A clinical evaluation of local anesthetic solutions of increased strength

New York University A CLINICAL

EVALUATION OF LOCAL ANESTHETIC OF INCREASED STRENGTH LEO

WINTER,

D.D.S., M.D.,

AND

L.

M.

SOLUTIONS

M.D.

TAIXTER,

ISTRODUCTION

URING the past fifty years there have appeared many publications on the clinical use of local anesthetic agents. Many of these reports have been of general or limited interest and usefulness. More recentlyl-a attempts have been made to devise critical methods of approach to the study of the large number of problems involved in local anesthesia and to establish the proper means for evaluation of the data obtained in these studies. There is still a crying need’ for further extensive quantitative critical and objective studies of the effects of local anesthetic agents in human subjects. It was the purpose of the present investigat,ion, a part of which is being presented here, to obtain extensive evidence on the important effects of repreData on two separate studies are sentative local anesthetic agents on patients. included here. In the first study attention was concentrated on the onset, duration, etc., while in the second study the patient reactions were the primary objective. The data included in Tables I to III are from the first study while those of Table IV are from the second. In this presentation an attempt will be made to dispel uncertainties about the absolute and relative tolerance of some commonly used anesthetic solutions.

D

STATEMEKT

OF

PROBLEM

Using the blind test technique on a large group of patients well distributed as to age, sex, and physical condition, we set out to study representative local anesthetic agents from the standpoint of the following: volume of solution required, onset time of anesthesia, duration of anesthesia, blood pressure changes, pulse rate changes, grade of anesthesia, amount of bleeding, and patient reactions. In this work we have been guided by the methods employed by Tainter, Throndson, and Moose.ll 3 Although studies have been initiated on some thirteen solutions, the present report is concerned only with the following four isotonic solutions: Novocain 2 per cent with Epinephrine 1:50,000 Novocain 2 per cent with Cobefrin 1 :lO,OOO Novocain 3 per cent with Epinephrine 1:50,000 Novocain 2 per cent, Yontocaine 0.15 per cent, Cobefrin 1 :lO,OOO Each was made isotonic by the addition of the appropriate amount of sodium chloride. As data on the other solutions become available, they will be presented in future publications. Bellevue New

From

This York

the Department of Oral Surgery, Hospital, New York. N. Y. investigation was made possible University.

College by 307

a grant

of

Dentistry, made

New by

York

Cook-Waite

University, Laboratories

and to

I’HOCWIJRIC

The solutions used in the clinic were provided in such form that the clinicians were at all times unaware of the identity of the products under test. The solutions were put up in cartridges in lots of fifty to each of twenty containers. Each container carried its own key number so that the observer could not know what formula he was using at any time. Furthermore, the solutions were frequently interchanged, alternating from one to another in an irregular manner, so that such factors as change in personnel and variation in patients observed were equalized as well as possible. This so-called blind test technique is absolutely necessary in clinical studies of this type if one is to arrive at reliable data which are not colored by subjective influences. All injections were made by senior dental students or instructors. At the time of injection the quantity of solution used was recorded and any objective symptoms were noted. All blood pressure readings and pulse rates were taken by a registered nurse before and one minute after injection. It was thought that since dentists have to recognize and cope with reactions, when they occurred in this four-solution clinical investigation they should be evaluated by a dentist. In the second series, recorded in Table IV, all observations were made by one person, a dentist, who devoted his time exclusively to interpreting and recording manifestations of paCent reactions and time of onset and duration of anesthesia. The dentist, like all operators concerned in this study, was unaware of the identity of the solutions being injected. The data sheets were assembled and statistically analyzed by different persons from those making the observations, so that subjective influences from this source were also rigidly excluded. In all cases the criterion used in determination of onset time was the presence of sufficient anesthesia for the performance of the operations. Duration was judged by recurrence of sensation as determined by the use of an explorer. The degree of bleeding was recorded by each observer in accordance with standards previously agreed upon. LOCAL

ANESTHESIA

Before an evaluation of an anesthetic solution can be made, it is necessary not only to evaluate and standardize the solutions, the patients, methods of recording and procedures entailed, but t,he technical processes involved in administering the anesthetic are also of paramount importance. Local anesthesia is dependent upon knowledge of the regional anatomy involved. With this in mind, a complete anatomic study of the head and neck was made prior to the survey. The basic anatomic considerations are illustrated in Plates I and II, and Figs. 1, 2, 3, 4, and 5.l” TECHNIQUE

OF INJECTIONS

The technique of these procedures is all-important in that comparable results will be achieved only if the procedure of the administration of the local Local anesthesia implies more than the anesthetic is completely systematized. administration of intraoral novocain anesthesia; it includes, as well, extraoral block and infiltration methods. Therefore, on the basis of the anatomic dissections and the procedures that have been employed in the past with success, the following techniques of injection anesthesia were employed. ‘,

Plate

I.--Ueep (Plates

dissection

to lateral

I to V from

Winter:

asDect

of mandible been rernowd.

Textbook

wherein

of Exoclontia,

nruscle The

and C. Y.

parotid Mosby

glantl Co.)

11~

WINTER AND TAINTER : OF LOCAL ANESTHETIC IX~REASED STREKGTH

Plate shows the tion of the

Ax

CLINICAL EVALUATION SOLUTIONS OF

II.-Posterior relation of mandibular

view of the topography the mandibular nerve to the nerve to the pterygoid muscles.

of the skeleton.

J. ORTIIODOXTICS MAY. 1945

manclibular The right

nerve. side

The shows

AND

Oa.4~

left the

side rela-

SUI

Inferior AZveoZur.-Blocking the inferior alveolar nerve at the lingula, on the inner border of the ramus, will secure anesthesia of that particular side of the mandible up to t,he lateral incisor. The technique employed is as follows : The patient’s head is in a vertical position and the mouth open to t,he fullest extent. With t,he body of the mandible parallel to the floor, the index finger is placed posterior to the third molar where the external oblique ridge

Fig. l.-Sagittal section through maxilla, mandible, (Fig. 1 to 9 from Winter: Textbook of l?xodonti:r,

an(l The

sinuses, right C. 1’. Mosby

sicre. Co.)

can be palpated. Directly lingual to this ridge lies t,he retromolar fossa. The index finger is placed inside the retromolar fossa, and the fingernail automatically touches the internal oblique ridge. The finger is kept in this position, sterile gauze is carried by means of thumb forceps to the point where the fingernail rests, and the mucous membrane lingually is dried. Tincture of aconite and iodine is then applied to the area, fixing the surface bacteria.

310

Leo Winter

and M. L. Tainter

The syringe, with the bevel edge of the needle toward the bone, is brought in from the opposite side in the area of the premolars and is made to penetrate the mucous membrane at a point approximately bisecting the fingernail. The needle is passed along the inner border of the ascending ramus until the rethe needle is passed sistance of the bone to the needle is lost. Thereafter beyond the lingula, the sharp prominence which guards the orifice of the inferior alveolar canal, and the solution is deposited by aid of a slow, pumping The anatomic relationships are illustrated in Fig. 6, and the techmotion. nique of the injection in Figs. 7 and 8.1°

Fig.

2.-Sagittal

section

revealing the

dissection of pterygomandibular

the

structures with raphe lifted.

the

MUCOUS

membrane

at

Posterior Superior Alveolar InJection.-The anesthetization of the posterior superior alveolar nerve, which supplies the three maxillary molar teeth with the exception of the lingual mucosa and the mesial buccal root of the first molar (which may be supplied by the middle superior alveolar nerve), is accom-

Local Anesthetic

i3oktions

of Increased

Strength

311

plished by the following technique: Index finger of the left hand is placed into the vestibule of the mouth under the zygomatic process with the mouth half open. The corpus adiposum buccae is drawn out of the field of operation by the natural lateral displacement of the index finger. The syringe is held in a pen grip with the point of insertion approximating the apex of the distal

BuccinaforMuscle Buccina for IVerve

wyqomandibular flaphi

&don of Temporal Muscle -

ire&ion of Approach for moval of Broken fleedle

MasseterMuscle -

Soft Palate *1.1 :..TI

Pharynx Sup. Constrictor of Pharynx

Parotid C

Fig.

3.-Horizontal

the

section through route which must

the face be taken

at for

the the

level of removal

the angle of the mouth of a broken needle.

to

show

root of the next to the last molar in position. The needle is then inserted upward, backward, and inward, at all times hugging the alveolar process. Fluid is deposited with a slow, pumping motion. It is highly vital that the mouth be kept in a half-open position so as to allow for the complete retraction of the corpus buccae, for if there is failure to accomplish this adequately,

312

_ Leo Winter

and

211. L. Taimter

there is the possibility that the injection will be made into the fatty mass with the resultant balloonlike swelling. Infruorbital Injection.-Infraorbital injection may be employed for the anesthetization of the area of the first and second premolars, cuspids, lateral and central incisors of the particular side involved. The index finger of the left hand is used to palpate the supraorbital notch, and in a direct line with

Fig.

4.-Infratemgoral

fossa. muscles

Zygomatic arch, removed ; inferior

masseter, alveolar

temporal and canal opened.

external

pterygoid

this notch below the infraorbital ridge, which can be palpated, is the infraThe thumb of the same hand is placed below the infraorbital orbital foramen. ridge in a direct line with the supraorbital notch. The ball of the thumb will .then be resting over the infraorbital foramen. The lip is everted with the index finger. The syringe is held in a pen grip, the bevel edge of the needle toward the bone, and the point of the needle is inserted in the reflection

Local Anesthetic

k?olutions of Increased

Xtvength

313

of the mucous membrane above t,he apex of the second premolar. The syringe and needle are directed upward and parallel to the long axis of the secondary premolar. The solution is depositdslowly and will be felt beneath the pa.lpating finger. This direction of the needle will avoid the canine fossa and

Fig.

3.-Sectiotl

of head

through

n~ol:rr

rcaion.

will pass through adipose tissue between the quatlratus labii superioris and of either muscle will prevent the caninus muscles. Avoiding the penetration ecchymosis. Light massage of the face in this region often aids in hastening the anesthetic effect.

314

Leo Winter

and $4. L. Tainter

Infiltration.-The technique employed consists of drying and fixing the surface bacteria. The needle, with the bevel directed toward the bone, is inserted at a point. midway between the gingival margin and the apex of the tooth. The solution is deposited with a slow, pumping motion.

Fig.

B.-Lingual

and

inferior

alveolar

nerves

piercing

external

pterygoid

muscle.

Extraoral Maxillary Nerve Ho&-With the patient opening and closing the mouth, the sigmoid notch of the mandible is outlined by placing the tip of the index finger of the left hand just beneath the zygomatic arch; the depression thus palpated is the notch ; the bisection of the tip of the index finger marks the middle point of the zygoma. Under infiltration, subdermal anesthesia, a wheal is created in the area of the sigmoid notch just beneath the skin surface. After skin anesthesia has been established, the index finger is placed at a point denoting the sigmoid notch, and a needle (80 mm. long-

Locab Anesthetic

Fig.

Fig.

S.-Point

7.-The

of penetration

ball

of

of

the

Solutions

the

needle

finger

restinK

into the injection.

of Increased

in

mucous

the

retromolar

membrane

315

Strength

fossa.

for

the

inferior

alveolar

316

Leo Winter

and M. 1;. Taintef

Labat) is passed through the point bisecting the fingernail and inserted until contact with the bone has been made. At this point the needle is in contact with the base of the pterygoid process. The needle is drawn out sufficiently to allow for a change of direction and is then reintroduced in a forward and upward direction to the same depth as it was originally introduced. The

Fig.

S.-Mandibular sigmoid notch

nerve with

block. Labat

Index needle

finger of left hand in position to puncture

palpating skin at

for inferior bisection of

border nail.

of

needle has now entered in front of the pterygoid process and is in the pterygopalatine fossa. The syringe with the anesthetic solution is connected, aspiration test is performed, and, if negative, the solution is slowly deposited. This produces complete anest,hesia of t,he maxillary division of the trigeminal nerve. The anatomy of this area and the routes of injection are illustrated in Plates III, IV, and V and Fig. 9.1°

AKD TAIKTER : 0~ Local A~vE~THETIO INCREASED STRENGTH

\~~NTER

Ax

CLINICAL EVAL~-ATION XIOLC~TIOSS OF

J. ORTIIODONTICS MAY, 1945

.WD

ORAL

ZGn tp-i urn Gasserian Mandibular in Foramen

Ganglion

IVeru Ouale

Common Stem of Buce MoiorlUerve to Chetoi

Plate lary nerve its passage

III.-Infratemporal in the pterygopalatine through the foramen

Blue fossa viewed from above. Black needle directed fossa. orale.

needle to the

dirxted mandibular

to

the nerve

maxilafter

E

~VINTER ns~ OF LOCAI, IWKEASED

Plate

TAINTER : ANESTHETIC STRENGTH

I\‘.--Superflcial

C’LIXICAL Eva~~r:a~ro~ SOI~ITTIONS OF

lateral

region of branches

AK

J. ORTHODONTICS MAP, 1945

the face showing the of the facial nerve.

profuse

AND ORAL

anastomoses

of

SITG.

the

I Plate

X’.-Position

of

needle in contact with and direction changed

external posteriorly

Xeedle pterygoid plate. to foramen ovale.

removed

sl,ightl3’

Local Anesthetic

Solutions

of Increased

Strenyth

317

Extraoral Mandibular Nerve Block.-The method employed for the blocking of the mandibular division of the t,rigeminal nerve is similar to that for the maxillary nerve wit.h the following deviation in technique: Instead of passing the needle in front of the pterygoid process, the needle is directed backward to the foramen ovale, which lies just posterior to the base and is at about the same depth as the outer surface of t,he lateral plate of the pterygoid process. The setting of the recorder at, a distance of 1 cm. from t,he surface of the skin in this situation is to prevent the introduction of the needle into deeper st.ructures where damage may be done. Paresthesias in t:he lower jaw are the best indications that the nerve has been reached. EXPERIMENTAL

PROCEDURE

AND

RESULTS

The results of our investigations on 2,382 patients injected according to t,he above techniques are recorded and summarized in the tables of data. For each value obtained in Tables II, III, and IV, the familiar standard error of the statistician is given. This indicates t,he extent of the variability of the average values. The procedure involved in arriving at these values is available in any standard textbook on statistics, and therefore need not be presented here. Suffice it to say that it is a measure of the range within which To be more the average value obtained might fluctuate from chance variation. specific, there is a two to one chance that there will not be a variation from the average value in either direction of more t,han one standard error if the entire study were to be conducted a second time. The percentage probability has also been included in Tables II, III, and IV. This gives quantitative expression to the probability that differences between the solutions indicated are or are not due to chance alone. If the probability value is equal to or less than 0.05, the difference between two solutions compared is considered statistically significant. Particular attention should be paid to the fact that we have used NovoCain* 2 per cent solution with epinephrine 1:50,000 as the standard against which each of the other three solutions is compared. This cornbinatjorl ureas selected as the reference solution because all dentists are familiar with its properties and it has been used for this purpose in previous publications. TABLE

I.

SUMMARY

OF ANESTHETIC AND TYPES

SOLUTIONS EMPLOYED, OF INJECTIOS IX FIRST

I

I

TYPE

OF CAsss

PER

SOLUTION,

OF If; IJEo’l?ON

INFERIOR ALVEOLAR

SoLI-TION

Novocain

NUMBER SEUIE:S

I

POSTERIOK SUPERIOR *Tlrx.Av ._

INFRAORBITAL

2%

with

epinephrine

Novmain

2%

with

eobefrin

326

156

48

139

43

28

8

3

3.0

Novocain 1:5ojooo Novocain 0.15%, Totals

3%

with

epinephrine

543

289

53

215

40

37

7

2

0.4

561

279

50

252

45

29

5

1

0.2

1,760

895

51

737

42

117

7

11

0.6

1:50,000

1:10,000 ‘-

u.

s

2%, pontocaine cobefrin 1 :lO,OOO

*Nowcain P.

is

the

Winthrop

Chemical,

Company,

Inc.,

brand

of

procaine

hydrochloride

318

Leo Winter

and M. L. Tainter

In Table I are summarized by solutions the types of injections used in the 1,760 patients in the first series. In Table IV is given the same information on. the 622 patients of the second series. As can be seen in these tables, the number of cases studied was sufficiently large to make statistical analysis reliable. It will be noted that from solution to solution there was achieved an This is further equal distribution of cases according to type of injection. evidence of the objectivity and effectiveness of the “random sampling” methods used in this study. Since it is obviously impossible to select matched groups, the effects due to individual variation may be cancelled out by using a large number of patients. The elements of the past history, age, sex, and any physical disabilities were recorded and have been analyzed and reported separately.8 Those which significantly affected the response to the local anesthetic were equa,lly distributed between the solutions under test by the method of randomization employed, and hence did not distort t,he average values. All of the patients presented themselves for dental treatment at New York University School of Dentistry and Bellevue Hospital. TABLE

II. COMPARISON OFRES~LTS OF THE FOPR SOLUTIONS IN FIRST SERIES oF 1,760 PATIENTS WITH RESPECT TO VOLUME INJECTED, ONSET TIME, DVRATION OF AKJSTHESIA, AND CIRCULATORY CHANGES 1

SOLUTlON

Novocain 2% with epinephrine 1:50,000 Novocain 2% with cobefrin 1:10,000 -~ Probability of no difference from novocain 2q0 with enineahrine 1:50.000 Novocain 3v0 with epinephrine 1:50,000 Probabilitv of no difference from nkocain 2y0 with epinephrine 1: 50,000 Novocain 2%, pontocaine0.15%‘,, cobefrin l:lO,OOO ProbabUy of no difference from novocain 2y0 with epinephrine 1: 50,000 L

OXSET TIMEOF ANESTHESIA (MIN.)

VOLIXE REQuIRED (C.C.)

1.4 t 0.03 3.3+0.10

3.1 t 0.17 8.3+0.15

.34

DIXATION OF ANESTHESIA (MIN.)

190.3

k 20.26

175.0 t 27.29

.,I“8

BLOOD ClIANGES

PRESSURE IN MM. HD

SYSTOLIC

DIASTOLIC

5.3 2 2.28

-3.12

9.0

3.71

.25

136.8 t 10.88

4.6 + 1.60

.02

230

CHANGES PER-WIN. -.

8.3 + 1.19 __

3.03

.66

1PULSERATE

-0.2 .12

r 1.21

<.OOl _

I

!.8

3.3

<.OOl

1.9+o.o(i <.OOl L

.GO

m

215.0 .06

2 15.00 .34

-2.9

2 1.08

7.8 2 0’.90

>.90

6.8 L 2.69

2.6 +- 1.04

.67

.14

.74 _

-9.2

+ 2.37

<.OOl I

In Table II are given the volumes of solution required for anesthesia in the first series. This should be compared with the same data on the patients in the second series, set forth in Table IV. It will be noted that the average values for each series are practically identical. This gives added confidence in the comparability of the two sets of data derived from the two series of observations. The volumes of solution required for novocain 2 per cent with epinephrine However, when or Cobefrin” as the vasoconstrictor were practically identical. 0.15 per cent Pontocaine* was added to the novocain-cobefrin solution the *Cobefrin is the Winthrop Chemical Company, Inc., name for racemic 3, 4 dihydroxyphenylpropanolamine hydrochloride. Pontocaine is the brand of tetracaine hydrochloride U. P. marketed by the Winthrop Chemical Company, Inc.

S.

Local Anesthetic

Xo1wtion.s of Increased

Stwzgth

319

volume of solution needed was sharply reduced by 0.4 to 0.5 CC. or about 14 per cent. The same sized reduction of the volume of anesthetic used was secured by raising the novocain concentration to 3 per cent, a 50 per cent These differences in volumes used increase in the amount of the anesthetic. are statistically significant. From the practical standpoint these figures are of interest, since at least a part of any added toxicity inherent in the stronger anesthetic solutions would be compensated for by the smaller volume of solution required. As might have been anticipated, the differences in the onset time of anesthesia for the four solutions are insignificant (Table JI). Each would he satisfactory when judged from this standpoint alone. The findings on duration of anesthesia summarized in Table 17 should be considered in light of condit,ions prevailing at the clinic, as well as the requirements for anesthesia in the operation performed. In all cases anesthesia was of sufficient average duration. The finding that the duration of anesthesia with 3 per cent novoeain solution is much less than that for 2 per cent solut,ion may be relat,ed in part to the smaller volume used of the more c.oncentrated solution but probably is due to the vasodilator action of the novocain, which in the higher concentration more effectively overcomes the vasoconstriction of the epinephrine and thus shortens the anesthesia. The longest duration of anesthesia occurred with novocain-pontocainecobefrin, which anesthet,ized twenty-five minutes longer than did the 2 per cent, novocain-epinephrine solution, and forty minut,es longer than the one with cobefrin. However, these differences are not fully significant statistically. There is no doubt that the seventy-eight-minute greater duration of the noToCain-pontocaine-cobefrin over the 3 per cent, novoca,in-epinephrine is significant and important, particularly in view of the equally small volumes of each injected. It must be pointed out, however, that the clinical experiments performed do not provide a completely satisfactory basis for comparing duration of anesthesia in these solutions, since the patients cannot always be kept under observation until the anesthesia is gone. For this purpose the use of prolonged operative procedures would give more reliable absolute values. The recognition of this restriction on the interpretation of the nbsolute values observed does not, however, deny their relative value in comparing solutions run in parallel under the identical conditions. It. is obvious, therefore, that the pontocainecontaining solution gives a longer-lastin, m a,nesthesia than do the others, which difference would doubtless be even more striking if identical volunr~s had been used for each. The blood pressure changes for the four solutions are small. There appear to be no significant differences between the solutions in this regard, except that the cobefrin produced a minimal rise in diastolic pl’essure as Ire11 as in systolic, whereas the epinephrine solutions produced a slight drop in diastolic pressure with a concomitant rise in systolic, thereby increasing the pulse pressure. This difference in the action of cobefrin and epinephrine was pointed out by Miller and Stuart.” It will be noted that there are differences in pulse rate changes produced by the four solutions. These differences, while not extreme, appear to be significant,. Actually the two solutions containing cobefrin allowed a slight decrease in the pulse ra,te, whereas the solutions con-

320

Leo Winter

and M. L. Taintel

taining epinephrine produced an increase in pulse rate. These findings are comparable to those of Tanner, Throndson, and Moose.2 Undoubtedly there will be an increase over the normal pulse rate when excitable individuals present for dental service. The pulse rate can be expected to return to normal following an injection, unless prevented by the stimulating action of the injected vasoconstrictor. Miller and Stuart? demonstrated that there was a greater increase following the injection of novocain solutions containing 1:20,000 epinephrine than with either epinephrine 1:50,000 or cobefrin 1 :lO,OOO and that the pulse rate returned to normal sooner following the injection of 1 :lO,OOO cobefrin with novocain 2 per cent than with either of the solutions containing epinephrine. TABLE III. COMPARISON OF RESPONSE TO LOCAL ANESTHETIC INJECTION OF PATIENW OF THE FIRST SERIES IN RESPECT TO DEGREE OF ANESTHESIA, OF BLEEDING,

AMOIJNT

AND

THE

1,760

ATTITT~DE

(The figures are in terms of percentage of patients responding in the manner indicated) GRADEOFANESTHESTA SOLUTION I

Novocain 2% with

NOPAIN

INJECTION I REPEATED

epineph- 89.5 +_1.79 5.42 1.30 rine 1:5O,OOQ Novocain 2$J0 with cobefrin 86.7 5 1.95 2.7 +- 0.94 1: 10,000 Probability of no difference <.OOl from novocain 2% with epinephrine 1: 50,000 Novocain 3‘$, with epineph- 92.9 + 1.14 2.9 k 0.73 rine 1:50,000 Probability of no difference .02 from novocain 2% with epinephrine 1:50,066 89.9 ?r 1.28 4.6 +- 0.89 Novoeain 2%, pontocaine 0.X%, cobefrin 1 :lO,OOO Probability of no diff’erence .63 from novocain 2% with epinephrine 1: 50,000

AMOUNT

(OF BLEEDING TNG_ OPERATION .~

SLIGHT

MODERATE

48.8 5 2.99 38.3 + 2.85 35.6 r

2.76

17.7 2~ 2.88

<.OOl

DUR-

EXCESSIVE

PATIENTATTITUDE CALM AND COOPERATIVE

VERY DlFFICULT

8.4 + 1.63 40.0 It 3.04

17.7 + 2.36

). 2.97

16.8 r 2.24

14.4

? 2.03

43.5

.47

28.7 ? 2.54 51.9 ). 2.79 10.8 + 1.79 43.4 + 2.28 <.OOl 30.9 k 2.67

< .OOl

44.6 + 2.88 22.8 + 2.39 48.12 2.18 <.ooa

11.1% 1.41

14.5 +- 1.53

<.OOl

In Table III it will be noted that the percentage of patients experiencing complete anesthesia seems to be approximately the same for the four solutions. However, with the novocain 2 per cent epinephrine 1:50,000, reinjection was required in 5.4 per cent of cases. Almost identical values were obtained for With the novocain-cobefrin soluthe novocain-pontocaine-cobefrin mixture. With the 3 per cent novocain there was tion, reinjections were less numerous. a significantly higher incidence of complete anesthesia and only a small number of reinjections. Since the differences represented only two or three patients out of each hundred, the practical significance is very low. All three test solutions appear to produce more instances of moderate or excessive bleeding than does the reference solution in which only slight bleeding occurred in almost 50 per cent of the cases. When the novocain strength was increased from 2 per cent to 3 per cent with epinephrine as the vasoconstrictor, the cases where there was only slight This lends support to the suggestion made bleeding were reduced by one-half.

Locnl Amsthetic

Solutions

of Iacrensed

Stl-ejtgth

321

above that the stronger novocain interferes with the vasoconstriction. Apparently the pont,ocaine also reduces the efficacy of the vasoconstrictor, as judged by the amount of bleeding observed. The patient attitude, such as apprehension, etc., before the injection, tended to favor the solution containing 3 per cent novocain in that a calm and cooperat,ive patient will be less likely to manifest objective symptoms of nervousness following injection than one who is excitable. Patients who were very difficult to handle were least frequent in the strong novocain group, with the number increasing in the pontocaine group and being greatest in the novocain 2 per cent with epinephrine 01 cobefrin. The variability of this type of data is high and its importance in the interpretation of the general results is not, entirely clear. The observations in Tables T, IT, and IT1 of the first series were obtained by registered nurses and the operators. ’ In order to get, a &ill more experienced appraisal of the reactions, a second series of 622 patients was run where all the observations were made by one dental surgeon skilled in oral surgery. This dentist devoted his time exclusively to interpreting and recortlitig manifestations of patient reactions. Therefore, all the results were comparable, as differences in individual judgment were eliminated. The data are summarized in Table IV. The findings in Table TV are of particular interest since they serve not only to give more pointed information on patient reactions, but also to give a check reading on the volumes of solutions required to produce satisfactory anesthesia.. Here again we find in a completely different set of patient,s that novocain 3 per cent and novocain-pontocnine-cobefrin require a lesser volume of solution to produce anesthesia than is the case with either novocain 2 pel cent with epinephrine 1:50,000 or novocain 2 per cent with cobefrin 1 :lO,OOO. In the group of patients receirin .g the novocain 2 per cent with epinephPine, 75 per cent had no reaction to the injection of the local anesthetic. X’hen cobefrin was used as the vasoconstrictor in the 2 per cent novocain, 70.7 pel cent had no reactions, a difference well within the limits of expected variation. It was anticipated, on theoretical grounds, that when the amount of local anesthetic in the solution was inc,reased there might be a,n increase ifi the frequency of reactions. The difference was scarcely detectable, however, since 3 per cent, novocain gave only a 71.2 per cent frequency of no reactions as compared with t,he 75.0 per cent control with the same vasoconstrictor. When the cobefrin was used as the vasoconstrictor, the incidence of patients with no reactions was 70.7 per cent. Adding pontocaine 0.15 per cent to this mixture did not increase the frequency of reactions but on the contrary diminished them if anything, since now 77.0 per cent of the patients were free of reactions. The difference between these two approaches statistical significance and most clearly rules out, the hypothetical possibility of an &c,/*eased clinical toxicity from the added pontocaine. When the individual t,ypes of reactions are considered as set forth under the headings of perspiration, tremor, respira,tory embarrassment, nervousness, and tears, it is seen that increasing the novocain concentration to 3 per cent in the epinephrine series decreased the incidence of perspiration and respiratory changes but doubled the frequency of tremors and greatly increased the

IV.

SOLUTIoN

SUMMARY

OF CASES

NO.

OF OBSERVATIONS

inephrine 1:50,000 Novocain 2%, pontocaine 0.15%,, cobefrin l:lO,OOO Probablhty of no difference from novocain 2% with epinephrine 1: 50,000

I

178

Novocain 27’ with epinephrine 120 1:50,000 Novocain 2y0 with cobefrin 133 1: Probability 10,poo of no difference from novocain 2% with epinephrine 1:5O,OOK Novocain 3% with epinephrine I 191

TABLE

THE

I

<.OOl

2.8 + 0.07

I 2.8 + 0.08

.15

I

----4548

47 I -------x-

-37 54

INFILTRATION

3.3 to.12

I

I

I

IN-

OF THE

11

-

-.

--

_-

3

0

2

0

I

I

0.6 + 0.6

.Ol

0.0

.03

0.0

3.3 2 1.6

I

1

1

I

I

TO VOLUMES

1.4

2.8 f. 1.2

.02

5.2 + 1.6

.13

4.5+1.8

2.5?

PATIENT

INJECTED,

23

0.0

.22

0.0

.30

0.0

0.8 2 0.8

AND

.

.62

16.9 ? 2.8

<.OOl

24.6 f. 3.1

.03

218k36 .

15.0 ?r 3.3

NERVOUSNESS

OF INJECTION,

REACTION I EMBARR. OF RESPIR.

TYPE

I .(j”I *04I *78

77.0 +_ 3.2

.22

71.2 f 3.3

I

1

.25

1

I

1

75.0 c 4.0

I

REGARD

/ 70.7 + 3.9

I

SKO~;D SERIES WITIT OF REACTION

OF INJECTION POST. I FERIOR STY. ALvEOALVEOC LAR LAR _-

TYPE

PATIENTS

---37 52

622

3.6 +_ 0.16

VOLUME REQUIRED (cc)

IN

1

.13

3.9 2 1.4

.50

6.2 C 1.7

50

6.0 +_ 2.1

8.3 + 2.5

TEARS

FREQUENCY

Local Anesthetic

Solutions

of Increased

323

Strength

incidence of nervousness. In contrast, producing a stronger anesthetic solution by adding pontocaine to the novocain in the presence of cobefrin did not appreciably alter the amount of perspiration and respiratory change, and actually decreased the frequency of tremor, nervousness, and tears. We do not wish to claim that these results prove novocain-pontocaine-cobefrin to be less toxic than novocain-cobefrin beyond a statistical doubt, but they make it extremely improbable that pontocaine has added to t,he clinical toxicity of the mixture. SUMMARY

AND

CONCLUSIONS

Using the blind test technique, the responses of 2,382 patients to a group of four local anesthetic solutions have been studied. The data obtained in these studies comprise observations on: volume of solution required, onset time .of anesthesia, grade of anesthesia, duration of anesthesia, blood pressure changes, pulse rate changes, amount of bleeding, and patient reactions. These data were subjected to statistical evaluation. From them the following conclusions seem warranted : 1. The longest duration of anesthesia occurred with a combination of novocain 2 per cent, pontocaine 0.15 per cent, and cobefrin l:lO,OOO. This was significantly longer t,han the 3 per cent novocain with epinephrine 1:50,000 solution, and moderately longer than novocain 2 per cent with either epinephrine 1:50,000 or cobefrin 1 :lO,OOOadded. 2. The novocain-pontocaine combination and the novocain 3 per cent both required a smaller volume to produce satisfactory anesthesia than did either of the other two. 3. The differences in the degree of anesthesia. produced by the four solutions, as judged by the incidence of incomplete loss of sensation, were not clinically important. All four gave generally satisfactory anesthesia. 4. The two solutions containing cobefrin appear to produce slowing of the pulse rate, whereas the two solutions containing epinephrine produce an increase. 5. The changes in both diastolic and systolic pressure are small for all of the solutions studied. No significant differences among the solutions for the circulation were found except that two of the solutions produced a slightly higher pulse pressure than did the others. 6. In general, freer bleeding occurred with the three test solutions than with the reference solution. 7. When considered from the standpoint of no reactions, perspiration, nervousness, tremor, tears, and embarrassment of respiration, it can be seen that (a) novocain 3 per cent with epinephrine differs from the reference solution in being somewhat more poorly tolerated, and (b) adding 0.15 per cent pontocaine to the novocain-cobefrin mixture does not increase, but possibly, even decreases, the incidence of reactions. 8. Each of the four solutions is a satisfactory anesthetic for the types of clinical procedures included in this investigation. The authors Schmitt, and the New York University

desire to express their staffs of the Department and of Bellevue Hospital

thanks to Dr. Martin E. Aronson, of Oral Surgery of the College of for their valued cooperation.

Dr.

Dentistry

Eugene

of

Leon J. Allen

324

REFERENCES 1. Tainter, 2.

3. 4. 5. 6. 7. 8. 9. 10.

M. L., Throndson, A. H., and Moose, S. M.: Comparison of Procaine Hydrochloride and Procaine Borate as Local Anesthetics. J. Am. .Dent. A. 24: 1480, 193i. Idem: Vasoconstrietors on the Clinical Effectiveness ‘and Toxicity of Local Anesthetic Solutions, J. Am. Dent. A. 25: 1321, 1938. Idem: Alleged Clinical Importance of Buffered Local Anesthetic Solutions, J. Am. Dent. AI 26: 920, 1939. Tainter, M. L., and Throndson, A. H.: Value of Pot,aswium in Local Anesthetic Solutions of Procaine and Epinephrine, J. Am. Dent. A. 27: 71, 1940. Tainter, M. L.: Summary of Studies on the Optimal Compositiou of Local Anesthetic Solutions, Anesthesiology 2: 489, 1941. Tainter, M. L., and Throndson, A. H.: Suitability of Butyn for Injection Anesthesia in Oral Surgery, J. Am. Dent. A. 28: 1979, 1941. Schneider, J. J.: Clinical Results in the Use of Local Anesthetic Solutions With Various pH values, Northwestern University Dentai Research and Graduate Study 40: 16, 1940. Tainter, M. L., and Winter, Leo: Some General Considerations in Evaluating Local Anesthetic Solutions in Patients, Anesthesiology 5: 470, 1944. Miller, Howard C., and Stuart, Carroll W.: Comparative Merits of Vasoconstrictors in Local Anesthetic Solutions, J. Am. Dent. A. 23: 1883, 1936. Winter, Leo: A Textbook of Exodontia, ed. 3, St. Louis, 1943, The C. V. Mosby Co.

ORAL

MANIFESTATIONS

OF ACUTE

MYELOGENOUS

LEUCEMIA

CASE REPORT LEON

J. ALLEN, D.D.S.,* MT.

VERNON,

N. Y.

HISTORY

M

RS. A. G., aged 31 years, presented herself at the Oral Surgery Clinic of the New York University College of Dentistry for relief from persistent pain and swelling in the right maxillary region, following an extraction of an upper right second premolar three weeks previous. Medical H&tory.-There was none except for the fact that nine years ago, prior to her first pregnancy, she was told she was anemic; she did not recall any particular treatment for the condition. Dental History.-Past: The patient had a full complement of teeth, except for the lower right first and second molars, and the lower left first molar which had been removed some time before. Present: About four weeks ago the patient suddenly developed swelling and pain on the upper right side of the face. She was told that she had a “gum infection” and was placed on a mouthwash. Two days later, under local anesthesia, a carious upper left second premolar was removed. The day following the extraction, the pain became increasingly severe, accompanied by temperature reading of 103” F. The patient was subsequently referred to a physician who prescribed sulfonamide therapy, 4 Gm. daily for ten days, a total of 40 Gm., along with the administration of liver and iron tablets. During this period the temperature fluctuated between 100” and 103” F. The pain did not subside completely. The tissue about the socket became puffy and the gingivae generally began to swell and hurt. Adenopathy in the submaxillary and sublingual areas be*Assistant

Professor

of Oral

Surgery,

New

York

University,

College

of Dentistry.