Early abolition of cough reflex predicts mortality in deeply sedated brain-injured patients

Stanislas Kandelman; Jérémy Allary; Raphael Porcher; Cássia Righy; Clarissa Francisca Valdez; Frank Rasulo; Nicholas Heming; Guy Moneger; Eric Azabou; Guillaume Savary; Djillali Annane; Fabrice Chretien; Nicola Latronico; Fernando Augusto Bozza; Benjamin Rohaut; Tarek Sharshar; Groupe d’Exploration Neurologique en Réanimation (GENeR)

doi:10.7717/peerj.10326

Early abolition of cough reflex predicts mortality in deeply sedated brain-injured patients

PeerJ. 2020 Nov 26:8:e10326. doi: 10.7717/peerj.10326. eCollection 2020.

Authors

Stanislas Kandelman^{1

2}, Jérémy Allary¹, Raphael Porcher³, Cássia Righy^{4

5}, Clarissa Francisca Valdez^{4

6}, Frank Rasulo^{7

8}, Nicholas Heming⁹, Guy Moneger⁹, Eric Azabou¹⁰, Guillaume Savary¹, Djillali Annane⁹, Fabrice Chretien¹¹, Nicola Latronico^{7

8}, Fernando Augusto Bozza^{5

12}, Benjamin Rohaut^{13

14}, Tarek Sharshar^{11

12

15}; Groupe d’Exploration Neurologique en Réanimation (GENeR)

Affiliations

¹ Department of Anesthesiology and Intensive Care Unit, Beaujon Hospital, University Denis Diderot, Clichy, France.
² Department of Anesthesia, Royal Victoria Hospital, McGill University Health Center, Montréal, QC, Canada.
³ Center for Clinical Epidemiology, Assistance Publique Hôpitaux de Paris, Hotel Dieu Hospital, University Paris Descartes, Paris, France.
⁴ Intensive Care Unit, Instituto Estadual do Cérebro Paulo Niemeyer, Rio de Janeiro, Brazil.
⁵ Instituto Nacional de Infectologia Evandro Chagas, Fundação Oswaldo Cruz (Fiocruz), Rio de Janeiro, Brazil.
⁶ Intensive Care Unit, Hospital das Américas, Rio de Janeiro, Brazil.
⁷ Department of Anesthesia, Critical Care and Emergency, Spedali Civili University Hospital, Brescia, Italy.
⁸ Department of Medical and Surgical Specialties, Radiological Sciences and Public Health, University of Brescia, Brescia, Italy.
⁹ General Intensive Care Unit, Assistance Publique Hôpitaux de Paris, Raymond-Poincaré Hospital, University of Versailles Saint-Quentin en Yvelines, Garches, France.
¹⁰ Department of Physiology, INSERM U 1179, Assistance Publique Hôpitaux de Paris, Raymond-Poincaré Hospital, University of Versailles Saint-Quentin en Yvelines, Garches, France.
¹¹ Laboratory of Human Histopathology and Animal Models, Institut Pasteur, Paris, France.
¹² D'Or Institute for Research and Education, Rio de Janeiro, Brazil.
¹³ Department of Neurology, Intensive Care Unit, Groupe Hospitalier Pitié-Salpêtrière, AP-HP, Paris, Sorbonne Universités, Faculté de Médecine Pitié-Salpêtrière, Paris, France, Paris, France.
¹⁴ Department of Neurology, Critical Care Neurology, Columbia University, New York, NY, USA.
¹⁵ Neuro-Anesthesiology and Intensive Care Unit, Sainte-Anne Teaching Hospital, University of Paris-Descartes, Paris, France.

Abstract

Background: Deep sedation may hamper the detection of neurological deterioration in brain-injured patients. Impaired brainstem reflexes within the first 24 h of deep sedation are associated with increased mortality in non-brain-injured patients. Our objective was to confirm this association in brain-injured patients.

Methods: This was an observational prospective multicenter cohort study involving four neuro-intensive care units. We included acute brain-injured patients requiring deep sedation, defined by a Richmond Assessment Sedation Scale (RASS) < -3. Neurological assessment was performed at day 1 and included pupillary diameter, pupillary light, corneal and cough reflexes, and grimace and motor response to noxious stimuli. Pre-sedation Glasgow Coma Scale (GCS) and Simplified Acute Physiology Score (SAPS-II) were collected, as well as the cause of death in the Intensive Care Unit (ICU).

Results: A total of 137 brain-injured patients were recruited, including 70 (51%) traumatic brain-injured patients, 40 (29%) vascular (subarachnoid hemorrhage or intracerebral hemorrhage). Thirty patients (22%) died in the ICU. At day 1, the corneal (OR 2.69, p = 0.034) and cough reflexes (OR 5.12, p = 0.0003) were more frequently abolished in patients that died in the ICU. In a multivariate analysis, abolished cough reflex was associated with ICU mortality after adjustment to pre-sedation GCS, SAPS-II, RASS (OR: 5.19, 95% CI [1.92-14.1], p = 0.001) or dose of sedatives (OR: 8.89, 95% CI [2.64-30.0], p = 0.0004).

Conclusion: Early (day 1) cough reflex abolition is an independent predictor of mortality in deeply sedated brain-injured patients. Abolished cough reflex likely reflects a brainstem dysfunction that might result from the combination of primary and secondary neuro-inflammatory cerebral insults revealed and/or worsened by sedation.

Keywords: Brain injury; Brainstem dysfunction; Cough reflex; Critical care; Deep sedation; Neurological examination; Neuroprognosis.

Grants and funding

The authors received no funding for this work.