What are the recommended dosing, administration, monitoring, contraindications, side effects, and alternative agents for using isoflurane in an adult undergoing general anesthesia?

Isoflurane for General Anesthesia in Adults

Isoflurane is a safe and effective volatile anesthetic for maintenance of general anesthesia in adults, particularly beneficial for hemodynamically stable patients at risk for myocardial ischemia, though newer agents like sevoflurane and desflurane offer faster recovery profiles. 1

Recommended Dosing

Maintenance Concentration:

• 1.15% (1 MAC) represents the minimum alveolar concentration for isoflurane, which is 1.5 times that of halothane and two-thirds that of enflurane 2
• Typical maintenance range: 0.5–3% end-tidal concentration in oxygen or oxygen-nitrous oxide mixtures 3
• MAC is reduced when co-administered with nitrous oxide; adjust concentration accordingly 3

Induction (if used):

• Rapid inhalational induction: 5% isoflurane in humidified oxygen produces induction in approximately 121 seconds, though this is slower and less well-tolerated than sevoflurane 4, 5
• Single vital capacity breath technique with 3.5% isoflurane (3.6 MAC equivalent) has only 75.8% success rate and 84.8% complication rate, making it inferior to sevoflurane for this purpose 5

Administration & Monitoring

Delivery System Requirements:

• Must be administered only in adequately equipped anesthetizing environments by trained personnel familiar with the drug's pharmacology 3
• Use calibrated vaporizers designed specifically for isoflurane 3
• Ensure fresh CO₂ absorbent; desiccated barium hydroxide lime or soda lime can react with isoflurane to produce carbon monoxide, elevating carboxyhemoglobin levels 3

Essential Monitoring:

• Continuous end-tidal anesthetic concentration monitoring 3
• Standard ASA monitors: ECG, blood pressure, pulse oximetry, capnography, temperature 3
• Neuromuscular monitoring when muscle relaxants are used, as isoflurane significantly potentiates nondepolarizing agents 3, 6
• Maintain normal hemodynamics to avoid myocardial ischemia in patients with coronary artery disease 3

Cardiovascular Effects & Cardioprotection

Hemodynamic Profile:

• Largest circulatory margin of safety among halogenated agents; produces the least myocardial depression at a given MAC multiple 2
• Decreases total peripheral resistance (SVR), thereby reducing systemic arterial pressure 2, 6
• May increase heart rate, particularly in younger patients; occasional tachycardia and hyperdynamic responses (HR/BP >20% above baseline) can occur during rapid deepening 2, 6
• Cardiac output typically increases or remains stable due to afterload reduction 6

Cardioprotective Benefits:

• ACC/AHA guidelines (Class IIa recommendation): It can be beneficial to use volatile anesthetic agents including isoflurane during noncardiac surgery for maintenance of general anesthesia in hemodynamically stable patients at risk for myocardial ischemia 1
• In cardiac surgery trials, isoflurane administered before cardiopulmonary bypass decreased troponin I release in patients with ejection fraction <50% and improved left ventricular function 1
• Demonstrates cardioprotective effects through preserved mitochondrial oxygen consumption and reduced troponin release 1
• Preconditions and postconditions the heart against infarction by activating intracellular signal transduction pathways 1

Respiratory Effects

Ventilatory Depression:

• Depresses ventilation less than enflurane but slightly more than halothane 2
• Dilates constricted bronchi, making it useful for patients with asthma or chronic obstructive pulmonary disease 2

Cerebral Effects:

• At 1.6 MAC, isoflurane increases cerebral blood flow less than halothane, making it preferable when increases in intracranial pressure should be avoided 1, 7
• Does not produce convulsive activity 2

Muscle Relaxation & Drug Interactions

Neuromuscular Blockade Enhancement:

• Significantly potentiates all muscle relaxants, most notably nondepolarizing agents 3
• ED₅₀ and ED₉₅ for pancuronium are significantly lower under isoflurane (both low and high MAC) compared to balanced anesthesia 6
• Enhancement is comparable to enflurane and greater than that produced by halothane or nitrous oxide-narcotic techniques 2
• Use neuromuscular monitoring and reduce muscle relaxant doses by approximately 30–50% 3

Contraindications

Absolute Contraindications:

• Known or suspected genetic susceptibility to malignant hyperthermia 3
• Known sensitivity to isoflurane or other halogenated anesthetics (risk of sensitivity hepatitis in previously sensitized patients) 3

Relative Contraindications:

• Severe hepatic dysfunction or prior halogenated anesthetic-induced hepatitis 3
• Situations requiring rapid sequence induction (due to pungency and slower induction compared to IV agents) 5, 4

Side Effects & Adverse Reactions

Common Side Effects:

• Respiratory irritation, coughing, breath-holding, and laryngospasm during induction (due to pungency) 5, 4
• Hypotension from peripheral vasodilation 2, 6
• Tachycardia, especially in younger patients 2, 6
• Transient increases in blood glucose and serum creatinine 3
• Transient decreases in BUN, serum cholesterol, and alkaline phosphatase 3

Serious Adverse Events:

• Malignant hyperthermia (rare but life-threatening) 3
• Sensitivity hepatitis in previously sensitized patients 3
• Carbon monoxide production when used with desiccated CO₂ absorbent 3
• Hyperdynamic cardiovascular response during rapid deepening (7/16 patients in one study vs. 1/16 with isoflurane) 6

Postoperative Effects:

• Slight decrease in intellectual function for 2–3 days following anesthesia 3
• Small changes in mood and symptoms may persist up to 6 days 3

Metabolism & Toxicity Profile

Minimal Biotransformation:

• Only 0.17% of absorbed isoflurane appears as urinary metabolites, the lowest of all halogenated agents 2
• This resistance to biodegradation explains the minimal or absent hepatotoxicity and nephrotoxicity 2
• No evidence of carcinogenicity in long-term animal studies 3
• Negative for mutagenicity in Ames test and chromosomal aberration assays 3

Alternative Agents

Sevoflurane:

• Preferred for inhalational induction due to lack of pungency, faster induction (45 vs. 71 seconds), 100% success rate vs. 75.8% with isoflurane, and fewer complications (11.8% vs. 84.8%) 5
• Similar cardioprotective profile with decreased troponin release and improved LV function in cardiac surgery 1
• Faster return of airway reflexes in obese patients compared to isoflurane 1

Desflurane:

• Similar to isoflurane in maintenance hemodynamics and muscle relaxant interaction 6
• Faster onset and offset than isoflurane due to lower blood-gas partition coefficient 1
• May cause more airway irritation during induction 6
• Faster return of airway reflexes compared to sevoflurane in obese patients 1

Propofol (Total Intravenous Anesthesia):

• In cardiac surgery trials, volatile anesthetics including isoflurane showed superior cardioprotection compared to propofol, with decreased troponin release, improved LV function, and decreased ICU length of stay 1
• May be preferred when volatile anesthetics are contraindicated or in obese patients requiring depth-of-anesthesia monitoring 1

Special Populations

Obese Patients:

• Fat-insoluble agents like desflurane or sevoflurane have faster onset and offset than isoflurane and are preferred 1
• Use depth-of-anesthesia monitoring to limit anesthetic load 1
• Ensure complete neuromuscular blockade reversal before extubation 1

Patients with Coronary Artery Disease:

• Volatile anesthetics including isoflurane can be beneficial for maintenance in hemodynamically stable patients at risk for myocardial ischemia (ACC/AHA Class IIa recommendation) 1
• Maintain normal hemodynamics throughout to avoid myocardial ischemia 3
• Evidence shows coronary blood flow remains adequate with isoflurane even in the presence of coronary artery disease 2

Pediatric Patients:

• Discuss with parents the potential negative effects on developing brains in children <3 years with repeated or prolonged exposure 3
• Balance benefits, risks, timing, and duration of anesthetic exposure 3

Critically Ill Patients:

• Do not use isoflurane for procedural pain management in ICU patients (strong recommendation, very low quality evidence from Society of Critical Care Medicine) 1
• Increased resource requirements, safety concerns outside operating rooms, and lack of efficacy data support this recommendation 1
• Use lowest effective doses of opioids for procedural pain instead 1

Common Pitfalls to Avoid

• Do not use desiccated CO₂ absorbent; replace if suspected to prevent carbon monoxide production 3
• Do not use isoflurane for rapid sequence induction or single vital capacity breath induction; sevoflurane is superior for these techniques 5
• Do not forget to reduce muscle relaxant doses by 30–50% due to significant potentiation 3, 6
• Do not use isoflurane for procedural sedation in ICU settings; it is not recommended for this indication 1
• Do not administer to patients with known or suspected malignant hyperthermia susceptibility 3
• Do not use in patients previously sensitized to halogenated anesthetics due to hepatitis risk 3
• Do not assume isoflurane is the best choice for all patients; sevoflurane and desflurane offer faster recovery, particularly important for obese patients and outpatient procedures 1, 5, 7