Vital Times 2017 - 88
of new inhaled anesthetics. Although these three
pursuits stand alone, they grew as deeply intertwined
threads of research, each drawing from the others.
Just imagine being an anesthesiologist before
publication of Ted's clinical investigations during the
1960s. You would have defined the clinical dose of
anesthesia as the vaporizer setting but not understand
that the concentration setting on the vaporizer meant
little, since the concentration delivered to the patient
depended on fresh gas flow, anesthetic uptake by the
lungs, anesthetic solubility in blood and tissue, cardiac
output and V/Q matching. You also wouldn't have a
standard language for potency. You would know that
it took about 1 percent halothane to keep the patient
still during surgery, but that meant nothing about how
much methoxyflurane might be required. Ted turned
this upside down and changed the language that we
speak.
In 1963 Ted and Giles Merkel published the first
paper describing depth of anesthesia in dogs as the
"the minimal anesthetic concentration (MAC) in the
alveolus required to keep a dog from responding by gross
movement to a painful stimulus such as tail clamping or
varying electrical currents applied to sensitive mucous
membranes." The unique insight was that the alveolar
concentration, rather than the inspired concentration,
was the basis of potency. The rationale behind this
concept is based on the assumption the alveolar
anesthetic partial pressure equals that in arterial blood
and consequently the brain and therefore monitoring
alveolar rather than inspired concentration represents
a reasonably accurate-albeit indirect- surrogate of
anesthetic depth. Ironically this revolutionary paper
was about halopropane, an anesthetic subsequently
discarded as clinically useless.
Years later, we learned that the anesthetic
concentration in the spinal cord was responsible for
immobility in response to surgical pain. It mattered
little, other than as a footnote about anesthesia
mechanisms, because Ted built MAC around a
88 | CSA Vital Times
clinical endpoint rather than around a model of the
neurobiology.
I was a fellow of Ted's in 1963 and 1964. Talk about
good luck! The first anesthesia publication of which
I was an author was the first MAC paper in humans.
This paper was awarded first prize in both the
California and the ASA Resident Research contests
and eventually became among the 100 most cited
papers in the anesthesia literature. It shows that "it is
better to be lucky than good." (Ted was both.)
MAC became our standard measure of clinical
potency, but Ted put MAC to work as a research tool.
Was MAC a common trait of anesthetics? Did MAC
align with the Meyer-Overton observation about
potency and lipophilicity? Was MAC stable over time?
Was MAC affected by age, illness, or other drugs?
Could MAC be used to calibrate different anesthetics
to the same anesthetic depth? Ted answered these
questions. The MAC riddle that eluded Ted, to which
he devoted his final decades of research, was the
neurobiology of MAC. It still remains unsolved.
Ted began his work in anesthetic pharmacokinetics,
his second seminal contribution, while stationed at
Ft. Leavenworth. The concentration and second gas
effects emerged unexpectedly from the mathematical
models he created. He later would demonstrate these
experimentally. Ted synthesized his years of research
in his classic textbook "Anesthetic Uptake and Action,"
published in 1974. In terse prose, Ted translated for
the initiate why we do what we do, how anesthetists
govern the rate of anesthetic onset and offset, and how
we titrate anesthetics in response to patient changes
in cardiac output, ventilation, V/Q matching, and
patient comorbidities. Ted completely nailed down
the concepts of uptake and distribution. They have
remained virtually unchanged since his book was
published four decades ago.
Ted's third contribution, introducing new anesthetics,
grew out of his deep understanding of MAC and
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