Observational Study

. 2025 Jun;51(6):1050-1061.

doi: 10.1007/s00134-025-07945-7. Epub 2025 Jun 13.

Altered lower brainstem neurophysiological response is associated with mortality in deeply sedated critically ill patients

Eléonore Bouchereau^{1

2}, Estelle Pruvost-Robieux^{3

2}, Shidasp Siami⁴, Cendrine Chaffaut^{5

6}, Adrien Bouglé⁷, Martine Gavaret^{3

2}, Nicholas Heming⁸, Sivanthiny Sivanandamoorthy⁴, Julie Zyss⁹, Vincent Degos¹⁰, Stanislas Kandelman¹¹, Cassia Righy Shinotsuka^{12

13}, Sarah Benghanem¹⁴, Lionel Naccache⁹, Benjamin Rohaut¹⁵, Bertrand Hermann^{1

2

16}, Eric Azabou¹⁷, Sylvie Chevret^{5

6}, Tarek Sharshar^{18

19}

Affiliations

¹ Anesthesia and Intensive Care Department, GHU Paris Psychiatrie et Neurosciences, Pole Neuro, Sainte‑Anne Hospital, Paris, France.
² Institute of Psychiatry, Neurosciences of Paris, INSERM U1266, Université Paris Cité, Paris, France.
³ Department of Clinical Neurophysiology, GHU Paris Psychiatrie et Neurosciences, Pole Neuro, Sainte‑Anne Hospital, Paris, France.
⁴ General Intensive Care Unit, Sud-Essonne Hospital, Etampes, France.
⁵ Department of Biostatistics, Hôpital Saint-Louis, AP-HP, Paris, France.
⁶ Université Paris Cité, Inserm UMR 1153, Paris, France.
⁷ Department of Anesthesiology and Critical Care Medicine, Cardiology Institute, Sorbonne University, GRC 29, AP-HP, Pitié-Salpêtrière Hospital, Paris, France.
⁸ General Intensive Care Unit, APHP, Raymond Poincaré Hospital, University of Versailles Saint-Quentin en Yvelines, Garches, France.
⁹ Department of Clinical Neurophysiology, Groupe Hospitalier Pitié-Salpêtrière, Assistance Publique-Hôpitaux de Paris (AP-HP), Paris, France.
¹⁰ Department of Anesthesiology and Critical Care, Sorbonne University, AP-HP, Pitié Salpêtrière - Charles Foix Hospital, Paris, France.
¹¹ Department of Anesthesiology, Royal Victoria Hospital, McGill University Health Center, Montreal, Canada.
¹² Department of Neurointensive Care, Paulo Niemeyer State Brain Institute, Rio de Janeiro, Brazil.
¹³ Laboratório de Medicina Intensiva, Fundação Oswaldo Cruz, Instituto Nacional de Infectologia, Rio de Janeiro, Brazil.
¹⁴ Medical Intensive Care Unit, Cochin Hospital, Assistance Publique - Hôpitaux de Paris-Centre (APHP-Centre), Paris, France.
¹⁵ Department of Neurology, Neuro-ICU & Brain Institute - ICM, Pitié-Salpêtrière Hospital APHP, Sorbonne Université, Paris, France.
¹⁶ Medical Intensive Care Unit, HEGP Hospital, Assistance Publique - Hôpitaux de Paris-Centre (APHP-Centre), Paris, France.
¹⁷ Department of Physiology and Department of Critical Care Medicine, Inserm UMR 1173 Infection and Inflammation, Raymond Poincaré Hospital, Assistance Publique - Hôpitaux de Paris (AP-HP), University of Versailles Saint Quentin (UVSQ), University Paris-Saclay, Garches, Paris, France.
¹⁸ Anesthesia and Intensive Care Department, GHU Paris Psychiatrie et Neurosciences, Pole Neuro, Sainte‑Anne Hospital, Paris, France. t.sharshar@ghu-paris.fr.
¹⁹ Neuro-Anesthesiology and Intensive Care Medicine, GHU-Paris Psychiatrie Et Neurosciences, Université de Paris, Paris, France. t.sharshar@ghu-paris.fr.

PMID: 40512201
DOI: 10.1007/s00134-025-07945-7

Observational Study

Altered lower brainstem neurophysiological response is associated with mortality in deeply sedated critically ill patients

Eléonore Bouchereau et al. Intensive Care Med. 2025 Jun.

. 2025 Jun;51(6):1050-1061.

doi: 10.1007/s00134-025-07945-7. Epub 2025 Jun 13.

Authors

Affiliations

¹ Anesthesia and Intensive Care Department, GHU Paris Psychiatrie et Neurosciences, Pole Neuro, Sainte‑Anne Hospital, Paris, France.
² Institute of Psychiatry, Neurosciences of Paris, INSERM U1266, Université Paris Cité, Paris, France.
³ Department of Clinical Neurophysiology, GHU Paris Psychiatrie et Neurosciences, Pole Neuro, Sainte‑Anne Hospital, Paris, France.
⁴ General Intensive Care Unit, Sud-Essonne Hospital, Etampes, France.
⁵ Department of Biostatistics, Hôpital Saint-Louis, AP-HP, Paris, France.
⁶ Université Paris Cité, Inserm UMR 1153, Paris, France.
⁷ Department of Anesthesiology and Critical Care Medicine, Cardiology Institute, Sorbonne University, GRC 29, AP-HP, Pitié-Salpêtrière Hospital, Paris, France.
⁸ General Intensive Care Unit, APHP, Raymond Poincaré Hospital, University of Versailles Saint-Quentin en Yvelines, Garches, France.
⁹ Department of Clinical Neurophysiology, Groupe Hospitalier Pitié-Salpêtrière, Assistance Publique-Hôpitaux de Paris (AP-HP), Paris, France.
¹⁰ Department of Anesthesiology and Critical Care, Sorbonne University, AP-HP, Pitié Salpêtrière - Charles Foix Hospital, Paris, France.
¹¹ Department of Anesthesiology, Royal Victoria Hospital, McGill University Health Center, Montreal, Canada.
¹² Department of Neurointensive Care, Paulo Niemeyer State Brain Institute, Rio de Janeiro, Brazil.
¹³ Laboratório de Medicina Intensiva, Fundação Oswaldo Cruz, Instituto Nacional de Infectologia, Rio de Janeiro, Brazil.
¹⁴ Medical Intensive Care Unit, Cochin Hospital, Assistance Publique - Hôpitaux de Paris-Centre (APHP-Centre), Paris, France.
¹⁵ Department of Neurology, Neuro-ICU & Brain Institute - ICM, Pitié-Salpêtrière Hospital APHP, Sorbonne Université, Paris, France.
¹⁶ Medical Intensive Care Unit, HEGP Hospital, Assistance Publique - Hôpitaux de Paris-Centre (APHP-Centre), Paris, France.
¹⁷ Department of Physiology and Department of Critical Care Medicine, Inserm UMR 1173 Infection and Inflammation, Raymond Poincaré Hospital, Assistance Publique - Hôpitaux de Paris (AP-HP), University of Versailles Saint Quentin (UVSQ), University Paris-Saclay, Garches, Paris, France.
¹⁸ Anesthesia and Intensive Care Department, GHU Paris Psychiatrie et Neurosciences, Pole Neuro, Sainte‑Anne Hospital, Paris, France. t.sharshar@ghu-paris.fr.
¹⁹ Neuro-Anesthesiology and Intensive Care Medicine, GHU-Paris Psychiatrie Et Neurosciences, Université de Paris, Paris, France. t.sharshar@ghu-paris.fr.

PMID: 40512201
DOI: 10.1007/s00134-025-07945-7

Abstract

Background and objectives: Absent cough reflex is associated with mortality in intensive care unit (ICU) patients requiring deep sedation, suggesting that lower brainstem dysfunction contributes to adverse outcomes. We conducted a multicenter observational cohort study to confirm this hypothesis by assessing the peak latency (PL) of the lower brainstem-generated P14 evoked potential (EP), which is slightly increased by sedatives. We aimed to demonstrate that a P14-PL > 16 ms is independently associated with day-28 mortality.

Patients and methods: Mechanically ventilated adult patients, comatose or deeply sedated, brain injured or not, were included. At day 3, EPs were performed in patients remaining unconscious. The Simplified Acute Physiological Score (SAPSII), initial Glasgow Coma Scale (GCS), sedation depth, and brainstem reflexes were collected. The primary outcome was day-28 mortality. The secondary outcomes were delayed awakening and delirium after sedation discontinuation.

Results: Between 2015 and 2019, 322 patients were included. EPs were performed in 264 (82%) patients, including 140 (53%) brain-injured and 251 (95%) deeply sedated patients. The median age, SAPSII and initial GCS were 62 [50; 71], 49 [40; 62] and 11 years [6; 15], respectively. A P14-PL > 16 ms was found in 76 (29%) patients and was associated with day-28 mortality (adjusted hazard ratio, 3.0; 95% confidence interval, [1.7-5.2]). Absent cough and pupillary light reflexes were associated with death. Only absent oculocephalogyric reflex was associated with delayed awakening (adjusted odds ratio, 2.1, 95%CI, [1.1-3.7]).

Interpretation: Impaired neurological and neurophysiological lower brainstem responses are associated with mortality in deeply sedated patients. Funded by the French Ministry of Health; PRORETRO; no. P120915; ClinicalTrials.gov registry: NCT02395861; date: 24 March 2015.

Keywords: Brain-injured patients; Coma; Critical care; Evoked potentials; Neuroprognostication.

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Conflict of interest statement

Declarations. Conflicts of interest: All authors declare no conflicts of interest.

References

1. Palakshappa JA, Batt JAE, Bodine SC et al (2024) Tackling Brain and Muscle Dysfunction in Acute Respiratory Distress Syndrome Survivors: National Heart, Lung, and Blood Institute Workshop Report. Am J Respir Crit Care Med. https://doi.org/10.1164/rccm.202311-2130WS (published online March 13)
1. Robba C, Zanier ER, Lopez Soto C et al (2024) Mastering the brain in critical conditions: an update. Intensive Care Med Exp 12:1 - PubMed - PMC
1. Benghanem S, Mazeraud A, Azabou E et al (2020) Brainstem dysfunction in critically ill patients. Crit Care 24:5 - PubMed - PMC
1. Sharshar T, Porcher R, Siami S et al (2011) Brainstem responses can predict death and delirium in sedated patients in intensive care unit. Crit Care Med 39:1960–1967 - PubMed
1. Rohaut B, Porcher R, Hissem T et al (2017) Brainstem response patterns in deeply-sedated critically-ill patients predict 28-day mortality. PLoS One 12:e0176012 - PubMed - PMC

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Altered lower brainstem neurophysiological response is associated with mortality in deeply sedated critically ill patients

Affiliations

Altered lower brainstem neurophysiological response is associated with mortality in deeply sedated critically ill patients

Authors

Affiliations

Abstract

Conflict of interest statement

References

Publication types

MeSH terms

Substances

Associated data

LinkOut - more resources

Full Text Sources

Medical

Research Materials