Table of Contents  
ORIGINAL ARTICLE
Year : 2015  |  Volume : 8  |  Issue : 3  |  Page : 388-395

Safety and efficacy of intrathecal adjuvants for cesarean section: bupivacaine, sufentanil, or dexmedetomidine


Department of Anesthesia, Ain Shams University, Cairo, Egypt, This work was carried out at Aljazeera Hospital, Riyadh, KSA

Date of Submission26-Oct-2014
Date of Acceptance10-Feb-2015
Date of Web Publication29-Jul-2015

Correspondence Address:
Ibrahim A Nasr
Hassan Bin Thabit St, PO Box 123444, Riyadh 11741

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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/1687-7934.159002

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  Abstract 

Context
Coadministration of adjuvants with bupivacaine for spinal anesthesia is advocated to reduce its dose and improve the quality of intraoperative and postoperative analgesia with the least number of side effects.
Aim
The aim of the study was to compare the efficacy and safety of three intrathecal regimens for cesarean section.
Patients and methods
Ninety patients of ASA grade I or II who were scheduled for cesarean section under spinal anesthesia were randomly allocated into three groups of 30 patients each. Group B was injected with 15 mg of 0.5% hyperbaric bupivacaine, group F was injected with 10 mg of 0.5% hyperbaric bupivacaine +10 mg of sufentanil, and group D was injected with 10 mg of hyperbaric bupivacaine +10 mg of dexmedetomidine. Study parameters were as follows: mean arterial blood pressure, heart rate, respiratory rate, oxygen saturation (SpO 2 ), sedation scores, side effects (such as hypotension, bradycardia, nausea/vomiting, shivering, pruritus, respiratory depression), neonatal outcome, onset and duration of sensory and motor block, intraoperative and postoperative analgesic requirements, and duration of complete and effective analgesia.
Results
There were no significant differences regarding mean arterial blood pressure, heart rate, respiratory rate, SpO 2 , and neonatal outcome among the study groups. Sedation scores were higher in group D compared with groups B and S. Onset of motor block was comparable among the three groups, whereas onset of sensory block, time to two-segment regression and regression time to sensory S1, and motor recovery time were longer in groups D and S compared with group B. Intraoperative analgesic requirements showed no significance among the three groups, whereas duration of complete and effective analgesia was longer in groups S and D compared with group B. Further, postoperative 24 h analgesic requirements were higher in group B compared with groups S and D. Side effects such as hypotension, bradycardia, shivering, and respiratory depression were comparable among the study groups, whereas nausea/vomiting and pruritus were higher in group S compared with groups B and D.
Conclusion
Addition of sufentanil or dexmedetomidine to hyperbaric bupivacaine for intrathecal block prolongs the duration of sensory and motor block and reduces postoperative analgesic requirements. Sufentanil has a higher incidence of nausea/vomiting and pruritus, whereas dexmedetomidine has better analgesic effects and sedation without respiratory depression.

Keywords: dexmedetomidine, intrathecal adjuvants, safety and efficacy, sufentanil


How to cite this article:
Nasr IA, Elokda SA. Safety and efficacy of intrathecal adjuvants for cesarean section: bupivacaine, sufentanil, or dexmedetomidine . Ain-Shams J Anaesthesiol 2015;8:388-95

How to cite this URL:
Nasr IA, Elokda SA. Safety and efficacy of intrathecal adjuvants for cesarean section: bupivacaine, sufentanil, or dexmedetomidine . Ain-Shams J Anaesthesiol [serial online] 2015 [cited 2019 Jul 22];8:388-95. Available from: http://www.asja.eg.net/text.asp?2015/8/3/388/159002


  Introduction Top


Spinal anesthesia is a universally accepted anesthetic technique for both elective and emergency cesarean sections [1] . Hyperbaric bupivacaine has been a popular choice for spinal anesthesia. Using bupivacaine as a sole agent results in a relatively short duration of analgesia, necessitating early analgesic requirement in the postoperative period [2] . Coadministration of adjuvants with bupivacaine for spinal anesthesia is advocated to reduce the dose of the local anesthetic drug and to improve the quality of intraoperative and postoperative analgesia with the least possible maternal and neonatal side effects [3] . We aimed in this prospective randomized double-blinded study to compare the efficacy and safety of three intrathecal regimens for cesarean section. The first regimen was hyperbaric bupivacaine 0.5% alone but at a higher dose than in the other groups (15 mg). The second regimen was a combination of 10 mg hyperbaric bupivacaine 0.5% along with 10 μg sufentanil. The third regimen was 10 mg hyperbaric bupivacaine 0.5% along with 10 μg dexmedetomidine.

Bupivacaine has been used at a relatively higher dose to detect the effect of increase in its dose on the quality of the spinal block and to detect any dose-dependent side effects.

Respiratory depression after intrathecal injection of 15 μg sufentanil during labor has been reported after 15 min of the injection [4] . That is why we considered 10 μg sufentanil as the accepted safe dose for the study purpose.

Administration of α2 adrenoceptor agonists (such as clonidine and dexmedetomidine) to intrathecal block has been reported to significantly prolong the duration of anesthesia produced by hyperbaric bupivacaine, with a good safety profile [5],[6],[7] . Clonidine at a dose of 150 μg was preferred to prolong the duration of bupivacaine spinal anesthesia without significant side effects [6] . Dexmedetomidine is a more selective α2 adrenoceptor agonist with a 1 : 10 dose ratio compared with clonidine [8],[9],[10] , which led to the hypothesis that 15 μg of intrathecal dexmedetomidine would be safe. However, it has been reported in a study by Eid et al. [11] that the sedation scores were significantly higher with 15 μg intrathecal dose of dexmedetomidine, which might precipitate respiratory depression. Because of this reason, and because of the lack of an adequate number of references supporting the use of a dose higher than 10 μg for dexmedetomidine, we considered in our study that 10 μg of intrathecal dexmedetomidine would be an acceptable safe dose for the study purpose.


  Patients and methods Top


After obtaining approval from the hospital ethics committee of Al-Jazeera Hospital (Riyadh, Saudi Arabia), written informed consent was taken from all patients. Ninety parturients of ASA grade I or II who were undergoing elective cesarean section were included in a prospective, randomized, double-blinded study spanning a period of 6 months (September 2013 to March 2014). Patients with hypertension, chronic users of adrenergic receptor blockers, calcium channel blockers, and anticoagulants, patients with COPD, and patients who refused to undergo spinal anesthesia were excluded from the study.

A routine preoperative assessment was carried out, during which patients were familiarized with the concept of the visual analog scale (VAS), with 0 indicating no pain and 10 indicating the worst imaginable pain [12] .

In the operating theater, ECG, heart rate (HR), noninvasive blood pressure, and oxygen saturation (SpO 2 ) were monitored, and baseline values were recorded. Following intravenous cannulation, preloading with 15 ml/kg of intravenous lactated ringer solution was performed over 30 min. Under aseptic precautions, subarachnoid block (SAB) was administered through a midline approach in the sitting position at the level of L3-L4 or L4-L5, interspine, using a 25-G Quinke needle (Becton Dicknson™, Spain), and the intrathecal drug was injected over 10-15 s. Patients were placed in the supine position with their head facing upward.

Using a computer-generated random list, patients were randomly allocated into one of three groups.

  1. Group B (n = 30): this group received 3 ml of 0.5% hyperbaric bupivacaine (15 mg).
  2. Group S (n = 30): this group received 2 ml of 0.5% hyperbaric bupivacaine (10 mg) +10 μg of sufentanil (0.2 ml) diluted in 0.8 ml normal saline in one syringe (the total volume was 3 ml).
  3. Group D (n = 30): this group received 2 ml of 0.5% hyperbaric bupivacaine (10 mg) +10 μg (0.1 ml) dexmedetomidine (Precedex 100 μg/ml, (Precedex®; 200 µg/2 ml Abbott laboratory)) diluted in 0.9 ml normal saline in one syringe (the total volume was 3 ml).
All patients received lactated ringer solution at a rate of 2 ml/kg/h as maintenance fluid. Oxygen at a rate 4 l/min was administered by means of a face mask when needed. Drugs for injection were prepared by another anesthesiologist who was not involved in the study. Patients, the attending anesthesiologist, and the operating room and recovery room personnel were blinded to patient allocations. The study parameters were designed to monitor the safety (hemodynamic and respiratory parameters, sedation scores, side effects, and neonatal outcomes) and efficacy (sensory block criteria, motor block criteria, and pain scores) of the drugs for SAB.

Hemodynamic parameters

HR and noninvasive blood pressure were recorded at baseline and every 3 min for 15 min after SAB, followed by every 10 min for 1 h, and then hourly for the next 6 h. Hypotension (defined as a decrease in systolic blood pressure >30% of baseline value or systolic blood pressure <90 mmHg) was treated with an additional 500 ml of intravenous lactated ringer solution and intravenous boluses of 5 mg of ephedrine. Bradycardia (defined as a HR <60 beats/min) was treated with boluses of 0.3-0.5 mg of atropine.

Respiratory parameters

Respiratory rate (RR) and SpO 2 were recorded at baseline and then every 5 min for 15 min following SAB, and then every 15 min for the next 2 h. Respiratory depression was defined as RR less than 8/min and/or SpO 2 less than 90% and treated with oxygen supplementation and respiratory support if required.

Sedation scores

Sedation scores were assessed using the Ramsay Sedation Scale [13] , in which 1 indicates that the patient is anxious, agitated, or restless; 2 indicates that the patient is cooperative, oriented, and tranquil alert; 3 indicates that the patient responds to commands; 4 indicates that the patient is asleep but with brisk response to a light glabellar tap or loud auditory stimulus; 5 indicates that the patient is asleep, with sluggish response to a light glabellar tap or loud auditory stimulus; and 6 indicates that the patient is asleep with no response. Scores were recorded before the block and then every 15 min. Intravenous midazolam was given at 1 mg increments for anxious patients after the baby was delivered.

Side effects

Side effects such as nausea, vomiting, shivering, and pruritus were recorded intraoperatively and postoperatively at 1, 2, 6, and 12 h. Nausea was treated with ondansetron 4 mg, intravenous, whereas pruritus was treated with 100 mg, intravenous, of hydrocortisone.

Neonatal outcome

Blood samples were collected from the umbilical vein for blood gas analysis. Apgar scores were evaluated at 1, 5, and 10 min by a pediatrician who was blinded to the patients' allocations.

Sensory block parameters

Onset, duration, and highest level of sensory block were assessed by loss of temperature discrimination to ice along the mid-clavicular line every 2 min after SAB until the level was stabilized for four consecutive readings. Time to two-segment regression was tested every 15 min and time to sensory regression to S1 was recorded. Surgery was started when the block reached the T4 level. If the sensory block did not reach the T4 level within 20 min, general anesthesia was administered.

Motor block parameters

Onset and duration of motor block were assessed with the modified Bromage scale [14] , where 0 = no motor loss, 1 = inability to flex the hips, 2 = inability to flex knees, and 3 = inability to flex ankles. Motor block assessment was performed at 5, 10, and 15 min after SAB and then every 15 min after surgery until recovery of motor power to Bromage 0 was detected.

Pain scores

Intraoperative pain was evaluated by means of the VAS [12] . Patients who reported VAS score greater than 3 were given 50 μg fentanyl as intravenous bolus. Patients who required more than 100 μg fentanyl were excluded from the study. Pain scores were recorded postoperatively using VAS during the first hour at 15, 30, 45, and 60 min, then every hour up to 8 h, followed by at 12 and 24 h after SAB. Duration of complete analgesia (time from intrathecal injection to VAS >0) and duration of effective analgesia (time from intrathecal injection to VAS >3) were recorded. At VAS greater than 3, patients received an intramuscular injection of 75 mg diclofenac sodium as rescue analgesia.

Statistical analysis

Data were collected and analyzed using a statistical software package (Graph Pad In Stat, version 3.00; Graph Pad Software Inc., San Diego, California, USA) for Windows and presented as mean ± SD, n (%), or ratio as appropriate. A power analysis of a = 0.05 and b = 0.90 showed that 24 patients were required per study group to detect sensory regression time of 30 min with standard deviation of 28 min. Groups were compared using the parametric or the nonparametric versions of analysis of variance followed by appropriate post-hoc analysis if significance was detected. Nominal data were compared using the χ2 -test or alternatively by Fisher's exact test, as appropriate. P values less than 0.05 were considered significant.


  Results Top


All patients (n = 90) completed the study. There was no significant difference regarding patients' age, height, weight, and parity among the study groups. In addition, operative data such as skin incision to delivery time, uterine incision to delivery time, and duration of surgery did not show significant difference among the study groups, as shown in [Table 1].
Table 5: Sedation scores among the study groups

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A comparable decrease in mean arterial blood pressure (MAP) 15-30 min after intrathecal injection was observed in all groups. HR showed no significant changes among the three groups, as shown in [Table 2] and [Table 3].
Table 1: Patients' demographics and operative data

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Table 2: Mean arterial blood pressure changes during the study

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Five patients in group B, three patients in group S, and two patients in group D developed hypotension. They were treated with intravenous fluids and one single dose of ephedrine 5 mg intravenous. The difference between groups was not statistically significant. Further, three patients in group B, four patients in group S, and four patients in group D developed bradycardia, which was treated with intravenous dose of atropine 0.4 mg without affecting the results significantly. Nausea and vomiting was detected significantly in group S compared with group B and group D, whereas shivering was comparable among all groups. Pruritus was reported significantly in group S (nine patients) compared with groups B and D, in which no cases of pruritus were reported. One patient in group S developed respiratory depression 30 min after injection (RR 8/min and SpO 2 90%) and was treated with physical stimulation and oxygen supplementation without any drug interference. The rest of the patients in group S did not show any cases of respiratory depression (RR not less than 10/min and SpO 2 not less than 95% along the procedure), nor did any of the patients in groups B and D. All reported side effects are shown in [Table 4].
Table 3: Heart rate changes during the study

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Group D reported significantly higher sedation scores 30 min after injection [2.9 (2-3)] compared with group B [1.9 (1-2)] and group S [2.0 (1-2)] (P < 0.001), which persisted until 135 min, as shown in [Table 5].

All fetal outcomes were comparable and within normal ranges. Apgar scores and umbilical vein blood gas analysis were comparable, without significant abnormalities, as shown in [Table 6].
Table 4: Side effects reported in the study groups

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Table 6: Neonatal outcome (Apgar score and umbilical vein gas analysis)

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Onset of sensory block to T 10 was significantly shorter in groups S and D compared with group B, whereas time to two-segment regression and regression time to sensory S1 were significantly longer in group S and group D compared with group B, with no significant difference between the two groups. Time to reach motor block Bromage III was comparable among the three groups but time to motor recovery to Bromage 0 was significantly longer in groups S and D compared with group B, with no significant difference between the two groups. The criteria of sensory and motor block are shown in [Table 7].
Table 7: Criteria of sensory and motor block

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Durations of complete and effective analgesia were significantly longer in group S and group D compared with group B without a statistically significant difference between the two groups. The number of patients who needed intraoperative fentanyl was comparable among the three groups, whereas postoperative analgesic requirements (total number of doses of diclofenac/24 h) were significantly higher in group B compared with group S and group D, as shown in [Table 8].
Table 8: Duration of analgesia and perioperative analgesic requirement

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  Discussion Top


SAB is a frequently used, simple and effective method for producing anesthesia and early postoperative analgesia in patients undergoing cesarean section. Many adjuvants have been used along with bupivacaine for spinal anesthesia to reduce its dose and improve the quality of intraoperative and postoperative analgesia with the least possible maternal and neonatal side effects [3] .

This study showed that bupivacaine 0.5% as a sole agent for spinal anesthesia has a relatively short duration of analgesia, whereas addition of 10 μg sufentanil to the injection allowed to reduce the dose of bupivacaine and significantly prolonged the duration of complete and effective analgesia and motor block with significant reduction in postoperative analgesic requirements; however, it had a higher incidence of nausea/vomiting and pruritus; moreover, addition of 10 μg dexmedetomidine to the injection allowed to reduce the dose of bupivacaine and resulted in a significant prolongation of complete and effective analgesia duration and motor block and better sedation scores without respiratory depression.

Opioids and α2 receptor agonists are important adjuvants for neuroaxial block to improve the quality of perioperative analgesia and minimize the local anesthetic dose particularly in high-risk patients and for short duration procedures [15] .

Sufentanil is a lipophilic m-receptor agonist opioid. It exerts its effect intrathecally by combining with opioid receptors in the dorsal horn of the spinal cord and may have a supraspinal spread and action [16] . It has been established that addition of sufentanil to subarachnoid local anesthetics reduces visceral and somatic pain [16],[17] .

In our study, addition of sufentanil to intrathecal bupivacaine prolonged the duration of analgesia, with a higher incidence of nausea and vomiting. This result is supported by Schug et al. [18] , who proved the analgesic effect of intrathecal sufentanil but showed a reduction in intraoperative and postoperative incidence of nausea and vomiting compared with bupivacaine alone, whereas Fournier et al. [19] reported a higher incidence of nausea and vomiting following intrathecal administration of sufentanil and fentanyl compared with the control group.

The study by Dahlgren et al. [1] supported the analgesic action of intrathecal sufentanil and reported a higher incidence of pruritus up to 95% postoperatively, but they attributed the nausea and vomiting to the uterine manipulations during surgery. Another study by Veena et al. [3] supported the analgesic effect of intrathecal sufentanil and reported a higher incidence of pruritus and somnolence but lower incidence of nausea and vomiting with intrathecal sufentanil compared with placebo. Also, Motiani et al. [20] supported the analgesic effect of intrathecal sufentanil and reported a higher incidence of pruritus. Also in agreement with our results, Wong et al. [21] supported the analgesic effect of intrathecal sufentanil with a lower dose (2.5 μg), but they reported a higher dose of nausea and vomiting with a dose of 10 μg only, whereas the higher incidence of pruritus has been reported at a dose of 7.5 μg of intrathecal sufentanil with hyperbaric bupivacaine in parous parturients.

Our study showed a comparable decrease in MAP among all patients in the three groups 15-30 min after intrathecal injection. Decrease in MAP is a known occurrence after intrathecal bupivacaine injection due to block of the sympathetic afferent activity and it is dose related [20] . Many other studies [22],[23],[24],[25] reported a lower incidence of hypotension with intrathecal sufentanil-bupivacaine compared with hyperbaric bupivacaine alone. This can be attributed to the fact that the combination of sufentanil and bupivacaine provides a potent synergistic analgesic effect but cannot cause any further depression of efferent sympathetic activity. Therefore, it is possible to enhance sensory blockade without inducing more hypotension [22] .

We reported one patient with respiratory depression with intrathecal sufentanil 30 min after injection, which is in agreement with a case report of respiratory depression in women in labor 10 min after intrathecal injection of 15 μg sufentanil [4] . Also, two cases of respiratory arrest were reported after injection of 10 μg intrathecal sufentanil [26] , and two cases of respiratory depression have been reported 30 min after intrathecal injection of 5 μg sufentanil [20] , in addition to the cases of respiratory depression reported with lipid-soluble opioids [27] .

This study showed that addition of dexmedetomidine 10 μg to hyperbaric bupivacaine 0.5% intrathecally reduces the onset of sensory block, prolongs the duration of complete and effective analgesia and the duration of motor block, and reduces intraoperative and postoperative analgesic requirements with better sedation scores compared with bupivacaine 0.5% alone.

Dexmedetomidine is a highly selective α2 adrenoceptor agonist that has 10 times higher affinity for α2 adrenoceptors than does clonidine [9],[28] . Clonidine has been proved to have a postoperative analgesic effect when added to intrathecal local anesthetics [5],[6],[7] .

Dexmedetomidine mediates its analgesic effect by inhibiting the release of C fiber transmitters and by hyperpolarization of postsynaptic dorsal horn neurons [29] . Prolongation of motor block might be caused by direct impairment of excitatory amino acid release from spinal interneurons [30] , whereas the sedative effect is produced by acting on α2 adrenergic receptors in the locus ceruleus [29],[31] .

Our results are supported by Kanazi et al. [14] , who proved that addition of 3 μg of dexmedetomidine to intrathecal bupivacaine 0.5% produces a significantly short onset as well as a longer duration of sensory and motor block without serious adverse events. Another study showed a dose-dependent prolongation of sensory and motor block by coadministration of dexmedetomidine to intrathecal hyperbaric bupivacaine with reduction in postoperative analgesic requirements and desirable level of sedation with good hemodynamic stability [11] . Many other studies revealed prolongation of spinal block by 5 and 10 μg intrathecal dexmedetomidine with no significant effect on blood pressure and HR [31],[32] . This limited hemodynamic effect can be explained by the fact that bupivacaine reduces the sympathetic outflow nearly up to maximum, and thus dexmedetomidine cannot produce any further sympathetic block [33] .

Use of intrathecal dexmedetomidine has been reported to be associated with decrease in HR and blood pressure [31] . Our results showed no significant changes in HRs with a dose of 10 μg intrathecal dexmedetomidine. These results are supported by some other studies [11],[34] , which reported insignificant changes in HR or blood pressure with a dose up to 15 μg of intrathecal dexmedetomidine.

Although we did not detect a significant difference in intraoperative or postoperative shivering, Talke et al. [35] had observed that α2 adrenergic agonists have antishivering properties.

The sedative effect of α2 agonist was observed in our study with a dose of 10 μg intrathecal dexmedetomidine. Some studies [11],[32] did not report the same effect with the same dose, but they observed a significant sedative effect with higher doses, such as with 15 μg [11] , which may be related to its systemic absorption and vascular redistribution to higher centers or cephalic migration in CSF [36] . The dose of 15 μg intrathecal dexmedetomidine used by Eid et al. [11] showed significantly higher sedation scores, which can be beneficial for patients undergoing lengthy and complex surgeries as an alternative to epidural or prolonged general anesthesia and can preclude the use of intravenous sedatives. However, such sedative sores can be harmful in elderly and high-risk surgical patients owing to the risk associated with excessive sedation and respiratory depression.

Many studies [14],[31],[34],[37],[38] have supported our results of intrathecal dexmedetomidine injection with respect to the prolongation of motor block, sensory block, effective analgesia, and significant reduction of postoperative 24 h analgesic requirements with a small dose of dexmedetomidine (5 μg), and some other studies have shown dose-dependent prolongation of motor and sensory blockade with reduction in analgesic requirements with increasing dose of intrathecal dexmedetomidine from 5 to 10 to 15 μg [11],[32] .


  Conclusion Top


Hyperbaric bupivacaine as a sole agent for intrathecal block - even at higher doses - is not effective as an analgesic compared with sufentanil and dexmedetomidine. Addition of sufentanil or dexmedetomidine to intrathecal hyperbaric bupivacaine prolongs the duration of sensory and motor block and reduces postoperative analgesic requirements. Sufentanil - as a bupivacaine adjuvant - results in a higher incidence of nausea/vomiting and pruritus, whereas dexmedetomidine - as a bupivacaine adjuvant - has better analgesic effect and better sedation without respiratory depression.


  Acknowledgements Top


Conflicts of interest

None declared.

 
  References Top

1.
Dahlgren G, Hultstrand C, Jakobsson J, Norman M, Eriksson EW, Martin H. Intrathecal sufentanil, fentanyl, or placebo added to bupivacaine for cesarean section. Anesth Analg 1997; 85:1288-1293.  Back to cited text no. 1
    
2.
Hunt CO, Naulty JS, Bader AM, Hauch MA, Vartikar JV, Datta S, et al. Perioperative analgesia with subarachnoid fentanyl-bupivacaine for cesarean delivery. Anesthesiology 1989; 71:535-540.  Back to cited text no. 2
    
3.
Veena A, Amit A, Jagdish SP, Gupta V. Comparison of intrathecal sufentanil and morphine in addition to bupivacaine for cesarean section under spinal anesthesia. Anaesth Pain Intensive Care 2010; 14:99-101.  Back to cited text no. 3
    
4.
Hays RL, Palmer CM. Respiratory depression after intrathecal sufentanil during labor. Anesthesiology 1994; 81:511-512.  Back to cited text no. 4
    
5.
Fogarty DJ, Carabine UA, Milligan KR. Comparison of the analgesic effects of intrathecal clonidine and intrathecal morphine after spinal anaesthesia in patients undergoing otal hip replacement. Br J Anaesth 1993; 71:661-664.  Back to cited text no. 5
    
6.
Strebel S, Gurzeler JA, Schneider MC, Aeschbach A, Kindler CH. Small-dose intrathecal clonidine and isobaric bupivacaine for orthopedic surgery: a dose-response study. Anesth Analg 2004; 99:1231-1238.  Back to cited text no. 6
    
7.
Van Tuijl I, Giezeman MJ, Braithwaite SA, Hennis PJ, Kalkman CJ, van Klei WA. Intrathecal low-dose hyperbaric bupivacaine-clonidine combination in outpatient knee arthroscopy: a randomized controlled trial. Acta Anaesthesiol Scand 2008; 52:343-349.  Back to cited text no. 7
    
8.
Kalso EA, Pöyhiä R, Rosenberg PH. Spinal antinociception by dexmedetomidine, a highly selective alpha 2-adrenergic agonist. Pharmacol Toxicol 1991; 68:140-143.  Back to cited text no. 8
    
9.
Asano T, Dohi S, Ohta S, Shimonaka H, Iida H. Antinociception by epidural and systemic alpha 2 adrenoreceptor agonists and their binding affinity in rat spinal cord and brain. Anesth Analg 2000; 90:400-407.  Back to cited text no. 9
    
10.
Brunelli C, Zecca E, Martini C, Campa T, Fagnoni E, Bagnasco M, et al. Comparison of numerical and verbal rating scales to measure pain exacerbations in patients with chronic cancer pain. Health Qual Life Outcomes 2010; 8:42-42.  Back to cited text no. 10
    
11.
Eid HE, Shafie MA, Youssef H. Dose-related prolongation of hyperbaric bupivacaine spinal anesthesia by dexmedetomidine. Ain Shams J Anesthesiol 2011; 4:83-95.  Back to cited text no. 11
    
12.
Huskisson EC. Visual analogue scale. In: Melzack R, editor. Pain measurement and assessment. New York: Raven Press; 1983. 33-37.  Back to cited text no. 12
    
13.
Ramsay MA, Savege TM, Simpson BRJ, Goodwin R. Controlled sedation with alphaxalone-alphadalone. BMJ 1974; 2:656-659.  Back to cited text no. 13
    
14.
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. 14
    
15.
Axelsson K, Gupta, A. Local anaesthetic adjuvants: neuraxial versus peripheral nerve block. Curr Opin Anaesthesiol 2009; 22:649-654.  Back to cited text no. 15
    
16.
Alahuhta S, Kangas-Saarela T, Hollmén AI, Edström HH. Visceral pain during caesarean section under spinal and epidural anaesthesia with bupivacaine. Acta Anaesthesiol Scand 1990; 34:95-98.  Back to cited text no. 16
    
17.
Julião MC, Lauretti GR. Low-dose intrathecal clonidine combined with sufentanil as analgesic drugs in abdominal gynecological surgery. J Clin Anesth 2000; 12:357-362.  Back to cited text no. 17
    
18.
Schug SA, Saunders D, Kurowski I, Paech MJ. Neuraxial drug administration: a review of treatment options for anaesthesia and analgesia. CNS Drugs 2006; 20:917-933.  Back to cited text no. 18
    
19.
Fournier R, Van Gessel E, Weber A, Gamulin Z. A comparison of intrathecal analgesia with fentanyl or sufentanil after total hip replacement. Anesth Analg 2000; 90:918-922.  Back to cited text no. 19
    
20.
Motiani P, Chaudhary S, Bahl N, Sethi AK. Intrathecal sufentanil versus fentanyl for lower limb surgeries: a randomized controlled trial. J Anaesth Clin Pharmacol 2010; 26:507-513.  Back to cited text no. 20
    
21.
Wong CA, Scavone BM, Loffredi M, Wang WY, Peaceman AM, Ganchiff JN. The dose-response of intrathecal sufentanil added to bupivacaine for labor analgesia. Anesthesiology 2000; 92:1553-1558.  Back to cited text no. 21
    
22.
Olofsson C, Nygårds EB, Bjersten AB, Hessling A. Low-dose bupivacaine with sufentanil prevents hypotension after spinal anesthesia for hip repair in elderly patients. Acta Anaesthesiol Scand 2004; 48:1240-1244.  Back to cited text no. 22
    
23.
Zaugg M, Lucchinetti E. Respiratory function in the elderly. Anesthesiol Clin North America 2000; 18:47-58; vi.  Back to cited text no. 23
    
24.
Singh NP, Chhatrapati S. Efficacy of sufentanil with low dose bupivacaine on subarachnoid block for vaginal hysterectomy. Anaesthesiology 2007; 107:107-111.  Back to cited text no. 24
    
25.
Kumar S, Bajwa SJ. Neuroaxial opioids in geriatrics: a dose reduction study of local anesthetic with addition of sufentanil in lower limb surgery for elderly patients. Saudi J Anaesth 2011; 5:142-149.  Back to cited text no. 25
[PUBMED]  Medknow Journal  
26.
Lu JK, Manullang TR, Staples MH, Kem SE, Balley PL. Maternal respiratory arrests, severe hypotension, and fetal distress after administration of intrathecal, sufentanil, and bupivacaine after intravenous fentanyl. Anesthesiology 1997; 87:170-172.  Back to cited text no. 26
    
27.
Palmer CM. Early respiratory depression following intrathecal fentanyl-morphine combination. Anesthesiology 1991; 74:1153-1155.  Back to cited text no. 27
    
28.
Coursin DB, Coursin DB, Maccioli GA. Dexmedetomidine. Curr Opin Crit Care 2001; 7:221-226.  Back to cited text no. 28
[PUBMED]    
29.
Correa-Sales C, Rabin BC, Maze M. A hypnotic response to dexmedetomidine, an alpha 2 agonist, is mediated in the locus coeruleus in rats. Anesthesiology 1992; 76:948-952.  Back to cited text no. 29
    
30.
Palmeri A, Wiesendanger M. Concomitant depression of locus coeruleus neurons and of flexor reflexes by an alpha 2-adrenergic agonist in rats: a possible mechanism for an alpha 2-mediated muscle relaxation. Neuroscience 1990; 34:177-187.  Back to cited text no. 30
    
31.
Al-Ghanem SM, Massad IM, Al-Mustafa MM, Al-Zaben KR, Qudaisat IY, Qatawneh AM, et al. Effect of adding dexmedetomidine versus fentanyl to intrathecal bupivacaine on spinal block characteristics in gynecological procedures: a double blind controlled study. Am J Appl Sci 2009; 6:882-887.  Back to cited text no. 31
    
32.
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. 32
    
33.
Klimscha W, Chiari A, Krafft P, Plattner O, Taslimi R, Mayer N, et al. Hemodynamic and analgesic effects of clonidine added repetitively to continuous epidural and spinal blocks. Anesth Analg 1995; 80:322-32227.  Back to cited text no. 33
    
34.
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. 34
[PUBMED]  Medknow Journal  
35.
Talke P, Tayefeh F, Sessler DI, Jeffrey R, Noursalehi M, Richardson C. Dexmedetomidine does not alter the sweating threshold, but comparably and linearly decreases the vasoconstriction and shivering thresholds. Anesthesiology 1997; 87:835-841.  Back to cited text no. 35
    
36.
Eisenach JC, De Kock M, Klimscha W. Alpha sub 2-adrenergic agonists for regional anesthesia. A clinical review of clonidine (1984-1995). Anesthesiology 1996; 85:655-674.  Back to cited text no. 36
    
37.
Mahendru V, Tewari A, Katyal S, Grewal A, Singh MR, Katyal R. A comparison of intrathecal dexmedetomidine, clonidine, and fentanyl as adjuvants to hyperbaric bupivacaine for lower limb surgery: a double blind controlled study. J Anaesthesiol Clin Pharmacol 2013; 29:496-502.  Back to cited text no. 37
[PUBMED]  Medknow Journal  
38.
Ibrahim FA. A comparative study of adding intrathecal dexmedetomidine versus sufentanil to heavy bupivacaine for postoperative analgesia in patients undergoing inguinal hernia repair. Benha Med J 2009; 26:207-217.  Back to cited text no. 38
    


    Figures

  [Table 1]
 
 
    Tables

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


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