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8/10/2019 Does Compounding of Local Anesthetic Agents.25
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579
Does Compounding
of
Local Anesthetic Agents
Increase Their Toxicity
in
Humans?
DANIEL C. MOORE, M.D.
L DONALD BRIDENBAUGH, M.D.
PHILLIP
0
RIDENBAUGH, M.D.
GALE E THOMPSON, M.D.
GEOFFREY
T.
TUCKER, Ph.D.t
Seatt le, Wash ing ton *
s
YET the ideal local anesthetic agent
A has not been produced. The pharma-
cologic and physiologic characteristics of
such an agent probably would include:
(1)
rapid onset;
(2)
wide and rapid spread,
with deep penetration of nerves; (3) low
tissue toxicity; 4 ) low systemic toxicity;
(5) rapid absorption from the site of injec-
tion, so as not to cause tumefaction; (6)
rapid detoxification, without accumulation
of the drug or its metabolic byproducts;
(7) stability, permitting heat sterilization;
8)
high solubility in cold physiologic
sa
line solutions; and
(9)
prolonged duration
of action,
so that a single-dose rather than
a continuous-dose technic might be em-
ployed. These characteristics should not de-
pend on the use
of
a vasoconstrictor drug
in the local anesthetic solution, but should
be maintained if vasoconstrictors are indi-
cated.
To approach these requirements, we and
others have used the technic of compound-
ing (mixing of two local anesthetic agents)
to take advantage of the rapid onset, spread,
and penetration of one agent and the pro-
longed duration of action
of
another.1-*
Either dibucaine or tetracaine has been
compounded with chloroprocaine, hexyl-
caine, lidocaine, mepivacaine, or procaine
in approximately 2098 patients for caudal
and epidural blocks.1-3
*The Mason Clinic, Seattle, Washington 98101.
?University of Washington School
of
Medicine, Seattle, Washington 98105. Virginia Mason Research
Center, Seattle, Washington 98101.
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580 ANESTHESIA
ND
ANALGESIA.
.Current Researches
VOL.51,
NO. ,
JULY-AUGUST972
In white rats, white mice, and in dogs,
the compounding of tetracaine with chloro-
procaine, lidocaine, mepivacaine, procaine,
and prilocaine has increased the incidence
of systemic toxic reactions and deaths in
comparison with the use of these agents
singly.5--7 Additive or synergistic action has
been considered the cause of increased tox-
icity, with the implication of similar effects
in
This paper presents the results of our
use of compounded solutions in humans, in
partial answer to the question, Is toxicity
increased when compounded solutions of
local anesthetic agents are injected into
humans?
METHOD
The following data were abstracted from
the anesthetic records of patients given com-
pounded so lu tion s of lo ca l anesthetic
agents: (1) types and number of blocks
administered; 2 ) dosage of the two local
anesthetic agents; (3) dosage of vasocon-
strictor drugs; 4) onset and establishment
of surgical anesthesia;
(5)
duration of the
block; (6) complications. Duration was de-
termined by noting the time in the postop-
erative period when the patient complained
of pain in the operated area, or during the
surgical procedure when there was evidence
of the block dissipating, indicated by pain
in the conscious patient, or, in the semicon-
scious or unconscious patient, restlessness;
increased respiration, blood pressure,
or
pulse rate; return of muscle tone; the need
for additional anesthesia to complete the
surgical procedure; or combi nati on s of
these. Complications included those from
the local anesthetic agents themselves, such
as local tissue toxicity, generalized systemic
toxic reactions, or neurologic sequelae, but
TABLE
1
Number
o f
Epidural Caudal an d Peripheral
Nerve Blocks Performed with Compounded
Solutions for Surgical and Obstetric
Procedures
N u m b e r o f N u m b e r o f
C o m p o u n d e d a g e n t s e p i d u r a l o n d p e r i p h e r a l
c oud o l b l oc k s ne r v e b l oc k s
Lidocaine + tetracaine 6277 1
Mepivacaine
+
tetracaine
2539 986
Chloroprocaine+ tetracaine
638 12
Propoxycaine + tetracaine
78
0
Prilocaine + tetracaine
3 4
9535 1003
Total
10,538
not those inherent in technic, such as hypo-
tension from sympathetic blockade follow-
ing epidural block.
RESULTS
All blocks were performed as described
earlier,4 and compounded solutions were
used in single-dose technics only.
NUMBER
F PATIENTS OCALANESTHET-
FORMED.
-From
1952,
when we
started
to
use compounded solutions (chloroprocaine,
lidocaine, mepivacaine, prilocaine, or pro-
poxycaine plus tetracaine) through 1970, a
total of 10,538 patients received such solu-
tions for (1) caudal block; 2 ) epidural
block;
(3)
brachial plexus block; or 4) sci-
atic and femoral nerve blocks, with or with-
out lateral femoral cutaneous nerve block,
obturator nerve block, or both (tables 1and
2). Compounding of solutions for periph-
eral nerve block was not started until
1967.
IC AGENTSEMPLOYED AND BLOCKS ER-
TABLE 2
Types and Numbers of Peripheral Ner ve Blocks Done wi th
Compounded Solutions for Operat ive Procedures
Blocks
L i d o c a i n e + M e p i v a c o i n e + Pr i l oc a i ne + C h l o r o p r a c a i n e +
t e t r ac o i ne te t r ac a i ne te t r ac a i ne te t r ac a i ne
Brachial plexus
Axillary
141
1
5
Supraclavicular
1 333 3 3
Sciatic
and
femoral
nerves,
with
o r
512
4
1 986 4 12
without lateral femoral cutaneous
nerve
and obturator nerve
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Local Anesthetic Toxici ty. ..Moore,
et
a1
Chloroprocaine, lidocaine, or mepivacaine
plus tetracaine were the principal com-
pounds employed. Prilocaine and propoxy-
caine were used in only 85 cases before
1966; because of the insignificant number,
these will not be considered further. Lido-
caine or chloroprocaine plus tetracaine were
the principal agents compounded through
1966. Lidocaine plus tetracaine was used in
only one peripheral nerve block during that
time; therefore this compound for such use
is given no further consideration. Prior to
1967 chloroprocaine was compounded with
tetracaine for 638 epidural blocks but for
only 12 peripheral nerve blocks, and the
peripheral nerve blocks will not
be
consid-
ered further. The use of chloroprocaine was
discontinued when the pharmaceutical com-
pany that originally developed the agent
stopped producing it.
After 1966, mepivacaine plus tetracaine
was used almost exclusively because the
time of onset, spread, penetration, and es-
tablishment of surgical anesthesia of mepi-
vacaine were comparable to those of lido-
caine, and the commercial packaging of the
agent was better suited for our method of
compounding.
DOSAGE. Solutions to be compounded
were mixed immediately before injection.
We incorporated epinephrine in all com-
pounded solutions. For epidural and caudal
block through
1966,
the epinephrine con-
centration varied depending on the volume
of the local anesthetic solution injected,
that is, where
12
to
25
ml. was administered
the concentration was 1:125,000 and when
26 to 50 ml. was used, 1:200,000.From 1967
on the maximum concentration of epineph-
581
rine was 1:200,000, hat
is,
0.1 ml. 0.1mg.)
of epinephrine
1:lOOO
in
20
ml. of solution,
and the maximum total milligram
dose
of
epinephrine for any regional block technic
was 0.25 mg. Even when regional block
technics requiring more than
50
ml. of the
local anesthetic solution were executed
(block of the sciatic, femoral, lateral fe-
moral cutaneous, and obturator nerves,
which require 100 ml.) 0.25 mg. of epineph-
rine was not exceeded since this amount
does not usually cause a severe epinephrine
reaction or initiate arrhythmias even in pa-
tients with cardiac disease. Therefore, in
peripheral nerve blocks requiring in excess
of 50 ml. of the local anesthetic solution the
concentration is less than 1:200,000 e.g.,
when 100 ml. is used the concentration of
epinephrine is
1
:400 000.
For lumbar epidural block used primar-
ily for intra-abdominal surgery, 2 mg. of
tetracaine was added to each milliliter of
either 1.5 percent lidocaine, 1.5 percent me-
pivacaine, or 2 percent chloroprocaine, and
a maximum of 20 ml. was injected into the
lumbar epidural space.4 In the majority of
cases the dose was 18 ml. or less.
For caudal block used primarily for
perineal surgery, 2 mg. of tetracaine was
added to each milliliter of
1.5
percent lido-
mine or 1.5 percent mepivacaine up to a
total volume of 25 to 30 ml. When between
31 and 50 ml. was used, as for vaginal hys-
terectomy, we selected a solution of
1
per-
cent lidocaine or 1 percent mepivacaine,
rather than 1.5 percent, to avoid exceeding
our approximate maximum dose of lidocaine
DANIEL . MOORE,M.D., is Clinical Associate Pro-
fessor of Anesthesiology at the University of Washington,
Seattle, and Director, Department of Anesthesiology, the
Mason Clinic and the Virginia Mason Hospital, Seattle,
Washington.
Dr. Moore is one of the most active mem-
bers of the specialty, holding honorary membership in
many organizations and having written four books and
over eighty papers. His principal interests have been
local anesthetic agents and regional technics.
In
1944
he
graduated from Northwestern University Medical School,
Evanston, Illinois, and was an intern and a Resident in Anesthesiology at
Wesley Memorial Hospital, Chicago. He is a Past President 1959) of the
American Society of Anesthesiologists.
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582
ANESTHESIAN D ANALGESIA..Current Researches VOL.
51,
No. 4, JULY-AUGUST972
or mepivacaine for a single-dose technic,
and we added 2 mg. of tetracaine to each
milliliter of lidocaine or mepivacaine.
For peripheral nerve block for extremity
procedures, with a volume of 50 ml. or less
of injected solution, 2 mg. of tetracaine was
added to each milliliter of
1
percent mepiva-
caine.
If
over 50 ml.
(60-100
ml.) were to
be used, tetracaine (1 mg./lb. of body
weight, not to exceed 200 mg. or a final tet-
racaine concentration of 0.25 percent) was
added to the 0.5 percent mepivacaine solu-
tion. The weaker solution of mepivacaine
was selected when volumes necessary for
the block were more than 50 ml., to avoid
exceeding our approximate maximum dose
of this drug.
OF SURGICALNESTHESIA. or epidural
and caudal block compounded solutions had
(1) onset within 5 to 8 minutes; (2) surgi-
cal anesthesia within 12 to 25 minutes; and
3)
duration of from 2% to 2y4 hours. In
caudal block, solutions containing 1.5 per-
cent lidocaine or 1.5 percent mepivacaine,
as compared with 1 percent, usually estab-
lished surgical anesthesia earlier, but dura-
tion of anesthesia was approximately the
same.
For
peripheral nerve block
onset and es-
tablishment of surgical anesthesia with com-
pounded solutions were similar to those for
caudal and epidural block, but duration
was significantly longer-from 4 to 51/2
hours, and occasionally longer.
COMPLICATIONS.-
o local tissue toxicity
resulted from the use of compounded solu-
tions in any block procedure.
Following
lumbar epidural block
6 pa-
tients exhibited systemic toxic reactions.
After receiving lidocaine plus tetracaine, 3
patients convulsed and
1
ost consciousness,
probably from the cerebral effects of the
lidocaine. Following mepivacaine plus tet-
racaine, one convulsed and one remained
conscious but was disoriented. All recovered
uneventfully after treatment with oxygen
by bag and mask.
One patient, in whom a lumbar epidural
block with 18 ml. of a 1.5 percent solution
of lidocaine (270 mg.) and 36 mg. of tetra-
caine with 1 125,000 epinephrine was ad-
ministered for an appendectomy, experi-
enced permanent bilateral weakness of the
quadriceps muscle.
Following
caudal block 4
patients ex-
hibited systemic toxic reactions progressing
O N S E T ESTABLISHMENT AND
DURATION
to convulsions-2 had received a solution
of lidocaine plus tetracaine and the other 2,
a solution of mepivacaine plus tetracaine.
All were treated with oxygen by bag and
mask and all recovered.
In 1 patient with cancer of the rectum,
a caudal block for biopsy, using
20
ml. of
1.5 percent lidocaine 300mg.) and 40 mg.
of tetracaine, with epinephrine
1
125,000,
was followed by a bilateral paralysis which
gradually extended from the 10th to the
6th thoracic dermatome over a 3-week pe-
riod. This complication resulted
was diagnosed as an ascending
tery syndrome.
No complications followed
nerve block.
from what
spinal ar-
peripheral
DISCUSSION
O P T I M A L
MILLIGRAMOSAGEF
TETRA-
CAINE AS
RELATED
O CHLOROPROCAINE
LIDOCAINE
OR
MEPIVACAINE.
or com-
pounding local anesthetic agents, our ap-
proximate maximum doses are
(1) 1000
mg.
of chloroprocaine; (2) 500 mg. of lidocaine
or mepivacaine; and
3)
1 mg./lb. (body
weight) of tetracaine, not to exceed 200
mg.4 These are the same maximum doses
which we would employ
if
the agents were
not compounded.
For
epidural block
we inject no more
than 20 ml. of the local anesthetic solution
into the epidural space, whether or not the
solution is ~ompounded.~hen the amounts
used for skin wheal, local infiltration, and
test dose are added to this, however, the
total of the compounded solution may reach
26 ml. Thus, maxima may reach 390 mg.
of lidocaine,
390
mg. of mepivacaine, 520
mg. of chloroprocaine, and 52 mg. of tetra-
caine, but the total milligram dosage of
these agents is markedly less than our maxi-
mum dose for any one agent used alone.
For caudal block when a volume of solu-
tion of 30ml. or less is to be used, including
skin wheal, local infiltration, test dose, and
amount injected into caudal canal, the ratio
of compounding
is
2 mg. of tetracaine to
each milliliter of 1.5 percent lidocaine or 1.5
percent mepivacaine. We seldom inject
more than
30
ml., equaling a maximum of
450 mg. of lidocaine or mepivacaine and
60
mg. of tetracaine. I n the unusual case, when
31 to 50 ml. of solution (including skin
wheal, local infiltration, test dose, and
amount injected into the caudal canal) is
used and 2 mg. of tetracaine
is
added to
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Local
Anesthetic Toxicity. . Moore, t
a1
583
each milliliter of 1 percent lidocaine or 1
percent mepivacaine, the maximum amount
injected
is
310 to 500 mg. of lidocaine or
of mepivacaine and 62 to 100 mg. of tetra-
caine. Therefore, in caudal block, the total
dosage of the compounded local anesthetic
agents is usually less than our approximate
maximum dosage of either agent injected
alone.
For peripheral nerve block as concentra-
tions of lidocaine or mepivacaine in excess
of 1 percent may produce neuritis, we do
not routinely employ them for this technic.4
For brachial plexus block, we use 50 ml.
of solution; for sciatic and femoral nerve
blocks, 50 ml.; and for sciatic and femoral
nerve blocks with either lateral femoral cu-
taneous nerve block or obturator block, or
both,
70
to 100 ml.4
When volumes of 50 ml. are employed,
2 mg. of tetracaine is added to each milli-
liter of
1
percent mepivacaine,
500
mg. of
mepivacaine and 100 mg. of tetracaine being
administered. When 70 to 100 ml. of solu-
tion is injected, tetracaine
(1
mg./lb., not
to exceed 200 mg.) is added to each milli-
liter of 0.5 percent mepivacaine, 350 to 500
mg. of mepivacaine and varying amounts
of tetracaine, depending on body weight,
being injected. Therefore, in peripheral
nerve blocks, the maximal dose of either
agent is not exceeded.
The reasons for such ratios in compound-
ing in order to produce the long duration of
action of tetracaine are not clearly under-
stood. However, this phenomenon has been
observed in man by us and in dogs by De-
falque and Stoelting.9
COMPARISON OF ONSET, ESTABLISHMENT
OF SURGICAL ANESTHESIAND DURATION
OF SURGICAL A N ES THES IAITH LIDOCAINE
A N D
MEPIVACAINE.-
When only lidocaine,
mepivacaine, or chloroprocaine
is
used for
epidural or caudal block onset occurs in 5
to 8 minutes, surgical anesthesia is estab-
lished within 12 to 25 minutes, and duration
of action is from 1 to 1 hours, when such
solutions contain epinephrine. When tetra-
caine is added, onset and establishment of
surgical anesthesia are not altered, but
duration of action is extended to 21/4 to 2%
hours.
For peripheral nerve
block,
when only
lidocaine or mepivacaine with epinephrine
is employed, onset
is
within 5 to 8 minutes,
surgical anesthesia resulting in 12 to 25
minutes (depending on accuracy of place-
ment of the local anesthetic solution), and
anesthesia lasts for 1 o 3 hours. The ad-
dition of tetracaine does not alter the time
of onset or establishment of surgical anes-
thesia, but duration
of
anesthesia is length-
ened to
4
to 59$ hours and occasionally
longer. For some unexplained reason, tetra-
caine alone, used for peripheral nerve block,
gives a duration of 6 to 9 hours or longer.
ADVANTAGESF
COMPOUNDING. Most
anesthesiologists prefer single-dose to con-
tinuous technics because (1) they are tech-
nically less difficult and time-consuming;
(2) the incidence of complications is less
-for example, broken plastic tubing; and
(3) the incidence of unsatisfactory anesthe-
sia is less. For most surgical procedures,
single-dose regional block requires the use
of a local anesthetic agent with a prolonged
duration. While the commonly employed
agents, such as chloroprocaine, lidocaine, or
mepivacaine, do have excellent diffusion
and penetrability as well as rapid onset and
rapid establishment of surgical anesthesia,
they do not produce prolonged sensory and
motor blockade. Therefore, they are not
satisfactory agents for single-dose technics
in the following circumstances: (1) teach-
ing of regional block, which may require 30
to 45 minutes prior to preparation and drap-
ing of the patient for surgery; (2) epidural
or caudal block, where the time needed for
establishment of surgical anesthesia and
for the surgical or obstetric procedure ex-
ceeds the duration of action of these agents;
(3) peripheral nerve block for surgical pro-
cedures requiring anesthesia in excess of 3
hours; or 4 ) prolonged pain relief, either
during the postoperative period or following
diagnostic and therapeutic blocks.
On the other hand, although tetracaine in
concentrations of 0.1, 0.15, or 0.25 percent
for single-dose peripheral nerve block pro-
vides
a
duration of anesthesia of 6 to
9
hours, or even 10 to 14 hours when the solu-
tion contains epinephrine, many anesthesi-
ologists do not use tetracaine because (1)
its onset time
is 5
to 10 minutes; (2) surgi-
cal anesthesia may not be established for 15
to 40 minutes;
(3)
diffusibility
is
limited,
requiring marked accuracy of placement on
or near the nerves; and 4) it has been
(falsely) accused of being too toXi~.4,10J1
Even if the time of onset and establish-
ment of maximum anesthesia were as rapid
with 0.1, 0.15, or 0.25 percent tetracaine as
with 1.5 percent lidocaine or 1.5 percent
mepivacaine, we would not
us
these con-
centrations of tetracaine for single-dose
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584
ANESTHESIA
ND
ANALGESIA.
Current Researches VOL.
51,
No
4, JULY-AUGUST
972
caudal or epidural block, as the resulting
sensory and motor anesthesia
is
more con-
sistently predictable with lidocaine or me-
pivacaine.
COMPLICATIONS. ocal toxicity from
compounded solutions-for example, slough
of tissue-d id not occur in our experience or
in that of other investigators.'-3 We ob-
served two unexplained neurologic compli-
cations following the use of compounded
solutions-one after caudal block and the
other after epidural block. This incidence is
not markedly different from that of neuro-
logic sequelae following epidural block re-
ported by Bonica and associates' 1:3637
patients), by .Lund3 2:
10,OOO
patients),
and by Hellmannl2 2:26,127patients). In
our cases, the epinephrine content may have
been too great, but this is debatable. Since
1966,
by maintaining the optimal maximum
epinephrine concentration of 1:200,000 for
all regional nerve blocks, no neurologic
se
quelae or alteration in duration of anesthe-
sia has resulted.
We observed 10 systemic toxic reactions
(eight of which progressed to convulsions)
following injection of compounded solutions
into the epidural space via a lumbar inter-
space or the sacral hiatus. In these cases,
routine tests were made to avoid intravas-
cular or subarachnoid injection of the dose
of the drug calculated to produce the de-
sired anesthesia. The tests, aspiration for
blood or spinal fluid and injection of 3 to 5
ml. of the local anesthetic solution, followed
by observation of the patient for 5 minutes
to detect either changes in sensorium or
onset of anesthesia, were in all cases nega-
tive.
Our incidence of systemic toxic reactions
progressing to convulsions does not differ
significantly from that reported by other
authors. Bonica's group' reported general-
ized systemic toxic reactions following
epi-
dural blocks in 116 of 3637 patients, with
8 convulsing, and LundS in 44 of 10,OOO
patients, with 11 convulsing. Hellmannlz
did not report the number of generalized
systemic reactions, but 17 of his 26,127 pa-
tients convulsed.
APPLICABILITYF EXTRAPOLATINGRE-
SULTS
FROM
ANIMALS
O
H u M A N s . ~ ~ ~ ~ ~
compounding of chloroprocaine, lidocaine,
mepivacaine, prilocaine, or procaine with
one another or with tetracaine was found to
increase the severity of systemic toxic reac-
tions and the incidence of death in certain
strains of white rats and mice and in dogs,
use of these compounds in humans was
pos-
tulated to be dangerou~.~-Towever, results
of such animal experiments, especially with
ester-type agents, cannot properly be extra-
polated to humans, as acute toxicity studies
in animals involve rapid administration of
drug until death, high brain levels being
produced within such a short time that
ca-
tabolism of the agent is negligible. In con-
trast, clinical tolerance involves the kinetics
of drug absorption, distribution, and elimi-
nation.
Furthermore, the animals used in these
studies catabolize ester derivatives quite
slowly,13-16 while humans metabolize them
rapidly.13~14~16 sing gas chromatography,
we could detect no tetracaine in the blood of
patients 2 to 30 minutes after administering
150 mg. for bilateral intercostal nerve
blocks.
The assay for tetracaine can determine 0.1
mcg./ml. of the drug when added to human
blood in vitro, and significantly less than
this can be detected. The assay
is
similar
to
that
for anilide derivatives, except that
arsenite solution is added and the blood is
frozen pending analysis, to prevent hydroly-
sis of tetracaine during and after sampl-
ing. OtherslcJ* have also found difficulty
in measuring tetracaine in vivo in humans
but have confirmed that it can be measured
in vitro.
Therefore, since lidocaine or mepivacaine
injected in humans for caudal, epidural, and
peripheral nerve blocks does not reach peak
blood levels for 10 to 30 minutes, as deter-
mined by gas chromatography, and since
tetracaine cannot be measured after normal
clinical doses, presumably because it is
rapidly metabolized, we can hypothesize
that high levels of the drugs do not coincide
and that generalized systemic toxic reac-
tions are not likely to occur in humans
as
a result of compounding an anilide with an
ester. This assumes, of course, that metabo-
lites of tetracaine are not significantly toxic.
At present, no methods are available for
determining precisely the levels
of
esterized
local anesthetic derivatives in human blood
following normal clinical doses. Such meth-
ods
should be sought,
so
that uptake
and
elimination of the ester derivatives can be
determined in man.
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Local Anesthetic Toxicity. . .Moore, et a1
585
CONCLUSIONS
In a retrospective study of the records of
over 10 000patients given local anesthetic
agents for caudal, epidural, brachial plexus,
or peripheral nerve blocks, compounding of
certain parenteral agents was found to give
more satisfactory results than use of the
agents singly.
The primary advantage of compounding
is that it permits the use of single-dose tech-
nics by taking advantage of the outstanding
qualities of each local anesthetic agent, that
is, the rapid establishment of surgical anes-
thesia of chloroprocaine, lidocaine or mepi-
vacaine, and the prolonged duration of tet-
racaine.
Compounded solutions permit single-dose
technics for epidural or caudal block in
many instances where a continuous technic
would be mandatory with a single agent.
Other advantages are also described.
Compounding as detailed herein is a safe
technic in man. Data indicating systemic
toxic reactions and deaths in animal experi-
ments with such compounded local anes-
thetic solutions do not appear subject to
extrapolation for clinical purposes.
Finally, when anesthesia
is
unsatisfac-
tory following
a
regional block performed
with the approximate maximum dose of
either an anilide or an ester derivative and
it is decided to repeat the block, a local
anesthetic agent of an alternate chemical
derivation
should
be used. For example, if
an anilide derivative
is
injected initially
and the resulting anesthesia is unsatsfac-
tory, reinjection should be done with an
ester derivative.
Generic and T rade Names
of Drugs
Chloroprocaine-Nesacaine
Dibucaine-Nupercaine
Epinephrine-Adrenalin
Hexylcaine-Cyclaine
Lidocaine-X y locaine
Mepivacaine-Carbocaine
Prilocaine-Citanest
Procaine-Novocain
Propoxycaine-Blockain
Tetracaine-Pontocaine
REFERENCES
1. Crawford
OB
Chester RV: Caudal anesthe-
sia in obstetrics: a combined procaine-pontocaine
single injection technic. Anesthesiology
10: 73-478,
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