|Year : 2019 | Volume
| Issue : 1 | Page : 132-137
Hepatic protective effect of dexmedetomidine after partial hepatectomy surgery: A prospective controlled study
Hani I Taman, Emad Elhefnawy
Department of Anesthesia and Surgical Intensive Care, Mansoura Faculty of Medicine, Mansoura University, Mansoura, Egypt
|Date of Web Publication||7-Mar-2019|
Hani I Taman
Mansoura Faculty of Medicine, Mansoura University, Mansoura
Source of Support: None, Conflict of Interest: None
| Abstract|| |
Background: Inflow occlusion of the portal triad is a common blood loss-reducing method during hepatectomy which may induce ischemic-reperfusion injury of the remaining parts of the liver. Dexmedetomidine is used for reducing ischemic-reperfusion injury in hepatectomy. Aim: The aim of this study was to assess the protective effect of dexmedetomidine on liver after partial hepatectomy using inflow occlusion. Setting and Design: This prospective controlled, double-blinded, randomized study included any patients of either sex with age between 20 and 70 years, those in physical status American Society of Anesthesiologists Classes I and II, and those who were planned for partial hepatectomy. Patients and Methods: Patients with elective hepatectomy were randomized into dexmedetomidine group, which received dexmedetomidine at 0.3 mg/kg/h, and control group, which received a placebo. Statistical Analysis: Statistical analysis was performed using IBM SPSS software version 18. Data were tested using Kolmogorov–Smirnov test, independent t-test or Mann–Whitney U-test, and Chi-square or Fisher's exact test. The statistical significance was considered at P < 0.05. Results: Serum albumin, aspartate aminotransferase, alanine aminotransferase, prothrombin time were higher in control group in comparison to dexmedetomidine group. Hypotension duration was lower in control group in comparison to dexmedetomidine group. Vasoconstrictor usage, amount of blood loss, and colloid, crystalloid, and blood given to patients were higher in control group in comparison to the study group. Conclusions: Dexmedetomidine can protect the liver during hepatic resection surgery with inflow occlusion with decreasing blood loss and need for blood transfusion.
Keywords: Dexmedetomidine, inflow occlusion, ischemic-reperfusion injury, protection
|How to cite this article:|
Taman HI, Elhefnawy E. Hepatic protective effect of dexmedetomidine after partial hepatectomy surgery: A prospective controlled study. Anesth Essays Res 2019;13:132-7
|How to cite this URL:|
Taman HI, Elhefnawy E. Hepatic protective effect of dexmedetomidine after partial hepatectomy surgery: A prospective controlled study. Anesth Essays Res [serial online] 2019 [cited 2019 Jun 18];13:132-7. Available from: http://www.aeronline.org/text.asp?2019/13/1/132/253110
| Introduction|| |
Inflow occlusion by clamping of the portal triad is a common method for bleeding reduction during hepatectomy. Reperfusion after portal vein occlusion may induce ischemic-reperfusion injury of the remaining parts of the liver with impairment of liver function and other organs.,
One of the recent drugs used to attenuate the effect of ischemic-reperfusion injury after inflow occlusion in hepatectomy procedures is dexmedetomidine. It is a selective α2-receptor agonist. It has been studied in ischemic-reperfusion injuries in many organ systems.,,, Furthermore, it can be used as an anesthetic adjuvant during the surgery to provide good perioperative cardiovascular stability and decreases the intraoperative anesthetic and analgesic requirements.
In previous studies, dexmedetomidine was given in a bolus followed by a maintenance dose as anesthetic adjuvants. Recently, a loading dose is unnecessary in most patients as it may increase the risk of hypotension and bradycardia. These studies also tried to evaluate the protective effect of dexmedetomidine on various organs against ischemic-reperfusion injury using various prognostic nonspecific indicators.,,,,
The aim of this study was to assess the protective effect of continuous infusion of dexmedetomidine without giving a loading dose on liver functions after inflow occlusion during partial hepatectomy.
| Patients and Methods|| |
This prospective, controlled, double-blinded, randomized study was created over 1 year and after approval of our Institutional Board Review and informed written consent from every patient was obtained first.
Any patients of either sex with age between 20 and 70 years and patient of American Society of Anesthesiologists Physical Status Classes I and II and planned for partial hepatectomy were included in the study. On the other hand, patient refusal, any renal diseases, cardiac ejection fraction <40%, myocardial infarction within 3 months or any anginal pain within 48 h, fulminant hepatitis, or pulmonary dysfunction were considered as exclusion criteria in the study.
On arrival to the preoperative area, enrolled patients were randomized into a dexmedetomidine (D) group or a control (C) group. The randomization sequence was generated by a computer program and consecutively numbered envelopes providing concealment of random allocation.
All patients were monitored using five leads electrocardiogram, peripheral oxygen saturation, entropy, and arterial pressure were invasively monitored through a radial artery cannula that used also for arterial blood gas sampling. The right internal jugular vein was cannulated using three-lumen catheter for central venous pressure (CVP) measurement, aspiration of air embolism if happened, and rapid infusion of blood or infusion of vasoactive drugs. Urine output was monitored through a urinary catheter right after the induction of anesthesia.
Anesthesia was started with air-oxygen mixture, FIO250%, then propofol 2 mg/kg fentanyl 2 μg/kg, and 1 mg/kg rocuronium. After tracheal intubation, anesthesia was maintained with isoflurane in oxygen Minimum Alveolar Concentration (MAC) 1, fentanyl 1–2 μg/kg/h, and rocuronium 0.3 mg/kg/h. The mean arterial pressure was kept at a target of 75% from its basal value. Ringer's lactate solution was used as primary fluids in volume replacement during the surgery.
In dexmedetomidine (D) group, dexmedetomidine was dissolved in 0.9% sodium chloride with the concentration of 4 mg/mL and infused at 0.3 mg/kg/h., While in the control (C) group, a maintenance dose from the same syringe at a relevant rate to the treatment group was administered as placebo. The infusion of dexmedetomidine and sodium chloride was started after intubation and stopped when the surgery finished.
After mobilization of the liver, inflow occlusion was achieved by a 4-mm mersilene tape around the portal triad in a standardized manner, and the CVP was maintained at 0–5 mmHg during resections and the surgeons determined the length of continuous inflow occlusion time.
All patients were transferred to postanesthesia care unit after surgery for further observation. Postoperative analgesia was managed by epidural block and patient-controlled analgesia using baseline infusion of morphine 3 mg/h with bloused 1 mg every 5 min according to patient requirement together with 1 g paracetamol every 6 h.
Total bilirubin, albumin, aspartate aminotransferase (AST), alanine aminotransferase (ALT) and prothtombin time postoperative care unit time, and length of hospital stay were recorded were measured at three times as follows: baseline (before surgery), 12, 24 and 48 h after surgery as indicators for liver function state. Duration of anesthesia, surgery, liver ischemia and inoperative hypotension were recorded. Volume of blood loss, colloid and crystalloid given were recorded both intra and postoperative respectively. The number of vasoactive drug usage and length of hospital stay were also recorded.
A sample size of this study was calculated using G Power version 3.0.10. Copyright © 1992-2008, Germany. according to differences in postoperative peak AST level in the pilot study of patients undergoing partial hepatectomy with inflow occlusion who received propofol anesthesia with or without dexmedetomidine. It revealed 21 patients in each arm to obtain the power of about 85%. We increased the number of patients up to 25 patients in each group to compensate 20% possible dropouts.
Statistical analysis was performed using IBM SPSS for Windows (Chicago, USA), version 18. Data were first tested for normality using the Kolmogorov–Smirnov test. Continuous data were analyzed with the independent t-test or Mann–Whitney U-test, respectively, and expressed as mean ± standard deviation or median and interquartile range. Categorical data were described as frequency or percentage and were analyzed with the Chi-square or Fisher's exact test when appropriate. Statistical significance was considered when P < 0.05.
| Results|| |
There were no differences between both groups as regard demographic data and BMI [Table 1].
|Table 1: Demographic data and BMI of the studied groups. Data are expressed as mean±SD, number and %|
Click here to view
Serum total bilirubin and AST were higher in control group when compared to dexmedetomidine group at 12, 24, and 48 h postoperative. Similarly, ALT was higher in the control group at 12 and 24 h postoperative in comparison to dexmedetomidine group. Meanwhile, albumin and prothrombin time (PT) was only lower in the control group than the study group at 12 h postoperative [Table 2].
|Table 2: Perioperative liver functions' results of the studied groups. Data are expressed as mean±SD|
Click here to view
Duration of hypotension was longer and the number of vasoconstrictor usage was higher in dexmedetomidine group in comparison to the control group [[Table 3] and [Table 4], respectively]. Meanwhile, the amount of blood loss, colloid, and blood given to the patients on need was lower in dexmedetomidine group when compared to similar amounts recorded in the control group both intraoperative and after the surgery. In the same way, the amount of crystalloids given to the patients were lower in dexmedetomidine group intraoperatively than the amount used in control group but showed no difference postoperatively [[Table 3] and [Table 5], respectively]. The length of hospital showed no differences between both groups when compared together [Table 4].
|Table 3: Intraoperative data of the studied groups. Data are expressed as mean±SD|
Click here to view
|Table 4: Vasoconstrictive use and length of hospital saty of the studied groups. Data are expressed as mean±SD, number and %|
Click here to view
|Table 5: Post-operative blood loss, blood, colloid and crystalloid given in the studied groups. Data are expressed as mean±SD|
Click here to view
| Discussion|| |
Liver dysfunction after hepatic resection encompasses a wide range from a transient rise in liver enzymes to liver failure and death. The features include coagulopathy, hyperbilirubinemia, encephalopathy, and associated multiple organ failure.
Furthermore, liver dysfunction can occur after any major surgery due to periods of intraoperative hypoxia, hypotension, blood transfusions or development of sepsis that can result in liver ischemia, and/or cellular dysfunction. Major blood loss after liver resection with the need for blood transfusion increases the risk of postoperative liver failure and sepsis., Sepsis itself has a detrimental effect on liver function and hepatic cell regeneration.
Especially in diseased liver, functional and regenerative capacity of the liver is reduced and therefore makes it more susceptible to damage. Furthermore, a sinusoidal injury which may occur as a result from small-for-size syndrome and steatosis from chemotherapy reduce the regenerative capacity of the liver cells and therefore increase the likelihood of postoperative failure., It is related to portal hyperperfusion of the graft, combined with poor venous outflow, resulting in sinusoidal congestion and endothelial dysfunction.
To reduce intraoperative bleeding, vascular occlusive techniques are used by either total occlusion of both inflow and outflow or total inflow occlusion (Pringle maneuver). This limits blood supply to the liver, with limiting the bleeding to hepatic venous pressure only, which itself can be reduced by maintaining a low CVP intraoperatively. Occlusion causes ischemia in the liver remnant, resulting in hepatic ischemia-reperfusion injury with the generation of free radicals and subsequent liver dysfunction. For this reason, the Pringle maneuver is restricted to 45 min in total during the surgery.,
Dexmedetomidine is a new drug which acts selectively on α2-adrenoceptor agonist with an imidazole structure and is up to eight times more selective than clonidine, an α2-agonist, for α2-receptor.
In cases with varying degrees of hepatic impairment (Child-Pugh Class A, B, or C), dexmedetomidine clearance is reduced than in healthy participants. The mean clearance values for participants with mild, moderate, and severe hepatic impairment were 74%, 64%, and 53%, of those observed in the normal healthy participants, respectively. Although dexmedetomidine hydrochloride is dosed to effect, it may be necessary to consider dose reduction depending on the degree of hepatic impairment.
The cardiovascular effects of dexmedetomidine are highly predictable. In the absence of a loading dose, an average of 10% fall in systolic blood pressure, heart rate, and cardiac output has been observed when a dose of 1 μg/kg/h is used. Although the currently licensed dose is 1 μg/kg/h, dexmedetomidine must not be given as a bolus at any time to avoid exaggerated cardiac depression.
In the present study, it was found that total serum bilirubin, alanine transferase, aspartate transferase, and PT were higher in the control group in comparison to the study group.
Previous studies have demonstrated that dexmedetomidine exhibited antiapoptotic and anti-inflammatory effects apart from its anesthetic features., Moreover, studies in animals have reported organ-protective effects of dexmedetomidine in ischemia-reperfusion injury., It also reduces the oxidative stress and cellular damage as a result of the imbalance between reactive oxygen species and decreased biological ability of the cell to repair itself. Similarly, the antioxidant and anti-inflammatory effects of dexmedetomidine have been confirmed in various experimental studies.
Furthermore, dexmedetomidine has a protective effect against high N Methyle D Aspartate (NMDA) levels and potent anti-inflammatory capacity.,, Dexmedetomidine attenuates interleukin-6 and tumor necrosis factor-α levels. Yang et al., in their research, suggested that therapeutic anti-inflammatory effects of dexmedetomidine might be associated with its α2-adrenergic activity which attenuates inflammation-triggered liver injury.
There is an increasing number of experimental studies that proved the protective effects of dexmedetomidine on pulmonary functions in acute lung injury secondary to sepsis, hemorrhagic shock, ischemia-reperfusion injury, and ventilator-induced lung injury and seriously ill patients in intensive care units.,,
In the same way, our previous study showed that dexmedetomidine administration before, but not after, ischemia had dose-dependent protective effects on ischemic-reperfusion-induced intestinal injury, partly by inhibiting inflammatory response and intestinal mucosal epithelial apoptosis through α2-adrenoreceptor activation in a rat model. Similar to the above findings, this study also showed that dexmedetomidine can confer protection on the intestine and liver for clinical patients during hepatic ischemic-reperfusion injury.
Our study proved hepatectomy with inflow occlusion caused postoperative liver injury which could be alleviated by dexmedetomidine. It is probably because the Pringle time in the present study was controlled mostly around 20 min and did not have too much influence on hemodynamic data; moreover, the dosage of dexmedetomidine administration in this study remained conserved compared with animal researches before for the sake of avoiding adverse cardiovascular side-effects, and drug accumulation in patients undergoing liver surgery.
Kocoglu et al. and Hall et al. reported that dexmedetomidine reduced the levels of NMDA and catecholamine in plasma in rats. Therefore, dexmedetomidine may prevent liver ischemic-reperfusion injury through the suppression of catecholamine released by activating presynaptic α2-receptors.
The duration of hypotension was longer and the number of vasoconstrictor usage was higher in dexmedetomidine group in comparison to control group.
Dexmedetomidine by activation of α2-receptors on the locus coeruleus in the central nervous system, promotes a significant reduction in circulating catecholamine, with moderate reduction in heart rate and blood pressure.
By decreasing norepinephrine release and renal sympathetic activity in the presynaptic region, dexmedetomidine enhances blood flow to the kidneys, which leads to vasodilatation. As a result of these effects in response to surgical stress, hypotension and/or bradycardia may occur.,
Our results showed higher occurrence of hypotension and the need for vasoconstrictors among patients of dexmedetomidine infusion groups compared with the placebo group. This effect is similar to the results proved by Balkanay et al. who proved rise in hypotension and/or bradycardia occurrence with dexmedetomidine use.
In contrast, as reported by Dere et al., a significant increase in mean arterial pressure was observed in relation to the control group. This fact may be related to the different regimens of drug administration and associated techniques. The amount of blood loss, colloid, and blood given to the patients on need were lower in dexmedetomidine group when compared to similar amounts recorded in control group both intraoperative and after the surgery. In the same way, the amount of crystalloids given to the patients was lower in dexmedetomidine group intraoperatively than the amount used in control group but showed no difference postoperatively.
Attenuated response of sympathetic nervous system to surgical stress has been suggested as a potential benefit of α2-adrenergic agonists that may lead to hypotension vasodilatation and increases the capacity of great vessels. These all factors may be the cause of reported lower blood loss in patients who received dexmedetomidine group when compared to control group.
Opposite to the current study, Leino et al. in his research stated that however the plasma norepinephrine level was reduced the surgery. It might have an influence on the greater blood loss in the dexmedetomidine group compared to the placebo group since high adrenergic output favors thrombosis.
This primitive trial was one of the earliest trials designed to detect liver protective effects of dexmedetomidine, and the dose of given dexmedetomidine was based on other studies on its renal or cardiac protective effect. To overcome this point, multicenter trials using different doses may be conducted at the same time to select the most proper dose. Furthermore, previous similar studies were conducted only on rates, but so long as, there are no contraindications for the use of dexmedetomidine in hepatic impairment, we decided to use it in human; however, there was a lack in comparative date.
| Conclusions|| |
This study strongly confirms that dexmedetomidine when given preoperatively may potentially protect the liver during hepatic resection surgery with inflow occlusion, also with decreasing blood loss and need for blood transfusion.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Kooby DA, Stockman J, Ben-Porat L, Gonen M, Jarnagin WR, Dematteo RP, et al.
Influence of transfusions on perioperative and long-term outcome in patients following hepatic resection for colorectal metastases. Ann Surg 2003;237:860-9.
van der Bilt JD, Livestro DP, Borren A, van Hillegersberg R, Borel Rinkes IH. European survey on the application of vascular clamping in liver surgery. Dig Surg 2007;24:423-35.
Dahmani S, Rouelle D, Gressens P, Mantz J. Effects of dexmedetomidine on hippocampal focal adhesion kinase tyrosine phosphorylation in physiologic and ischemic conditions. Anesthesiology 2005;103:969-77.
Kocoglu H, Ozturk H, Ozturk H, Yilmaz F, Gulcu N. Effect of dexmedetomidine on ischemia-reperfusion injury in rat kidney: A histopathologic study. Ren Fail 2009;31:70-4.
Engelhard K, Werner C, Eberspächer E, Bachl M, Blobner M, Hildt E, et al.
The effect of the alpha 2-agonist dexmedetomidine and the N-methyl-D-aspartate antagonist S(+)-ketamine on the expression of apoptosis-regulating proteins after incomplete cerebral ischemia and reperfusion in rats. Anesth Analg 2003;96:524-31.
Okada H, Kurita T, Mochizuki T, Morita K, Sato S. The cardioprotective effect of dexmedetomidine on global ischaemia in isolated rat hearts. Resuscitation 2007;74:538-45.
Arcangeli A, D'Alò C, Gaspari R. Dexmedetomidine use in general anaesthesia. Curr Drug Targets 2009;10:687-95.
Wang ZX, Huang CY, Hua YP, Huang WQ, Deng LH, Liu KX, et al.
Dexmedetomidine reduces intestinal and hepatic injury after hepatectomy with inflow occlusion under general anaesthesia: A randomized controlled trial. Br J Anaesth 2014;112:1055-64.
Yahya S, John B, David E, Ross F, Michael R, Brigit R, et al
. Clinical application, the use of dexmedetomidine in intensive care sedation. Crit Care Shock 2010;13:40-50.
Tüfek A, Tokgöz O, Aliosmanoglu I, Alabalik U, Evliyaoglu O, Çiftçi T, et al.
The protective effects of dexmedetomidine on the liver and remote organs against hepatic ischemia reperfusion injury in rats. Int J Surg 2013;11:96-100.
Sahin T, Begeç Z, Toprak Hİ, Polat A, Vardi N, Yücel A, et al.
The effects of dexmedetomidine on liver ischemia-reperfusion injury in rats. J Surg Res 2013;183:385-90.
Yeh YC, Sun WZ, Ko WJ, Chan WS, Fan SZ, Tsai JC, et al.
Dexmedetomidine prevents alterations of intestinal microcirculation that are induced by surgical stress and pain in a novel rat model. Anesth Analg 2012;115:46-53.
Rolando N, Wade J, Davalos M, Wendon J, Philpott-Howard J, Williams R, et al.
The systemic inflammatory response syndrome in acute liver failure. Hepatology 2000;32:734-9.
Blaudszun G, Lysakowski C, Elia N, Tramèr MR. Effect of perioperative systemic α2 agonists on postoperative morphine consumption and pain intensity: Systematic review and meta-analysis of randomized controlled trials. Anesthesiology 2012;116:1312-22.
Gurbet A, Basagan-Mogol E, Turker G, Ugun F, Kaya FN, Ozcan B, et al.
Intraoperative infusion of dexmedetomidine reduces perioperative analgesic requirements. Can J Anaesth 2006;53:646-52.
Song JC, Sun YM, Yang LQ, Zhang MZ, Lu ZJ, Yu WF, et al.
Acomparison of liver function after hepatectomy with inflow occlusion between sevoflurane and propofol anesthesia. Anesth Analg 2010;111:1036-41.
Chris J, Leigh K, Colin B, Nial Q, Chris J, Leigh K. Acute liver failure following hepatic resection: Incidence, presentation, prevention and management in ICU. Intensive Care Soc 2013;14:112-9.
Jensen LS, Andersen AJ, Christiansen PM, Hokland P, Juhl CO, Madsen G, et al.
Postoperative infection and natural killer cell function following blood transfusion in patients undergoing elective colorectal surgery. Br J Surg 1992;79:513-6.
Garcea G, Maddern GJ. Liver failure after major hepatic resection. J Hepatobiliary Pancreat Surg 2009;16:145-55.
Hammond JS, Guha IN, Beckingham IJ, Lobo DN. Prediction, prevention and management of postresection liver failure. Br J Surg 2011;98:1188-200.
Behrns KE, Tsiotos GG, DeSouza NF, Krishna MK, Ludwig J, Nagorney DM, et al.
Hepatic steatosis as a potential risk factor for major hepatic resection. J Gastrointest Surg 1998;2:292-8.
Karoui M, Penna C, Amin-Hashem M, Mitry E, Benoist S, et al
. Influence of preoperative chemotherapy on the risk of major hepatectomy for colorectal liver metastases. Ann Surg 2006;12:243-50.
Paugam-Burtz C, Wendon J, Belghiti J, Mantz J. Case scenario: Postoperative liver failure after liver resection in a cirrhotic patient. Anesthesiology 2012;116:705-11.
Brooks AJ, Hammond JS, Girling K, Beckingham IJ. The effect of hepatic vascular inflow occlusion on liver tissue pH, carbon dioxide, and oxygen partial pressures: Defining the optimal clamp/release regime for intermittent portal clamping. J Surg Res 2007;141:247-51.
Lordan JT, Worthington TR, Quiney N, Fawcett WJ, Karanjia ND. Operative mortality, blood loss and the use of Pringle manoeuvres in 526 consecutive liver resections. Ann R Coll Surg Engl 2009;91:578-82.
Sugiyama Y, Ishizaki Y, Imamura H, Sugo H, Yoshimoto J, Kawasaki S, et al.
Effects of intermittent Pringle's manoeuvre on cirrhotic compared with normal liver. Br J Surg 2010;97:1062-9.
Murthy TV, Ranju S. A 2 adrenoceptor agonist – Dexmedetomidine role in anaesthesia and intensive care: A clinical review. J Anaesthesiol Clin Pharmacol 2009;25:267-72. [Full text]
Sanders RD, Sun P, Patel S, Li M, Maze M, Ma D, et al.
Dexmedetomidine provides cortical neuroprotection: Impact on anaesthetic-induced neuroapoptosis in the rat developing brain. Acta Anaesthesiol Scand 2010;54:710-6.
Taniguchi T, Kidani Y, Kanakura H, Takemoto Y, Yamamoto K. Effects of dexmedetomidine on mortality rate and inflammatory responses to endotoxin-induced shock in rats. Crit Care Med 2004;32:1322-6.
Gu J, Chen J, Xia P, Tao G, Zhao H, Ma D, et al.
Dexmedetomidine attenuates remote lung injury induced by renal ischemia-reperfusion in mice. Acta Anaesthesiol Scand 2011;55:1272-8.
Hanci V, Erol B, Bektaş S, Mungan G, Yurtlu S, Tokgöz H, et al.
Effect of dexmedetomidine on testicular torsion/detorsion damage in rats. Urol Int 2010;84:105-11.
Valko M, Leibfritz D, Moncol J, Cronin MT, Mazur M, Telser J, et al.
Free radicals and antioxidants in normal physiological functions and human disease. Int J Biochem Cell Biol 2007;39:44-84.
Can M, Gul S, Bektas S, Hanci V, Acikgoz S. Effects of dexmedetomidine or methylprednisolone on inflammatory responses in spinal cord injury. Acta Anaesthesiol Scand 2009;53:1068-72.
Yang CL, Tsai PS, Huang CJ. Effects of dexmedetomidine on regulating pulmonary inflammation in a rat model of ventilator-induced lung injury. Acta Anaesthesiol Taiwan 2008;46:151-9.
Yang CH, Tsai PS, Wang TY, Huang CJ. Dexmedetomidine-ketamine combination mitigates acute lung injury in haemorrhagic shock rats. Resuscitation 2009;80:1204-10.
Yang CL, Chen CH, Tsai PS, Wang TY, Huang CJ. Protective effects of dexmedetomidine-ketamine combination against ventilator-induced lung injury in endotoxemia rats. J Surg Res 2011;167:e273-81.
Memiş D, Hekimoǧlu S, Vatan I, Yandim T, Yüksel M, Süt N, et al.
Effects of midazolam and dexmedetomidine on inflammatory responses and gastric intramucosal pH to sepsis, in critically ill patients. Br J Anaesth 2007;98:550-2.
Zhang XY, Liu ZM, Wen SH, Li YS, Li Y, Yao X, et al.
Dexmedetomidine administration before, but not after, ischemia attenuates intestinal injury induced by intestinal ischemia-reperfusion in rats. Anesthesiology 2012;116:1035-46.
Ebert TJ, Hall JE, Barney JA, Uhrich TD, Colinco MD. The effects of increasing plasma concentrations of dexmedetomidine in humans. Anesthesiology 2000;93:382-94.
Helbo-Hansen S, Fletcher R, Lundberg D, Nordström L, Werner O, Ståhl E, et al.
Clonidine and the sympatico-adrenal response to coronary artery by-pass surgery. Acta Anaesthesiol Scand 1986;30:235-42.
Taoda M, Adachi YU, Uchihashi Y, Watanabe K, Satoh T, Vizi ES. Effect of dexmedetomidine on the release of [3H]-noradrenaline from rat kidney cortex slices: Characterization of alpha2-adrenoceptor. Neurochem Int 2001;38:317-22.
Balkanay OO, Goksedef D, Omeroglu SN, Ipek G. The dose-related effects of dexmedetomidine on renal functions and serum neutrophil gelatinase-associated lipocalin values after coronary artery bypass grafting: A randomized, triple-blind, placebo-controlled study. Interact Cardiovasc Thorac Surg 2015;20:209-14.
Dere K, Sucullu I, Budak ET, Yeyen S, Filiz AI, Ozkan S, et al.
Acomparison of dexmedetomidine versus midazolam for sedation, pain and hemodynamic control, during colonoscopy under conscious sedation. Eur J Anaesthesiol 2010;27:648-52.
Bekker A, Sturaitis MK. Dexmedetomidine for neurological surgery. Neurosurgery 2005;57:1-0.
Leino K, Hynynen M, Jalonen J, Salmenperä M, Scheinin H, Aantaa R, et al.
Renal effects of dexmedetomidine during coronary artery bypass surgery: A randomized placebo-controlled study. BMC Anesthesiol 2011;11:9.
[Table 1], [Table 2], [Table 3], [Table 4], [Table 5]