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ORIGINAL ARTICLE
Year : 2017  |  Volume : 11  |  Issue : 4  |  Page : 946-951  

Clinical study to determine the efficacy of clonidine as an adjuvant to intrathecal bupivacaine in patients undergoing cesarean section


Department of Anaesthesia, Karnataka Institute of Medical Sciences, Hubli, Karnataka, India

Date of Web Publication28-Nov-2017

Correspondence Address:
Basavaraj Kallapur
Department of Anaesthesia, Karnataka Institute of Medical Sciences, Hubli - 580 021, Karnataka
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/aer.AER_49_17

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   Abstract 


Introduction: Spinal anesthesia with bupivacaine is associated with hypotension and inadequate postoperative analgesia. The addition of clonidine as an adjuvant to intrathecal bupivacaine is beneficial in reducing the dose of the local anesthetic and also provides prolonged postoperative analgesia. Methodology: One hundred and five American Society of Anesthesiologists physical status Classes 1 and 2 parturient women undergoing elective cesarean section were randomly divided into three groups. Patients in Group C (control) received 2 ml of 0.5% of heavy bupivacaine (10 mg) with 0.5 ml of 0.9% saline to a total volume of 2.5 ml, those in Group H (high dose of bupivacaine) received 2 ml of 0.5% of heavy bupivacaine (10 mg) with 1 μg/kg of clonidine and 0.9% saline to make a total volume of 2.5 ml, and those in Group L (low dose of bupivacaine) received 1.5 ml of 0.5% of heavy bupivacaine (7.5 mg) with 1 μg/kg clonidine and 0.9% saline to make a total volume of 2.5 ml. Patients were observed for onset and duration of sensory and motor block and for postoperative analgesia. Results: Patients who received clonidine as adjuvant had effective prolonged postoperative analgesia (Group H – 480 ± 40 min, Group L – 480 ± 34 min) as compared to control group (180 ± 19 min). Conclusion: The dose of intrathecal bupivacaine 0.5% was effectively reduced to 7.5 mg by adding 1 μg/kg of clonidine as adjuvant in patients undergoing elective cesarean section.

Keywords: Bupivacaine, cesarean section, clonidine, intrathecal, postoperative analgesia


How to cite this article:
Kallapur B, Ravikumar D N, Shaikh SI, Marutheesh M. Clinical study to determine the efficacy of clonidine as an adjuvant to intrathecal bupivacaine in patients undergoing cesarean section. Anesth Essays Res 2017;11:946-51

How to cite this URL:
Kallapur B, Ravikumar D N, Shaikh SI, Marutheesh M. Clinical study to determine the efficacy of clonidine as an adjuvant to intrathecal bupivacaine in patients undergoing cesarean section. Anesth Essays Res [serial online] 2017 [cited 2019 Jul 22];11:946-51. Available from: http://www.aeronline.org/text.asp?2017/11/4/946/214242




   Introduction Top


Cesarean section is one of the most common surgical procedures that women in childbearing age group undergo. Subarachnoid block is the most common type of anesthesia performed for cesarean section as technically it is easy to perform and it provides quick and adequate anesthesia. It also has several benefits over general anesthesia such as avoiding intubation which may be difficult in parturients, decreasing the risk of gastric regurgitation and aspiration, avoiding exposure of both mother and fetus to cardiorespiratory depressant medications, and providing postoperative analgesia.[1],[2],[3]

However, subarachnoid block is also associated with some adverse effects such as occurrence of sudden and significant hypotension and bradycardia, respiratory depression, nausea and vomiting, and these events can also affect the neonate adversely. The incidence of these adverse effects can be decreased by reducing the effective dose of local anesthetic used for subarachnoid block which can be accomplished by adding an adjuvant to the local anesthetic agent such as opioids, ketamine, clonidine, and neostigmine. Use of some of these adjuvants is associated with significant adverse effects such as pruritus, urinary retention, respiratory depression, hemodynamic instability, nystagmus, and severe nausea and vomiting.[2],[4],[5]

Clonidine is a selective partial agonist for alpha two receptors. When administered intrathecally, the analgesic action is mediated by its action on the postsynaptic alpha 2 receptors in substantia gelatinosa. It is known to increase both sensory and motor block of local anesthetics. Intrathecal clonidine at 1 mcg/kg dose may not produce significant adverse hemodynamic effects in healthy patients.[3],[5],[6]

We hypothesized that the addition of clonidine as an adjuvant at the dose of 1 mcg/kg to bupivacaine 0.5% would reduce the effective dose of bupivacaine required to achieve adequate anesthesia and also prolong the postoperative period of analgesia. It would also reduce the incidence of adverse effects of spinal anesthesia with bupivacaine in parturients undergoing cesarean section.


   Methodology Top


A double-blind randomized controlled clinical study was conducted on 105 parturients undergoing elective cesarean section under subarachnoid block at Karnataka Institute of Medical Sciences, Hubli, during the period of January 2014 to May 2015. The approval of Institutional Ethical Committee was obtained. Parturients in the age group of 18–31 years belonging to the American Society of Anesthesiologists (ASA) physical status Classes 1 and 2 and undergoing elective cesarean section were included in the study. Exclusion criteria were patients with obstetric complications such as placenta previa and preeclampsia. Patients <150 cm tall, patients with spinal deformity such as kyphoscoliosis, patients who had known allergy to study drugs, and patients belonging to ASA grade more than 2.

Routine preanesthetic evaluation was done 1 day before the surgery. Basic laboratory investigations such as complete hemogram, bleeding time, clotting time, blood sugar, blood urea, serum creatinine, and urine analysis were carried out routinely on all patients.

Patients were informed about usage of clonidine for spinal anesthesia and explained regarding expressing postoperative pain as per visual analog scale (VAS) (score 0 being “no pain” and score 10 being “worst possible pain”). Written informed consent was taken from them. Weight and height were recorded.

Procedure

The patients were randomly allotted into one of three groups as per computer-generated randomization table. Each group consisted of 35 patients. Patients in Group C (control) received 2 ml of 0.5% of heavy bupivacaine (10 mg) with 0.5 ml of 0.9% saline to a total volume of 2.5 ml, those in Group H (high dose of bupivacaine) received 2 ml of 0.5% of heavy bupivacaine (10 mg) with 1 μg/kg of clonidine added as adjuvant along with 0.9% saline to make a total volume of 2.5 ml, and those in Group L (low dose of bupivacaine) received 1.5 ml of 0.5% of heavy bupivacaine (7.5 mg) with 1 μg/kg clonidine added as adjuvant along with 0.9% saline to make a total volume of 2.5 ml. The anesthetic drug solution was prepared by an anesthesiologist who was not taking part in the study. The patient and the anesthesia provider were unaware of the medication used to perform the block. The medications used for the study, i.e., bupivacaine (Anawin) and clonidine (Cloneon) were manufactured by Neon Laboratories. The dose of intrathecal clonidine was measured using insulin syringe.

Emergency drugs and equipment necessary for resuscitation and general anesthesia were kept ready. Routine monitors such as noninvasive blood pressure, pulse oximetry, and electrocardiogram were connected. Baseline blood pressure, heart rate (HR), and respiratory rate (RR) were noted. Peripheral intravenous (IV) line was secured with 18-gauge IV cannula. The parturients were preloaded with 10 ml/kg of Ringer's lactate solution before the initiation of spinal anesthesia.

Under strict aseptic precautions, with patients being in sitting position, subarachnoid block was performed using 26 guage spinal needle with 2.5ml of any one of the medications mentioned above depending on the group the patient belonged to. Immediately after the block, the patient was put in the supine position with 15° left side tilt by placing a wedge under right hip. Oxygen at 5 l/min through simple face mask administered.

Time of onset of sensory block was defined as time taken to achieve the loss of sensation to pinprick up to T6 level. Degree of motor block was assessed by modified Bromage scale (0 = able to lift extended leg at hip, 1 = able to flex knee but unable to lift extended leg, 2 = able to move foot only, and 3 = unable to move even foot). The surgeon was asked to start the surgery once the level of sensory block was at T6 and motor paralysis was of Grade 3. During the procedure, we observed if patient complained of any somatic or visceral pain. If these complaints were significant it was managed with sedation with IV midazolam and/or propofol.

Duration of sensory block defined as time from intrathecal injection of the drug to the time till regression of anesthesia below T12 dermotome level was noted. Duration of motor blockade defined as time from intrathecal injection of the drug to the time till modified bromage scale reached Grade 0 was noted.

Pulse rate, blood pressure, RR, and oxygen saturation were monitored every 5 min for the first 30 min, then every 10 min till the end of the surgery. Hypotension was defined as decrease in systolic blood pressure (SBP) by >20% of the baseline. It was treated with IV fluid boluses and IV administration of ephedrine 5 mg. Bradycardia was defined as pulse rate of <50 bpm and treated with IV administration of atropine 0.6 mg. Duration of analgesia was defined as time elapsed since the subarachnoid block was performed till the patient's pain score as per VAS was >3.

Neonatal apgar score at 1 and 5 min was assessed. Side effects such as pruritus, nausea, vomiting, and sedation (Campbell's sedation score:[7] 1 – wide awake, 2 – sedated, easily arousable, 3 – drowsy and difficult to arouse, and 4 – unarousable), were monitored throughout the procedure and postoperatively for 24 h. Nausea and vomiting was treated with IV administration of ondansetron 4 mg.

Statistical analysis

The statistical analysis of data is done using statistical package for social science (SPSS) evaluation version 22 (IBM Corp. Released 2013. IBM SPSS Statistics for Windows, Version 22.0. Armonk, NY: IBM Corp.). Results are expressed as mean and standard deviation. Frequencies expressed as number and percentage. One-way ANOVA, Kruskal–Wallis test used for multiple group comparison, and categorical data analyzed by Chi-square test. P ≤ 0.05 is considered for statistical significance.


   Results Top


In our study, 105 parturients were randomized into three groups. Demographically, there was statistically significant difference between Group L and Group C and between Group L and Group H with regard to mean age, height, and weight of the patients as shown below. However, no differences were seen with regard to mean gestational age in all three groups.

Time for onset of sensory and motor block were faster in Group C (sensory 5 ± 1.16 min and motor 6.66 ± 1.03 min) and Group H (sensory 5.23 ± 0.81 min and motor 6.71 ± 0.99 min) as compared to Group L (sensory 6.77 ± 0.69 min and motor 7.89 ± 0.96 min) and this was statistically significant.

There were statistically and clinically significant difference between clonidine groups and control group in terms of duration of postoperative analgesia. Group H (480 ± 40 min), Group L (480 ± 34 min) had longer period of postoperative analgesia as compared to the Group C (180 ± 19 min). Almost all patients who requested first rescue analgesia in our study had VAS score of ≥3.

Duration of sensory block was significantly shorter in Group C (135 ± 11 min) as compared to Group H (195 ± 14 min) and Group L (195 ± 10 min). Time for recovery of motor block was prolonged in groups with high dose of bupivacaine compared to that with low dose of bupivacaine which was statistically significant, i.e., Group H (195 ± 40 min), Group C (195 ± 32 min) versus Group L (165 ± 13 min).

In our study, the baseline mean pulse rate was 86.17 ± 14.11 bpm in Group C, 76.40 ± 12.25 bpm in Group H, and 82.06 ± 13.30 bpm in Group L which was statistically significant. In addition, there was significant difference in mean pulse rate between the groups at various time interval (at 3, 6, 9, 12, 15, 18, 24, 30, 40, and 50 min) after spinal anesthesia. However, these differences were not clinically significant. The mean baseline SBP in Group C, Group H, and Group L were 113.89 ± 7.59, 114.74 ± 8.30, and 113.54 ± 8.0 mmHg. However, the mean SBP showed statistically significant difference between the three groups at 50th, 60th, and 90th min. No hypotension was observed at these time instances; hence, this difference in mean SBP was clinically insignificant.

Overall, the incidence of side effects was less in Group L as compared to other two groups. Incidence of bradycardia (HR <50 bpm) was maximum in Group H (11.43%) compared to Group C (8.57%) and Group L (0%). Nausea was maximum in Group C (20%) than in Group H (11.43%) and Group L (5.71%). Vomiting was seen in four patients (11.43%) in Group C and in one patient (2.86%) in Group H. None of patients in Group L had vomiting. Shivering was seen in four patients (11.43%) in Group C as compared to one patient (2.86%) in each of Group H and Group L. None of the patients had dry mouth in our study. Intraoperatively, visceral pain was seen only in Group C patients (17.14%), i.e., in six patients. Incidence of hypotension (SBP <20% baseline) was higher in Group H (62.71%) (n = 22) and Group C (68%) (n = 24) when compared to Group L (31%) (n = 11) which was statistically significant. Not much significant difference was noted between control Group C and Group H.

None of the patients in Group C were sedated (Grade 1 sedation) while twenty patients (57%) in Group H and seven patients (20%) in Group L had Grade 2 sedation.

No clinically significant differences were observed with respect to RR and SpO2 among our study groups. No significant differences in Apgar score were seen among the groups in our study [Graph 1],[Graph 2],[Graph 3],[Graph 4],[Graph 5],[Graph 6],[Graph 7] and [Table 1], [Table 2], [Table 3], [Table 4], [Table 5].

Table 1: Comparison of three groups (C, H, L) with mean age by one-way ANOVA

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Table 2: Comparison of three groups (C, H, L) with mean gestational age by one-way ANOVA

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Table 3: Comparison of three groups (C, H, L) with height and weight scores by one-way ANOVA

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Table 4: Comparison of three groups (C, H, L) with onset time of sensory block and onset time of motor block scores by one-way ANOVA

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Table 5: Comparison of three groups (C, H, L) with status of incidence of side effects

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   Discussion Top


Intrathecal clonidine produces dose-dependent analgesia in patients with postoperative pain. Intrathecal clonidine is known to cause dose-dependent decrease in blood pressure and HR. It causes hypotension by causing the inhibition of preganglionic sympathetic activity in the spinal cord. Clonidine produces bradycardia by presynaptic-mediated inhibition of norepinephrine release and direct inhibition of atrioventricular node. It also causes dose-dependent sedation by its α2-adrenergic agonistic action on locus ceruleus and this can be reversed by specific antagonist yohimbine.[8]

In our study adding clonidine as an adjuvant to intrathecal bupivacaine in cesarean sections was effective in reducing the dose of bupivacaine and provide prolonged postoperative analgesia. The onset of sensory and motor block was quicker in the patients who received 10 mg of intrathecal bupivacaine, i.e., Group C and Group H when compared to those who received 7.5 mg of bupivacaine, i.e. Group L. Hence, onset of sensory and motor block is more dependent on bupivacaine dose rather than the addition of clonidine as adjuvant. Duration of motor block is significantly less in patients who received 7.5 mg of bupivacaine along with clonidine (165 ± 13 min) when compared to those who received 10 mg of bupivacaine with or without clonidine (195 ± 40 min and 195 ± 32 min, respectively). Decreasing the duration of motor block may benefit the patient by allowing for early ambulation. However, the duration of sensory block was significantly prolonged when clonidine was added as adjuvant in both low and high-dose bupivacaine groups (Group H = (195 ± 14 min), Group L = (195 ± 10 min), and Group C = 135 ± 11 min).

Kothari et al. conducted a study on parturients undergoing cesarean section under spinal anesthesia. In their study, Group 1 received 12.5 mg of plain intrathecal bupivacaine, Group 2 received 8 mg bupivacaine with 50 mcg of clonidine as adjuvant, and Group 3 received 10 mg bupivacaine with 50 mcg of clonidine as adjuvant. The patients receiving clonidine as adjuvant had significantly prolonged analgesia. The onset of sensory block and duration of motor block were similar to our study, i.e., onset of senory block was quicker in groups receiving higher dose of bupivacaine and duration of motor block was shorter in the group receiving lower dose of bupivacaine. Similar results were seen in few other studies where duration of analgesia and sensory block were significantly prolonged in patients receiving clonidine as adjuvant to intrathecal bupivacaine.[2],[6]

Bradycardia was observed in three parturients each in Group C and Group H. None of the parturients in Group L had intraoperative bradycardia. Incidence of hypotension was least in Group L, and it was almost same in the other two groups. Findings similar to our study were seen in the study conducted by Kothari et al.[1] and other studies.[2],[3],[5]

Incidence of side effects such as nausea, vomiting, and shivering were higher in high-bupivacaine dose group. Hence by effecting a reduction in dose of bupivacaine by adding clonidine as an adjuvant helps in reducing the incidence of side effects.

Similarly in the study conducted by Islam et al.,[9] the incidence of side effects such as nausea/vomiting, chest pain, and shivering were lesser in the group which received reduced amount of bupivacaine (1.75 ml) with clonidine (75 mcg) as adjuvant. Kothari et al. also had similar results.[1]

Intraoperative sedation was assessed by campbell's scoring. None of the patients in control group were sedated while twenty patients in Group H and 7 patients in Group L had Grade 2 sedation (patients were drowsy but easily arousable to verbal commands). Several other studies have observed increased incidence of sedation when clonidine is added as an adjuvant to intrathecal bupivacaine.[1],[2]


   Conclusion Top


We conclude that intrathecal clonidine as an adjuvant to bupivacaine at the dose of 1 μg/kg was effective in reducing the dose of the local anesthetic required to provide adequate anesthesia for cesarean section. It also provided significantly prolonged postoperative analgesia with minimum perioperative side effects.

Limitations of our study

Only one dose of clonidine, i.e., 1 μg/kg was chosen for our study as it was the optimal dose through intrathecal route as suggested by earlier studies. The total number of patients studied was 105. Studies including larger number of patients are required to establish our results emphatically.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
   References Top

1.
Kothari N, Bogra J, Chaudhary AK. Evaluation of analgesic effects of intrathecal clonidine along with bupivacaine in cesarean section. Saudi J Anaesth 2011;5:31-5.  Back to cited text no. 1
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2.
Singh R, Gupta D, Jain A. The effect of addition of intrathecal clonidine to hyperbaric bupivacaine on postoperative pain after lower segment caesarean section: A randomized control trial. Saudi J Anaesth 2013;7:283-90.  Back to cited text no. 2
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3.
Shah BB, Joshi SS, Shindhaye RV, Lakhe JN. Comparison of different doses of clonidine as an adjuvant to intrathecal bupivacaine for spinal anesthesia and post operative analgesia in patients undergoing caesarean section. Anesth Pain Intensive Care 2012;16:266-72.  Back to cited text no. 3
    
4.
Etches RC, Sandler AN, Daley MD. Respiratory depression and spinal opioids. Can J Anaesth 1989;36:165-85.  Back to cited text no. 4
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5.
Bajwa SJ, Bajwa SK, Kaur J, Singh A, Singh A, Parmar SS. Prevention of hypotension and prolongation of postoperative analgesia in emergency cesarean sections: A randomized study with intrathecal clonidine. Int J Crit Illn Inj Sci 2012;2:63-9.  Back to cited text no. 5
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Sethi BS, Samuel M, Sreevastava D. Efficacy of analgesic effects of low dose intrathecal clonidine as adjuvant to bupivacaine. Indian J Anaesth 2007;51:415-9.  Back to cited text no. 6
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Campbell DC, Camann WR, Datta S. The addition of bupivacaine to intrathecal sufentanil for labor analgesia. Anesth Analg 1995;81:305-9.  Back to cited text no. 7
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8.
Chiari A, Lorber C, Eisenach JC, Wildling E, Krenn C, Zavrsky A, et al. Analgesic and hemodynamic effects of intrathecal clonidine as the sole analgesic agent during first stage of labor: A dose-response study. Anesthesiology 1999;91:388-96.  Back to cited text no. 8
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9.
Islam MM, Ali NP, Begum R, Akhtaruzzaman AK. Subarachnoid clonidine or fentanyl with low dose hyperbaric bupivacaine for elective caesarean section – A comparative study. J Dhaka Natl Med Coll Hosp 2011;17:14-7.  Back to cited text no. 9
    



 
 
    Tables

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



 

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