European Journal of Cardiovascular Medicine

Central neuraxial blocks are commonly used for surgeries involving the abdomen and lower limbs. Subarachnoid block (SAB) with hyperbaric bupivacaine is often favored over epidural anesthesia due to its quicker onset and more substantial block. It is also economical and straightforward to perform. A variety of agents have been employed intrathecally as additives to local anesthetics to enhance effectiveness and extend the duration of the subarachnoid block, with opioids and α2 agonists being the most frequently utilized.

Dexmedetomidine is a strong α2 agonist that displays high selectivity for α2 receptors. These receptors are located in various areas throughout the body, including the central nervous system (CNS), as well as spinal and peripheral tissues. The receptors situated in the locus coeruleus play a crucial role in sedation, analgesia, anxiolysis, and sympatholysis. Within the spinal cord, activation of α2 receptors in the substantia gelatinosa of the dorsal horn inhibits the release of substance P. While the spinal mechanism is key to the analgesic properties of dexmedetomidine, there is also evidence supporting action at both supraspinal and peripheral sites.

Dexmedetomidine has been demonstrated to extend the duration of sensory and motor blockade achieved with spinal anesthesia while allowing patients to remain responsive. Several studies have used an intravenous loading dose of dexmedetomidine at 1 mcg/kg over 10 to 20 minutes, followed by a maintenance dose of 0.4-0.5 mcg/kg/hr, and found that it prolonged both sensory and motor blocks from spinal anesthesia, providing good sedation with minimal side effects when added to prilocaine, hyperbaric ropivacaine, isobaric, and hyperbaric bupivacaine ^[1-4]. There was no evidence of cognitive impairment or disinhibition associated with its use.

In this randomized double-blind placebo-controlled clinical trial, we proposed that administering an alpha-2 agonist intravenously might extend the duration of spinal anesthesia achieved with bupivacaine. The purpose of this investigation was to examine how intravenous dexmedetomidine affects the length of sensory and motor blockade caused by the intrathecal delivery of bupivacaine, as well as to evaluate any adverse events associated with this treatment.

Aim: To assess effect of intravenous dexmedetomidine in prolongation of sensory and motor blockade obtained with bupivacaine spinal anaesthesia in patients undergoing lower abdominal and lower limb surgeries.

The objectives of my study were:

1) To compare duration of sensory and motor blockade.

2) To compare sedation level.

3) To compare rescue analgesia time.

Study Design:    It is          a randomized,      double blinded, prospective, placebo             controlled comparative study.

Study area: Department of Anaesthesiology, Dr Pinnamaneni Siddhartha Institute of Medical Sciences and Research Foundation, Chinnaoutpally, Andhra Pradesh.  

Study Period: January 2018 to June 2018.

Study population: Study is in patients undergoing lower limb and lower abdominal surgeries.

Sample size:  60.

Inclusion criteria:

• ASA I-II patients
• Age between 18-60years
• Height more than 150cms
• Body mass index <30 kg/m2

Exclusion criteria:

• Unwilling patients
• Known case of hypersensitivity to local anaesthetics
• Patients with coagulation disorders or on anticoagulant therapy
• Local infection at the site of proposed puncture of spinal anesthesia
• Pre-existing neurological deficits or musculoskeletal disorders
• Use of any opioid or sedative medications prior to surgery
• Patient on beta blockers and bradycardia were excluded from study.

Ethical consideration: Institutional Ethical committee permission was taken before the commencement of the study.

Study tools and Data collection procedure:

A detailed history, complete physical examination was done for all patients. Before the commencement of anaesthesia, patients were instructed on the methods of sensory and motor assessments. Intravenous line was secured and ringer lactate solution 15ml/kg was infused 10 minutes before initiation of procedure. Monitors connected and baseline values of heart rate, blood pressure and oxygen saturation were noted before the procedure.

Spinal anaesthesia was performed with the patient in left lateral position in L3-L4 space. After skin infiltration with 2% lignocaine, 3 ml of 0.5% heavy bupivacaine was injected intrathecally at rate of 0.2ml/second through 25 g spinal needle and patient was kept in supine position. The level of anaesthesia was assessed with a hypodermic needle in a cephalad to caudal direction in mid-axillary line by an anaesthesiologist and level of sensory block was assessed. After 20 minutes, when the level of analgesia was assessed, patients were randomly assigned into two groups, by sealed envelope method, group D (dexmedetomidine) and group C (control). Patients in group D received loading dose of 0.5µg/kg of dexmedetomidine over 10 min. Patients in group C received intravenous loading dose of normal saline at equivalent volume of the calculated dose of dexmedetomidine.

The anaesthesiologist marking the sensory level was blinded to drug given intravenously. Pulse rate, blood pressure and oxygen saturation were recorded every 2 minutes for first 10 minutes and every 5 minutes for next 30 minutes and every 10 minutes for next 40 minutes and at end of procedure. Hypotension (defined as systolic blood pressure <90 mm Hg or 20 % fall in blood pressure from baseline or mean arterial pressure lower than 60 mm hg) was treated with additional ringer lactate and bolus dose of intravenous mephenteramine 6mg.

Bradycardia (less than 50) was treated as per ACLS algorithm. Nausea or vomiting was treated with antiemetics intravenous ondansetron 4 mg or metoclopramide 10mg and decrease in SpO2 to 90% was defined as hypoxia and treated with supplemental oxygen. Assessment of sensory blockade was done using a hypodermic needle by pin prick sensation test. Sensory level after 20 minutes of spinal block, highest level of sensory blockade after the drug given, time for two dermatome regression (duration) was noted. Assessment of motor blockade tested by Bromage scale and degree of motor blockade and duration of motor blockade were noted.

Motor block in the lower limb was assessed by using a modified Bromage scale ⁽⁵⁾: 0= no motor block 1=inability to raise extended leg;able to move knees and feet 2=inability to raise extended leg and move knee;able to move feet 3=complete block of motor limb

These motor assessments were performed immediately after the assessments of sensory level.

Assessment of sedation was done using Ramsay sedation score ⁽⁵⁾:

1 = anxious and agitated

2 = cooperative and tranquil

3 = drowsy but responsive to command

4 = asleep but responsive to glabellar tap

5 = asleep with a sluggish response to tactile stimulation

6 = asleep and no response

Score was evaluated every 10 minutes for 30 minutes after the drug is given and every 15 minutes for next 30 minutes and at the end of procedure. Excessive sedation was defined as a score greater than 4/6. All the above tests were performed while monitoring and recording hemodynamic status of the patient.

Pain score was done using visual analogue scale in post operative period. Patients were educated pre-operatively on the usage of Visual Analogue Scale (VAS) and reminded in the post operative period to alert the investigator when the VAS is greater than 3. First dose of analgesia was given when VAS score was greater than 3. The choice of the drug was deemed appropriate by the treating consultant. Time required for the first dose was noted.

VAS score using

Statistical analysis:

Statistical analysis was performed using SSPS 17 software. Student’s unpaired T-test was used for analysis of mean age, height and weight distribution, duration of surgery, duration of motor blockade, time to 2 segment regression, time to highest sensory level, rescue analgesic time, Ramsay sedation score. Chi square was used for ASA grade, sex, level after 20 minutes, highest sensory level. P value <0.05 was considered statistically significant.

Table-1: Demographic Data

D-study C-control

Age distribution, weight, height of patients in both groups were compared using unpaired t test. There was no statistical difference between the two groups.

Sex in both groups were compared using chi square test and was found to be statistically not significant (p value=.766). Groups were compared for ASA grade using chi-square test and was found to be statistically not significant (p value= 0.796).

Table 2: level after 20 minutes of spinal block

D-study C-control

Using chi-square test as the statistical comparison between the two groups it was found p value=0.850. It signifies level after 20 minutes of spinal block in both the groups to be statistically not significant.

Table 3: Highest sensory level

χ2=49.091 p<0.001 vhs(very highly significant) D-study C-control

Sensory level was very highly significant in study group compared to that of control group based on statistical analysis (p value< 0.001). Using student unpaired t test p value=0.575 implying duration of surgery in both the groups were similar.

Table 4: Duration of motor block(min)

Mean duration of motor blockade was almost similar in both the groups. Statistical value and p value were found to be 1.18 and 0.243 respectively and were thus not statistically significant.

Table 5: Time to two segment regression (min)

Vhs(very highly significant) D-study C-control

Applying student unpaired t test, p value was found to be <0.001 implying time to two segment regression was very highly significantly in study group.

Table 6: Ramsay sedation score

Here p value was found to be <0.001 which is statistically significant implying sedation score was higher in study group compared to that of control group.

Table7: Rescue analgesia time (min)

Mean time for analgesic dose was found to be higher in study group and p value < 0.001 implying requirement of analgesia was significantly prolonged in study group.

Table 8: Bradycardia

3 patients in study group were found to have bradycardia. Using fisher’s extract test it was found that p value=0.076 implying statistically not significant.

In this study, Dexmedetomidine has been used as intravenous adjunct to assess prolongation of spinal anaesthesia using bupivacaine. All the patients in this study were comparable with respect to demographic profiles. In the present study level after 20 minutes of spinal block in both the groups was found to be statistically insignificant (p value= .850). Administration of study drug was done 20 minutes after spinal block and hence level was similar in both the groups.

Kaya et al. ⁽⁵⁾ in their study, the first group received dexmedetomidine 0.5 mcg kg-1 (n = 25), the second group received midazolam 0.05 mg kg-1 (n = 25), and the third group received physiologic saline (n = 25), before spinal anaesthesia with bupivacaine 0.5% 15mg, showed that the intravenous dexmedetomidine increased the maximum upper levels of sensory block. In the present study it was found that there was significant increase in sensory levels in study group as compared to the control group (p value<0.001).

Harsoor et al. ⁽⁶⁾ in their study used dexmedetomidine in loading dose of 0.5 mcg/kg diluted to 20 ml with normal saline and infused over 10 min as a loading dose, prior to spinal block and followed by maintenance infusion of dexmedetomidine at the rate of 0.5 mcg/kg/hr throughout the duration of surgery have found significant increase in duration of motor block in their study group. However, Kaya et al ⁽⁵⁾ in their study with use of single dose of 0.5 mcg/kg dexmedetomidine did not find significant increase in motor blockade.

In the present study it was found that mean duration of motor blockade was almost similar in both the groups. Statistical value and p value were found to be 1.18 and 0.243 respectively implying statistically not significant. This could be explained that conduction of sensory nerve fiber might be more inhibited than motor nerve fiber at the same concentration of dexmedetomidine, as similarly reported with clonidine ⁽⁷⁾. The prolongation of motor blockade in the study done by Harsoor et al. ⁽⁶⁾ might be attributed to the continuous infusion of dexmedetomidine.

Balwinder Kaur Rekhi et al. ⁽⁸⁾ in their study Group D (n=20) received dexmedetomidine (a loading dose of 1 µg/kg over 10 minute followed by maintenance dose of 0.5 µg / kg/hr in form of infusion); Group M (n=20) received midazolam (loading dose of 0.05 mg/kg, followed by infusion at the rate of 0.02 mg/kg/hr), and Group C (n=20) received physiologic saline ,time to achieve peak motor and sensorial blockade revealed no statistically significant difference (p- value=0.08). The time (mean±SD) to reach peak sensory level was similar in the three groups [Group D, (6.13±0.96 min); Group M, (6.5±1.16 min); Group C, (5.88±1.12 min)]. The times to achieve peak motor blockade were (7.33±0.97 min) in Group D, (8.05±1.02 min) in Group M and (8.28±1.86 min) in Group C (p>0.05). There was no statistically significant difference amongst the three groups with respect to the upper level of sensory block achieved.

In present study time to two dermatome regression was found to be significantly (p value<0.001) prolonged in study group. Harsoor et al ⁽⁶⁾ in their study used dexmedetomidine in loading dose of 0.5 mcg/kg prior to spinal block and followed by maintenance infusion of dexmedetomidine at the rate of 0.5 mcg/kg/hr have found that time to two segment regression was significantly prolonged in their study group. Tekin et al ⁽⁹⁾ in their study group 1 received a loading dose of dexmedetomidine 1 mcg/kg IV, followed by a maintenance dose of 0.4 mcg/kg/ hr for 50 minutes, group 2 (control) received the same amount of physiologic saline in the same time frame found that dexmedetomidine IV significantly prolonged both the time required for the maximal level of the sensory blockade to regress 2 dermatomes and the time for complete reversal of motor blockade compared with the control group.

Balwinder kaur Rekhi et al. (2017) ⁽⁸⁾ in their study found that the time for sensory regression of two dermatomes in Dexmedetomidine group was significantly greater than that in Midazolam group. Elcicek et al. (2010) in their study found that the time for two dermatomes regression of the blockade and complete resolution of motor blockade were significantly prolonged in the Dexmedetomidine group compared to control group.

Although the present study has showed that the intravenous dexmedetomidine prolonged the duration of sensory block of bupivacaine spinal anaesthesia and increased the maximum upper levels of sensory block, the underlying mechanism of this effect remains not clear. The supra-spinal, direct analgesic, and/or vasoconstricting actions of dexmedetomidine are thought to be involved in this mechanism. Tekin et al. ⁽⁹⁾ in their study have found that deeper sedation was induced in group 1 than group 2, indicating that dexmedetomidine may reduce the need for extra sedative agents. In a study done by Al-Mustafa et al. ⁽¹⁰⁾ found that Ramsay sedation scores ranged from 2-5, the maximum score in group D(dexmedetomidine) was 3.96 ± 0.55.

In the present study it was found that sedation scores were significantly higher in study group with mean of 4.03 compared to that of control group with mean of 2.03. This may be due to presynaptic activation of the alpha2-A adrenoceptor in the Locus Ceruleus inhibits the release of norepinephrine (NE) and results in the sedative and hypnotic effects ⁽¹¹⁾.

Kaya et al ⁽⁵⁾ concluded that the addition of intravenous dexmedetomidine before spinal block provided similar pain relief with delayed-onset of postoperative pain and significantly less analgesic requirements. Balwinder kaur Rekhi et al. ⁽⁸⁾ (2017) in their study found that Dexmedetomidine increased the time until first request of analgesic for postoperative pain relief and decreased the requirement of supplemental analgesic.

In the present study, mean time for analgesic dose was found to be higher (211.7) in study group and p value < .001 implying requirement of analgesia was significantly prolonged in study group. This may be attributed to the fact that the stimulation of the alpha2-adrenoceptors at Locus Ceruleus, which is the site of origin for the descending medullospinal noradrenergic pathway, known to be an important modulator of nociceptive neurotransmission, terminates the propagation of pain signals leading to analgesia ⁽¹¹⁾.

When dexmedetomidine is administered intravenously, it induces hypotension and bradycardia until the central sympatholytic effect is established, after which it causes moderate drops in mean arterial pressure and heart rate. Postsynaptic activation of alpha2-adrenoceptors in the CNS results in decrease in sympathetic activity leading to hypotension and bradycardia. Also, activation of the alpha2- adrenoceptors in the CNS results in an augmentation of cardiac-vagal activity. In a study done by Elcicek et al ⁽¹²⁾ the incidence of bradycardia in group I (dexmedetomidine loading dose of 1 mcg/kg administered within 10 min, followed by maintenance at a dose of 0.4 mcg/kg/h for 50 min) was found to be 30% and the mean arterial pressures were found to be significantly lower in group I than group II at the 20th, 25th and 30th minutes. This higher incidence of bradycardia in this study could probably be explained due to continuous infusion of dexmedetomidine. Kaya et al. ⁽⁵⁾ observed no biphasic change or significant cardiovascular variability in their study consisting mainly of healthy patients which they attribute to sympathetic blockade associated with spinal anaesthesia, slow administration of a low dose, and sufficient preoperative hydration.

In the present study bradycardia was found in 3 patients (10.0%) treated with dexmedetomidine whereas hypotension was not found in either of the groups. Though bradycardia was clinically significant in this study it was not statistically significant (p-value=.076). At clinically effective doses, dexmedetomidine has been shown to cause much less respiratory depression than other sedatives ⁽¹³⁾. In a study done by Harsoor et al. ⁽⁶⁾ it was found that respiratory rate was lower in patients receiving dexmedetomidine, but clinically not significant enough to be considered as respiratory depression and oxygen saturation was maintained equally well in both groups. In the present study no respiratory depression was found in either of the groups.

Based on our research, we determine that administering a single intravenous dose of dexmedetomidine at 0.5 mcg/kg over 10 minutes, delivered 20 minutes after a spinal block, extends the duration of sensory blockade, provides an enhanced level of sedation, and lengthens the time needed for postoperative rescue analgesia. Consequently, we suggest using dexmedetomidine as an intravenous adjunct in spinal anesthesia for the effects mentioned, which could benefit patients undergoing surgeries of the lower abdomen and lower limbs.

1. Intravenous dexmedetomidine prolongs bupivacaine spinal analgesia. Al-Mustafa MM, Badran IZ, Abu-Ali HM, Al-Barazangi BA, Massad IM, Al-Ghanem SM. https://pubmed.ncbi.nlm.nih.gov/19583070/ Middle East J Anaesthesiol. 2009; 20:225–231.
2. Effect of intravenous dexmedetomidine on spinal anaesthesia with 0.5% hyperbaric bupivacaine in lower abdominal surgeries: a prospective randomized control study. Santpur MU, Kahalekar GM, Saraf N, Losari A. Anesth Essays Res. 2016;10:497–501.
3. The effects of intravenous dexmedetomidine on spinal hyperbaric ropivacaine anesthesia. Elcicek K, Tekin M, Kati I. J Anesth. 2010; 24:544–548.
4. Effect of Dexmedetomidine IV on the duration of spinal anesthesia with prilocaine: a double-blind, prospective study in adult surgical patients. Tekin M, Kati I, Tomak Y, Kisli E. Curr Ther Res Clin Exp. 2007;68:313–324.
5. Kaya FN, Yavascaoglu B, Turker G, Yildirim A, Gurbet A, et al. Intravenous dexmedetomidine, but not midazolam, prolongs bupivacaine spinal anaesthesia. Canadian journal of anaesthesia. 2010 Jan;57(1):39–45.
6. 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 Journal of Anesthesia. 2013;57(3):265.
7. Rhee K, Kang K, Kim J, Jeon Y. Intravenous clonidine prolongs bupivacaine spinal anaesthesia. Acta Anaesthesiologica Scandinavica. 2003; Vol 47(8):1001–5.
8. Rekhi BK,Kaur T,Arora D,Dugg P.Comparison of Intravenous Dexmedetomidine with Midazolam in Prolonging spinal Anaesthesia with Ropivacaine,Journal of Clinical and Diagnostic Research.2017 Feb;11(2): UC01- UC04.
9. Tekin M, Kati I, Tomak Y, Kisli E. Effect of Dexmedetomidine IV on the Duration of Spinal Anaesthesia with Prilocaine: A Double-Blind, Prospective Study in Adult Surgical Patients. Current Therapeutic Research. 2007 Sep;68(5):313–24.
10. Al-Mustafa MM, Badran IZ, Abu-Ali HM, Al-Barazangi B a, Massad IM, Al- Ghanem SM. Intravenous dexmedetomidine prolongs bupivacaine spinal analgesia. Middle East journal of anesthesiology. 2009 Jun;20(2):225–31.
11. Aram Vagya. Perioperative Uses of Dexmedetomidine.  E.J.  Anesth. 1999;18(6):1043–58. 
12. Elcicek K, Tekin M, Kati I. The effects of intravenous dexmedetomidine on spinal hyperbaric ropivacaine anaesthesia. Journal of anaesthesia. 2010 Aug;24(4):544–8.
13. Gertler R, Brown HC, Mitchell DH, Silvius EN. Dexmedetomidine: a novel sedative-analgesic agent. Proceedings (Baylor University. Medical Center). 2001 Jan;14(1):13–21.