Interleukin-6 plays an important role in inflammatory responses and synthesis of acute hepatic phase proteins and its plasma level changes are used as a reliable prognostic factor for mortality in hospitalized patients. On the other hand, various methods for reducing inflammatory responses, including proper control of pain during and after surgery, and correction of hemodynamic disorders, can be monitored by monitoring of plasma levels of IL-6. Epidural anesthesia is an appropriate method for controlling pain in lower limb surgeries. The aim of this study was to evaluate the effect of adding Dexmedetomidine to lidocaine in the epidural injection for better control of post-surgical inflammatory responses by measuring interleukin-6 plasma levels.Patients referred to Taleghani Hospital in 1396 who suffered from lower limb fractures and requiring surgery were evaluated. 52 patients in two groups receiving Dexmedetomidine doses of media and controls for the quality of epidural anesthesia and IL-6 index. After obtaining written consent, the Dexmedetomidine treatment group and the normal saline control group were prescribed epidural with lidocaine. Finally, the level of IL-6 before surgery and 6 hours after surgery were evaluated.According to the results of statistical analysis, the two groups did not show a significant difference in age and level of interleukin prior to the operation. The mean age of patients in this study was 15.84639 ± 53.4038. The sex distribution of the study included 19 women (36.5%) and 33 men (63.5%). According to the U Mann Whitney test, the second injection time and total drug volume had a significant difference between the control and intervention groups and Dexmedetomidine reduced the volume of total drug needed and increase the time interval until the second injection (p &lt;0.001). There was also a significant difference between the two groups in the level of interleukin 6 after 6 hours of operation and this was lower in the Dexmedetomidine group.keywords: Interleukin-6, Dexmedetomidine, lidocaine, Anesthesi

Dahi-Taleghani, Mastaneh

Ebrahimpour, Adel

Ghorbani, Ehsan

Malek, Bahman

Moshari, Mohammadreza

Seyed-Alshohadaei, Seyed Mohammad

Vosoughian, Maryam

English

Interleukin-6 plays an important role in inflammatory responses and synthesis of acute hepatic phase proteins and its plasma level changes are used as a reliable prognostic factor for mortality in hospitalized patients. On the other hand, various methods for reducing inflammatory responses, including proper control of pain during and after surgery, and correction of hemodynamic disorders, can be monitored by monitoring of plasma levels of IL-6. Epidural anesthesia is an appropriate method for controlling pain in lower limb surgeries. The aim of this study was to evaluate the effect of adding Dexmedetomidine to lidocaine in the epidural injection for better control of post-surgical inflammatory responses by measuring interleukin-6 plasma levels.

Patients referred to Taleghani Hospital in 1396 who suffered from lower limb fractures and requiring surgery were evaluated. 52 patients in two groups receiving Dexmedetomidine doses of media and controls for the quality of epidural anesthesia and IL-6 index. After obtaining written consent, the Dexmedetomidine treatment group and the normal saline control group were prescribed epidural with lidocaine. Finally, the level of IL-6 before surgery and 6 hours after surgery were evaluated.

According to the results of statistical analysis, the two groups did not show a significant difference in age and level of interleukin prior to the operation. The mean age of patients in this study was 15.84639 ± 53.4038. The sex distribution of the study included 19 women (36.5%) and 33 men (63.5%). According to the U Mann Whitney test, the second injection time and total drug volume had a significant difference between the control and intervention groups and Dexmedetomidine reduced the volume of total drug needed and increase the time interval until the second injection (p <0.001). There was also a significant difference between the two groups in the level of interleukin 6 after 6 hours of operation and this was lower in the Dexmedetomidine group.

keywords: Interleukin-6, Dexmedetomidine, lidocaine, Anesthesi

Mohammadreza Moshari

Bahman Malek

Adel Ebrahimpour

Maryam Vosoughian

Mastaneh Dahi-Taleghani

Ehsan Ghorbani

Seyed Mohammad Seyed-Alshohadaei

Directory of Open Access Journals

  Journal of Cellular & Molecular Anesthesia (JCMA)  Vol 3, No 3,  Summer 2018 103 1. Anesthesiology Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran 2. Department of Orthopedic Surgery, Taleghani Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran             Corresponding Author: Mohammadreza Moshari, MD, Assistant Professor, Anesthesiology Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran; Tel/Fax: +98-21-22432572  Email: rmoshari@sbmu.ac.ir Original Article    Epidural Anesthesia with Lidocaine and Dexmedetomidine, Versus Lidocaine Alone on Plasma Levels of IL-6 in Patients with Proximal Femoral Fracture   Mohammadreza Moshari1 , Bahman Malek1, Adel Ebrahimpour2, Maryam Vosoughian1 , Mastane Dahi-Taleghani1 , Ehsan Ghorbani1, Seyed Mohammad Seyed-Alshohadaei1   Abstract Background: Interleukin-6 (IL-6) plays an important role in inflammatory. Epidural anesthesia is an appropriate method for controlling pain in lower limb surgeries. The aim of this study was to evaluate the effect of Dexmedetomidine and Lidocaine in the epidural injection by measuring IL-6 plasma levels. Materials and Methods: Fifty-two patients with lower limb fractures in two groups receiving Dexmedetomidine doses and controls for the quality of epidural anesthesia and IL-6 index. After explaining the design and obtaining informed written consent, patients were randomly divided into two groups. After 4–6 minutes of administering the test dose, patients in group RC received 5 ml of 1.5% Lidocaine solution via epidural catheter. Patients in group RD were administered 15 ml solution of 1.5% ropivacaine and 0.6 μg/kg of Dexmedetomidine. The levels of IL-6 were evaluated before surgery and 6 hours after surgery. Results: The two groups did not show a significant difference in age and level of interleukin prior to the operation. There was a significant difference in the second injection time and total drug volume between the control and intervention groups. Dexmedetomidine reduced the volume of total drug needed and increased the time interval from the first injection to the second one (p <0.001).There was also lower levels of interleukin 6 in the Dexmedetomidine group at the 6th hour after the operation.  Conclusion: Dexmedetomidine does not only reduce the need for patients on the amount and frequency of analgesic drugs, but also reduces stress and cellular damage. Keywords: Interleukin-6, Dexmedetomidine, Lidocaine, Anesthesia   Please cite this article as: Moshari MR, Malek B, Ebrahimpour A, Vosoughian M, Dahi-Taleghani M, Ghorbani E, et al. Epidural Anesthesia with Lidocaine and Dexmedetomidine, Versus Lidocaine Alone on Plasma Levels of IL-6 in Patients with Proximal Femoral Fracture. J Cell Mol Anesth. 2018;3(3):103-7.    Introduction The increasing use of topical anesthetic, major and minor neural blocks has led to the selective use of general anesthesia. This is because avoiding general anesthesia risks, better postoperative pain control, and some other factors in long-term surgery and long-term postoperative pain control, local anesthetic drugs with a long-lasting effect are common. Meanwhile, auxiliary drugs are also used to maximize the length of the base drug (1). Considering the history of local anesthesia and Moshari et al.                               Comparison of the Effect of Epidural Anesthesia with Lidocaine and Dexmedetomidine … Journal of Cellular & Molecular Anesthesia (JCMA) 104 many studies in this field, today, the tendency of anesthesiologists to perform local block has increased and this may reduce the need for general anesthesia (1). This method is used to carry out surgical procedures or control postoperative pain in order to remove pain and to create anesthesia (2), creating favorable conditions during surgery and faster postoperative patient mobility, and decreasing the risks of general anesthesia and hospital costs (3). Lidocaine reduces inflammatory processes. The substance acts by lowers the release of cytokines from epithelial cells and neutrophils and reducing the production of cytokines caused by damage to endothelial cells (4). These cytokines are of the pro-inflammatory type (5). Dexmedetomidine is an α-agonist (11). Some studies have shown that the use of this drug (due to its low toxicity) can reduce cell death. (6). This drug lowers the concentration of tumor necrosis alpha (TNF-α) (7,8). On the other hand, in various studies on apoptosis of the epithelial cells of the intestine, it has reduced the inflammatory response and accelerated the intestinal improvement after trauma (9,10). In several studies, the positive effect of intravenous Dexmedetomidine on the control of inflammatory responses and the reduction of levels of inflammatory mediators such as IL-6 has been confirmed (12-15). The purpose of this study was to learn whether the use of this drug as an adjuvant in epidural injection has meaningful effects. Confirmation of this positive effect can provide a low cost and easy method to reduce the complications of inflammatory response after lower limb surgery. Methods In this study, all patients were referred to Taleghani Hospital (affiliated to Shahid Beheshti University of Medical Sciences, Tehran, Iran) in 2017, who suffered from lower limb fractures and who needed surgery were evaluated. The inclusion criteria were: 18-75 years old, lower limb fractures, ASA Class I & II, and no history of allergy. However, the following patients were not included in the study: absolute contraindication for using local anesthetics, and the presence of these comorbidities: diabetes mellitus, myocardial infarction, major cardiovascular events, cerebrovascular accidents, hypertension, malignancy, renal failure, liver dysfunction and coagulation disorders.  After explaining the design and obtaining informed written consent, patients were randomly divided into two groups. Patients were administered epidural block with 18-gauge Tuohy needle and catheter was secured 3–4 cm into epidural space and a test dose of 3 ml of 2% Lidocaine solution containing adrenaline 1:200,000 was injected. After 4–6 minutes of administering the test dose, patients in group RC received 5 ml of 1.5% Lidocaine solution. Patients in group RD were administered 15 ml solution of 1.5% ropivacaine and 0.6 μg/kg of Dexmedetomidine. The bilateral pin-prick method was used to evaluate and check the sensory level while a modified Bromage scale (0 = no block, 1 = inability to raise extended leg, 2 = inability to flex knee and 3 = inability to flex ankle and foot) was used to measure the motor blockade effect at 5, 10, 15, 20, 25 and 30 minutes intervals after the epidural administration of the drugs. The second dose was injected every 45-60 minutes based on need (VAS> 3; Visual Analog Scale: VAS), then 8 mL of 1.5%, Lidocaine and the final dose of the received drug was recorded at the end of the operation. Blood samples were taken from all patients before entering the operating room to determine the level of the interleukin-6. During surgery, the onset of anesthesia, time to second injection, duration of operation and volume of blood loss, the volume of intake and output, and the amount of injected drug by the epidural catheter were recorded. In order to control the pain in all patients, intravenous morphine infusion pump was given at a dose of 3 to 5 mg/hr. Additional drug doses were prescribed if necessary to maintain VAS <3 in the first 24 hours. Blood samples were taken at 6 hours after surgery to measure the level of interleukin-6 in all patients. IL-6 detection method 5 cc blood samples were taken from the patient and placed in a simple test tube. After blood clotting at room temperature (15-30 minutes), it was centrifuged (3000 to 3500) at room temperature for 15 minutes. The yielding plasma was poured into the microtube and stored in -70˚C. Collected samples evaluated by Bio-Science ELISA Kits. The obtained data was collected and using descriptive statistics, the results of IL-6 were reported according to the variables in question. In addition, to compare the IL-6 level among the patients in both groups, independent t-test was used. Results Comparison of the Effect of Epidural Anesthesia with Lidocaine and Dexmedetomidine …                             Moshari et al. Vol 3, No 3, Summer 2018 105 In this study, 52 patients, 19 women (36.5%) and 33 men (63.5%), were divided into two groups of 26 patients. The mean age of the patients was 15.8±53.4 years (Table 1). Based on the results, the mean of the second injection requirement (51 out of 52) was 60.7 ± 21.7. Duration of surgery was same between the two groups. Also no significant difference in volume of received fluid during surgery and the level of baseline interleukin was seen. On the other hand, based on independent t-test, there was a significant difference between the two groups regarding the bleeding and urine volumes (p <0.05) (Table 2).According to the U Mann Whitney test, the second injection and drug levels were significantly different between the control and intervention groups. Dexmedetomidine reduced the need for a second injection (p <0.001) (Table 3). There was a significant difference between the two groups in terms of IL-6 after 6 hours of operation, and this was lower in the Dexmedetomidine group (Table 4). Discussion Today, use of regional anesthesia is superior to general anesthesia in many procedures, because it has fewer side effects and makes it easier for the patient to have mobility and daily activities. In recent years, however, stress and cellular damage have become a problem that attracts the attention of experts and researchers and has attracted efforts to reduce it. This study also considers the importance of the present method using two different drugs. Lidocaine and relevant drugs, which are used primarily as positional anesthetics and antiarrhythmic factors. Lidocaine exerts immunoregulatory effects on a variety of cell types. For example, lidocaine-related local anesthetics were shown to inhibit lymphocyte maturation and proliferation, the migration of macrophages into tissues (16), the expression of CD11b/CD18 by polymorphonuclear cells (19), the adhesion of leucocytes to injured venules (17–19) and the LPS-stimulated secretion of LTB4 and IL-1a from peripheral blood mononuclear cells (20). Moreover, the anti-inflammatory effects of lidocaine were shown by in vivo studies as well. Taniguchi  et al., have shown that lidocaine treatment of rabbits injected with endotoxin reduced the serum concentrations of IL-8 and IL-6 (21). Previous studies have shown DEX has a low cytotoxic effect, which in some studies reduces cell death (6). On the other hand, this drug lowers the concentration of tumor necrosis alpha (TNF-α) (7,8). In various studies on apoptosis of the epithelial cells of the intestine, it reduces the inflammatory response and accelerates the intestinal improvement after trauma (9,10). In several studies, the positive effect of intravenous Dexmedetomidine on the control of inflammatory responses and the decrease, of levels of inflammatory mediators such as IL-6 has been confirmed (12-15). Accordingly, based on these results, dexmedetomidine not only reduces the amount and frequency of analgesic drug administration, but also reduces stress and cellular damage. So, dexmedetomidine is suggested as a good option for Table 1: Descriptive statistics of variables  N Minimum Maximum Mean Std. Deviation Age (years) 52 24.00 75.00 53.4038 15.8439 Onset time (min) 52 10.00 22.00 15.8846 3.12268 Second injection(min) 51 35.00 165.00 60.7647 21.71690 LA Final Vol (ml) 52 20.00 65.00 42.0385 9.48469 Received fluid (L) 52 1.50 28.00 3.0808 3.55500 Blooding volume (ml) 52 50.00 600.00 257.3077 122.60434 Urine volume (ml) 52 50.00 1000.00 595.1923 173.56120 Base Serum IL (pg/ml) 52 0.20 23.50 4.1892 5.70042 Six hours IL_6 (pg/ml) 52 1.1 120 20.07 19.93 Surgery time (min) 52 75.00 300.00 177.2115 43.81796 Valid Number of cases 51      Moshari et al.                               Comparison of the Effect of Epidural Anesthesia with Lidocaine and Dexmedetomidine … Journal of Cellular & Molecular Anesthesia (JCMA) 106 similar surgeries. Of course, further studies are needed in order to evaluate the best application and other effects of the drugs used in this study can lead to better anesthesia plans.  Conclusion Not only does dexmedetomidine reduce the need for patients on the amount and frequency of analgesic drugs, but also it lowers stress and cellular damage. Acknowledgment The authors would like to acknowledge the kind help of all physicians and nurses of Taleghani Hospital, SBMU, Tehran, Iran for their kind assistance. Conflicts of Interest The authors declare that they have no conflict of interest.  References 1. Charles B, Strichantz B&GR. Local anesthetics: In Miller, RD, editor. Anesthesia. Vol 1, 5th ed.Philadelphia: Churchill Livingstone; 2000, P. 491-517. 2. Turkan H, Baykal B, Ozisik T. Axillary brachial plexus blockade: an evaluation of three techniques. Mil Med. 2002;167(9):723-5. 3. Bergendahl H, Lönnqvist PA, Eksborg S. Clonidine: an alternative to benzodiazepines for premedication in children. Current opinion in anesthesiology. 2005;18(6):608-13. 4. Hollmann MW, Durieux ME. Local anesthetics and the inflammatory response: a new therapeutic indication. Anesthesiology. 2000;93:858–75. 5. Lahav M, Levite M, Bassani L. Lidocaine inhibits secretion of IL-8 and IL-1beta and stimulates secretion receptor antagonist by epithelial cells. ClinExpImmunol. 2002;127:226–33. 6. Sinclair R, Eriksson AS, Gretzer C, et al. Inhibitory effects of amide local anesthetics on stimulus-induced human leukocyte metabolic activation, LTB4 release and IL-1 secretion in vitro. Acta Anaesthesiol Scand. 1993;37:159–65. 7. Sanders RD, Xu J, Shu Y, Januszewski A, Halder S, Fidalgo A, Sun P, Hossain M, Ma D, Maze M. Dexmedetomidine attenuates isoflurane-induced neurocognitive impairment in neonatal rats. Anesthesiology. 2009;110:1077–85. 8. Li B, Li Y, Tian S, Wang H, Wu H, Zhang A, et al. Anti-inflammatory effects of perioperative dexmedetomidine administered as an adjunct to general anesthesia: a meta-analysis, Sci. Rep. 5(2015):12342. 9. Kuru S, Bozkirli OB, Barlas AM, Duymus ME, Senes M, Yumusak N, et al. The preventive effect of dexmedetomidine against postoperative intra-abdominal adhesions in rats, Int. Surg. 2015;100(1):87–95. 10. Liu YE, Tong CC, Zhang YB, Jin HX, Gao Y, Hou MX. Effect of dexmedetomidine on rats with renal ischemia-reperfusion injury and the expression of tight junction protein in kidney, Int. J. Clin. Exp. Med. 2015;8(10):18751–7. 11. Riquelme JA, Westermeier F, Hall AR, Vicencio JM, Pedrozo Z, Ibacache B, et al. Dexmedetomidine protects the heart against ischemia-reperfusion injury by an endothelial eNOS/NO-dependent mechanism, Pharmacol. Res. 2016;103:318–27. 12. Xin Y, Xie K, Xie H. Effects of Dexmedetomidine on Survival Rate, IL-6, and IL-10 of Rats with Sepsis. Sepsis. 2012;5:020. 13. Yun SH, Park JC, Kim SR, Choi YS. Effects of Dexmedetomidine on Serum Interleukin-6, Hemodynamic Stability, and Postoperative Pain Relief in Elderly Patients under Spinal Anesthesia. ActaMedica Okayama. 2016;70(1):37-43. 14. Farghaly HS, Mahmoud AM, Abdel-Sater KA. Effect of dexmedetomidine and cold stress in a rat model of neuropathic pain: Role of interleukin-6 and tumor necrosis factor-α. European journal of pharmacology. 2016;776:139-45 15. Ebrahimpour A, Okhovatpour MA, Sadighi M, Sarejloo AH, Sajjadi MR. Comparative investigation of percutaneous plating and intramedullary nailing effects on IL-6 production in patients with tibia shaft fracture. Acta orthopaedica et traumatologica turcica. 2017;51(6):478-81. 16. Dickstein R, Kiremidjian-Schumacher L, Stotzky G. Effects of lidocaine on the function of immunocompetent cells. I. In vitro exposure of mouse spleen lymphocytes and peritoneal macrophages. Immunopharmacology. 1985;9(3):117-25. 17. Giddon DB, Lindhe J. In vivo quantitation of local anesthetic suppression of leukocyte adherence. The American journal of pathology. 1972;68(2):327. 18. MacGregor RR, Thorner RE, Wright DM. Lidocaine inhibits granulocyte adherence and prevents granulocyte delivery to inflammatory sites. Blood. 1980;56(2):203-9. 19. Martinsson T, Oda T, Fernvik E, Roempke K, Dalsgaard CJ, Svensjö E. Ropivacaine inhibits leukocyte rolling, adhesion and CD11b/CD18 expression. Journal of Pharmacology and Experimental Therapeutics. 1997;283(1):59-65. 20. Sinclair R, Eriksson AS, Gretzer C, Cassuto J, Thomsen P. Inhibitory effects of amide local anaesthetics on stimulus‐induced human leukocyte metabolic activation, LTB4 release and IL‐1 secretion in vitro. Acta anaesthesiologica scandinavica. 1993;37(2):159-65. 21. Taniguchi T, Shibata K, Yamamoto K et al. Effects of lidocaine administration on hemodynamics and cytokine responses to endotoxemia in rabbits. Crit Care Med 2000; 28:755–9    Comparison of the Effect of Epidural Anesthesia with Lidocaine and Dexmedetomidine …                             Moshari et al. Vol 3, No 3, Summer 2018 107   Table 2- Based on independent t-test, among the variables studied in this study, the mean volume of bleeding and volume of urine show a significant difference between the control and intervention groups.  Leven,s Test for Equality of Variances  t-test for Equality of Means F Sig. t d.f Sig.(2-tailed) Mean Difference Std. Error Difference 95% Confidence interval of the Difference Lower Upper  Blooding volume Equal variances assumed 0.205 0.653 3.315 50 0.02 103.07692 31.09539 40.62000 165.53385 Equal variances not assumed   3.315 49.843 0.02 103.07692 31.09539 40.61514 165.53871  Urine volume Equal variances assumed 2.370 0.130 2.472 50 0.017 113.46154 45.89188 21.28498 205.63810 Equal variances not assumed   2.472 46.173 0.017 113.46154 45.89188 21.09528 205.82779  Surgery time Equal variances assumed 1.405 0.241 0.424 50 0.674 5.19231 12.25186 -19.41627 29.80089 Equal variances not assumed   0.424 46.215 0.674 5.19231 12.25186 -19.46630 29.85092   Table 3- According to the U Mann Whitney test, the second injection and drug levels had a significant difference between the control and intervention groups  Group N Mean Rank Sum of Ranks   Drug rate Normal saline 26 14.00 364.00 Dexmedetomidine 26 39.00 1014.00 Total 52     Second injection Normal saline 26 18.58 483.00 Dexmedetomidine 25 33.72 843.00 Total 51     Received fluid Normal saline 26 27.71 720.50 Dexmedetomidine 26 25.29 657.50 Total 52     Base serum IL-6 level Normal saline 26 26.15 680.00 Dexmedetomidine 26 26.85 698.00 Total 52     Table 4: The mean level of interleukin six hours after surgery, which was the main presumption in this study, is also p <0.05, which shows a significant difference between the two groups.  Group N Mean Std. Deviation Std. Error Mean Six hours IL-6 level Normal saline 27 26.6333 24.44054 4.70358 Dexmedetomidine 25 12.9800 9.81411 1.96282  

Epidural Anesthesia with Lidocaine and Dexmedetomidine, Versus Lidocaine Alone on Plasma Levels of IL-6 in Patients with Proximal Femoral Fracture.

Journals Portal, Shahid Beheshti University of Medical Sciences

https://journals.sbmu.ac.ir/jcma/article/download/21115/15869

Epidural Anesthesia with Lidocaine and Dexmedetomidine, Versus Lidocaine Alone on Plasma Levels of IL-6 in Patients with Proximal Femoral Fracture.

Abstract

Similar works

Full text

Available Versions

Directory of Open Access Journals

Journals Portal, Shahid Beheshti University of Medical Sciences