Spinal anaesthesia represents an attractive proposition for day-case anaesthesia.[1,2] The advantages of spinal anesthesia include avoidance of airway complications and depressant agents. [3,4] Intrathecal clonidine is  routinely are administered to surgical patients to provide prolonged postoperative analgesia.[5] Transdermal nitroglycerine (tNTG) has been found to be useful for enhancing the post-operative analgesic effect of intrathecal (IT) local anesthetic by release of nitric oxide (NO). Studies have been done which show the prolongation of post operative analgesia in patients receiving transdermal nitroglycerine (NTG) patch along with intrathecal bupivaciane and clonidine,but none have been done in lower limb surgeries so far. In this study, we compare the effects of NTG patch on duration of analgesia in post operative period  following subarachnoid block for lower limb surgeries.”

This randomized controlled study was carried out in Department of Anaesthesiology,Government Medical College, Srinager,Jammu and Kashmir, after obtaining approval from the Hospital Ethics Committee and written informed consent from the patients. Total 60 patients of the American Society of Anesthesiologists Classes I or II of either sex and of age 20–60 years of age posted for lower limb orthopedic surgery were randomly divided into two groups (n = 30).Any patient with cardiac comorbidity,renaldysfunction,hepatic dysfunction, coagulation abnormality or any patients posted for emergency surgery were excluded. The patients were divided into two groups of 30 and 30, namely Group BC (Inj. 15mg hyperbaric bupivacaine hydrochloride with 50 mcg of Inj. Clonidine) and Group BCN (Inj. 15mg hyperbaric bupivacaine with inj. 50 mcg of intrathecal clonidine and tNTG patch (3 cm × 5 cm, 5 mg/24 h) at chest wall in nonanesthetized area 20 min after intrathecal administration of drug solution). Preanesthetic checkup was done 1 day earlier and nil per oral explained. All the patients were familiarized with 0–10 cm visual analog scale (VAS) for pain and nausea. Zero equal to “no pain” and ten equal to “worst possible pain”. On arrival to the operation theater table, an intravenous (IV) infusion line was secured, and monitors were connected. Baseline recordings of pulse, systolic blood pressure (SBP), diastolic blood pressure (DBP), respiratory rate, (pulse oximetry) SpO2 , and electrocardiography (ECG) tracings were taken. Preloading of the patients with ringer lactate 10 ml/kg was done 15 min before procedure. Lumbar puncture was performed at L3–L4 level under aseptic conditions, with 25 gauge spinal needle, and the drug solution was injected intrathecally over 30 s as per the group allocation. The level of sensory loss was assessed by pinprick test. Heart rate, SBP, DBP, Respiratory rate, ECG, and SpO2 were monitored intraoperatively. Blood pressure and heart rate were monitored every 5 min throughout the surgery and a decrease >20% below the baseline value was treated by injection 6 mg mephenteraminei.v. Any fall in the heart rate below 50 beats/min was treated with incremental doses of injection atropine. Sensory and motor block was monitored at 2, 4, 6, 8, 10, 15 min, and after that at 15 min interval. Sensory block was tested by pinprick method. The motor block was assessed according to the modified Bromage scale. Any side effects such as nausea, vomiting, pain, shivering, pruritus, sedation, hypotension, bradycardia, and respiratory discomfort were noted.[8] Postoperatively, patients were assessed for pain by VAS rating scale at 15 min, 2 h, 4 h, 10 h, 18 h, and 24 h after the surgery was over. Sedation score was evaluated at the above mentioned time intervals and was recorded using Ramsay scale.Patients were also assessed for side effects such as nausea, vomiting, sedation, hypotension, bradycardia, sweating, and palpitation at the above mentioned time intervals. Rescue analgesia was administered at VAS 4 or >4 (moderate pain). Patients were given injection tramadol (1 mg/kg) IV as a rescue analgesic. The total amount of tramadol consumed by the patients in each group was also recorded. Duration of effective analgesia was measured from the time of IT drug administration to the patient’s first request for analgesic.The nitroglycerine patch was subsequently removed after 24 hours.

Table 1: Comparison of age in Group I (BC) and Group II (BCN)

The table no.1 Mean age in group BC was 36.36+-11.52 and in group BCN was also 38.46+-10.60. This was statistically not significant.

Table 2: Sex wise distribution of cases in Group I (BC) and Group II (BCN)

Table 3: Type of surgery wise distribution of cases in Group I (BC) and Group II (BCN)

Table No.3 shows distribution of patients on basis of type of surgery.Types of surgeries were similar and almost equal in both the groups.

Table 4: Comparison of Heart rate in Group I (BC) and Group II (BCN)

Table No. 4 shows comparison between heart rates in the two groups from subarachnoid block to demand of first rescue analgesic. It was not significant statistically.

Table 5: Comparison of Systolic Blood Pressure in Group I (BC) and Group II (BCN)

Table No. 5 shows comparison between systolic blood pressures in the two groups from subarachnoid block to demand of first rescue analgesic. It was not significant statistically.

Table 6: Comparison of Diastolic Blood Pressure in Group I (BC) and Group II (BCN)

Table No. 6 shows comparison between diastolic blood pressures in the two groups from subarachnoid block to demand of first rescue analgesic. It was not significant statistically.

Table 7: Comparison of Mean Arterial Pressure in Group I (BC) and Group II (BCN)

Table No.7 shows comparison between mean arterial pressures in the two groups from subarachnoid block to demand of first rescue analgesic. It was not significant statistically.

Table 8: Comparison of VAS score,time to first rescue analgesia and total no. of rescue analgesias in Group I (BC) and Group II (BCN)

Table 8 compares VAS in the 2 groups,time to first rescue analgesia and total no. of rescue analgesias in the 2 group,all are statistically significant.

Figure 1 compares the total duration of analgesia in the two groups. In group BC it was 5.08+-0.78 and in group BCN it was 7.1+-0.91. The comparison was highly significant statistically in group BCN.

Various drugs have been tried in the subarachnoid block along with local anaesthetics with the aim of improving the duration of post-operative analgesia. Clonidine, an alpha2-adrenoceptor agonists, is among such adjuvants. In this study, we aimed to find out whether quality of anaesthesia and post-operative analgesia is better when clonidine is used along with an additional transdermal nitroglycerine patch in lower limb surgeries (orthopedic surgeries). We also studied the onset, quality and duration of sensory and motor blockade produced in 2 groups: Group 1 (BC)(30cases): Inj. hyperbaric Bupivacaine hydrochloride(15mg) + Inj.Clonidine (50mcg) Group 2 (BCN)(30 cases): Inj. hyperbaric Bupivacaine (15mg)+ Inj. clonidine (50 mcg) and transdermal nitroglycerine patch. Transdermal nitroglycerine acts as an analgesic by release of nitric oxide (NO). Nitric oxide produces pain modulation via release of cyclic guanosine monophosphate (cGMP). [10,11] Following are the observations from our study.  There were no statistically significant differences in patient’s age, gender, type of surgery, duration of surgery between the groups. In our study we compared the variation in heart rate, systolic blood pressure, diastolic blood pressure, mean arterial pressure, using T test at various time intervals which were clinically as well as statistically insignificant.

Postoperative Analgesia

The duration of effective postoperative analgesia was defined as the interval between administration of the intrathecal injection and the first request for rescue analgesia. The requirement for rescue analgesia was assessed using the Visual Analog Scale (VAS) score. The comparison of postoperative pain scores between the two groups demonstrated that the mean VAS score was significantly higher in Group BC (7.10 ± 0.88) compared with Group BCN (5.03 ± 0.92). This difference was found to be highly statistically significant, indicating superior postoperative analgesia in patients receiving the combination of intrathecal clonidine with transdermal nitroglycerine. The time to first rescue analgesic requirement was significantly prolonged in Group BCN (7.10 ± 0.91 hours) as compared to Group BC (5.08 ± 0.78 hours). This finding was highly statistically significant and suggests that the addition of a transdermal nitroglycerine patch delayed the need for postoperative rescue analgesia. Furthermore, comparison of the total number of rescue analgesic doses required postoperatively revealed a significantly lower requirement in Group BCN (2.16 ± 0.46) compared to Group BC (3.13 ± 0.57). This observation further supports the enhanced analgesic efficacy achieved with the addition of transdermal nitroglycerine. Postoperative complications such as headache and postoperative nausea and vomiting (PONV) were observed in a few patients in both groups. However, the difference in incidence between the groups was not statistically significant.

*

The two study groups were comparable with respect to demographic characteristics including age, gender, and type of surgery performed. The findings of the present study demonstrate that the addition of a transdermal nitroglycerine patch to intrathecal clonidine as an adjuvant to hyperbaric bupivacaine (0.5% heavy) resulted in significant improvement in postoperative analgesia compared with intrathecal clonidine alone. Patients receiving the combination therapy experienced a significant delay in the time to first rescue analgesic requirement along with a reduction in the total number of rescue analgesic doses required postoperatively. In addition, the combination of intrathecal clonidine with transdermal nitroglycerine was associated with prolonged duration of analgesia and extended duration of motor blockade when compared with intrathecal clonidine alone. The study therefore supports the efficacy and safety of using a transdermal nitroglycerine patch in combination with intrathecal clonidine as an adjuvant to bupivacaine for spinal anesthesia. The combination was associated with: • Significant prolongation of postoperative analgesia • Delayed requirement for first rescue analgesic • Reduced total rescue analgesic consumption • Improved postoperative VAS scores • Stable hemodynamic profile • No significant increase in adverse effects or complications Thus, the present study suggests that transdermal nitroglycerine enhances the postoperative analgesic effect of intrathecal clonidine without causing significant hemodynamic instability or increasing the incidence of postoperative nausea and vomiting. Conflicts of Interest The authors declare that there are no conflicts of interest related to this study. Financial Support No financial support or external funding was received for this study.

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