Pain comparison of unbuffered versus buffered lidocaine in local wound infiltration

The Journal of Emergency

Medicine,

Vol 10. pp 411-415,

Printed in the USA . Copyright

1992

0 1992 Pergamon

Press Ltd.

PAIN COMPARISON OF UNBUFFERED VERSUS BUFFERED LIDOCAINE IN LOCAL WOUND INFILTRATION Michael Orlinsky, *Department

MD,

of Emergency Reprint

Address:

* Curtis Hudson, Medicine,

Michael

MD, *

Linda Chan,

and Richard Deslauriers,

MD’

tDepattment of Pediatrics, Los Angeles County and University of Southern California Medical Center, Los Angeles, California Orlinsky, MD, 1200 N. State Street, GNH 1060-S, Los Angeles, CA 90033-l 064

ante to buffered setting.

Cl Abstract -The purpose of this study was to compare the pain of infiltration between unbuffered lidocaine and buffered lidocaine in a traumatic laceration. Solutions of unbuffered 1% lidocaine and buffered 1% lidocaine were randomly assigned to Site I or Site II of a single laceration for each subject, with the patient serving as self-control. Pain scores were recorded for each site, and an anesthetic preference was determined for each patient. It was found that buffered lidocaine had a preference ratio of 3.0 over unbuffered lldocaine (95% confidence interval, 1.86 to 4.84; P < O.OOtR).It was also found that Site I was preferred more often than Site II regardless of which medication was used. The conclusion is that buffered lidocaine is preferred over unbuffered iidocaine and that the order of injection is an important factor in trials that involve multiple sequential injections in the same patient.

lidocaine holds true in the clinical

MATERIALS

AND METHODS

Procedure This was a prospective, randomized, double-blinded study designed to compare the pain level experienced upon subcutaneous infiltration of unbuffered lidoCaine (UBL) with pH buffered lidocaine (BL). Patients were enrolled from the Minor Trauma area of the Los Angeles County and University of Southern California Medical Center in Los Angeles, California, during the Cweek period from April 27, 1990, to May 21, 1990. Institutional approval of the protocol was obtained from the Research Committee of the hospital prior to beginning the study. Our study included adult patients with a laceration 2 cm or greater in length that required sutures. Patients with a history of allergic or other adverse reaction to lidocaine or sodium bicarbonate, those with an altered mental status, and those with major traumatic injuries that would pose a distraction to pain perception were excluded. To insure uniformity of information given to the patients, preparation of solutions, and execution of the anesthetic technique, the entire protocol was performed by one of the authors, C. H. Patients were told that the purpose of the study was to compare the amount of pain experienced with the initial injection of wound anesthesia using the usual lidocaine with that experienced with a mixture of lidocaine and

0 Keywords - lidocaine; buffered lidocaine; pain comparison; laceration; local anesthesia

INTRODUCTION

Lidocaine is a commonly used local anesthetic. Unfortunately its use is associated with discomfort during infiltration, often the only painful part of wound repair (1,2). It has been reported that adding sodium bicarbonate to lidocaine solutions prevents the “sting” experienced during injection (3). Studies in healthy volunteers have shown a dramatic reduction in the pain of local anesthetic injection by buffering the anesthetic prior to its infiltration (4,5). These studies were limited in that they involved nontraumatized volunteers. The purpose of this study was to determine whether improved toler-

RECEIVED: 26February1991; ACCEPTED: 3 January 1992

PhD,*t

FINALSUBMISSIONRECEIVED: 13 November 1991; 411

0736~4679/92 $5.00 + .OO

412

sodium bicarbonate. It was explained that we hoped to learn whether adding the bicarbonate decreases the amount of pain experienced on injection. Subjects were asked to compare the pain experienced upon injection of two different solutions, and were told that neither the subject nor the doctor would know which medication was injected to which site. Each patient’s wound was divided into two sample injection sites, with Site I always receiving the first injection and Site II receiving the second. For longitudinally oriented wounds, the most central aspect of the medial wound edge was designated Site I and the corresponding segment of the lateral wound edge Site II. For transverse wounds, the medial corner was designated Site I and the lateral corner Site II. In stellate or irregularly shaped wounds, the sites were chosen to be as similar as possible and far enough apart so that no crossover would occur. With each wound receiving both solutions, each patient served as a self-control. To simulate a typical emergency department, a 7.5% solution (0.9 mEq/mL) of sodium bicarbonate was used, the same concentration as that contained in the disposable single-dose ampules for emergency cardiac use. Normal saline 0.9% (without preservative) was used as the control. Solutions were randomly assigned to Site I or Site II for each patient, based on a balanced randomization scheme. Each solution was mixed just before injection by taking 1 mL from each vial and adding it to a correspondingly labeled syringe filled with 10 mL plain 1% lidocaine to form a 1O:l dilution. Anesthesia technique was limited to subcutaneous wound edge infiltration with a 25gauge needle infiltrating at a rate of 1 mL per 5 seconds. A pause for a few seconds occurred between needle puncture and infiltration to allow time for puncture pain to abate. Site I was infiltrated with 0.5 mL from the “Site I” syringe and Site II was infiltrated with 0.5 mL from the “Site II” syringe. Immediately after each site was injected the patient was asked to rate the pain experienced during infiltration using a linear pain scale ranging from 0 to 10 (0 = no pain, 10 = worst pain imaginable). After the entire study was completed the solutions were prepared as described above and the pH measured within 1 to 2 minutes with an Orion Research Microprocessor pH/millivolt meter 811.

Statistical Analysis Comparison of the characteristics of patients who preferred BL to patients who preferred UBL was

M. Orlinsky,

C. Hudson,

L. Chan, R. Deslauriers

made. The Mann-Whitney test was used to determine statistical significance between the groups with respect to average age, length of wound, and pain score at the two sites. Yate’s corrected chi-square was used to determine statistical significance between the groups with respect to ethnicity, location of wound, and site of preference. A P value of co.05 was used as the level of significance. Preference rates were derived by treatment and by site. An overall relative preference ratio of BL over UBL was also calculated. Statistical testing was based on the EPI-INFO statistical software package.

RESULTS A total of 61 patients were studied. Characteristics of patients and their wounds in those who preferred BL as compared to those who preferred UBL were similar (Table 1). The average ( f standard deviation) pain score at Site I was 2.3 (~t2.3) among those preferring UBL, and 2.2 (f 2.5) among those preferring BL (P = 0.80). The average pain score at Site II was 4.4 (h2.5) and 3.8 (*3.0), respectively (P = 0.41). The pH of the solutions was measured at the completion of the study (Table 2). The results showed a significant preference for BL over UBL with an overall relative preference ratio of 3.0 (95% confidence interval, 1.86 to 4.84; P < 0.0001) (Table 3). An unexpected finding was the significant difference in preference rate between Site I and Site II (which represented the order of injections) regardless of which medication was used. Of 56 patients, 40 (7 1Vo) preferred the medication that was given in Site I (i.e., given first) and only 16 of 56 patients (29%) preferred the medication given in Site II (that is, given last). The UBL had a 46% preference rate at Site I and only a 7% preference rate at Site II (P = 0.002); BL had a 93% preference rate at Site I and a 54% preference rate at Site II (P = 0.002) (Table 4).

DISCUSSION Lidocaine, a basic tertiary amine, is combined with HCl to create a weak acid salt solution. In solution, lidocaine dissociates into charged and uncharged components. Upon injection, the anesthetic diffuses through tissue and crosses the nerve membrane in the uncharged form and once within the axoplasm, dissociates again into both the charged and uncharged forms (6,7). Receptors for lidocaine are believed to lie on the inner surface of the nerve mem-

413

Unbuffered versus Buffered Lidocaine Table 1. Comparison of Patient Chamcteristics UBL and Those Who Preferred BL Characteristics

between Those Who Preferred

Preferred UBL

Number of cases Average age (SD) Race black N (%) Hispanic A! (0~) white N (0~) Wound location face N (%) scalp N (%) palm N (%) extremity N (0~) Average wound length (SD) Average pain score at Site I (SD) Number of cases Average Pain score at Site II (SD) Number of cases

iz

(9.1)

1: 0

($iJ

15 ;

‘?Z g:;;

.

3.04 (1:06) 2.3 (2.3) 12 4.4 (2.5) 2

Preferred BL

P value’

42 30

(11.1)

0.79

6 26 6

(15.0) (70.0) (15.0)

0.22

16 5

(42.1) (13.2)

0.39

1: (# 3.05 (1.25) 2.2 (2.5) 26 3.6 (3.0) 14

0.79 0.06 0.41

‘P values for continuous variables were based on Mann-Whitney test; differences between frequency distributions were tested by Yates’ corrected chi-square test.

Table 2. Measured pH of Solutions Solution

PH

Lidocaine, 1% plain UBL: Lidocaine + 0.9% normal saline (10 : 1) BL: Lidocaine + 7.5% sodium bicarbonate (10 : 1)

6.44 6.45 7.45

One sample was measured per solution.

brane about halfway down the sodium channel(8). Anesthesiais achievedwhen the chargedform combineswith the receptor,therebyblocking sodium influx (7,9,10,11).A more minor role for the unchargedform hasalsobeenpostulated(10,ll). Commercial preparationsof lidocaine are acidic solutions (12) (pH = 6.31) that improve solubility and stability, thereby increasing the shelf life (4,5,13). By buffering lidocaine toward its pKa of 7.9, a greater proportion will be in the uncharged form, allowing the anestheticto diffuse more rapidly through tissuesand penetratethe nerve membrane (7). This hasbeenshownto significantlyincreasethe speedof onsetof epidural anesthesia(13,14)as well Table 3. Patient Preference

of Treatment

Regardless

Parameters Total number Patients who Patients who Patients with

of patients preferred BL preferred UBL no preference

Overall preference 4.64; P < 0.0001)

ratio: 3.0 (95% confidence

of Site

N

%

61 42 14 5

100 69 23 6

interval, 1.66 to

as speedthe onsetof axillary nerveblock (15).Since it has been shown that the pain on infiltration between different anestheticsdoes not correlatewith acidity per se(1) (that is, etidocainepH 4.7 is more painful than chloroprocainepH 3.4), it is likely the increasedratio of unchargedto chargedmoleculesof any givenanestheticis responsiblefor the decreasein pain, perhapsby increasingthe speedof onset of anesthesia. The relationship betweenthe anesthetic-induced pain of infiltration andthe pH of the anestheticagent has been evaluated.McKay and colleagues(4) increasedthe pH of lidocaine, with and without epinephrine,by adding sodium bicarbonateto make a 1O:l dilution (lidocaineto bicarbonate)and injected the preparationsalongwith their controlssubcutaneously into the left volar forearm of 24 healthy, nontraumatizedvolunteers.The subjectsrated the pain experiencedusing a lo-cm linear analog pain scale. The authorsconcludethat the BL (pH 7.37)results Table 4. Comparison Treatment’

of Patient’s

Preference

Site I

Site II

P valuet

30 ;; (93%)

26 14 (54%)

0.002

12 (46%)

3i (7%)

0.002

Parameters Number Number Number Number

given chose given chose

BL BL (%) UBL UBL (%)

of Site by

‘5 patients giving no preference were excluded. TYates’ corrected chi-square test for difference between Site I and Site II on percentage preferring the treatment that was given.

414

M. Orlinsky, C. Hudson,

in a statistically significant reduction in pain as compared to UBL and UBL with epinephrine (pH 6.49 and 6.39, respectively). Christoph and colleagues (5), using a methodology similar to that of McKay, found a statistically significant reduction in pain when BL, BL with epinephrine, or buffered mepivicaine, along with their respective controls, were subcutaneously injected into the dorsum of the hands and volar forearms of 25 healthy, nontraumatized volunteers. Utilizing study solutions of 9 mL plain lidocaine diluted by either 1 mL sodium bicarbonate or 1 mL normal saline, Bartfield and colleagues (16) studied 91 patients with traumatic linear lacerations. Each patient received two solutions, one for each side of the wound, thereby creating four groups of patients: group 1 received UBL on the first edge and BL on the second edge; group 2 received the same solutions in the reverse order; group 3 received BL in both edges; and group 4 received UBL in both edges. Using a visual analog pain scale, they determined that BL was significantly less painful than UBL, both for the entire study population and for groups 1 and 2 where each patient served as a self-control. The present study evaluated the effects of pHadjusted lidocaine on the injured patient presenting to the emergency department. A significant preference for BL (pH 7.45) compared to UBL (pH 6.45) was found. This was consistent over a wide range of age, race, and wound locations and sizes. This confirms that even in the clinical setting, where fear and anxiety may alter pain perception, a BL solution makes the laceration repair less painful. For each site, although more patients preferred BL, the pain score recorded for each preferred solution was the same. This may indicate that there exists a pain threshold at which a preference of solution can be made. In the present study this threshold appeared to be dependent on site and independent of solution. The significantly higher preference for the first injection over the second for either solution is an interesting finding. For the same medication, patients preferred what was given first more often than what was given second. This indicates that patients respond differently to injections given in different order. Such a psychological reaction might be explained by the difference in the expectation of pain and the actual level of pain produced by the stimulus. If the patient was told that the injection would be painful or if the patient did not know what to expect,

L. Chan, R. Deslauriers

the patient’s anticipation of pain would usually be heightened and the actual pain produced by the stimulus relatively diminished. On the second injection, however, the patient has already experienced the pain and the anticipation of pain would be very close to what would actually happen. Such a difference in expectation of pain would make the first injection of the same medication seem less painful than the second injection. Although the present study shows a significant patient preference for Site I over Site II, Bartfield’s study (16) reported that more pain is perceived on the first wound edge injected compared to the second, as determined by pain score comparison within their groups 3 and 4. One of their explanations was that as anxiety decreases with the second injection, so does the perceived pain. This is counter to our explanation that for increased anxiety (Site I) there is a lower pain perception because of the difference between expected pain and the stimulus. However, another explanation that Bartfield and colleagues offered may account for the difference in the findings between the two studies: that a cross-diffusion of local anesthetic from the first wound edge to the second may have decreased pain in the second wound edge. In their study, the entire edge was infiltrated, whereas we only infiltrated a very small portion of each edge (0.5 mL anesthetic). How anxiety actually affects pain perception, and if cross-diffusion of anesthetic is a factor, are subjects for further investigation. These findings indicate that the order of injection may be an important factor in trials that involve multiple sequential injections in the same patient. In the present study, although the overall ratio of preference of BL over UBL was 3.0, we found that the ratio preference was 2.0 at the first site and 7.7 at the second site.

CONCLUSION Infiltration of local anesthesia is often the only painful part of wound repair. This study compared the pain experienced during infiltration of BL with that of UBL in a clinical setting. The results show a significant preference for BL. For investigative purposes, the order of injection in the patient is an important factor.

REFERENCES 1. Morris, R, McKay W, Mushlin P. Comparison of pain associated with intradermal and subcutaneous infiltration with var-

ious local anesthetic solutions. Anesth Analg. 1987;66:11802.

Unbuffered versus Buffered Lidocaine 2. Arndt KA, Burton C, Noe JM. Minimizing the pain of local anesthesia. Plast Reconstr Surg. 1983;72:676-9. 3. Korbon GA, Hurley DP, Williams GS. pH-adjusted lidocaine does not sting. Anesthesiology. 1987;66:855-6. 4. McKay W, Morris R, Mushlin P. Sodium bicarbonate attenuates pain on skin infiltration with lidocaine, with or without epinephrine. Anesth Analg. 1987;66:572-4. 5. Christoph RA, Buchanan L, Begalla K, Schwartz S. Pain reduction in local anesthetic administration through pH buffering. Ann Emerg Med. 1988;17: 117-20. 6. Narahashi T, Frazier DT, Yamada M. The site of action and active form of local anesthetics; 1: theory and pH experiments with tertiary compounds. J Pharmacol Exp Ther. 1970;171: 32-44. 7. Ritchie JM, Ritchie B, Greengard P. The active structure of local anesthetics. J Pharmacol Exp Ther. 1965;150:152-9. 8. Strichartz CR. The inhibition of sodium currents in myelinated nerve by quaternary derivatives of lidocaine. J Gen Physiol. 1973;62:37-57. 9. Frazier DT, Narahashi T, Yamada M. The site of action and active form of local anesthetics; 2: experiments with quaternary compounds. J Pharmacol Exp Ther. 1970;171:45-51.

415 10. Hille B. Mechanisms of block. In: Hille B, ed. Ionic channels of excitable membranes. Sunderland, MA: Sinaver Assoc.: 1984:285-302. 11. Strichartz GR, Ritchie JM. Action of local anesthetics on ion channels of excitable tissues. In: Strichartz. GR ed. Handbook of experimental pharmacology. New York: Springer-Verlag; 1985:26-47. 12. Moore DC. The pH of local anesthetic solutions. Anesth Analg. 1981;60:833-4. 13. DiFazio CA, Carron H, Grosslight KR, Moscicki JCC, Bolding WR, Johns RA. Comparison of pH-adjusted lidocaine solutions for epidural anesthesia. Anesth Analg. 1986;65:7604. 14. McMorland GH, Douglas MJ, Jeffrey WK, Ross PLE. Effect of pH-adjustment of bupivacaine on onset and duration of epidural analgesia in parturients. Can Anaesth Sot J. 1986;33: 537-41. 15. Hilgier M. Alkalinization of bupivacaine for brachial plexus block. Reg Anesth. 1985;10:59-61. 16. Bartfield JM, Gennis P, Barbera J, Brever B, Gallagher EJ. Buffered versus plain lidocaine as a local anesthetic for simple laceration repair. Ann Emerg Med. 1990;19:1387-9.