CPM Summer 2018 - 25

daup h i n c m s .o rg

irst, it is important to understand
that the "day-to-day" brain processing (which actually stated
more appropriately is "nanosecond-to-nanosecond") occurs using multiple
chemicals such as norepinephrine, serotonin,
dopamine, glutamate, opioids, endocannabinoids, and GABA; as well as electrical
conduction and gases such as nitric oxide
(NO) (Not nitrous oxide (N2O) for all
you Jimmy Buffet fans!). The complexity
of our nervous system as well as its speed of
function is truly impossible to replicate. We
in anesthesia use it to our advantage since
any short-term change in the balances of
the above will lead to altered consciousness.
Second, anesthesia has four important
components: 1] Hypnosis (sleep) 2] Amnesia
(loss of memory) 3] Analgesia (pain suppression) and 4] Muscle Relaxation (paralysis).
Therefore, to produce an appropriate surgical
state of anesthetic depth, all four need to be
obtained at some reasonable level. Paralysis
is included because it is important for the
surgeons to have a "quiet" field without
intense muscle contractions inhibiting
their ability to access the organ, bone and
tissue they are operating on or around to
achieve success.
Since the dawn of "modern" anesthesia
utilizing gases such as N2O or ether, the goal
was to find the one "magic bullet" that can
cover all four components of anesthesia with a
single agent. But, the brain has proven to be
way too complex to allow a single molecule
to achieve all four goals to an adequate degree
without leading to significant side effects.
For example, ether was too slow in onset and
recovery an N2O was too impotent. Agents
such as chloroform and cyclopropane showed
promise however both seemed a little too "fatal"
at times whether due to chloroform's tendency
to kill livers and kidneys or cyclopropane's
tendency to blow up operating rooms. The
fluorinated hydrocarbons such as halothane
and its many offspring have come close, but
still to achieve all four at each's desired level
has been less than successful. The solution has
been to use multiple medications to achieve
surgical anesthesia: Anesthetic polypharmacy.
(Most agents used in anesthesia commonly

effect more than one component but rarely
each to the same degree.)
Hypnosis is usually obtained by a short
acting "hypnotic" such as propofol (2,6-diisopropylphenol), ketamine (NMDA receptor
antagonist), etomidate (positive allosteric
modulator at the GABA receptor) and the
barbiturates. Maintenance of the appropriate
level of hypnosis after induction (onset of
hypnosis) usually is obtained with the above
mentioned fluorinated hydrocarbons mixed
with pure oxygen and air.
The most potent amnestics are the benzodiazepines such as midazolam (versed) which
we commonly give prior to the induction of
anesthesia to reduce anxiety. Maintenance of
amnesia is usually obtained with continued
administration of benzodiazepines as well as
with the fluorinated hydrocarbons.
Analgesia is most famously achieved with
powerful opioids such as fentanyl, morphine
and hydromorphone (Dilaudid). Although,
today, we commonly use a "multimodal
approach" to reduce opioid induced side
effects. Other agents used for pain suppression include: local anesthetics such as
lidocaine, ketamine, magnesium, acetaminophen, NSAIDs, alpha 2 agonists such as

dexmedetomidine, steroids, gabapentinoids
such as gabapentin (Neurontin), and in the
future possibly cannabinoids.
Paralysis of the muscles is achieved using
agents that block transmission of electrical
signals from the motor nerves to the skeletal
muscle. These agents include succinylcholine,
the benzylisoquinoliniums, and steroidal
neuromuscular blockers such as the most
commonly used, rocuronium.
There are also a supporting cast of medications that we use in the OR for controlling
nausea and vomiting such as serotonin,
dopamine, muscarinic, neurokinin 1 and
histamine receptor blockers; controlling
blood pressure and heart rate such as beta,
alpha, and calcium receptor blockers as well as
stimulants at those same receptors to have the
reverse effect; and agents such as sugammadex
and neostigmine to reverse the paralysis of
the skeletal muscles. And, there are many
more depending on the patients, their health
and the surgical procedure being performed.
Therefore, as you can see, that "sleep"
that you commonly refer to when you
describe your anesthetic involves multiple
chemicals in the correct amounts to be
achieved successfully.
Central PA Medicine Summer 2018 25


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Table of Contents for the Digital Edition of CPM Summer 2018

CPM Summer 2018 - 1
CPM Summer 2018 - 2
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