|Ahead of print publication
The effect of midazolam and dexmedetomidine sedation on block characteristic following spinal bupivacaine: A randomized comparative study
Sanjay Kumar1, Mumtaz Hussain1, Nidhi Arun1, Arvind Kumar1, Mukesh Kumar2
1 Department of Anaesthesia, Indira Gandhi Institute of Medical Sciences, Patna, Bihar, India
2 Department of General Surgery, Indira Gandhi Institute of Medical Sciences, Patna, Bihar, India
|Date of Submission||08-Sep-2020|
|Date of Decision||17-Oct-2020|
|Date of Acceptance||21-Oct-2020|
|Date of Web Publication||07-Dec-2020|
E/302, Jalalpur Heights, Mansarovar Colony, RPS More, Patna - 801 503, Bihar
Source of Support: None, Conflict of Interest: None
| Abstract|| |
Background: Dexmedetomidine is widely used as an adjunct to general as well as regional anesthesia. Aims: This study was conducted to compare and evaluate the synergistic effect of single intravenous (i.v.) bolus dose of dexmedetomidine with midazolam on spinal block duration, analgesia, and sedation in patients undergoing infra-umbilical surgeries. Settings and Design: Prospective, randomized, comparative, and double-blinded study. Materials and Methods: One hundred patients between 18 and 60 years of age of American Society of Anesthesiologists physical status I and II posted for elective infra-umbilical surgery under subarachnoid block were randomly divided into two groups (Group D and Group M). Patients of Group D received i.v. dexmedetomidine 0.5 mg.kg−1 and of Group M received i.v. midazolam 0.05 mg.kg−1 as premedication 5 min before spinal anesthesia over 10 min. Vital parameters, Ramsay sedation score, level of sensory and motor block, recovery time for sensory blockade, postoperative numerical rating scale, time of requirement of the first dose of postoperative rescue analgesic, and duration of analgesia were recorded and analyzed. Statistical Analysis: Chi-square test, t-test, and analysis of variance test were applied to analyze data using SPSS package for Windows. Results and Conclusion: Premedication with single i.v. dexmedetomidine prolonged the duration and increased the maximum upper level of only sensory component of spinal anesthesia (6.42 ± 3.21 vs. 4.8 ± 1.21 thoracic segments higher than with midazolam sedation). This property can be beneficial in preventing undesirable prolongation of motor block and facilitating early ambulation in shorter duration of infra-umbilical surgeries. In addition, dexmedetomidine slowed the regression of sensory block and increased the time of the first request of analgesic.
Keywords: Dexmedetomidine, single-dose intravenous premedication, spinal anesthesia
|How to cite this URL:|
Kumar S, Hussain M, Arun N, Kumar A, Kumar M. The effect of midazolam and dexmedetomidine sedation on block characteristic following spinal bupivacaine: A randomized comparative study. Anesth Essays Res [Epub ahead of print] [cited 2021 Jan 18]. Available from: https://www.aeronline.org/preprintarticle.asp?id=302590
| Introduction|| |
Dexmedetomidine is a highly selective α2-adrenoreceptor agonist. It is widely used as an adjunct to general as well as regional anesthesia for better hemodynamic stability, sedation, and prolonged duration of regional anesthesia.,,,,, Synergistic interaction between intrathecal dexmedetomidine and local anesthetic agents has also been found in previous studies., Intravenous midazolam premedication is commonly used for conscious sedation, anxiolysis, and amnesia with spinal anesthesia., To isolate the analgesic effect of dexmedetomidine from its sedative effects, a comparison was made with midazolam.
There are limited clinical data comparing the effect of intravenous (i.v.) dexmedetomidine and midazolam premedication on spinal anesthesia. This study was conducted to compare and evaluate the synergistic effect of i.v. dexmedetomidine with i.v. midazolam on spinal block duration, requirement of analgesia and sedation in patients undergoing infra-umbilical surgeries.
Aims and objectives
Our primary objective was to assess the effect of i.v. dexmedetomidine and i.v. midazolam on the onset of sensory and motor block, prolongation of block, sedation, and postoperative analgesia. The secondary objective was to study any adverse effect of these drugs.
| Materials and Methods|| |
This is a randomized and comparative study conducted after obtaining ethical clearance from the Institute Ethical Committee. The trial was registered with Clinical Trial Registry, India (ctri.nic. in) vide registration number CTRI/2019/06/019605. Written informed consent was obtained from all the patients before enrolling them for the study. Based on the previous study keeping alpha error <0.05 and beta error <0.2, power of study <0.001, 100 patients between 18 and 60 years of age, of either sex, of American Society of Anesthesiologists (ASA) physical status I and II, posted for elective infraumbilical surgery under subarachnoid block (SAB) were included in this study. Patients who refused to take part in the study, with any contraindication to SAB like coagulopathy, deformity of the spine, raised intracranial tension, preexisting neurological disease, and with a history of alcohol or drug abuse and those who have received any opioids or sedative medication in the week prior to surgery were excluded from this study.
After enrolment in the study, clinical examination and routine investigation of all patients were done. All patients were educated about 11-point numerical rating scale (NRS) from 0 to 10, where 0 means no pain and 10 means maximum pain. Patients were kept overnight fasting and then shifted to the operation theater. On arrival to the operation theater, the standard monitors (like electrocardiogram, noninvasive blood pressure, and pulse oximeter) were attached to the patients, i.v cannula of 18-Gauze was secured in all patients, and 500 mL of loading dose of lactated Ringer’s solution was administered before spinal anesthesia. Patients were randomly divided into two groups (Group D and Group M), 50 in each group using a closed envelope technique. Patients of Group D received i. v. dexmedetomidine 0.5 mg.kg−1 and patients in Group M received i.v. midazolam 0.05 mg.kg−1 as premedication 5 min before spinal anesthesia. The study drugs were premixed to a total volume of 5 mL in the 5 mL syringe and prepared by an independent anesthesiologist for blinding. The patient and attending anesthesiologist were unaware of the group allocation. The study drug was administered intravenously over a period of 10 min as a single dose. Five minutes after the end of infusion, patients were placed in the lateral position and dural puncture was performed at the interspace between third and fourth lumbar vertebrae (L3–L4), using a standard midline approach with a 25-Gauze Quincke-type spinal needle, and 3 mL of 0.5% bupivacaine was injected intrathecally. All patients received oxygen (O2) 4 L min − 1 via a facemask throughout the procedure.
Baseline vital parameters such as heart rate (HR), systolic blood pressure (SBP), diastolic blood pressure (DBP), mean arterial blood pressure (MAP), and oxygen saturation (SPO2) were recorded. Then, these parameters were recorded after dural puncture and every 5 min for 15 min and then every 15 min interval up to 90 min after spinal anesthesia. The Ramsay sedation score was used for assessment of level of sedation at an interval of 10 min after administration of spinal block till 120 min. Postprocedure level of sensory block achieved was assessed using pinprick and cold (iced) tube in the mid-axillary line. Recovery time for sensory blockade defined as two-dermatome regression of anesthesia from the maximum level was recorded. Motor block was assessed using a modified Bromage scale. Postoperative pain was assessed by NRS at the interval of 4 h, 8 h, 12 h, and 24 h after the administration of SAB. The time of requirement of the first dose of postoperative rescue analgesic was recorded. The duration of analgesia was recorded as the time from the onset of analgesia to the time when the patient demanded rescue analgesia.
Episode of hypotension (defined by a decrease in MAP below 20% of baseline or SBP <90 mmHg) was treated with i.v. ephedrine 5 mg and additional lactated Ringer’s solution (200 mL over a 5 min period). Bradycardia (HR <50 beats per min) was treated with i.v. atropine 0.6 mg. The presence of any other complication in the preoperative and postoperative period was recorded.
The recorded data were presented as descriptive statistics for continuous variables and percentage for categorical variables and was subjected to Chi-square test, t-test, and analysis of variance test. All the data were analyzed using the SPSS package (Stata, version 23.0 SPSS INC, Chicago, IL, USA) for Windows. In all parameters, the value of P < 0.05 was considered significant.
| Results|| |
A total of 100 patients were enrolled and randomly allocated into two groups in this study; various predecided outcome parameters were recorded and analyzed, as shown in the consort diagram [Figure 1]. The demographic data of all the patients and duration of surgery were comparable [Table 1].
All patients of both the groups were hemodynamically stable throughout the surgical procedure. Mean HR, mean SBP, mean DBP, MAP, and mean SPO2 were comparable in both the groups [Graph 1],[Graph 2],[Graph 3],[Graph 4],[Graph 5]. The mean SBP and DBP decreased after SAB but remained stable after 90 min [Graphs 2 and 3]. The mean sedation score at all time intervals in both the groups was found to be comparable [Graph 6]. There was no statistically significant difference. Maximum Ramsay sedation score of 5 was found in 6 patients of the Group D and in 15 patients of the Group M.
The mean time of onset of sensory block in both the groups, Group D (2.52 ± 0.32 min) and Group M (2.97 ± 0.64), was comparable (P = 0.169). The maximum level of sensory block achieved in Group D patients was 6.42 ± 3.21 thoracic segments higher, which was found to be significantly higher (P = 0.001) than in Group M patients which was recorded to be 4.8 ± 1.21 thoracic segments higher. While observing the pattern of regression of spinal block, we found that there was not any statistically significant difference (P = 0.181) in the regression time of motor block in Group D (4.28 ± 0.09) and Group M (3.16 ± 0.13), while the mean time for two-segment regression of sensory block was recorded to be significantly earlier (P = 0.001) in Group M (2.12 ± 0.21), as compared to Group D (3.24 ± 0.12) [Table 2].
The mean NRS score of Group D at 4 h, 8 h, 12 h, and 24 h after spinal block was 2.23, 4.5, 5.8, and 4.3, respectively. The mean NRS score of Group M at 4 h, 8 h, 12 h, and 24 h was 4.9, 5.1, 5.2, and 5.12, respectively. At 4 h after spinal block, the mean NRS of Group D was recorded to be significantly lower than of Group M (P < 0.001). However at 8 h, 12 h, and 24 h, the mean NRS was comparable in both the groups. There was no statistically significant difference [Table 3]. There was a statistically significant difference (P < 0.001) in the time of first request of analgesia in Group D (5.39 ± 0.34 h) and Group M (3.29 ± 0.14 h) [Table 2].
Incidence of episode of hypotension and bradycardia was recorded to be significantly greater in Group D (6 patients [12%] and 3 patients [4%], respectively), as compared to in Group M (2 patient [4%] and 1 patient [2%], respectively) [Table 4].
| Discussion|| |
Dexmedetomidine when combined with intrathecal bupivacaine facilitates spinal block. It has been suggested that the spinal mechanism is the principal mechanism for the analgesic action of dexmedetomidine. Although dexmedetomidine has supraspinal and peripheral sites of action, when administered intravenously, it produces analgesia by acting at both spinal and supraspinal levels.,
In a meta-analysis conducted by Abdallah et al., 364 patients were analyzed from 7 intermediate to high-quality randomized controlled trials investigating the facilitatory effects of i.v. administration of dexmedetomidine compared with placebo on spinal anesthesia. It was found that the duration of sensory and motor block was prolonged by 34% and 17%, respectively and the time to the first analgesic request was increased by 53%. It was associated with a 3.7-fold increase in transient reversible bradycardia without any difference in the incidence of hypotension, sedation, and respiratory depression.
These clinical advantages of dexmedetomidine premedication compared with midazolam premedication are contributed by its supraspinal, direct analgesic, and vasoconstricting actions. i.v dexmedetomidine acts by terminating the propagation of pain signal by inhibiting norepinephrine release in descending medullo-spinal-norepinephrine pathway. It produces sedation by suppressing neuronal firing in the locus coeruleus. At the spinal level, it acts by inhibition of glutamate and substance P. It also causes activation of potassium channels causing hyperpolarization of interneurons., The effect of dexmedetomidine is not dependent on the route of administration.? Midazolam has been reported to have an antinociceptive effect through the neuraxial pathway, but this effect was not seen after systemic administration., This explains why i.v. midazolam premedication did not enhance the analgesic effect of spinal block.
Rapid administration of dexmedetomidine might produce bradycardia and hypertension so it should be administered slowly over 10 min. A study was conducted on healthy volunteers by Liu et al. in 2013 to evaluate the analgesic effect of different doses of i.v. dexmedetomidine (0.25, 0.5 and 1 mg.kg−1) on ischemic pain and they demonstrated moderate analgesia with a ceiling effect at a dose of 0.5 mg.kg−1. An intravenous dose of 0.05 mg.kg−1 of midazolam was reported to induce sedation and amnesia without any adverse effects on hemodynamic parameters and respiration in adults under spinal anesthesia. Keeping this in mind, 0.5 mg.kg−1 and 0.05 mg.kg−1 i.v. doses of dexmedetomidine and midazolam, respectively, were used in this study. Both the drugs were administered intravenously over 10 min for blinding. We did not observe biphasic changes associated with dexmedetomidine. This may be due to sympathetic blockade associated with spinal anesthesia, slow administration of a low dose of drug, and adequate preoperative hydration.
Harsoor et al. and Kolarkar et al. had concluded that i. v. dexmedetomidine in a bolus dose of 0.5 mg.kg−1 followed by infusion at the rate of 0.5 mg.kg−1 h−1 prolonged the duration of sensory as well as motor blockade of spinal bupivacaine with hemodynamic stability and arousable sedation., Prolongation in the duration of sensory and motor block was also found in a similar study done by Shmruthi et al. where dexmedetomidine was administered in a bolus dose of 1 mg.kg−1 followed by infusion at the rate of 0.5 mg.kg h−1.
Interestingly, we found prolongation in only the sensory component of the spinal block. There was no statistically significant difference in the regression time of motor block. Then, we searched for the studies by different investigators who also found only prolongation in sensory block. Annamalai et al. while comparing the effect of single i.v. bolus doses of dexmedetomidine 1 mg.kg − 1 at different times (10 min before and 30 min after) on SAB, they found that sensory block was higher and prolonged in the group receiving premedication later, without any difference in duration of motor block. Observation of Kaya et al. with single i.v. dose of dexmedetomidine is also similar to ours. In all the above studies with a similar outcome as ours, dexmedetomidine was given in only a single bolus dose, whereas in all the studies where the prolongation of both sensory and motor blockade was found, dexmedetomidine was given as a bolus, followed by continuous infusion throughout the surgery. The difference in the amount of dexmedetomidine received as an infusion by the study group might explain the difference in effect on the regression time of motor block. Thus, it can be assumed that single-dose i.v. dexmedetomidine premedication affects only regression time of sensory component of SAB, sparing motor component. Rhee et al. had observed that clonidine had a concentration-dependent effect on motor blockade of bupivacaine spinal anesthesia. The same theory might be the possible explanation with dexmedetomidine as well. This property can be beneficial in preventing undesirable prolongation of motor block, facilitating early ambulation and decreasing patient’s discomfort in a shorter duration of infraumbilical surgeries.
A randomized controlled trial was conducted by Sivachalam et al. to compare the effect of conscious sedation with i.v. dexmedetomidine at a loading dose of 0.5 mg.kg − 1, followed by 0.5 mg.kg − 1 h − 1 infusion to i.v. midazolam at a loading dose of 0.03 mg.kg − 1 followed by 0.03 mg.kg h − 1 infusion on spinal anesthesia in patients undergoing infraumbilical surgeries. They found that the mean time for sensory regression was prolonged in dexmedetomidine group (5.2 ± 0.83 h) than in midazolam group (4.4 ± 0.87 h, P = 0.01). They did not mention anything about the prolongation in motor block.
Kumar compared i.v. dexmedetomidine and clonidine as premedication in pediatric patients undergoing SAB and found that dexmedetomidine is superior to clonidine as a premedication drug in pediatric patients. Agrawal et al. have also concluded that i.v. α2 agonists are useful adjuvants for prolongation of the duration of spinal block. Similar effects of i.v. dexmedetomidine premedication were also observed on ropivacaine spinal block by Rekhi et al. CosKuner et al. had investigated that i.v. administration of dexmedetomidine might also prolong the recovery time of the sensory blockade of bupivacaine during epidural anesthesia.
In our study, patients of both the groups were equally hemodynamically stable (P = 0.12 for HR and P = 0.41 for MAP). We recorded more episodes of hypotension and bradycardia with dexmedetomidine premedication, which were easily reversed by a bolus dose of 5 mg ephedrine and fast infusion of 200 mL Ringer Lactate over 5 min. This can be explained by the healthy ASA I and II study population and single-dose administration of study drugs.
However, midazolam is known to cause arterial desaturation in sedative doses. No respiratory depression was found in any patients in this study, and respiratory parameters (respiratory rate and SpO2) remained within normal limits throughout the procedure. Previous studies have also shown that sedation caused by dexmedetomidine is of better quality than that of midazolam sedation in terms of easy arousability, hemodynamic stability, respiratory depression, and anxiolysis.,
Our observations and results indicate that premedication with single-dose i.v. dexmedetomidine before spinal anesthesia increased the maximum upper level and prolonged the duration of bupivacaine induced sensory blockade without affecting motor blockade. In addition, dexmedetomidine slowed the regression of sensory block and thus increased the time of the first request of analgesic for postoperative pain relief. It also provided sedation comparable to midazolam premedication. Although the incidence of bradycardia and hypotension was more, it was reversible and easily treatable.
| Conclusion|| |
i.v. premedication of dexmedetomidine in a single dose of 0.5 mg.kg − 1 over 10 min is comparable with bolus dose, followed by continuous infusion throughout the surgery. It has a synergistic and facilitating effect on the sensory component of bupivacaine-induced SAB. It has the added advantage of sparing of undesirable prolongation of motor block. However, further studies are required to validate our observations.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Basar H, Akpinar S, Doganci N, Buyukkocak U, Kaymak C, Sert O, et al
. The effects of preanesthetic, single-dose dexmedetomidine on induction, hemodynamic, and cardiovascular parameters. J Clin Anesth 2008;20:431-6.
Peden CJ, Cloote AH, Stratford N, Prys-Roberts C. The effect of intravenous dexmedetomidine premedication on the dose requirement of propofol to induce loss of consciousness in patients receiving alfentanil. Anaesthesia 2001;56:408-13.
Taittonen MT, Kirvelä OA, Aantaa R, Kanto JH. Effect of clonidine and dexmedetomidine premedication on perioperative oxygen consumption and haemodynamic state. Br J Anaesth 1997;78:400-6.
Karaaslan D, Peker TT, Alaca A, Ozmen S, Kirdemir P, Yorgancigil H, et al
. Comparison of buccal and intramuscular dexmedetomidine premedication for arthroscopic knee surgery. J Clin Anesth 2006;18:589-93.
Jaakola ML. Dexmedetomidine premedication before intravenous regional anesthesia in minor outpatient hand surgery. J Clin Anesth 1994;6:204-11.
Kanazi GE, Aouad MT, Jabbour-Khoury SI, Al Jazzar MD, Alameddine MM, Al-Yaman R, et al
. Effect of low-dose dexmedetomidine or clonidine on the characteristics of bupivacaine spinal block. Acta Anaesthesiol Scand 2006;50:222-7.
Coskuner I, Tekin M, Kati I, Yagmur C, Elcicek K. Effects of dexmedetomidine on the duration of anaesthesia and wakefulness in bupivacaine epidural block. Eur J Anaesthesiol 2007;24:535-40.
Memiş D, Turan A, Karamanlioğlu B, Pamukçu Z, Kurt I. Adding dexmedetomidine to lidocaine for intravenous regional anesthesia. Anesth Analg 2004;98:835-40.
Koyama S, Ohashi N, Kurita S, Nakatani K, Nagata N, Toyoda Y. Conscious sedation and amnesic effect of intravenous low-dose midazolam prior to spinal anesthesia. Masui 2008;57:713-8.
Nishiyama T, Yokoyama T, Hanaoka K. Sedation guidelines for midazolam infusion during combined spinal and epidural anesthesia. J Clin Anesth 2004;16:568-72.
Liu S, Zhao P, Cui Y, Lu C, Ji M, Liu W, et al
. Effect of 5-mg dose of dexmedetomidine in combination with intrathecal bupivacaine on spinal anesthesia: A systematic review and meta-analysis. Clin Ther 2020;42:676‐90.
Talke P, Richardson CA, Scheinin M, Fisher DM. Postoperative pharmacokinetics and sympatholytic effects of dexmedetomidine. Anesth Analg 1997;85:1136-42.
Kubre J, Sethi A, Mahobia M, Bindal D, Narang N, Saxena A. Single dose intravenous dexmedetomidine prolongs spinal anesthesia with hyperbaric bupivacaine. Anesth Essays Res 2016;10:273-7.
] [Full text]
Al-Mustafa MM, Badran IZ, Abu-Ali HM, Al-Barazangi BA, Massad IM, Al-Ghanem SM. Intravenous dexmedetomidine prolongs bupivacaine spinal analgesia. Middle East J Anaesthesiol 2009;20:225-31.
Abdallah FW, Abrishami A, Brull R. The facilitatory effects of intravenous dexmedetomidine on the duration of spinal anesthesia: A systematic review and meta-analysis. Anesth Analg 2013;117:271-8.
Gertler R, Brown HC, Mitchell DH, Silvius EN. Dexmedetomidine: A novel sedative-analgesic agent. Proc (Bayl Univ Med Cent) 2001;14:13-21.
Patel CR, Engineer SR, Shah BJ, Madhu S. Effect of intravenous infusion of dexmedetomidine on perioperative haemodynamic changes and postoperative recovery: A study with entropy analysis. Indian J Anaesth 2012;56:542-6.
] [Full text]
Niv D, Davidovich S, Geller E, Urca G. Analgesic and hyperalgesic effects of midazolam: Dependence on route of administration. Anesth Analg 1988;67:1169-73.
Ho KM, Ismail H. Use of intrathecal midazolam to improve perioperative analgesia: A meta-analysis. Anaesth Intensive Care 2008;36:365-73.
Jaakola ML, Salonen M, Lehtinen R, Scheinin H. The analgesic action of dexmedetomidine A novel alpha 2-adrenoceptor agonist in healthy volunteers. Pain 1991;46:281-5.
Liu C, Hang YZ, She S, Xu L, Ruan X. A randomized controlled trial of dexmedetomidine for suspension laryngoscopy. Anaesthesia 2013;68:60-6.
Nishiyama T, Hirasaki A, Odaka Y, Iwasaki T, Seto K. Midazolam sedation during spinal anesthesia: Optimal dosage (Japanese). J Jpn Soc Clin Anesth 1994;14:257-62.
Harsoor S, Rani DD, Yalamuru B, Sudheesh K, Nethra S. Effect of supplementation of low dose intravenous dexmedetomidine on characteristics of spinal anaesthesia with hyperbaric bupivacaine. Indian J Anaesth 2013;57:265-9.
] [Full text]
Kolarkar P, Badwaik G, Kalbande J, Watve A, Bhalerao A, Giri A. Does intravenous low dose dexmedetomidine supplementation has beneficial effects on spinal anaesthesia? Int J Contemp Med Res 2016;3:1547-50.
Shmruthi S, Rajeshwar P, Srinivas B. Effects of intravenous dexmedetomidine on spinal anaesthesia with hyperbaric bupivacaine. JMSCR 2018;8:255-62.
Annamalai A, Singh S, Singh A, Mahrous DE. Can intravenous dexmedetomidine prolong bupivacaine intrathecal spinal anesthesia? J Anesth Clin Res 2013;4:372.
Kaya FN, Yavascaoglu B, Turker G, Yildirim A, Gurbet A, Mogol EB, et al
. Intravenous dexmedetomidine, but not midazolam, prolongs bupivacaine spinal anesthesia. Can J Anaesth 2010;57:39-45.
Rhee K, Kang K, Kim J, Jeon Y. Intravenous clonidine prolongs bupivacaine spinal anesthesia. Acta Anaesthesiol Scand 2003;47:1001-5.
Sivachalam SN, Puthenveettil N, Rajan S, Paul J, Kumar L. Comparison of prolongation of spinal anesthesia produced by intravenous dexmedetomidine and midazolam: A randomized control trial. Anesth Essays Res 2019;13:330-3.
] [Full text]
Kumar RA. Comparative study between intravenous dexmedetomidine and clonidine as premedication in pediatric patients undergoing spinal anesthesia. Egypt J Anaesth 2018;34:129-34.
Agrawal A, Agrawal S, Payal YS. Comparison of block characteristics of spinal anesthesia following intravenous dexmedetomidine and clonidine. J Anaesthesiol Clin Pharmacol 2016;32:339-43.
] [Full text]
Rekhi BK, Kaur T, Arora D, Dugg P. Comparison of intravenous dexmedetomidine with midazolam in prolonging spinal anaesthesia with ropivacaine. J Clin Diagn Res 2017;11:UC01-4.
Koroglu A, Demirbilek S, Teksan H, Sagir O, But AK, Ersoy MO. Sedative, haemodynamic and respiratory effects of dexmedetomidine in children undergoing magnetic resonance imaging examination: Preliminary results. Br J Anaesth 2005;94:821-4.
Eren G, Cukurova Z, Demir G, Hergunsel O, Kozanhan B, Emir NS. Comparison of dexmedetomidine and three different doses of midazolam in preoperative sedation. J Anaesthesiol Clin Pharmacol 2011;27:367-72.
] [Full text]
[Table 1], [Table 2], [Table 3], [Table 4]