After the approval by the ethical committee of Indira Gandhi Medical College, Shimla, we conducted a randomized double blind study on 90 patients of either sex belonging to ASA physical status I and II, scheduled for surgery below the level of umbilicus in spinal anaesthesia over a period of six months. The patients with bradyarrythmia, atrioventricular heart block, having epilepsy or depressive neurological disorder and other relative or absolute contraindications to spinal anaesthesia were excluded from the study. All the patients were informed of the procedure to be carried out on them in the operative and the recovery room and written consent was obtained. The patients were allotted to either of the 3 study groups of 30 patients each as per random number list. To achieve a double blind study, the trial drug was prepared, coded and administered by an anesthetist not otherwise participating in the study. Both, the patient as well the investigator observing the results, were blind to the test drug by giving serial numbers to the patients which were decoded at the end of the study. All observations were made by the same observer to eliminate subjective error.

All routine investigations were done prior to the surgery. All the patients were kept nil per oral for at least six hours prior to the surgery.

Premedication in the form of tablet alprazolam 0.25mg was given on the night before the operation. After shifting the patient to operation theatre, baseline parameters like ECG, HR, NIBP, RR, peripheral oxygen saturation (spO₂) were recorded by the candidate who was blinded to the adjuvant drug used. In the operation theatre intravenous line was secured in all patients and 5ml/kg of isotonic normal saline was given before giving subarachnoid block. Monitoring of the heart rate, ECG, NIBP and oxyhaemoglobin saturation was established. Under all aseptic conditions subarachnoid puncture was performed using midline lumbar approach, with patient in sitting position using 26 gauge Quincke needle in L₃-L₄ interspace and after confirmation of the free flow of CSF, drugs were given according to the three groups in a double blind way.

The patients were then turned supine with no head tilt. Baseline values for monitored variables were taken. Heart rate, NIBP, oxyhaemoglobin saturation was monitored every minute for the first 10 minutes, every 5 minutes for the next 20 minutes and then at an interval of 15 minutes for one hour after subarachnoid block. Respiratory rate, level of sedation (Ramsay’s scoring), grade of motor block (Bromage scale) and level of sensory block (pin prick test) were monitored every 1 hour after injecting the drug until end of the study. Level of sensory block was seen by pin prick method after 7 minutes of injecting the drug. Time taken for the onset of action was noted from the time of injecting the drug into subarachnoid space to complete analgesia at the level of lower border of umbilicus. Duration of sensory block was calculated as the time taken for regression to two lower levels compared to that at the onset, which was taken as end point of the study. Duration of motor block was calculated as the time from the onset of action to no block on Bromage scale. A fall of more than 30% in systolic arterial pressure of baseline value or a reading of less than 90 mm Hg was treated with an intravenous bolus of 6 mg of mephenteramine. Any episode of bradycardia (heart rate < 50/min) was treated with 0.6 mg of i.v. atropine.

The data of the study was recorded in the record chart and results were evaluated using statistical tests (ANOVA test, post-hoc turkey hsd test, paired t-test and chi-square test).

The age, sex and weight were comparable in all the three groups as shown in [Table/Fig-1]. The difference between baseline parameters was also insignificant. The time taken for the onset of action and the level of sensory block achieved was comparable in all groups. Although, the heart rate decreased significantly in group 2 and group 3 as compared to their baseline values, but it remained comparable when group 2 was compared to group 3 as shown in [Table/Fig-2]. Incidence of bradycardia was statistically insignificant. The systolic blood pressure showed significant decrease in all the groups as compared to the baseline value. The intergroup comparison showed significant decrease in the systolic blood pressure of group 2 and group 3 from 25^th minute to 60^th minute as compared to group 1 as shown in [Table/Fig-3]. There was no significant difference noted in between group 2 and group 3. However, the incidence of hypotension requiring intervention was significantly more in group 2 as compared to group 1 and group 3. Other monitored parameters were comparable in all the groups throughout the study. No other untoward side effects were noticed in this study. The duration of sensory and motor block of the three groups are shown in [Table/Fig-4].

[Table/Fig-2]:

Comparison of Mean Heart Rates in Groups 1, 2 & 3.

[Table/Fig-3]:

Comparison of Systolic Blood Pressure in Groups 1, 2 & 3.

These results showed that the duration of sensory as well as motor block increased significantly in a dose dependent manner in groups in which clonidine was administered than in the control group. These findings support the observation made by Niemi et al., and Strebel et al., [7,8]. However, Benhamou and co-workers did not find prolongation of anaesthesia in their study [9], which in all probability must be due to the use of repeated boluses of intravenous fentanyl and epidural lignocaine whenever intraoperative analgesia was insufficient. This intervention may have lead to delay in regression of sensory blockade even in control group. Also, all the patients in the study were undergoing elective caesarean section that required consistently higher level of sensory blockade. Haemodynamically, heart rate was comparable in all the groups but as compared to its respective baseline value in group 3 and group 2, the heart rate decreased significantly from 7^th and 15^th minute, respectively. This is explained by the fact that following intrathecal injection, clonidine is rapidly redistributed into plasma with a t_1/2 alpha of 7.3 minutes with peak arterial levels at 10 minutes and venous level within 30-45 minutes [10]. Clonidine after systemic absorption decreases heart rate by enhancing baseline vagal activity and by a direct action on the heart. Incidence of bradycardia was 2, 1 and 0 in group 1, group 2 and group 3, respectively. These findings coincide with that of De Negri et al., and BS Sethi et al., [11,12]. However, Niemi et al., reported a significant reduction in the heart rate [7]. That may be due to the greater dose of hyperbaric bupivacaine (15 mg) as well as clonidione (3 μg/kg). Systolic blood pressure in clonidine groups exhibited a decrease as compared to the control group. Similar trend was observed by Niemi et al., [7]. But the incidence of hypotension was more in groups 3 and 2 than group 1. Exact explanation could not be found but JC Eisenach reported increased haemodynamic stability with use of intermediate to large doses of clonidine in sheep that resulted in activation of both α1 and α2 receptors [13]. A detailed dose response study in humans may indicate a favourable intermediate dose. Haemodynamic derangement occurs in clonidine groups after 20 minutes as compared to control group and stabilizes near 60 minutes. NIBP monitoring for some more duration may clear the exact pattern of recovery to baseline values. Other side effects such as sedation and dry mouth were not found in this study as they were found in the study by Niemi et al., and BS Sethi et al., [7,12]. The former used diazepam per os to their patients on the morning of surgery and the latter used double the maximum dose of clonidine used in this study.

This study concludes that intrathecal clonidine as an adjuvant to bupivacaine is an effective and convenient method to prolong spinal anaesthesia in a dose dependent manner for prolonged surgeries below the level of umbilicus with a limitation of close monitoring of NIBP and need of further studies with different doses to find the ideal dose of clonidine.