Table of Contents  
ORIGINAL ARTICLE
Year : 2016  |  Volume : 9  |  Issue : 2  |  Page : 240-244

Studying the sedative effect of dexmedetomidine administered by two different routes, a randomized comparative trial


Department of Anesthesiology, Intensive Care, and Pain Management, Faculty of Medicine, Ain-Shams University, Cairo, Egypt

Date of Submission06-Jan-2015
Date of Acceptance27-Jun-2015
Date of Web Publication11-May-2016

Correspondence Address:
Dina Salah
Department of Anesthesiology, Intensive Care, and Pain Management, Faculty of Medicine, Ain-Shams University, 11371 Cairo
Egypt
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/1687-7934.179901

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  Abstract 

Background
Efforts to find a better adjuvant in spinal anesthesia have been underway for a long time to achieve both effective analgesia and targeted sedation. We evaluated whether we can use dexmedetomidine in spinal anesthesia through its multiple modes of action and reduced adverse events in comparison with its intravenous use to achieve desirable patient comfort and sedation.
Patients and methods
A total of 100 patients classified as American Society of Anesthesiologists class I and II scheduled for inguinal hernia repair were studied. Patients were allocated randomly to receive either 15 mg of 0.5% hyperbaric bupivacaine plus 0.5 ml normal saline intrathecally and an intravenous infusion of dexmedetomidine 1 mg/kg over 10 min (group V, n = 50) or 15 mg of 0.5% hyperbaric bupivacaine plus 5 mg of dexmedetomidine diluted in 0.5 ml normal saline intrathecally and an intravenous infusion of same volume normal saline over 10 min (group S, n = 50).
Results
Patients in both groups were comparable in the characteristics of the spinal block and sedation score.
Conclusion
Intrathecal dexmedetomidine can act both as an adjuvant to bupivacaine and as a sedative without the need for other intravenous sedation drugs.

Keywords: adjuvant to spinal anesthesia, dexmedetomidine, spinal anesthesia


How to cite this article:
Sayed W, Salah D, Adib F. Studying the sedative effect of dexmedetomidine administered by two different routes, a randomized comparative trial. Ain-Shams J Anaesthesiol 2016;9:240-4

How to cite this URL:
Sayed W, Salah D, Adib F. Studying the sedative effect of dexmedetomidine administered by two different routes, a randomized comparative trial. Ain-Shams J Anaesthesiol [serial online] 2016 [cited 2021 Apr 18];9:240-4. Available from: http://www.asja.eg.net/text.asp?2016/9/2/240/179901


  Introduction Top


Spinal anesthesia offers a number of advantages to both the patient and the physician. However, patients are often reluctant to remain awake during a procedure. Sedation has been shown to increase patient satisfaction during regional anesthesia and may be considered as a means to increase the patient's acceptance. Therefore, provision of adequate sedation is important if the advantages of spinal anesthesia are to be fully appreciated. Several agents including midazolam, ketamine, remifentanil, propofol, and dexmedetomidine have been used for this purpose [1].

Dexmedetomidine is a highly selective centrally acting a2 adrenoceptor agonist that is used widely for procedural sedation, sedation during regional anesthesia, and sedation in an intensive care setting [2-7].

Intrathecal dexmedetomidine has also been used as an adjuvant to local anesthetics that results in prolongation of duration of sensory and motor blockade [8]. As an adjuvant, neuraxial administration is the appropriate route to dexmedetomidine because the analgesic effect of a2-agonists mostly occurs at the spinal level, and dexmedetomidine has high lipophilicity that facilitates rapid absorption into the cerebrospinal fluid and binding to the spinal cord a2-adrenoreceptor.


  Aims of the work Top


This study was designed to evaluate the sedative effect of dexmedetomidine when administered intravenously and intrathecally as an adjuvant to bupivacaine in lower abdominal surgeries.


  Patients and methods Top


This prospective randomized double-blind clinical trial included 100 patients who were American Society of Anesthesiologists physical status I or II aged 18 to 40 years; they were scheduled for elective inguinal hernia repair under spinal anesthesia. After obtaining approval from the ethics committee of Ain-Shams University Hospital and informed written consent from all patients, they were allocated randomly by computer-generated random numbers into two groups in a double-blind manner using numbered sealed envelopes. Patients in group V received 15 mg of 0.5% hyperbaric bupivacaine plus 0.5 ml normal saline (NS) intrathecally and an intravenous infusion of dexmedetomidine 1 mg/kg for 10 min. Patients in group S received 15 mg of 0.5% hyperbaric bupivacaine plus 5 mg of dexmedetomidine diluted in 0.5 ml NS intrathecally, and an intravenous infusion of NS of the same volume for 10 min. Exclusion criteria for this study were patients with diabetes mellitus, cardiovascular diseases, age younger than 18 or older than 40 years, patients with psychiatric, neurological, or coagulation abnormalities, patients with any contraindications to axial block, patients with BMI more than 35 kg/m 2 , or pregnant women. The study solution was prepared by an anesthetist who did not participate in patient care. All patients were preloaded with 6 ml/kg lactated Ringer's solution through a peripheral venous cannula 18 G 20-30 min before induction of spinal anesthesia. All patients did not receive any sedation preoperatively and throughout the procedure. On arrival to the operating room ECG, pulse oximetry, and noninvasive blood pressure were connected to the patient. Bispectral index (BIS) monitoring was performed using a BIS XP model 3.4 monitor and a quatrosensor electrode system (Aspect MedicalSystems, Norwood, Massachusetts, USA). Baseline heart rate, mean arterial pressure, modified observer's assessment of alertness/sedation score, and BIS were recorded from the monitors at the time of arrival to operating room and 5, 10, 15, 30, 45, and 60 min after spinal injection. All patients received spinal anesthesia in the lateral decubitus position at the L3-L4 interspace using 25 G Whitacre spinal needles. The study solution, which was prepared by another researcher, was injected immediately after obtaining a free flow of cerebrospinal fluid. The patient was repositioned immediately after spinal injection to the supine position with the head elevated (for 15°-20°). Increments of 5 mg intravenous ephedrine were administered if systolic blood pressure was less than 20% below baseline or less than 100 mmHg. If heart rate decreased below 50 beats/min, 0.5 mg atropine sulfate was administered to the patient. Sensory block was assessed using the cold ice test after intrathecal drug administration and every 5 min. Onset time from completion of injection till sensory block to reach T5 dermatome was recorded; also, the time for sensory regression to S1 dermatome was recorded. Time for motor block to reach Bromage score 1 was also recorded. All patients received oxygen through a face mask at a rate of 4 l/min. If discomfort or pain was experienced during surgery or if the initial block failed to reach the specified T5 height, the patient was withdrawn from the study and general anesthesia was administered as appropriate. Side effects such as nausea, vomiting, bradycardia, hypotension, and itching were observed and recorded [Table 1].
Table 1 The modified observer's assessment of alertness/sedation scale [9]

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Statistical analysis

Our primary outcome variable was the incidence of sedation. A power analysis showed that we needed to include 50 patients in each group to show a 70% difference in the incidence of sedation between the groups with a power of 80% and a 5% significance level. Data are presented as number, mean + SD, or percentage as appropriate. All categorical and numerical data were analyzed using c2 analysis or analysis of variance or Student's t-test whenever appropriate. A P-value less than 0.05 was considered significant.


  Results Top


The two groups were comparable in age, sex, height, American Society of Anesthesiologists physical status, and duration of the surgery [Table 2].
Table 2 Demographic data of the patients and drugs consumption in the two groups

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The patients in both groups remained hemodynamically stable intraoperatively as shown in [Table 3] and [Table 4].
Table 3 Intraoperative heart rate changes

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Table 4 Intraoperative blood pressure changes

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The characteristics of the spinal block are summarized in [Table 5], showing no difference between groups V and S in the highest level of the block, time to reach peak value block regression, and onset time to Bromage 3 motor block. Intraoperative ephedrine and atropine requirements in both groups were comparable.
Table 5 Characteristics of spinal block and regression times

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There were two patients in group V and three patients in group S who had nausea and vomiting. No patient experienced itching; four patients with bradycardia in group V and five patients in group S were successfully managed with atropine 0.4 mg intravenously, whereas there two patients in group V and three patients in group S who had hypotension were successfully managed with ephedrine [Table 6].
Table 6 Side effects recorded during the procedure

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The sedation scores in both groups were comparable [Table 7] and [Table 8], and there was no statistical difference between the two groups.
Table 7 Changes in bispectral index values during the study

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Table 8 Changes in MOAA/S scores during the study

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  Discussion Top


Our study has shown that the addition of 5 mg of dexmedetemidine with hyperbaric bupivacaine shortens the onset of motor block and prolongs the duration of motor and sensory block with hemodynamic stability; this is in agreement with Al Ghanem et al. [9] and Al Mustafa et al. [10], who found that dexmedetomidine prolongs motor and sensory block of spinal anesthesia intravenous dexmedetomidine used in our study at a dose of 1 mg/kg over a period of 10 min was also found to prolong both sensory and motor block. This is in agreement with several studies such as Tekin et al. [11] and Al Oweidi et al. [12], whereas in a study carried out by Whizar-Lugo et al. [13], no change was detected in the onset time of motor block between the control group and the dexmeditomidine group, which may be have been because the dose of dexmeditomidine administered in this study was over a period of 20 min whereas in our study, it was administered over 10 min only.

The mechanism by which intrathecal a2 adrenoceptor agonists prolong the motor and sensory block of local anesthetics is not well known. They act by binding to presynaptic C-fibers transmitters and hyperpolarization of postsynaptic dorsal horn neurons [14], while local anesthetic agents act by blocking sodium channels. The prolongation of effect may result from synergism between local anesthetic and a2- adrenoceptor agonists while prolongation of the motor block may result from binding of a2 adrenoceptor agonists to motor venus in dorsal horn (15).

Dexmedetomidine is a highly selective a2-adrenoreceptor agonist with both analgesic and sedative effects [16]. Dexmedetomidine causes sedation and anxiolysis, which is mediated by hyperpolarization of noradrenergic neurons in the locus ceruleus in the brain stem. Activation of a2-adrenergic receptors leads to inhibition of adenyl cyclase, which catalyzes the formation of cyclic AMP, which is a second messenger for many catabolic cell processes. Simultaneously, efflux of potassium through calcium-activated potassium channels and inhibition of calcium influx occur through calcium channels in nerve terminals [17]. Hyperpolarization of the membrane suppresses the neuronal firing in the locus ceruleus and the ascending noradrenergic pathway [18]. Dexmedetomidine is better than other commonly used hypnotics. As it produces sedation, analgesia, and anxiolysis [19], it does not cause ventilatory depression [20]. Activation of a2-adrenoreceptors in the locus ceruleus decreases the release of norepinephrine and inhibits the sympathetic system, thus decreasing blood pressure and heart rate [21]. Hypotension and bradycardia are the most common adverse effects that occur after the administration of dexmedetomidine [22,23]. Spinal anesthesia has been observed to cause sedation, and there is a positive correlation between the extent of the block and the degree of sedation [24]. The explanation for this observation is the hypothesis of a decrease in afferent sensory input and inhibition of reticulothalamocortical pathways. The distribution half-life of dexmedetomidine is reported to be 5 to 10 min and the termination half-life is reported to be within 2-3 h. Dexmedetomidine is characterized by linear pharmacokinetics and dose-dependent sedation effects [25]. Intravenous dexmedetomidine has been used in doses ranging from 0.1 to 10 mg/kg/h without a statistically significant occurrence of hypotension and bradycardia [26,27]. Also, it has been assessed as a sedative administered as a loading dose of also 1 mg/kg without infusion lasting about 70-80 min [28].

The results of our study clearly indicate the effectiveness of spinal dexmedetemidine compared with the intravenous route as they both produce profound sedation in patients under spinal anesthesia.

In general, the most common side effects of dexmedetomidine are hypotension and bradycardia. When dexmedetomidine is used with spinal anesthesia, it may increase the frequency of such side effects. In this study, hypotension occurred in five patients in two groups, with no statistically significant difference between the two groups. Also, bradycardia occurred in nine patients in two groups, with no statistically significant difference between the two groups. There were two limitations in our study: first, the plasma concentrations of dexmedetomidine in the two groups were not measured. Second, further studies are needed with a control group in which an intrathecal local anesthetic is administered.


  Conclusion Top


In conclusion, this double-blind randomized-controlled clinical trial on patients undergoing elective inguinal hernia repair using spinal anesthesia with intrathecal or intravenous dexmedetomidine proved that intrathecal dexmedetomidine as an adjuvant yields equally effective sedation scores as those administered intravenously.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

 
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    Tables

  [Table 1], [Table 2], [Table 3], [Table 4], [Table 5], [Table 6], [Table 7], [Table 8]


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