Inhaled volatile anesthetics in the intensive care unit

Table 1 Pharmacology and overview of halogenated volatile anesthetics[8,78-81]

	MAC (%)	Blood:Gas at 37oC	Boiling point (oC)	Odor	Metabolism (%)	Cardiovascular effects	Central nervous system effects
Halothane	0.75	2.4	122	Organic solvent	15-20	Decrease CO, decrease HR	Decrease CPP, increase CBF
Isoflurane	1.15	1.4	48	Ethereal/pungent	0.2	Decrease CO, increase HR, decrease SVR	Decrease CPP, increase CBF
Desflurane	6.0	0.4	23	Ethereal/pungent	0.02	Increase HR, decrease SVR	Decrease CPP, increase CBF
Sevoflurane	2.0	0.68	59	Organic solvent	5	Decrease SVR	Decrease CPP, increase CBF. Can induce epileptiform EEG

CBF: Cerebral blood flow; CO: Cardiac output; CPP: Cerebral perfusion pressure; EEG: Electroencephalogram; HR: Heart rate; MAC: Minimum alveolar concentration; SVR: Systemic vascular resistance.

Table 2 Indications, advantages, and disadvantages of volatile anesthetics in the intensive care unit

Indication	Agents studied	Advantages	Disadvantages
Short-term postoperative	Desflurane, isoflurane, sevoflurane	Quick awakening; Faster extubation; Titratability; Minimal drug interactions; Minimal metabolism; Provides analgesia	No benefit on ICU length of stay; Reduces blood pressure
Prolonged sedation during mechanical ventilation	Isoflurane, sevoflurane	Faster return to spontaneous breathing; Titratability; Minimal drug interactions; Minimal metabolism; Provides analgesia	Special equipment required in ICU; Reduces blood pressure
Status asthmaticus	Isoflurane, sevoflurane	Bronchodilation	Reduces blood pressure
Status epilepticus	Isoflurane, desflurane	Sustained EEG burst suppression	May increase intracranial pressure through cerebral vasodilation
ARDS	Isoflurane, sevoflurane	Lung protective; Anti-inflammatory	Special equipment required in ICU; Reduces blood pressure
COVID-19	Isoflurane, sevoflurane	Decreased sedative, NMBA requirements	Special equipment required in ICU; Reduces blood pressure
Other high sedative requirements (burn, alcohol or opioid use at baseline)	Isoflurane, sevoflurane	Decreased inflammation in burns; Decreased sedative requirements	Not proven in literature, hypothesis generating at this time

ARDS: Acute respiratory distress syndrome; COVID-19: Coronavirus infectious disease 2019; EEG: Electroencephalogram; ICU: Intensive care unit; NMBA: Neuromuscular blocking agent.

Table 3 Summary of short-term postoperative volatile anesthetic studies

Ref.	Treatment	Surgeries	Sedation duration	Time to awakening/extubation	Other outcomes
Non-cardiac surgery
Bellgardt et al[3], 2019, Randomized trial	Isoflurane with MIRUS™ (n = 10)	Major surgery (aortic, pancreatic, esophagectomy, spinal fusion, hyperthermic intraperitoneal chemotherapy, necrotizing fasciitis)	17.9 (16.6–20.6) h	NR	Isoflurane had longest awakening times followed by sevoflurane, with desflurane the shortest (open eyes, follow verbal commands, extubation, tell birthday). Desflurane was most expensive followed by sevoflurane, with isoflurane the cheapest (per hour)
	Sevoflurane with MIRUS™ (n = 10)		16.5 (10.4–37.4) h	NR
	Desflurane with MIRUS™ (n = 10)		18.8 (14.1–33.8) h	NR
Jung et al[27], 2020, Prospective interventional	Sevoflurane with AnaConDa (n = 25)	Head and neck surgery with tracheostomy	771 ± 338.4 min	NR	Sevoflurane required less continuous opioid. Similar vasopressor use and length of stay
	Propofol (n = 24)		1508 ± 2074.7 min	NR
Romagnoli et al[28], 2017, Prospective interventional	Sevoflurane with MIRUS™ (n = 62)	Laparoscopic and robotic-assisted noncardiac	3.33 (2.33–5.75) h	4 (2.2–5) min (awakening after drug cessation)	No adverse effects. Pollution < 1 ppm at all timepoints assessed
Cardiac surgery
Hellström et al[29], 2011, Randomized trial	Sevoflurane with AnaConDa (n = 50)	Elective or subacute coronary artery bypass grafting using cardiopulmonary bypass	176 min	NR	Sevoflurane had less intense increase in troponin at 12 h. Similar hemodynamics and length of stay
	Propofol (n = 50)		221 min	NR
Jerath et al[30], 2015, Randomized trial	Isoflurane or sevoflurane with AnaConDa (n = 67)	Elective coronary artery bypass grafting using cardiopulmonary bypass	NR	182 (140–255) min (extubation after ICU arrival)	No adverse effects. Similar hemodynamics and lengths of stay
	Propofol (n = 74)		NR	292 (210–420) min (extubation after ICU arrival)
Röhm et al[31], 2008, Randomized trial	Sevoflurane with AnaConDa (n = 35)	Elective coronary artery bypass grafting using cardiopulmonary bypass	8.1 ± 3.5 h	9.0 ± 4.0 h (extubation after ICU arrival)	Sevoflurane had faster times of recovery after sedation cessation (eye opening, following commands, hand grip, and extubation). Similar ICU length of stay, sevoflurane with lower hospital length of stay
	Propofol (n = 35)		8.4 ± 4.2 h	12.5 ± 5.8 h (extubation after ICU arrival)
Soro et al[32], 2012, Randomized trial	Sevoflurane with AnaConDa (n = 36)	Elective coronary artery bypass grafting using cardiopulmonary bypass	NR	NR	No differences in postoperative cardiac biomarkers, hemodynamics, or lengths of stay
	Propofol (n = 37)		NR	NR
Steurer et al[33], 2012, Randomized trial	Sevoflurane with AnaConDa (n = 46)	Valve replacement with cardiopulmonary bypass	At least 4 h	NR	Sevoflurane had lower troponin T and creatine kinase concentrations on postoperative day 1
	Propofol (n = 56)		At least 4 h	NR
Wąsowicz et al[34], 2018, Randomized trial	Isoflurane (n = 30) or sevoflurane (n = 30) with AnaConDa	Elective or urgent coronary artery bypass grafting using cardiopulmonary bypass	NR	172.1 ± 175.5 min (extubation after ICU arrival)	No difference in postoperative troponin values or ICU or hospital length of stay
	Propofol (n = 67)		NR	219.6 ± 104.9 min (extubation after ICU arrival)

NR: Not reported; ICU: Intensive care unit.