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 Table of Contents  
ORIGINAL ARTICLE
Year : 2019  |  Volume : 9  |  Issue : 1  |  Page : 71-75

The pain reduction efficacy of granisetron, dexmedetomidine and lidocaine after etomidate injection for surgery under general anaesthesia


Departments of Anesthesiology and Critical Care, Arak University of Medical Sciences, Arak, Iran

Date of Web Publication4-Jan-2019

Correspondence Address:
Esmail Moshiri
Department of Anesthesiology and Critical Care, Arak University of Medical Sciences, Arak
Iran
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/AIHB.AIHB_52_18

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  Abstract 


Introduction: Pain on injection of anaesthetics is significant for patients' dissatisfaction. The present study aimed to compare the efficacy of granisetron, dexmedetomidine and lidocaine on the reduction of etomidate injection pain. Materials and Methods: A clinical trial was performed on 132 patients aged 18–50 years undergoing elective surgery under general anaesthesia. Two cannulas were inserted into the veins on the dorsum of both hands, and arterial drainage of both was occluded. The patients were randomised into three groups and injected with 6 mg granisetron, 40 mg lidocaine and 5 mcg dexmedetomidine, respectively, into one arm, while injecting normal saline into the other arm. Two minutes later, the tourniquet was released in each group, and 2 mg etomidate was injected into each arm. Participants were asked to rate their pain using the visual analogue scale for each arm on injection, as well as 5 min after injection. Results: A significant difference was found in pain scores of etomidate injection in the three groups of dexmedetomidine, lidocaine and granisetron. Moreover, the pain reduction effect was lower both immediately and at 5 min after injection in dexmedetomidine group than other groups (P = 0.03). In addition, the mean of pain score was lower in lidocaine group than granisetron group (P = 0.01). Nevertheless, the trend of haemodynamic parameters was not significant and different among studied groups (P > 0.05). Conclusion: Dexmedetomidine seems to have been more efficient than the others in reducing etomidate injection pain. However, the adverse effect of the three interventions was not different, and the haemodynamic parameters were stable during anaesthesia.

Keywords: Dexmedetomidine, etomidate, granisetron, injection pain, lidocaine


How to cite this article:
Modir H, Moshiri E, Yazdi B, Kamali A, Soltani S. The pain reduction efficacy of granisetron, dexmedetomidine and lidocaine after etomidate injection for surgery under general anaesthesia. Adv Hum Biol 2019;9:71-5

How to cite this URL:
Modir H, Moshiri E, Yazdi B, Kamali A, Soltani S. The pain reduction efficacy of granisetron, dexmedetomidine and lidocaine after etomidate injection for surgery under general anaesthesia. Adv Hum Biol [serial online] 2019 [cited 2020 Jan 17];9:71-5. Available from: http://www.aihbonline.com/text.asp?2019/9/1/71/243758




  Introduction Top


While limited by their diverse side effects, numerous different anaesthetics are used to induce anaesthesia, among which etomidate is a common intravenous anaesthetic agent of choice to induce general anaesthesia or sleep before short surgical procedures.[1],[2],[3] Although the anaesthetic is known to ensure cardiovascular stability, but some unpleasant side effects are including pain on injection, and postoperative nausea, and vomiting. Pain can occur due to the propylene glycol formulation which may cause direct injury to vascular endothelium.[2],[4] Intravenous lidocaine is one of the most common interventions to reduce the incidence of pain on injection of anaesthetics such as propofol and etomidate, but about 13% to 32% of cases fail.[5]

Ondansetron is a specific antagonist of 5-HT3 serotonin receptors which greatly affects in reducing numbness on subcutaneous injection. Granisetron is also another antagonist with a longer effect than ondansetron which some studies have proven its effectiveness on injection pain.[6],[7] Dexmedetomidine is a potent and highly specific α2-receptor agonist with sedative, sympatholytic, analgesic and anxiolytic effects and used for pain reduction in some studies.[8],[9] Since the α2-receptor agonist in blood vessels prevents norepinephrine release, it causes venous dilation and thus reduces injection pain,[9],[10],[11] which is a major cause of patients' dissatisfaction, while increasing their satisfaction with perioperative care by reducing unpleasant side effects.[6],[12] While no study has compared the triple anaesthetics with each other, this study aims to improve patients' satisfaction by comparing the anaesthetics used in the study to control pain on etomidate injection and to determine the most efficient anaesthetic.


  Materials and Methods Top


This double-blind clinical trial involved 132 American Society of Anaesthesiologists (ASA) I-II patients (aged 18–50 years of both sexes) undergoing elective surgeries under general anaesthesia, after taken informed consent and verification of exclusion criteria. The Ethical Committee of Arak University of Medical Sciences approved this project by IR.ARAKMU.REC.1395.273. Exclusion criteria of this study were as follows: age under 18 or above 50, ASA greater than II, poor blood pressure (BP) control, history of vascular disease, addiction to opioids, thrombophlebitis, diabetes, previous chronic pain, history of the upper extremity tumour, patients with burns on each hand and contraindications for the injection of dexmedetomidine, granisetron and lidocaine. In the preoperative examination, all participants were fully explained about visual analogue scale (VAS): 0 means no pain and 10 is the worst pain imaginable. On arrival to the operating room, all patients were monitored by electrocardiogram, pulse oximetry and non-invasive BP. Two 22-gauge cannulas were inserted into the veins on the dorsum of both hands. All needed drugs were prepared into opaque syringes and then administered.

The study was double blind, since neither symptom examiner nor patients were aware about the type of anaesthetic used and the target group. In other hand, the patients and physician were not aware about the assigned groups.

In this study, each patient was the control of itself and one arm was intervention while another arm was control. First, the informed consent was obtained from all patients and they signed that form. Then, 100 ml of normal saline (0.9%) was injected through each venous cannula on the dorsum of the control hand within 10 min and recording demographic information. Random allocation was conducted by block randomisation method and the size of block was 6 and patients were randomised in three groups. Limbs were exsanguinated and then a tourniquet placed on the forearm which inflated to 250–350 mmHg, arterial drainage of both hands was then occluded. Participants were assigned into three groups: Group G (granisetron): 6 mg granisetron (2 ml, Caspian Tamin Pharmaceutical Co.) was injected into intervention arm and 2 mL of normal saline 0.9% at the same time into the left arm; Group L: 2 mL of lidocaine 2% (40 mg, Caspian Co.) was injected into intervention arm and 2 mL of normal saline into the control arm at the same time; and Group D: 5 mcg dexmedetomidine (2 mL, Hospira Inc.) was injected into intervention arm and 2 mL of normal saline into the control arm at the same time.

Two minutes later, the tourniquet was then released in each group, and 2 mg etomidate (1 mL, Hospira Inc.) was injected into each arm. The patients were asked to give a VAS pain score for each arm immediately and 5 min after injection. Moreover, we recorded the score for each arm and the unwanted side effects of anaesthetics in each group. Mean arterial BP (MBP), arterial oxygen saturation (SaO2) and heart rate (HR) were recorded on arrival to the operating room, 5 and 10 min after administration of the anaesthetics studied, at induction and up to 30 min post-induction and at intervals of 10 min. Each patient received general anaesthetic induction and tracheal intubation by injection of 1 mg/kg/iv sodium thiopental, 1 μg/kg/iv fentanyl, 1 mg/iv midazolam and 0.5 mg/kg/iv atracurium, 10 min after administration of etomidate (2 mg/10 ml, Hospira Inc.). Then, anaesthesia was maintained by isoflurane (0.5–1.5%) and N2O (50%), and ventilation was adjusted to maintain normocapnia. Data on VAS, MBP and SaO2 were collected from different groups, and then, the results were analysed statistically using PASW Statistics version 18 (IBM Co., Armonk, NY, USA). Chi-square test was used to compare the three groups regarding to qualitative factors such as sex. Moreover, the mean of age, maximum heart rate (MHR), MBP and SaO2 were compared among the three groups by analysis of variance test, and Tukey's post hoc test was used for more comparisons.


  Results Top


A double-blind clinical trial enrolled 132 ASA I-II patients (aged 18–50 years of both sexes) undergoing elective surgeries under general anaesthesia. The participants were assigned into three groups of granisetron, dexmedetomidine and lidocaine. Based on the Chi-square test, there were no significant differences among the three groups in sex distribution (P = 0.993). Moreover, the mean age of participants in the study was 34.94 ± 7.927 years, and the patients in granisetron group have higher age than other two groups (P = 0.001).

As shown in [Table 1], a significant difference was seen in scores for pain in both hands of patients in the Group D immediately and 5 min after injection (P = 0.0001), i.e., dexmedetomidine being greatly effective in reducing etomidate injection pain. In addition, a significant difference was observed in scores for pain in both hands of patients in the Group L immediately and 5 min after injection (P = 0.0001), i.e., lidocaine being greatly effective in reducing etomidate injection pain. Moreover, a significant difference was seen in scores for pain in both hands of patients in the Group G immediately and 5 min after injection (P = 0.01, P = 0.001, respectively). Simply put, granisetron was greatly effective in reducing etomidate injection pain.
Table 1: Comparison of pain score due to etomidate injection in both hands of patients in granisetron, dexmedetomidine and lidocaine groups

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As shown in [Table 2], significant differences were found in scores for etomidate injection pain in the Groups D, L and G, so that the score was also lower in the Group D than the other two groups immediately and 5 min after injection, whereas this was also found lower in the Group L compared to the Group G (P = 0.01, P = 0.03, respectively). Simply put, dexmedetomidine was found to be much more efficient in reducing etomidate injection pain than the other two anaesthetics. However, the mean of pain scores in control hand was not statistically significant among the three groups immediately and 5 min after etomidate injection (P > 0.05).
Table 2: Comparison of the visual analogue scale scores for pain of injection of etomidate in intervention group in granisetron, dexmedetomidine and lidocaine groups

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The analysis of variance [Table 3] showed that there was a significant difference among studied groups in MBP 20th and 30th min after induction of anaesthesia. Nevertheless, the MBP was not significantly different at baseline, 5th and 10th min after injection of etomidate, at induction time and 10th min after induction (P > 0.05). Moreover, the analysis of variance for repeated measurements [Figure 1] was not significant in each group (P > 0.05).
Table 3: Comparison of mean of blood pressure in granisetron, dexmedetomidine and lidocaine groups at different time of intervention

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Figure 1: The trend of mean of blood pressure in granisetron, dexmedetomidine and lidocaine groups at different time of the study.

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According to the analysis of variance test [Table 4], a significant difference was observed among studied groups in MHR at the induction time, 10th, 20th and 30th min after induction of anaesthesia. Nevertheless, the MHR was not significantly different at baseline, 5th and 10th min after injection of etomidate (P > 0.05). Moreover, the analysis of variance for repeated measurements [Figure 2] was not significant in granisetron group (P > 0.05). However, a decreasing trend was observed in MHR in dexmedetomidine and lidocaine groups (P < 0.05).
Table 4: Comparison of mean heart rate in granisetron, dexmedetomidine and lidocaine groups at different time of intervention

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Figure 2: The trend in mean of heart rate in granisetron, dexmedetomidine and lidocaine groups at different time of the study.

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The results in [Table 5] showed that based on analysis of variance test, a significant difference was observed among studied groups in SaO2 at the induction time, 10th and 20th min after induction of anaesthesia. Nevertheless, the SaO2 was not significantly different at baseline, 5th and 10th min after injection of etomidate as well as at induction time and 30th min after induction of anaesthesia (P > 0.05). Moreover, the analysis of variance for repeated measurements was not significant in the three studied groups (P < 0.05).
Table 5: Comparison of mean saturation oxygen in granisetron, dexmedetomidine and lidocaine groups at different time of intervention

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  Discussion Top


The study aims to compare the efficacy of granisetron, dexmedetomidine and lidocaine in reducing pain on etomidate injection. Based on our results, no significant differences were found in sex distribution among all groups. Based on our results, there were observed significant differences in the mean scores of pain in both hands of patients in the dexmedetomidine, lidocaine and granisetron groups, immediately and 5 min after injection. Moreover, a significant differences were observed in scores for etomidate injection pain in the groups, i.e., the score in the Group D was lower than the other two groups immediately and 5 min after injection, whereas this was also lower in the Group L than the Group G (P = 0.03, P = 0.01). Simply put, dexmedetomidine seemed greatly more effective in reducing etomidate injection pain than the other anaesthetics. Nevertheless, there was a significant difference among studied groups in MHR, MBP and SaO2% at the 20th and 30th min after induction of anaesthesia. Nevertheless, the mean of MHR, MBP and SaO2% were not significantly different at baseline, 5th and 10th min after injection of etomidate. Therefore, the granisetron, dexmedetomidine and lidocaine have not important effect on the MHR, MBP and SaO2%.

The mean of VSA scores for pain was different in the study groups, and the dexmedetomidine has more reducing effect on the etomidate injection pain than the lidocaine and granisetron drugs. Similar results were obtained by another studies.[5],[12],[13] A study by Singh et al. conducted to explore the efficacy of dexmedetomidine and lidocaine on relieving propofol injection pain and concluded that dexmedetomidine decreases pain compared with placebo group that received lidocaine.[5] However, their results were consistent with our study since dexmedetomidine is superior to placebo for relief of injection pain but are not consistent on the superiority of lidocaine versus dexmedetomidine, since dexmedetomidine had a better effect on pain management than the other two anaesthetics in our study. Nevertheless, another study by Thukral et al. deduced that administration of ketamine is effective than dexmedetomidine in reducing moderate-to-severe pain on propofol injection.[13] Different results by our study were due to a different method for pain assessment, and they used McCririck and Hunter scale for assessing pain while we used VAS pain scale. Moreover, He et al. study showed pre-treatment with 1 mg/kg of intravenous dexmedetomidine is effective in reduction of incidence and severity of pain due to propofol injection.[12] In addition, another same study by Alipour et al. conducted a study on 336 patients and concluded that both granisetron and lidocaine were effective in reducing pain on propofol injection.[14] The results of the present study showed that dexmedetomidine and then lidocaine are more effective and granisetron less effective in reducing pain. This difference can be attributed to different anaesthetics compared (etomidate in our study vs. propofol in theirs). Moreover, Sai and Kamath carried out a trial to compare the effect of granisetron pre-treatment to relieve pain of propofol injection on 104 patients and concluded that lidocaine was more effective at relieving pain on propofol injection.[7]

Our study showed that after induction of anaesthesia, the mean of HR and MBP decease in granisetron and lidocaine groups while these haemodynamic parameters are more stable in dexmedetomidine. The Thukral et al. study[13] also showed that hypertension and tachycardia were higher in the ketamine group in comparison to the dexmedetomidine to reduce pain on propofol injection. In our study, granisetron, lidocaine and dexmedetomidine were used for pain reduction from etomidate injection, and the HR, BP and SaO2% were not different in the groups studied until induction time of anaesthesia. Moreover, Li et al. study showed that pre-treatment with dexmedetomidine could decrease the propofol injection pain in electroconvulsive therapy change in other outcomes and occurrence adverse effects including bradycardia and hypotension.[15]

Ahmed et al. also performed a study to assess the pre-treatment with intravenous granisetron to alleviate pain due to propofol injection and reported that granisetron was highly effective in reducing propofol injection pain,[6] which is consistent with our study results. Moreover, Ayoğlu et al. study assessed the effect of dexmedetomidine on relief of pain on propofol and rocuronium injections on 50 patients, concluding that dexmedetomidine was not effective in reducing propofol injection pain,[16] whose results differ from those of our study and seem to be due to small samples and different anaesthetics, i.e., propofol and rocuronium in their study versus etomidate in ours. With results in line with our study, El-Radaideh et al. carried out a study and deduced that the administration of lidocaine and lidocaine-fentanyl is efficient in reducing pain of propofol injection.[17] However, the systematic review suggested that a small dose of opioids before induction of anaesthesia could be effective in reduction of pain due to injection in all patients.[4]


  Conclusion Top


Significant differences were found in scores for pain on etomidate injection in the three groups of dexmedetomidine, lidocaine and granisetron, so that the score was lower in the Group D than the other groups immediately and 5 min after injection, while it was also lower in the Group L than the Group G. The Group D is found to greatly reduce pain due to etomidate injection than the others.

Acknowledgements

This article is derived from a thesis no. 823 which was approved under the Code of Ethics: IR.ARAKMU.REC.1395.273 at Arak University of Medical Sciences and registered in the Iranian Registry of Clinical Trials with registration number ID: IRCT2016122720258N21. Hereby, we would like to thank the Clinical Research Council at Valiasr Hospital for their guidance and the deputy of the Arak Medical University Research Centre owing to their full support.

Financial support and sponsorship

This study was financially supported by Arak University of Medical Sciences.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

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Levins T. Etomidate in procedural sedation. Air Med J 2011;30:45-8.  Back to cited text no. 1
    
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Mizrak A, Koruk S, Bilgi M, Kocamer B, Erkutlu I, Ganidagli S, et al. Pretreatment with dexmedetomidine or thiopental decreases myoclonus after etomidate: A randomized, double-blind controlled trial. J Surg Res 2010;159:e11-6.  Back to cited text no. 3
    
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Jalota L, Kalira V, George E, Shi YY, Hornuss C, Radke O, et al. Prevention of pain on injection of propofol: Systematic review and meta-analysis. BMJ 2011;342:d1110.  Back to cited text no. 4
    
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He L, Xu JM, He T, Liu L, Zhu R. Dexmedetomidine pretreatment alleviates propofol injection pain. Ups J Med Sci 2014;119:338-42.  Back to cited text no. 12
    
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Thukral S, Gupta P, Lakra A, Gupta M. Dexmedetomidine versus ketamine infusion to alleviate propofol injection pain: A prospective randomized and double-blind study. Indian J Anaesth 2015;59:488-92.  Back to cited text no. 13
    
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Alipour M, Tabari M, Alipour M. Paracetamol, ondansetron, granisetron, magnesium sulfate and lidocaine and reduced propofol injection pain. Iran Red Crescent Med J 2014;16:e16086.  Back to cited text no. 14
    
15.
Li X, Chen CJ, Tan F, Pan JR, Xing JB, Zhu QQ, et al. Effect of dexmedetomidine for attenuation of propofol injection pain in electroconvulsive therapy: A randomized controlled study. J Anesth 2018;32:70-6.  Back to cited text no. 15
    
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Ayoğlu H, Altunkaya H, Ozer Y, Yapakçi O, Cukdar G, Ozkoçak I, et al. Does dexmedetomidine reduce the injection pain due to propofol and rocuronium? Eur J Anaesthesiol 2007;24:541-5.  Back to cited text no. 16
    
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El-Radaideh KM. Effect of pretreatment with lidocaine, intravenous paracetamol and lidocaine-fentanyl on propofol injection pain. Comparative study. Rev Bras Anestesiol 2007;57:32-8.  Back to cited text no. 17
    


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