Clonidine as a Sole Epidural Adjuvant in Combined Spinal-epidural: Clinical Study

Abstract

Background and Aims:

Clonidine has been used as an epidural adjuvant along with local anesthetics; however, its use as a sole epidural adjuvant in combined spinal-epidural (CSE) anesthesia has not been explored; thus, this study aimed to assess the effects of clonidine as a sole epidural adjuvant in CSE on sensory and motor characteristics of 0.5% hyperbaric bupivacaine given by subarachnoid route.

Methodology:

A total of 60 patients belonging to the American Society of Anesthesiologists Classes I and II aged 18–60 years were randomized in two groups; group G300 and group GNS. G300 group received 300 mg clonidine and GNS received normal saline through epidural route followed by 15 mg of 0.5% hyperbaric bupivacaine as subarachnoid block. Onset of sensory block (time to T10) and motor block (time to Bromage 3), level of sedation (using Modified Ramsay Sedation Score), and hemodynamic changes were recorded. Two-segment regression, duration of analgesia (time for 1^st rescue analgesia), and motor block (time to Bromage 0) were recorded. Student's t-test (two-tailed, independent) and Chi-square/Fisher's exact probability test were used for statistical analysis.

Results:

The demographic data were comparable between the groups. The onset of sensory and motor block was significantly faster in G300 (sensory-71.63 ± 4.51 s, motor-55.63 ± 2.54 s) as compared to GNS (sensory-90.13 ± 4.88 s, motor-118.43 ± 9.50 s) (P < 0.001 and < 0.001, respectively). The two-segment regression was 199.33 ± 19.11 min and 79 ± 9.77 min in G300 and GNS, respectively, (P < 0.001). Duration of analgesia was 317.90 ± 15.32 min and 207 ± 20.66 min for G300 and GNS, respectively (P < 0.001), and duration of motor block was 409.9 ± 34.87 min and 204 ± 22.79 min for G300 and GNS, respectively (P < 0.001). The side effects such as hypotension and bradycardia were statistically and clinically not significant.

Conclusion:

Clonidine used as a sole epidural adjuvant in dose of 300 mg, for infraumbilical surgeries, has significantly faster onset of sensory and motor block with prolonged duration of analgesia and motor blockade and no significant side effects on a conventional subarachnoid block performed with 0.5% hyperbaric bupivacaine.

INTRODUCTION

Adjuvant is an agent possessing little effect by themselves but potentiates the actions of other drugs when given at the same time. The α₂ adrenergic agonists have commonly used adjuvants. The analgesic and sedative properties and lack of opioid-related side effects make them a suitable alternative as an adjuvant in regional anesthesia. Clonidine, a selective partial agonist for α₂ adrenoreceptors,[1] has long been used as adjuvant in a variety of regional techniques. The combined spinal-epidural (CSE) technique offers the benefit of rapid onset of spinal block while the epidural catheter can be used for prolongation of anesthesia and postoperative analgesia.[2]

Although numerous studies have been made on clonidine as an adjuvant in epidural/spinal anesthesia,[3,4,5] the knowledge of its effect as an epidural adjuvant when given alone on a routine spinal block using hyperbaric bupivacaine 0.5% is however limited. Thus, the present study was undertaken to study the analgesic and sedative effects of clonidine when used without any local anesthetic epidurally as an adjuvant to conventional spinal anesthesia in CSE technique.

METHODOLOGY

Ethical committee approval was obtained. Sixty patients aged between 18 and 60 years belonging to the American Society of Anesthesiologists Classes I and II undergoing infraumbilical surgeries were involved in this prospective, randomized, and double-blind study. They were randomly allocated into two groups, group G300 and group GNS of 30 each, based on computer-generated random numbers (http://www.randomization.com). Patients who refused to participate and those with systemic disorders, psychiatric diseases, history of drug abuse, allergy to local anesthetics of the amide type, spine abnormalities and local skin infection, bleeding or coagulation test abnormalities, patients weighing <40 kg and >80 kg, patients with height <150 cm or more than 180 cm, and patients on antihypertensive and antipsychiatric medications were excluded from the study.

The computer-generated random numbers for group allotment was kept in sealed envelopes to maintain allocation concealment, and the envelope was opened just before preparation of drug solution. The group allocation sequence was maintained by the principal investigator and not revealed to others till the end of the study.

Patients were assessed on the previous day of surgery, and the study protocol was explained. Informed consent was obtained from all the patients. Premedication with sedatives was avoided. In the operation theater, all patients were prehydrated with 500 ml Ringer's lactate just before induction of anesthesia. Electrocardiogram, noninvasive blood pressure, and pulse oximeter monitors were connected, and baseline values of heart rate (HR), systolic blood pressure (SBP), diastolic blood pressure (DBP), mean arterial pressure (MAP), and peripheral oxygen saturation (SpO₂) were recorded. Oxygen was given by a facemask. The patient was placed in the lateral position. With all aseptic precautions, at L1–L2 interspace, an 18G Tuohy needle was passed and epidural space was identified by the loss of resistance to air. An 18G epidural catheter was passed through epidural space in the cephalad direction. After securing the epidural catheter, the L3–L4 interspace was utilized for performing the subarachnoid block (SAB) using Quincke spinal needle of 25G, subarachnoid space identified by the free flow of cerebrospinal fluid (CSF). Group G300 received 300 mcg of clonidine (diluted with 0.9% normal saline to make up to volume of 5 ml), and group GNS received 0.9% normal saline (5 ml), through epidural route. This was followed by administration of 15 mg of 0.5% hyperbaric bupivacaine into the subarachnoid space. The drug solutions were prepared under aseptic precautions by the anesthesia technician, who was not a part of the study team, as per the directions of the principal investigator. Neither the patient nor the monitoring anesthesiologist was aware of the drug solution administered. The time of completion of spinal injection was designated as SAB time and all other time points were measured from this time point. Sensory block was assessed using an alcohol swab, and the onset of sensory block was defined as loss of cold sensation at T10 dermatome. Maximum level of sensory block attained was recorded after 30 min of administration of SAB. Time for regression of sensory block by two segments from the maximum level was noted. Motor block was assessed using modified Bromage scale.[6] The time of onset of motor block was defined as time required for motor block to attain modified Bromage score of 3. Duration of motor block considered from the time of SAB to time when motor block reached modified Bromage score of 0. Sedation was evaluated by a five-point scale of Ramsay.[7]

Epidural supplementation with 5 ml of 0.25% bupivacaine was done if there was weaning of effect of spinal anesthesia during surgery and number of top-ups required was noted. If the level of sensory block did not reach T10 following SAB, epidural supplementation with local anesthetics was done and those patients were excluded from the study. Patients in whom both techniques failed, general anaesthesia was administered and were subsequently exclude from the study.

Hemodynamic parameters (HR, SBP, DBP, MAP, and SpO₂) were recorded every 5 min till the end of surgery and at 15 min intervals during 1^st h and every hour for next 6 h and every 4^th hourly till next 18 h postoperatively. Duration of analgesia was recorded from the time of administration of spinal anesthesia to the time when patient requested for first rescue analgesic in the postoperative period.

Side effects such as hypotension, bradycardia, dry mouth, excessive sedation, nausea and vomiting, and other effects, if any, during intraoperative or postoperative period were recorded. Results on continuous measurements are presented on mean + standard deviation (Min–Max), and results of categorical measurements are presented in number (%). Significance is assessed at 5% level of significance. Student's t-test (two-tailed, independent) has been used to find the significance of study parameters on continuous scale between two groups (intergroup analysis) on metric parameters. Chi-square/Fisher's exact probability test has been used to find the significance of study parameters on categorical scale between two or more groups. The Statistical software, namely, SAS 9.2, SPSS 15.0, Stata 10.1, MedCalc 9.0.1, Systat 12.0, and R environment ver. 2.11.1, were used for the analysis of the data and Microsoft Word Excel (2007) has been used to generate graphs and tables.

RESULTS

The demographic profile was comparable and statistically similar in both groups [Table 1]. All the patients enrolled completed the study, and there were no dropouts. None of the patients required epidural supplementation with local anesthetics or general anesthesia.

Table 1.

Demographic data

The mean time for onset of sensory block at T10 was 71.63 ± 4.51 s for Group G300 and 90.13 ± 4.88 s for Group GNS (P < 0.001). Onset of motor block was 55.63 ± 2.54 s in Group G300 and 118.43 ± 9.50 s in Group GNS (P < 0.001). The time for two-segment regression of sensory block was 199.33 ± 19.11 min in Group G300 and 79 + 9.77 min in Group GNS (P < 0.001). Duration of analgesia was 317.90 ± 15.32 min for Group G300 and 207.00 ± 20.66 min for Group GNS (P < 0.001). Total duration of motor block was 409.90 ± 34.87 min in Group G300 and 204.50 ± 22.79 min in Group GNS (P < 0.001) [Table 2 and Figures 1, 2]. The incidence of hypotension and bradycardia was comparable in both groups [Table 3].

Table 2.

Comparison of sensory and motor parameters

Figure 1.

2 segment regession, total duration of motor block, first rescue analgesia time for both groups

Figure 2.

Onset of sensory block, time to bromage grade 2 for both the groups

Table 3.

Comparison of side effects

DISCUSSION

The present study showed that clonidine (300 mcg) administered through epidural route as a sole epidural adjuvant to SAB in CSE produced faster onset and prolonged duration of sensory and motor blockade. It also significantly prolonged the duration of analgesia.

Clonidine is a centrally acting partial α₂ adrenoceptor agonist with selectivity ratio of 200:1. Its analgesic effect is mediated by binding to postsynaptic α₂ receptors (G-protein-coupled inhibitory receptors) in the dorsal horn of the spinal cord. This mimics the effects of noradrenaline which is released from the descending inhibitory pathways in the central nervous system. Thus, decreased activity of the second-order neurons and wide dynamic range neurons in the dorsal horn occurs which in turn attenuates the input from peripheral nociceptive Aδ and C fibers. It does not affect proprioception or produce motor blockade. Studies in rats show that clonidine partially inhibits voltage-gated sodium and potassium channels and suppresses generation of action potentials in tonic firing spinal dorsal horn neuron. Clonidine is rapidly and extensively absorbed into the spinal CSF compartment after epidural administration, with concentrations peaking 30–60 min after injection and coincides with near maximal analgesia,[8] and this may be the probable reason for prolongation of effects of spinal anesthesia in the present study. After epidural administration, clonidine produces peak concentrations in arterial blood within 10 min and venous blood within 30–45 min. Further, local vasoconstrictor effect of clonidine may delay systemic absorption of intrathecal local which also may contribute to prolonged effect of SAB.[8]

In this study, we used 300 mcg clonidine epidurally as some studies have shown increased incidence of adverse effects such as bradycardia, hypotension, and sedation with doses >600 mcg of clonidine.[8]

The onset of sensory and motor block was significantly faster in patients receiving epidural clonidine along with ropivacaine as an epidural adjuvant.[3] Duration of analgesia was also prolonged with epidural clonidine as noted by other authors.[4,9,10] Although our study used only clonidine epidurally, it too showed the same findings.

One hundred and sixty micrograms clonidine decreases arterial blood pressure by 18% and HR by 5%–20% with conclusion that epidural clonidine does not induce hemodynamic instability.[10] Our study also had shown the relatively low incidence of hypotension and bradycardia when epidural clonidine is used in dosage of 300 mcg. The α₂ agonists, when used in regional anesthesia, are shown to hasten onset of action of local anesthetics with rapid establishment of both sensory and motor blockade, prolongation of analgesia into the postoperative period, with dose-sparing action of local anesthetics and stable cardiovascular parameters.

In a study similar to ours, authors showed similar hemodynamic stability, significantly faster onset of motor and sensory block, and prolonged duration of analgesia using clonidine 150 mcg as a sole epidural adjuvant in an SAB with 3 cc hyperbaric bupivacaine.[4] This is in agreement with our study.

Limitation of the study

There exists only a few literature and study that precisely show the mechanism of action of clonidine in epidural route and its action on SAB by hyperbaric bupivacaine. Thus, more studies are needed to better understand the mechanism of action under such circumstances.

Scope of the study

The dosage of local anesthetic used through SAB can be reduced to obtain excellent anesthetic conditions using clonidine as a sole epidural adjuvant in various dosages.

CONCLUSION

Administration of 300 μg clonidine as a sole epidural adjuvant in CSE significantly shortens the onset and prolongs the duration of sensory and motor blockade and also the duration of analgesia without any clinically significant hemodynamic changes.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.