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From the Department of Anesthesiology, University of Tsukuba Institute of Clinical Medicine, Tsukuba City, Ibaraki, Japan.
Address correspondence to: Dr. Y. Fujii, Department of Anesthesiology, University of Tsukuba Institute of Clinical Medicine, 2-1-1, Amakubo, Tsukuba City, Ibaraki 305-8576, Japan. Phone: +81-29-853-3763; Fax: +81-29-853-3765; E-mail: yfujii{at}md.tsukuba.ac.jp
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Abstract |
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Methods: In a randomized, double-blind, placebo-controlled trial, 90 patients, 40 males and 50 females, scheduled for elective plastic surgery received either lidocaine 20 mg plus metoclopramide 10 mg iv, lidocaine 20 mg iv, or placebo (saline); (n = 30 in each), with venous occlusion for one minute, followed by administration of propofol 0.5 mg•kg–1 into a dorsal hand vein. Pain was assessed on a four-point scale (0 = none, 1 = mild, 2 = moderate, 3 = severe) during propofol injection.
Results: 25 patients (83%) complained of pain in the placebo group, compared with 12 (40%) in the lidocaine group (P < 0.05) and three (10%) in the combination group (P < 0.05). Pain score (median) was less in the lidocaine (0) and combination (0) groups than in the placebo group (2); (P < 0.05). The difference in the incidence of pain between the combination and lidocaine groups was significant (P < 0.05).
Conclusion: A lidocaine/metoclopramide combination is more effective than lidocaine alone for reducing pain on injection of propofol in a peripheral vein.
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Methods |
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All patients received ranitidine 150 mg po as pre-medication 90 min before the induction of anesthesia. On arrival in the holding area of the operating room, a 20-G cannula was inserted into a vein of the dorsum of the hand without sc lidocaine infiltration. Patients were randomly assigned into three groups to receive iv either lidocaine 20 mg plus metoclopramide 10 mg, lidocaine 20 mg, or placebo (saline). A randomization list was generated by a random number function on a computer spreadsheet, resulting in a list of 30 assigned to patients receiving the study drug. Identical coded syringes were prepared by personnel not involved in the study. If the volume to be administered was < 3 mL, saline was added to a total volume of 3 mL. Venous occlusion involved occluding the forearm with a rubber tourniquet. The study drug was injected over ten seconds. After one minute, the occlusion was released and propofol (at room temperature) 2 mg•kg–1 was delivered through the iv cannula. During a ten-second pause after the first 25% of the calculated propofol dose had been given, the patients were asked standard questions regarding comfort of the injection. A blinded researcher (M.N.) evaluated propofol-induced pain using a verbal rating scale: 0 = none (negative response to questioning), 1 = mild pain (pain reported only in response to questioning without any behavioural signs), 2 = moderate pain (pain reported in response to questioning and accompanied by a behavioural sign or pain reported spontaneously without questioning, 3 = severe pain (strong vocal response or response accompanied by facial grimacing, arm withdrawal, or tears).8,9 Thereafter, induction of anesthesia continued with the remainder of the calculated dose of propofol. Vecuronium 0.2 mg•kg–1 iv was administered for muscle relaxation and to facilitate tracheal intubation, and anesthesia was maintained with sevoflurane 1.0% to 3.0% and nitrous oxide 66% in oxygen, with controlled ventilation. Within 24 hr after the operation, the injection site was checked for pain, edema and wheal and flare response by a researcher blinded to group assignment. Also, extrapyramidal reactions, such as dytonic-dyskinetic reactions, were recorded.
Based upon previously published data,4,8,9 the incidence of pain on injection of propofol is approximately 80%. An absolute reduction of 40% (from 80%–40%) with lidocaine or lidocaine plus metoclopramide would be considered to be of clinical importance. A sample size of 30 patients per group was estimated to provide 80% power to detect such a difference using a two-sided test with an 
= 0.05. Data were analyzed using ANOVA, Chi-square test (with Yate’s continuity correction), and Mann-Whitney U-test, where appropriate. Data are presented as mean ± SD, number (%), or median. P < 0.05 was considered significant.
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). The overall incidence and severity of pain during injection of propofol in the three groups is shown in Table II. The incidence of pain was less in patients receiving lidocaine (40%); (P < 0.05) or lidocaine plus metoclopramide (10%); (P < 0.05) than in those receiving placebo (83%). The difference was statistically significant between the lidocaine and lidocaine/metoclopramide groups (P < 0.05). The pain score (median) was 0 in the lidocaine group (P < 0.05) and 0 in the lidocaine/metoclopramide group (P < 0.05), compared with the placebo group (2). No complications such as pain, edema, wheal and flare response were observed at the injection site within the first 24 hr after the operation. Extrapyramidal reactions were not observed.
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Discussion |
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Although various pharmacological and nonpharmacological methods to decrease pain due to propofol injection have been tried, the most effective methods have been identified.3 Picard et al. have carried out a meta-analysis of 56 studies (n = 6,264 patients) in the prevention or mitigation of pain on propofol injection, and have concluded that lidocaine administration is the most effective method for minimizing pain during propofol injection.3 However, pretreatment with lidocaine cannot entirely control propofol-induced pain. The exact mechanism by which lidocaine reduces pain on injection of propofol is unknown, but there is a possibility that lidocaine, a local anesthestic, reversibly blocks peripheral nerve pathways through the action on excitable membranes in the arm.13 The dose (20 mg) of lidocaine used in the present study was based upon previous studies investigating the analgesic effect on pain during propofol injection.4,5 We found that with lidocaine pretreatment 12 patients (40%) still had pain with propofol injection, an incidence comparable with other studies.4,5
In a previous report by Gajraj et al.,14 patients receiving lidocaine 40 mg, without venous occlusion, experienced less pain on injection of propofol, compared with those receiving lidocaine 20 mg. Picard et al. compared three different techniques that include lidocaine administered iv before injection of propofol, after mixing with propofol, and lidocaine given iv with a tourniquet.3 They concluded that iv retention of lidocaine with a tourniquet was the most effective technique for controlling pain due to propofol injection. Using this technique, lidocaine 20 mg is sufficient to reduce propofol-induced pain.4,5 Further studies are needed to evaluate the analgesic efficacy of lidocaine 40 mg plus metoclopramide for minimizing such pain.
Metoclopramide shares structural and physicochemical properties with lidocaine,15 and is a weak local anesthetic in its own right.3 There are no established data to indicate the time for lidocaine and metoclopramide to access a potential peripheral bio-phase. In a previous report by Liaw et al.,7 lidocaine and metoclopramide were injected iv and retained in the veins for one minute, followed by tourniquet release and propofol injection. Similarly, in this study, we accepted that one minute was enough time for the study drug to achieve its peripheral actions. Increasing the tourniquet time may result in greater discomfort to the patient.
Larger doses (more than 20 mg) of metoclopramide occasionally cause dystonic and extrapyramidal reactions.6,14 However, in the present study, patients in the combination group received metoclopramide 10 mg, and none experienced extrapyramidal reactions. Also, no complications, such as pain, edema, or wheal and flare response were observed at the injection sites within the first 24 hr after the operation. Thus, the dose (10 mg) of metoclopramide used in this study appears to be safe.
In conclusion, a pretreatment with lidocaine 20 mg iv or lidocaine 20 mg plus metoclopramide 10 mg iv is effective in attenuating pain on injection of propofol. The lidocaine/metoclopramide combination is more effective than lidocaine alone for reducing such pain. Further studies are needed to determine the optimal dose of metoclopramide that should be added to lidocaine 20 mg to control propofol-induced pain.
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Footnotes |
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References |
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2 Scott RP, Saunders DA, Norman J. Propofol: clinical strategies for preventing the pain of injection. Anaesthesia 1988; 43: 492–4.[Medline]
3 Picard P, Tramer MR. Prevention of pain on injection with propofol: a quantitative systematic review. Anesth Analg 2000; 90: 963–9.
4 King SY, Davis FM, Wells JE, Murchison DJ, Pryor PJ. Lidocaine for the prevention of pain due to injection of propofol. Anesth Analg 1992; 74: 246–9.[Abstract]
5 O’Hara JR Jr, Sprung J, Laseter JT, et al. Effects of topical nitroglycerin and intravenous lidocaine on propofol-induced pain on injection. Anesth Analg 1997; 84: 865–9.[Abstract]
6 Watcha MF, White PF. Postoperative nausea and vomiting. Its etiology, treatment, and prevention. Anesthesiology 1992; 77: 162–84.[Medline]
7 Liaw WJ, Pang WW, Chang DP, Hwang MH. Pain on injection of propofol: the mitigating influence of metoclopramide using different techniques. Acta Anaesthesiol Scand 1999; 43: 24–7.[Medline]
8 Memis D, Turan A, Karamanlioglu B, Sut N, Pamukcu Z. The use of magnesium sulfate to prevent pain on injection of propofol. Anesth Analg 2002; 95: 606–8.
9 Agarwal A, Ansari MF, Gupta D, et al. Pretreatment wih thiopental for prevention of pain associated with propofol injection. Anesth Analg 2004; 98: 683–6.
10 Macario A, Weinger M, Truong P, Lee M. Which clinical anesthesia outcomes are both common and important to avoid? The perspective of a panel of expert anesthesiologists. Anesth Analg 1999; 88: 1085–91.
11 McCrirrick A, Hunter S. Pain on injection of propofol: the effect of injectate temperature. Anaesthesia 1990; 45: 443–4.[Medline]
12 Mangar D, Holak EJ. Tourniquet at 50 mm Hg followed by intravenous lidocaine diminishes hand pain associated with propofol injection. Anesth Analg 1992; 74: 250–2.[Abstract]
13 Lai YY, Chang CL, Yeh FC. The site of action of lidocaine in intravenous regional anesthesia. Ma Zui Xue Za Zhi 1993; 31: 31–4.[Medline]
14 Gajraj NM, Nathanson MH. Preventing pain during injection of propofol: the optimal dose of lidocaine. J Clin Anesth 1996; 8: 575–7.[Medline]
15 Desmond PV, Watson KJ. Metoclopramide: a review. Med J Aust 1986; 144: 366–9.[Medline]
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