03.2019 | THE SCIENTIST 39
B
efore the advent of general anes-
thesia in the mid-19th century,
surgery was a traumatic experi-
ence for everyone involved—the
patient, of course, but also the medical
staff and anyone who happened to walk
by the surgery room and could hear the
screams. The practice of putting patients
in a reversible coma-like state changed
surgery to a humane and often life-saving
therapy. Because general anesthesia was
such a game changer in medicine, these
drugs were implemented in the operat-
ing room many decades before research-
ers understood how they worked.
Nowadays, researchers and anesthesi-
ologists know much more about the mech-
anisms underlying the effects of anesthetic
drugs and how they produce the profound
change in behavioral state that implies a
total lack of perception. Anesthetics pri-
marily act on receptors located in the brain
and produce oscillations in the brain’s cir-
cuits, leading to a state of consciousness that
it is much more similar to a coma than to
sleep. Anesthesiologists typically used vital
signs, such as heart rate and blood pres-
sure, to assess the adequacy of the anesthe-
tized state and the processing of pain sig-
nals. However, the effects of anesthetics in
brain circuits result in conspicuous oscilla-
tions in the brain’s electrical activity, which
prompted the addition of electroencepha-
lography (EEG) measurements to monitor
the brain state of an anesthetized patient.
Starting in the 1990s, researchers devel-
oped algorithms to consolidate the signals
recorded from several EEG electrodes into
a single number that provided a simpli-
fied measurement of arousal level. More
recently, direct observation of the raw EEG
signals and their breakdown in time by fre-
quencies, the spectrogram, is gaining trac-
tion for monitoring patients during general
anesthesia. Learning to interpret the raw
brain activity and its spectrogram, rather
than relying on a single-number summary,
has allowed anesthesiologists to assess how
different anesthetics affect brain activity
and produce the anesthetic state.^1
By tracking brain activity during general
anesthesia, researchers are also uncovering a
wealth of new information that helps them
understand the biological basics of how
brain function is altered in an anesthetized
state. In addition, general anesthesia has
provided new options to treat a range of ail-
ments, from sleep problems to depression.
Ether follies
Humans have practiced surgical pro-
cedures for thousands of years, and the
search for ways to minimize pain and
discomfort during invasive interventions
is probably just as old. Wine and opium
are among the first substances known to
have been tried. Opium is a potent anal-
gesic and mild sedative, and the ethyl
alcohol in wine is a sedative, but nei-
ther of these drugs succeeds in making
patients unaware of the trauma their bod-
ies undergo during surgery.
In the first half of the 19th century,
dentists stumbled upon two promising
leads: nitrous oxide, which soon after its
discovery became widely used in the US
and Europe to perform tooth extractions,
and chloroform, which was used for both
veterinary and human surgeries for a few
decades before it fell out of favor due to
safety concerns. In the 1840s, Boston
dentist William Morton was looking for
ways to perform pain-free dental proce-
dures and considered using nitrous oxide.
But, Charles Jackson, a chemist at Har-
vard Medical School, advised him to try
another option: ether.
At that time, it was common in aca-
demic and other social circles to hold
parties, called “ether follies,” where peo-
ple would inhale ether for its exhilarating
properties. Jackson had seen a man sustain
a considerable leg injury during one such
escapade. The man, who had been high on
ether, showed no signs of pain. Morton took
Jackson’s advice and proceeded to experi-
ment with ether on himself and his dog,
and subsequently performed several den-
tal procedures on his patients after admin-
istering the drug to them.
Morton contacted Harvard Medi-
cal School surgeon Henry Bigelow, and
together they organized what would
become known as the first public demon-
stration of surgery performed under gen-
eral anesthesia. On October 16, 1846, in the
operating theater now known as the Ether
Dome at Massachusetts General Hospital,
John Collins Warren, the founding dean
of Harvard Medical School and the hospi-
tal’s chief surgeon, removed a tumor from
the neck of patient Edward Gilbert Abbott,
while Morton held a glass flask contain-
ing an ether-soaked sponge that spouted
ether vapor through a glass tube that was
attached to Abbott’s nose. Several promi-
nent surgeons and physicians watched
from the viewing area of the theater.
Warren performed the surgery with the
patient showing minimal signs of pain;^2 at
the end of the procedure, Warren famously
declared: “Gentlemen, this is no humbug.”
Afterward Abbott did state that he had
experienced sensations, though not pain,
during surgery. The following d ay, flaws in
ether administration were corrected, and
a second tumor removal patient declared
that she had felt and known nothing. Sur-
geries using ether-induced anesthesia
were soon performed at nearby hospitals,
and within a couple of months it began to
change medical practice the world over.
General anesthesia is a drug-induced
reversible state defi ned by fi ve end points:
- Unconsciousness, lack of awareness
of sensory input
- Analgesia, lack of pain
- Akinesia, lack of movement
- Amnesia, lack of recall
- Physiological stability, the preser-
vation of normal levels of all vital
physiological functions, such as res-
piration, heart rate, blood pressure,
and temperature
E.N. Brown et al., “General anesthesia, sleep and
coma,” New Engl J Med, 363:2638–50, 2010.
