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Sedation with volatile anesthetics in the intensive care unit: a new option with old agents

INTRODUCTION

Since December 2019, when the first cases were described in China, the coronavirus disease 2019 (COVID-19) pandemic has impacted health systems around the world. A significant number of patients have the severe form of the disease, requiring admission to the intensive care unit (ICU).(11 Wu Z, McGoogan JM. Characteristics of and important Lessons From the Coronavirus Disease 2019 (COVID-19) Outbreak in China: Summary of a Report of 72314 Cases From the Chinese Center for Disease Control and Prevention. JAMA. 2020;323(13):1239-42.) The shortage of beds, equipment and drugs represented an even greater challenge in the management of these patients. The improvised use of operating rooms, which served as ICU beds, and the use of anesthesia equipment for sedation and mechanical ventilation have been described and were employed as heroic measures in the management of these patients.(22 da Silva Ramos FJ, de Freitas FG, Machado FR. Sepsis in patients hospitalized with coronavirus disease 2019: how often and how severe? Curr Opin Crit Care. 2021;27(5):474-9., 33 Jerath A, Ferguson ND, Cuthbertson B. Inhalational volatile-based sedation for COVID-19 pneumonia and ARDS. Intensive Care Med. 2020;46(8):1563-6., 44 Flinspach AN, Zacharowski K, Ioanna D, Adam EH. Volatile isofllurane in critically ill coronavirus disease 2019 patients-A case series and systematic review. Crit Care Explor. 2020;2(10):e0256.) In this context, the use of volatile anesthetics (VAs) has reappeared as an option for the sedation of critically ill patients.(33 Jerath A, Ferguson ND, Cuthbertson B. Inhalational volatile-based sedation for COVID-19 pneumonia and ARDS. Intensive Care Med. 2020;46(8):1563-6.)

The use of VAs in the ICU has been described for more than 2 decades and is mainly used in Europe and Canada;(55 Jerath A, Parotto M, Wasowicz M, Ferguson ND. Volatile anesthetics. Is a new player emerging in critical care sedation? Am J Respir Crit Care Med. 2016;193(11):1202-12.) however, the equipment to administer VAs was only recently approved for use in Brazil. The main VAs used as sedatives in the ICU are sevoflurane and isoflurane. The development of equipment with compact vaporizers adapted for mechanical ventilators in ICUs made it possible to use these agents as an option for sedation. Among the main advantages of using VAs rather than opioids in critically ill patients are earlier awakening, lower use of opioids and shorter time on mechanical ventilation. Other reported benefits of VAs are bronchodilator effects and improved oxygenation, especially in patients with acute respiratory distress syndrome (ARDS). Among the contraindications and limitations of VAs are a personal or family history of malignant hyperthermia, suspected or confirmed intracranial hypertension, severe hemodynamic instability and significant pulmonary secretion with the need for frequent aspiration due to the risk of system obstruction.(55 Jerath A, Parotto M, Wasowicz M, Ferguson ND. Volatile anesthetics. Is a new player emerging in critical care sedation? Am J Respir Crit Care Med. 2016;193(11):1202-12.)

Three meta-analyses showed that compared to venous sedation, the use of VAs in the ICU resulted in faster awakening and extubation times.(66 Landoni G, Pasin L, Cabrini L, Scandroglio AM, Baiardo Redaelli M, Votta CD, et al. Volatile agents in medical and surgical intensive care units: a meta-analysis of randomized clinical trials. J Cardiothorac Vasc Anesth. 2016;30(4):1005-14., 77 Jerath A, Panckhurst J, Parotto M, Lightfoot N, Wasowicz M, Ferguson ND, et al. Safety and efficacy of volatile anesthetic agents compared with standard intravenous midazolam/propofol sedation in ventilated critical care patients: a meta-analysis and systematic review of prospective trials. Anesth Analg. 2017;124(4):1190-9., 88 Kim H Y, Lee JE, Kim H Y, Kim J. Volatile sedation in the intensive care unit: a systematic review and meta-analysis. Medicine (Baltimore). 2017;96(49):e8976.) More recently, Meiser et al., in a multicenter noninferiority study of isoflurane compared to propofol, showed that isoflurane was an effective and safe option. Additionally, in the isoflurane group, opioid consumption was lower.(99 Meiser A, Volk T, Wallenborn J, Guenther U, Becher T, Bracht H, Schwarzkopf K, Knafelj R, Faltlhauser A, Thal SC, Soukup J, Kellner P, Drüner M, Vogelsang H, Bellgardt M, Sackey P; Sedaconda study group. Inhaled isoflurane via the anaesthetic conserving device versus propofol for sedation of invasively ventilated patients in intensive care units in Germany and Slovenia: an open-label, phase 3, randomised controlled, non-inferiority trial. Lancet Respir Med. 2021;9(11):1231-40.)

Experimental studies have shown that sevoflurane has the ability to reduce lung inflammation in ARDS models.(1010 Suter D, Spahn DR, Blumenthal S, Reyes L, Booy C, Z’Graggen BR, et al. The immunomodulatory effect of sevoflurane in endotoxin-injured alveolar epithelial cells. Anesth Analg. 2007;104(3):638-45., 1111 Steurer M, Schläpfer M, Steurer M, Z’Graggen BR, Booy C, Reyes L, et al. The volatile anaesthetic sevoflurane attenuates lipopolysaccharide-induced injury in alveolar macrophages. Clin Exp Immunol. 2009;155(2):224-30.) Jabaudon et al., in a randomized study, demonstrated that compared with midazolam, the use of sevoflurane in patients with ARDS for a period of 48 hours was related to improved oxygenation and reduced markers of lung epithelial lesions.(1212 Jabaudon M, Boucher P, Imhoff E, Chabanne R, Faure JS, Roszyk L, et al. Sevoflurane for Sedation in acute respiratory distress syndrome. a randomized controlled pilot study. Am J Respir Crit Care Med. 2017;195(6):792-800.)

The use of VAs in the ICU has been more frequently reported in populations of surgical patients. Although there are no contraindications for VAs use in other populations of critically ill patients (e.g., patients with sepsis), further studies are needed.

How can volatile agents be used in intensive care units?

Volatile anesthetics are an option for sedation in critically ill patients. Table 1 presents the main indications and options for VAs use in the ICU. An example of the assembly of the sedation device for the delivery of volatile agents is presented in figure 1. A humidifier and antibacterial filter are attached to the vaporizer. Although the equipment is easy to assemble and use, the need to acquire specific equipment may be a limitation to the use of VAs. Cost-effectiveness evaluation studies on VAs use in the ICU are still needed. An advantage of using these VAs is the clearance of the drug through pulmonary expiration and a systemic metabolism rate lower than 0.2% for isoflurane and close to 5% for sevoflurane.(55 Jerath A, Parotto M, Wasowicz M, Ferguson ND. Volatile anesthetics. Is a new player emerging in critical care sedation? Am J Respir Crit Care Med. 2016;193(11):1202-12.)

Table 1
Potential use of sedation with volatile agents in the intensive care unit

Figure 1
Example of the assembly and arrangement of sedation equipment with volatile agents in the intensive care unit

Regarding the occupational safety of VAs in ICU environments and mechanical ventilators, several studies have evaluated the environmental contamination risk and occupational risk of this equipment, demonstrating safe use under certain conditions and with the appropriate equipment.(1313 Sackey PV, Martling CR, Nise G, Radell PJ. Ambient isoflurane pollution and isoflurane consumption during intensive care unit sedation with the Anesthetic Conserving Device. Crit Care Med. 2005;33(3):585-90., 1414 González-Rodríguez R, Muñoz Martínez A, Galan Serrano J, Moral García MV. Health worker exposure risk during inhalation sedation with sevoflurane using the (AnaConDa®) anaesthetic conserving device. Rev Esp Anestesiol Reanim. 2014;61(3):133-9., 1515 Wong K, Wasowicz M, Grewal D, Fowler T, Ng M, Ferguson ND, et al. Efficacy of a simple scavenging system for long-term critical care sedation using volatile agent-based anesthesia. Can J Anaesth. 2016;63(5):630-2.)

In conclusion, the use of sevoflurane and isoflurane and inhaled sedation equipment developed for the ICU seems to be an option for specific groups of critically ill patients.

REFERENCES

  • 1
    Wu Z, McGoogan JM. Characteristics of and important Lessons From the Coronavirus Disease 2019 (COVID-19) Outbreak in China: Summary of a Report of 72314 Cases From the Chinese Center for Disease Control and Prevention. JAMA. 2020;323(13):1239-42.
  • 2
    da Silva Ramos FJ, de Freitas FG, Machado FR. Sepsis in patients hospitalized with coronavirus disease 2019: how often and how severe? Curr Opin Crit Care. 2021;27(5):474-9.
  • 3
    Jerath A, Ferguson ND, Cuthbertson B. Inhalational volatile-based sedation for COVID-19 pneumonia and ARDS. Intensive Care Med. 2020;46(8):1563-6.
  • 4
    Flinspach AN, Zacharowski K, Ioanna D, Adam EH. Volatile isofllurane in critically ill coronavirus disease 2019 patients-A case series and systematic review. Crit Care Explor. 2020;2(10):e0256.
  • 5
    Jerath A, Parotto M, Wasowicz M, Ferguson ND. Volatile anesthetics. Is a new player emerging in critical care sedation? Am J Respir Crit Care Med. 2016;193(11):1202-12.
  • 6
    Landoni G, Pasin L, Cabrini L, Scandroglio AM, Baiardo Redaelli M, Votta CD, et al. Volatile agents in medical and surgical intensive care units: a meta-analysis of randomized clinical trials. J Cardiothorac Vasc Anesth. 2016;30(4):1005-14.
  • 7
    Jerath A, Panckhurst J, Parotto M, Lightfoot N, Wasowicz M, Ferguson ND, et al. Safety and efficacy of volatile anesthetic agents compared with standard intravenous midazolam/propofol sedation in ventilated critical care patients: a meta-analysis and systematic review of prospective trials. Anesth Analg. 2017;124(4):1190-9.
  • 8
    Kim H Y, Lee JE, Kim H Y, Kim J. Volatile sedation in the intensive care unit: a systematic review and meta-analysis. Medicine (Baltimore). 2017;96(49):e8976.
  • 9
    Meiser A, Volk T, Wallenborn J, Guenther U, Becher T, Bracht H, Schwarzkopf K, Knafelj R, Faltlhauser A, Thal SC, Soukup J, Kellner P, Drüner M, Vogelsang H, Bellgardt M, Sackey P; Sedaconda study group. Inhaled isoflurane via the anaesthetic conserving device versus propofol for sedation of invasively ventilated patients in intensive care units in Germany and Slovenia: an open-label, phase 3, randomised controlled, non-inferiority trial. Lancet Respir Med. 2021;9(11):1231-40.
  • 10
    Suter D, Spahn DR, Blumenthal S, Reyes L, Booy C, Z’Graggen BR, et al. The immunomodulatory effect of sevoflurane in endotoxin-injured alveolar epithelial cells. Anesth Analg. 2007;104(3):638-45.
  • 11
    Steurer M, Schläpfer M, Steurer M, Z’Graggen BR, Booy C, Reyes L, et al. The volatile anaesthetic sevoflurane attenuates lipopolysaccharide-induced injury in alveolar macrophages. Clin Exp Immunol. 2009;155(2):224-30.
  • 12
    Jabaudon M, Boucher P, Imhoff E, Chabanne R, Faure JS, Roszyk L, et al. Sevoflurane for Sedation in acute respiratory distress syndrome. a randomized controlled pilot study. Am J Respir Crit Care Med. 2017;195(6):792-800.
  • 13
    Sackey PV, Martling CR, Nise G, Radell PJ. Ambient isoflurane pollution and isoflurane consumption during intensive care unit sedation with the Anesthetic Conserving Device. Crit Care Med. 2005;33(3):585-90.
  • 14
    González-Rodríguez R, Muñoz Martínez A, Galan Serrano J, Moral García MV. Health worker exposure risk during inhalation sedation with sevoflurane using the (AnaConDa®) anaesthetic conserving device. Rev Esp Anestesiol Reanim. 2014;61(3):133-9.
  • 15
    Wong K, Wasowicz M, Grewal D, Fowler T, Ng M, Ferguson ND, et al. Efficacy of a simple scavenging system for long-term critical care sedation using volatile agent-based anesthesia. Can J Anaesth. 2016;63(5):630-2.

Edited by

Responsible editor: Antonio Paulo Nassar Jr.

Publication Dates

  • Publication in this collection
    05 June 2023
  • Date of issue
    2023

History

  • Received
    25 Nov 2022
  • Accepted
    10 Dec 2022
Associação de Medicina Intensiva Brasileira - AMIB Rua Arminda, 93 - 7º andar - Vila Olímpia, CEP: 04545-100, Tel.: +55 (11) 5089-2642 - São Paulo - SP - Brazil
E-mail: ccs@amib.org.br