|Year : 2017 | Volume
| Issue : 3 | Page : 715-720
|Analgesic effects of ketorolac/lidocaine compared to dexmedetomidine/lidocaine in intravenous regional anesthesia
Hesameddin Modir1, Bijan Yazdi1, Hushang Talebi1, Majid Golestani Eraghi2, Ahmadreza Behrouzi3, Amirreza Modir4
1 Department of Anesthesiology, Arak University of Medical Sciences, Arak, Iran
2 Tracheal Diseases Research Center, Masih Daneshvari Hospital, National Research Institute of Tuberculosis and Lung Diseases, Shahid Beheshti University of Medical Science, Tehran, Iran
3 Department of Orthopedic Surgery, Arak University of Medical Sciences, Arak, Iran
4 Student of Medicine, Arak University of Medical Sciences, Arak, Iran
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|Date of Web Publication||21-Aug-2017|
| Abstract|| |
Introduction: Intravenous regional anesthesia is known as a safe and reliable technique for anesthesia and reduction of bleeding during limb surgeries. The aim of this study is to compare the addition of ketorolac or dexmedetomidine to lidocaine in intravenous regional anesthesia. Materials and Methods: In this double-blind clinical trial, ninety patients who were admitted for surgery on hand or forearm in Vali-Asr Hospital, Arak city, entered the study. Then, the patients divided into three equal groups. The first group received 3 mg/kg lidocaine 0.5%, the second group received 1 μg/kg dexmedetomidine with lidocaine, and the third group received 30 mg ketorolac with lidocaine. The time to analgesia, pain during surgery, onset of pain after tourniquet deflation, and the pain after tourniquet deflation were measured. Results: The mean duration to analgesia was 7.37 ± 0.67 min in control group, 5.23 ± 0.68 min in dexmedetomidine group, and 4.90 ± 0.76 min in ketorolac group (P = 0.164). In total of 3 times of measurement of pain after injection, the mean visual analog scale in ketorolac group was significantly lower than lidocaine (P = 0.0001) and dexmedetomidine (P = 0.009) groups. In all time intervals after tourniquet deflation, the mean score of pain was significantly lower in ketorolac group. Conclusion: Ketorolac could control the perioperative pain and the pain after tourniquet deflation. It seems that ketorolac is a useful and effective choice for pain relief for patients undergoing intravenous regional anesthesia.
Keywords: Biers block, dexmedetomidine, ketorolac, regional anesthesia
|How to cite this article:|
Modir H, Yazdi B, Talebi H, Eraghi MG, Behrouzi A, Modir A. Analgesic effects of ketorolac/lidocaine compared to dexmedetomidine/lidocaine in intravenous regional anesthesia. Ann Trop Med Public Health 2017;10:715-20
|How to cite this URL:|
Modir H, Yazdi B, Talebi H, Eraghi MG, Behrouzi A, Modir A. Analgesic effects of ketorolac/lidocaine compared to dexmedetomidine/lidocaine in intravenous regional anesthesia. Ann Trop Med Public Health [serial online] 2017 [cited 2020 Jun 2];10:715-20. Available from: http://www.atmph.org/text.asp?2017/10/3/715/213151
| Introduction|| |
Intravenous regional anesthesia has been known as a safe and reliable technique for creating anesthesia and lack of bleeding during organs' surgery. The advantage of such method includes the return of the natural feeling and power to move as the surgery ends and it allows the organ's performance to return to its natural state quickly, and also, the neurologic signs can be reviewed after the fractures are fixed., However, some of the disadvantages of this method are lack of continuity of anesthesia, concern about toxicity of the local anesthetic medicines, beginning of the slow effect of the medicine, less muscle relaxation, pain caused by tourniquet, and also lack of pain after surgery. Among these, the role of nerve fibers A and nonmyelinated fibers C in creating pain caused by tourniquet has been considered influential because the ischemia caused by the inflation of tourniquet leads to the increase of the peripheral nerve compression. Now, to increase the quality of the nerve block, elongation of analgesia after tourniquet deflation and also reduction of pain caused by tourniquet, numerous medicines which affect peripheral nerves such as tramadol, alpha-2 agonists, meperidine, neostigmine, or nonsteroidal anti-inflammatory drugs (NSAIDs) can be used such along with local anesthetic medicines.
NSAID prevent ischemia caused by tourniquet inflation during operation by inhibiting release of inflammatory mediators. Among these medicines, ketorolac, due to ease of prescription and beginning of quick effect, is a proper option for calming pain in the emergency room  and various studies have proved the effect of this medicine on the reduction of pain caused by tourniquet and after in intravenous regional anesthesia.,
Dexmedetomidine is an alpha-2 agonist which has the sedative and anesthetic effects in the opinion of many researchers. Dexmedetomidine is a more selective alpha-2 agonist with a 1620 greater selectivity for the alpha-2 receptor compared with the alpha-1 receptor. Therefore, it can be said that this drug is a special agonist of alpha-2 receptor which has more neurologic and less cardiovascular effects. Numerous studies have shown the positive effects of this medicine in intravenous regional anesthesia., However, no study has compared the effects of this medicine with ketorolac in intravenous regional anesthesia. Thus, the purpose of this study is to compare dexmedetomidine and ketorolac along with lidocaine in intravenous regional anesthesia.
| Materials and Methods of Execution|| |
In this study, which is a double-blind clinical trial, a number of ninety patients who had visited Vali Asr Hospital of Arak for hand or forearm operations entered the study after getting individual consent and by considering the criteria of entering and exiting the study. Patients of the age between 20 and 50-year-old and American Society of Anesthesiologists of Class I and II were evaluated. Patients would be eliminated from the study in case of these: history of heart disease, history of blood pressure being treated with alpha methyldopa and clonidine, bradycardia, pregnancy, blood and clotting disorders, kidney disease, history of gastrointestinal bleeding, operation time <40 min and >90 min, a history of narcotic drugs or other analgesics consumption, and history of allergy to medicines of the research. According to the visual analog scale (VAS) mean after surgery and an alpha error of 5% and beta error of 10%, the rate of the sample volume in each group was considered to be 30 persons. This study has been approved in the Ethics Committee of the Arak University of Medical Sciences with the code 92-158-5.
After getting the demographic information and recording the vital signs and percentage of saturation of arterial oxygen, two intravenous ways were provided one in the dorsal vein of the hand being operated and the other in the other hand to receive crystalloid fluids. At first, 5 milligram of midazolam was injected as premedication and a double tourniquet was inflated 3–4 cm higher than the elbow of the considered hand, and then, the hand of the patient is put higher for 2 min for the blood to be discharged, and then, it was bandaged with Esmarch bandage. Then, the double tourniquet proximal cuff was filled with air up to a pressure of 250 mmHg and Esmarch bandage was taken out.
After making sure that there was no pulse through pulse oximetry, the patients were randomly divided into three groups. In the first group, or the control group, the patients received 3 mg/kg 0.5% lidocaine which was diluted to 40cc with 0.9% saline in 90 s. In the second group, patients received 3 mg/kg of 0.5% lidocaine and 1 μg/kg of dexmedetomidine  which was diluted to 40cc with 0.9% saline in 90 s. Patients of the third group received 3 mg/kg of 0.5 lidocaine with 30 mg ketorolac  dissolved in 0.9% saline and with the total volume of 40cc. After making sure of the sensory block, distal cuff was filled with air up to 250 mmHg and the proximal tourniquet was deflated. At this point, the elapsed time after the initial injection up to the onset of analgesia was recorded.
The VAS criterion which includes a 10 cm ruler stretched between 0 and 10 longitudinally was used for measuring the pain of tourniquet. In this ruler, the number 0 showed lack of pain and the number 10 showed unbearable pain. The patients were asked to mark the rate of their pain in this ruler and the distance of the place marked by the patient from the number 0 expressed the rate of pain of the patient. The rate of VAS of the patients 15, 30, and 45 min after the beginning of surgery was measured and recorded by a person who had no information about the classifications and in case VAS >3, the patients would receive 1 μg/kg of fentanyl.
After the end of surgery, tourniquet was emptied with the alternate technique. It is necessary to mention that tourniquet is inflated for at least 40 min and at most 90 min after the injection of the medicine. After the deflation of the tourniquet, the elapsed time till the beginning of the pain was measured. The vital signs of the patient and the percentage of saturation of arterial oxygen during the operation and after the deflation of the tourniquet were measured. The rate of analgesia of the patient was measured every 30 min until 2 h based on the VAS criterion after the tourniquet is emptied and the highest measured VAS is expressed as the rate of the pain of the patient after surgery.
Demographic information and other variables of the patient were measured and extracted and recorded in the form. Then, the data were put in the statistical software IBM SPSS Statistics V20.0.0 (IBM Co., Armonk, NY, USA) and the qualitative variables were analyzed using the Chi-square test and quantitative variables were analyzed by the t-test and Toki posttest. To review the changes of the quantitative data at different times, the ANOVA test was used with repeated observations. This study has been recorded in the website of Iranian registry of clinical trials with the code IRCT2014090614056N3.
| Results|| |
Ultimately, ninety patients who were candidates for hand or forearm surgery entered the study. The basic demographic and hemodynamic variables have been presented in [Table 1].
|Table 1: Demographic variables and basic values of the hemodynamic parameters in the groups|
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After injection of medicines, the elapsed time till the beginning of anesthesia is measured. Accordingly, the average time of the beginning of analgesia in the control group was equal to 7.37 ± 0.67 min, in the dexmedetomidine group 5.23 ± 0.68 min, and in the ketorolac group 4.90 ± 0.76 min. The data analysis using ANOVA test and Toki posttest showed that the difference between the control group with the other two groups is statistically significant (P = 0.0001); but the difference between the two experimental groups has not been significant (P = 0.164).
Pain of patients was recorded using the VAS criterion 15, 30, and 45 min after the injection. In the average rate of pain in the 15th min after injection, there was a significant difference between the control group and the dexmedetomidine group (P = 0.019) and ketorolac group (P = 0.0001), but the difference between the two experimental groups has not been significant (P = 0.226). Thirty minutes after the injection, there was a significant difference between the control group and the two experimental groups (P = 0.0001), but the difference between the two experimental groups has not been significant (P = 0.133). Forty-five minutes after the injection, there was a significant difference between the control group and the two experimental groups (P = 0.0001) and the difference between the two experimental groups was statistically significant (P = 0.043).
The data analysis using repeated measure test also showed that in the total of three measurements of the pain of patients after the injection, the average rate of the pain in the ketorolac group was significantly lower than the lidocaine group (P = 0.0001) and dexmedetomidine group (P = 0.009) [Graph 1].
After the deflation of the tourniquet, the period until the beginning of the patients' pain was recorded. Accordingly, the average time until the beginning of pain in the control group was equal to 44.17 ± 3.60 min, in the dexmedetomidine group 52.53 ± 5.91 min, and in the ketorolac group 55.70 ± 4.30 min. The data analysis showed that the difference between the control group with the other two groups are statistically significant (P = 0.0001), and the difference between the two groups of dexmedetomidine and ketorolac was also statistically significant (P = 0.029).
In terms of the average rate of the pain of patients 30 min after the deflation of the tourniquet, there was a significant difference between the control group and the two groups of dexmedetomidine and ketorolac (P = 0.0001) and the difference between the two groups of dexmedetomidine and ketorolac was statistically significant (P = 0.001) [Table 2]. Sixty minutes after the deflation of the tourniquet, there was a significant difference between the control group and two experimental groups (P = 0.0001) and the difference between the experimental groups of dexmedetomidine and ketorolac was statistically significant (P = 0.023).). Ninety minutes after the deflation of the tourniquet, there was a significant difference between the control group and the two experimental groups (P = 0.0001) and the difference between the experimental groups of dexmedetomidine and ketorolac was statistically significant (P = 0.037). Ultimately, 120 min after the deflation of the tourniquet, there was a significant difference between the control group and the two groups of dexmedetomidine and ketorolac (P = 0.0001) and the difference between the two groups of dexmedetomidine and ketorolac was statistically significant (P = 0.0001) [Table 2].
The data analysis using repeated measure test also showed that during the 2 h after the deflation of the tourniquet, the average rate of the pain in the ketorolac group was significantly lower than the lidocaine group (P = 0.0001) and dexmedetomidine group (P = 0.0001) [Graph 2].
After the deflation of the tourniquet, the values of the hemodynamic parameters are again measured. The mean of systolic blood pressure in the control group was 117.10 ± 11.03 mmHg, 122.10 ± 6.65 mmHg in the dexmedetomidine group, and 119.17 ± 9.23 mmHg in the ketorolac group (P = 0.110). The mean of diastolic blood pressure in the control group was 73.87 ± 5.80 mmHg, 77.30 ± 5.27 mmHg in the dexmedetomidine group, and 75.52 ± 6.61 mmHg in the ketorolac group (P = 0.086).
The average of the heart rate in the control group was 80.10 ± 10.40, 79.93 ± 8.17 in the dexmedetomidine group, and 80.60 ± 11.13 in the ketorolac group (P = 0.964). The average of the percentage of the saturation of arterial oxygen was 97.37 ± 0.93 in the control group, 96.90 ± 1.09 in the dexmedetomidine group, and 97.33 ± 0.88 in the ketorolac group (P = 0.123).
The average duration of the surgery was 57.47 ± 11.3 min in the control group, 59.43 ± 9.9 in the dexmedetomidine group, and 55.30 ± 7.4 in the ketorolac group and the difference between the groups was not significant in this field (P = 0.261).
| Discussion|| |
The results obtained from the present research showed that the beginning of analgesia in the two experimental groups was significantly lesser in contrast with the control group. The average of the pain of the patients in the experimental groups has been lower than that of the patients of the control group in the minutes 15, 30, and 45 after the beginning of the injection and it was only in the 45th min that the average of the pain in the ketorolac group was considerably lower than the dexmedetomidine group. After the deflation of the tourniquet, the duration of the time of analgesia of the patients receiving ketorolac was significantly longer than the other two groups. The average pain of the patients up to 2 h after the deflation of the tourniquet was also evaluated and at all those times, the average of pain in the ketorolac group was significantly lower.
Alpha-2 adrenergic receptors in the nerve endings have an important role in pain relief and some medicines such as dexmedetomidine induce their antipain function by preventing release of norepinephrine of these receptors. Gentili et al. were the first ones to find out that clonidine can lead to the reduction of the pain of tourniquet. After them, some studies were done in the field of adding alpha-2 agonists to lidocaine in intravenous regional anesthesia all of which showed the positive effect of this medicinal category in reducing the pain of patients., Dexmedetomidine was firstly used in 2004 by Memis et al. combined with lidocaine. The results of this study showed that the beginning of analgesia, pain of the patients, and pain after the deflation of tourniquet were significantly lower in the patients receiving dexmedetomidine. In the study of Esmaoglu et al., similar results were obtained which were indicative of the considerable effects of dexmedetomidine in comparison with the control group. In the study of Nasr and Waly, the beginning of analgesia and average pain of patients during and after surgery were significantly lower in the dexmedetomidine group. In this study, patients receiving dexmedetomidine experienced a considerable bradycardia, but no such thing occurred in our study.
Ketorolac is a NSAID which is derived from arachidonic acid and it interferes with the synthesis of pain and inflammatory mediators. The analgesia caused by the NSAIDs is usually due to the peripheral suppression of the cyclooxygenase (COX) enzymes which leads to the reduction of the activity of the arachidonic acid cascade. Colocalization of prostaglandins E and I2 is a direct result of surgical trauma and leads to the sensitivity of the pain receptors. Inhibition of the synthesis of the prostaglandin in the damaged area leads to the reduction of sensitivity and reduction of postsurgery pain. The prostaglandins E2 are produced by COX-1 and also by COX-2, and ketorolac effectively inhibits the both enzymes.
Steinberg et al., in their study, used ketorolac with 5, 10, 15, 20, 30, and 60 mg dosages along with lidocaine. The results of this study showed that ketorolac will lead to the reduction of pain during surgery after the intravenous regional anesthesia. In the study of Jankovic et al., ketorolac along with dexamethasone and lidocaine could lead to the creation of a considerable analgesia during the hand surgery. Reuben et al. showed that adding ketorolac to lidocaine will lead to a better controlling of the pain of tourniquet and postsurgery pain. Ko et al. also compared paracetamol at the dose of 300 mg and ketorolac at the dose of 10 mg as an adjuvant medicine to lidocaine. In this study, paracetamol could create a higher rate of analgesia in comparison with ketorolac and the pain of tourniquet also began with more delay in this group. Of course, the dose of the ketorolac consumed in this study was one-third of that of our study and other valid studies in this field and these differences can be because of the lower dose of ketorolac.
This is the first time that a clinical trial study is done to review the effects of the two medicines dexmedetomidine and ketorolac in intravenous regional anesthesia. Before this, it was only in the study of Mirkheshti et al. published in 2014 that evaluated the effects of these two medicines in the brachial plexus infraclavicular block. In this study, the beginning of the sensory block did not have a significant difference in the three groups, but the motor block began considerably sooner in the dexmedetomidine group; whereas in our study, there was no significant difference in the beginning of anesthesia between the two experimental groups. Duration of the block created in the study of Mirkheshti was significantly longer in the dexmedetomidine group than the others. We did not review the block in this study and unlike Mirkheshti et al., we attempted to evaluate the patients' pain which shows that the duration of analgesia is longer in the ketorolac group. In the present study, there was no significant difference in the field of hemodynamic parameters between the groups; whereas in the mentioned study, dexmedetomidine could reduce blood pressure and heart rate of the patients significantly.
The tourniquet pain is the main factor of the difficulty of the patients during intravenous regional anesthesia. The tourniquet pain occurs as an ambiguous pain which is created despite sufficient usage of the local anesthetic medicines and it increases as the tourniquet is filled. Studies say that the tourniquet pain might be created due to ischemia and oxidative stress. By considering this issue, using NSAID and their probable effect in reducting the oxidative stress are useful. Lack of evaluation of the side effects of each of these drugs in the first 24 h after surgery is one of the limitations of this study. By considering the conflicted results of the two studies, it is suggested to conduct the future researches in this field with a higher sample volume and using various doses of these two drugs.
| Conclusion|| |
Ketorolac could control pain during surgery and pain after the tourniquet deflation in patients well; therefore, due to the lower price and better accessibility of this medicine in our country, Islamic Republic of Iran, it seems that this medicine is considered as a useful and effective choice for the patients who are candidates for intravenous regional anesthesia.
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Conflicts of interest
There are no conflicts of interest.
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Department of Anesthesiology, Arak University of Medical Sciences, Arak
Source of Support: None, Conflict of Interest: None
[Table 1], [Table 2]
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