Over-Sedation in Patients With COVID-19, ARDS, Linked to Delirium Risk

September 4, 2021

By Nancy Melville

BRUSSELS -- September 3, 2021 -- Critically-ill patients with coronavirus disease 2019 (COVID-19) and/or acute respiratory distress syndrome (ARDS) who are over-sedated are at an increased risk of delirium, regardless of their age, according to a study presented at the 40th International Symposium on Intensive Care and Emergency Medicine.

“This study shows that, besides age, over-sedation represents an important risk factor for delirium in mechanically-ventilated patients, and that over-sedation and delirium were more common in patients with ARDS compared with patients without ARDS,” said Mattia Marchesi, MD, Universitia degli Studi di Brescia, Brescia, Italy.

Deep sedation for critically ill patients with COVID-19 on mechanical ventilation, particularly among those with ARDS, is often necessary; however a balance is necessary to provide the correct depth of sedation while considering the known complications, which can include a higher incidence of delirium.

To compare the incidence of excessive sedation in patients with COVID-19 and/or ARDS and subsequent delirium, Dr. Marchesi and colleagues evaluated data on 78 critically ill patients (21 with COVID-19) requiring intubation and sedation for mechanical ventilation who were admitted to intensive care units at the Spedali Civili University Hospital of Brescia, and the Addenbrooke’s University Hospital, Cambridge United Kingdom, from July, 2018 to April, 2020.

The main intravenous sedatives used included propofol or midazolam, followed by dexmedetomidine and ketamine. For analgesia, fentanyl and remifentanil were primarily administered. For induced muscle paralysis, the most commonly used neuromuscular blocking agents were rocuronium or cisatracurium through continuous infusion, and depth of sedation was monitored with continuous processed electroencephalogram (EEG).

After patients were removed from sedation and reached a Richmond Agitation Sedation Scale (RASS) of -3 or above, delirium was evaluated using the Confusion Assessment Method for the ICU (CAM-ICU), which was applied to all patients every 6 hours during their ICU stay.

With a mean monitoring time of 43 hours in patients with COVID-19 and 50 hours for patients without COVID-19, 38 patients (49%) met the criteria for over-sedation, defined as having a patient state index (PSI) of 2 for more than 10% of the total sedation time.

The results showed that those who had delirium were significantly more likely to have over-sedation (odds ratio [OR] = 11.4; P P = .017). Even after adjusting for age, over-sedation had a significant association with delirium (OR = 8.35; P = .002).

Patients with COVID-19 showed a non-significant higher percentage of delirium versus the group without COVID-19 (92.3% vs 63.4%; P = .076), and, though non-significant, patients with ARDS had a higher incidence of over-sedation (60.5% vs 37.5%; P = .069), and delirium (84% vs 58.6%, P = 0.07) versus patients without ARDS.

Marchesi noted that the high incidence of over-sedation with ARDS could have been because clinicians may have used neuromuscular blocking agents and did not know how deep the sedation level was.

He added that further analysis showed that, in addition to a higher risk of delirium, those who were over-sedated also had a longer length of stay.

“Our study supports the continued use of EEG-derived monitoring systems for the quantification of sedation depth and highlights the necessity for larger, randomised trials to verify if monitoring the depth of sedation can improve outcome,” he said.

[Presentation title: Over-Sedation as a Risk Factor for Delirium in Critically-Ill COVID-19 and Non-COVID-19 Patients With ARDS: a Dual Center Analysis. Abstract A234]