General Anesthetics: Inhaled Agents

Inhaled Agents

Overview

Inhaled anesthetics enter the body and form an equilibrium between the alveoli, blood, and tissues within the body.
Note that inhaled anesthetics differ from other drugs because they are absorbed and eliminated through the same organ, the lungs.
The concentration at the target tissue, in this case the CNS, causes the action we see.

Mechanism of Action (MOA)

Note that the mechanism of action for inhaled anesthetics MOA is not fully known but they probably act on a multitude of targets; namely they increase the inhibitory effects of GABA and glycine and reduce the excitatory effects of serotonin, acetylcholine at nicotinic receptors, and glutamate at NMDA and AMPA receptors.
We consider MAC, B/G PC, and lipophilicity in order to determine the onset of action and recovery from these drugs.

Drugs

General Effects

As a general rule, the inhaled anesthetics cause

Myocardial depression with blood pressure reduction and either reduced cardiac output or peripheral vasodilation.
Respiratory depression with reduction in tidal volume and minute ventilation and a consequential rise in arterial CO2 tension.
Postoperative nausea/vomiting.
Decreased cerebral metabolic rate and increased cerebral blood flow, which can increase intracranial pressure.

Side Effects

Halothane

For halothane, think of hepatotoxicity; this is rare and is thought to occur through a reactive metabolite that either produces direct toxicity or indirect toxic immune-mediated responses.
And also catecholamine sensitivity. In the setting of catecholamines, halothane (and isoflurane) are known to cause cardiac arrhythmia.

Methoxyflurane

For methoxyflurane (also, possibly enflurane and sevoflurane), think of nephrotoxicity. This can occur in prolonged exposure.

Enflurane

For enflurane, think if epileptogenicity (it can cause spike-and-wave activity on EEG) and resultant muscle twitching.

Nitrous oxide

Nitrous oxide (NO) is often referred to as laughing gas because it produces a mild euphoria.
Nitrous oxide serves as a great review of the general principles we introduced at the beginning:

Indicate that of the inhaled agents, it has the highest MAC, so it has the lowest potency and it has a fast onset due to a low B/G PC.

Importantly, it produces marked analgesia and amnesia and it has the smallest effect on blood pressure reduction and respiratory depression.
From a toxicity standpoint, know that prolonged exposure can inhibit vitamin B12 and thus produce spinal cord degeneration, called subacute combined degeneration (damage to the dorsal columns of the spinal cord).

Sevoflurane

Sevoflurane is the least pungent of the agents; it is sweet smelling whereas Enflurane, isoflurane, and desflurane are known to be pungent agents with airway irritation and spasm.

Malignant Hyperthermia

Overview

Trigger

A key trigger can be the combination of inhaled anesthetics and neuromuscular blockade (especially succinylcholine).

Symptoms/Signs

Symptoms and signs include rapid-onset of hyperthermia, muscle rigidity, hypertension, and tachycardia.

Diagnostics

Labs show hyperkalemia and acidosis.
We follow creatine kinase (CK) levels and urine myoglobin levels as markers of muscle injury.

Treatment

We treat it with dantrolene, which is also used to treat neuroleptic malignant syndrome because it is a direct-acting skeletal muscle relaxant, as well as cooling and supportive care.

Genetic susceptibility

Certain genetic susceptibilities are key causes, including ryanodine receptor (RyR1) mutations and mutations in the genes that encode skeletal muscle L-type calcium channels.