- Email: [email protected]
Effects of lidocaine and epinephrine on cutaneous blood flow
Journal of Plastic, Reconstructive & Aesthetic Surgery (2008) 61, 1226e1231
Effects of lidocaine and epinephrine on cutaneous blood flow* S. Ghali a, K.R. Knox a, J. Verbesey b, U. Scarpidis c, K. Izadi c, P.A. Ganchi d,* a
Laboratory for Microvascular Research and Vascular Tissue Engineering, New York University, New York, NY, USA Massachusetts General Hospital, Department of Plastic Surgery, Boston, MA, USA c University of Medicine and Dentistry of New Jersey, Division of Plastic Surgery, Newark, NJ, USA d Ganchi Plastic Surgery, 342 Hamburg Turnpike, Suite 202, Wayne, NJ 07470, USA b
Received 26 September 2006; accepted 13 September 2007
KEYWORDS Cutaneous blood flow; Lidocaine; Epinephrine; Laser Doppler
Summary Background: Local anaesthetic agents in combination with epinephrine are frequently used in local reconstructive procedures such as skin tumour excision and local flap closure. The purpose of this study was to measure the effect of subdermal injection of lidocaine combined with epinephrine on cutaneous blood flow in the forearm and in the face. Methods: Thirty injections were performed on the forearm and 40 injections were performed on the face in five healthy volunteers. In both anatomical regions, 0.9% phosphate buffered saline (PBS) was used as a control, and experimental injections included 1% lidocaine either alone or in combination with 1:100 000 epinephrine, and an additional combination of 1% lidocaine with 1:200 000 epinephrine used in the facial experiments. Cutaneous blood flow was measured indirectly using laser Doppler imaging (moorLDI-Mark 2). Results: A statistically significant increase in blood flow was achieved with injection of lidocaine in the forearm compared to saline, whereas a non-statistically significant increase was achieved with saline injection compared to lidocaine in the face. This occurred in the first 5 min in the forearm and 2 min in the face. The addition of 1:100 000 epinephrine to lidocaine resulted in an immediate decrease in cutaneous blood flow which was maximal at 10 min in the forearm and 8 min in the face. This was statistically significant compared to all other injections except for the combination of 1:200 000 epinephrine with lidocaine, injected in the face. Conclusions: The vascularity of different anatomical areas may account for blood flow differences following injection with saline and lidocaine. Incisions should be delayed for 10 min in the forearm and 8 min in the face following lidocaine þ epinephrine injection to
*
This work was presented at the 2004 Northeastern Society of Plastic Surgeons, Naples, Florida, USA. * Corresponding author. Tel.: þ1 973 942 6600; fax: þ1 973 595-5964. E-mail address: [email protected] (P.A. Ganchi).
1748-6815/$ - see front matter ª 2008 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved. doi:10.1016/j.bjps.2007.09.011
Effects of lidocaine and epinephrine
1227
allow maximal benefit to take effect. There were no significant differences between 1:100 000 and 1:200 000 epinephrine combined with lidocaine in facial injections his study. ª 2008 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved.
Local anaesthesia plays an integral part in modern surgical practice. It offers a viable alternative to general anaesthesia in patients with significant co-morbidities. A number of local anaesthetic agents are currently available, each with its own onset time, duration of action and local and systemic side effect profile. With the exception of the older aminoester cocaine and the newer ropivicaine (Naropin), the aminoamides such as lidocaine (xylocaine-AstraZeneca), prilocaine (xylonest-AstraZeneca) and bupivicaine (carbostesin-AstraZeneca) produce varying degrees of local vasodilatation secondary to sympathetic blockade. This property results in an increased rate of absorption of these agents with an associated increase in systemic levels and potential adverse effects, decrease in duration of action, and increase in local bleeding.1 Vasoconstrictors have been used to reduce the extent of these unwanted effects. Epinephrine is a sympathomimetic amine with both a- and b-adrenergic receptor agonist effects. Skin, mucosa, and kidney arterioles display vasoconstriction due to a-receptor predominant stimulation. Low concentrations of epinephrine result in preferential b-2 receptor stimulation resulting in vasodilatation in bronchiolar smooth muscle while higher levels stimulate a-receptor-mediated vasoconstriction in vascular smooth muscle.2 Epinephrine therefore reduces the absorption of local anaesthetic agents in the circulation, resulting in decreased systemic effects, increased duration of action and decreased surgical blood loss.3 The combination of epinephrine with a local anaesthetic such as lidocaine results in a predominant vasoconstrictive effect, producing a significant decrease in perfusion.4 This combination as well as lidocaine alone are frequently used in reconstructive procedures such as skin tumour excision and local flap closure in addition to cosmetic surgical procedures.5 This prompted our study, the aim of which was to measure the effect of subdermal injection of lidocaine and epinephrine on cutaneous blood flow in two different areas of the body of healthy human subjects relevant to plastic surgical procedures. Laser Doppler blood imaging was used to provide an objective indirect measure of skin blood flow.
Materials and method Forearm flow measurements Thirty subdermal injections were performed on five healthy volunteers aged 25e40 years old, three male and two female. The participants were all non-smokers, with no history of cardiovascular disease, asthma or hypersensitivity to amide local anaesthetics. The procedure was discussed with the study participants and written consent was obtained. Three injection groups were evaluated:
(1) The control group was injected with 0.5 cc of 0.9% phosphate buffered saline (PBS) (GIBCO) pH 7.4 and sequential blood flow measurements were acquired over time. (2) The first experimental group was injected at an independent site using 0.5 cc of 1% lidocaine (AstraZeneca) pH 5.0e7.0 and sequential blood flow measurements were acquired over time. (3) The second experimental group was injected with 0.5 cc of 1% lidocaine þ 1:100 000 epinephrine (AstraZeneca) pH 3.3e5.0 and sequential blood flow measurements were acquired over time. Although recent studies suggest that warming local anaesthetic solutions to body temperature prior to injection reduces the pain of injection,6,7 all solutions were stored at 4 C prior to injection to standardise for temperature and new vials were used for each experiment. All injections were carried out with a 24 G needle (Becton Dickinson, Franklin Lakes, NJ, USA) and 1 cc syringe (Becton Dickinson, Franklin Lakes, NJ, USA) and the skin was prepared by cleaning with an alcohol swab. The three injection sites were a minimum of 5 cm apart and performed on both forearms and in all study participants. Injections were randomised over both forearms and were unknown to the participant or investigator. No incisions were made.
Facial flow measurements Forty subdermal injections were performed on five male volunteers aged 25e35. Again, the participants were all non-smokers, with no history of cardiovascular disease, asthma or hypersensitivity to amide local anaesthetics. The procedure was discussed with the study participants and written consent was obtained. This part of the experiment involved four injection groups: (1) The control group was injected with 0.5 cc of 0.9% PBS (GIBCO) pH 7.4 and blood flow measurements were acquired over time. (2) The first experimental group was injected at an independent site using 0.5 cc of 1% lidocaine (AstraZeneca) pH 5.0e7.0 and blood flow measurements were acquired over time. (3) The second experimental group was injected with 0.5 cc of 1% lidocaine þ 1:100 000 epinephrine (AstraZeneca) pH 3.3e5.0 and blood flow measurements were acquired over time. (4) The third experimental group was injected with 0.5 cc of 1% lidocaine þ 1:200 000 epinephrine (AstraZeneca) pH 3.3e5.0 and blood flow measurements were acquired over time.
1228
S. Ghali et al.
All solutions were stored at 4 C prior to injection to standardise for temperature and new vials were used for each experiment. All injections were carried out with a 24 G needle (Becton Dickinson, Franklin Lakes, NJ, USA) and 1 cc syringe (Becton Dickinson, Franklin Lakes, NJ, USA) and the skin was prepared by cleaning with an alcohol swab. Two of the injection sites were situated in the pre-auricular region 3 cm anterior to the tragus, bilaterally. The other two were situated in the brow region 2 cm superior to the eye brow on a vertical line running through the lateral canthus. Sites for injection were randomised to normalise for regional variations in facial blood flow with no more than four injections applied per experiment in a 72-h period. Goggles were used to protect subjects from laser-induced retinal damage. No incisions were made (Figure 1). Microvascular cutaneous blood flow was measured using laser Doppler imaging (moorLDI-Mark 2, Moor Instruments Ltd, Axminster, Devon, UK). Doppler shifts are collected and processed by the instrument, producing a colour-coded image representing relative flux in two dimensions.8 Of note, the laser Doppler imaging system measures fluid flux which is an indirect measure of cutaneous blood flow. To standardise for the effect of injection volume on fluid flux, this was maintained at a constant 0.5 cc between injections. The laser head was positioned 30 cm above the measuring site, with each injection site scanned individually over an area of 2 cm 2 cm. This translated to an area of 264 264 pixels on screen. Images were recorded over 42 min in the forearm and 60 min in the face and analysed using dedicated imaging software (Moor Instruments Ltd, Axminster, Devon, UK). Blood flow was obtained by calculating the median laser Doppler flux within the 2 cm 2 cm square centred on the point of injection. Data points were averaged for each of the volunteers at each time point. Results are expressed as a percentage of
Figure 1
Face injection site.
background normal cutaneous blood flow measured over the area of interest pre-injection, allowing comparative analysis of averaged data points for all volunteers at each time point, in each of the different injection groups. Repeat measures ANOVA was used to compare differences between volunteers. A P value < 0.05 was considered statistically significant.
Results Forearm experiments Laser Doppler blood flow measurements post injection with both PBS and 1% lidocaine resulted in an increase in cutaneous blood flow which was maximal in the first 5 min (133% and 207% normal blood flow, respectively) for both groups. Blood flow returned to just above baseline as early as 7 min post injection with PBS but remained elevated in the 1% lidocaine group for over 40 min. The decrease in blood flow following injection with 1:100 000 epinephrine combined with 1% lidocaine was immediate and maximal by 10 min (68.7% normal blood flow). This decrease was prolonged for over 40 min. Compared to PBS the increase in blood flow resulting from injection with 1% lidocaine was statistically significant (P < 0.001), as was the decrease in blood flow resulting from injection with 1:100 000 epinephrine combined with 1% lidocaine (P < 0.001). The increase in blood flow following 1% lidocaine injection was also statistically significant compared to the decrease in blood flow following 1:100 000 epinephrine þ 1% lidocaine injection (P < 0.001) (Figure 2).
Face experiments As with experiments conducted in the forearm, both PBS and 1% lidocaine injection resulted in an increase in cutaneous blood flow, although this response was maximal earlier, at 2 min for PBS (167.7% normal blood flow) and 1 min for 1% lidocaine (138.5% normal blood flow). In contrast to the forearm experiments, however, the increase in cutaneous blood flow achieved by facial injection of PBS was higher than that achieved by facial injection of 1% lidocaine (Figures 2 and 3). This increase in facial blood flow rapidly fell to a plateau after a further 2e3 min in both groups but remained raised above baseline for the following 15 min for PBS and remained prolonged for up to 60 min for 1% lidocaine. There was no statistically significant difference between 1% lidocaine and saline injection (P Z 0.097) (Figure 3). The addition of epinephrine 1:100 000 to 1% lidocaine resulted in an immediate decrease in cutaneous blood flow which was maximal at 8 min (56% normal blood flow). This decrease persisted for 60 min (64.9% normal blood flow) and was statistically significant compared to blood flow changes resulting from facial injection of both PBS (P < 0.001) and 1% lidocaine (P < 0.001) (Figure 3). The combination of epinephrine 1:200 000 with 1% lidocaine resulted in an initial increase in cutaneous blood flow for the first minute followed by a rapid decrease similar to that observed with 1:100 000 epinephrine which
Effects of lidocaine and epinephrine
1229
250 Control-PBS
Lidocaine 1%
Lidocaine 1% + Epinephrine 1:100,000
% normal blood flow
200 x 150 x 100 x 50
0 0
5
10
15
20
25
30
35
40
45
minutes
Figure 2
Forearm cutaneous blood flow measurements. x Z P < 0.001.
was also maximal at 8 min (59.7% normal blood flow). This also persisted for 60 min (75% normal blood flow) and was statistically significant at all time points compared to blood flow changes resulting from facial injection of both PBS (P < 0.001) and 1% lidocaine (P < 0.001) (Figure 3). Apart from the initial increase in cutaneous blood flow observed with 1:200 000 epinephrine þ 1% lidocaine compared to 1:100 000 epinephrine þ 1% lidocaine, the two concentrations of epinephrine resulted in similar decreases in cutaneous blood flow. There was no significant difference between the two (P Z 0.20) and this decrease in blood flow was attenuated with the lower dose of epinephrine (1:200 000) at all time points (Figure 4).
Discussion Epinephrine coupled with a local anaesthetic used for infiltration anaesthesia of skin incision sites is commonly used to provide postoperative pain relief following surgical
procedures such as inguinal hernia repair,9 laparoscopic surgery,10 and vaginal hysterectomy.11 Plastic surgical procedures are increasingly performed under local anaesthesia. In a recent national survey, Koeppe et al.5 reported the use of different concentrations of lidocaine in over 28% of cosmetic procedures of the head and neck with 47.3% of the respondents using epinephrine 1:100 000 for vasoconstriction. The results of this study clearly demonstrate the vasodilatory effect of subdermal injection with 1% lidocaine as well as PBS in both the forearm and the face. This was maximal as early as 5 min post injection in the forearm and after only 1 min in the face for 1% lidocaine. The superior vascularity of the face compared to the forearm may account for this difference resulting in accelerated uptake of the local anaesthetic and therefore an accelerated onset of action. Interestingly, in contrast to the forearm, vasodilatation in the face was initially higher in the PBS injection group compared to 1% lidocaine, although this did not reach statistical significance.
Lidocaine 1% + Epinephrine 1:200,000
180
Lidocaine 1% + Epinephrine 1:100,000
% normal blood flow
160
Lidocaine 1%
140
Control-PBS
120 100 80 60 40 20 0 0
10
20
30
40
50
60
minutes
Figure 3 Facial cutaneous blood flow measurements. PBS vs 1% lidocaine P Z 0.097. Lidocaine 1% þ epinephrine 1:200 000 vs 1% lidocaine P < 0.001. Lidocaine 1% þ epinephrine 1:200 000 vs PBS P < 0.001. Lidocaine 1% þ epinephrine 1:100 000 vs 1% lidocaine P < 0.001. Lidocaine 1% þ epinephrine 1:100 000 vs PBS P < 0.001.
1230
S. Ghali et al. 130 Lidocaine 1% + Epinephrine 1:200,000
% normal blood flow
120
Lidocaine 1% + Epinephrine 1:100,000
110 100 90 80 70 60 50 0
10
20
30
40
50
60
minutes
Figure 4 Effect of increasing epinephrine concentration on facial cutaneous blood flow measurements. Lidocaine 1% þ epinephrine 1:200 000 vs lidocaine 1% þ epinephrine 1:100 000 P Z 0.20.
The vasodilatation caused by subdermal PBS injection may be a cutaneous response to the mechanical effect of the injection itself, i.e. hydropressure. This is supported by the fact that it occurred in both the forearm and the face and also by the fact that the vasodilatation resolved relatively quickly initially, probably as a result of redistribution in the surrounding tissue followed by a later slower resolution due to local tissue absorption. Differences in the vasodilatory response between the forearm and the face may be a reflection of local neural reflexes which may be more sensitive in the face on account of anatomical variations in sympathetic innovation. These findings are supported in part by the those of O’Malley et al.12 following subdermal injection of saline and 1% lidocaine with different concentrations of epinephrine in a double-blinded study of 23 patients undergoing head and neck surgery. They determined that both normal saline and 1% lidocaine caused significant vasodilatation albeit greater in the latter in the head and neck, in contrast to our findings. The pH of the solutions injected may account for this discrepancy. Normal saline has a pH of 5.5 (4.5e7.0) compared to that of PBS used in this study, pH 7.4. With respect to local anaesthetics, McKay et al.13 suggested that increasing the pH decreased pain on administration, as nociceptors are less sensitive to the non-ionised form of the local anaesthetic, with a greater diffusion ability, present in higher pH solutions. Maximal vasoconstriction induced by the addition of epinephrine to 1% lidocaine occurred after 10 min in the forearm and 8 min in the face. This is corroborated by the findings of Larrabee et al.14 who compared the onset of vasoconstriction, the magnitude of diminished blood flow, and the duration of effect following injection of epinephrine in combination with saline or lidocaine in a piglet model. Maximal vasoconstriction occurred by 5e7 min in most cases, and by 10 min in all cases. They also reported that the use of combinations of 1:200 000 epinephrine or greater concentrations stayed maximally effective for 60e120 min. This trend was observed in our study although not definitively followed.
The results of this study suggest that, at least in the face, there is no significant difference between 1:100 000 and 1:200 000 combinations of epinephrine with lidocaine in terms of onset of vasoconstriction as well as duration of action up to 60 min. Other investigators have also suggested that a dose of 1:200 000 epinephrine was the safest concentration yielding the maximal vasoconstricting effects.14,15 Locally, tissue sloughing has also been described after administration of greater than 1:200 000 epinephrine.16 In summary, we have used the objective method of laser Doppler imaging to show that subdermal injection of 1% lidocaine causes more vasodilatation than PBS in the forearm. In the face, this relationship is reversed and the onset of action of both solutions is accelerated. This may be related to differences in the vascularity and therefore local sympathetic innovation of capillary beds in different anatomical areas as well as the inherent properties of the solution injected. Maximal vasoconstriction following injection of 1% lidocaine in combination with epinephrine occurs after 10 min in the forearm and 8 min in the face. This would suggest delaying incisions or other painful stimuli following injections of these combinations to allow maximal benefit to take effect. Our findings also suggest no objective benefit of using 1:100 000 compared to 1:200 000 epinephrine combined with 1% lidocaine in facial procedures. Further work will concentrate on applying different doses of both epinephrine and local anaesthetic, as well as different control solutions, to various anatomical sites in order to further elucidate the relative contribution of local vascularity and solution properties, including pH and temperature, to cutaneous blood flow.
References 1. Baresh P, Cullen F, Stoelting R. Clinical Anesthesia. 2nd ed. Lippincott JB; 1992. 2. Katzung B. Basic & Clinical Pharmacology. 9th ed. Lange; 2003. 3. Fink BR, Aasheim GM, Levy BA. Neural pharmacokinetics of epinephrine. Anesthesiology 1978;48:263e6.
Effects of lidocaine and epinephrine 4. Guinard JP, Carpenter RL, Morell RC. Effect of local anesthetic concentration on capillary blood flow in human skin. Reg Anesth 1992;17:317e21. 5. Koeppe T, Constantinescu MA, Schneider J, et al. Current trends in local anesthesia in cosmetic plastic surgery of the head and neck: results of a German national survey and observations on the use of ropivacaine. Plast Reconstr Surg 2005; 115:1723e30. 6. Bainbridge LC. Comparison of room temperature and body temperature local anaesthetic solutions. Br J Plast Surg 1991;44:147e8. 7. Clark V, McGrady E, Sugden C, et al. Speed of onset of sensory block for elective extradural caesarean section: choice of agent and temperature of injectate. Br J Anaesth 1994;72:221e3. 8. Essex TJ, Byrne PO. A laser Doppler scanner for imaging blood flow in skin. J Biomed Eng 1991;13:189e94. 9. Suraseranivongse S, Chowvanayotin S, Pirayavaraporn S, et al. Effect of bupivacaine with epinephrine wound instillation for pain relief after pediatric inguinal herniorrhaphy and hydrocelectomy. Reg Anesth Pain Med 2003;28:24e8.
1231 10. Carbonell AM, Harold KL, Mahmutovic AJ, et al. Local injection for the treatment of suture site pain after laparoscopic ventral hernia repair. Am Surg 2003;69:688e91 [discussion 691e2]. 11. O’Neal MG, Beste T, Shackelford DP. Utility of preemptive local analgesia in vaginal hysterectomy. Am J Obstet Gynecol 2003; 189:1539e41 [discussion 1541e2]. 12. O’Malley TP, Postma GN, Holtel M, et al. Effect of local epinephrine on cutaneous bloodflow in the human neck. Laryngoscope 1995;105:140e3. 13. McKay W, Morris R, Mushlin P. Sodium bicarbonate attenuates pain on skin infiltration with lidocaine, with or without epinephrine. Anesth Analg 1987;66:572e4. 14. Larrabee Jr WF, Lanier BJ, Miekle D. Effect of epinephrine on local cutaneous blood flow. Head Neck Surg 1987;9:287e9. 15. Millay DJ, Larrabee Jr WF, Carpenter RL. Vasoconstrictors in facial plastic surgery. Arch Otolaryngol Head Neck Surg 1991; 117:160e3. 16. Siegel RJ, Vistnes LM, Iverson RE. Effective hemostasis with less epinephrine. An experimental and clinical study. Plast Reconstr Surg 1973;51:129e33.
CLINICAL TERMINOLOGY Antihelix, antehelix or anthelix? Comments on ‘Upping the Anti?’
In the March 2008 volume of the Journal of Plastic, Reconstructive and Aesthetic Surgery, Sainsbury et al.1 tried to elucidate the correct term for the curved inner fold of the ear, i.e. the anthelix. Searching PubMed for the above-mentioned anatomical area, the antihelix and the antehelix are not the only medical words used. The anthelix is also a term mentioned in 60 articles in the literature. Appreciating the number of medical terms derived from Latin, we argue that the origin of the word anthelix is even older and has a Greek root. Anthelix first appeared in the literature by Roufos Efesios (55A.C.) in the book ‘About the name of the human particles’ (Greek-English Dictionary by Liddell & Scott). The word ‘aq3lix’ (anthelix) describes the anatomical structure that is located ‘opposite the helix’. It is an ancient Greek composite word and its etymology is from the preposition ‘atı´’ (anti Z opposite) and the word ‘3lix’ (helix Z scroll, coil, spiral). The beauty of Greek grammar also
explains why the composition of ‘atı´þ 3lix’ (anti þ helix) becomes ‘aq3lix’ (anthelix): the initial vowel ‘3-’ of the Greek word ‘helix’ was pronounced with rough breathing which transforms the anti- into anth-. Therefore, the precise terminology is anthelix. Antibacterial, antihistamine, antiaircraft gun, antifreeze and antipasto are generally good examples, but not on this occasion.
Reference 1. Sainsbury DCG, Cavale N, Gilbert PM. Upping the anti? J Plast Reconstr Aesthet Surg 2008;61:351.
Dimitrios Dionyssiou Efterpi Demiri Queen Victoria Hospital, East Grinstead, UK E-mail address: [email protected] ª 2008 Published by Elsevier Ltd on behalf of British Association of Plastic, Reconstructive and Aesthetic Surgeons. doi:10.1016/j.bjps.2008.03.068
Effects of lidocaine and epinephrine on cutaneous blood flow* S. Ghali a, K.R. Knox a, J. Verbesey b, U. Scarpidis c, K. Izadi c, P.A. Ganchi d,* a
Laboratory for Microvascular Research and Vascular Tissue Engineering, New York University, New York, NY, USA Massachusetts General Hospital, Department of Plastic Surgery, Boston, MA, USA c University of Medicine and Dentistry of New Jersey, Division of Plastic Surgery, Newark, NJ, USA d Ganchi Plastic Surgery, 342 Hamburg Turnpike, Suite 202, Wayne, NJ 07470, USA b
Received 26 September 2006; accepted 13 September 2007
KEYWORDS Cutaneous blood flow; Lidocaine; Epinephrine; Laser Doppler
Summary Background: Local anaesthetic agents in combination with epinephrine are frequently used in local reconstructive procedures such as skin tumour excision and local flap closure. The purpose of this study was to measure the effect of subdermal injection of lidocaine combined with epinephrine on cutaneous blood flow in the forearm and in the face. Methods: Thirty injections were performed on the forearm and 40 injections were performed on the face in five healthy volunteers. In both anatomical regions, 0.9% phosphate buffered saline (PBS) was used as a control, and experimental injections included 1% lidocaine either alone or in combination with 1:100 000 epinephrine, and an additional combination of 1% lidocaine with 1:200 000 epinephrine used in the facial experiments. Cutaneous blood flow was measured indirectly using laser Doppler imaging (moorLDI-Mark 2). Results: A statistically significant increase in blood flow was achieved with injection of lidocaine in the forearm compared to saline, whereas a non-statistically significant increase was achieved with saline injection compared to lidocaine in the face. This occurred in the first 5 min in the forearm and 2 min in the face. The addition of 1:100 000 epinephrine to lidocaine resulted in an immediate decrease in cutaneous blood flow which was maximal at 10 min in the forearm and 8 min in the face. This was statistically significant compared to all other injections except for the combination of 1:200 000 epinephrine with lidocaine, injected in the face. Conclusions: The vascularity of different anatomical areas may account for blood flow differences following injection with saline and lidocaine. Incisions should be delayed for 10 min in the forearm and 8 min in the face following lidocaine þ epinephrine injection to
*
This work was presented at the 2004 Northeastern Society of Plastic Surgeons, Naples, Florida, USA. * Corresponding author. Tel.: þ1 973 942 6600; fax: þ1 973 595-5964. E-mail address: [email protected] (P.A. Ganchi).
1748-6815/$ - see front matter ª 2008 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved. doi:10.1016/j.bjps.2007.09.011
Effects of lidocaine and epinephrine
1227
allow maximal benefit to take effect. There were no significant differences between 1:100 000 and 1:200 000 epinephrine combined with lidocaine in facial injections his study. ª 2008 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved.
Local anaesthesia plays an integral part in modern surgical practice. It offers a viable alternative to general anaesthesia in patients with significant co-morbidities. A number of local anaesthetic agents are currently available, each with its own onset time, duration of action and local and systemic side effect profile. With the exception of the older aminoester cocaine and the newer ropivicaine (Naropin), the aminoamides such as lidocaine (xylocaine-AstraZeneca), prilocaine (xylonest-AstraZeneca) and bupivicaine (carbostesin-AstraZeneca) produce varying degrees of local vasodilatation secondary to sympathetic blockade. This property results in an increased rate of absorption of these agents with an associated increase in systemic levels and potential adverse effects, decrease in duration of action, and increase in local bleeding.1 Vasoconstrictors have been used to reduce the extent of these unwanted effects. Epinephrine is a sympathomimetic amine with both a- and b-adrenergic receptor agonist effects. Skin, mucosa, and kidney arterioles display vasoconstriction due to a-receptor predominant stimulation. Low concentrations of epinephrine result in preferential b-2 receptor stimulation resulting in vasodilatation in bronchiolar smooth muscle while higher levels stimulate a-receptor-mediated vasoconstriction in vascular smooth muscle.2 Epinephrine therefore reduces the absorption of local anaesthetic agents in the circulation, resulting in decreased systemic effects, increased duration of action and decreased surgical blood loss.3 The combination of epinephrine with a local anaesthetic such as lidocaine results in a predominant vasoconstrictive effect, producing a significant decrease in perfusion.4 This combination as well as lidocaine alone are frequently used in reconstructive procedures such as skin tumour excision and local flap closure in addition to cosmetic surgical procedures.5 This prompted our study, the aim of which was to measure the effect of subdermal injection of lidocaine and epinephrine on cutaneous blood flow in two different areas of the body of healthy human subjects relevant to plastic surgical procedures. Laser Doppler blood imaging was used to provide an objective indirect measure of skin blood flow.
Materials and method Forearm flow measurements Thirty subdermal injections were performed on five healthy volunteers aged 25e40 years old, three male and two female. The participants were all non-smokers, with no history of cardiovascular disease, asthma or hypersensitivity to amide local anaesthetics. The procedure was discussed with the study participants and written consent was obtained. Three injection groups were evaluated:
(1) The control group was injected with 0.5 cc of 0.9% phosphate buffered saline (PBS) (GIBCO) pH 7.4 and sequential blood flow measurements were acquired over time. (2) The first experimental group was injected at an independent site using 0.5 cc of 1% lidocaine (AstraZeneca) pH 5.0e7.0 and sequential blood flow measurements were acquired over time. (3) The second experimental group was injected with 0.5 cc of 1% lidocaine þ 1:100 000 epinephrine (AstraZeneca) pH 3.3e5.0 and sequential blood flow measurements were acquired over time. Although recent studies suggest that warming local anaesthetic solutions to body temperature prior to injection reduces the pain of injection,6,7 all solutions were stored at 4 C prior to injection to standardise for temperature and new vials were used for each experiment. All injections were carried out with a 24 G needle (Becton Dickinson, Franklin Lakes, NJ, USA) and 1 cc syringe (Becton Dickinson, Franklin Lakes, NJ, USA) and the skin was prepared by cleaning with an alcohol swab. The three injection sites were a minimum of 5 cm apart and performed on both forearms and in all study participants. Injections were randomised over both forearms and were unknown to the participant or investigator. No incisions were made.
Facial flow measurements Forty subdermal injections were performed on five male volunteers aged 25e35. Again, the participants were all non-smokers, with no history of cardiovascular disease, asthma or hypersensitivity to amide local anaesthetics. The procedure was discussed with the study participants and written consent was obtained. This part of the experiment involved four injection groups: (1) The control group was injected with 0.5 cc of 0.9% PBS (GIBCO) pH 7.4 and blood flow measurements were acquired over time. (2) The first experimental group was injected at an independent site using 0.5 cc of 1% lidocaine (AstraZeneca) pH 5.0e7.0 and blood flow measurements were acquired over time. (3) The second experimental group was injected with 0.5 cc of 1% lidocaine þ 1:100 000 epinephrine (AstraZeneca) pH 3.3e5.0 and blood flow measurements were acquired over time. (4) The third experimental group was injected with 0.5 cc of 1% lidocaine þ 1:200 000 epinephrine (AstraZeneca) pH 3.3e5.0 and blood flow measurements were acquired over time.
1228
S. Ghali et al.
All solutions were stored at 4 C prior to injection to standardise for temperature and new vials were used for each experiment. All injections were carried out with a 24 G needle (Becton Dickinson, Franklin Lakes, NJ, USA) and 1 cc syringe (Becton Dickinson, Franklin Lakes, NJ, USA) and the skin was prepared by cleaning with an alcohol swab. Two of the injection sites were situated in the pre-auricular region 3 cm anterior to the tragus, bilaterally. The other two were situated in the brow region 2 cm superior to the eye brow on a vertical line running through the lateral canthus. Sites for injection were randomised to normalise for regional variations in facial blood flow with no more than four injections applied per experiment in a 72-h period. Goggles were used to protect subjects from laser-induced retinal damage. No incisions were made (Figure 1). Microvascular cutaneous blood flow was measured using laser Doppler imaging (moorLDI-Mark 2, Moor Instruments Ltd, Axminster, Devon, UK). Doppler shifts are collected and processed by the instrument, producing a colour-coded image representing relative flux in two dimensions.8 Of note, the laser Doppler imaging system measures fluid flux which is an indirect measure of cutaneous blood flow. To standardise for the effect of injection volume on fluid flux, this was maintained at a constant 0.5 cc between injections. The laser head was positioned 30 cm above the measuring site, with each injection site scanned individually over an area of 2 cm 2 cm. This translated to an area of 264 264 pixels on screen. Images were recorded over 42 min in the forearm and 60 min in the face and analysed using dedicated imaging software (Moor Instruments Ltd, Axminster, Devon, UK). Blood flow was obtained by calculating the median laser Doppler flux within the 2 cm 2 cm square centred on the point of injection. Data points were averaged for each of the volunteers at each time point. Results are expressed as a percentage of
Figure 1
Face injection site.
background normal cutaneous blood flow measured over the area of interest pre-injection, allowing comparative analysis of averaged data points for all volunteers at each time point, in each of the different injection groups. Repeat measures ANOVA was used to compare differences between volunteers. A P value < 0.05 was considered statistically significant.
Results Forearm experiments Laser Doppler blood flow measurements post injection with both PBS and 1% lidocaine resulted in an increase in cutaneous blood flow which was maximal in the first 5 min (133% and 207% normal blood flow, respectively) for both groups. Blood flow returned to just above baseline as early as 7 min post injection with PBS but remained elevated in the 1% lidocaine group for over 40 min. The decrease in blood flow following injection with 1:100 000 epinephrine combined with 1% lidocaine was immediate and maximal by 10 min (68.7% normal blood flow). This decrease was prolonged for over 40 min. Compared to PBS the increase in blood flow resulting from injection with 1% lidocaine was statistically significant (P < 0.001), as was the decrease in blood flow resulting from injection with 1:100 000 epinephrine combined with 1% lidocaine (P < 0.001). The increase in blood flow following 1% lidocaine injection was also statistically significant compared to the decrease in blood flow following 1:100 000 epinephrine þ 1% lidocaine injection (P < 0.001) (Figure 2).
Face experiments As with experiments conducted in the forearm, both PBS and 1% lidocaine injection resulted in an increase in cutaneous blood flow, although this response was maximal earlier, at 2 min for PBS (167.7% normal blood flow) and 1 min for 1% lidocaine (138.5% normal blood flow). In contrast to the forearm experiments, however, the increase in cutaneous blood flow achieved by facial injection of PBS was higher than that achieved by facial injection of 1% lidocaine (Figures 2 and 3). This increase in facial blood flow rapidly fell to a plateau after a further 2e3 min in both groups but remained raised above baseline for the following 15 min for PBS and remained prolonged for up to 60 min for 1% lidocaine. There was no statistically significant difference between 1% lidocaine and saline injection (P Z 0.097) (Figure 3). The addition of epinephrine 1:100 000 to 1% lidocaine resulted in an immediate decrease in cutaneous blood flow which was maximal at 8 min (56% normal blood flow). This decrease persisted for 60 min (64.9% normal blood flow) and was statistically significant compared to blood flow changes resulting from facial injection of both PBS (P < 0.001) and 1% lidocaine (P < 0.001) (Figure 3). The combination of epinephrine 1:200 000 with 1% lidocaine resulted in an initial increase in cutaneous blood flow for the first minute followed by a rapid decrease similar to that observed with 1:100 000 epinephrine which
Effects of lidocaine and epinephrine
1229
250 Control-PBS
Lidocaine 1%
Lidocaine 1% + Epinephrine 1:100,000
% normal blood flow
200 x 150 x 100 x 50
0 0
5
10
15
20
25
30
35
40
45
minutes
Figure 2
Forearm cutaneous blood flow measurements. x Z P < 0.001.
was also maximal at 8 min (59.7% normal blood flow). This also persisted for 60 min (75% normal blood flow) and was statistically significant at all time points compared to blood flow changes resulting from facial injection of both PBS (P < 0.001) and 1% lidocaine (P < 0.001) (Figure 3). Apart from the initial increase in cutaneous blood flow observed with 1:200 000 epinephrine þ 1% lidocaine compared to 1:100 000 epinephrine þ 1% lidocaine, the two concentrations of epinephrine resulted in similar decreases in cutaneous blood flow. There was no significant difference between the two (P Z 0.20) and this decrease in blood flow was attenuated with the lower dose of epinephrine (1:200 000) at all time points (Figure 4).
Discussion Epinephrine coupled with a local anaesthetic used for infiltration anaesthesia of skin incision sites is commonly used to provide postoperative pain relief following surgical
procedures such as inguinal hernia repair,9 laparoscopic surgery,10 and vaginal hysterectomy.11 Plastic surgical procedures are increasingly performed under local anaesthesia. In a recent national survey, Koeppe et al.5 reported the use of different concentrations of lidocaine in over 28% of cosmetic procedures of the head and neck with 47.3% of the respondents using epinephrine 1:100 000 for vasoconstriction. The results of this study clearly demonstrate the vasodilatory effect of subdermal injection with 1% lidocaine as well as PBS in both the forearm and the face. This was maximal as early as 5 min post injection in the forearm and after only 1 min in the face for 1% lidocaine. The superior vascularity of the face compared to the forearm may account for this difference resulting in accelerated uptake of the local anaesthetic and therefore an accelerated onset of action. Interestingly, in contrast to the forearm, vasodilatation in the face was initially higher in the PBS injection group compared to 1% lidocaine, although this did not reach statistical significance.
Lidocaine 1% + Epinephrine 1:200,000
180
Lidocaine 1% + Epinephrine 1:100,000
% normal blood flow
160
Lidocaine 1%
140
Control-PBS
120 100 80 60 40 20 0 0
10
20
30
40
50
60
minutes
Figure 3 Facial cutaneous blood flow measurements. PBS vs 1% lidocaine P Z 0.097. Lidocaine 1% þ epinephrine 1:200 000 vs 1% lidocaine P < 0.001. Lidocaine 1% þ epinephrine 1:200 000 vs PBS P < 0.001. Lidocaine 1% þ epinephrine 1:100 000 vs 1% lidocaine P < 0.001. Lidocaine 1% þ epinephrine 1:100 000 vs PBS P < 0.001.
1230
S. Ghali et al. 130 Lidocaine 1% + Epinephrine 1:200,000
% normal blood flow
120
Lidocaine 1% + Epinephrine 1:100,000
110 100 90 80 70 60 50 0
10
20
30
40
50
60
minutes
Figure 4 Effect of increasing epinephrine concentration on facial cutaneous blood flow measurements. Lidocaine 1% þ epinephrine 1:200 000 vs lidocaine 1% þ epinephrine 1:100 000 P Z 0.20.
The vasodilatation caused by subdermal PBS injection may be a cutaneous response to the mechanical effect of the injection itself, i.e. hydropressure. This is supported by the fact that it occurred in both the forearm and the face and also by the fact that the vasodilatation resolved relatively quickly initially, probably as a result of redistribution in the surrounding tissue followed by a later slower resolution due to local tissue absorption. Differences in the vasodilatory response between the forearm and the face may be a reflection of local neural reflexes which may be more sensitive in the face on account of anatomical variations in sympathetic innovation. These findings are supported in part by the those of O’Malley et al.12 following subdermal injection of saline and 1% lidocaine with different concentrations of epinephrine in a double-blinded study of 23 patients undergoing head and neck surgery. They determined that both normal saline and 1% lidocaine caused significant vasodilatation albeit greater in the latter in the head and neck, in contrast to our findings. The pH of the solutions injected may account for this discrepancy. Normal saline has a pH of 5.5 (4.5e7.0) compared to that of PBS used in this study, pH 7.4. With respect to local anaesthetics, McKay et al.13 suggested that increasing the pH decreased pain on administration, as nociceptors are less sensitive to the non-ionised form of the local anaesthetic, with a greater diffusion ability, present in higher pH solutions. Maximal vasoconstriction induced by the addition of epinephrine to 1% lidocaine occurred after 10 min in the forearm and 8 min in the face. This is corroborated by the findings of Larrabee et al.14 who compared the onset of vasoconstriction, the magnitude of diminished blood flow, and the duration of effect following injection of epinephrine in combination with saline or lidocaine in a piglet model. Maximal vasoconstriction occurred by 5e7 min in most cases, and by 10 min in all cases. They also reported that the use of combinations of 1:200 000 epinephrine or greater concentrations stayed maximally effective for 60e120 min. This trend was observed in our study although not definitively followed.
The results of this study suggest that, at least in the face, there is no significant difference between 1:100 000 and 1:200 000 combinations of epinephrine with lidocaine in terms of onset of vasoconstriction as well as duration of action up to 60 min. Other investigators have also suggested that a dose of 1:200 000 epinephrine was the safest concentration yielding the maximal vasoconstricting effects.14,15 Locally, tissue sloughing has also been described after administration of greater than 1:200 000 epinephrine.16 In summary, we have used the objective method of laser Doppler imaging to show that subdermal injection of 1% lidocaine causes more vasodilatation than PBS in the forearm. In the face, this relationship is reversed and the onset of action of both solutions is accelerated. This may be related to differences in the vascularity and therefore local sympathetic innovation of capillary beds in different anatomical areas as well as the inherent properties of the solution injected. Maximal vasoconstriction following injection of 1% lidocaine in combination with epinephrine occurs after 10 min in the forearm and 8 min in the face. This would suggest delaying incisions or other painful stimuli following injections of these combinations to allow maximal benefit to take effect. Our findings also suggest no objective benefit of using 1:100 000 compared to 1:200 000 epinephrine combined with 1% lidocaine in facial procedures. Further work will concentrate on applying different doses of both epinephrine and local anaesthetic, as well as different control solutions, to various anatomical sites in order to further elucidate the relative contribution of local vascularity and solution properties, including pH and temperature, to cutaneous blood flow.
References 1. Baresh P, Cullen F, Stoelting R. Clinical Anesthesia. 2nd ed. Lippincott JB; 1992. 2. Katzung B. Basic & Clinical Pharmacology. 9th ed. Lange; 2003. 3. Fink BR, Aasheim GM, Levy BA. Neural pharmacokinetics of epinephrine. Anesthesiology 1978;48:263e6.
Effects of lidocaine and epinephrine 4. Guinard JP, Carpenter RL, Morell RC. Effect of local anesthetic concentration on capillary blood flow in human skin. Reg Anesth 1992;17:317e21. 5. Koeppe T, Constantinescu MA, Schneider J, et al. Current trends in local anesthesia in cosmetic plastic surgery of the head and neck: results of a German national survey and observations on the use of ropivacaine. Plast Reconstr Surg 2005; 115:1723e30. 6. Bainbridge LC. Comparison of room temperature and body temperature local anaesthetic solutions. Br J Plast Surg 1991;44:147e8. 7. Clark V, McGrady E, Sugden C, et al. Speed of onset of sensory block for elective extradural caesarean section: choice of agent and temperature of injectate. Br J Anaesth 1994;72:221e3. 8. Essex TJ, Byrne PO. A laser Doppler scanner for imaging blood flow in skin. J Biomed Eng 1991;13:189e94. 9. Suraseranivongse S, Chowvanayotin S, Pirayavaraporn S, et al. Effect of bupivacaine with epinephrine wound instillation for pain relief after pediatric inguinal herniorrhaphy and hydrocelectomy. Reg Anesth Pain Med 2003;28:24e8.
1231 10. Carbonell AM, Harold KL, Mahmutovic AJ, et al. Local injection for the treatment of suture site pain after laparoscopic ventral hernia repair. Am Surg 2003;69:688e91 [discussion 691e2]. 11. O’Neal MG, Beste T, Shackelford DP. Utility of preemptive local analgesia in vaginal hysterectomy. Am J Obstet Gynecol 2003; 189:1539e41 [discussion 1541e2]. 12. O’Malley TP, Postma GN, Holtel M, et al. Effect of local epinephrine on cutaneous bloodflow in the human neck. Laryngoscope 1995;105:140e3. 13. McKay W, Morris R, Mushlin P. Sodium bicarbonate attenuates pain on skin infiltration with lidocaine, with or without epinephrine. Anesth Analg 1987;66:572e4. 14. Larrabee Jr WF, Lanier BJ, Miekle D. Effect of epinephrine on local cutaneous blood flow. Head Neck Surg 1987;9:287e9. 15. Millay DJ, Larrabee Jr WF, Carpenter RL. Vasoconstrictors in facial plastic surgery. Arch Otolaryngol Head Neck Surg 1991; 117:160e3. 16. Siegel RJ, Vistnes LM, Iverson RE. Effective hemostasis with less epinephrine. An experimental and clinical study. Plast Reconstr Surg 1973;51:129e33.
CLINICAL TERMINOLOGY Antihelix, antehelix or anthelix? Comments on ‘Upping the Anti?’
In the March 2008 volume of the Journal of Plastic, Reconstructive and Aesthetic Surgery, Sainsbury et al.1 tried to elucidate the correct term for the curved inner fold of the ear, i.e. the anthelix. Searching PubMed for the above-mentioned anatomical area, the antihelix and the antehelix are not the only medical words used. The anthelix is also a term mentioned in 60 articles in the literature. Appreciating the number of medical terms derived from Latin, we argue that the origin of the word anthelix is even older and has a Greek root. Anthelix first appeared in the literature by Roufos Efesios (55A.C.) in the book ‘About the name of the human particles’ (Greek-English Dictionary by Liddell & Scott). The word ‘aq3lix’ (anthelix) describes the anatomical structure that is located ‘opposite the helix’. It is an ancient Greek composite word and its etymology is from the preposition ‘atı´’ (anti Z opposite) and the word ‘3lix’ (helix Z scroll, coil, spiral). The beauty of Greek grammar also
explains why the composition of ‘atı´þ 3lix’ (anti þ helix) becomes ‘aq3lix’ (anthelix): the initial vowel ‘3-’ of the Greek word ‘helix’ was pronounced with rough breathing which transforms the anti- into anth-. Therefore, the precise terminology is anthelix. Antibacterial, antihistamine, antiaircraft gun, antifreeze and antipasto are generally good examples, but not on this occasion.
Reference 1. Sainsbury DCG, Cavale N, Gilbert PM. Upping the anti? J Plast Reconstr Aesthet Surg 2008;61:351.
Dimitrios Dionyssiou Efterpi Demiri Queen Victoria Hospital, East Grinstead, UK E-mail address: [email protected] ª 2008 Published by Elsevier Ltd on behalf of British Association of Plastic, Reconstructive and Aesthetic Surgeons. doi:10.1016/j.bjps.2008.03.068