Sevoflurane, Desflurane and Isoflurane

Mechanism

💨 Sevoflurane

• Blood/gas ratio: 0.65 to 37^
• Vapor pressure: 160 mmHg at 20^
• Does not irritate the upper respiratory tract; It is the agent of choice for inhalation induction in pediatric patients.

⚡ Desflurane

• Blood/gas ratio: 0.42 to 37^
• Vapor pressure: 669 mmHg at 20^
• Requires a special thermoheated vaporizer (Tec 6) due to its boiling point close to room temperature (22.8^).

Pharmacokinetics

Pharmacokinetics and Pharmacodynamics

The speed of induction and recovery of an inhalation anesthetic is determined by its solubility in blood, represented by the blood/gas partition coefficient (λ). Agents with low λ (such as desflurane, λ = 0.42) quickly reach equilibrium between the alveolar partial pressure (P_A) and the partial pressure in arterial blood (P_a), which results in a rapid increase in cerebral partial pressure and a rapid awakening after discontinuing its administration.

The alveolar uptake of the anesthetic is described by the relationship between the alveolar concentration and the inspired concentration (F_A/F_I), represented by the following mathematical approximation of alveolar lavage:

Where V_A is the alveolar ventilation and V_FRC is the lung functional residual volume. This theoretical model is continually modified by the uptake of the drug into the pulmonary capillary blood, which depends on the cardiac output (Q) and the alveolovenous partial pressure gradient.

Security

Absolute and Relative Contraindications

• Genetic susceptibility to Malignant Hyperthermia: Absolute contraindication for all halogenated liquids.
• Pre-existing Renal Failure (Sevoflurane): Relative. The degradation of sevoflurane by dehydrated soda or baryta lime from anesthesia machines generates a nephrotoxic vinyl ether called Compound A (fluoromethyl-2,2-difluoro-1-(trifluoromethyl)vinyl ether). It is advisable not to use fresh gas flows lower than 1 L/min to limit its accumulation in the circuit.
• Severe Intracranial Hypertension: Relative contraindication. All halogenated drugs produce dose-dependent cerebral vasodilation, and may increase cerebral blood volume and intracranial pressure (ICP) if administered at doses greater than 1 MAC without prior protective hyperventilation.

Critical Adverse Effects

• Halogenated Hepatitis: Rare autoimmune condition mediated by antibodies against liver proteins modified by trifluoroacetyl radicals derived from drug metabolism (extremely low frequency with desflurane and sevoflurane compared to halothane).
• Vasodilation and Cardiodepression: They decrease central sympathetic outflow and block L-type calcium channels in the myocardium, causing dose-dependent arterial hypotension.
• QTc Interval Prolongation: All halogenated drugs can alter cardiac ventricular repolarization.

Carbon Monoxide in Closed Circuits

Desflurane and isoflurane can react with extremely dry carbon dioxide absorbents (dehydrated soda lime) to generate toxic levels of carbon monoxide (CO) within the anesthesia circuit. To avoid this critical risk, the hydration status of the absorbent should be checked and systematically replaced if the fresh gas flow has been left on for prolonged periods in disused anesthesia machines.

Clinical

Concept of MAC and its Clinical Modulation

The Minimal Alveolar Concentration (MAC) is the alveolar concentration of an anesthetic gas at 1 atmosphere of pressure that suppresses motor movement in response to a nociceptive surgical stimulus (1 cm skin incision) in 50% of patients. The MAC is additive and varies inversely with the patient's age.

Factors that decrease MAC: hypothermia, hyponatremia, pregnancy, acute alcohol intoxication, severe anemia, hypoxia, metabolic acidosis and concomitant administration of opioids, clonidine, dexmedetomidine or intravenous anesthetics. Factors that increase MAC: hyperthermia, hyperthyroidism, infants under 6 months of age and chronic intake of alcohol or other enzyme inducers.

Class Technical Sheets