Comparison of Oral versus Intramuscular Clonidine for the Prolongation of Bupivacaine Spinal Anesthesia in Patients Undergoing Lower Abdominal and Lower Limb Surgeries.

Background: Spinal subarachnoid block (SAB) is the first choice anesthesia in lower abdominal and lower limb surgeries. It produces a varying degree of sensory analgesia, motor blockade, and sympathetic blockade depending on the dose, concentration, and volume of the local anesthetic given. This study was undertaken to assess the degree of sensory and motor block with 150 μg of oral versus intramuscular clonidine as an adjuvant to bupivacaine for spinal anesthesia. Aims and Objective: To compare the efficacy of oral versus intramuscular clonidine as an adjuvant to bupivacaine for the prolongation of sensory and motor block in patients undergoing lower abdominal and lower limb surgeries under SAB. Materials and
Methods: After institutional ethical clearance, 90 patients were randomized into three groups scheduled for lower abdominal and lower limb surgeries under spinal anesthesia. • Group O: Bupivacaine 0.5% (heavy) 3.0 mL and oral clonidine 150 μg 1 h before spinal anesthesia. • Group I: Bupivacaine 0.5% (heavy) 3.0 mL and intramuscular clonidine 150 μg 1 h before spinal anesthesia. • Group C: Control group - 3 mL bupivacaine 0.5% (heavy) alone. Result: The onset of sensory block in Group O was 4.9 ± 0.52 min, whereas in Group I, it was 4.6 ± 0.42 min than Group C (5.1 ± 0.60). Onset of motor block was also significantly lower in Group O and Group I (3.9 ± 0.53 and 3.7 ± 0.42 min) than in Group C (4.4 ± 0.6 min) which was a control group. There was also a significant difference in the duration of the sensory block between Group O (206.4 ± 9.2 min), Group I (219 ± 8.6 min), and Group C (184.3 ± 9.1 min). The duration of motor block was significantly higher in Group O (183.6 ± 8.2 min) and Group I (197.8 ± 9.6 min) when compared to Group C (162.8 ± 8.9 min). The timing of rescue analgesia in Group O was 222.4 ± 11.7 min, whereas in Group I, it was 243.46 ± 10.9.
Conclusion: On the basis of finding of our study, we conclude that the use of clonidine as a premedication at a dose of 150 μg significantly increased the duration of sensory block, motor block, and duration of analgesia and shortened the time of onset of sensory and motor blockade. Copyright:

INTRODUCTION

Spinal subarachnoid block (SAB) is the first choice anesthesia in lower abdominal and lower limb surgeries. It is a cost-effective option and also produces rapid-onset, superior blockade with a lower failure rate. It produces a varying degree of sensory analgesia, motor blockade, and sympathetic blockade depending on the dose, concentration, and volume of local anesthetic given.[1] Various drugs have been used as an adjunct to increase the duration as well as to improve safety profile in the past. Bupivacaine is a long-acting amide, metabolized in the liver, and offers the advantage of providing a long duration of action and a favorable ratio of sensory to motor neural block. Bupivacaine can be used appropriately for the procedures lasting for 2–2.5 h.[2]

Many drugs have been used as an adjuvant to local anesthetics to enhance their effects with varying benefits, e.g., epinephrine, neostigmine, and opioids.[3] Traditionally used as an antihypertensive, clonidine is now being used for sedative and analgesic properties. Clonidine, an imidazole derivative, is an alpha-2 adrenergic agonist. It is lipid soluble and rapidly enters the brain from circulation and is metabolized in the liver. Plasma level of clonidine peaks at approximately 3–5 h, and the half-life ranges from 12 to 16 h. The effect starts within 30–60 min of administration. This study was undertaken to assess the degree of sensory and motor block with 150 μg of oral versus intramuscular clonidine as an adjuvant to bupivacaine for spinal anesthesia.

Aims

This study aimed to compare the efficacy of oral versus intramuscular clonidine as an adjuvant to bupivacaine for the prolongation of sensory and motor block in patients undergoing lower abdominal and lower limb surgeries under SAB. The timing of rescue analgesia and any adverse events recorded were also compared.

MATERIALS AND METHODS

After institutional ethical clearance vide letter no. 1501/IEC/IGIMS/2020, this prospective, randomized interventional study was conducted between July 2020 and December 2021 in a tertiary care teaching hospital. This research was conducted after following the ethical principles for medical research involving human subjects in accordance with the Helsinki declaration. This study adhered to CONSORT guidelines (http://www.consort-statement.org) [Figure 1].

Figure 1

CONSORT flow diagram

After written informed consent for the study and use of data for educational research purposes, 90 patients of American Society of Anesthesiologists Physical Status (ASA PS) classes I and II, aged between 18 and 65 years, of both genders, scheduled for lower abdominal and lower limb surgeries under spinal anesthesia, were enrolled and randomly allocated into three equal groups (n = 30) after applying inclusion and exclusion criteria by computer-generated randomization. Exclusion criteria were patients refusal, any contraindications for regional anesthesia, ASA PS classes III and IV, history of allergy to study drugs, patients with cardiovascular diseases, renal failure, hepatic dysfunction and chronic pulmonary disease, obesity (body mass index ≥35), bleeding disorders (platelet count <50,000/mm3), and infections at the site of block.

Group O: Bupivacaine 0.5% (heavy) 3.0 mL and oral clonidine 150 μg 1 h before spinal anesthesia

Group I: Bupivacaine 0.5% (heavy) 3.0 mL and intramuscular clonidine 150 μg 1 h before spinal anesthesia

Group C: Control group – 3 mL bupivacaine 0.5% (heavy) alone.

Group O patients were given oral clonidine 150 μg 1 h before surgery, whereas Group I patients received intramuscular clonidine 150 μg 1 h before surgery. On arrival of patients in the operation theater, the patient was connected to the monitors, baseline parameters were recorded, and an intravenous line was initiated with an 18G cannula. All patients were preloaded with 20 mL.kg−1 of Ringer's lactate. Heart rate (HR), noninvasive blood pressure (NIBP), respiratory rate (RR), and peripheral oxygen saturation (SpO2) were recorded as a baseline and monitored throughout the surgery. Spinal anesthesia was given as per the standard norms with 25G Quincke needle in L2–L3 interspace in a sitting position. The surgeries were carried out under spinal anesthesia. Sensory blockade was assessed using a cotton wick test, and motor blockage was assessed using a modified Bromage scale. After achieving the sensory block up to T6 dermatome level and motor block of 3 on the modified Bromage scale, we allowed surgery to begin.

Description of the modified Bromage score for a motor block.[4]

Grade criteria

Able to move the hip, knee, and ankle

Unable to move the hip but able to move knee and ankle

Unable to move the hip and knee but able to move ankle

Unable to move the hip, knee, and ankle.

Recovery time for the sensory blockade was defined as dermatome regression of anesthesia from the max level to T12. Motor block duration was the time for return to Bromage scale score of “0.” The highest sensory block level and recovery time of both sensory and motor blocks were recorded. Adverse effects such as nausea/vomiting, bradycardia, hypotension, and dry mouth were observed and managed symptomatically. HR, NIBP, RR, and peripheral oxygen saturation (SpO2) were recorded. Hypotension (defined by a decrease in mean arterial pressure below 20% of baseline or systolic blood pressure <90 mmHg) was treated by mephentermine 6 mg intravenous (i.v.) stat. Bradycardia (HR <50 bpm) was treated by atropine 0.6 mg i.v. stat. Respiratory depression (RR <8 breaths per min or SpO2 <95%) was managed by oxygen supplementation and respiratory support if required.

Times for recording

T0 → Before administration of the drug

T1 → Just after administration of the drug

T2 → 5 min after administration of the drug

T3 and so on → Every 5 min thereafter till the end of surgery.

Statistical analysis of the data obtained was carried out using the analysis of variance test by GraphPad Prism by Dotmatics, GraphPad Software,2365 Northside Dr. Suite 560, San Diego, California. The sample size was based on keeping alpha and beta errors of 5% and 10% and the power of the study at 90%.

RESULTS

Patients were comparable in all three groups in terms of a demographic profile such as age, weight, height, gender, and ASA PS classification. No statistically significant differences were found in their age, weight, height, and their ASA PS class between all the three groups. However, most of the patients in all three groups were male [Table 1].

Table 1

Demographic profile

	Group O (n=30)	Group I (n=30)	Group C (n=30)	P
Age	46.6±9.6	48.8±10.2	49±10.7	>0.05
ASA Grade I and II	22:18	20:20	19:21	>0.05
Male:female	24:6	23:7	25:5
Mean weight (kg)	58.8±8.6	59.2±7.4	60.7±9.1	>0.05
Mean height (cm)	160.4±13.2	162.8±11.6	159.8±12.8	>0.05

ASA=American Society of Anesthesiologists

The onset of sensory block in Group O was 4.9 ± 0.52 min, whereas in Group I, it was 4.6 ± 0.42 min than Group C (5.1 ± 0.60). The onset of sensory block was earlier in Group I patients than Group O patients, which was statistically significant. Onset was more significant earlier in both the groups when compared to Group C. Onset of motor block was also significantly lower in Group O and Group I (3.9 ± 0.53 and 3.7 ± 0.42 min) than in Group C (4.4 ± 0.6 min) which was a control group [Table 2].

Table 2

Block characteristics

	Group O	Group I	Group C	P
Onset of sensory block (min)	4.9±0.52	4.6±0.42	5.1±0.60	<0.001
Onset of motor block	3.9±0.53	3.7±0.42	4.4±0.6	<0.001
Duration of sensory block	206.4±9.2	219±8.6	184.3±9.1	<0.001
Duration of motor block	183.6±8.2	197.8±9.6	162.8±8.9	<0.001
Timing of rescue analgesia	222.4±11.7	243.46±10.9	201.9±9.9	<0.001

There was also a significant difference in the duration of the sensory block between Group O (206.4 ± 9.2 min), Group I (219 ± 8.6 min), and Group C (184.3 ± 9.1 min). The duration of motor block was significantly higher in Group O (183.6 ± 8.2 min) and Group I (197.8 ± 9.6 min) when compared to Group C (162.8 ± 8.9 min). The timing of rescue analgesia in Group O was 222.4 ± 11.7 min, whereas in Group I, it was 243.46 ± 10.9. On statistical analysis, it was found to be statistically significant [Table 2].

There were few side effects encountered in all three groups. There were incidences of nausea and vomiting, but the differences were insignificant between the groups. When the incidence of bradycardia was compared, the incidence was lower in Group C, which is the control group, than in Group O and Group I, which is significant. The incidence of hypotension was 8 in Group O and 12 in Group I, whereas in Group C, it was in 6 patients. This showed a significant difference among the group. There was an incidence of dryness of mouth in Group O and Group I (6 and 10 respectively), whereas in Group C, none had dryness of mouth, which showed a significant difference when compared to the control group (Group C) [Table 3].

Table 3

Side effects

	Group O	Group I	Group C	P
Nausea/vomiting	4	6	3	>0.05
Bradycardia	5	8	3	<0.05
Hypotension	8	12	6	<0.05
Dryness of mouth	6	10	0	<0.05

DISCUSSION

The spinal SAB is the first choice anesthesia in lower abdominal and lower limb surgeries. It is a cost-effective option and also produces a rapid-onset, superior blockade with a lower failure rate. We have compared the use of oral clonidine versus intramuscular clonidine along with subarachnoid bupivacaine for the prolongation of sensory and motor blockade. Most commonly, clonidine is an alpha-2 agonist used for spinal anesthesia along with bupivacaine. In our study, we found that the use of clonidine orally as well as intramuscular caused a significantly increased duration of sensory and motor block compared to the use of bupivacaine alone but with minimal side effects such as bradycardia and hypotension.

Montazeri and Ghobadian[5] conducted a study in a double-blind controlled clinical trial and found the effect of oral clonidine premedication on the duration of SAB in 90 patients and concluded that the mean duration of sensory and motor blockade with oral clonidine (150 μg) was increased, which was comparable to our study. In our study, we found that the duration of sensory block in the oral clonidine group was 240 min, whereas in the intramuscular clonidine had 264 min.

Dziubdziela et al.[6] studied the effect of oral and intramuscular clonidine premedication on the duration of sensory and motor blockade and postoperative analgesia during bupivacaine spinal anesthesia in patients scheduled for lower limb orthopedic surgery and concluded that prolongation of bupivacaine sensory analgesia may be produced by premedication with 0.15 mg of oral and intramuscular clonidine. The application of clonidine reduces the early postoperative analgesic requirements. The side effects are more pronounced with the intramuscular route of administration, which is according to our study.

In our study, we had used clonidine 150 μg, whereas, in a study, Sudar Codai et al.[7] used lower oral clonidine premedication on the duration of analgesia produced by spinal bupivacaine and concluded that oral clonidine (100 μg) premedication 2 h before spinal anesthesia prolonged the duration of analgesia with spinal bupivacaine, which clearly signifies that oral as well as intramuscular clonidine increased the duration of sensory and motor block. Kumari et al.[8] carried out a randomized, double-blind study in 60 patients to assess the potential beneficial effects of prolongation of spinal analgesia with two different doses of oral clonidine and concluded that clonidine at the dose of 0.15 mg and 0.3 mg increases the duration of spinal anesthesia in comparison to the placebo, but 0.3 mg caused more hemodynamic changes compared with 0.15 mg. Kolarkar et al.[9] evaluated postoperative analgesic benefit in patients administered clonidine (150 μg) or placebo for below umbilical surgeries to be performed under the SAB using 3 mL 0.5% bupivacaine and to compare their postoperative efficacy with respect to duration of analgesia and concluded that clonidine group had more sedation throughout the postoperative period than in the control group and that it proved to have a better analgesic effect, reducing the total consumption of postoperative analgesia and prolonging first rescue analgesic dose. Gupta et al.,[10] in a prospective study, evaluated the efficacy of preemptive analgesia of oral clonidine for gynecological procedures under the SAB and concluded that it enhanced the onset of spinal anesthesia, prolonged the duration of analgesia, and provided clinically effective sedation without any respiratory depression. Harjai et al.[11] conducted a placebo-controlled double-blind study on 120 patients using different doses of clonidine (3, 4, and 5 μg.kg− 1 body weight) and concluded that preoperative oral clonidine 4 μg.kg-1 body weight appears to be the optimum dose for optimization of spinal anesthesia with bupivacaine as it prolongs the sensory block maximally with minimal side effects. Singh et al.[4] conducted a study to establish the efficacy and safety of intrathecal clonidine 50 μg as an adjuvant to bupivacaine and concluded that the use of clonidine 50 μg added to bupivacaine for spinal anesthesia effectively increased the duration of sensory block, duration of motor block, and duration of analgesia. Jagadale and Kelkar[12] conducted a study with intravenous dexmedetomidine versus intravenous clonidine to prolong bupivacaine spinal anesthesia and found that both intravenous dexmedetomidine and clonidine prolong the action of spinal anesthesia and postoperative analgesia than 0.5% hyperbaric bupivacaine. Dexmedetomidine has a longer duration of action than clonidine due to its alpha-2 receptor selectivity. Mishra et al.[13] in 2021 conducted a study on comparison of oral versus intramuscular clonidine for the prolongation of bupivacaine spinal anesthesia in patients undergoing total abdominal hysterectomy and found that preoperative intramuscular clonidine is a better alternate of oral clonidine for bupivacaine spinal anesthesia in terms of long duration of motor and sensory block and less requirement of analgesic with clinically insignificant side effects, which was similar to our study.

In our study, we have encountered a few side effects in all three groups. There were incidences of nausea and vomiting, but the difference was insignificant between the groups. When we compared the incidence of bradycardia, we found that the incidence was lower in Group C which is the control group than in Group O and I.

CONCLUSION

On the basis of findings of our study, we conclude that the use of clonidine as a premedication at a dose of 150 μg significantly increased the duration of sensory block, motor block, and duration of analgesia and shortened the time of onset of sensory and motor blockade. However, intramuscular clonidine is superior to oral clonidine with fewer side effects such as dryness of the mouth as well as bradycardia and hypotension.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.