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Anesthesia & Analgesia:
doi: 10.1213/ane.0b013e31816174c3
Regional Anesthesia: Research Report

Vasoconstriction and Analgesic Efficacy of Locally Infiltrated Levobupivacaine for Nasal Surgery

Demiraran, Yavuz MD*; Ozturk, Ozcan MD†; Guclu, Ender MD†; Iskender, Abdulkadir MD*; Ergin, Mehmet Hakan MD*; Tokmak, Abdurahman MD†

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From the Departments of *Anesthesiology, and †Otorhinolaryngology, University of Duzce, Duzce Faculty of Medicine, Duzce, Turkey.

Accepted for publication November 1, 2007.

Address correspondence and reprint requests to Yavuz Demiraran, MD, Department of Anesthesiology, Faculty of Medicine, University of Duzce, Duzce, Turkey. Address e-mail to

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BACKGROUND: In this study, we compared the use of preincisional lidocaine 2% with epinephrine (LA) and levobupivacaine 0.25% plain (LB) for postoperative analgesia and vasoconstriction in patients undergoing nasal surgery.

METHODS: Sixty patients were randomly assigned to receive preincisional local infiltration under general anesthesia. Group LB received levobupivacaine 0.25%, and group LA received epinephrine plus lidocaine 2% (add volume injected). Intraoperative hemodynamic changes, pre- and postoperative hemoglobin and hematocrit values were recorded. Visual analog scale values 30 min and 1, 2, 8, 12, and 24 h postoperatively and the need for rescue analgesic treatment in the first 24 h of all patients was recorded.

RESULTS: At 30 min and 1, 2, 8, and 12 h postoperatively, visual analog scale values were lower in group LB than in group LA (P < 0.0001, P = 0.002, P = 0.023, P < 0.0001, and P = 0.011, respectively). The analgesic requirement was significantly lower in group LB when compared with that in group LA (P = 0.038). Group LB had significant differences between preoperative and postoperative hemoglobin and hematocrit values (P = 0.014 and 0.025). Group LA had significant differences between preoperative and postoperative hemoglobin and hematocrit values (P = 0.031 and 0.024).

CONCLUSIONS: We conclude that postoperative analgesia in nasal surgery with local infiltration of levobupivacaine was significantly more potent and longer lasting than that achieved by lidocaine plus epinephrine.

Infiltrative local analgesia combined with moderate sedation is a well accepted and safe anesthetic method for many surgical procedures.1,2 Combined with general anesthesia, local anesthetic infiltration can reduce the need for systemic analgesia3; the addition of vasoconstricting drugs may reduce intraoperative bleeding.4 Although the use of vasoconstrictive substances such as epinephrine, norepinephrine, and ornipressin decreases the local perfusion and almost doubles the duration of local anesthetic activity, a reactive hyperemia is often observed, thus adding to an increased swelling in the operative area.5 Likewise, there is also concern of complications due to systemic absorption of epinephrine in patients with arteriosclerosis, hypertension, ischemic heart disease and other cardiac problems, anemia, preexistent liver or renal damage, and endocrinologic dysfunction (hyperthyroidism, phaeochromocytoma, diabetes mellitus).6

Levobupivacaine is a long-acting local anesthetic that has vasoconstrictive activity in concentrations of ≤0.25%.7 Clinical studies have tested the efficacy of levobupivacaine in a wide spectrum of operations and anesthetic methods including local infiltration. The duration of action has been reported to be between 4 and 24 h with local infiltration of levobupivacaine.8–10 The goal of this study was to compare the analgesic efficacy and blood loss of preincisional lidocaine 2% with epinephrine (LA) and levobupivacaine (LB) 0.25% in patients undergoing nasal surgery.

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The study was approved by our IRB, and written informed consent was obtained from all subjects. Sixty patients with ASA physical status of I–II, aged 18–55 yr, and scheduled for elective nasal surgery under general anesthesia were prospectively studied. The exclusion criteria included contraindications to any of the drugs used in the study; age <18 or >65 yr; evidence of severe cardiovascular, renal, hematologic, hepatic, or respiratory disease; preexisting neurological or psychiatric illness; diabetes or peripheral neuropathy; as well as patients receiving chronic analgesic therapy or having a history of alcohol or drug abuse.

On arrival in the anesthetic room, a vein was cannulated, arterial blood pressure was measured with an automated oscillometer, and monitoring of arterial oxygen saturation and the electrocardiogram were commenced. Anesthesia was induced with 1–2 μg/kg fentanyl, 0.6 mg/kg rocuronium, and 1–3 mg/kg propofol, and maintained with nitrous oxide 66% in oxygen and sevoflurane. The end-tidal concentration of sevoflurane was monitored using a respiratory gas monitor and adjusted to 1.5 MAC adjusted for age and concomitant use of nitrous oxide (1.5%–1.8% sevoflurane). Patients were randomly allocated into two groups to receive either 0.25% levobupivacaine (Chirocaine® 0.25% (2.5 mg/mL); Abbott, Nycomed Pharma AS NO-2418 Elverum, Norway) (group LB; n = 30) or lidocaine 2%, 1.25:100,000 epinephrine (Jetocaine® amp, Adeka, Turkey) (group LA; n = 30) preincisional local infiltration of the nasal region. Septoplasty patients received 5 mL and rhinoplasty and functional endoscopic sinus surgery patients received 10 mL of either solution. To avoid operator dependence, all infiltrations were performed by the same physician. The surgeon and the anesthesiologist were blinded to the contents of the local anesthetic solutions until the end of the study.

Criteria for home discharge were stable vital signs and the capability to walk and void spontaneously without nausea or pain. The use of the visual analog scale (VAS) was described at the postoperative visit and the effectiveness of analgesia was measured by visual analog pain scores on movement (VAS score, 0–100) at postoperative periods 30 min and 1, 2, 8, 12, and 24 h. Patients with a pain score more than 40 were treated with 20 mg tenoxicam (Tilcotil® flk, Roche Farma, 4153 Reinach, Switzerland) IV. The occurrence of adverse events, including hypotension (decrease in systolic arterial blood pressure from 30% of baseline), hypertension (increase in systolic arterial blood pressure from 30% of baseline), and bradycardia (heart rate of <50 bpm) were also recorded. A follow-up evaluation was performed the day after the surgery by asking the patients about occurrence of pain.

A power calculation ensured that 30 patients were recruited to provide 90% power for a difference in VAS from 10 mm versus 20 mm at the 5% significance level. Data were recorded and calculations were made using the software program SPSS for Windows version 10.0. The χ2 test, Student's t-test, and Mann–Whitney U-test were used for statistical analysis. Results were expressed as mean standard deviation, and P values <0.05 were accepted as statistically significant.

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There were no differences between groups regarding age, body mass index, gender, duration of surgery, and operation types (Table 1). At 30 min and 1, 2, 8, and 12 h postoperatively, VAS values were lower in group LB than in the LA group (P < 0.0001, P = 0.002, P = 0.023, P < 0.0001, and P = 0.011, respectively) (Table 2). The need for supplemental analgesia was significantly lower in patients of group LB when compared with that of group LA (P = 0.038) (Table 3).

Table 1
Table 1
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Table 2
Table 2
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Table 3
Table 3
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Hemoglobin and hematocrit values in both groups showed significant decreases postoperatively (group LB P = 0.014 and 0.025, and group LA P = 0.031 and 0.024, respectively; Table 3) compared with preoperative (baseline) values. No significant difference was observed between study groups regarding the preoperative and postoperative hemoglobin values (P = 0.133 and 0.942, respectively) and preoperative and postoperative hematocrit values (P = 0.519 and 0.978, respectively).

No patient experienced hypotension, hypertension, and bradycardia in the perioperative period.

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This study demonstrates that, compared with infiltration with lidocaine 2% with epinephrine, infiltration of levobupivacaine 0.25% locally in the nasal region improves postoperative analgesia and reduces the need for supplemental analgesia during the first 24 h after nasal surgery.

Although local tissue infiltration has long been established as a reliable pain relief technique,10 interest in the use of this technique has increased. The main advantages of this technique are its simplicity and safety. Specifically, the use of local anesthetics for tissue infiltration, in combination with general anesthesia, has been investigated during some operations in several studies.11,12 Local infiltrative analgesia has been used successfully in combination with general anesthesia for facial cosmetic operations.13 Local infiltration of epinephrine-containing local anesthetics is widely used in clinics particularly for surgeries on vascular areas, to provide good analgesia and hemostasis. Levobupivacaine has been introduced for infiltration anesthesia with concentrations of ≤0.25% and reportedly has vasoconstrictive effects at these concentrations.7

It has been reported that the clinical efficacy of levobupivacaine and racemic bupivacaine are similar when they are used for infiltration anesthesia after herniorrhaphy.14 Bay-Nielsen et al.14 found no difference between the use of 50 mL of 0.25% levobupivacaine and the use of an equivalent amount of 0.25% bupivacaine in effecting pain relief after inguinal hernia repair. Likewise, levobupivacaine was found to achieve better postoperative analgesia than ropivacaine when used as preincisional local infiltration for inguinal hernia repair, laparoscopic cholecystectomy, and mastopexy.15–17 Preclinical and clinical studies of levobupivacaine have demonstrated lower risk profiles compared with racemic bupivacaine, historically, the long-acting local anesthetic of choice. Thus, levobupivacaine can be regarded as equipotent, but with significantly fewer reported cardiotoxic and neurotoxic effects compared with bupivacaine.18–20 Its vascoconstrictive effects may also be advantageous for infiltrative techniques.

In the present study, although postoperative hematocrit and hemoglobin values were significantly decreased in both groups when compared with preoperative values, no significant difference was observed between postoperative hematocrit and hemoglobin values in either group (Table 2). These results indirectly suggest the presence of the vasoconstrictive activity of levobupivacaine in these concentrations. A control group undergoing saline injection may have validated our hypothesis regarding the vasoconstrictive effects of levobupivacaine.

In conclusion, postoperative analgesia achieved by locally infiltrated levobupivacaine was significantly more potent and longer lasting than that achieved by lidocaine plus epinephrine in patients undergoing nasal surgery. In addition, 0.25% levobupivacaine alone is as effective as lidocaine plus epinephrine for the control of bleeding during nasal surgery.

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1. O'Donoghue JM, Chaubal ND, Haywood RM, Rickard R, Desai SN. An infiltration technique for reduction mammaplasty: results in 192 consecutive breasts. Acta Chir Plast 1999;41:103–6

2. Klein JA. Anesthesia for liposuction in dermatologic surgery. J Dermatol Surg Oncol 1988;14:1124–32

3. Bisgaard T, Klarskov B, Kristiansen VB, Callesen T, Schulze S, Kehlet H, Rosenberg J. Multi-regional local anesthetic infiltration during laparoscopic cholecystectomy in patients receiving prophylactic multi-modal analgesia: a randomized, double-blinded, placebo-controlled study. Anesth Analg 1999;89: 1017–24

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5. Koeppe T, Constantinescu MA, Schneider J, Gubisch W. Current trends in local anesthesia in cosmetic plastic surgery of the head and neck: results of a German national survey and observations on the use of ropivacaine. Plast Reconstr Surg 2005;115:1723–30

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8. Ausems ME, Hulsewe KW, Hooymans PM, Hoofwijk AG. Postoperative analgesia requirements at home after inguinal hernia repair: effects of wound infiltration on postoperative pain. Anaesthesia 2007;62:325–31

9. Alessandri F, Lijoi D, Mistrangelo E, Nicoletti A, Ragni N. Effect of presurgical local infiltration of levobupivacaine in the surgical field on postsurgical wound pain in laparoscopic gynecological surgery. Acta Obstet Gynecol Scand 2006;85: 844–9

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12. Ure BM, Troidl H, Spangenberger W, Neugebauer E, Lefering R, Ullmann K, Bende J. Preincisional local anesthesia with bupivacaine and pain after laparoscopic cholecystectomy. A double-blind randomized clinical trial. Surg Endosc 1993;7: 482–8

13. Mottura AA. The tumescent technique for face lifts? Plast Reconstr Surg 1995;96:231–2

14. Bay-Nielsen M, Klarskov B, Bech K, Andersen J, Kehlet H. Levobupivacaine vs bupivacaine as infiltration anaesthesia in inguinal herniorrhaphy. Br J Anaesth 1999;82:280–2

15. Kakagia D, Fotiadis S, Tripsiannis G. Levobupivacaine versus ropivacaine infiltration analgesia for mastopexy: a comparative study of 2 long-acting anesthetic drugs in infiltrative anesthesia for mastopexy. Ann Plast Surg 2005;55:258–61

16. Kingsnorth AN, Cummings CG, Bennett DH. Local anaesthesia in elective inguinal hernia repair: a randomised, double-blind study comparing the efficacy of levobupivacaine with racemic bupivacaine. Eur J Surg 2002;168:391–6

17. Louizos AA, Hadzilia SJ, Leandros E, Kouroukli IK, Georgiou LG, Bramis JP. Postoperative pain relief after laparoscopic cholecystectomy: a placebo-controlled double-blind randomized trial of preincisional infiltration and intraperitoneal instillation of levobupivacaine 0.25%. Surg Endosc 2005;19: 1503–6

18. Denson DD, Behbehani MM, Gregg RV. Enantiomer-specific effects of an intravenously administered arrhythmogenic dose of bupivacaine on neurons of the nucleus tractus solitarius and the cardiovascular system in the anesthetized rat. Reg Anesth 1992;17:311–6

19. Foster RH, Markham A. Levobupivacaine: a review of its pharmacology and use as a local anaesthetic. Drugs 2000;59: 551–79

20. Mazoit JX, Boico O, Samii K. Myocardial uptake of bupivacaine: II. Pharmacokinetics and pharmacodynamics of bupivacaine enantiomers in the isolated perfused rabbit heart. Anesth Analg 1993;77:477–82

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