Table of Contents  
ORIGINAL ARTICLE
Year : 2014  |  Volume : 7  |  Issue : 4  |  Page : 534-538

Dexmedetomidine versus clonidine as an adjunct to intrathecal small dose ropivacaine in patients undergoing transurethral resection of prostate


Department of Anaesthesiology, King George's Medical University, Lucknow, Uttar Pradesh, India

Date of Submission01-Jun-2014
Date of Acceptance06-Jul-2014
Date of Web Publication28-Nov-2014

Correspondence Address:
Satish Dhasmana
Department of Anaesthesiology, King George's Medical University, Lucknow - 226 003, Uttar Pradesh
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/1687-7934.145705

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  Abstract 

Context
It is important to limit the cephalad spread of local anesthetic above T10 dermatome during spinal anesthesia in patients undergoing transurethral resection of prostate (TURP). This can be achieved by using small dose of local anesthetics in combination with intrathecal additives such as α2 -agonists, which improve the quality of block without altering the height of block.
Aims
The aim of the study was to compare dexmedetomidine and clonidine when added to intrathecal ropivacaine in patients undergoing TURP.
Settings and design
The study was designed as a prospective, randomized, and double-blind study.
Materials and methods
Fifty patients of ASA grade I-III, scheduled for elective TURP, were allocated into two groups. Group I received 7.5 mg ropivacaine+15 μg clonidine and group II received 7.5 mg ropivacaine+5 μg dexmedetomidine. Spinal anesthesia was administered in the sitting position after preloading the patients with 10 ml/kg Ringer's lactate. Onset, duration, and peak sensory level, intensity of motor block, and analgesic requirements were recorded.
Results
Patients in both groups had comparable baseline and demographic characteristics. Peak sensory block was similar in both groups. Patients in group II had faster onset and longer duration of sensory block. Intensity and duration of motor block were also greater in group II. The quality of intraoperative and postoperative analgesia was better in group II.
Conclusion
Intrathecal dexmedetomidine with ropivacaine provides faster onset, better operating conditions, and patient comfort in patients undergoing TURP. However, it is associated with delayed motor recovery.

Keywords: additives, anesthesia, clonidine, dexmedetomidine, local anesthetic, ropivacaine, spinal, surgery, transurethral resection of prostate


How to cite this article:
Dhasmana S, Singh V, Raman R, Pal M. Dexmedetomidine versus clonidine as an adjunct to intrathecal small dose ropivacaine in patients undergoing transurethral resection of prostate. Ain-Shams J Anaesthesiol 2014;7:534-8

How to cite this URL:
Dhasmana S, Singh V, Raman R, Pal M. Dexmedetomidine versus clonidine as an adjunct to intrathecal small dose ropivacaine in patients undergoing transurethral resection of prostate. Ain-Shams J Anaesthesiol [serial online] 2014 [cited 2019 Sep 15];7:534-8. Available from: http://www.asja.eg.net/text.asp?2014/7/4/534/145705


  Introduction Top


Spinal anesthesia is the most frequently used technique for transurethral resection of prostate (TURP). Sensory block until T10 is considered optimal to eliminate the discomfort caused by bladder distension and other aspects of this procedure and sensory block cephalad to this mask the capsular signs associated with bladder perforation and may interfere with its early diagnosis and treatment. Moreover, because of the limited cardiovascular and respiratory reserve in older patients undergoing TURP, it is desired to avoid the cephalad distribution of the intrathecal local anesthetics. Smaller dose of local anesthetics in combination with additives provides the desired sensory level with adequate analgesia [1].

Ropivacaine is the pure S[-] enantiomer of propivacaine and a new long-acting amino-amide anesthetic, which combines the anesthetic potency and long duration of action of bupivacaine with a toxicity profile intermediate between bupivacaine and lidocaine. Clonidine, an α2 -agonist, when combined with bupivacaine, has prolonged duration of motor and sensory blockade and reduced incidence of intraoperative pain without influencing the peak sensory block height [2]. Dexmedetomidine, a newer, more selective α2 -adrenergic agonist, has been shown to increase the duration of motor and sensory blockade and speed up the onset of motor blockade when combined with intrathecal bupivacaine for urological procedures [3]. Kanazi et al. [4] used 3 μg dexmedetomidine and 30 μg clonidine in conjugation with 12 mg bupivacaine and found the median peak height of sensory block to be similar to the control with the favorable block profile.

On reviewing the literature, to date, there has been no study comparing dexmedetomidine and clonidine with ropivacaine in patients undergoing TURP. Therefore, the present study was designed to compare the block characteristics and cardiorespiratory effects with the addition of intrathecal clonidine or dexmedetomidine with low-dose ropivacaine in this clinical setting.


  Materials and methods Top


After getting approval from Ethical Committee of the King George's Medical University, informed consent was taken from all patients. Patients belonging to ASA physical status I-III planned for elective TURP under spinal anesthesia were included for this study.

Exclusion criteria were as follows:

(1) patient's refusal for consent;

(2) contraindication for spinal anesthesia;

(3) patients on analgesic therapy, α-adrenergic antagonists, or steroid therapy for past 1 month;

(4) allergy to study medications; and

(5) patients with neurological diseases.

The monitors were applied and baseline hemodynamic variables [heart rate (HR), systolic blood pressure (SBP), diastolic blood pressure (DBP), mean arterial pressure (MAP), SpO 2 , and ECG] were recorded. After establishing an intravenous line, Ringer's lactate (10 ml/kg) was infused before the intrathecal injection over 15 min to preload the intravascular compartment.

Using a computer-generated random number table, patients were divided into the following groups. Group I patients received 1 ml isobaric ropivacaine 0.75% (Ropin; Neon, Mumbai, India) + 15 μg clonidine (Cloneon; Neon). Group II patients received 1 ml isobaric ropivacaine 0.75% + 5 μg dexmedetomidine (Dexem; Themis, Mumbai, India). In both groups, total volume of the drug was exactly same.

The study solution was prepared by an anesthesia technician not involved in the patient's care.

With all aseptic precautions, a midline spinal puncture was performed at L3/L4 interspace (at L2/L3, if for an anatomical reason it was not possible at L3/L4) with 25-G pencil-point needle (Pancan; B. Braun, Melsungen, Germany) in the sitting position, and the anesthetic solution was injected without barbotage or aspiration at the beginning or at the end of injection. The injection was made over a span of 15 s with hole in the spinal needle facing upward and the patients were returned to the supine position; the legs were wrapped in elastic bandage, and subsequently placed in the lithotomy position.

Hemodynamic data including HR and MAP were recorded every 2 min in the first 10 min after spinal anesthesia, then every 5 min until 30 min, and then every 30 min until motor and sensory recovery (defined as regression of sensory blockade to L4 dermatome). Sensory dermatomal level of block was tested with pin prick in midclavicular line, and the highest level was noted. The anesthesiologist recording the data, the surgeon, the patients, and the nursing staff were all blinded to the patient group assignment.

Complications during surgery were treated as follows: hypotension (defined as an SBP of <90 mmHg) was treated with increments of 5 mg ephedrine; bradycardia (defined as an HR of <50 beats/min) was treated with 0.3 mg of atropine; and oxygen desaturation (defined as SpO 2 <90% on room air) was treated with oxygen through Hudson's face mask. If a patient complained about discomfort or pain, midazolam (0.05 mg/kg) and fentanyl (25 μg) was administered intravenously by the anesthesiologist in incremental doses. In the event of inadequate spinal block (defined as pain severe enough to interfere with the surgical procedure), general anesthesia was induced and the patient was excluded from the study. Adverse events (hypotension, bradycardia, sedation, nausea, vomiting, shivering, and pruritus) were recorded during surgery and recovery.

Motor block in the lower limb was assessed using a modified Bromage scale [5] (1 = complete motor blockade; 2 = almost complete motor blockade, the patient is able only to move the feet; 3 = partial motor blockade, the patient is able to move the knees; 4 = detectable weakness of hip flexion, the patient is able to raise the leg but is unable to keep it raised; 5 = no detectable weakness of hip flexion, the patient is able to keep the leg raised for 10 s at least; 6 = no weakness at all, the patient is able to perform partial knee bend while lying supine). These measurements were performed every 15 min after surgery and the time to complete motor recovery (modified Bromage score = 6) was noted.

During surgery, the surgeon assessed the quality of motor blockade as: 1 = perfect, 2 = adequate, 3 = inadequate, or 4 = poor. The quality of intraoperative analgesia was evaluated by patient using the following four-point scale: 1 = perfect analgesia, no sensation at all from the surgical site; 2 = adequate analgesia, sensation of motion only; 3 = inadequate analgesia, discomfort, but the patient declined additional analgesia; 4 = major discomfort, additional analgesics necessary [6].

Pain at rest was assessed using a visual analogue scale (VAS) (0 for no pain, 10 for the worst pain the patient had ever experienced). Level of sedation was determined using the following scale: 1 = wide awake; 2 = sleepy but easily aroused; 3 = sleepy and difficult to arouse. VAS and sedation scores were assessed hourly for the first 8 h after operation, and every 4 h thereafter for a total of 24 h.

In the postanesthesia care unit, pain was treated with intravenous injection of tramadol (50-100 mg) titrated to patient comfort. No other analgesic and/or sedative agents, including NSAIDs, were allowed during the first 24 h after surgery. Ondansetron (4 mg) intravenously and diphenhydramine (25 mg) intramuscularly as needed were prescribed for nausea/vomiting and itching, respectively.

The amount of tramadol administered after operation, time to first analgesic dose, postoperative length of stay, and the occurrence of any intraoperative or postoperative adverse events, including (but not limited to) nausea, vomiting, itching, respiratory depression (defined as a respiratory rate <12/min), and postdural puncture headache, were documented and treated accordingly.

Statistical analysis

Twenty-five patients per group were required to detect a significant difference of 25% or more in the requirement of rescue analgesia between the two groups (power of 85%, α = 0.05). Data are being expressed as mean and SD, median, or number/percentages as appropriate. HR, SBP, DBP, and mean blood pressure of the two groups over the periods were compared by repeated measures two-factor (periods and groups) analysis of variance, and the significance of mean difference between the periods was performed by the Newman-Keuls test after ascertaining the homogeneity of variance by Bartlett's χ2 -test. The discrete (categorical) variables were compared by the χ2 -test. The scores of two independent groups were compared by the nonparametric Mann-Whitney U-test. P value less than 0.05 was considered statistically significant. All analyses were performed on STATISTICA software (version 6; StatSoft Inc., Tulsa, Oklahoma, USA).


  Results Top


No patient had to be excluded from the study. The baseline demographic characteristics (age, height, weight, ASA grade), SBP, DBP, MAP, and HR of the two groups of patients were comparable ([Table 1] and [Table 2]).
Table 1 Comparison of demographic and baseline characteristics

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Table 2 Comparison of baseline cardiovascular parameters

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The mean time taken to reach T10 sensory block was significantly lower in group II (12.72 ± 0.45 min) compared with group I (16.64 ± 0.59 min). Maximum level of sensory block achieved was comparable among the groups. Duration of two-segment sensory regression was 104.80 ± 6.53 min in group I compared with 133.40 ± 14.20 min in group II, and sensory regression to L4 was 184.40 ± 10.83 min in group I compared with 263.00 ± 20.31 min in group II (P < 0.05, [Table 5]) - that is, it was significantly prolonged in patients receiving dexmedetomidine.

Motor block was more intense and lasted for a longer duration in group II than in group I ([Table 5]) patients. Cardiovascular parameters (HR and MAP) were comparable in both groups ([Table 3] and [Table 4]). None of the study patients developed severe hypotension (MAP < 50) or bradycardia (HR < 40).

Group II patients had better quality of analgesia, low values of VAS, and reduced analgesic requirements intraoperatively and postoperatively ([Table 5]). Level of sedation in both groups was comparable. No side effects, other than bradycardia and hypotension, were observed in our study.
Table 3 Comparison of heart rate at different time intervals

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Table 4 Comparison of mean blood pressure at different time intervals

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Table 5 Comparison of block characteristics

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  Discussion Top


The mechanism by which intrathecal α2 -adrenoceptor agonists enhance the motor and sensory block of local anesthetics is not well understood [4]. They act by binding to presynaptic C-fibers and postsynaptic dorsal horn neurons. Their analgesic action is a result of depression on the release of C-fiber neurotransmitters and hyperpolarization of postsynaptic dorsal horn neurons [7]. The prolongation of sensory effect of local anesthetics may result from synergism between local anesthetic and α2 -adrenoceptor agonist, whereas the prolongation of the motor block may result from the attachment of α2 -adrenoceptor agonists to motor neurons in the dorsal horn [8]. Clonidine is a well-established adjuvant to intrathecal local anesthetics. Dexmedetomidine has been used as adjuvant to spinal anesthetics in doses ranging from 3 to 10 μg in humans without any evidence of neurologic deficits after 2-week follow-up [3,4]. Use of dexmedetomidine in higher (up to 100 μg) doses in experiments on sheep, rat, and rabbits has not shown any signs of neurotoxicity [9-14]. In the present study, dexmedetomidine hastened the onset of sensory block (defined as time taken to reach T10 sensory block), extended the duration of sensory block, and enhanced the intensity and duration of motor block more than clonidine. The effects of dexmedetomidine on the onset and duration of sensory and motor block were found to be dose dependent [3]. Dexmedetomidine (3 μg) and clonidine (15 μg) had equal effects on sensory and motor block [4].

In the present study, the quality of intraoperative and postoperative analgesia was also better in patients receiving intrathecal dexmedetomidine as indicated by intraoperative VAS scores and rescue analgesic requirements. None of the patients in the studies conducted by Al-Mustafa et al. [3] and by Kanazi et al. [4] required intraoperative or postoperative analgesics. This could be due to use of higher dose bupivacaine used in their studies.

Cardiovascular parameters (SBP, DBP, MAP, HR) were comparable in the two groups as well as in the studies conducted by Al-Mustafa et al. [3] and Kanazi et al. [4]. Use of different doses of dexmedetomidine in the studies led us to conclude that the effect of dexmedetomidine on the cardiovascular system is minimal and independent of the dose administered [11-14]. No other adverse effects were found in the present study.


  Conclusion Top


The present study establishes that dexmedetomidine is a superior drug when used as an adjuvant to intrathecal ropivacaine in comparison with clonidine in patients undergoing TURP, as it provides faster onset of anesthesia, better intraoperative and postoperative analgesia, and patient comfort and better operating conditions.


  Acknowledgements Top


 
  References Top

1.
Healy TEJ, Knight PR. 2003. Wylie Churchill-Davidson's a practice of anesthesia7th ed.USA; CRC Press: 929-940.  Back to cited text no. 1
    
2.
Elia N, Culebras X, Mazza C, Schiffer E, Tramèr MR. Clonidine as an adjuvant to intrathecal local anesthetics for surgery: systematic review of randomized trials. Reg Anesth Pain Med 2008; 33:159-167.  Back to cited text no. 2
    
3.
Al-Mustafa MM, Abu-Halaweh SA, Aloweidi AS, Murshidi MM, Ammari BA, Awwad ZM, et al. Effect of dexmedetomidine added to spinal bupivacaine for urological procedures. Saudi Med J 2009; 30:365-370.  Back to cited text no. 3
    
4.
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; 50:222-227.  Back to cited text no. 4
    
5.
Bromage PR. Epidural Analgesia. Philadelphia: WB Saunders; 1978.  Back to cited text no. 5
    
6.
Mahmut A, Mehmet C, Dilºen O, Mehmet G, Yaºar P, Bayazit D, et al. Regional intravenous anesthesia in knee arthroscopy. Clinics 2010; 65:831-835.  Back to cited text no. 6
    
7.
Gupta R, Verma R, Bogra J, Kohli M, Raman R, Kushwaha JK. A comparative study of intrathecal dexmedetomidine and fentanyl as adjuvants to bupivacaine. J Anaesthesiol Clin Pharmacol 2011; 27:339-343.  Back to cited text no. 7
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8.
Eisenach JC, De Kock M, Klimscha W. a 2 -Adrenergic agonists for regional anesthesia: a clinical review of clonidine (1984-1995). Anesthesiology 1996; 85:655-674.  Back to cited text no. 8
    
9.
Harada Y, Nishioka K, Kitahata LM, Kishikawa K, Collins JG. Visceral antinociceptive effects of spinal clonidine combined with morphine, enkephalin, or U50, 488H. Anesthesiology 1995; 83:344-352.  Back to cited text no. 9
    
10.
Eisenach JC, Shafer SL, Bucklin BA, Jackson C, Kallio A. Pharmacokinetics and pharmacodynamics of intraspinal dexmedetomidine in sheep. Anesthesiology 1994; 80:1349-1359.  Back to cited text no. 10
    
11.
Lo WC, Harris J, Clarke RW. Endogenous opioids support the spinal inhibitory action of an alpha 2-adrenoceptor agonist in the decerebrated spinalised rabbit. Neurosci Lett 2003; 340:95-98.  Back to cited text no. 11
    
12.
Talke P, Xu M, Paloheimo M, Kalso E. Effects of intrathecally administered dexmedetomidine, MPV-2426 and tizanidine on EMG in rats. Acta Anaesthesiol Scand 2003; 47:347-354.  Back to cited text no. 12
    
13.
Xu H, Aibiki M, Seki K, Ogura S, Ogli K. Effects of dexmedetomidine, an alpha 2-adrenoceptor agonist, on renal sympathetic nerve activity, blood pressure, heart rate and central venous pressure in urethane-anesthetized rabbits. J Auton Nerv Syst 1998; 71:48-54.  Back to cited text no. 13
    
14.
Horvath G, Joo G, Dobos I, Klimscha W, Toth G, Benedek G. The synergistic antinociceptive interactions of endomorphin-1 with dexmedetomidine and/or S(þ)-ketamine in rats. Anesth Analg 2001; 93:1018-1024.  Back to cited text no. 14
    



 
 
    Tables

  [Table 1], [Table 2], [Table 3], [Table 4], [Table 5]



 

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