Thermochemical Ablation - Physics of Thermal Therapy - page 339

Is this sufficient for a thermal ablation? To answer that
question we must consider several factors. Concentration and
volume clearly play a role in the amount of energy released
from any exothermic chemical reaction, so these must be
factored into any range calculations. We chose to assess con-
centration ranges of 1-10 mole/liter and volumes of 1-10 mL.
These concentrations span a wide practical range, and the vol-
umes are in the range of what is already clinically used for
chemical ablation. These conditions would provide a range of
energy release spanning 0.5-5000 W depending on the time
over which the reaction is carried out. We concluded that
acid-base neutralization reactions do have the potential to
release enough energy to raise the desired volume of tissue by
the desired amount. Indeed, even with such small quantities
this analysis highlights why general chemistry laboratory stu-
dents are required for lab safety to store acids in one cupboard
and bases in another.
Thus far, we have concerned ourselves with simple acids.
Additional energy could be obtained from polyprotic acids such
as sulfuric (H 2 SO 4 ) and phosphoric acid (H 3 PO 4 ). With these
reagents, there are two acidic protons. Translated into practical
terms, this means that more heat would be released if a second
equivalent of base were added to the reaction to react with the
additional available proton. The third proton of phosphoric acid
is not sufficiently acidic (indeed, it is far on the alkaline side of
the spectrum) to yield any useful amount of energy.
The energy release from some other familiar biochemical
reactions is helpful in placing this kind of chemistry in context,
as shown in Figure 19.2.
Perhaps the best known is the ubiquitous molecule we know
as ATP, which releases 31 kJ/mole when broken down into
ADP and P i . This equates to a K eq of 10 5 , which is irreversible.
Hydrolysis of this compound provides the energy for many of
the essential functions of life and is also the reason our bodies
stay warmer than our surroundings. The highest energy com-
pound familiar in biochemistry is PEP, or phosphoenolpyru-
vate. Hydrolysis of PEP releases 62 kJ/mole, so it is apparent
that formation of water, then, releases nearly as much energy
as the most exothermic reaction that commonly occurs in the
body.
Neutralization chemistry is only one category of exothermic
chemistry. A brief examination of several other kinds of reac-
tions (listed in Table 19.1) is useful in order to appreciate the
full potential of potential inherent in thermochemical ablation.
Some, for example, combustion of fuels such as hydrocarbons,
rocket fuel, and explosives, clearly are not useful despite the enor-
mous energy release possible. This is due in part to the fact that
delivery of adequate amounts of oxygen to combine with fuel is
challenging, but also to the fact that such reactions generate copi-
ous amounts of exhaust gases in situ that would have to be safely
and quickly removed.
Hydrolysis reactions are another category, exemplified by the
breakdown of ATP and PEP just described. However, this kind
of chemistry can be further extended through the application of
other electrophilic species. One example is acetyl chloride, the

hydrolysis of which has been measured in the range of 90 kJ/
mole, 30 or nearly half again as energetic as PEP and approaching
twice that of the formation of water and illustrated in Figure 19.3.
The product of this reaction is acetic acid, which as noted ear-
lier on is itself a chemical ablation agent. However, in addition
to the equivalent of acetic acid, the byproduct of the hydrolysis
reaction is itself an acid. This product, hydrochloric acid, is even
stronger than acetic acid. Thus, not only does the reaction release
a substantial amount of heat energy, it produces two equivalents
of acid. Strong electrophiles may therefore find utility, particu-
larly where small volumes yet higher ablation efficiency is useful.
Oxidation-reduction or redox chemistry is another category
with potential. For example, thermite reactions can be an order
of magnitude more energetic than acid-base chemistry, with exo-
therms on the order of 800 kJ/mole or even more. At first glance,
a more-is-better approach might seem to be the best of all pos-
sible worlds. However, the extreme conditions required to initiate
these reactions are usually beyond practical reach (often exceed-
ing 400°C), and they can be very difficult or impossible to control
once started. Translated into practical terms, this means that a
molten bolus could easily burn a hole through a patient, the table,
and potentially even the floor of the IR suite much like flowing
lava. This kind of reaction is also not readily extinguished and
must burn itself out. Clearly, there are some practical upper limits
to how much energy is released and how quickly.
A more controlled example of redox chemistry is the perman-
ganate oxidation of carbohydrates and similar structures. 31 Here
the oxidizing agent is soluble in water, and concentration and
substrate both can play a role in the amount of energy released.
Relatively simple carbohydrates and related alcohols, such as eth-
ylene glycol, glycerol, and simple sugars such as glucose, fructose,
and sucrose provide an easily accessible fuel source. More com-
plex carbohydrates and other fuel substrates such as glycogen and
some polymers are not as accessible to the oxidizer and do no
react as readily, and neither does tissue. The resulting exotherms
are progressively smaller as the rate of reaction is slowed down.
Heat of solvation is an abundant source of energy. This area
revolves around the greater stability (lower energy state) of
hydrated reagents and the heat evolved as this occurs. Examples
would include the hydration of sulfuric acid or sodium hydroxide.
The dilution of concentrated sulfuric acid releases approximately
95 kJ/mole of energy. Another solvation process that has particu-
lar appeal would be in situ hydration of quicklime, also known as
slaking of lime. Calcium oxide hydrates and becomes calcium
hydroxide in a very vigorous reaction that releases approximately
64 kJ/mole of energy. In either case, the pH would be drastically
altered as well. Indeed, in the unfortunate situation of an indus-
trial accident with an acid burn, both effects, heat from solvation
and drastic pH change, are in full operation with a resulting bad
outcome. Handling of quicklime is always done with protective
equipment for similar reasons.
A final source of heat is release of energy that is intrinsic to a
molecular structure itself rather than bond energies. An example
is ring-strain energy found in three- and four-membered ring
compounds such epoxides, cylcopropanes, aziridines, and the like.