Acta Anaesthesiol Scand 1991 : 35: 208-2 15

Effect of intradermal injection of saline or a local anaesthetic agent on skin blood flow a methodological study in man

-

I. CEDERHOLM, H. EVERSand J. B. LOFSTROM Drpartment of Anaesthrsiology. Univrrsity Hospital, Linkijping. and Astra Pain Control, Dcpartmrnt of Clinical Pharmac.ology. Sildcrtiljc.. Swrdcn

The influrnw of intradrrmal iicrdle insertion and lluid injection on skin hlmd Ilow was investigated using laser Dnppler th~wmetry.~ c v i ~ n t c ehralthy, n young male volunteers participated. E'ciur tcst sites on CWII Ibrc.arm I volar surfarr) wrre used in a randomized, d o u t h h l i n d study. Rrcordings w t w madr at '10, 40, (ill and in Group 111 also at 90 min after nrrdlc insertion or intradrrmal in,jrction. In Group I ( n = 6 ) dilliwnt volunirs of saline (0.05, 0.1, 0 2 , 0.3 and 0.5 ml) werr injrrted, producing a n incrc:isc i n llnw, thcrr bring no tliIkrrnrc.s betwren thc various volumes. In Grciup I I ( n = Ij nredlt- insertions wcrr mad[. using dillkrcnt nerdlr sin-s (20 C, 23 G and '10 G ) , thc larger ones being impractical IO usc.. Incrrasrs i n flow wc.ri. sccii, and wcrc sonirwhat higher h i the larger nerdlrs. Croup Ill ( n = 1'1) was studird regarding tlir c.lli.c.ts of three local an;iesthetir agents on skin blood flow (0.I nil, 30 (; nt*tdle). Injection o f lxtpivaciiinc 0.7.5",, produced a marked increase i n flow, similar to lidoeainr I " i , hut apparrntly longrr lasting. Bupivacitini. 0.'15",, caused less increase in tlow, similar to the flow scen with saline. Irijrrtions orropivarainr 0.75",,and 0.25'!;,, i.r. in rlinical roncentr.itions, caused a decrease in blood flow, this being most marked artrr 1).2.5",,, indicating a unique flow-decre;tsing elFect of this new local anaesthetic drug. Rec.eived 3 .Voiiember 1989, accepted Jbr publication 22 August 1990

A-ty uiords: Bupivarainr; intradrrmal injection; lasrr Dopplrr Ilowmrtry; lidocainc.; local anrsthrtic agcntc; ropivacainc; skin blood flow.

Intradermal injection of local anaesthetic agents has been used in several studies to evaluate their bloching erects with respect to time of onset and duratioii of action (1-1 1 ) . Attempts have also been made to use this method when assessing the erects of such agcmts on skin circulation. Changes in skin colour (8- 10, 12-14) and temperature (15), and the inflammatory reaction (4, 5) have been interprc.trd as being an efrect on local circulation. Previous observations using laser Doppler flowmetry (16) have shown that skin circulation at the volar surface of the forearm in a person resting supine at a room temperature of about 22°C is low. At this temperature skin vasoconstriction is required to conserve body heat. Since resting skin blood flow is low at room temperature, increases i n flow can be provoked. This is illustrated by the marked increase in skin blood flow produced, for example, by a brachial plexus block (17) or by spinal anaesthesia (16). A significant vasoconstrictor emect, however, is more tlifGcult to demonstrate. In a pilot study we observed that the insertion of an intradermal needle as well as an injection of saline provoked a marked increase in blood flow as measured

by laser Doppler flowmetry, which is in line with previous reports (18, 19). Thus, an intradermal injection might still be a suitable test method, elucidating dru,g erects on skin blood flow (i.e. showing not only a i l increase but also a decrease in Ilow) if the e k t s ol' the needle insertion or saline injection are considercd in the evaluation of the net circulatory e1Iec.t of the test drug. The present investigation was divided into two parts. The aim of' Part 1 was to investigate I'ic ., tor5 possibly influencing skin blood Ilow using laser 1)oppler flowmetry, as follows: 1 . Measurement of blood llow (laser Doppler Ilowmetry) at the volar surfaces of both forearms t o determine if four measuring sites on each arm could be used in a randomized, double-blind study, without needle insertion or fluid in,jection causing interference from one site to another. 2. Measurement over a period of time of the blootiflow-increasing erect of intradernial needle inspi tion. 3. Measurement of the circulatory dT.ct of intradcrma1 needle insertion plus thc injection of v;trious volumes of saline.

209

INTRADERMAL INJECTION AND SKIN BLOOD FLOW Table I The \.trious measuring sites in Groups 1-111. Inj. of bupivacaine

Inj. of ropivacaine

1 Yo

0.25"!,

0.750,:,

0.25"/,

-

-

-

-

0. I

0.1

0.1

0. I

Inj. of lidocaine Needle insertion

Ini. of saline

0.75'70

0.3, 0.5 I1 I11

+ +

20 G , 23 G, 30 G 30 G

4. \4'hat influences does the needle size have?

5. Is there any variation in the shape of laser Doppler flowmetry curves at different injection sites? Previous studies (20, 21) have shown rhythmical variations in human skin blood flow measured with lriser Doppler flowmetry. 6 . '1.0 design a suitable test procedure to evaluate the dfects of drugs on skin blood flow (randomization, control injections, etc.), taking into account the hidings of 1-5 above. In Part 2, the test method derived from Part 1 was used to evaluate the skin blood flow changes provoked by the intradermal injection of local anaesthetic agents in clinical use. The drugs tested were lidocaine (Xylocaine"', Astra, Sweden), bupivacaine (Marcainm, Astra. Sweden) and a new long-acting local anaesthetic agent, ropivacaine (LEA 103, Astra, Sweden) (7).

-

0.1

-

0.1

different test sites on each forearm, with a minimum separation of 3 cm (Fig. 1). Plastic probe holders were then attached to the tape rings, the probe attached at each test site and baseline blood flow values were recorded for about 2 min at each site, i.e. until a stable plateau recording had been obtained (original values). Each probe holder was then removed, leaving one adhesive ring still attached t o the skin. Intradermal needle insertion or fluid injection was carried out, the insertion or injection was made precisely in the centre of thr ring. The probe holder was then reattached to thr plastic ring, each having a pointer so that the probe could be replaced in exactly thr same position as during the original recordings. The probe was thus fixed in the same position for all recordings. Laser Doppler flowmetry was used for the measurement of the skin blood flow (21-24). The apparatus used was a Periflux@(Perimed, Sweden). The analogue output signal was fed to a pen-recorder krr continuous recording of skin blood flow (Linear Chart Recorder", Model 585). The band width of the instrument was set at 4 kHz and the time constant of the damping filter to 0.2 s throughout this studv. This combination enables the recording of low flow rates as well a s

MATERIAL AND METHODS Thr studies were carried out on healthy, young male volunteers. Appoval was obtained from the University Hospital Ethics Committee bind from the Pharmacothrrapeutics Section of the Swedish Natioiwl Board of Health and Wrlfare. Informed consent was obtained from each volunteer. 111 Group I (series B). ( n = 6 , mean agr 32.5 years, range 25-45), the intradermal injection of various volumes of saline (0.9%) was invuntigated. In Group I1 lserirs C), ( n = 4 , mean age 33.5 years, rangr 27--39),thr erects on skin blood flow of intradermal needle inswtion using needles of various sizes were studied. In Group I11 (srrics A), ( n = 12, mean age 31.7 years, range 25-45), the effects of needle insertion, injection of saline, injection of lidocaine, of bupivacaiac and of the new local anaesthetic agent, ropivacaine, on skin blmd flow were studied. An untreated site served as a control (Table I J. 'I'wo volunteers from Group I and three from Group I1 also took part i n Group 111. There was at least a 2-week interval between the testing procedures for these five volunteers.

Pror vdurcs Sukijrcts lay on a couch and were covered with a blanket to minimize heat loss. The temperature in the laboratory was thermostatically cotitrolled and kept at 21-22", and varied no more than 0.2% during any rxperiment. Afirr rxposure of the volar surface of both forearms, two doubleadlicsive probe-fixation tape rings were attached to the skin at four

A

Fig. I . The experimental set-up and the procedures. Double adhesive rings were attached to the skin and the original recordings were done at each test area. The outer adhesive ring was then removed and the intradermal injection was made. The test probe was then again attached to adhesive tape, each having a pointer so that the probe could be repositioned in exactly the same position as during original recordings. Flow determinations wrre done at each of the test sites at 20, 40,60 and 90 min.

210

I. CEDERHOLM E T AL.

rapid changes in microvascular flow at low noise levels. The instrument records flow not as absolute values as ml/min/100 g tissue, but in Volts, which are linearly related to flow for low and moderate flow rates. The range of full scale deflection was from 0 to 10 Volts. It is of greatest importance when using this instrument that the probe is placed in exactly the same position for all measurements. This was achieved by the arrangement using two double-adhesive rings as desrrihed above. 'The following procedures were then carried ciut in a sequence at the various test sites (Fig. 1 and Table 1). In Group I, there was one untreated control site, one sile for needle insertion (made with a 30-Gauge needle attached to a plastic I -ml insulin-syringe, Monoject", Sherwood Medical, U.K.) and sites for injection of saline in various volumes (0.05, 0.1, 0.2, 0.3 and 0.5 ml) and injection of lidocaine 1 ":o (0.I ml of 10 mg/ml) Xylocaine", Astra, Sweden). The rate ofinjertion was 0.1 ml per 10 s in all cases. In Group 11, three needle sizes were compared: a 30-Gauge needle (Monoject", Sherwood Medical, U.K.), a 23-Gauge and a PO-Gauge needle (Becton Dickinson & Co., USA). l h r e e needle insertions were rarried out on each forearm in a randomized fashion and a fiiurth untreated site was used as a control. In Group 111, measurements were madc at an untreated control site, after needle insertion (30 G ) , after injection of saline and of a local anaesthetic agent (0.I ml via a 3 0 4 needle) as follows: lido( aine I ".;, (0.1 ml of 10 mglml), bupivaraine 0.25'V0 (0.I ml of 2.5 mg/ml) and 0.754, (0.1 ml of 7.5 mglml), ropivacaine 0.25'; (0.1 ml (if 2.5 mg/ml] and 0.75'),, (0.1 ml of 7.5 mglml). 'I'he solutions were coded, enabling the studies to be double blind. All solutions were prepared by Astra Laboratories in Sodertalje, Sweden. The pH ofsaline was 6.0, of lidocaine 6.7 and of all solutions of hupivaraine and ropivacaine 5.5. All intradermal injections were made by one and the same person (H.E.). The volume of solution injection (Group I ) as well as the nredle size (Group 11) was not known to thr person making and evaluiiting the recordings. After the original blood flow levels had been drtermined, intradermal needle insertions or fluid injections were made exartly 2 min apart. In earh subject, measurements after nredlr insertion (30 C) or fluid injection werc started within 30 s at onc' site of the eight used and rontinued for 1@-12 min to elucidate the early circulatory effect on this site and to evaluate if there was any interference from treatment at the other nearby sites.

V

0

0

4

2

I

I

10 12 14 16

la

1

20

n m (min) Fig. 3. Initial effect of needle insertion (30 G ) on skin blood flow in four volunteers.

Twenty minutes after the first injection at the first site, the recording was started again. After 2 min the recording probe was moved to the next site and a new recording was made, etc. In this way recordings were made at each site at 20, 40 and 60 min in the first two series. In the third series a recording was also made 90 min after the needle insertion or fluid injection. Stntisliri O u r recorded data are presented in Fig. 2-10. The Wilcoxon Signed Rank Test was used for statistical evaluation. In Table 2 differences in flow values (Volts) at 20 min after a treatment are presented with P-values. I n Tables 3 and 4, comparisons between treatment values and saline values have been carried out.

Needle insertion

Control V

V

7

7

4-

321-

" I

2Q

40 0Q nme (min) Medlan 0.4 0.4 0.4 0.4 Q

Qi-7niTT-Q

9Q

Time (mln)

ModIan 0.33

0.4

Fig, 2. Skin blood flow at untreated control sites, Group 111 12).

(11

=

1.B 1.2 0.8

0.5

Fig. 4. Skin blood flow after needle insertion (30 C). Group 111 ( n = 12).

INTRADERMAL INJECTION AND SKIN BLOOD FLOW

211

Table 3 shows the differences in flow at 20 min after a treatment, and Table 4 differences in computer-estimated Area Under the Curve (AUCi. The calculations in Tables 3 and 4 were carried out as follows. The flow (Volts) of a treatment (e.g. lidocaine 1";) was divided by the flow produced by saline, minus the flow produced by anothrr treatment (e.g. bupivacaine 0.75O/,,), divided by the flow after d i n e injection. Analysis of variance was usrd to see if the site of tre.ilinrnt influenced the recorded values.

RESULTS For statistical evaluation, see Tables 2, 3 and 4.

Part I Original skin blood flow was low in all volunteers, similar at all sites tested, and similar in both arms beforr any treatment (original values). The original and control recordings at the untreated areas were low and remained unchanged throughout the various test periods. This observation was constant in all series. The results from Group I11 are presented graphically (Fig. 2). The increase in blood flow following an intradermal needle insertion started within 30 s, its peak appeared after about 5-7 min and it then declined slowly (Fig. 3). An increase in blood flow was seen as late as 90 min after needle insertion (Fig. 4). Needle insertion plus the injection of 0.1 ml of saline was also followed by an increase in blood flow of a magnitude similar to the effect of needle insertion (Fig. 5). Injection of the various volumes of saline was followed by a significantly higher blood flow than at control sites, there being no differences in flow related

-

04 0

.

.

20

.

-

I

00

I0

Time (mln)

Fig. 6. Skin blood flow after injection of different volumes of saline, (values as mean), Group I (n = 6 ) .

to volume injected (Fig. 6 ) . The larger volumes produced a marked local pallor, but even so the blood flow was higher than at the control sites. Neither needle insertion nor needle insertion plus the injection of 0.1 ml of fluid influenced the blood flow at remote or nearby test sites. There was no difference in reactions at the various test sites described above. Needle insertion with the 30-Gauge needle produced an increase in skin blood flow that was slightly less than after insertion of the 20-Gauge and 23-Gauge needles. The thin 30-Gauge needle was found to be

Saline

Lidocaine 1.0%

V

V

0 Median 0.4

20

40 60 Time (min)

1.8 0.9

0.7

90

0.5

Fig. 5. Skin blood flow after intraderrnal injection of 0. I ml of saline, Group 111 ( n = 12).

0 Median 0.4

20

40 60 Time (min)

2.7 2.0 1.6

90

1.2

Fig. 7. Skin blood flow after intraderma] injection of 0.1 ml of I " ( , lidocaine, Group 111 (n= 12).

212

1. CEDERHOLM ET AL.

most suitable for standard intradermal injection of a small (0.1 ml) volume of a test drug, whereas 20-G and 23-G needles are technically more difficult to use for this purpose. Part 2 The injection of lidocaine lolo (0.1 ml, 30-G nevdle) produced a markedly higher skin blood flow than that seen after the injection of saline (Fig. 7, compare Fig. 2, 4 and 5 ) . Injection of bupivacaine 0.2514 produced a flow similar to that of saline injection (Fig. 8). Skin blood flow after the injection of bupivacaine 0.75% was similar to that produced by the injection of lidocaine lyh, but seems to be longer lasting (Fig. 9 ) . Ropivacaine 0.25% given intradermally was followed by a low skin blood flow, lower than after the injection of saline. The same was seen after the injection of ropivacaine 0.75%, though not quite as low (Fig. 10 and 1 1 ) . Skin blood flow changes lasted more than 90 inin. Large waves in the flow curves were by and large not seen after injection of ropivacaine (0.25% and 0.75(yo) and of bupivacaine 0.25yo, indicating vasoconstriction in the skin arterioli (20).

DISCUSSION Laser Doppler flowmetry has been shown to be an excellent method of demonstrating changes in skin blood flow (21-24). Control recordings are stable and the method provides reproducible results, as illustrated in our figures. The untreated control sites showed constantly low and unchanged skin blood flow throughout

Bupivacaine 0.75% V

0

40 00 Tlmo (mln)

Msdlan 0.4 2.2 2.9

2.7

90

2.1

Fig. 9. Skin blood flow after intraderma] injection ofO.1 ml of0.75",, bupivacaine, Group 111 ( n = 12).

the test procedure. There was no interference between the various sites, as is illustrated. Needle insertion provoked a significant increase in blood flow, probably due to an inflammatory reaction to the trauma. Comparison of the three needle sizes showed a somewhat greater increase in flow after the insertion with 20Gauge and 23-Gauge needles than when a 30-Gauge needle was used. The 30-G needle was found to be better, since it is technically easier to inject a small volume (0.1 ml) precisely intradermally. Furthermore, the results from testing local anaesthetic agents in Part

Bupivacaine 0.25% V

20

Ropivacaine 0.25% V

451

3

41 3

2 1

0

0

Median 0.4

20

40 00 Tlms (mln)

1.2 0.6 0.5

90

0

-0

20

So so

90

Tlms (mln)

0.4

Fig. 8. Skin blood flow after intradermal in,jrction of0.l rnl of0.25", bupivacaine, Group 111 ( n = 12).

Msdlan 0.4 0.5 0.3

0.3

Fig. 10. Skin blood flow after intradcrmal 0.25'1,, ropivacaine, Group 111 ( n = 12).

0.3 iti,jrtticin

of 0. I

nil of

213

IN'I'RADERMAL IN.JEC?'ION AND SKIN BLOOD FLOW Tablv 2 1ntr.bdrrmal tests: DifFerences in flow v.ilues (Volts) at 20 min, inducril bv different test orocedures Wilcoxon Sign Rank Test Nerdlr NaCI -

NaCl Lidoc Bupi 0.25"" Bupi C1.75°, Bupi 0.25", Bupi 0.75", Bupi 0.75'1, Bupi 0.25",, Ropi i1.25",, Ropi 0.75",, Ropi 0.25",,

versus versus versus versus versus versus versus versus versus versus versus

versus versus

Control Control Needle NaCl NaCl NaCl Bupi 0.75",, Lidoc I?,, Ropi 0.75", Ropi 0.25",, NaCI NaCl Ropi 0.75c,',

P=0.003 P=0.003

N.S. P=0.005 N.S. N.S. P=0.05 N.S. P=0.003 P=0.003 P= 0.003 P= 0.009 P = 0.006

U n d d i n e d treatment indicatrs higher flow.

for the injection of saline and one site for a reference drug, e.g. lidocaine (when testing local anaesthetic drugs), should be included: The intradermal test procedure described above was applied to bupivacaine and ropivacaine. Injection of bupivacaine 0.750/, produced a marked increase in blood flow, similar to the increase seen after lidocaine 1% but it seemed to be longer lasting. The injection of bupivacaine 0.25% showed a lesser increase in skin blood flow, similar to that seen after the injection of saline. These findings are in line with previous studies showing more marked increase in flow with higher concentrations of local anaesthetics compared to weaker concentrations (25). The injection of ropivacaine Table 4 Intradermal tests: DifFerences in Area Under the Curves (AUC drug versus AUC NaCI) between treatments. Wilcoxon Sign Rank 'Test

2 of this study support this opinion, since significant chariges (increase or decrease) in skin blood flow were easily demonstrated using a 30-G needle. Varying volumes of saline did not differ in respect of their flowincreasing effect, but since a low volume of a test drug is drsirable, we suggest 0.1 ml to be a suitable test volume. The Ilow-increasing effect of intradermal needle insertion of fluid injection started within 30 s and there was i i maximum at about 5-7 min. Taking these findings into consideration, the intermittent recordings were begun 20 min after needle insertion or intraderma1 injection. In this way we found it possible to use 8 diflerent test sites, 4 on each forearm, allowing us to test srveral drugs simultaneously in a double-blind, randomized fashion. One untreated control site, possibly cine test site for needle insertion only, one test site

test

Needle NaCl -

NaCl Lidoc l o o Bupi 0.257, Bupi 0.7501, Bupi 0.25c>/, Bupi 0.75"/, Bupi 0.754d Bupi 0.25"/, Ropi 0.25°/, Ropi 0.751:/, Ropi 0.25?:,

versus versus versus versus versus versus versus versus versus versus versus versus versus

P = 0.003 P-0.003 N.S. P=0.003 N.S.

Control Control Needle NaCl NaCl NaCl Bupi 0.754, Lidoc I?,, Ropi 0.75"/, Ropi 0.25"6

P=0.004 P=O.O03 N.S. P=0.003 P=0.007

P = 0.003 P = 0.006 P = 0.005

& C J

NaCl Ropi 0.757,

Underlined treatment indicates higher flow.

Ropivacaine 0.75% V

Tablr j Intradrrinal tests: DifFerences in flow between treatments (treatment Volt/N.~(:l Volt) at 20 minutes.

54-

Wilroxon Sign Rank 'Iest Needlit NaCI NaCl Lidoc I Bupi 0 :'5",, Bupi (J 75",, Bupi 0 25",, Bupi I)73",, Bupi 0 i.5",, Bupi 0 Y",, Ropi Il.25",, Ropi 0.75",, Ropi l l . ? Y ' ( , L'ndcrliiicd

versus versus versus versus versus versus versus versus versus w-rsus

versus versus versus

ireatment

Control Control Needle NaCl NaCl NaCl Bupi 0.750, l.idoc I l l o Kupi 0.75",, Rqii 0.25",, NaCl -

NaCl

Kopi 0.75",,

indicatrs higher flow.

P = 0.003 P = 0.005 N.S. P=0.005 N.S. N.S. P=0.04 N.S. /'= 0.003 /'= 0.003 P = 0.005 P = 0.04 P = 0.006

32-

Time (min) Median 0.4

1.0 0.5 0.4

0.3

Fig. 1 I . Skin blood flow after intradermal injection of 0.1 ml of 0.75'!,,ropivaraine, Group 111 ( n = 12).

214

1. CEDERHOLM ET AL.

in clinically used concentrations, however, caused a decrease in blood flow compared to saline. This was most marked with the weaker solution (0.25%) tested, indicating a unique effect of this new local anaesthetic drug (26, 27).

CONCLUSION The present study indicates that the effect of drugs on local circulation may well be studied by intradermal injection and recording of changes in skin blood flow, using laser Doppler flowmetry. A suitable test procedure would be to use 4 different test sites on each volar surface of the forearm (i.e. 8 test sites), injections done at least 3 cm apart, as illustrated in Fig. 1. All such test procedures should include one untreated control site, one site for injection of saline, possibly a third site for intradermal needle insertion only, and a fourth site for injection of a reference drug, such as lidocaine when testing local anaesthetic agents. The test procedure was applied to lidocaine, bupivacaine and a new local anaesthetic drug, ropivacaine. A marked increase in flow was seen after the injection of lidocaine 1 yo and of bupivacaine 0.75%. A marked decrease in skin blood flow was seen after the injection of ropivacaine, compared to the effect of saline, indicating a unique effect of this new local anaesthetic drug.

ACKNOWLEDGEMENTS The authors thank Anna Torrang for statistical advice, Jan S,jovall, Associate Professor and Head of the Department of Clinical Pharmacology, Astra Pain Control for valuable suggestions and lngemar Ideholm, Astra Reklam for his help with the graphic presentations. Financial support was received from the Medical Faculty, Linkoping University, Linkoping, Sweden and from Astra Pain C~introl, Sodertalje, Sweden. The drugs tested were provided by Astric Pain Control, Sodertalje, Sweden. Presented at the 20th Congress of the Scandinavian Society of Anaesthesiologists in Copenhagen, Denmark, June 30, 1989.

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-7Pharmacol Exp Ther 1945: 85: 78-84. 3. Mongar J L. A study of two methods for testing local anaehthetics in man. Br J Pharmacol 1955: 10: 24&246.

4. Padfield A. The intradermal local analgesic action ol' priloixine. Anaesthesia 1967: 22: 556-561. 5. Luduena F P. Duration of local anaesthrsia. Ann Heti !'harmmo/ 1969: 9: 503-520. 6. Swerdlow M, Jones R. The duration of artioii of bupivacainc, prilocaine and lignocaine. Br J Anaesth 1970: 42: 335-339. 7. Akerman B, Hellberg 1-8, Trossvik C:. Primary evaluation of thr local anaesthetic properties of the amino amide agrrit ropivacaine (LEA 103). Acta Anaesthesiol &and 1988: 32: 571-578. 8. Aps C, Reynolds F. The effect of concentration 011 vasoactivity of bupivacaine and lignocainc. Rr J Anaesth 1976: 48: I 1 7 1 I 1 74. 9. Fairley J W, Reynolds F. .4n intradermal study of the local anaesthetic and vascular elkcts of thr isomrrs of mrpivaraine. Br J Anaesth 1981: 53: 1211-1216. 10. Willatts D C , Reynolds F. Comparison of the vasoactivity of amide and ester local anaesthetirs. An intradermal study. Rr J Anaesth 1985: 57: 1006-101 I . I I . Patel M A. Modification of intradcrmal wheal method. Indian .7 Ex) Biol 1968: 6: 64-66. 12. DhunCr K G. Mepivacaine and vasoconstrictors in rcgional anaesthesia. A d a Anaesfhesiol &and 1972: suppl. 48. 13. Luduena F P, Bogado E F, Tullar B F. Optical isomrrs of mepivacaine and bupivacaine. Arch In! Pharrnacodyn 1972: 200: 359-369. 14. Reynolds F, Bryson T H L, Nicholas A D G. Iutradrrmal study of a new local anaesthetic agent: aptoraine. Br J Anaesth 1976: 48:347-354. 15. Aberg G , Adler R.Thermographic registrations of some vascular effects of a local anaesthetic compound. Szoed Den1 .7 1970: 63: 67 1-67 7. 16. Bengtsson M , Nilsson G E, Lofstriim J B. T h r effect of spinal analgesia on skin blood flow, evaluated by laser Dopplt-r llowmetry. Acta Anaesthesiol Scand 1983: 27: 206-2 10. 17. Katz J . Skin blood flow after axillary brachial plexus block, use of laser Doppler flowmetry. Regions/ dnesth 1984: 9: 6869. 18. Holloway G A. Cutaneous blood flow responsrs to injtactioti trauma measured by laser Doppler vclorimrtry. J Invest Dumato/ 1980: 74: 1 4 . 19. Carpenter R L, Morel1 K C. Bupivacaine and lidocaine arr more potent vasodilators than mepivaraine: effects determiiird by anesthetic concentration. Aneslhesiolozy 1988: 69: A R73. 20. Fischer J C, Parker P M, Shaw W W. Waveform analysis applied to laser Doppler flowmetry. Microsurgery 1986: 7: 67-71. 21. Tenland 'I. On laser Doppler flowmetry - methods and micrtlvascular applications. Linkoping Unnivcrsity Medical Dissrrtations, Sweden, 1982: No. 136. 22. Westerman R A, Widdop K E, Hannaford J rt al. Laser Doppler velocimetry in the measurement of nrurovascular function. AuJ.tralasian Physical &? Engineering, Sciencrs in Medicine 1988: 11: 53-66. 23. Salerud G . Laser Doppler tissut- ilowmetry fiberoptic methods in microvascular research. Linkiiping University Mediral Dissertations, Sweden, 1986: No. 216. 24. Nilsson G E, Tenland T, o b c r g I' A. Evaluation of a I;tsrr Doppler flowmeter for measuremrnt of tissue blood flow. IEEE Trans Bio-Med Eng 1980: 27: 597-604. 25. Lijfstrom J B. Physiological efferts of local anaesthetics on circulation and respiration. In: Lofstrom J B, U. Sjostrand, eds. Loral anaesthesia and regional blockadr, Pharmarology, physiology and clinical effects. Amsterdam: Elsrvier Scienrr Publishers, 1988: 45-56. 26. Akerman B, Evers H. A comparative study of hupivacairic a ~ i t l the enantiomers of ropivacainr in intradcrmal wheals in tlic guinea-pig and man. European Society of Regional Anaesthcsi;c. Congress in Paris, 1987. -

INTRADERMAL INJECTION AND SKIN BLOOD FLOW

27. Kopacz D J, Carpenter R L, Mackey D C. Effect of ropivacaine 011 cutaneous capillary blood flow in pigs. Anesthesiology 1989: 71: 69-74.

Address: Ingemar Cederholm, M.D. Dept. of Anaesthesiology University Hospital S-58185 Linkoping Sweden

215