|Year : 2015 | Volume
| Issue : 1 | Page : 31-34
Effects of dexmedetomidine and lidocaine in alleviating propofol injection pain: A randomized controlled trial
Huidrom Shubhaschandra Singh, Lairenlakpam Deban Singh, Nongthombam Ratan Singh, Takhelmayum Hemjit Singh, Rupendra Singh Thokchom, Priyadarshini Sharma Monohar
Department of Anaesthesiology, Regional Institute of Medical Sciences, Imphal, Manipur, India
|Date of Web Publication||17-Jun-2015|
Dr. Takhelmayum Hemjit Singh
Department of Anaesthesiology, Regional Institute of Medical Sciences, Imphal - 795 004, Manipur
Source of Support: None, Conflict of Interest: None
Objective: Propofol, an intravenous (IV) anesthetic, can irritate the skin, mucous membrane, and venous intima. The main drawback is the pain on injecting it. We compared the analgesic effects of lidocaine, dexmedetomidine, and saline (placebo) in ameliorating propofol injection pain. Materials and Methods: Following the approval of the hospital's Ethics Committee, 105 adult patients of both sexes [aged 18-70 years, American Society of Anesthesiologists (ASA) I and II] were divided into three groups (n = 35) to receive 5 ml of IV saline (placebo), 0.25 μg/kg of dexmedetomidine, and 0.5 μg/kg of lidocaine diluted in 5 ml of saline at an ambient operating room temperature in a randomized and double blinded fashion to compare the pain-relieving effects of the drugs during propofol injection before the patients lost consciousness. The propofol injection pain was assessed according to the McCrirrick and Hunter scale. Result: Dexmedetomidine (as seen in 62.86% of the patients) and lidocane (as seen in 80% of the patients) had complete pain relief as compared to placebo. Conclusion: Pretreatment with 0.25 µg/kg of dexmedetomidine with venous occlusion for one min is also as effective as IV lidocaine pretreatment in alleviating propofol injection pain when compared to placebo, even though lidocaine is better than dexmedetomidine.
Keywords: Dexmedetomidine, Lidocaine, Pain, Propofol
|How to cite this article:|
Singh HS, Singh LD, Singh NR, Singh TH, Thokchom RS, Monohar PS. Effects of dexmedetomidine and lidocaine in alleviating propofol injection pain: A randomized controlled trial. J Med Soc 2015;29:31-4
|How to cite this URL:|
Singh HS, Singh LD, Singh NR, Singh TH, Thokchom RS, Monohar PS. Effects of dexmedetomidine and lidocaine in alleviating propofol injection pain: A randomized controlled trial. J Med Soc [serial online] 2015 [cited 2020 Oct 22];29:31-4. Available from: https://www.jmedsoc.org/text.asp?2015/29/1/31/158929
| Introduction|| |
Propofol, a widely used induction agent in anesthesia, has the main drawback of pain on injection that ranged 24-70%; , this ranks seventh in order of frequency and clinical importance. 
Several interventions have been advocated to alleviate the pain associated with propofol injection, which include addition of lidocaine, cooling of propofol, dilution of propofol, injection of propofol into a large vein, and prior administration of ephedrine, ondansetron, metoclopramide, opioids, thiopental, ketamine,  acetaminophen,  tramadol,  different doses of lidocaine,  and different concentrations of propofol  and topical nitroglycerin. 
Among the interventions, intravenous (IV) lidocaine, a time-tested local anesthetic of the amide group, is the most commonly used drug but it has a failure rate of 13-32%. 
On the other hand, dexmedetomidine, a highly selective, specific, and potent α2 adrenoceptor agonist, has sedative, analgesic, and sympatholytic actions, along with supraspinal, spinal, and peripheral actions and anxiolytic property. It has been shown to promote antinociception and can be used to provide relief to propofol injection pain. 
The purpose of this study is to compare the effects of prior administration of dexmedetomidine, lidocaine, and normal saline in reducing propofol injection pain.
| Materials and Methods|| |
A prospective, randomized, double blinded, and placebo-controlled study was conducted in the department of anesthesiology of a tertiary care hospital in Imphal, Manipur during the period of 2 years from October 2011 to September 2013. After obtaining consent from the hospital's Ethics Committee and informed consent from the patients, 105 adult patients of American Society of Anesthesiologists (ASA) I and II status, aged 18-70 years of both sexes who were scheduled for elective surgeries, were undergoing general anesthesia, and fulfilled the inclusion criteria were enrolled for a standardized generalized anesthetic procedure, and the patients were divided into three groups.To detect a 50% reduction at a significant level of 5% and probability of 80%, this study required at least 35 patients per group, estimating the frequency of 80% of the patients who were to experience pain withdrawal movement on injection of propofol based on a previous study. 
The patients with difficulty in communication, history of adverse effects to propofol, study drugs, and also those who required rapid sequence induction, along with those having difficulty in venous access were excluded from the study.
The patients enrolled were asked to report their pain according to the scale provided to them in the form of none, mild, moderate, and severe (verbal rating scale). 
In the operation room, a 20G cannula was inserted in the dorsa of both hands: One for IV saline and another for drug injection. Standard monitors, namely, electrocardiogram (ECG) device, pulse oximeter, and automatic noninvasive arterial blood pressure monitor were instituted. All the patients were premedicated with injections of 50 mg of IV ranitidine and 0.005 mg/kg of intramuscular (IM) glycopyrrolate at least 1 h before the surgery. The study drug kept at room temperature was prepared by an independent anesthesiologist not involved in the study and was divided into equal volumes of 5 ml with the addition of normal saline. The patients received normal saline (5 ml IV) in Group I, 0.2µg/kg of dexmedetomidine IV diluted in 5 ml normal saline in Group II, and 0.5 mg/kg of lidocaine IV diluted in 5 ml normal saline in Group III.
With the aim of keeping the drug within the vein, the forearm was squeezed with a pneumatic tourniquet up to 70 mmHg to occlude the vein for 1 min. , The study drug was injected through the cannula over 5 s. After 1 min, the occlusion was released and 25% of the induction dose of propofol (2 mg/kg) was administered over 10 s by a mechanical syringe. During propofol injection, the patients were asked standard questions regarding the comfort of the injection and were continuously observed for vocal response, facial grimacing, arm withdrawal, or tears suggesting severe pain. Pain was graded using the four point scale of McCrirrick et al. 
After the assessment of pain, induction of anesthesia was completed with the remaining dose of propofol, and tracheal intubation was facilitated with the injection of succinylcholine. Anesthesia was maintained with isoflurane, injection of atracurium, nitrous oxide (66%) in oxygen, and injection of tramadol with controlled ventilation.
The data collected were tabulated and analyzed by using the statistical package for social sciences, Windows-based version 16.0 (SPSS Inc., Chicago, IL, USA). The patients' characteristics were analyzed by using one-way analysis of variance (one-way ANOVA) and chi-square test was used for comparison of the categorical data.
| Results|| |
The demographic profiles of the three groups are shown in [Table 1]. The sex distribution was as follows: Males/females of 9/26, 10/25, and 7/28 in Group I, Group II, and Group III, respectively. There was a female preponderance in all the groups, which was statistically insignificant (P = 0.69).
[Table 2] and [Figure 1] show the distribution of the pain in the three groups during the injection of propofol. The number of patients with no pain were 12 (34.29%) in Group I, 22 (62.86%) in Group II, and 28 (80%) in Group III. Mild pain was experienced by 22 (62.86%), 12 (34.29%), and 6 (17.14%) patients in Group I, Group II, and Group III, respectively. Moderate pain was observed in 2.86% of patients in Group II; however, it was absent in Group I and Group III. Severe pain was observed in only one patient (2.86%) in Group I. Overall, the pain during injection was experienced by 23 (65.71%) patients in Group I, followed by 13 (37.14%) and 7 (20%) patients in Group II and Group III, respectively. This distribution of pain grades was statistically significant (P = 0.004).
|Figure 1 : Bar diagram showing the distribution of pain during propofol injection among the patients in the three groups|
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|Table 2: The distribution of pain during propofol injection among the patients in the three groups|
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| Discussion|| |
Propofol, an excellent IV anesthetic belonging to the phenol group, can irritate the skin, the mucous membrane, and the venous intima. The mechanism of pain is attributed to the activation of the kinin-kallikrein system that releases bradykinin,  causing vasodilatation and hyperpermeability, thereby increasing contact between the aqueous phase propofol and the free nerve endings.
In the present study, the patients were equally distributed in all the three groups according to their age, weight, and height. A higher number of female patients in the study (male: female ratio being 26:79) was due to the fact that most of the operations performed were cholecystectomy, as cholelithiasis has a female preponderance.
Several authors have studied the mechanisms and methods of reducing propofol injection pain. In a study by King et al.,  it was found that lidocaine (20 mg IV) significantly reduced the incidence and severity of pain with propofol injection, but about 6% of patients still suffered pain if the dorsum of the hand was used. Cameron et al.  reported that the minimum effective dose of lignocaine, required to prevent propofol injection pain was 0.2 mg/kg when veins of the dorsum of the hand were used, and they concluded that injection pain should not limit the use of propofol in children if an adequate amount of lignocaine was immediately mixed prior to injection. In the present study, we used veins of the dorsum of the hand for propofol injection.
Robert et al.  showed that lidocaine, (2 ml of 2% i.e. 40 mg ) when mixed with propofol was more effective in reducing the pain on propofol injection (P < 0.001) than when given as a pretreatment. Lee and Russel  reported a decreased incidence of propofol injection pain in the propofol mixed group (2 ml of 2% lidocaine) compared to the lidocaine (4 ml 1%) pretreatment group. We used 2% lidocaine concentration at a dose of 0.5 mg/kg, which was effective in reducing the pain of propofol injection.
In our study, 80% of the cases had no pain and 17.14% had mild pain in the lidocaine group (P = 0.004) that is comparable to the study conducted by Tsubokura et al.,  who observed that the incidence of propofol-induced pain was significantly more frequent (P < 0.001) in the control group (70%) than in the other groups (20% each). The application of tourniquet in the lignocaine group is an undeniably effective method and also simple to perform. 
We observed that 37.14% of the patients in the dexmedetomidine group experienced pain as compared to 20% in the lidocaine group. These findings were comparable to that of Turan et al.  who had reported pain in 33.34% of the patients in the dexmedetomidine group as compared to 23.34% in the lidocaine group. Our study also showed the pain grading in which 34.29% of the patients in the dexmedetomidine group experienced mild pain as compared to 17.14% in the lidocaine group. The number of patients with moderate and severe pain in the dexmedetomidine group was 2.86% and 0% as compared to 0% and 2.86%, respectively, in the lidocaine group. This pain grading was also comparable to that of Turan et al.  who showed that 30%, 3.33%, and 0% of the patients had experienced mild, moderate, and severe pain in the dexmedetomidine group as compared to 20%, 3.33% and 0% of the patients respectively in the lidocaine group. Our findings were also comparable to the ones in studies by Uzun et al.  and Sarkilar et al.  who demonstrated pain in 43% (0.25 μg/kg) and 45.5-66.3% (0.5-1 μg/kg) of the patients, respectively, in the dexmedetomidine group. However, the number of patients who had experienced pain in the control group of our study was 65.71% that was different from the studies of Turan et al.,  Uzun et al.,  and Sarkilar et al.  who reported pain in 86.7%, 80%, and 71.1% of the patients, respectively, in their control groups (normal saline). The possible mechanism involved in decreasing propofol injection pain by dexmedetomidine is not fully understood. The possible mechanism might be due to alpha1 and alpha2 stimulation causing release of vasodilator prostaglandins that antagonize the vasoconstrictor response. This modulation of the sympathetic response of the venous smooth muscle might be important in endothelial dysfunction caused by propofol.  It may be due to hyperpolarization-activated conductance in the peripherally mediated antinociception, but the peripheral analgesic effects of dexmedetomidine have not yet been fully elucidated. But as dexmedetomidine is more potent α2 adrenergic agonist compared to clonidine, the peripheral antinociception produced by clonidine-like drugs mediating the local release of enkephalin-like substances is also possible. ,
| Conclusion|| |
From the present study, it may be concluded that compared to placebo, pretreatment with 0.25 μg/kg of dexmedetomidine with venous occlusion for 1 min is also as effective as IV lidocaine pretreatment in alleviating propofol injection pain and may be a useful alternative for reducing pain on propofol injection, even though lidocaine is better than dexmedetomidine.
| References|| |
Fuji Y, Itakura M. Comparison of lidocaine, metoclopramide, and flurbiprofen axetil for reducing pain on injection of propofol in Japanese adult surgical patient: A prospective, randomized, double blind, parallel-group, placebo-controlled study. Clin Ther 2008;30:280-6.
Picard P, Tramèr MR. Prevention of pain on injection with propofol: A quantitative systematic review. Anesth Analg 2000;90:963-9.
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.
Koo SW, Cho SJ, Kim YK, Ham KD, Hwang JH. Small-dose ketamine reduces the pain of propofol injection. Anesth Analg 2006;103:1444-7.
Canbay O, Celebi N, Arun O, Karagöz AH, Saricaoğlu F, Ozgen S. Efficacy of intravenous acetaminophen and lidocaine on propofol injection pain. Br J Anaesth 2008;100:95-8.
Pang WW, Huang PY, Chang DP, Huang MH. The peripheral analgesic effect of tramadol in reducing propofol injection pain: A comparison with lidocaine. Effect of mixed versus unmixed lidocaine with propofol. Reg Anesth Pain Med 1999;24:246-9.
Tsubokura H, Inagaki Y, Adachi H, Otsuki A, Harada T, Hirosawa J, et al
. Efficacy of simultaneous bolus injection of lidocaine with propofol on pain caused by propofol injection. Masui 2001;50:1196-200.
Sen H, Sizlan A, Yanarates O, Dogru S, Mutlu M, Ozkan S, Dagli G et al
. The effects of propofol concentration on propofol injection pain. Anatol J Clin Investig 2009;3:127-30.
O′Hara JR Jr, Sprung J, Laseter JT, Maurer WG, Carpenter T, Beven M, et al.
Effects of topical nitroglycerin and intravenous lidocaine on propofol-induced pain on injection. Anesth Analg 1997;84:865-9.
Nathanson MH, Gajraj NM, Russel JA. Prevention of pain on injection of propofol:A comparison of lidocaine with alfentanil. Anesth Analg 1996;82:469-71.
Sapate M, Andurkar U, Markandeya M, Gore R, Thatte W. To study the effect of injection dexmedetomidine for prevention of pain due to propofol injection and to compare it with injection lignocaine. Rev Bras Anestesiol. 2013;1-4.
Turan A, Memis D, Kaya G, Karamanlyoglu B. The prevention of pain from injection of propofol by dexmedetomidine and comparison with lidocaine. Can J Anaesth 2005;52:548-9.
McCrirrick A, Hunter S. Pain on injection of propofol: The effect of injected temperature. Anaesthesia 1990;45:443-4.
Nakane M, Iwama H. A potential mechanism of propofol-induced pain on injection based on studies using nafamostat mesilate. Br J Anaesth 1999;83:397-404.
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.
Cameron E, Johnston G, Clofts S, Morton NS. The minimum effective dose of lignocaine to prevent injection pain due to propofol in children. Anaesthesia 1992;47:604-6.
Overbaugh R, Jones P, Nguyen A, Swaney G. Effect of mixed versus unmixed lidocaine with propofol. Internet J Anesthesiol 2003; vol. 7 no.2. Available from https://ispub.com/IJA/7/2/5826;
accessed on 12 th
Lee P, Russell WJ. Preventing pain on injection of propofol: A comparison between lignocaine pre-treatment and lignocaine added to propofol. Anaesth Intensive Care 2004;32:482-4.
Uzun S, Karagoz HA, Kose AE, Canbay O, Ozgen S. Dexmedetomidine for prevention of propofol injection pain. Anaesthesiol Clin Pharmacol 2008;24:406-8.
Sarkilar G, Kara I, Duman A, Aygin F, Okesli S. Effect of dexmedetomidine on pain caused by injection of propofol. Nobel Med 2012;8:83-8.
Callow ID, Campisi P, Lambert ML, Feng Q, Arnold JM. Enhanced in vivo
alpha1- and alpha2-adrenoceptor-mediated vasoconstriction with indomethacin in humans. Am J Physiol 1998; 275:H837-43.
Dalle C, Schneider M, Clergue F, Bretton C, Jirounek P. Inhibition of the I(h) current in isolated peripheral nerve: A novel mode of peripheral antinociception. Muscle Nerve. 2001;24:254-61.
[Table 1], [Table 2]
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