Sandeep Shankar¹, Shibu Sreedhar^2*, Ravi Kumar³, Abdu Razak K⁴

¹Assistant Professor, ²Associate Professor, ³Professor, ⁴Professor & HOD, Department of Anaesthesia, MMCH, Modakkallur, Calicut, Kerala.

Email: shibusreedhar8@gmail.com

RESULTS

A total of 100 patients belonging to ASA I and II posted for lower abdominal and lower limb surgeries were randomly selected. 50 of them belonging to group A or study group received 0.5% bupivacaine heavy 2.5 ml (12.5 mg) with 0.5 ml of injection buprenorphine 50 g intrathecally and other 50 patients belonging to group B or control group received 0.5% bupivacaine heavy 2.5 ml (12.5 mg) with 0.5% of normal saline intrathecally.

Table 1: Age wise distribution of the patients

The mean age in the both groups was 37.3  10.7 with a t value of 0.22 and p value of 0.83 which is not significant with respect to the age.

Table 2: Sex wise Distribution

This study included both male and female patients. In group A there were 26 male and 24 female patients and in group B there were again 23 male and 27 female patients.

Table 3: Height and Weight

The mean values of age, sex, weight and height those statistically comparable, they were not clinically relevant.

Table 4: Onset of Analgesia

statistically highly significant p-value being < 0.001

Table 5: Duration of Analgesia

p-value is < 0.01 is highly significant.

Table 6: Effect on Heart Rate

Intraoperatively at 15 minutes, 45 minutes there was an increase in heart rate which is statistically significant

Table 7: Systolic Blood Pressure

Intraoperatively at 45 minutes, 90 minutes there was a fall in systolic blood pressure and it slowly returned back to normal at 180 minutes which is highly significant (p < 0.001).

Table 8: Diastolic Blood Pressure

At 180 min, p-value was < 0.001 which was highly significant.

Table 9: Respiratory Rate

At 15 minutes, p-value being < 0.01 which is highly significant, and at 45 minutes, p-value being < 0.01 which is significant

Table 10: Saturation of Oxygen (SPO₂)

At 180 minutes p-value being > 0.05 which is significant.

DISCUSSION

As we all know that subarachnoid block is one of the commonest local anaesthetic technique and would probably maintain its place in the developing countries because of simplicity minimal skill requirement, onset, economy and minimum post-operative complications. This has the advantage that it is easy to perform and requires small dose of the drug making systemic absorption an important and also the patient will be most of the time conscious throughout the procedure. The disadvantage is limited duration of action and lack of post-operative pain relief by this local anaesthetic drugs like bupivacaine where in the analgesic action ends with the regression of the block which means that there is an early post-operative need for analgesia. The use of neuraxial opioids has increased dramatically in recent years augmenting the analgesia produced by local anaesthetics by binding directly to the opioid receptors. Animal studies have also demonstrated antinociceptive synergism between intrathecal opioid and local anaesthetics during visceral and somatic nociception. The synergistic action of local anaesthetics and morphine is well known but buprenorphine may have advantages because of its high potency and poor dissociation from opioid receptors which offers an attractive means of post-operative analgesia. Recent studies have also shown that narcotic drugs produces intense prolonged and segmental analgesic action when injected into the subarachnoid space. Buprenorphine is compatible with CSF and produces no adverse inflammatory reaction when administered intrathecally. Its high lipid solubility and high affinity for opioid receptors which is twice that of morphine, prolonged duration of action and as it is non-ionized drug which rapidly passes through the arachnoid membrane into the venous and lymphatic vessels. Buprenorphine has highest affinity for opioid receptors which is about 50 times greater than that of morphine and hence produce a longer duration of analgesia.

Dose of the drug⁵

Table 11: The dose of the drug can be calculated from the table 20 as follows:

The volume of the drug required i.e. bupivacaine (hyperbaric) will be affected by a number of factors apart from the position that the patient adopts during and immediately after injection. The factors are: Barbotage. Height of the patient. Specific gravity and pH of the drug. Level of the injection. Speed of injection of the drug.

Based on the above table we have used 2.5 ml of bupivacaine (0.5% heavy) with 0.5 ml of placebo like normal saline in control group and same amount of local anaesthetic along with 0.5 ml of normal saline with buprenorphine 50 g in our study to make the volume of the drug equal to 3 ml which accordingly is the ideal volume required for spinal blockade for surgeries below the umbilicus.

Patients characteristics across the group

In the present study, the patients studied in both the groups did not vary much with respect

to age, sex, weight, height, etc. Majority of the patients were middle age in both the groups i.e. between 20-60 years with a mean age of 37.3  10.7 years in both the groups. In the study group females were 48% and in control group females were around 54% whereas in study group males were around 52% and in control group males were around 46%. The mean weight in both the groups was more than 50 kgs. Hence, we selected the dose of injection buprenorphine to be around 50 g to be injected intrathecally along with injection bupivacaine. Height of the patient though statistically significant was not clinically relevant. The type of surgeries performed in both the groups were identical and the parameters were kept identical to minimize the bias.

Specific gravity of the drug combinations⁶

The specific gravity of bupivacaine alone is 1.037 and pH is 5.12. after combining bupivacaine and normal saline with buprenorphine the specific gravity was 1.028 and pH was 5.02.

Onset of analgesia

The onset of analgesia in the study group was 126.1  21.9 seconds with a range from 90 – 180 seconds whereas in the control group it was from 496.4  45.4 seconds with a range from 422 – 600 seconds. Thus the difference in the onset of analgesia between the two groups was highly significant. Thomas W et al.⁷ in their study showed that the onset of sensory analgesia was about 157 seconds with a range of 30 – 306 seconds and in the control group the onset time was 373 seconds with a range of 240 – 666 seconds. The result of this study shows that there is a statistical difference in the onset of analgesia and that addition of buprenorphine hastens the onset of action of bupivacaine.

Level of blockade after 30 minutes (intraoperatively)

In the study group, the level of blockade was until T6 in 23 patients, T8 in 20 patients and T10 in 7 patients, whereas in control group the T6 level was attained only in one patient, until T8 in 29 patients and in 20 patients it was until T10 only. from the above parameters we can see the highest level obtained was T6 in the study group which is very significant. Lipp M. et al.⁸ in 1987 showed in list study that 29 patients undergoing orthopaedic surgery, addition of buprenorphine elevated the sensory blockade by 2 – 3 segments both during spread and regression of anaesthesia.

Duration of blockade

In our study the time for rescue medication in study group was 584  19.11 minutes (9 hrs 40 min) and in the control group it was 170.3  6.7 minutes which was statistically significant. Lalla R.K.⁹ in the study in 1997 with 2 doses of buprenorphine 40 g (A group) and 80 g (B group) along with lignocaine showed that mean duration of analgesia with 40g was 11 hours and with 80 g it was 22 hours. Thomas W. et al.⁷ in the year 1997 in their study using 1 g/kg of buprenorphine (not > 50 g) along with bupivacaine 15 mg as their study group and bupivacaine 15 g alone as a control group showed that minimum duration of analgesia was 4 hours and maximum was 24 hours with a mean duration of 15.28 hours in study group, whereas in control group the duration of analgesia varied from 2.5 hours to a maximum of 3.8 hours with a mean duration of 3.17 hours. Nalini Damle et al.¹⁰ in the year 1990 in their study using 300 g of buprenorphine along with lignocaine 1 ml of 5% (heavy) as a study group and lignocaine 5% 2 ml alone as control group showed that the sensory block in buprenorphine group was about 9.2  0.9 hours. Sen¹⁰ in the year 1990 in her study using buprenorphine 300 g alongwith hyperbaric bupivacaine as a study group and hyperbaric bupivacaine alone as control group showed that the pain increased from 12 hours in study group whereas in control group pain increased gradually from 4 hours. Capogna G. et al.¹² in the year 1988 in his study using 30 g and 45 g of buprenorphine along with bupivacaine 30 mg and bupivacaine alone 30 mg showed that the mean pain free interval was 103.45 minutes in the control group but buprenorphine 30 g and 45 g along with bupivacaine was associated with longer post-operative analgesia i.e. about 430.16 minutes. Thus we conclude that intrathecal buprenorphine provided prolonged duration of action.

Effects of Intrathecal Buprenorphine on the Cardiovascular System

In our study all the patients were monitored clinically in the intraoperative as well as post-operative period. The pulse rate, systolic blood pressure and diastolic blood pressure were monitored at regular intervals. The incidence of hypotension was noticed in 5 patients of study group and in control group it was in 4 patients. hypotension was corrected by administration of injection mephenteramine 5 mg I.V. in incremental doses along with I.V. fluids and foot end elevation. The incidence of bradycardia was found in one patient of study group which was adequately treated with injection atropine 0.6 mg I.V. Systolic and diastolic blood pressure in both groups did not vary significantly in two groups until 180 minutes, as this was taken as a end point for comparison of both the groups because rescue medication was given to control group patients (VAS score > 6). Lalla R.K.⁹ in the year 1997 demonstrated that with 40 g of buprenorphine no side effects were observed while 80 g prolonged analgesia with easily manageable side effects and adequate preloading with crystalloids and intravenous atropine premedication can prevent haemodynamic side effects. Thomas W. et al.⁷ in the year 1997 demonstrated that there was no statistical significant change in pulse rate, blood pressure in the two groups. Sen¹² in 1992 in her study demonstrated that blood pressure and pulse rate remained within physiological limits. Nalini Damle et al.¹⁰ in the year 1990 demonstrated that the incidence of hypotension and bradycardia were comparable in the two groups where in 3 patients from control group and 4 patients in buprenorphine group developed hypotension which was treated by a rapid intravenous fluids and none of them required vasopressors. From the above discussions we can conclude that use of low dose buprenorphine 50 g along with bupivacaine for spinal anaesthesia can be administered safely without any adverse effect on the cardiovascular parameters.

Effects of Intrathecal Buprenorphine on Respiratory System

None of the patients in our study had respiratory rate less than 10 breaths/min or SPO₂ less than 90% in either groups. Sen¹⁴ in the year 1992 in her study demonstrated that the tidal volume, blood gas analysis did not show any significant differences between the two groups. Varma R.S.¹³ in the year 1991 in his study demonstrated that they did not observe respiratory depression in any patients. Rudra A. et al.⁶ in the year 1991 in his study demonstrated that there was no significant changes in respiration in any of the patients. Capogna G. et al.¹² in the year 1988 in their study demonstrated the mean respiratory rates in all the groups during the first 12 hours after surgery did not differs significantly and remained within the physiological limits. From the above studies we conclude that low dose of intrathecal buprenorphine 50 g along with bupivacaine can be safely given and this does not cause much respiratory function impairments especially immediate and late respiratory depression. In this study the adverse effects in study group (A) were nausea and vomiting in one patient, shivering in one patient, bradycardia in one patient and hypotension in 5 patients, whereas in control group (B) 4 patients had hypotension. 80 patients out of 100 patients were catheterized who had undergone lower abdominal, lower limb and perineal surgeries. Urinary retention could not be made out because most of the patients undergoing these surgeries were catheterized and those patients around 20 patients who underwent appendectomy who were not catheterized did not complain of urinary retention. Lalla R.K.⁹ in the year 1997 in his study showed that there was no major demonstrable side effects. Thomas W. et al.¹⁰ in his study showed that drowsiness was the major side effect of buprenorphine which could be desirable intraoperatively and all patients were arousable on verbal command and other than this there was major side effects. Sen¹¹ in the year 1992 showed that intrathecal buprenorphine provide a post-operative analgesia ith minimal side effects. Varma R¹³ in the year 1991 studying the effects of various doses of buprenorphine intrathecally i.e. 0.15 mg, 0.3 mg, 0.45 mg, 0.6 mg and 0.9 mg showed that the mean side effects observed in group 1, 2, and 3 were nausea, vomiting, headache, but with increasing concentration of buprenorphine as in groups 4 and 5 other side effects like urinary retention, drowsiness were observed. With the above considerations we can conclude that low dose buprenorphine 50 g along with bupivacaine gives better and prolonged duration of analgesia with minimal side effects. Although drowsiness is a major side effect of this drugs combination given intrathecally, this is of an advantage to the anaesthetist as there is no need for supplemental medication for e.g. sedation intraoperatively to the patient and other side effects are minimal and easily treatable.

CONCLUSION

1 g/kg not > 50 g of buprenorphine to 0.5% hyperbaric bupivacaine decreases the time of onset of sensory blockade, increases the duration and quality of analgesia without causing any gross hemodynamic disturbances or adverse effects in lower abdominal and lower limb surgeries

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