7)	0.175
F3P3a Amp
GCS	15 (11, 15)	13 (11.75, 13.25)	0.217
SOFA	6 (4, 10)	9 (7, 11)	0.147
APACHE II	17 (13, 22)	21 (19, 25.25)	0.041*
CAM-ICU (n, %)	6 (33.3)	13 (72.2)	0.032*
Mortality (n, %)	1 (5.6)	3 (16.7)	0.175
FzP3a Amp
GCS	15 (12, 15)	13 (11, 14.25)	0.286
SOFA	8 (5, 11)	8.5 (4.75, 9.5)	0.913
APACHE II	18 (13, 21)	23 (19, 26)	0.009*
CAM-ICU (n, %)	7 (38.9)	12 (66.7)	0.037*
Mortality (n, %)	1 (5.6)	3 (16.7)	0.175