|Year : 2013 | Volume
| Issue : 3 | Page : 265-269
Effect of supplementation of low dose intravenous dexmedetomidine on characteristics of spinal anaesthesia with hyperbaric bupivacaine
SS Harsoor, D Devika Rani, Bhavana Yalamuru, K Sudheesh, SS Nethra
Department of Anaesthesiology, Bangalore Medical College and Research Institute, Bangalore, Karnataka, India
|Date of Web Publication||25-Jul-2013|
S S Harsoor
Department of Anaesthesiology, Victoria Hospital, Bangalore Medical College and Research Institute, Bangalore - 560 002, Karnataka
Source of Support: None, Conflict of Interest: None
Aims: Intravenous (IV) dexmedetomidine with excellent sedative properties has been shown to reduce analgesic requirements during general anaesthesia. A study was conducted to assess the effects of IV dexmedetomidine on sensory, motor, haemodynamic parameters and sedation during subarachnoid block (SAB). Methods: A total of 50 patients undergoing infraumbilical and lower limb surgeries under SAB were selected. Group D received IV dexmedetomidine 0.5 mcg/kg bolus over 10 min prior to SAB, followed by an infusion of 0.5 mcg/kg/h for the duration of the surgery. Group C received similar volume of normal saline infusion. Time for the onset of sensory and motor blockade, cephalad level of analgesia and duration of analgesia were noted. Sedation scores using Ramsay Sedation Score (RSS) and haemodynamic parameters were assessed. Results: Demographic parameters, duration and type of surgery were comparable. Onset of sensory block was 66±44.14 s in Group D compared with 129.6±102.4 s in Group C. The time for two segment regression was 111.52±30.9 min in Group D and 53.6±18.22 min in Group C and duration of analgesia was 222.8±123.4 min in Group D and 138.36±21.62 min in Group C. The duration of motor blockade was prolonged in Group D compared with Group C. There was clinically and statistically significant decrease in heart rate and blood pressures in Group D. The mean intraoperative RSS was higher in Group D. Conclusion: Administration of IV dexmedetomidine during SAB hastens the onset of sensory block and prolongs the duration of sensory and motor block with satisfactory arousable sedation.
Keywords: Dexmedetomidine, intravenous, subarachnoid block, supplementation
|How to cite this article:|
Harsoor S S, Rani D D, Yalamuru B, Sudheesh K, Nethra S S. Effect of supplementation of low dose intravenous dexmedetomidine on characteristics of spinal anaesthesia with hyperbaric bupivacaine. Indian J Anaesth 2013;57:265-9
|How to cite this URL:|
Harsoor S S, Rani D D, Yalamuru B, Sudheesh K, Nethra S S. Effect of supplementation of low dose intravenous dexmedetomidine on characteristics of spinal anaesthesia with hyperbaric bupivacaine. Indian J Anaesth [serial online] 2013 [cited 2018 Dec 10];57:265-9. Available from: http://www.ijaweb.org/text.asp?2013/57/3/265/115616
| Introduction|| |
Subarachnoid block (SAB) is a widely used regional anaesthetic technique, particularly advantageous for lower abdominal and lower limb surgeries.  The intrathecal local anaesthetic 0.5% bupivacaine with dextrose, is appropriate for surgeries lasting for 2-2.5 h.  Several additives such as opioids, alpha agonists among others have been used with local anaesthetics to prolong the duration of SAB.  Alpha 2 adrenoceptor agonists have been studied as adjuvants to spinal anaesthesia with promising results. Clonidine, an alpha 2 adrenoceptor agonist was found to prolong the duration of sensory and motor block when administered intrathecally.  It was also found to prolong spinal anaesthesia when administered as an oral premedication and when administered by the intravenous (IV) route. ,
Dexmedetomidine is a more selective alpha 2 adrenoceptor agonist with sedative and analgesic properties. Though approved for intensive care unit sedation, studies are being conducted on its off-label uses. IV dexmedetomidine has been found to reduce the anaesthetic requirements during the general anaesthesia.  Dexmedetomidine has been found to exert its analgesic actions both at the spinal and supraspinal levels.  Kanazi et al. demonstrated a significant prolongation in the duration of sensory and motor block with dexmedetomidine used as intrathecal additive for 0.5% heavy bupivacaine.  However, literature pertaining to effect of IV administered dexmedetomidine on spinal anaesthesia are sparse and all published studies have used 1 mcg/kg bolus followed by infusion. ,
We hypothesised that IV dexmedetomidine at a lower loading dose followed by infusion might prolong the duration of SAB with 0.5% heavy bupivacaine. The primary aim of this study was to assess the onset and duration of sensory and motor blockade following IV dexmedetomidine supplementation during SAB. We also evaluated the effect of IV dexmedetomidine supplementation on haemodynamic parameters, sedation and adverse effects if any.
| Methods|| |
A randomised, double-blind, prospective study was conducted on 50 patients of American Society of Anaesthesiologists Grades I and II, aged between 18 and 55 years undergoing lower abdominal and lower limb surgeries under SAB.
After obtaining institutional ethical approval and informed consent, patients were randomly allocated into 2 groups, Group D (dexmedetomidine) and Group C (control) using computer generated random numbers. Patients with infection at the puncture site, coagulopathy, having true hypersensitivity to drugs used, diabetes and hypertension, psychiatric and neurological diseases were excluded from the study. All patients were kept nil per oral overnight and pre-medicated on the previous night of surgery with oral tablet alprazolam 0.5 mg. In the operation theatre, all patients were connected to electrocardiography, peripheral oxygen saturation (SpO 2 ) and non-invasive blood pressure monitor and all the basal parameters were recorded. An IV line was obtained with 18 gauge cannula and all patients were preloaded with Ringer lactate solution 10 ml/kg body weight.
Group D patients received IV dexmedetomidine 0.5 mcg/kg diluted to 20 ml with normal saline and infused over 10 min as a loading dose, prior to SAB. Group C received similar volume of normal saline. Immediately following the initial loading dose, patients were put in lateral position and operating table was kept flat. SAB was administered at L3-L4 or L4-L5 level using standard technique with 12.5 mg of hyperbaric bupivacaine. After SAB, patients in Group D received maintenance infusion of dexmedetomidine at the rate of 0.5 mcg/kg/h and the same rate of infusion of normal saline was administered in Group C, throughout the duration of surgery. Sensory block was assessed by loss of temperature sensation and motor blockade was determined using Bromage Scale  (0 = no paralysis; 1 = unable to raise extended leg; 2 = unable to flex knee; 3 = unable to flex ankle).
The level of sensory and motor blockade was checked every 2 min until the maximum level of the block was achieved and at 5 min interval subsequently. The level of sedation was evaluated throughout the study period using Ramsay Sedation Score (RSS).  Intraoperatively, heart rate, blood pressures and SpO 2 were recorded every 5 min until the end of surgery and every 15 min in the first post-operative hour followed by every half hourly for next 3 h. Hypotension was defined as more than 25% decrease in mean arterial pressure and was treated with fluid boluses and injection ephedrine 6 mg IV. Bradycardia was defined as heart rate less than 50 beats/min and treated with injection atropine 0.6 mg IV.
Parameters observed were time for the onset of sensory and motor blockade, maximum cephalad level of sensory block achieved, time for two segment regression, total duration of analgesia and motor blockade.
Onset of sensory block was considered when the loss of temperature sensation to cold was noted at T10 and onset of motor block when complete loss of motor power was achieved (Bromage Scale 3). Post-operatively, pain was assessed using visual analogue scale (VAS). Total duration of analgesia was defined as time from administration of SAB until the first complaint of pain (VAS ≥ 3). Injection diclofenac 75 mg intramuscular was used as rescue analgesic. Complications such as hypotension, bradycardia, nausea, vomiting, shivering, urinary retention and headache were noted and treated accordingly. An Anaesthesiologist, who was blinded to the study drug used, documented all the parameters.
Keeping the power at 80% and confidence interval at 95%, to detect at least 15% difference in duration of analgesia, the minimum sample size required was 16 patients in each group. However, we included 25 patients in each group for better validation of results.
All parametric data are presented as mean±SD and non-parametric data tabulated. All parametric data were statistically analysed using Student's t-test and non-parametric data analysed using Chi-square test and Fischer exact test as appropriate. P>0.05 was considered as statistically significant. Statistical analysis was performed using the Statistical Package for the Social Sciences version 16.0 (IL, Chicago) software.
| Results|| |
The demographic data are presented in [Table 1]. Age, gender, height, weight and duration of surgery were comparable. Type of surgeries was uniformly distributed between the groups.
Onset of sensory block was significantly faster in Group D (66±44.14 s) compared to Group C (129.6±102.4 s) withP>0.001. The time required for two segment regression was also significantly prolonged in Group D (111.52±30.9 min) compared with Group C (53.6±18.22 min), P<0.001. The duration of analgesia was significantly prolonged in Group D (222.8±123.4 min in Group D, 138.36±21.62 min in Group C, P>0.001). The median level of cephalad spread of sensory blockade in Group D was T10 (T8-T12) compared with T8 (T6-10) in Group C. Mean time for the onset of motor blockade in Group D was 3.76±2.02 min whereas in Group C, it was 4.2±2.08 min, P=0.136. Complete regression of motor blockade took longer time in Group D (256.44±53.10 min) compared with Group C (231.16±32.2 min), P>0.001 [Table 2].
Basal haemodynamic variables were comparable between the groups. Intra-operatively, there was a clinically and statistically significant decrease in heart rate in Group D from 15 min following SAB and persisted to be lower for 90 min. Bradycardia requiring atropine administration was noted in four patients in Group D compared with none in Group C (P=0.055). Similar trend was observed in systolic, diastolic and mean arterial pressures 60 min following SAB in Group D [Figure 1]. Hypotension was observed in two patients in Group D and in one patient belonging to Group C (P=0.5).
|Figure 1: Comparison of intra‑operative haemodynamic parameters. Heart rate significantly low (P<0.05) in Group D from 30th min to 60th min. MAP significantly low (P<0.05) from 60th min until the end of surgery|
Click here to view
Post-operatively, heart rate was comparable between the groups, but the systolic, diastolic and mean arterial pressures continued to be significantly lower in Group D for the initial 2 h [Figure 2].
|Figure 2: Post‑operative haemodynamic parameters. MAP significantly low (P<0.05) in Group D for initial 2 h|
Click here to view
The mean intra-operative RSS in Group D was 2.34±1.1 where as in Group C, it was 2.0±0.0 (P=0.034). However, RSS was comparable in both groups in the post-operative period. Respiratory rate was lower in Group D (Group D - 14.81±0.96 vs. Group C - 16.64±1.26/min, Pgt;0.001), but oxygen saturation was comparable between both groups (Group D 98% vs. Group C 97.85%, P=0.153). Respiratory rate and oxygen saturation were comparable between both groups in the post-operative period.
The incidences of side effects were comparable between the two groups [Table 3].
| Discussion|| |
IV administered dexmedetomidine has been shown to produce analgesic effects by acting at both spinal and supraspinal levels. The analgesic effect primarily results from the inhibition of locus ceruleus at the brain stem. In addition, dexmedetomidine infusion may result in increased activation of alpha-2 receptors at the spinal cord resulting in inhibition of nociceptive impulse transmission. The effect seems to be mediated through both presynaptic and the post-synaptic alpha-2 receptors. , The results of this study indicate that infusion of dexmedetomidine hastens the onset of sensory block, though the onset of motor blockade was not affected. Faster onset of the sensory block may be due to alpha-2 receptor activation induced inhibition of nociceptive impulse transmission.
Dexmedetomidine infusion used as a loading dose followed by an infusion has been found to prolong the duration of analgesia and motor blockade in the present study. Lugo et al.  in their study noted prolongation of sensory block and duration of analgesia without significant effect on motor block while using 1 mcg/kg bolus followed by 0.5 mcg/kg/h infusion of dexmedetomidine. Al-Mustafa et al.  also observed similar findings in their study and in addition, there was prolongation of motor blockade with a similar dose of dexmedetomidine. In another study observing the effect of dexmedetomidine infusion on spinal anaesthesia with ropivacaine, it was observed that dexmedetomidine bolus of 1 mcg/kg followed by infusion at 0.4 mcg/kg/h prolonged the duration of sensory and motor regression.  Recently, administration of a single bolus of 1 mcg/kg,  and 0.5 mcg/kg,  also were reported to prolong the duration of analgesia and sensory blockade. The duration of sensory block and analgesia in our study were comparable with above studies despite using a lower initial loading dose of 0.5 mcg/kg, compared with 1 mcg/kg. Furthermore, an evaluation of the analgesic effect of different doses of IV dexmedetomidine (0.25, 0.5 and 1 mcg/kg) on ischemic pain in healthy volunteers demonstrated moderate analgesia with a ceiling effect at 0.5 mcg/kg. 
Several studies reported prolonged duration of motor block following use of 1 mcg/kg initial bolus dose followed by infusion. However, in a study by Kaya et al.  use of a single dose of 0.5 mcg/kg of dexmedetomidine did not affect the duration of motor block. It was observed that effect of clonidine on motor blockade was concentration dependant  and the same theory might explain this phenomenon with dexmedetomidine as well. The prolongation of motor block in spite of use of 0.5 mcg/kg initial loading dose, observed by us may be attributed to continuous infusion following loading dose.
Haemodynamic response following dexmedetomidine infusion depends upon the dose and speed of infusion. A sequence of transient hypertension with reflex bradycardia, followed by hypotension is seen with higher dose and rapid infusion. , The subsequent decrease in heart rate and blood pressure may be due to decrease in central sympathetic outflow.  There was a minimal decrease in heart rate and blood pressure in patients receiving dexmedetomidine in our study, similar to observations of other authors.  Most of studies have noted bradycardia as a prominent side effect, with incidence varying from 30% to 40% sometimes requiring treatment with atropine, following use of a bolus dose of 1 mcg/kg and infusion greater than 0.4 mcg/kg/h. ,,, However, the incidence of bradycardia in our study was low and also transient, probably owing to a lower bolus dose used and augers well with observations of Kaya et al.  Incidence of hypotension in our study was comparable with other studies. , The infusions were continued during episodes of hypotension and/or bradycardia and the severity of these effects did not warrant stoppage of infusions at any point of time.
Intra-operative sedation provided by dexmedetomidine eliminates the need for additional sedatives. Dexmedetomidine produces sedation by its central effect and seems to be dose dependant. , Most of patients receiving dexmedetomidine were sedated, but easily arousable in the present study. Contrary to observations of Al-Mustafa et al.  and Hong et al.  who used higher doses of dexmedetomidine and noted excessive sedation in 3 out of 25 and 2 out of 26 patients respectively in their study, none of our patients had RSS greater than 3 at any point of observation highlighting the advantage of lower dose. Kaya et al.  also had similar observations regarding sedation in their study.
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. However, Hong et al. noted desaturation in two patients, which was attributed to the advanced age of the patients in their study, though Jaakola  did not observe similar incidence of desaturation.
| Conclusion|| |
IV supplementation of loading dose of dexmedetomidine 0.5 mcg/kg followed by infusion at 0.5 mcg/kg/h hastens the onset of sensory block and prolongs the duration of sensory block, analgesia and motor block with lesser incidence of bradycardia. Further, IV dexmedetomidine supplementation during SAB produces satisfactory arousable sedation without causing respiratory depression.
| References|| |
|1.||Collins VJ. Spinal anaesthesia principles. In: Cann CC, DiRienzi DA, editors. Principles of Anaesthesiology, General and Regional Anaesthesia. 3 rd ed. Philadelphia: Lea and Febiger; 1993. p. 1484. |
|2.||Brown DL. Spinal epidural and caudal anaesthesia. In: Miller RD, Eriksson LI, Fleisher LA, Wiener-Kronish GP, Young WL, editors. Millers' Anaesthesia. 7 th ed. Philadelphia, PA: Elsevier Churchill Livingstone; 2010. p. 1624. |
|3.||Mikko Pitkänen. Spinal (Subarachnoid) blockade. In: Cousin MJ, Bridenbaugh PO, Carr DB, Horlocker TT, editors. Neural Blockade in Clinical Anaesthesia and Management of Pain. 4 th ed. Philadelphia: Lippincot Williams and Wilkins; 2009. p. 213-38. |
|4.||Rhee K, Kang K, Kim J, Jeon Y. Intravenous clonidine prolongs bupivacaine spinal anesthesia. Acta Anaesthesiol Scand 2003;47:1001-5. |
|5.||Bonnet F, Buisson VB, Francois Y, Catoire P, Saada M. Effects of oral and subarachnoid clonidine on spinal anesthesia with bupivacaine. Reg Anesth 1990;15:211-4. |
|6.||Reves JG, Glass P. Intravenous anesthetics. In: Miller RD, Eriksson LI, Fleisher LA, Wiener-Kronish GP, Young WL, editors. Miller's Anaesthesia. 7 th ed. Philadelphia, PA: Elsevier Churchill Livingstone; 2010. p. 756. |
|7.||Jorm CM, Stamford JA. Actions of the hypnotic anaesthetic, dexmedetomidine, on noradrenaline release and cell firing in rat locus coeruleus slices. Br J Anaesth 1993;71:447-9. |
|8.||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. |
|9.||Lugo VW, Gomez IA, Cisneros-Corral R, Martinez-Gallegos N. Intravenous dexmedetomidine versus intravenous clonidine to prolong bupivacaine spinal anaesthesia. A double blind study. Anestesia en Mexico 2007;19:143-6. |
|10.||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 Anesthesiol 2009;20:225-31. |
|11.||Bromage PR, Burfoot MF, Crowell DE, Pettigrew RT. Quality of epidural blockade. I. influence of physical factors. Br J Anaesth 1964;36:342-52. |
|12.||Ramsay MA, Savege TM, Simpson BR, Goodwin R. Controlled sedation with alphaxalone-alphadolone. Br Med J 1974;2:656-9. |
|13.||Guo TZ, Jiang JY, Buttermann AE, Maze M. Dexmedetomidine injection into the locus ceruleus produces antinociception. Anesthesiology 1996;84:873-81. |
|14.||Elcicek K, Tekin M, Kati I. The effects of intravenous dexmedetomidine on spinal hyperbaric ropivacaine anesthesia. J Anesth 2010;24:544-8. |
|15.||Hong JY, Kim WO, Yoon Y, Choi Y, Kim SH, Kil HK. Effects of intravenous dexmedetomidine on low-dose bupivacaine spinal anaesthesia in elderly patients. Acta Anaesthesiol Scand 2012;56:382-7. |
|16.||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. |
|17.||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. |
|18.||Mason KP, Zurakowski D, Zgleszewski S, Prescilla R, Fontaine PJ, Dinardo JA. Incidence and predictors of hypertension during high-dose dexmedetomidine sedation for pediatric MRI. Paediatr Anaesth 2010;20:516-23. |
|19.||Sudheesh K, Harsoor S. Dexmedetomidine in anaesthesia practice: A wonder drug? Indian J Anaesth 2011;55:323-4. |
|20.||Belleville JP, Ward DS, Bloor BC, Maze M. Effects of intravenous dexmedetomidine in humans. I. Sedation, ventilation, and metabolic rate. Anesthesiology 1992;77:1125-33. |
|21.||Hall JE, Uhrich TD, Barney JA, Arain SR, Ebert TJ. Sedative, amnestic, and analgesic properties of small-dose dexmedetomidine infusions. Anesth Analg 2000;90:699-705. |
|22.||Jaakola ML. Dexmedetomidine premedication before intravenous regional anesthesia in minor outpatient hand surgery. J Clin Anesth 1994;6:204-11. |
[Figure 1], [Figure 2]
[Table 1], [Table 2], [Table 3]