Intensive Care Med (2020) 46:1563–1566

https://doi.org/10.1007/s00134-020-06154-8

NARRATIVE REVIEW

Inhalational volatile‑based sedation

for COVID‑19 pneumonia and ARDS
Angela Jerath1,3,4,5* , Niall D. Ferguson2,3 and Brian Cuthbertson2,4,5

© 2020 Springer-Verlag GmbH Germany, part of Springer Nature

Abstract
Hospitals worldwide are experiencing a shortage in essential intravenous sedative medications. This is attributable
to high number and high sedative needs of COVID-19 critical care patients with disruption of drug supply chains.
Inhaled volatile anesthetic agents are an abundant resource and readily implementable solution for providing ICU
sedation. Inhaled volatile agents may also provide important pulmonary benefits for COVID-19 patients with ARDS
that could improve gas exchange and reduce time spent on a ventilator. We review the use of volatile agents, and
provide a technical overview and algorithm for administering inhaled volatile-based sedation in ICUs.
Keywords: Sedation, Volatile anesthetics, COVID-19, ARDS, Ventilation

Global shortage of essential intravenous sedatives and However, evidence indicates that inhaled agents like iso-
neuromuscular blocking agents has emerged to be a flurane and sevoflurane offer more than just sedation and
major problem in delivering safe care for critically ill may be advantageous for patients with COVID-19 ARDS.
patients during the COVID-19 pandemic. Government These benefits may include anti-inflammatory effects
agencies and medical organizations are reporting major and lower airway resistance via dose-dependent bron-
shortages of benzodiazepines, opioids, propofol and chodilatation [3-6] Volatile agents also dilate pulmonary
paralytics [1, 2]. Drug shortages may arise because of dis- vascular beds, but the specific effect in ARDS and at low
rupted supply chains combined with increased demand doses remains understudied. These combined benefits
from the large number of ventilated COVID-19 patients have shown moderate improvements in patient oxygena-
who exhibit high sedative requirements and commonly tion, nonsignificant trend to increase ventilator free days,
need neuromuscular blockade. Low drug stocks have but studies lack sufficient power to show any mortality
wider impact beyond intensive care units (ICU) on other or ICU length of stay benefit [3]. Beyond ARDS studies,
essential hospital services including operative surgery inhaled sedative regimens have shown modest benefits in
and end-of-life care. Resource scarcity has led to diffi- faster extubation times upon drug discontinuation, which
cult ethical triaging of resources and re-introduction of is attributable to their unique clearance via pulmonary
older long-acting agents such as barbiturates in many exhalation with negligible systemic metabolism [7, 8].
jurisdictions. There are several technical and personnel prerequi-
During this crisis, many hospitals have moved to or sites when commencing inhaled volatile-based sedation
are considering the use of sedation using inhaled vola- in ICUs. Sevoflurane, desflurane or isoflurane can all be
tile anesthetics to conserve intravenous sedatives agents. used, but isoflurane offers the greatest potency with the
lowest dosing requirements for ICU patients. Volatiles
are delivered using either an anesthesia machine or ICU
*Correspondence: [email protected] ventilator with an in-line miniature vaporizer. The lat-
1
Department of Anesthesia, Sunnybrook Health Sciences Centre, 2075 ter option provides high flow rates, more sophisticated
Bayview Avenue, Toronto, ON M4N 3M5, Canada
Full author information is available at the end of the article ventilation options and better management of air leaks
that would be preferable in severe ARDS patients with
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high minute volume requirements (15–25 L/min). Mini- shown good safety with equivalent hemodynamic sta-
vaporizers (for example, MIRUS or Anesthesia Conserv- bility, no hepatorenal toxicity and possibly less agitation
ing Device) are placed close to the endotracheal tube compared to intravenous agents [3, 8, 10]. Prolonged
adding circuit dead space (50–150 ml) with minimal tidal use of sevoflurane may be associated with diabetes
volume requirements (200–350 ml, device dependent) to insipidus in some rare cases [11]. Rare adverse effects
prevent re-breathing of carbon dioxide [6]. These vapor- include malignant hyperthermia within genetically sus-
izers contain a reflector that recycles expired agent that ceptible individuals, which is identified by hyperther-
allows sedation to be maintained using very low amounts mia, hypercarbia and hemodynamic instability. These
of agent (i.e., isoflurane 2–5 ml/h, sevoflurane 3–8 ml/h). hypermetabolic symptoms need to be separated from
Devices also include humidification/anti-microbial filter, more common ICU problems such as new sepsis and
which filters over 99.9% of particles measuring at least deteriorating lung function.
27 nm. This provides protection to the ventilator from Several important technology and drug features need
SARS-CoV-2 which is a larger microbe measuring 120– to be considered using these systems. Device changes
160 nm. An additional filter could also be placed on the may be more frequent (< 24 h) in patients with high-
expiratory port of the circuit after discussion with the volume secretions. Addition of miniature vaporizers
manufacturer. Delivering volatile agents must be per- mildly elevates circuit resistance (and airway pressures)
formed in conjunction with scavenging of gas from the that is partially lowered by infusing volatile agent. Dur-
ventilator exhaust to keep occupational levels below rec- ing weaning or sedation holidays when volatiles are dis-
ommended limits [6, 9]. Bedside end-tidal gas monitor- continued, removal of mini-vaporizers from the circuit
ing (correlate of cerebral concentration) can be used to is vital to minimize work of breathing [12]. Overlapping
ensure gas delivery, assess concentration of drug needed good management of delirium and pain while tapering
to achieve a specific clinical sedation endpoint, re-breath- off volatile agents will help transition to a more suc-
ing of carbon dioxide and device obstruction. Monitoring cessful weaning process. Recently, Gattinoni et al. have
can be performed using a portable monitor or gas mod- suggested two COVID-19 lung phenotypes with differ-
ule compatible with the ICU monitoring system. Prac- ent physiological features and ventilation recommen-
tical management and regimen for inhaled sedation is dations; type-L (low lung recruitability with high tidal
summarized in Fig. 1. Given the differences of delivering volumes > 6 ml/kg and lower PEEP ventilation) and
volatile agents, institution of inhaled sedation regimens is type-H (high lung recruitability with low tidal volumes
often simpler in European ICUs that are staffed predomi- and higher PEEP ventilation) [13]. Patients with either
nantly by anesthesiology-trained intensivists who are phenotype may exhibit high ventilatory ratio indicat-
familiar with the physicochemical and delivery nuances ing increased dead space [14]. Maintaining adequate
of volatile agents. In North American ICUs where staff- sedation is determined clinically (i.e., sedation score,
ing models have a greater concentration of internal med- motor activity) as end-tidal gas monitoring maybe an
icine-trained intensivists, optimal delivery of inhalational inaccurate measure of alveolar and cerebral concentra-
techniques may be better managed using a cross-disci- tion in the presence of significant ventilation–perfusion
plinary sedation team that encompasses an anesthesiolo- mismatch. Patients with a deterioration in lung func-
gist, respiratory therapist or certified nurse anesthetist at tion and/or new sepsis may show a reduction in tidal
least during early stages of implementation. volumes below the recommended device thresholds
Volatile agents are effective in complex and high- that can lead to re-breathing and hypercarbia. Optimiz-
sedation-need patients with significant reduction or ing ventilation settings to increase tidal volumes will
removal of intravenous sedatives. Volatile agents pos- overcome this issue, but inability to provide sufficient
sess mild muscle relaxation properties and may lower tidal volumes should lead to device removal unless
usage of paralytic agents, but neuromuscular block- patients are commenced on extracorporeal support
ing agents will likely still be required for patients with where external gas exchangers or sweep gas efficiently
severe ARDS. Volatile agents possess little analgesic removes carbon dioxide [15].
effect and are typically co-administered with intra- In conclusion, trained teams can safely deliver inhaled
venous opioids. Inhaled volatile agents show similar volatile sedation regimens with a good sedation profile
pharmacodynamics properties to intravenous sedative, that may have benefits in the lung while easing pressure
i.e., dose-dependent hypnosis, respiratory depression on essential sedative medications.
and hypotension. Prolonged use of volatile agents has
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Fig. 1 Algorithm for initiating and commencing inhaled volatile-based sedation regimen for ARDS
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Author details of the inflammatory response to one-lung ventilation. Anesthesiology

1
Department of Anesthesia, Sunnybrook Health Sciences Centre, 2075 110:1316–1326
Bayview Avenue, Toronto, ON M4N 3M5, Canada. 2 Interdepartmental Division 5. Ferrando C, Aguilar G, Piqueras L, Soro M, Moreno J, Belda FJ (2013) Sevo-
of Critical Care Medicine, University of Toronto, University Health Network, flurane, but not propofol, reduces the lung inflammatory response and
Toronto, Canada. 3 Toronto General Hospital Research Institute, 200 Elizabeth improves oxygenation in an acute respiratory distress syndrome model: a
St, Toronto, ON M5G 2C4, Canada. 4 Sunnybrook Research Institute, Sun- randomised laboratory study. Eur J Anaesthesiol 30:455–463
nybrook Health Sciences Centre, 2075 Bayview Ave, Toronto, ON M4N 3M5, 6. Jerath A, Parotto M, Wasowicz M, Ferguson ND (2016) Volatile anesthetics.
Canada. 5 Department of Anesthesiology and Pain Management, University is a new player emerging in critical care sedation? Am J Respir Crit Care
of Toronto, Room 1201, 123 Edward St, Toronto, ON M5G 1E2, Canada. Med 193:1202–1212
7. Jerath A, Beattie SW, Chandy T, Karski J, Djaiani G, Rao V, Yau T, Wasowicz
Compliance with ethical standards M (2015) Volatile-based short-term sedation in cardiac surgical patients: a
prospective randomized controlled trial. Crit Care Med 43:1062–1069
Conflict of interest 8. Jerath A, Panckhurst J, Parotto M, Lightfoot N, Wasowicz M, Ferguson ND,
AJ and NDF have consulted for Sedana Medical, Sweden. NDF has received Steel A, Beattie WS (2017) Safety and efficacy of volatile anesthetic agents
fees from Getinge and Xenios. AJ and BC have received funds from the Inno- compared with standard intravenous midazolam/propofol sedation in
vation Fund of the Alternative Funding Plan for the Academic Health Sciences ventilated critical care patients: a meta-analysis and systematic review of
Centres of Ontario. prospective trials. Anesth Analg 124:1190–1199
9. Wong K, Wasowicz M, Grewal D, Fowler T, Ng M, Ferguson ND, Steel A,
Jerath A (2016) Efficacy of a simple scavenging system for long-term criti-
Publisher’s Note cal care sedation using volatile agent-based anesthesia. Can J Anaesth
Springer Nature remains neutral with regard to jurisdictional claims in pub- 63:630–632
lished maps and institutional affiliations. 10. Jerath A, Steel A, Ferguson N, Wasowicz M (2016) High fluoride levels
with isoflurane critical care sedation does not cause nephrotoxicity. Am J
Received: 21 April 2020 Accepted: 5 June 2020 Respir Crit Care Med 193:A3639
Published online: 25 June 2020 11. Maussion E, Combaz S, Cuisiner A, Chapuis C, Payen JF (2019) Renal
dysfunction during sevoflurane sedation in the ICU. Eur J Anaesthesiol
36:375–385
12. Chabanne R, Perbet S, Futier E, Ait Ben Said N, Jaber S, Bazin JE, Pereira
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