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Damage to tissue defenses by vasoconstrictors
ORIGINAL CONTRIBUTIONS
Damage to Tissue Defenses By Vasoconstrictors Thomas R. Stevenson, MD* George T. Rodeheaver, MD* Gerald T. Golden, MD* Milton T. Edgerton, MD* James H. Wells, MD* Richard F. Edlich, MD, PhD** Charlottesville, Virginia
T h e p a p e r i n v e s t i g a t e s t h e e f f e c t o f s o l u t i o n s of l o c a l a n e s t h e t i c a g e n t s o n t h e a b i l i t y o f w o u n d s to r e s i s t i n f e c t i o n as w e l l as t h e i n f l u e n c e o f t h e i n j e c t i o n t e c h n i q u e s o n t h e d i s s e m i n a t i o n o f b a c t e r i a t h r o u g h the w o u n d . On t h e b a s i s o f t h e s e s t u d i e s , t h e f o l l o w i n g r e c o m m e n d a t i o n s are m a d e : (1) a r e g i o n a l n e r v e b l o c k w i t h 1% l i d o c a i n e a d m i n i s t e r e d t h r o u g h a 27 g a u g e n e e d l e is i n d i c a t e d b e f o r e w o u n d c l e a n s i n g ; (2) i f t h e w o u n d is n o t s u s c e p t i b l e to a r e g i o n a l n e r v e b l o c k , a n e s t h e t i z e the w o u n d by injecting the agent through the skin around the periphery of the w o u n d ; (3) a v o i d t h e u s e o f e p i n e p h r i n e w i t h t h e a n e s t h e t i c a g e n t . StevensonTR, RodeheaverGT, GoldenGT, etal:
Damage to tissue defenses
by vasoconstrictors. JACEP 4: 532-535, November/December 1975. vasoconstrictors; anesthesia; wound infection; lidocaine; epinephrine. INTRODUCTION
W h e n faced w i t h a t r a u m a t i c woui~d, the physician initiates therapy t h a t will rapidly induce loss of local sensation. Local a n e s t h e s i a not only e n s u r e s the p a t i e n t ' s comfort b u t aids the physician in wound man*Department of Plastic Surgery, University of Virginia Medical Center, Charlottesville. **Department of Plastic Surgery, University of Virginia Medical Center, Charlottesville. Junior Faculty Climcal Fellow of the American Cancer Society. Supported in part by a grant from the United States Army Medical Research and Development Command, Washington, DC. Address for reprints: Richard F. Edlich, MD, Department of Plastic Surgery, University of Virginia Medical Center, Jefferson Park Avenue, Charlottesville, Virginia 22901.
Page 532 Volume 4 Number 6
agement. C l e a n s i n g of bacteria, soil and other debris from t r a u m a t i c injuries and surgical d e b r i d e m e n t of infected w o u n d s c a n n o t be accomplished w i t h o u t local anesthesia. Anesthetic agents should have rapid onset of action locally without any adverse systemic effects. They should also not i m p a i r the wound's ability to resist infection. This is p a r t i c u l a r l y i m p o r t a n t in t r a u m a t i c wounds cont a m i n a t e d with moderate n u m b e r s of bacteria. A n y i n h i b i t i o n of tissue defenses will predispose the wound to infection. The effect of the local anesthetic agent on the viability of microorg a n i s m s is a n o t h e r i m p o r t a n t consideration. For infected wounds, an agent that displays antimicrobial activity m a y e l i m i n a t e the pathogen and interfere with its identification. L i d o c a i n e h y d r o c h l o r i d e is t h e
most c o m m o n l y employed local anesthetic agent. Loss of sensation occurs w i t h i n five m i n u t e s and lasts an average of 97 to 156 minutes. ~ The clinical usefulness ofilidocaine can be enhanced by adding the hemostatie agent, epinephrine. Epinephrine is a p o t e n t v a s o c o n s t r i c t o r t h a t overcomes the vasodilatory effects of lidocaine_ The reduction in blood flow induced by e p i n e p h r i n e limits the clearance of the anesthetic agent from the tissue prolonging the duration of anesthesia." As a result of this, the'toxic dose of lidocaine solutions containing epinephrine for local wound infiltration (7 mglkg, not to exceed 500 mgt0tal) is considerably higher than for the same anesthetic solution without epinephrine (4.5 mg/kg, n o t to exceed 300 rag). However, the beneficial effect of e p i n e p h r i n e 'must be weighed a g a i n s t its serious side effects of hypertension, cardiac arrhythmias, and cerebral hemorrhage. T h e series of i n v e s t i g a t i o n s reported here will aid the physician in deciding how to Employ local aneSthetic agents in p a t i e n t s withtrauma" tic tissue injuries or infected wounds. MATERIALS AND METHODS Resistance to Infection
.
The first series of'expel:imentS ex" amined the influence of solutions of local anesthetic agents on the tisstl~'~
November/December 1 9 7 5 " ~
bility to resist infection. Male albi:.N0rabbits, w e i g h i n g 2 to 3 kg, were [. esthetized with sodium pentobarbi(~ (33 mg/kg), a d m i n i s t e r e d i n t r a ~,e~ously. E a c h a n i m a l ' s back was h~ved, depilated and prepped with a 0~ ethyl alcohol solution.
These tissues were homogenized separately (Sorvall Omnimixer). The n u m b e r of viable bacteria in the homogenate was d e t e r m i n e d by r o u t i n e serial dilution techniques, a
Each i n o c u l a t i o n site in the aniCals' p a r a v e r t e b r a l skin was separated by a distance of 5 cm. A n intra*~errnal injection of 0,1 ml of a desigilated solution was delivered to each inoculation site t h r o u g h a 25 gauge heedle- After injection, the inocula10N s i t e s were covered by s t e r i l e ~gauze followed by an adhesive tape ressing-
This study d e t e r m i n e d the spread of bacteria r e s u l t i n g from the introduction of a needle directly t h r o u g h the cut edges of the wounds_ Utilizing aseptic technique standardized 3 cm wounds were made in the backs of anesthetized rabbits prepared for surgery as previously described. The incis i o n e x t e n d e d d o w n to, b u t n o t through, the p a n n i c u l u s carnosus. A designated n u m b e r ofS. aureus were d e l i v e r e d to t h e s u r f a c e of e a c h w o u n d . I n h a l f t h e w o u n d s , a 27 g a u g e n e e d l e was passed t h r o u g h the h e a v i l y c o n t a m i n a t e d wound edge in four different directions for a distance of 5 ram_ We employ this size needle in our medical center for delivery of local anesthetic agents to traumatic wounds. The pain from puncture of the skin with a 27 gauge needle is considerably less t h a n from a 25 gauge needle. The r e m a i n i n g wounds, not s u b j e c t e d to n e e d l e p u n c t u r e , served as the controls.
l
The test solutions contained varied i0ncentrations of e p i n e p h r i n e alone ir epinephrine and lidocaine. A saiine solution served as the control. Thesolutions were prepared immediiIely before use to p r e v e n t the autoIxidation of epinephrine. A sufficient ~umber of S t a p h y l o c o c c u s a u r e u s tmerican Type C u l t u r e Collection, 0ckville, M a r y l a n d [ATCC] #12600) as added to each test solution so Ihat 0.1 ml contained a subinfective t0seof bacteria. W h e n a test solution @airs t i s s u e d e f e n s e s , i n f e c t i o n ill follow injection of this level of in'.ulum. In a separate experiment, a dilute llution of s o d i u m m e t a - b i s u l f i t e 1.005mg/ml) was e x a m i n e d for its inuence on tissue defenses. This conentration is e q u i v a l e n t to that com!ercially used as a preservative in llutions of 1:30,000 e p i n e p h r i n e . iandom i n o c u l a t i o n sites were inIcled with sodium meta-bisulfite or 19%sodium chloride In one experilent, the solutions contained 106 ornisms/0.1 ml while in a s u b s e q u e n t periment t h e t e s t s o l u t i o n s conined 10 v organisms/0.1 ml.
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~'0ur days later the i n f l a m m a t o r y fsponses of t h e i n o c u l a t i o n sites re determined_ The i n d u r a t e d mar~0feaeh inoculation site was meased and r e p o r t e d in m i l l i m e t e r s . hen skin necrosis was evident, the araeter of i n v o l v e m e n t was re'tried. An incision was made, with a erile No. 15 surgical blade, through lehinoculation site. Gross infection asjudged to be present when puruldischarge was evident. The inocti0n sites were excised with a 2 to %rn m a r g i n of u n i n f l a m e d skin.
i
' ~ P November/December 1975
Needle InjectionTechnique
A 1 m m m a r g i n was carefully outlined a r o u n d each wound. The wounds were t h e n completely excised and discarded. After o u t l i n i n g a 4 mm m a r g i n around the defect, this designated skin m a r g i n was excised. The level of c o n t a m i n a t i o n throughout the wound periphery reflects the spread of bacteria by the needle.
AntimicrobialActivity(In Vitro) The purpose of this e x p e r i m e n t was to e x a m i n e the effect of a local anesthetic agent on the v i a b i l i t y of barteria. T h e b a c t e r i a s e l e c t e d for t h i s study were a s t r a i n of Escherichia coli, a facultative organism, and Pseudomonas aeruginosa, a n obligate aerobe. The E. coli and Ps. aeruginosa were grown overnight, separately, in b r o t h c u l t u r e s i n a n i n c u b a t o r at 98.6F (37 C). The suspensions of bacteria were centrifuged at 4000 rpm for ten m i n u t e s to separate the barteria from the culture media. The button of bacteria at the bottom of the centrifuge t u b e was t h e n w a s h e d twice with s a l i n e to remove r e m n a n t s of the culture media. The inocula were then diluted in a 0.9% saline solution
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Fig. 1. Concentrated solutions of epinephrine impair tissue defenses. so t h a t a specified volume of d i l u e n t contained designated n u m b e r s of bacteria. Suspensions (0.1 ml) ofE. coli and Ps. aeruginosa were also added to 4.0 ml of 2% l i d o c a i n e s o l u t i o n . T h i s same volume of suspensions ofE. coli and Ps. aeruginosa were added to 4_0 ml of n o r m a l saline, to serve as controls. The bacterial suspensions were t h e n placed in the incubator for two hours. The n u m b e r of viable bacteria in all s u s p e n s i o n s was d e t e r m i n e d at the b e g i n n i n g of the experiment, after one and two hours. The changes in bacterial counts in the tubes cont a i n i n g l i d o c a i n e c o m p a r e d to the control t u b e s reflect the antimicrobial activity of lidocaine.
RESULTS Resistanceto Infection E p i n e p h r i n e i m p a i r s the wound's ability to resist infection (Figure 1). The deleterious effect of this powerful local vasoconstrictor is proportional to its c o n c e n t r a t i o n . Concerttrated solutions of e p i n e p h r i n e (1:30,000 and 1:100,000) markedly potentiated the development of infection. The infection rates of wounds subjected to these concentrated solutions were s i g n i f i c a n t l y greater t h a n the control wounds. Necrotic skin tissue was c o m m o n l y e n a o u n t e r e d i n the c e n t r a l portions of the i n o c u l a t i o n sites r e c e i v i n g c o n c e n t r a t e d solutions of e p i n e p h r i n e . The i n d u r a t e w o u n d m a r g i n s a n d the b a c t e r i a l
Volume 4 Number 6 Page 533
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Fig. 2. Effect of dilute epinephrine solutions with lidocaine HC1 on the wound's ability to resist infection. counts of the c o n t a m i n a t e d wounds subjected to concentrated solutions of ep i n ep h ri n e were significantly higher t h a n those of the control contaminated wounds. The i n f l a m m a t o r y responses of the c o n t a m i n a t e d wounds to the more dilute solutions of e p i n e p h r i n e (1:200,000, 1:400,000 and 1:800,000) were less t h a n to the c o n c e n t r a t e d solutions of epinephrine. However, it is i m p o r t a n t to note t h a t the i n f l a m m a tory responses to the dilute solutions of e p i n e p h r i n e were still g r e a te r t h a n to saline. The i n d u r a t e d m a r g i n of the c o n t a m i n a t e d wounds subjected to e p i n e p h r i n e w a s s i g n i f i c a n t l y wider t h a n t h a t of the control wounds. While the n u m b e r o f S . aureus recovered from wounds t r e a t e d with epinep h r i n e and the control wounds did not differ significantly, infection was detected in a s u b s t a n t i a l n u m b e r of the e p i n e p h r i n e t r e a t e d wounds. It is i m p o r t a n t to point out t h a t no infection was en c o u n te r e d in the control wounds. The addition of a 2% lidocaine solution (Xylocaine) to the 1:800,000 solution of e p i n e p h r i n e appeared to minimize the i n f l a m m a t o r y response to e p i n e p h r i n e ( F i g u r e 2). In t h e s e w o u n d s , as w e l l as t h e c o n t r o l wounds, no gross infection or induration was detected. The c o n t a m i n a t e d wounds subjected to more dilute sol u t i o n s of 1% l i d o c a i n e w i t h epin e p h r i n e (1:400,000 and 1:800,000) r e s u l t e d in a s i g n i f i c a n t a m o u n t of wound i n d u r a t i o n as compared to the control wounds.
Page 534 Volume 4 Number 6
10~S. aureus
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Fig. 3. Effect of sodium meta-bisul-
rite on the inflammatory response of the contaminated wound.
The p r eser v at i v e, sodium meta-bisulfite, employed in solutions containing epinephrine, did not i m p a i r tissue defenses (Figure 3). The inflamm a t o r y r e s p o n s e of c o n t a m i n a t e d wounds to this reducing agent did not differ from t h a t to saline.
c o n t a m i n a t i o n was e n c o u n t e r e d in the p er i p h er y of control wounds. Antibacterial
Activity
The local a n e s t h e t i c agent, 2% lidoc a i n e , e x h i b i t e d no a n t i m i c r o b i a l activity (Figure 5). After treatment with this agent, the bacterial count of the lidocaine solution was not significantly different from t h a t of the control solutions. DISCUSSION
Route
of Administration
T h e p a s s a g e of a f i n e n e e d l e t h r o u g h the cut edges of a wound diss e m i n a t e d b a c t e r i a ( F i g u r e 4). In wounds c o n t a i n i n g 107 bacteria/0.1 ml, the needle carried 1000 bacteria into the u n i n v o l v e d tissue surrounding the wound. No significant level of
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These e x p e r i m e n t a l studies have considerably influenced our surgical t r e a t m e n t of soft tissue injuries and infected wounds. We prefer to use a regional nerve block for h e a vi l y co,ntam: inated, t r a u m a t i c soft tissue injuries an d i n f e c t e d w o u n d s . In cases in which this is not possible , the anes-
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November/December 1975 - J ~
fl~etic a g e n t is i n j e c t e d t h r o u g h t h e in at t h e w o u n d p e r i p h e r y . Injecon t h r o u g h t h e c u t e d g e s of t h e #und disseminates bacteria through~L;t the u n i n v o l v e d t i s s u e a r o u n d ~e wound and should be avoided.
IcoNCLUSION ; We r e c o m m e n d a 1% solution of liJ0caine as t h e local a n e s t h e t i c agent. 'this drug does n o t i m p a i r t h e t i s s u e ' s ibility to r e s i s t i n f e c t i o n and has no ~timicrobial activity. 4 E p i n e p h r i n e hould be a v o i d e d in t h e a n e s t h e t i c soution. C o n c e n t r a t e d s o l u t i o n s of
!
e p i n e p h r i n e i m p a i r defenses and inv i t e i n f e c t i o n . D i l u t e s o l u t i o n s of e p i n e p h r i n e also s u b s t a n t i a l l y enh a n c e t h e i n f l a m m a t o r y r e s p o n s e of t h e c o n t a m i n a t e d wound. The d e l e t e r ious effects of e p i n e p h r i n e w e r e recognized p r e v i o u s l y by E v a n s et al, '~ who suggested that epinephrine immobilized t i s s u e d e f e n s e s and t h e r e b y limited r e s i s t a n c e to infection.
REFERENCES 1. Covino BG: Comparative clinical pharmacology of local anesthetic agents. Anesthesiology 35:158-167, 1971.
2. Albert J, Lofstrom B: Effects of epinephrine in solutions of local anesthetic agents. Acta Anesthesiology Scand, (suppl) 16:71-77, 1965. 3. Edlich RF, Tsung MS, Rogers W, et ah Studies in the management of the contaminated wound. 1. Technique of closure of such wounds together with a note on a reproducible experimental modeh J Surg Res 8:585-592, 1968. 4. Roettinger W, Edgerton MT, Kurtz LD, et ah Role of inoculation site as a determinant of infection in soft tissue wounds. Am J Surg 126:354-358, 1973. 5. Evans DG, Miles AA, Niven JSF: The enhancement of bacterial infections by adrenaline. Br J Exp Pathol 29:20, 1948.
Correction: In "Professional Productivity and Quality Assurance" by Richard S. Evans, MD, and Harvey W. Rosenberg, MD,(September/OctoberJACEP),thethird paragraph on page 407 should read: "The class Follow-up(F/U) visit would be anticipated to elicit a physician response similar to a progress note. Hence, only th()se parameters directed at the immediate problem and its interval progress would receive attention, ie, 'ACC' would be tantamount to a progress note and 'date of onset,' 'CC' 'PMH' and 'MED' would elicit negative physician performance score." Also, on page 411, the second paragraph should read "scatter in all bands - - ' p r o b l e m identity,' 'ACC,' 'primary area,' 'patient education' and 'disposition' revealed a positive reliability by physician O, but unreliable and negative reliability by the other physicians."
~)
November/December 1975
Volume 4 Number 6 Page 535
Damage to Tissue Defenses By Vasoconstrictors Thomas R. Stevenson, MD* George T. Rodeheaver, MD* Gerald T. Golden, MD* Milton T. Edgerton, MD* James H. Wells, MD* Richard F. Edlich, MD, PhD** Charlottesville, Virginia
T h e p a p e r i n v e s t i g a t e s t h e e f f e c t o f s o l u t i o n s of l o c a l a n e s t h e t i c a g e n t s o n t h e a b i l i t y o f w o u n d s to r e s i s t i n f e c t i o n as w e l l as t h e i n f l u e n c e o f t h e i n j e c t i o n t e c h n i q u e s o n t h e d i s s e m i n a t i o n o f b a c t e r i a t h r o u g h the w o u n d . On t h e b a s i s o f t h e s e s t u d i e s , t h e f o l l o w i n g r e c o m m e n d a t i o n s are m a d e : (1) a r e g i o n a l n e r v e b l o c k w i t h 1% l i d o c a i n e a d m i n i s t e r e d t h r o u g h a 27 g a u g e n e e d l e is i n d i c a t e d b e f o r e w o u n d c l e a n s i n g ; (2) i f t h e w o u n d is n o t s u s c e p t i b l e to a r e g i o n a l n e r v e b l o c k , a n e s t h e t i z e the w o u n d by injecting the agent through the skin around the periphery of the w o u n d ; (3) a v o i d t h e u s e o f e p i n e p h r i n e w i t h t h e a n e s t h e t i c a g e n t . StevensonTR, RodeheaverGT, GoldenGT, etal:
Damage to tissue defenses
by vasoconstrictors. JACEP 4: 532-535, November/December 1975. vasoconstrictors; anesthesia; wound infection; lidocaine; epinephrine. INTRODUCTION
W h e n faced w i t h a t r a u m a t i c woui~d, the physician initiates therapy t h a t will rapidly induce loss of local sensation. Local a n e s t h e s i a not only e n s u r e s the p a t i e n t ' s comfort b u t aids the physician in wound man*Department of Plastic Surgery, University of Virginia Medical Center, Charlottesville. **Department of Plastic Surgery, University of Virginia Medical Center, Charlottesville. Junior Faculty Climcal Fellow of the American Cancer Society. Supported in part by a grant from the United States Army Medical Research and Development Command, Washington, DC. Address for reprints: Richard F. Edlich, MD, Department of Plastic Surgery, University of Virginia Medical Center, Jefferson Park Avenue, Charlottesville, Virginia 22901.
Page 532 Volume 4 Number 6
agement. C l e a n s i n g of bacteria, soil and other debris from t r a u m a t i c injuries and surgical d e b r i d e m e n t of infected w o u n d s c a n n o t be accomplished w i t h o u t local anesthesia. Anesthetic agents should have rapid onset of action locally without any adverse systemic effects. They should also not i m p a i r the wound's ability to resist infection. This is p a r t i c u l a r l y i m p o r t a n t in t r a u m a t i c wounds cont a m i n a t e d with moderate n u m b e r s of bacteria. A n y i n h i b i t i o n of tissue defenses will predispose the wound to infection. The effect of the local anesthetic agent on the viability of microorg a n i s m s is a n o t h e r i m p o r t a n t consideration. For infected wounds, an agent that displays antimicrobial activity m a y e l i m i n a t e the pathogen and interfere with its identification. L i d o c a i n e h y d r o c h l o r i d e is t h e
most c o m m o n l y employed local anesthetic agent. Loss of sensation occurs w i t h i n five m i n u t e s and lasts an average of 97 to 156 minutes. ~ The clinical usefulness ofilidocaine can be enhanced by adding the hemostatie agent, epinephrine. Epinephrine is a p o t e n t v a s o c o n s t r i c t o r t h a t overcomes the vasodilatory effects of lidocaine_ The reduction in blood flow induced by e p i n e p h r i n e limits the clearance of the anesthetic agent from the tissue prolonging the duration of anesthesia." As a result of this, the'toxic dose of lidocaine solutions containing epinephrine for local wound infiltration (7 mglkg, not to exceed 500 mgt0tal) is considerably higher than for the same anesthetic solution without epinephrine (4.5 mg/kg, n o t to exceed 300 rag). However, the beneficial effect of e p i n e p h r i n e 'must be weighed a g a i n s t its serious side effects of hypertension, cardiac arrhythmias, and cerebral hemorrhage. T h e series of i n v e s t i g a t i o n s reported here will aid the physician in deciding how to Employ local aneSthetic agents in p a t i e n t s withtrauma" tic tissue injuries or infected wounds. MATERIALS AND METHODS Resistance to Infection
.
The first series of'expel:imentS ex" amined the influence of solutions of local anesthetic agents on the tisstl~'~
November/December 1 9 7 5 " ~
bility to resist infection. Male albi:.N0rabbits, w e i g h i n g 2 to 3 kg, were [. esthetized with sodium pentobarbi(~ (33 mg/kg), a d m i n i s t e r e d i n t r a ~,e~ously. E a c h a n i m a l ' s back was h~ved, depilated and prepped with a 0~ ethyl alcohol solution.
These tissues were homogenized separately (Sorvall Omnimixer). The n u m b e r of viable bacteria in the homogenate was d e t e r m i n e d by r o u t i n e serial dilution techniques, a
Each i n o c u l a t i o n site in the aniCals' p a r a v e r t e b r a l skin was separated by a distance of 5 cm. A n intra*~errnal injection of 0,1 ml of a desigilated solution was delivered to each inoculation site t h r o u g h a 25 gauge heedle- After injection, the inocula10N s i t e s were covered by s t e r i l e ~gauze followed by an adhesive tape ressing-
This study d e t e r m i n e d the spread of bacteria r e s u l t i n g from the introduction of a needle directly t h r o u g h the cut edges of the wounds_ Utilizing aseptic technique standardized 3 cm wounds were made in the backs of anesthetized rabbits prepared for surgery as previously described. The incis i o n e x t e n d e d d o w n to, b u t n o t through, the p a n n i c u l u s carnosus. A designated n u m b e r ofS. aureus were d e l i v e r e d to t h e s u r f a c e of e a c h w o u n d . I n h a l f t h e w o u n d s , a 27 g a u g e n e e d l e was passed t h r o u g h the h e a v i l y c o n t a m i n a t e d wound edge in four different directions for a distance of 5 ram_ We employ this size needle in our medical center for delivery of local anesthetic agents to traumatic wounds. The pain from puncture of the skin with a 27 gauge needle is considerably less t h a n from a 25 gauge needle. The r e m a i n i n g wounds, not s u b j e c t e d to n e e d l e p u n c t u r e , served as the controls.
l
The test solutions contained varied i0ncentrations of e p i n e p h r i n e alone ir epinephrine and lidocaine. A saiine solution served as the control. Thesolutions were prepared immediiIely before use to p r e v e n t the autoIxidation of epinephrine. A sufficient ~umber of S t a p h y l o c o c c u s a u r e u s tmerican Type C u l t u r e Collection, 0ckville, M a r y l a n d [ATCC] #12600) as added to each test solution so Ihat 0.1 ml contained a subinfective t0seof bacteria. W h e n a test solution @airs t i s s u e d e f e n s e s , i n f e c t i o n ill follow injection of this level of in'.ulum. In a separate experiment, a dilute llution of s o d i u m m e t a - b i s u l f i t e 1.005mg/ml) was e x a m i n e d for its inuence on tissue defenses. This conentration is e q u i v a l e n t to that com!ercially used as a preservative in llutions of 1:30,000 e p i n e p h r i n e . iandom i n o c u l a t i o n sites were inIcled with sodium meta-bisulfite or 19%sodium chloride In one experilent, the solutions contained 106 ornisms/0.1 ml while in a s u b s e q u e n t periment t h e t e s t s o l u t i o n s conined 10 v organisms/0.1 ml.
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~'0ur days later the i n f l a m m a t o r y fsponses of t h e i n o c u l a t i o n sites re determined_ The i n d u r a t e d mar~0feaeh inoculation site was meased and r e p o r t e d in m i l l i m e t e r s . hen skin necrosis was evident, the araeter of i n v o l v e m e n t was re'tried. An incision was made, with a erile No. 15 surgical blade, through lehinoculation site. Gross infection asjudged to be present when puruldischarge was evident. The inocti0n sites were excised with a 2 to %rn m a r g i n of u n i n f l a m e d skin.
i
' ~ P November/December 1975
Needle InjectionTechnique
A 1 m m m a r g i n was carefully outlined a r o u n d each wound. The wounds were t h e n completely excised and discarded. After o u t l i n i n g a 4 mm m a r g i n around the defect, this designated skin m a r g i n was excised. The level of c o n t a m i n a t i o n throughout the wound periphery reflects the spread of bacteria by the needle.
AntimicrobialActivity(In Vitro) The purpose of this e x p e r i m e n t was to e x a m i n e the effect of a local anesthetic agent on the v i a b i l i t y of barteria. T h e b a c t e r i a s e l e c t e d for t h i s study were a s t r a i n of Escherichia coli, a facultative organism, and Pseudomonas aeruginosa, a n obligate aerobe. The E. coli and Ps. aeruginosa were grown overnight, separately, in b r o t h c u l t u r e s i n a n i n c u b a t o r at 98.6F (37 C). The suspensions of bacteria were centrifuged at 4000 rpm for ten m i n u t e s to separate the barteria from the culture media. The button of bacteria at the bottom of the centrifuge t u b e was t h e n w a s h e d twice with s a l i n e to remove r e m n a n t s of the culture media. The inocula were then diluted in a 0.9% saline solution
pURULENCE NEC~IO$1S
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Fig. 1. Concentrated solutions of epinephrine impair tissue defenses. so t h a t a specified volume of d i l u e n t contained designated n u m b e r s of bacteria. Suspensions (0.1 ml) ofE. coli and Ps. aeruginosa were also added to 4.0 ml of 2% l i d o c a i n e s o l u t i o n . T h i s same volume of suspensions ofE. coli and Ps. aeruginosa were added to 4_0 ml of n o r m a l saline, to serve as controls. The bacterial suspensions were t h e n placed in the incubator for two hours. The n u m b e r of viable bacteria in all s u s p e n s i o n s was d e t e r m i n e d at the b e g i n n i n g of the experiment, after one and two hours. The changes in bacterial counts in the tubes cont a i n i n g l i d o c a i n e c o m p a r e d to the control t u b e s reflect the antimicrobial activity of lidocaine.
RESULTS Resistanceto Infection E p i n e p h r i n e i m p a i r s the wound's ability to resist infection (Figure 1). The deleterious effect of this powerful local vasoconstrictor is proportional to its c o n c e n t r a t i o n . Concerttrated solutions of e p i n e p h r i n e (1:30,000 and 1:100,000) markedly potentiated the development of infection. The infection rates of wounds subjected to these concentrated solutions were s i g n i f i c a n t l y greater t h a n the control wounds. Necrotic skin tissue was c o m m o n l y e n a o u n t e r e d i n the c e n t r a l portions of the i n o c u l a t i o n sites r e c e i v i n g c o n c e n t r a t e d solutions of e p i n e p h r i n e . The i n d u r a t e w o u n d m a r g i n s a n d the b a c t e r i a l
Volume 4 Number 6 Page 533
100
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Fig. 2. Effect of dilute epinephrine solutions with lidocaine HC1 on the wound's ability to resist infection. counts of the c o n t a m i n a t e d wounds subjected to concentrated solutions of ep i n ep h ri n e were significantly higher t h a n those of the control contaminated wounds. The i n f l a m m a t o r y responses of the c o n t a m i n a t e d wounds to the more dilute solutions of e p i n e p h r i n e (1:200,000, 1:400,000 and 1:800,000) were less t h a n to the c o n c e n t r a t e d solutions of epinephrine. However, it is i m p o r t a n t to note t h a t the i n f l a m m a tory responses to the dilute solutions of e p i n e p h r i n e were still g r e a te r t h a n to saline. The i n d u r a t e d m a r g i n of the c o n t a m i n a t e d wounds subjected to e p i n e p h r i n e w a s s i g n i f i c a n t l y wider t h a n t h a t of the control wounds. While the n u m b e r o f S . aureus recovered from wounds t r e a t e d with epinep h r i n e and the control wounds did not differ significantly, infection was detected in a s u b s t a n t i a l n u m b e r of the e p i n e p h r i n e t r e a t e d wounds. It is i m p o r t a n t to point out t h a t no infection was en c o u n te r e d in the control wounds. The addition of a 2% lidocaine solution (Xylocaine) to the 1:800,000 solution of e p i n e p h r i n e appeared to minimize the i n f l a m m a t o r y response to e p i n e p h r i n e ( F i g u r e 2). In t h e s e w o u n d s , as w e l l as t h e c o n t r o l wounds, no gross infection or induration was detected. The c o n t a m i n a t e d wounds subjected to more dilute sol u t i o n s of 1% l i d o c a i n e w i t h epin e p h r i n e (1:400,000 and 1:800,000) r e s u l t e d in a s i g n i f i c a n t a m o u n t of wound i n d u r a t i o n as compared to the control wounds.
Page 534 Volume 4 Number 6
10~S. aureus
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Fig. 3. Effect of sodium meta-bisul-
rite on the inflammatory response of the contaminated wound.
The p r eser v at i v e, sodium meta-bisulfite, employed in solutions containing epinephrine, did not i m p a i r tissue defenses (Figure 3). The inflamm a t o r y r e s p o n s e of c o n t a m i n a t e d wounds to this reducing agent did not differ from t h a t to saline.
c o n t a m i n a t i o n was e n c o u n t e r e d in the p er i p h er y of control wounds. Antibacterial
Activity
The local a n e s t h e t i c agent, 2% lidoc a i n e , e x h i b i t e d no a n t i m i c r o b i a l activity (Figure 5). After treatment with this agent, the bacterial count of the lidocaine solution was not significantly different from t h a t of the control solutions. DISCUSSION
Route
of Administration
T h e p a s s a g e of a f i n e n e e d l e t h r o u g h the cut edges of a wound diss e m i n a t e d b a c t e r i a ( F i g u r e 4). In wounds c o n t a i n i n g 107 bacteria/0.1 ml, the needle carried 1000 bacteria into the u n i n v o l v e d tissue surrounding the wound. No significant level of
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These e x p e r i m e n t a l studies have considerably influenced our surgical t r e a t m e n t of soft tissue injuries and infected wounds. We prefer to use a regional nerve block for h e a vi l y co,ntam: inated, t r a u m a t i c soft tissue injuries an d i n f e c t e d w o u n d s . In cases in which this is not possible , the anes-
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November/December 1975 - J ~
fl~etic a g e n t is i n j e c t e d t h r o u g h t h e in at t h e w o u n d p e r i p h e r y . Injecon t h r o u g h t h e c u t e d g e s of t h e #und disseminates bacteria through~L;t the u n i n v o l v e d t i s s u e a r o u n d ~e wound and should be avoided.
IcoNCLUSION ; We r e c o m m e n d a 1% solution of liJ0caine as t h e local a n e s t h e t i c agent. 'this drug does n o t i m p a i r t h e t i s s u e ' s ibility to r e s i s t i n f e c t i o n and has no ~timicrobial activity. 4 E p i n e p h r i n e hould be a v o i d e d in t h e a n e s t h e t i c soution. C o n c e n t r a t e d s o l u t i o n s of
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e p i n e p h r i n e i m p a i r defenses and inv i t e i n f e c t i o n . D i l u t e s o l u t i o n s of e p i n e p h r i n e also s u b s t a n t i a l l y enh a n c e t h e i n f l a m m a t o r y r e s p o n s e of t h e c o n t a m i n a t e d wound. The d e l e t e r ious effects of e p i n e p h r i n e w e r e recognized p r e v i o u s l y by E v a n s et al, '~ who suggested that epinephrine immobilized t i s s u e d e f e n s e s and t h e r e b y limited r e s i s t a n c e to infection.
REFERENCES 1. Covino BG: Comparative clinical pharmacology of local anesthetic agents. Anesthesiology 35:158-167, 1971.
2. Albert J, Lofstrom B: Effects of epinephrine in solutions of local anesthetic agents. Acta Anesthesiology Scand, (suppl) 16:71-77, 1965. 3. Edlich RF, Tsung MS, Rogers W, et ah Studies in the management of the contaminated wound. 1. Technique of closure of such wounds together with a note on a reproducible experimental modeh J Surg Res 8:585-592, 1968. 4. Roettinger W, Edgerton MT, Kurtz LD, et ah Role of inoculation site as a determinant of infection in soft tissue wounds. Am J Surg 126:354-358, 1973. 5. Evans DG, Miles AA, Niven JSF: The enhancement of bacterial infections by adrenaline. Br J Exp Pathol 29:20, 1948.
Correction: In "Professional Productivity and Quality Assurance" by Richard S. Evans, MD, and Harvey W. Rosenberg, MD,(September/OctoberJACEP),thethird paragraph on page 407 should read: "The class Follow-up(F/U) visit would be anticipated to elicit a physician response similar to a progress note. Hence, only th()se parameters directed at the immediate problem and its interval progress would receive attention, ie, 'ACC' would be tantamount to a progress note and 'date of onset,' 'CC' 'PMH' and 'MED' would elicit negative physician performance score." Also, on page 411, the second paragraph should read "scatter in all bands - - ' p r o b l e m identity,' 'ACC,' 'primary area,' 'patient education' and 'disposition' revealed a positive reliability by physician O, but unreliable and negative reliability by the other physicians."
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November/December 1975
Volume 4 Number 6 Page 535