The Indian Anaesthetists’ Forum

ORIGINAL ARTICLE
Year
: 2019  |  Volume : 20  |  Issue : 1  |  Page : 26--31

To assess and compare dexamethasone, lignocaine, and tramadol in reduction of propofol-induced vascular pain


Bhavna Gupta1, Anju Bhalotra2,  
1 Department of Anaesthesia, AIIMS, Rishikesh, Uttarakhand, India
2 Department of Anaesthesia, MAMC and Lok Nayak Hospital, New Delhi, India

Correspondence Address:
Dr. Bhavna Gupta
Department of Anaesthesia, AIIMS, Rishikesh, Uttarakhand
India

Abstract

Introduction: Propofol (2,6 di-isopropyl phenol) is a widely used agent for induction of anesthesia, although pain during its injection remains a concern for all anesthesiologists. Pain on intravascular injection of propofol is very incapacitating, and the trouble still remains and has never been eradicated. Materials and Methods: After taking approval from the Institutional Review Board, this randomized controlled study was conducted on patients undergoing elective surgeries under general anesthesia. Two hundred and ten adult patients of either sex aged 28–60 years weighing between 40 and 80 kg were included into three groups: Group L – received 60 mg of preservative-free lignocaine hydrochloride, Group D – received 12 mg of dexamethasone sodium phosphate, and Group T – received 100 mg of tramadol hydrochloride. Venous occlusion was done at the level of mid-fore-arm by inflating a noninvasive blood pressure cuff to a pressure of 60 mmHg. Study drug was then injected over 10 s by consultant who was blinded to the procedure. After 2 min of study drug, venous occlusion was released following which propofol 0.5 mg/kg was injected over 5 s. Spontaneous complaints of pain and behavioral signs which included facial grimace, arm withdrawal, vocal and verbal rating score were recorded by the second anesthesiologist who was unaware of the group allocation. Results: All three drugs reduced the intensity and severity of propofol-induced vascular pain. Incidence of pain in lignocaine, dexamethasone, and tramadol Groups were 15%, 32.8%, and 31.4%, respectively. There was significant pain relief (P = 0.045 and 0.042, respectively) when comparing Group L and D, Group L and T. Pain relief between Group D and T was statistically similar (P = 0.8). The incidence of hand withdrawal was significantly higher in the tramadol group (P < 0.05) as compared to dexamethasone and lignocaine. The incidence of facial grimace was similar in dexamethasone and tramadol group and was higher as compared to that of lidocaine group; however, the incidence was not statistically significant (P = 0.25 between D and L, 0.3 between T and L group). Conclusion: Use of pretreatment with drugs is required to prevent propofol-induced vascular pain. Both tramadol and dexamethasone are equally efficacious in reducing propofol-induced vascular pain, though both are less effective when compared with lignocaine. Dexamethasone has an added advantage of preventing postoperative nausea and vomiting when compared with both lignocaine and tramadol.



How to cite this article:
Gupta B, Bhalotra A. To assess and compare dexamethasone, lignocaine, and tramadol in reduction of propofol-induced vascular pain.Indian Anaesth Forum 2019;20:26-31


How to cite this URL:
Gupta B, Bhalotra A. To assess and compare dexamethasone, lignocaine, and tramadol in reduction of propofol-induced vascular pain. Indian Anaesth Forum [serial online] 2019 [cited 2019 Oct 22 ];20:26-31
Available from: http://www.theiaforum.org/text.asp?2019/20/1/26/257675


Full Text



 Introduction



Propofol (2, 6 di-isopropyl phenol) is oil in water-based emulsion of soya bean oil, glycerol, and egg lecithin and is available as 1% (10 mg/ml) aqueous solution. It is considered as drug of choice for day-care surgeries and short procedures.[1],[2],[3] The major disadvantages of propofol include pain on intravenous injection, occasional bradycardia, and hypotension at the time of induction. Pain on intravascular injection of propofol is very incapacitating, trouble still remains and has never been eradicated.[4],[5],[6],[7] The immediate vascular pain on injection of propofol is because of the direct irritant effect of the drug by stimulation of nociceptive receptors or free nerve endings carried through thin myelinated A delta fibers.[4] Many factors affect the incidence of propofol-induced vascular pain which include: site of injection, vein caliber, speed of injection, temperature of propofol, concomitant use of drugs such as local anesthetic agents, and opioids.[5],[6],[7],[8],[9]

Lignocaine is a short-acting local anesthetic agent and is known to reduce pain on propofol injection owing to its local anesthetic properties. It is considered as a gold standard yet is not effective in preventing pain in all cases.[5] Dexamethasone in low dosage is commonly used as an antiemetic and in larger dosage provides postoperative analgesia. Similarly, dexamethasone is known to reduce pain on propofol injection. The mechanism is probably related to the effect of dexamethasone on the production of nitric oxide associated with intravenous propofol injection.[10] Concerns of altered hyperglycemic responses are now resolved and dexamethasone even high single doses of dexamethasone are not known to increase the risk of infection.[11],[12] Tramadol is a centrally acting pain killer, its role in perioperative pain management is well known and is similar in structure to codeine and morphine. The two known mechanisms of the drug include a week-opioid agonist effect and inhibition of reuptake of monoamine neurotransmitter. Studies have shown that it has a peripheral action as well and helps decrease pain on injection of propofol.[13],[14],[15],[16]

The purpose of this study was to compare pain scores and behavioral signs of discomfort among groups pretreated with dexamethasone or lignocaine or tramadol before propofol bolus injection.

 Methods



After taking approval from the Institutional Review Board, this randomized controlled study was conducted in the Department of Anaesthesiology at a tertiary care hospital, on patients undergoing elective procedures under general anesthesia requiring endotracheal intubation. Two hundred and ten adult patients of either sex aged 28–60 years weighing between 40 and 80 kg, scheduled for various elective surgical procedures under general anaesthesia were included in the study. Patients with known hypersensitivity to either of the study drugs (dexamethasone, lignocaine, and tramadol) and propofol were excluded from the study. Exclusion criteria included patients having communication problems, psychiatric illness or central nervous system or neuromuscular disorder; patients with chronic pain taking analgesics or sedatives preoperatively; a history of drug or alcohol abuse; patients requiring rapid sequence induction, allergic to drugs, and patients with difficult intravenous access and small caliber veins. Pregnant and lactating females were also excluded from the study.

Sample size

On the basis of results of a previous investigation,[12] for achieving a power of study equal to 80% and a P = 0.05 with pain on injection, being the primary outcome, a sample size of 70 patients in each group has been calculated, taking an attrition of 10%, using the under-mentioned formula:

[INLINE:1]

σ = Standard deviation of population.

d = Difference between means.

H = Sample size.

Zα =1.96.

Zβ =0.842.

Group allocation

Randomization was done by computergenerated random number tables, and group assignment to one of the following three pretreatment groups was done by opening sealed sequentially numbered opaque envelopes immediately before surgery. Patients were blinded to their group allocation. All the pretreatment drugs were made into a total volume of 10 ml with normal saline to allow blinding. The investigator was blinded to the content and syringes were prepared by an independent anesthesiologist and all appeared identical.

Flow of participants through a randomized doubleblind study investigating the efficacy of pretreatment with either lignocaine or dexamethasone or tramadol in attenuating propofolinduced vascular pain is listed in [Figure 1].{Figure 1}

Group L; Received 60 mg of preservative-free lignocaine hydrochlorideGroup D; Received 12 mg of dexamethasone sodium phosphateGroup T; Received 100 mg of tramadol hydrochloride.

Preoperative anaesthesia check-up

Prior to surgery, the patients underwent thorough pre-anaesthetic check-up and required investigations. The procedure was explained to patients, and they were asked to rate the severity of pain using a verbal rating score (VRS).

No pain score 0Mild pain Score 1Moderate pain 2Severe pain 3.

Patients were wheeled inside operation theater, wide bore 18G cannula was inserted in the dorsum of either hand, and infusion of Ringer lactate was started at the rate of 5 ml/kg/h. Venous occlusion was done at the level of mid-fore-arm by inflating an noninvasive blood pressure cuff to a pressure of 60 mmHg. Study drug was then injected over 10 s by consultant who was blinded to the procedure. After 2 min of study drug, venous occlusion was released following which propofol 0.5 mg/kg was injected over 5 s. Spontaneous complaints of pain and behavioral signs which included facial grimace, arm withdrawal, and vocal response were recorded by the second anesthesiologist who was unaware of the group allocation. Although the verbal analog scale is considered reference standard for measuring acute pain, it has several limitations in its use, especially in this scenario, in which we are measuring pain just before the patient loses consciousness after the effect of propofol. Patients were asked to rate VRS at 15 and 30 s following propofol injection.

Observations

Spontaneous complaints of pain or comfort during injectionBehavioral signs such as facial grimace, arm withdrawal, and vocal responseVRS at 15 and 30 s after propofol 0.5 mg/kg.

After the last recording, anaesthesia was induced in the standard manner, and further anesthetic management was at the discretion of the attending anesthesiologist. Patients were contacted 24 h following surgery and questioned about pain or swelling at the injection site.

Statistical analysis

Continuous variables were presented as a mean ± standard deviation. If the values were unevenly distributed, categorical variables were expressed as frequencies (%). Categorical variables were compared between the groups using the Chi-square test with the Fisher's exact test where applicable. Continuous variables were compared between the groups using analysis of variance. Post-hoc analysis was performed using the Bonferroni test. VRS, an ordered categorical variable, was compared between the groups using the Wilcoxon signed-rank test. Value of P < 0.05 was considered statistically significant. The analyses were done using Statistical Package for the Social Sciences software, Version 21.0 (IBM Corp., Armonk, NY, USA).

Ethical considerations

The objectives and procedure of the study were explained to all the patientsInformed consent was taken from all the patients willing to participate in the studyThe option to opt out of the study was kept open without any clausesComplete confidentiality was maintained regarding patient information throughout all the stages of the study.

Observations

A total of 210 patients were enrolled in this study, and there were 70 patients in each group. Groups were similar with respect to age and weight. Baseline vital parameters such as heart rate, systolic blood pressure, diastolic blood pressure, and peripheral oxygen saturation were also comparable in all the three groups. None of the patients had any significant change in hemodynamic variables after giving the test drug or propofol.

Demographic characteristics of patients undergoing general anesthesia, included in the study comparing attenuation of propofolinduced vascular pain in all the three groups is listed in [Table 1]. The overall incidence of pain during injection of propofol in various groups is shown in [Table 2]. All three drugs reduced the intensity and severity of propofol-induced vascular pain. The incidence of pain in lignocaine, dexamethasone, and tramadol groups were 15%, 32.8%, and 31.4%, respectively. The severity of pain among different groups included a significant pain relief (P = 0.045) when comparing Group L and D, and (P = 0.042) when comparing Group L and T. Pain relief between Group D and T was nonsignificant (P = 0.8). None of the patients had any side effects such as erythema, itching, bradycardia, etc., Dexamethasone has an added advantage of preventing postoperative nausea and vomiting when compared with both lignocaine and tramadol. The incidence of hand withdrawal was significantly higher in the tramadol group (P < 0.05) as compared to dexamethasone and lignocaine. Incidence of facial grimacing was similar in dexamethasone and tramadol group and was higher as compared to that of lidocaine group; however, the incidence was not statistically significant (P = 0.25 between D and L, 0.3 between T and L group).{Table 1}{Table 2}

 Discussion



Propofol is an intravenous sedative and hypnotic agent commonly used as induction agent. It is a rapid-acting agent causing reliable loss of consciousness and loss of airway reflexes, and providing quick and smooth recovery during anesthesia. Pain on injection of propofol is a known entity and is still a limitation of this drug in clinical usage despite its known excellent anesthetic properties. The incidence of pain in studies of propofol injection into an intravenous catheter in forearm cephalic vein or back of the hand was 68%–72%.[6],[7] It is thought to correlate with the amount of propofol in the aqueous phase. Initial component of pain on propofol injection involves the stimulation of nociceptors and nerve endings stimulation. Delayed component of pain occurs after a minute and is caused through the plasma kallikrein-kinin system mediated via bradykinins. Bradykinins cause hyperpermeability and local vasodilatation which increase the contact between the aqueous phase and free nerve endings, thereby causing pain. Asik et al. have suggested mediation of pain through prostanoids, particularly prostaglandin E2. Pain interferes with patient satisfaction and bad memories related to induction. The other factors responsible for pain include osmolality of solvent used for preparation, pH of solution, and propofol concentration in the aqueous phase.[8],[9]

The study compared and evaluated the incidence of propofol-induced vascular pain between lignocaine (considered gold standard), dexamethasone and tramadol. All the three drugs reduced severity and intensity of pain; however, lignocaine was the most effective and tramadol and dexamethasone had comparable results. Severe pain was noted in the tramadol group as compared to that of dexamethasone and lignocaine and the difference was statistically significant (P < 0.05). Various drugs have been used in isolation or in combination to reduce propofol-induced pain, but none is 100% effective till date. Drugs such as lignocaine, ketorolac, ketoprofen, ketamine, and clonidine-ephedrine have been used and compared in the reduction of propofol-induced vascular pain.[10],[11],[12],[13],[14],[15],[16],[17],[18],[19] Different methods have been suggested to decrease propofol injection pain such as cooling the extremity, dilution of the propofol solution, application of topical nitroglycerin on the skin overlying the tip of the intravenous catheter, mixing it with lignocaine, pretreatment with lidocaine or sodium thiopentone, ondansetron, pretreatment with ketamine and injecting into large and antecubital veins, but that too is not 100% effective. However the literature reports the failure rate between 13% and 32%.[5],[6],[7],[8],[9]

Lidocaine has been used to alleviate propofol injection pain, because of its local anesthetic action.[20] Sasaki et al. found that the analgesic effect of preinjected lidocaine increased when a tourniquet was applied concomitantly.[21] A meta-analysis by Picard and Tramèr confirmed that lidocaine should be administered before propofol injection for the best prevention of propofol-induced vascular pain.[22] Kaya et al. also proved that pre-treatment with lidocaine plus venous occlusion for 60 s significantly reduced the incidence of propofol-induced pain compared to lidocaine without venous occlusion.[23] The results of our study very well collaborated with the previous studies reported in the literature and showed that lidocaine is most effective when compared with dexamethasone and tramadol.

Propofol has also been shown to release nitric oxide from vessels in humans and animal models and the same has been linked to the generation of pain in veins in humans.[10] The efficacy of steroids to alter nitric oxide have been seen in several disease conditions. Furthermore, the effect of corticosteroids on NO production has also been demonstrated.[11],[24],[25] Ahmad et al. studied 114 female patients and used 5 ml of 0.5 mg/kg lignocaine, 0.25 mg/kg dexamethasone intravenously following exsanguination and occlusion of veins of the arm, followed by 0.5 mg/kg injection of propofol.[12] The incidence of propofol-induced pain was significantly reduced with both lignocaine and dexamethasone. The added advantage of using dexamethasone was good analgesia and reduced postoperative nausea and vomiting. Nearly 15% of the patients in the lignocaine group had pain; on the contrary, 32.8% of patients in the dexamethasone group had pain. Our results were contrary to the results suggested by Ahmad et al. though the dose of dexamethasone in both the studies were same.[12]

Only 31.4% of patients had pain in the tramadol group and there was no statistical difference in dexamethasone and tramadol group. However, significant difference (P < 0.05) was found between when lignocaine was compared with dexamethasone and tramadol group. Tramadol is a centrally-acting receptor agonist and inhibits norepinephrine reuptake as well as promoting serotonin release. The literature has reported local anaesthetic effects of tramadol when used into an occluded being when propofol was injected in peripheral vein.[13],[14],[15] Borazan et al. compared tramadol with lidocaine mixed with propofol. Tramadol was used in 1 mg/kg dosage, whereas lignocaine was used with propofol as 18 ml (180 mg) propofol and 2 ml l% lignocaine.[26] Propofol-induced pain occurred in 35% of patients pre-treated with tramadol, whereas in 10% of patients treated with the lignocaine-propofol mixture. Their study demonstrated that there was no statistically significant difference (P > 0.05) between tramadol and lignocaine. They also found that intraoperative fentanyl consumption and postoperative analgesic requirement was significantly less in those pre-treated with tramadol. Biswal et al. have shown that both tramadol and acetaminophen were clinically equivalent to lidocaine and were able to reduce propofol-induced vascular pain.[27] Jou et al. have suggested that tramadol causes sensory and motor nerve conduction blockade, mediated through voltage-gated sodium channels leading to the axonal blockade.[28] Pang et al. Transient minor injection pain and local skin reactions were significantly greater with tramadol than with lidocaine (P < 0.05). Both tramadol and lidocaine significantly reduced the incidence and intensity of propofol injection pain when compared with normal saline (P < 0.05).[15]

 Conclusion



Use of pretreatment with drugs is required to prevent propofol-induced vascular pain. Both tramadol and dexamethasone are equally efficacious in reducing propofol-induced vascular pain, though both are less effective when compared with lignocaine. Dexamethasone has an added advantage of preventing postoperative nausea and vomiting when compared with both lignocaine and tramadol.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

References

1Huang CL, Wang YP, Cheng YJ, Susetio L, Liu CC. The effect of carrier intravenous fluid speed on the injection pain of propofol. Anesth Analg 1995;81:1087-8.
2Aitkenhead AR, Rowbotham DJ, Smith G. Textbook of Anaesthesia. 5th ed. New York: Churchill Livingston; 2006.
3Hussain N. Propofol for induction and maintenance of anaesthesia for day case short gynecological procedures. Pak Armed Forces Med J 1995;45:43-6.
4Basbaum AL, Woolf CJ. Concepts of pain mechanism: The contribution of functional imaging of brain. Prog Brain Res 2000;129:277-87.
5Gehan G, Karoubi P, Quinet F, Leroy A, Rathat C, Pourriat JL. Optimal dose of lignocaine for preventing pain on injection of propofol. Br J Anaesth 1991;66:324-6.
6Shimizu T, Inomata S, Kihara S, Toyooka H, Barimacombe JR. Rapid injection reduces pain on injection with propofol. Eur J Anaesthesiol 2005;22:394-6.
7Dubey PK, Kumar A. Pain on injection of lipid-free propofol and propofol emulsion containing medium-chain triglyceride: A comparative study. Anesth Analg 2005;101:1060-2.
8Aşik I, Yörükoǧlu D, Gülay I, Tulunay M. Pain on injection of propofol: Comparison of metoprolol with lidocaine. Eur J Anaesthesiol 2003;20:487-9.
9Fujii Y, Nakayama M. A lidocaine/metoclopramide combination decreases pain on injection of propofol. Can J Anaesth 2005;52:474-7.
10Bolac CS, Wallace AH, Broadwater G, Havrilesky LJ, Habib AS. The impact of postoperative nausea and vomiting prophylaxis with dexamethasone on postoperative wound complications in patients undergoing laparotomy for endometrial cancer. Anesth Analg 2013;116:1041-7.
11Abdelmalak BB, Bonilla AM, Yang D, Chowdary HT, Gottlieb A, Lyden SP, et al. The hyperglycemic response to major noncardiac surgery and the added effect of steroid administration in patients with and without diabetes. Anesth Analg 2013;116:1116-22.
12Ahmad S, De Oliveira GS Jr., Fitzgerald PC, McCarthy RJ. The effect of intravenous dexamethasone and lidocaine on propofol-induced vascular pain: A randomized double-blinded placebo-controlled trial. Pain Res Treat 2013;2013:734531.
13Scott LJ, Perry CM. Tramadol: A review of its use in perioperative pain. Drugs 2000;60:139-76.
14Nossaman VE, Ramadhyani U, Kadowitz PJ, Nossaman BD. Advances in perioperative pain management: Use of medications with dual analgesic mechanisms, tramadol and tapentadol. Anesthesiol Clin 2010;28:647-66.
15Pang WW, Huang PY, Chang DP, Huang MH. The peripheral analgesic effect of tramadol in reducing propofol injection pain: A comparison with lidocaine. Reg Anesth Pain Med 1999;24:246-9.
16Agarwal A, Raza M, Dhiraaj S, Pandey R, Gupta D, Pandey CK, et al. Pain during injection of propofol: The effect of prior administration of butorphanol. Anesth Analg 2004;99:117-9.
17Bano F, Zafar S, Sabbar S, Aftab S, Haider S, Sultan ST. Intravenous ketamine attenuates injection pain and arterial pressure changes during the induction of anesthesia with propofol: A comparison with lidocaine. J Coll Physicians Surg Pak 2007;17:390-3.
18Huang YW, Buerkle H, Lee TH, Lu CY, Lin CR, Lin SH, et al. Effect of pretreatment with ketorolac on propofol injection pain. Acta Anaesthesiol Scand 2002;46:1021-4.
19Johnson RA, Harper NJ, Chadwick S, Vohra A. Pain on injection of propofol. Methods of alleviation. Anaesthesia 1990;45:439-42.
20King 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.
21Sasaki T, Okamura S, Kisara A, Ito M, Yogosawa K, Yagishita Y, et al. Effect of lidocaine on pain caused by injection of propofol: Comparison of three methods at two injection rates. J Anesth 1999;13:14-6.
22Picard P, Tramèr MR. Prevention of pain on injection with propofol: A quantitative systematic review. Anesth Analg 2000;90:963-9.
23Kaya S, Turhanoglu S, Karaman H, Ozgün S, Basak N. Lidocaine for prevention of propofol injection-induced pain: A prospective, randomized, double-blind, controlled study of the effect of duration of venous occlusion with a tourniquet in adults. Curr Ther Res Clin Exp 2008;69:29-35.
24Kindgen-Milles D, Arndt JO. Nitric oxide as a chemical link in the generation of pain from veins in humans. Pain 1996;64:139-42.
25Kharitonov SA, Yates DH, Barnes PJ. Inhaled glucocorticoids decrease nitric oxide in exhaled air of asthmatic patients. Am J Respir Crit Care Med 1996;153:454-7.
26Borazan H, Sahin O, Kececioglu A, Uluer MS, Et T, Otelcioglu S. Prevention of propofol injection pain in children: A comparison of pretreatment with tramadol and propofol-lidocaine mixture. Int J Med Sci 2012;9:492-7.
27Biswal S, Moningi S, Ramachandran G. Effects of intravenous tramadol, acetaminophen in attenuating pain on propofol injection: Comparison with lignocaine: A randomized double blind controlled study. Karnataka Anaesth J 2015;1:118-22.
28Jou IM, Chu KS, Chen HH, Chang PJ, Tsai YC. The effects of intrathecal tramadol on spinal somatosensory-evoked potentials and motor-evoked responses in rats. Anesth Analg 2003;96:783-8.