Comparison of isoflurane and propofol sedation in critically ill COVID-19 patients—a retrospective chart review

Abstract

Purpose In this retrospective study, we compared inhaled sedation with isoflurane to intravenous propofol in invasively ventilated COVID-19 patients with ARDS (Acute Respiratory Distress Syndrome). Methods Charts of all 20 patients with COVID-19 ARDS admitted to the ICU of a German University Hospital during the first wave of the pandemic between 22/03/2020 and 21/04/2020 were reviewed. Among screened 333 days, isoflurane was used in 97 days, while in 187 days, propofol was used for 12 h or more. The effect and dose of these two sedatives were compared. Mixed sedation days were excluded. Results Patients’ age (median [interquartile range]) was 64 (60–68) years. They were invasively ventilated for 36 [21–50] days. End-tidal isoflurane concentrations were high (0.96 ± 0.41 Vol %); multiple linear regression yielded the ratio (isoflurane infusion rate)/(minute ventilation) as the single best predictor. Infusion rates were decreased under ECMO (3.5 ± 1.4 versus 7.1 ± 3.2 ml∙h−1; p < 0.001). In five patients, the maximum recommended dose of propofol of 4 mg∙hour−1∙kg−1ABW was exceeded on several days. On isoflurane compared to propofol days, neuro-muscular blocking agents (NMBAs) were used less frequently (11% versus 21%; p < 0.05), as were co-sedatives (7% versus 31%, p < 0.001); daily opioid doses were lower (720 [720–960] versus 1080 [720–1620] mg morphine equivalents, p < 0.001); and RASS scores indicated deeper levels of sedation (− 4.0 [− 4.0 to − 3.0] versus − 3.0 [− 3.6 to − 2.5]; p < 0.01). Conclusion Isoflurane provided sufficient sedation with less NMBAs, less polypharmacy and lower opioid doses compared to propofol. High doses of both drugs were needed in severely ill COVID-19 patients.

Inhaled Sedation in Patients with COVID-19-Related Acute Respiratory Distress Syndrome: An International Retrospective Study

“…In our study, inhaled sedation was not associated with improved oxygenation, in contrast to previous reports in patients without [19] and with COVID-19, [33][34][35] and our longitudinal analyses suggested a potential increase in the partial pressure of arterial carbon dioxide and dynamic inspiratory plateau pressure with inhaled sedation. However, there was no strict protocol for mechanical ventilation in our study, and time × group interactions were only significant on day 5 for carbon dioxide and on day 0 for plateau pressure, which is inconsistent with the available evidence in non-COVID-19 and COVID-19 patients [9,[23][24][25][33][34][35][36].…”

“…They also support the efficacy of volatile anesthetics for ICU sedation, as recently confirmed by a large phase 3, randomized controlled non-inferiority trial of isoflurane vs. propofol in critically ill patients without COVID-19 [25]. In that trial, as in other studies, [19,22,24] volatile anesthetics were efficacious as the sole sedatives in non-COVID-19 patients and significantly reduced the requirement for other sedative and opioid agents in COVID-19 patients [9,[33][34][35]. Consistent with these findings, the use of inhaled sedation was associated with shorter durations of intravenous sedation (regression coefficient: −0.43; Table 4) in our study.…”

“…However, inhaled sedation was initiated later than day 0 in some patients in our study and was not always administered on successive days, which complicates the interpretation of our results, such as those from the sensitivity analyses. Fourth, we were unable to capture opioid requirements and further to evaluate whether they could be reduced with inhaled sedation, as suggested by previous reports [9,22,[33][34][35]. However, consistent with previous findings, the need for intravenous sedatives was decreased when inhaled sedation was used.…”

“…The surge in severe coronavirus disease 2019 (COVID-19) cases has led to an overwhelmed hospital and intensive care unit (ICU) capacity [1][2][3][4] and an international shortage of drugs [5]. Patients with COVID-19 requiring mechanical ventilation often need prolonged and high-dose sedation with hypnotics, opioids, and neuromuscular blocking agents to achieve sufficient comfort and to manage patient-ventilator dyssynchrony compared to patients with acute respiratory distress syndrome (ARDS) from other causes [6][7][8][9][10]. Ideally, sedation should be integrated into the ABCDEF bundle for ICU liberation: assessment and management of pain, both awakening and breathing trials, choosing the optimal sedative and titrating to the lightest sedation level possible, delirium assessment and management, early mobilization, and family engagement [11].…”

Metformin alleviates prolonged isoflurane inhalation induced cognitive decline via reducing neuroinflammation in adult mice

“…These results hinted that sub-MAC isoflurane inhalation induced neuroinflammation and cognitive decline also in a dose- and exposure length-dependent manner in adult mice. In clinical, the duration of isoflurane sedation for COVID-19 pneumonia and acute respiratory distress syndrome patients was more than 100 h [47] , [48] , [49] . The length of use in mice might not exactly mimic the time used in humans in consideration of their length of life respectively.…”