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Original Article

Effects of dexmedetomidine on the duration of anaesthesia and wakefulness in bupivacaine epidural block

Coskuner, I.*; Tekin, M.*; Kati, I.*; Yagmur, C.*; Elcicek, K.*

Author Information
European Journal of Anaesthesiology: June 2007 - Volume 24 - Issue 6 - p 535-540
doi: 10.1017/S0265021506002237



Regional anaesthesia is frequently and successfully used in several surgical procedures. During surgery, the most important advantages of regional anaesthesia are that the patient is conscious and breathing spontaneously, has intact reflexes such as cough and swallowing and analgesia continues postoperatively [1]. Particularly, the sympathetic blockade that occurs in the lower extremities during epidural anaesthesia reduces blood loss during the peroperative period, and postoperative analgesia facilitates mobilization of the patient and, therefore, reduces the risk of thromboembolism [2].

Use of bupivacaine, a drug with long-lasting local anaesthetic effect, in epidural anaesthesia, provides an effective and safe anaesthesia [3]. Sedation is frequently induced during regional anaesthesia. The sedation induced for this purpose should cause minimal depression in the consciousness level of the patient, prevent inhibition of protective reflexes and not lead to respiratory depression [4,5]. These are the reasons why monitoring the depth of sedation is important. Thus, several sedation scales and monitors are employed. In recent years, bispectral index (BIS) has been suggested to be helpful to monitor the depth of anaesthesia [6,7]. The level of sedation and hypnosis can be quantitatively monitored as a value ranging from 0 to 100 using a sensor placed over the fronto-temporal region. While a value of 100 reflects the state of complete wakefulness, 80 reflects mild sedation, 60 means moderate level of hypnosis and 40 means deep hypnotic level [8]. It has been reported that employment of BIS reduces drug dosage and peroperative awareness, shortens waking time and postoperative healing time, without increasing adverse clinical events, and eventually, reduces the costs of hospitalization [9-11].

To prolong the duration of regional anaesthesia, intravenous (i.v.) clonidine, an α2-agonist, has also been used with several other drugs [12]. However, to our knowledge there is no study in the English literature about the effects of dexmedetomidine, an α2-agonist, more potent than clonidine, on wakefulness and duration of anaesthesia during bupivacaine-induced epidural anaesthesia.

The purpose of this study was to examine the effects of i.v.-administered dexmedetomidine on the duration of bupivacaine-induced epidural anaesthesia and level of wakefulness, and the respective side-effects.


In this prospective, double-blind study after obtaining approval of the Ethics Committee and written informed consent from the patients, 60 patients, ASA I–II, who were aged 20–60 yr and candidates for lower extremity surgery under epidural anaesthesia, were included in the study. Patients with ischaemic heart disease, congestive heart failure, renal or hepatic dysfunction, chronic respiratory diseases, obesity, history of waist and back pain, history of allergy to agents to be used, or chronic use or abuse of analgesics, opioids, antidepressants or anticonvulsants were not included in the study. Consecutive patients were allocated to groups according to the last digit (odd/even) of their admission numbers.

The patients did not receive any premedication due to the possibility of affecting the BIS value in either the premedication room or the operation room. A venous line was placed on the dorsum of the hand in each patient, and Ringer's lactate solution, 10 mL kg−1, was administered. Then, other crystalloid solutions, as needed, were administered during epidural anaesthesia. Electrocardiogram, non-invasive blood pressure and peripheral oxygen saturation (SPO2) were monitored and the values were recorded (Petaş-KMA 800 Model, Turkish Republic). Oxygen 3 L min−1 was administered through a face-mask. After cleaning the forehead and placing the BIS sensor, the electrodes were pressed over for 10–15 s for impedance testing. Following the impedance test, the BIS values were recorded (Aspect Medical Systems A-2000 Bispectral Index, Netherlands).

Following the guidelines for asepsis and antisepsis, the epidural space was penetrated through the L4-5 or L5-S1 space with an 18-G Tuohy needle in the sitting position and an epidural catheter (Perifix; B/Braun Melsungen AG, Germany) was placed. Bupivacaine 0.5% was administered at a test dose of 3 mL. Following confirmation that the catheter was not in the spinal space, an additional bupivacaine 13–15 mL was administered into the epidural space. Soon after this procedure, dexmedetomidine 1 μg kg−1 was i.v. administered in Group I as a loading dose, followed by continuous administration at a dose of 0.4 μg kg−1 h−1 throughout the operation, whereas in Group II patients physiologic saline was administered at same duration and amount.

In each patient, heart rate (HR), mean arterial pressure (MAP), SPO2 and BIS values and the level of sedation were assessed. These values were also recorded before commencement of surgery, after commencement of surgery at 5 min intervals, after termination of surgery at 20 min intervals and at the 1st, 15th, 30th, 45th and 60th min following the cessation of dexmedetomidine (infusion was ceased soon after the surgery was over). A perioperative 30% or more blood pressure (BP) decrease, when compared to the resting value, was considered as hypotension, whereas HR below 50 min−1 was considered as bradycardia. While hypotension was treated with fluid replacement and ephedrine at doses of 5 mg as i.v. bolus, bradycardia was treated with atropine 0.01 mg kg−1 i.v.

Sensorial blockade was determined with the pin-prick test. The recovery time of sensorial blockade was defined as the two-dermatome regression of anaesthesia from the maximum level. Complications such as paraesthesia, headache, allergy, hypotension, bradycardia, nausea, vomiting, shivering, waist and back pain, total spinal anaesthesia and difficulty in micturition were also recorded.

The patients were followed up for 1 h in the recovery room regarding haemodynamic parameters, sensory level, sedation (BIS) and side-effects by an anaesthesiologist, unaware of this study. After stable vital signs were achieved, the patients were discharged to their wards. The patients were observed at 30 min intervals for the first 6 h, and at 1 h interval following for 18 h in their wards by the same anaesthesiologist.

The data were statistically evaluated by t-test and analysis of variance (ANOVA) for repeated measurements (post hoc Bonferroni's test), side-effects were evaluated with Fisher's exact test and χ2-test, P < 0.05 was considered as statistically significant. SPSS 13.0 for Windows was used for data analysis.


There was no statistically significant difference between the groups regarding patient characteristics data (Table 1).

Table 1
Table 1:
Patient characteristics data and operation times (mean ± SD).

HR was significantly lower (P = 0.043) in Group I compared to Group II at the 5th (P < 0.05), 7th (P < 0.01) and 10th (P < 0.001) minutes following blockade (Fig. 1). Regarding the MAP, no statistically significant difference was observed between the groups (P = 0.062).

Figure 1.
Figure 1.:
Heart rates (mean ± SD). *P < 0.05; **P < 0.01; ***P < 0.001. BS: before commencement of surgery; AS: after commencement of surgery; TS: after termination of surgery; AI: after cessation of the infusion.

In Group I, mean BIS was significantly lower (P = 0.000) than Group II at the 7th minute following blockade (P < 0.01). This statistically significant difference was continued for all measurements beginning from the 10th minute following blockade, until the 30th minute following the cessation of infusion (P < 0.001) (Fig. 2).

Figure 2.
Figure 2.:
Bispectral index (mean ± SD). ***P < 0.001. BS: before commencement of surgery; AS: after commencement of surgery; TS: after termination of surgery; AI: after cessation of the infusion.

No statistically significant difference was found between groups regarding SPO2 (P = 0.536) and respiration rate (P = 0.991) (Table 2). Mean time to reach the peak sensory level was 19.93 ± 4.47 min in Group I and 21.68 ± 327 min in Group II (P > 0.05), median and range of the reached peak sensory level were T6 (T4–T10) in Group I and T6 (T4–T10) in Group II, (P > 0.05). In either group, hypotension severe enough to require ephedrine administration was not observed. No patient received additional bupivacaine and epidural or parenteral opioid during epidural anaesthesia and postoperative period (6 h). Patients received a mean of 86.83 ± 5.16 mg bupivacaine in Group I and 87.83 ± 4.29 mg in Group II (P > 0.05). Group II patients also received a mean of 112.46 ± 16.78 μg dexmedetomidine. While six patients in Group I received atropine, no patient required atropine in Group II (P = 0.024).

Table 2
Table 2:
Respiratory rate and peripheral oxygen saturation (overall mean ± SD).

The recovery time of sensory blockade was longer in Group I (245.26 ± 16.85) compared to Group II (192.50 ± 12.04) (P < 0.001). No patients experienced paresthesias, allergy, total spinal anaesthesia, difficulty in micturition, nausea and vomiting, whereas six patients in both groups each complained about waist and back pain. Shivering was not observed in Group I, whereas it was seen in four patients in Group II (P > 0.05).


Epidural anaesthesia is frequently and successfully applied in various surgical procedures. Its main advantages are that during the operation, the patient is conscious and breathes spontaneously and reflexes such as cough and swallowing are intact, while analgesia continues after surgery [1]. In surgery of the lower extremities, epidural anaesthesia is believed to have some advantages as regards to general anaesthesia. Particularly, sympathetic blockade induced in the lower extremities reduces blood loss during the peroperative period, and provision of analgesia in the postoperative period facilitates mobilization of the patient, thus protecting from the risk of thromboembolism [2].

The plasma levels of local anaesthetics are directly related with the total dose. Employment of bupivacaine, a long-acting local anaesthetic, in epidural anaesthesia provides an effective and safe level of anaesthesia [3]. The total dosage of bupivacaine should not exceed 2–2.5 mg kg−1; administration of this drug at a dose of 3 mg kg−1 results in a peak plasma level of 4 μg mL−1. The toxic plasma concentration is 4–5 μg mL−1 [13]. Anaesthetists are wary of administering additional doses in epidural anaesthesia due to requirement of high local anaesthetic doses and possible systemic side-effects that may be caused by local anaesthetics. These concerns have meant that anaesthestists have sought ways of prolonging the duration of epidural anaesthesia using the same local anaesthetic doses [14]. Drugs such as epinephrine, phenylephrine, clonidine, opioids, ketamine and neostigmine have been employed to prolong the duration of epidural anaesthesia [15-18].

It has been reported that the α2-agonists, which are thought to induce an opioid independent analgesia, exert their analgesic action at several levels via central effects. Probably, sub-type-selective α2-agonists provide anaesthesia and analgesia via stimulating the intended receptor population without causing haemodynamic effects. Besides, the α2-adrenergic receptors within nerve endings have also been reported to be possible contributors to the analgesic effect via inhibiting norepinephrine release [19].

To our knowledge, there is no study regarding the effects of dexmedetomidine on the level of sedation during epidural anaesthesia and its interactions with the local anaesthetics. We found that dexmedetomidine, administered at a dose of 0.4 μg kg−1 h−1, prolonged the recovery time of sensory blockade by about 50 min when compared with the control groups. Kanazi and colleagues [20] reported that intrathechal dexmedetomidine did not produce a significant difference on the times to reach peak sensorial level. Wahlander and colleagues [21] reported that in post thoracotomy patients, i.v. dexmedetomidine is a potentially effective analgesic adjunct to thoracic epidural bupivacaine infusion and may decrease the requirement for opioids and potential for respiratory depression. In our study, i.v. dexmedetomidine did not effect the onset time of sensorial block but prolonged the recovery time of sensory blockade.

Apprehension, anxiety and fear may significantly increase the severity of pain and disturbance sensed during regional blockade [4]. In patients who require sedation for control of emotional stress and inhibition of sympathetic activation, hypnotic and sedative opioids are preferred [22]. Propofol, midazolam, clonidine and dexmedetomidine are used for this purpose [23-25].

In determination of the depth of sedation, several techniques and scales have been used. Pollack and colleagues [26] have used BIS and Observer Assessment of Alertness/Sedation Scales in order to determine the level of sedation in volunteers who were candidates for regional anaesthesia application and not given premedication. BIS monitoring has been reported to be superior. Liu and colleagues [23] have shown that BIS is helpful in monitoring the depth of sedation induced with midazolam. In our study, BIS monitoring was used to determine the depth of sedation. In previous studies conducted with dexmedetomidine, the intended level of sedation was reported to be achieved at doses of 0.2–0.7 μg kg−1 h−1. Increases in depth of sedation have been reported to parallel the increment in dosage [27]. In our study, dexmedetomidine was administered at an infusion dose of 0.4 μg kg−1 h−1. We have observed that sufficient depth of sedation was achieved during regional anaesthesia.

The haemodynamic effects of dexmedetomidine are biphasic. When it is administered i.v., it causes hypotension and bradycardia until central sympathomimetic effect is achieved, which then causes moderate decreases in MAP and HR. This limits the application of dexmedetomidine in day-surgery patients due to the risk of hypotension and bradycardia in the postoperative period [28]. The incidence of hypotension following epidural anaesthesia has been reported to vary between 30% and 40%. This has been attributed to sympathetic blockade [15]. The incidence of decrease in MAP following dexmedetomidine infusion has been reported to be 14% at a dose of 0.25 μg kg−1, 17% at a dose of 0.5 μg kg−1, 23% at a dose of 1.0 μg kg−1 and 27% at a dose of 2.0 μg kg−1 [29]. In our study, there was no significant difference between the groups regarding MAP. Hypotension that was severe enough to require ephedrine administration was not seen in any patient. The absence of severe hypotension has been attributed to the sufficient hydration of the patients preoperatively.

Lesser and colleagues [30] have reported the incidence of bradycardia following epidural anaesthesia as 10%. The incidence of reduction in HR following dexmedetomidine infusion has been reported as 25% [31]. In our study, the HRs were found to be significantly lower in the dexmedetomidine group than those of the controls beginning from the 5th minute of infusion until the end of the blockade. Besides, while the incidence of bradycardia was 20% in the dexmedetomidine group, none of the control patients developed bradycardia. This result has been attributed to the bradycardia-inducing effects of dexmedetomidine.

One of the main objectives in usage of sedative agents is that the respective agent should not cause respiratory depression. In previous studies, it has been shown that α2-adrenergic agonists cause no or minimal respiratory depression [28]. In our study, respiratory depression was not observed in any patient.

Previously, the incidence of waist and back pain due to epidural anaesthesia was reported as 18–49% [31]. The aetiology of back pain is unclear. It has been proposed to be because of needle trauma, local anaesthetic-induced irritation or strain of the ligaments secondary to muscle relaxation [15]. The incidence of waist and back pain was 20% in our study, which is compliant with the literature.

The incidence of shivering following epidural anaesthesia has been reported to vary from 29% to 33% [32]. In our study, shivering was not observed in the dexmedetomidine group.

In conclusion, we have shown that i.v. administration of dexmedetomidine might prolong the recovery time of the sensory blockade of bupivacaine-induced sensorial blockade during epidural anaesthesia and also provide significant depth of sedation when compared with controls. Thus, this approach may be preferable when a prolonged operation time is expected.


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