Lidocaine Priming Reduces Tourniquet Pain During Intravenous Regional Anesthesia: A Preliminary Study Jean-Pierre Este`be, M.D., Ph.D., Marc E. Gentili, M.D., M.Sc., Gre´goire Langlois, M.D., Philippe Mouilleron, M.D., Franck Bernard, M.D., and Claude Ecoffey, M.D. Background and Objectives: Tourniquet pain often limits the use of intravenous regional anesthesia (IVRA). Intravenous (IV) lidocaine has been shown to be effective in the management of acute and neuropathic pains. We tested the hypothesis that a priming IV injection of lidocaine might have an analgesic effect on tourniquet pain during IVRA. Methods: A prospective, randomized, double- blind study was conducted on 40 patients scheduled for carpal tunnel decompression. No sedation was given. Each patient received either 1 mg/kg of IV lidocaine (group L) or 0.1 mL/kg of IV isotonic saline (group control ⫽ C) 5 minutes before IVRA. Thereafter, they received 3 mg/kg of plain 0.5 % lidocaine into the isolated and exsanguinated arm. A double-cuffed tourniquet was used. Pain at the tourniquet and the surgical sites was assessed every 5 minutes using a linear visual analog scale (VAS) and a verbal rating scale (VRS) during the surgical procedure and the immediate postoperative period (60 minutes). Results: Demographic data and duration of proximal and distal tourniquet were similar in each group. Significant differences in the pain scales were observed for the distal tourniquet at tourniquet inflation time and 15 minutes after (P ⫽ .03 and .005, respectively) in the group L. For the proximal tourniquet, only the VRS was significantly improved (P ⫽ .03). No analgesic benefit was observed in the immediate postoperative period. Conclusions: Priming IV lidocaine when compared with isotonic saline is effective in reducing tourniquet pain in IVRA. Reg Anesth Pain Med 2003;28:120-123. Key Words: Acute pain, Anesthetic techniques, Intravenous, Regional, Complications, Tourniquet pain, Local anesthetics, Lidocaine.
I
ntravenous regional anesthesia (IVRA) provides safe and effective anesthesia for hand surgery of 1-hour duration or less. However, tourniquet pain may limit its use in long-lasting surgical procedures.1 Theories regarding the etiology of tourniquet pain support that nerve ischemia and compression are the main cause of pain. Unmyelinated C-fibers have been recognized as representing an
From the Department of Anesthesia Intensive Care and Pain Clinic (University of Rennes 1), University Hospital of Rennes, France, and the Centre Me´dico-Chirurgical Saint–Vincent, SaintGre´goire, France. Accepted for publication January 21, 2003. Supported by the Department of Anesthesia Intensive Care and Pain Clinic, University Hospital of Rennes, France. Presented in abstract form in ASA Meeting, Orlando, FL, 2002. Reprint requests: Marc E. Gentili, M.D., M.Sc., Centre Me´dicoChirurgical Saint–Vincent, Saint-Gre´goire, 35760 France. E-mail:
[email protected] © 2003 by the American Society of Regional Anesthesia and Pain Medicine. 1098-7339/03/2802-0009$30.00/0 doi:10.1053/rapm.2003.50123
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important nociceptive pain pathway.2 Tourniquet pain is described as a dull and aching pain sensation that increases in severity with duration of tourniquet inflation despite otherwise adequate regional anesthesia.3 In an attempt to improve perioperative analgesia with IVRA, various adjuncts having local analgesic activity on peripheral nerves, such as meperidine4 or clonidine,5 have been added to the local anesthetic solution with varying degrees of effectiveness. In various acute painful states, intravenous lidocaine has been shown to have an analgesic effect.6-10 We therefore conducted a prospective study to examine the effect on tourniquet tolerance of a priming intravenous injection of lidocaine before IVRA.
Methods After local ethics committee approval and written informed consent, we investigated 40 ASA I-II ambulatory patients undergoing carpal tunnel decompression under IVRA. Patients treated with opioids,
Regional Anesthesia and Pain Medicine, Vol 28, No 2 (March–April), 2003: pp 120 –123
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tramadol, clonidine, beta-blockers, and calcium or sodium channel blockers were excluded, in consideration of potential adverse effects because of the combination with lidocaine or even an analgesic effect per se. Patients were allocated randomly into 2 groups according to the anesthetic regimen and were not sedated before or during the procedure. After application of standard monitoring and contralateral intravenous catheter, each patient received either 0.1 mL/kg of lidocaine 1% (group L ⫽ lidocaine) or isotonic saline (group C ⫽ control) intravenously 5 minutes before performing IVRA. The dose of 1mg/kg of IV lidocaine was chosen based on reports that low-doses of lidocaine could reduce hyperalgesia.11 A delay of 5 minutes before the IVRA was chosen to obtain peak plasma levels of lidocaine at the start of IVRA.12 A double tourniquet was positioned on the upper limb, which was then elevated and wrapped with an Esmarch bandage for exsanguination. The proximal tourniquet was inflated to 100 mm Hg above the systolic arterial blood pressure. All patients received 3 mg/kg of plain lidocaine 0.5% (Xylocaine®, Astra Zeneca, Rueil–Malmaison, France). Anesthetic solutions were administered by a blinded anesthesiologist unaware of the injected priming solutions. Symptoms of dizziness, nystagmus, tinnitus, facial dysesthesia, dysphoria, convulsions, depression of the central nervous system, and depression of the cardiovascular system (ie, bradypnea, bardycardia, hypotension) were recorded by a blinded resident. When patients complained of pain at the tourniquet site, the distal tourniquet was inflated at the same pressure and the proximal cuff was then deflated. A blinded observer assessed pain every 15 minutes after tourniquet placement and every 15 minutes after tourniquet release for a total of 60 minutes. Pain evaluation used a visual analog scale (VAS) graded from 0-100 mm and a verbal rating scale (VRS) graded as no pain ⫽ 0, mild pain ⫽ 1, moderate pain ⫽ 2, severe pain ⫽ 3, and excruciating pain ⫽ 4. When patients complained of pain (VAS ⬎ 3) postoperatively, they received 1,000 mg of paracetamol orally and were subsequently treated as necessary with the same drug before discharge. We considered a preliminary clinical study (unpublished data) exhibiting that a clinically significant benefit of using priming IV lidocaine would reduce the final pain score (VAS) of the distal cuff by 15% (primary endpoint) when compared with the isotonic saline group control. The study was designed to detect a difference between groups on this primary endpoint with 95% power and the type I error (2 sided) being set at 5%. Enrollment of at least 15 patients in each group was required (40
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patients were included). Results are reported as mean ⫾ standard deviation and median. Comparison of categorical variables was carried out with the chi-squared test. Data were analyzed using an analysis Kruskal-Wallis test (P ⬍ .05 was significant) when variances were not comparable.
Results There was no significant difference between groups in patient demographic data (Table 1) or length and type of surgery (27 ⫾ 8 v 28 ⫾ 9 minutes for group C and group L, respectively). After IV priming, a mild dysphoria was reported in 4 patients in group L, although no light headedness, tinnitus or metallic taste were claimed and it was resolved at the time of performing the IVRA. No patient complained of any similar symptoms when the distal cuff was deflated. No other adverse effect was noticed. Duration of application of the proximal tourniquet (17 ⫾ 4 v 20 ⫾ 6 minutes for group C and group L, respectively) and of the distal tourniquet (26 ⫾ 4 and 25 ⫾ 6 minutes for group C and group L, respectively) was similar in both groups. For the proximal tourniquet, despite the lack of significant difference between the 2 groups with regard to VAS and VRS, patients with a VAS ⬎30 was more frequent in group C when compared with group L (⬎0 % v 35 % at TO; 20 % v 45 % at T15 minutes and 15 % v 50 % at the deflation of the proximal cuff). A significantly lower VAS and VRS in group L was observed for the distal tourniquet at T0 and T15 (P ⫽ .03 and .005, respectively) (see Table 2 and Fig 1). For the proximal tourniquet, only the VRS was significantly lower in group L (P ⫽ .03). Despite a tendency for decreased pain scores in group L, no significant benefit was observed in the immediate postoperative period. The duration of postoperative analgesia was slightly prolonged in group L (delay before the first paracetamol request: 20 ⫾ 15 v 35 ⫾ 20 minutes for group C and group L, respectively; P ⫽ .05) (Table 3). Arterial pressure, heart rate, respiratory rate, and pulse oxymetry remained stable during the study, and no adverse effect because of the use of local anesthetic was recorded. No patient complained of postoperative nausea and vomiting. Table 1. Demographic Data
Group L Group C
Age (yr)
Weight (kg)
Height (cm)
Sex Ratio (F/M)
53 ⫾ 15 51 ⫾ 14
71 ⫾ 16 69 ⫾ 12
164 ⫾ 9 166 ⫾ 8
12/8 9/11
NOTE. Group L ⫽ lidocaine, Group C ⫽ control, and values ⫽ mean ⫾ SD.
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Regional Anesthesia and Pain Medicine Vol. 28 No. 2 March–April 2003 Table 2. Intraoperative Pain Data T0 (min)
VAS
Group C
(0-100)
Group L
VRS (0-4)
Group C Group L
T15 (min)
T defl (min)
PT
DT
Surg
PT
DT
Surg
PT
DT
22 ⫾ 21 (0-63) 13 ⫾ 14 (0-30) 2 (0-4) 1 (0-4)
23 ⫾ 18 (0-60) 12 ⫾ 12* (0-45) 3 (0-4) 1 (0-3)*
17 ⫾ 16
28 ⫾ 19 (0-70) 17 ⫾ 11 (0-35) 3 (0-4) 2 (0-3)*
22 ⫾ 17 (0-60) 14 ⫾ 14* (0-55) 3 (0-4) 2 (0-3)*
3⫾3
32 ⫾ 22 (0-80) 22 ⫾ 15 (0-60) 3 (1-4) 2 (1-4)
25 ⫾ 22 (0-80) 20 ⫾ 17 (0-65) 3 (1-4) 2 (1-4)
8⫾8 1 (0-3) 1 (0-2)
8⫾7 1 (0-4) 0 (0-1)
NOTE. Mean value ⫾ SD or median and range. Abbreviations: VAS, visual analog scale; VRS, verbal rating scale; PT, proximal tourniquet; DT, distal tourniquet; surg, surgical site; T defl, tourniquet deflation. *P ⬍ 0.05.
Discussion Lidocaine has been administered for a broad variety of painful disorders.6-9 In our study, the priming intravenous injection of lidocaine before IVRA improved tourniquet tolerance to a statistically significant extent. The role of A␦ fibers and unmyelinated C-fibers1,2 may be considered to be partly involved in tourniquet pain because of the circumferential compression of peripheral nerves enhanced by ischemia. After our preliminary clinical study (unpublished data) using a dose ranging from 0.5 to 1.5 mg/kg, we chose a 1 mg/kg dose of lidocaine, believing this dose might provide a systemic effect without side effects. A similar dose has also been used in an IV analgesic study with lidocaine.13 The delay of 5 minutes before IVRA was chosen to coincide with the systemic peak plasma lidocaine concentration when administered intravenously.12 We considered that at the time of de-
flation of the distal cuff (around 50 minutes), lidcaine was still largely retained in the isolated arm14 and therefore the total systemic dose would remain moderate. Two previous studies aimed to evaluate and correlate the analgesic effect of intravenous lidocaine with blood levels. In volunteers undergoing tourniquet-induced ischemia, no analgesic effect was shown at lidocaine levels of 2 to 3 g/ml. The authors concluded that these blood levels might produce sedation but not analgesia.15 In the second study, pain in 5 patients with various neuropathic syndromes was reduced when toxic lidocaine levels (⬎3 g/mL) were achieved following a total dose of 3 mg/kg.16 Non–sodium channel mechanisms are also plausible explanations for the antihyperalgesic actions of lidocaine, including inhibition of substance P,17 NMDA receptors,18 and glutamate activity.19 A study using the isolated arm technique in humans20 supports a peripheral analgesic effect of regional intravenous infusion of lidocaine on the development of mechanical-induced hyperalgesia and histamine-induced itching, but not touch perception and heat-induced nociception.
Conclusion Our results suggest an analgesic effect of lidocaine (1 mg/kg) administered intravenously 5 minutes Table 3. Postoperative Pain Data
Fig 1. VAS during IVRA. Box plots represents median (50th), range (25th-75th), and whisker (10th-90th) for control (group C) and lidocaine groups (group L) with proximal (PT) and distal tourniquet (DT).
VAS
Group C
(0-100)
Group L
VRS (0-4)
Group C Group L
T0
T30
T60
15 ⫾ 17 (0-35) 14 ⫾ 14 (0-30) 2 (0-3) 1 (0-3)
22 ⫾ 22 (0-60) 19 ⫾ 19 (0-45) 2 (0-4) 1 (0-4)
30 ⫾ 17 (0-60) 20 ⫾ 20 (0-50) 3 (1-4) 2 (0-4)
NOTE. Mean value ⫾ SD or median and range. Abbreviations: VAS, visual analog scale; VRS, verbal rating scale.
Lidocaine Priming Improves IVRA
before tourniquet inflation in IVRA. Whether our statistically significant results are ultimately clinically significant is unclear, particularly considering that pain was consistently reduced only during distal tourniquet cuff inflation. Therefore, this study could be a preliminary basis for subsequent investigations to evaluate the dose ranging and the timing of lidocaine priming in IVRA as a means of reducing tourniquet pain.
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