The_20Scientist_20March_202019 (1)

40 THE SCIENTIST | the-scientist.com

The modern definition of general

anesthesia requires that five endpoints

are achieved. (See Box on page 39.)

Ether provides all of these endpoints

to some degree. Most modern inhaled

anesthetics, such as isoflurane, des-

flurane, and sevoflurane, are chemical

derivatives of ether but are more potent,

less flammable, and are delivered using

modern vaporizers and techniques.

Improvements to the hypodermic nee-

dle achieved in the second half of the

19th century made possible the devel-

opment of intravenous anesthesia, and

physicians began combining anesthetic

drugs with opioids to more effectively

achieve analgesia. Later, muscle relax-

ants were added to ensure immobility.

The modern practice of general

anesthesia, known as balanced anes-

thesia, uses combinations of drugs

with the goal of distancing the patient

from the trauma the body is undergoing

while minimizing side effects. Recently,

researchers have detailed the mecha-

nism underlying the action of modern

anesthetics, identifying links between

the neural receptors on which the drugs

act and patterns of overall brain activ-

ity that are linked to changes in neu-

ronal firing. These connections allow

anesthesiologists to track brain activ-

ity patterns during general anesthesia

to improve patient experiences and out-

comes, as well as to learn more about

how the anesthetized brain functions.

How is general anesthesia

achieved?

One of the most conspicuous features of

general anesthesia is the profound state

of unconsciousness that it produces. Up

until the 1980s, the prevailing hypoth-

esis on how the unconscious state was

achieved was influenced by the observa-

tion that anesthetic potency directly cor-

related with solubility in olive oil, suggest-

ing a hydrophobic site of action such as

the lipid bilayer membranes of neurons.

Researchers speculated that the drugs dis-

rupted normal membranes function and

prevented the conduction of action poten-

tials. This idea was known as the lipid

ANESTHETICS AND

NEURONAL RECEPTORS

General anesthetics work by altering the activity of specifi c neurons in the brain. One

main class of these drugs, which includes propofol and the ether-derivative sevofl urane,

work primarily by increasing the activity of inhibitory GABAA receptors, while a second

class that includes ketamine primarily blocks excitatory NMDA receptors.

PROPOFOL AND SEVOFLURANE

The GABAA receptor is a channel that allows chloride ions to fl ow into the neuron,

decreasing the voltage within the cell relative to the extracellular space. Such hyper-

polarization decreases the probability that the neuron will fi re. Propofol and sevofl urane

increase the chloride current going into the cell, making the inhibition more potent.

KETAMINE

The NMDA receptor allows sodium and calcium ions to fl ow into the cell, while

letting potassium ions out, increasing the voltage within the cell relative to the extra-

cellular space and increasing the probability of neural fi ring. Ketamine blocks this

receptor, decreasing its excitatory actions.

© LUCY

READING-IKKANDA

Propofol/

sevofl urane

GABAA

receptor

Cl-

WITHOUT ANESTHETIC WITH ANESTHETIC

WITHOUT ANESTHETIC WITH ANESTHETIC

Na+

NMDA

receptor Ketamine

K+

Ca2+