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adrenaline-containing local anaesthetic solution causes increase in acute postoperative pain after gingivectomy
British Journal of Oral and Maxillofacial Surgery (2000) 38, 230–234 © 2000 The British Association of Oral and Maxillofacial Surgeons doi:10.1054/bjom.1999.0447
B BR RIIT TIIS SH H JJO OU UR RN NA AL L O OF F O OR RA AL L
& &M MA AX XIIL LL LO OFA FAC CIIA AL LS SU UR RG GE ERY RY
Increase in volume of lignocaine/adrenaline-containing local anaesthetic solution causes increase in acute postoperative pain after gingivectomy L. Jorkjend,* L. A. Skoglund† *Private Practitioner in Periodontology, Skien; †Section of Dental Pharmacology and Pharmacotherapy, University of Oslo, Norway SUMMARY. A randomized, single-blind, within-patient, crossover study was done in 44 patients (27 women and 17 men mean age 47 years, range 29–63) who had bilateral ‘identical’ gingivectomies. On one occasion a standard volume of local anaesthetic containing lignocaine 2% and adrenaline (1/80 000) was infiltrated into the mucosal tissue before operation. On the other occasion double the standard volume was infiltrated. The intensity of pain postoperatively was recorded by the patients on 100 mm visual analogue scale every hour for an 11-hour observation period. The intensity of pain when double volume had been given was significantly higher than that after the standard volume from 2 to 8 hours postoperatively (P < 0.04), the median (range) being 52.0 mm (0.0–434.0) compared with 30.5 mm (0.0–359.0) after the standard volume (P < 0.005). Doubling the volume of local anaesthetic containing adrenaline that was infiltrated increased the intensity of acute pain after gingivectomy.
INTRODUCTION
PATIENTS AND METHODS
Local anaesthetic agents are the most commonly used analgesics for relieving the peroperative and postoperative pain associated with dental treatment.1 There are many local anaesthetics available with a wide selection of vasoconstricting agents that improve the clinical efficacy and the duration of the local anaesthetic by decreasing the absorption rate of the local anaesthetic agent.2–4 In Scandinavia there seems to be a general clinical preference, irrespective of type of dental treatment, for local anaesthetics that contain lignocaine 2% combined with adrenaline in a concentration of 1/80 000. Little attention has been focused on the clinical phenomenon that patients who are given local anaesthetics sometimes report pain from the injected area when the effect of the local anaesthetic has waned. This pain is not associated with the pain of the injection, but appears apparently without any additional damage to soft tissues or mineralized tissues. This pain was more often reported after experimental buccal submucosal injection of lignocaine 2% with adrenaline (1/80 000) than after 4% prilocaine.5 Controlled clinical trials have shown that lignocaine 2% combined with adrenaline (1/80 000) causes more post-operative pain than local anaesthetics that do not contain lignocaine and adrenaline after surgical removal of gingival mucosa as in gingivectomy.6 These clinical observations may suggest that the combination of lignocaine and adrenaline used primarily as a local anaesthetic has a potential to induce secondary pain after certain oral surgical procedures. The aim of this paper was to investigate the effect of lignocaine 2% with adrenaline (1/80 000) on postoperative pain after gingivectomy in a dose-dependent (i.e. volume-dependent) manner.
Study design and ethical considerations The trial was a randomized, single-blind, withinpatient, crossover study of patients referred for gingivectomy to a specialist practice in periodontology. Initial conservative periodontal treatment was given by a dental hygienist for three sessions after which the specialist surgeon (LJ) scaled and root-planed the teeth for at least two sessions. Patients who had achieved good oral hygiene but had persistent bilateral diseased areas were asked to take part in the study. Those with furcation involvement of teeth were not asked to participate. Informed consent was obtained from all subjects after the nature and intentions of the study had been explained to them. The trial protocol was approved (S-92079) by the Ethics Committee for Medical Research, Health Region II, Norway.
PATIENTS AND OPERATIVE TECHNIQUE Fifty-seven white Norwegians participated in the study. Thirteen patients (seven women and six men) (23%) had no pain during the 11-hour observation periods after each operation. Forty-four patients (77%) (27 women and 17 men, mean age 47 years, range 29–63) had some pain and were included for statistical analyses. The patients were allocated to one of two possible treatment groups by the toss of a coin at the time of the first gingivectomy. Before the first operation the patients received either the standard volume or a double volume of local anaesthetic. The standard volume was defined as the volume of local anaesthetic an 230
Increased volume of lignocaine increases postoperative pain after gingivectomy
experienced specialist in periodontology would use for gingivectomy of a defined gingival area. Double volume was defined as twice the standard volume. All actual volumes were noted. The patients who assessed their subjective postoperative pain independently of the surgeon were unaware of the amount of anaesthetic that they had been given, while the surgeon was not. Commercially available lignocaine hydrochloride 20 mg/ml (2%) with adrenaline 12.5 µg/ml (1/80 000) (Xylocain Adrenalin, Astra, Södertälje, Sweden) in capped vials was used. Neither premedication nor topical anaesthetic was given. Local anaesthetic was infiltrated into the gingival areas to be operated on surgery with thin 27 G (0.4 × 0.4 mm, B. Braun Melsungen AG, Melsungen, FRG) hypodermic needles for dental use. The needle was inserted gently in one continuous movement into the gingival target area where the local anaesthetic solution was injected supraperiostally; movements that could induce scraping of the periosteum were avoided. No local anaesthetic solution leaked during infiltration and successful infiltration was confirmed by transient tissue ischaemia. The operation started two minutes after the anaesthetic injection had been given. All gingivectomies were done by the same surgeon (LJ) as described by Ramfjord and Ash without removing any bone.7 The gingivectomies comprised buccal and palatinal soft tissue that was encircling the teeth in all cases. Periodontal packs (Coe-pak, Coe Laboratories Inc., Chicago, IL, USA) were applied as wound dressings. Efforts were made to make the periodontal packs similar in shape and extension for all comparable bilateral surgical areas. The time used from incision to finished periodontal pack was noted.
PAIN ASSESSMENTS AND STATISTICAL ANALYSES The patients were given clinical record forms on which they were instructed to assess their subjective postoperative pain intensity subjectively on visual analogue scales (VAS) running from ‘no pain’ (0) to ‘pain cannot be worse’ (100 mm). The assessments started when the operation had been completed, and continued hourly for the next 11 hours. This observation period was chosen because it had previously been shown that the major transitory pain course in this pain model occurs on the day of the operation.8 The sum of pain intensity was calculated by adding the
hourly VAS scores over the 11-hour observation period. The patients were instructed not to drink any alcohol during the 11-hour observation period, and not to take any analgesic medication unless it was absolutely necessary. If any analgesic was taken, the time, the number of tablets, and type of medication was to be noted on the form. If any analgesic was taken, the pain score at the time of medication should represent any consecutive score until the end of the observation period. The patients returned to the clinic 14 days after each gingivectomy for removal of the periodontal packs and wound control. The record forms were collected and the patients were asked if they had taken any analgesic drugs. The verbal answer to that question was checked with the patients’ record form. Any wound complication was also noted. The significance of differences were assessed with a two-tailed Wilcoxon matched-pairs signed-ranks test using the Statistical Package for the Social Sciences (SPSS).9 Probabilities of 0.05 or less were accepted as significant.
RESULTS Clinical details of the patients included in the statistical analyses and the operations are shown in Tables 1 and 2. There were no significant differences between the bilateral surgical treatments with respect to number of teeth involved in the gingivectomies or the duration of operation. The median double volume of local anaesthetic was significantly different and numerically twice as large as the standard volume. The time courses of the median acute intensity of postoperative pain are shown in Table 3. The intensity was higher after the double volume of local anaesthetic than after the standard volume from one hour until the end of the observation period 11 hours later. The maximum median observed intensity, which was found after double volume of local anaesthetic, did not exceed 7.5 mm (observed mean 14 mm) in this study. The observed difference was significant from 2–8 hours postoperatively (Table 3). After the standard volume of local anaesthetic 12 of the 44 patients (27%) had a summed pain score equal to zero. After the double volume three out of the 44 patients (7%) had a summed pain score equal to zero. The median (range) sum of pain intensity after the standard volume, 30.5 mm (0.0–359.0), was found to be significantly lower (P < 0.005) than that after the double volume, 52.0 mm (0.0–434.0).
Table 1 – Median (range) volume of local anaesthetic (lignocaine 2% and adrenaline 1/80 000) and duration of operations in 44 patients who underwent bilateral gingivectomy on two separate occasions with a mean of 41 days apart (range 12–175)
Volume of local anaesthetic (ml) Duration of gingivectomy (min)
231
Gingivectomy standard volume
Gingivectomy double volume
P value
1.3 (0.5–2.7) 14.3 (5.0–26.5)
2.6 (1.5–4.2) 15.7 (7.0–29.0)
< 0.0001 0.08
232
British Journal of Oral and Maxillofacial Surgery Table 2 – Median (range) number of teeth and areas involved in gingivectomy in 44 patients after bilateral `identical’ gingivectomy on two separate occasions Areas involved in gingivectomy
Lignocaine 2% + adrenaline 1/80 000 (standard volume)
Lignocaine 2% + adrenaline 1/80 000 (double volume)
P value
Maxillary molars Mandibular molars Maxillary premolars including canines Mandibular premolars including canines Maxillary incisors Mandibular incisors Total number of teeth
1 (0–3) 0 (0–2) 2 (0–3) 0 (0–4) 0 (0–2) 0 (0–4) 4 (1–9)
1 (0–3) 0 (0–3) 2 (0–3) 0 (0–3) 0 (0–4) 0 (0–3) 4 (1–7)
0.42 0.11 0.32 1.00 0.13 0.17 0.16
Table 3 – Median (range) pain intensity scores on 10 cm VAS on two separate occasions after bilateral `identical’ gingivectomy with standard or double volume lignocaine 2% and adrenaline 1/80 000 Hours after
Standard
Double
P value
0 1 2 3 4 5 6 7 8 9 10 11
0.0 (0.0–3.0) 0.0 (0.0–18.0) 1.0 (0.0–29.0) 2.0 (0.0–35.0) 2.5 (0.0–36.0) 3.0 (0.0–37.0) 4.0 (0.0–38.0) 4.5 (0.0–40.0) 4.0 (0.0–41.0) 2.0 (0.0–40.0) 0.5 (0.0–34.0) 0.0 (0.0–34.0)
0.0 (0.0–4.0) 0.5 (0.0–38.0) 3.5 (0.0–58.0) 5.0 (0.0–62.0) 6.0 (0.0–62.0) 6.5 (0.0–63.0) 7.5 (0.0–58.0) 5.5 (0.0–56.0) 5.0 (0.0–57.0) 2.0 (0.0–56.0) 0.5 (0.0–56.0) 0.0 (0.0–56.0)
0.66 0.24 < 0.003 < 0.01 < 0.006 < 0.01 < 0.005 < 0.02 < 0.04 0.08 0.21 0.23
Four patients took analgesics during the observation period. After the standard volume of local anaesthetic one patient took a tablet of paracetamol 500 mg and one a tablet of aspirin 300 mg, and after the double volume one patient took two tablets of paracetamol 500 mg six hours apart, one took a tablet of paracetamol 500 mg and one took aspirin 300 mg. The same patient took aspirin after both operations. All analgesics medications were bought over the counter, and gave sufficient pain relief. No patient experienced any wound complication (including signs of fibrinolytic activity or impaired epithelialization under the wound dressings) during the observation period or until the control visit 14 days after each operation.
DISCUSSION The duration and effectiveness of both volumes of local anaesthetics used were adequate for the operations done. The time used for infiltration anaesthesia was sufficient to allow the anaesthetic to start acting before the operation.10 The only clinical difference between the two treatments was in the intensity of pain during the postoperative period, and there was a dose-dependent (i.e. volume-dependent) increase in postoperative pain after gingivectomy with lignocaine
2% combined with adrenaline (1/80 000). By using an identical concentration of local anaesthetic solution, while increasing the infiltrated volume (which also increase the gingival tissue fluid content), we increased the amount of lignocaine and adrenaline in the gingival tissue.11 There are several possible mechanisms that explain the increase. Ischaemia caused by alterations in the peripherial blood flow in gingival tissue by the volume of local anaesthetic infiltrated, or caused by the local anaesthetic itself, may contribute to nociception. Ischaemia-induced accumulation of acid metabolites in gingival tissue together with biochemical mediators produced as a consequence of the surgical trauma, favour nociceptive mechanisms.12,13 The volume of fluid of the local anaesthetic may increase the pressure within the tissue space. Experiments with increased tissue expansion of human skin show reduced tissue circulation with subsequent transient effects on tissue oxygen tension,14,15 which generate increased cyclic adenosine monophosphate (cAMP) concentrations16 associated with nociceptive mechanisms.13 This is confirmed by a report that showed an increase in pain when the volume of injected subcutanously saline in the thigh of humans was increased from 0.5 ml to 1.5 ml.17 By contrast, subcutaneous tissue is organized differently from the well-perfused gingival tissues, and the ischaemia by the time of injection in our study was short-lived judged by the speed of the change of the gingival colour back to normal. One seems to be left with a likely option that the postoperative pain may be caused by the pharmacodynamic properties of the lignocaine or adrenaline, or both, constituent in the local anaesthetic combination. Lignocaine 2% given alone as a local anaesthetic does tend to increase peripheral blood flow in human gingiva, but lignocaine 1% with adrenaline 1/100 000 and lignocaine 2% with adrenaline 1/80 000 caused a reduction in blood flow that lasts for 60 to 90 minutes.18 There is apparently little reason to assume that the lignocaine itself contributed to the postoperative pain in the present study. Adrenaline is a potent stimulator of the adrenergic α-, β1-, and β2- receptors, and it is particularly effective on the oral mucosa, submucosa, and periodontium because of its α-receptor agonist effect that causes vascular constriction.19 cAMP is synthesized
Increased volume of lignocaine increases postoperative pain after gingivectomy
from adenosine triphosphate by the enzyme adenyl cyclase.20 Catecholamines, including adrenaline, act as adenyl cyclase activators and induce hyperalgesia, possibly through a cAMP-dependent process.13,21 Lignocaine 2% with adrenaline 1/100 000 infiltrated into the attached gingiva in experimental animals causes a rapid and obvious increase in gingival cAMP compared with non-anaesthesized gingiva.22 Infiltration of lignocaine 2% does not cause any rise in the cAMP concentrations.22 Periodonititis is a chronic inflammation that is associated with the production of hyperalgesic substances. Continuous release of inflammatory substances may have sensitized nociceptive mechanisms in the patients participating in our study, making them more susceptible to the effects of adrenaline.13 However, as all patients had completed the initial treatment and their chronic inflammation was reduced to the lowest possible minimum, it seems unlikely that this factor introduced bias into the study. It has been reported that 51–92% of patients after periodontal interventions reported pain.23–25 In the present study, 77% of the participants reported pain on at least one occasion after bilateral periodontal surgery. This incidence is in general agreement with those reported by others. The maximum mean pain index observed after double volume of local anaesthetic did not exceed 14 mm in the present study. The mean pain intensities after other types of oral surgery have been reported to range from as high as 65–70 mm26 to 40–50 mm27 after removal of impacted third molars down to about 30–35 mm after apiectomies.26 The most severe mean pain intensity observed in our study cannot be categorized as `severe pain’, but it was enough to differentiate between the postoperative pain intensities of the two different volumes of local anaesthetics. Several factors that may possibly be associated with increased postoperative pain after local anaesthetics containing lignocaine and adrenaline may have affected the results of this study. It is our experience that many clinicians think that large volumes of local anaesthetics ensure better local anaesthesia. Our study shows that the opposite seems true regarding the postoperative course, at least after gingivectomy, when using lignocaine 2% combined with adrenaline (1/80 000). We conclude that the use of large volumes of local anaesthetic containing lignocaine 2% and adrenaline (1/80 000) should be avoided in oral soft tissue surgery such as gingivectomy. Further clinical studies on the effect of adrenaline on postoperative pain after oral soft tissue surgery are advocated.
4. 5. 6.
7. 8.
9. 10. 11. 12.
13.
14. 15. 16. 17. 18. 19. 20. 21. 22. 23. 24. 25.
References 1. 2. 3.
Malamed SF. What’s new in local anesthesia? Anesth Prog 1992; 39: 125–131. Malamed SF, Sykes P, Kubota Y, Matsuura H, Lipp M. Local anesthesia: a review. Anesth Pain Control Dent 1992; 11–24. Sisk Al. Vasoconstrictors in local anesthesia for dentistry. Anesth Prog 1992; 39: 187–193.
26. 27.
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Jage J. Circulatory effects of vasoconstrictors combined with local anesthetics. Anesth Pain Control Dent 1993; 2: 81–86. Oikarinen VJ, Ylipaavalniemi P, Evers H. Pain and temperature sensation related to local analgesia. Int J Oral Surg 1975; 4: 151–156. Skoglund LA, Jorkjend L. Postoperative pain experience after gingivectomies using different combinations of local anaesthetic agents and periodontal dressings. J Clin Periodontol 1991; 18: 204–209. Ramfjord SP, Ash MM. Periodontology and Periodontics. Philadelphia: WB Saunders, 1979: 543–565. Jorkjend L, Skoglund LA. Effect of non-eugenol and eugenol containing periodontal dressings on the incidence and severity of pain after peridontal soft tissue surgery. J Clin Periodontol 1990; 17: 341–344. Norusis MJ. SPSS/PC+ for the IBM PC/XT/AT. Chicago: SPSS, 1986. Nordenram Á, Danielsson KH. Local anaesthesia in elderly patients. An experimental study of oral infiltration anaesthesia. Swed Dent J 1990; 14: 19–24. Sinha HK. Factors influencing the duration of local anaesthesia. J Pharmacol Exp Ther 1939; 66: 42–53. Eberhardt B. Dental local anaesthesia in high-risk patients. In: Frenkel G, ed. Local Anaesthsia in Dentistry Today. Two Decades of Articaine. Frankfurt am Main: Hoechst, 1989: 83–111. Skjelbred P, Løkken P. Pain and other sequelae after surgery – mechanisms and management. In: Andreasen JO, Petersen JK, Laskin DM, eds. Textbook and Color Atlas of Tooth Impactions. Diagnosis, Treatment and Prevention. Copenhagen: Munksgaard, 1997; 369–437. Hallock GG, Rice DC. Objective monitoring for safe tissue expansion. Plast Reconstr Surg 1986; 77: 416–420. Hallock GG, Rice DC. Increased sensitivity in objective monitoring of tissue expansion. Plast Reconstr Surg 1993; 91: 217–222. Yoshikawa K, Adachi K, Halprin KM, Levine V. Cyclic AMP in skin: effects of acute ischaemia. Br J Dermatol 1975; 92: 249–254. Jorgensen JT, Roamsing J, Rasmussen M. Is the pain of a subcutanous injection related to the injection volume? Dolor Inv Clin Ther 1997; 12: 33. Suzuki T, Sano K, Kanri T. The influence of various local anesthetics on peripheral blood flow in human gingiva. Anesth Prog 1989; 36: 183. Milam SB, Giovannitti JA. Local anesthetics in dental practice. Dent Clin North Am 1984; 28: 493–508. Pohl SL, Birnbaumer L, Rodbell M. Glucagon-sensitive adenyl cyclase in plasma membrane hepatic parenchymal cells. Science 1969; 164: 566–567. Ferreira SH. Peripheral analgesia: mechanism of the analgesic action of aspirin-like drugs and opiate antagonists. Br J Clin Pharmacol 1980; 10: 237–245. Grower MF, Chandler D, Kramer G, Stow JA. Effects of local anesthesia on gingival cAMP levels. J Periodontol 1979; 50: 38–42. Strahan JD, Glenwright HD. Pain experience in periodontal surgery. J Periodontal Res 1967; 1: 163–166. Curtis JW, McLain JB, Hutchinson RA. The incidence and severity of complications and pain following periodontal surgery. J Periodontol 1985; 56: 597–601. Pra DJ, Strahan JD. A clinical evaluation of the benefits of a course of oral penicillin following periodontal surgery. Aust Dent J 1972; 17: 219–221. Seymour RA, Blair GS, Wyatt EAR. Post-operative dental pain and analgesic efficacy. I. Br J Oral Surg 1983; 21: 290–297. Skoglund LA, Skjelbred P. Comparison of a traditional paracetamol medication and a new paracetamol/paracetamol-methionine ester combination. Eur J Clin Pharmacol 1984; 26: 573–577.
234
British Journal of Oral and Maxillofacial Surgery
The Authors L. Jorkjend DDS, Dr Odont & LicOdont L. A. Skoglund DDS, DrSci Section of Dental Pharmacology and Pharmacotherapy University of Oslo Norway
Correspondence and requests for offprints to: Professor Dr. L. A. Skoglund, Section of Dental Pharmacology and Pharmacotherapy, University of Oslo, P.O. Box 1057 Blindern, N-0316 Oslo, Norway. Tel: + 47 22 85 60 62; Fax: + 47 22 85 44 40; E-mail: [email protected] Paper received 11 May 1998 Accepted 24 November 1999
B BR RIIT TIIS SH H JJO OU UR RN NA AL L O OF F O OR RA AL L
& &M MA AX XIIL LL LO OFA FAC CIIA AL LS SU UR RG GE ERY RY
Increase in volume of lignocaine/adrenaline-containing local anaesthetic solution causes increase in acute postoperative pain after gingivectomy L. Jorkjend,* L. A. Skoglund† *Private Practitioner in Periodontology, Skien; †Section of Dental Pharmacology and Pharmacotherapy, University of Oslo, Norway SUMMARY. A randomized, single-blind, within-patient, crossover study was done in 44 patients (27 women and 17 men mean age 47 years, range 29–63) who had bilateral ‘identical’ gingivectomies. On one occasion a standard volume of local anaesthetic containing lignocaine 2% and adrenaline (1/80 000) was infiltrated into the mucosal tissue before operation. On the other occasion double the standard volume was infiltrated. The intensity of pain postoperatively was recorded by the patients on 100 mm visual analogue scale every hour for an 11-hour observation period. The intensity of pain when double volume had been given was significantly higher than that after the standard volume from 2 to 8 hours postoperatively (P < 0.04), the median (range) being 52.0 mm (0.0–434.0) compared with 30.5 mm (0.0–359.0) after the standard volume (P < 0.005). Doubling the volume of local anaesthetic containing adrenaline that was infiltrated increased the intensity of acute pain after gingivectomy.
INTRODUCTION
PATIENTS AND METHODS
Local anaesthetic agents are the most commonly used analgesics for relieving the peroperative and postoperative pain associated with dental treatment.1 There are many local anaesthetics available with a wide selection of vasoconstricting agents that improve the clinical efficacy and the duration of the local anaesthetic by decreasing the absorption rate of the local anaesthetic agent.2–4 In Scandinavia there seems to be a general clinical preference, irrespective of type of dental treatment, for local anaesthetics that contain lignocaine 2% combined with adrenaline in a concentration of 1/80 000. Little attention has been focused on the clinical phenomenon that patients who are given local anaesthetics sometimes report pain from the injected area when the effect of the local anaesthetic has waned. This pain is not associated with the pain of the injection, but appears apparently without any additional damage to soft tissues or mineralized tissues. This pain was more often reported after experimental buccal submucosal injection of lignocaine 2% with adrenaline (1/80 000) than after 4% prilocaine.5 Controlled clinical trials have shown that lignocaine 2% combined with adrenaline (1/80 000) causes more post-operative pain than local anaesthetics that do not contain lignocaine and adrenaline after surgical removal of gingival mucosa as in gingivectomy.6 These clinical observations may suggest that the combination of lignocaine and adrenaline used primarily as a local anaesthetic has a potential to induce secondary pain after certain oral surgical procedures. The aim of this paper was to investigate the effect of lignocaine 2% with adrenaline (1/80 000) on postoperative pain after gingivectomy in a dose-dependent (i.e. volume-dependent) manner.
Study design and ethical considerations The trial was a randomized, single-blind, withinpatient, crossover study of patients referred for gingivectomy to a specialist practice in periodontology. Initial conservative periodontal treatment was given by a dental hygienist for three sessions after which the specialist surgeon (LJ) scaled and root-planed the teeth for at least two sessions. Patients who had achieved good oral hygiene but had persistent bilateral diseased areas were asked to take part in the study. Those with furcation involvement of teeth were not asked to participate. Informed consent was obtained from all subjects after the nature and intentions of the study had been explained to them. The trial protocol was approved (S-92079) by the Ethics Committee for Medical Research, Health Region II, Norway.
PATIENTS AND OPERATIVE TECHNIQUE Fifty-seven white Norwegians participated in the study. Thirteen patients (seven women and six men) (23%) had no pain during the 11-hour observation periods after each operation. Forty-four patients (77%) (27 women and 17 men, mean age 47 years, range 29–63) had some pain and were included for statistical analyses. The patients were allocated to one of two possible treatment groups by the toss of a coin at the time of the first gingivectomy. Before the first operation the patients received either the standard volume or a double volume of local anaesthetic. The standard volume was defined as the volume of local anaesthetic an 230
Increased volume of lignocaine increases postoperative pain after gingivectomy
experienced specialist in periodontology would use for gingivectomy of a defined gingival area. Double volume was defined as twice the standard volume. All actual volumes were noted. The patients who assessed their subjective postoperative pain independently of the surgeon were unaware of the amount of anaesthetic that they had been given, while the surgeon was not. Commercially available lignocaine hydrochloride 20 mg/ml (2%) with adrenaline 12.5 µg/ml (1/80 000) (Xylocain Adrenalin, Astra, Södertälje, Sweden) in capped vials was used. Neither premedication nor topical anaesthetic was given. Local anaesthetic was infiltrated into the gingival areas to be operated on surgery with thin 27 G (0.4 × 0.4 mm, B. Braun Melsungen AG, Melsungen, FRG) hypodermic needles for dental use. The needle was inserted gently in one continuous movement into the gingival target area where the local anaesthetic solution was injected supraperiostally; movements that could induce scraping of the periosteum were avoided. No local anaesthetic solution leaked during infiltration and successful infiltration was confirmed by transient tissue ischaemia. The operation started two minutes after the anaesthetic injection had been given. All gingivectomies were done by the same surgeon (LJ) as described by Ramfjord and Ash without removing any bone.7 The gingivectomies comprised buccal and palatinal soft tissue that was encircling the teeth in all cases. Periodontal packs (Coe-pak, Coe Laboratories Inc., Chicago, IL, USA) were applied as wound dressings. Efforts were made to make the periodontal packs similar in shape and extension for all comparable bilateral surgical areas. The time used from incision to finished periodontal pack was noted.
PAIN ASSESSMENTS AND STATISTICAL ANALYSES The patients were given clinical record forms on which they were instructed to assess their subjective postoperative pain intensity subjectively on visual analogue scales (VAS) running from ‘no pain’ (0) to ‘pain cannot be worse’ (100 mm). The assessments started when the operation had been completed, and continued hourly for the next 11 hours. This observation period was chosen because it had previously been shown that the major transitory pain course in this pain model occurs on the day of the operation.8 The sum of pain intensity was calculated by adding the
hourly VAS scores over the 11-hour observation period. The patients were instructed not to drink any alcohol during the 11-hour observation period, and not to take any analgesic medication unless it was absolutely necessary. If any analgesic was taken, the time, the number of tablets, and type of medication was to be noted on the form. If any analgesic was taken, the pain score at the time of medication should represent any consecutive score until the end of the observation period. The patients returned to the clinic 14 days after each gingivectomy for removal of the periodontal packs and wound control. The record forms were collected and the patients were asked if they had taken any analgesic drugs. The verbal answer to that question was checked with the patients’ record form. Any wound complication was also noted. The significance of differences were assessed with a two-tailed Wilcoxon matched-pairs signed-ranks test using the Statistical Package for the Social Sciences (SPSS).9 Probabilities of 0.05 or less were accepted as significant.
RESULTS Clinical details of the patients included in the statistical analyses and the operations are shown in Tables 1 and 2. There were no significant differences between the bilateral surgical treatments with respect to number of teeth involved in the gingivectomies or the duration of operation. The median double volume of local anaesthetic was significantly different and numerically twice as large as the standard volume. The time courses of the median acute intensity of postoperative pain are shown in Table 3. The intensity was higher after the double volume of local anaesthetic than after the standard volume from one hour until the end of the observation period 11 hours later. The maximum median observed intensity, which was found after double volume of local anaesthetic, did not exceed 7.5 mm (observed mean 14 mm) in this study. The observed difference was significant from 2–8 hours postoperatively (Table 3). After the standard volume of local anaesthetic 12 of the 44 patients (27%) had a summed pain score equal to zero. After the double volume three out of the 44 patients (7%) had a summed pain score equal to zero. The median (range) sum of pain intensity after the standard volume, 30.5 mm (0.0–359.0), was found to be significantly lower (P < 0.005) than that after the double volume, 52.0 mm (0.0–434.0).
Table 1 – Median (range) volume of local anaesthetic (lignocaine 2% and adrenaline 1/80 000) and duration of operations in 44 patients who underwent bilateral gingivectomy on two separate occasions with a mean of 41 days apart (range 12–175)
Volume of local anaesthetic (ml) Duration of gingivectomy (min)
231
Gingivectomy standard volume
Gingivectomy double volume
P value
1.3 (0.5–2.7) 14.3 (5.0–26.5)
2.6 (1.5–4.2) 15.7 (7.0–29.0)
< 0.0001 0.08
232
British Journal of Oral and Maxillofacial Surgery Table 2 – Median (range) number of teeth and areas involved in gingivectomy in 44 patients after bilateral `identical’ gingivectomy on two separate occasions Areas involved in gingivectomy
Lignocaine 2% + adrenaline 1/80 000 (standard volume)
Lignocaine 2% + adrenaline 1/80 000 (double volume)
P value
Maxillary molars Mandibular molars Maxillary premolars including canines Mandibular premolars including canines Maxillary incisors Mandibular incisors Total number of teeth
1 (0–3) 0 (0–2) 2 (0–3) 0 (0–4) 0 (0–2) 0 (0–4) 4 (1–9)
1 (0–3) 0 (0–3) 2 (0–3) 0 (0–3) 0 (0–4) 0 (0–3) 4 (1–7)
0.42 0.11 0.32 1.00 0.13 0.17 0.16
Table 3 – Median (range) pain intensity scores on 10 cm VAS on two separate occasions after bilateral `identical’ gingivectomy with standard or double volume lignocaine 2% and adrenaline 1/80 000 Hours after
Standard
Double
P value
0 1 2 3 4 5 6 7 8 9 10 11
0.0 (0.0–3.0) 0.0 (0.0–18.0) 1.0 (0.0–29.0) 2.0 (0.0–35.0) 2.5 (0.0–36.0) 3.0 (0.0–37.0) 4.0 (0.0–38.0) 4.5 (0.0–40.0) 4.0 (0.0–41.0) 2.0 (0.0–40.0) 0.5 (0.0–34.0) 0.0 (0.0–34.0)
0.0 (0.0–4.0) 0.5 (0.0–38.0) 3.5 (0.0–58.0) 5.0 (0.0–62.0) 6.0 (0.0–62.0) 6.5 (0.0–63.0) 7.5 (0.0–58.0) 5.5 (0.0–56.0) 5.0 (0.0–57.0) 2.0 (0.0–56.0) 0.5 (0.0–56.0) 0.0 (0.0–56.0)
0.66 0.24 < 0.003 < 0.01 < 0.006 < 0.01 < 0.005 < 0.02 < 0.04 0.08 0.21 0.23
Four patients took analgesics during the observation period. After the standard volume of local anaesthetic one patient took a tablet of paracetamol 500 mg and one a tablet of aspirin 300 mg, and after the double volume one patient took two tablets of paracetamol 500 mg six hours apart, one took a tablet of paracetamol 500 mg and one took aspirin 300 mg. The same patient took aspirin after both operations. All analgesics medications were bought over the counter, and gave sufficient pain relief. No patient experienced any wound complication (including signs of fibrinolytic activity or impaired epithelialization under the wound dressings) during the observation period or until the control visit 14 days after each operation.
DISCUSSION The duration and effectiveness of both volumes of local anaesthetics used were adequate for the operations done. The time used for infiltration anaesthesia was sufficient to allow the anaesthetic to start acting before the operation.10 The only clinical difference between the two treatments was in the intensity of pain during the postoperative period, and there was a dose-dependent (i.e. volume-dependent) increase in postoperative pain after gingivectomy with lignocaine
2% combined with adrenaline (1/80 000). By using an identical concentration of local anaesthetic solution, while increasing the infiltrated volume (which also increase the gingival tissue fluid content), we increased the amount of lignocaine and adrenaline in the gingival tissue.11 There are several possible mechanisms that explain the increase. Ischaemia caused by alterations in the peripherial blood flow in gingival tissue by the volume of local anaesthetic infiltrated, or caused by the local anaesthetic itself, may contribute to nociception. Ischaemia-induced accumulation of acid metabolites in gingival tissue together with biochemical mediators produced as a consequence of the surgical trauma, favour nociceptive mechanisms.12,13 The volume of fluid of the local anaesthetic may increase the pressure within the tissue space. Experiments with increased tissue expansion of human skin show reduced tissue circulation with subsequent transient effects on tissue oxygen tension,14,15 which generate increased cyclic adenosine monophosphate (cAMP) concentrations16 associated with nociceptive mechanisms.13 This is confirmed by a report that showed an increase in pain when the volume of injected subcutanously saline in the thigh of humans was increased from 0.5 ml to 1.5 ml.17 By contrast, subcutaneous tissue is organized differently from the well-perfused gingival tissues, and the ischaemia by the time of injection in our study was short-lived judged by the speed of the change of the gingival colour back to normal. One seems to be left with a likely option that the postoperative pain may be caused by the pharmacodynamic properties of the lignocaine or adrenaline, or both, constituent in the local anaesthetic combination. Lignocaine 2% given alone as a local anaesthetic does tend to increase peripheral blood flow in human gingiva, but lignocaine 1% with adrenaline 1/100 000 and lignocaine 2% with adrenaline 1/80 000 caused a reduction in blood flow that lasts for 60 to 90 minutes.18 There is apparently little reason to assume that the lignocaine itself contributed to the postoperative pain in the present study. Adrenaline is a potent stimulator of the adrenergic α-, β1-, and β2- receptors, and it is particularly effective on the oral mucosa, submucosa, and periodontium because of its α-receptor agonist effect that causes vascular constriction.19 cAMP is synthesized
Increased volume of lignocaine increases postoperative pain after gingivectomy
from adenosine triphosphate by the enzyme adenyl cyclase.20 Catecholamines, including adrenaline, act as adenyl cyclase activators and induce hyperalgesia, possibly through a cAMP-dependent process.13,21 Lignocaine 2% with adrenaline 1/100 000 infiltrated into the attached gingiva in experimental animals causes a rapid and obvious increase in gingival cAMP compared with non-anaesthesized gingiva.22 Infiltration of lignocaine 2% does not cause any rise in the cAMP concentrations.22 Periodonititis is a chronic inflammation that is associated with the production of hyperalgesic substances. Continuous release of inflammatory substances may have sensitized nociceptive mechanisms in the patients participating in our study, making them more susceptible to the effects of adrenaline.13 However, as all patients had completed the initial treatment and their chronic inflammation was reduced to the lowest possible minimum, it seems unlikely that this factor introduced bias into the study. It has been reported that 51–92% of patients after periodontal interventions reported pain.23–25 In the present study, 77% of the participants reported pain on at least one occasion after bilateral periodontal surgery. This incidence is in general agreement with those reported by others. The maximum mean pain index observed after double volume of local anaesthetic did not exceed 14 mm in the present study. The mean pain intensities after other types of oral surgery have been reported to range from as high as 65–70 mm26 to 40–50 mm27 after removal of impacted third molars down to about 30–35 mm after apiectomies.26 The most severe mean pain intensity observed in our study cannot be categorized as `severe pain’, but it was enough to differentiate between the postoperative pain intensities of the two different volumes of local anaesthetics. Several factors that may possibly be associated with increased postoperative pain after local anaesthetics containing lignocaine and adrenaline may have affected the results of this study. It is our experience that many clinicians think that large volumes of local anaesthetics ensure better local anaesthesia. Our study shows that the opposite seems true regarding the postoperative course, at least after gingivectomy, when using lignocaine 2% combined with adrenaline (1/80 000). We conclude that the use of large volumes of local anaesthetic containing lignocaine 2% and adrenaline (1/80 000) should be avoided in oral soft tissue surgery such as gingivectomy. Further clinical studies on the effect of adrenaline on postoperative pain after oral soft tissue surgery are advocated.
4. 5. 6.
7. 8.
9. 10. 11. 12.
13.
14. 15. 16. 17. 18. 19. 20. 21. 22. 23. 24. 25.
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British Journal of Oral and Maxillofacial Surgery
The Authors L. Jorkjend DDS, Dr Odont & LicOdont L. A. Skoglund DDS, DrSci Section of Dental Pharmacology and Pharmacotherapy University of Oslo Norway
Correspondence and requests for offprints to: Professor Dr. L. A. Skoglund, Section of Dental Pharmacology and Pharmacotherapy, University of Oslo, P.O. Box 1057 Blindern, N-0316 Oslo, Norway. Tel: + 47 22 85 60 62; Fax: + 47 22 85 44 40; E-mail: [email protected] Paper received 11 May 1998 Accepted 24 November 1999