|Year : 2019 | Volume
| 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
|Date of Submission||06-Feb-2019|
|Date of Acceptance||04-Apr-2019|
|Date of Web Publication||6-May-2019|
Dr. Bhavna Gupta
Department of Anaesthesia, AIIMS, Rishikesh, Uttarakhand
Source of Support: None, Conflict of Interest: None
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.
Keywords: Dexamethasone, injection, lidocaine, pain, propofol, 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 Aug 22];20:26-31. Available from: http://www.theiaforum.org/text.asp?2019/20/1/26/257675
| 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.,, 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.,,, 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. 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.,,,,
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. 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. 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., 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.,,,
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.
On the basis of results of a previous investigation, 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:
σ = Standard deviation of population.
d = Difference between means.
H = Sample size.
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: Flow of participants through a randomized double-blind study investigating the efficacy of pretreatment with either lignocaine or dexamethasone or tramadol in attenuating propofol-induced vascular pain (CONSORT)|
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- Group L; Received 60 mg of preservative-free lignocaine hydrochloride
- Group D; Received 12 mg of dexamethasone sodium phosphate
- Group 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 0
- Mild pain Score 1
- Moderate pain 2
- Severe 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.
- Spontaneous complaints of pain or comfort during injection
- Behavioral signs such as facial grimace, arm withdrawal, and vocal response
- VRS 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.
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).
- The objectives and procedure of the study were explained to all the patients
- Informed consent was taken from all the patients willing to participate in the study
- The option to opt out of the study was kept open without any clauses
- Complete confidentiality was maintained regarding patient information throughout all the stages of the study.
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: Demographic characteristics of patients undergoing general anesthesia, included in the study comparing attenuation of propofol-induced vascular pain in all the three groups|
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|Table 2: Propofol-induced vascular pain being compared in all the three groups|
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| 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%., 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.,
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.,,,,,,,,, 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%.,,,,
Lidocaine has been used to alleviate propofol injection pain, because of its local anesthetic action. Sasaki et al. found that the analgesic effect of preinjected lidocaine increased when a tourniquet was applied concomitantly. 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. 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. 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. 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.,, 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. 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.
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.,, 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. 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. 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. 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).
| 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
Conflicts of interest
There are no conflicts of interest.
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[Table 1], [Table 2]