Effect of Fentanyl on Block Characteristics as Adjuvant to Intrathecal Bupivacaine for Lower Limb Surgeries.

BACKGROUND: Regional anesthesia is the preferred technique for most of lower abdominal and lower limb surgeries as it allows the patient to remain awake and minimize the problems associated with airway management. Hyperbaric bupivacaine 0.5%, although extensively used for spinal anesthesia, has a limitation of short duration. The addition of fentanyl, a synthetic lipophilic opioid, is known to prolong postoperative analgesia. AIMS: We aimed to study the effect of the addition of different doses of fentanyl to hyperbaric bupivacaine about hemodynamic changes, the extent of sensory and motor block, duration of analgesia, and complications that occur during the procedure. SETTINGS AND
DESIGN: This study was a prospective, comparative, randomized, and double-blind study.
MATERIALS AND METHODS: Patients were randomly allocated to three groups of 30 each. Group I (n [number of patients] = 30) received bupivacaine 0.5% heavy 2.0 mL diluted up to 2.5 mL with normal saline. Group II (n = 30) received bupivacaine 0.5% heavy 2.0 mL and fentanyl 20 μg diluted up to 2.5 mL with normal saline, and Group III (n = 30) received bupivacaine 0.5% heavy 2.0 mL and fentanyl 50 μg diluted up to 2.5 mL with normal saline. STATISTICAL ANALYSIS: The data were analyzed using Chi-square and Student's t-test. RESULTS AND
CONCLUSIONS: The onset of sensory and motor block was early in Group III in comparison to Group I and Group II (P < 0.05). The duration of analgesia was significantly longer in Group III, followed by Group II, and least in Group I. None of the patients in Groups I and II had any complications such as hypotension, nausea, vomiting, bradycardia, and pruritus. However, the incidence of hypotension, nausea, and pruritus was more in Group III. 2 mg intrathecal bupivacaine with 20 μg fentanyl provides reliable and satisfactory sensory and motor block without increasing the incidence of side effects. Copyright:

INTRODUCTION

Spinal anesthesia provides adequate surgical anesthesia. The increasing acceptance of this technique is due to maintenance of consciousness, spontaneous breathing, adequate muscle relaxation, minimal disturbances of body chemistry, and a pleasant recovery from anesthesia. The main disadvantage of spinal anesthesia is its shorter duration of action.[1] Recently, there has been increasing interest in using various additives to local spinal anesthetics to decrease the dose of local anesthetics, enhancing the duration of action, and minimizing adverse effects of local anesthetics. Bupivacaine is the most commonly used local anesthetic for subarachnoid block.[2] Opioids are widely used in conjunction with local anesthetics as they permit the use of a lower dose of local anesthetics while providing adequate anesthesia and analgesia. However, there is no consensus over the dose of fentanyl to be used safely. The present study is to compare the addition of different doses of fentanyl to hyperbaric bupivacaine in the spinal block as a primary outcome. The present study is done to study the effect of addition of different doses of fentanyl to hyperbaric bupivacaine aouut hemodynamic changes, the extent of sensory and motor block, duration of analgesia and complications that occure during the procedure.

MATERIALS AND METHODS

A prospective, randomized, double-blind study was conducted after getting approval from the Hospital Ethical Committee. Informed written consent was obtained from all the patients after explaining the procedure. The preanaesthetic checkup included general, physical and systemic examination was done.

Routine relevant biochemistry investigations were carried out in all patients, and echocardiogram (ECG) and X-ray chest were done in patients wherever indicated. The patients were kept fasting 6 h before the surgery. 90 patients of physical status ASA classes I and II of either sex between 18 and 60 years undergoing lower abdominal surgeries were included in the study. Patients with hemorrhagic diathesis, peripheral neuropathy, psychiatric disorders, and allergy to local anesthetics and patients on opioid therapy/analgesics were excluded from the study. Standard monitoring included noninvasive arterial blood pressure, ECG, heart rate (HR), and oxygen saturation (SpO2). All the patients received premedication with midazolam 0.5 mg at bedtime. In preoperative anesthesia room, intravenous line was secured with 20G cannula and patients were preloaded with 500 mL of Ringer's lactate. Baseline blood pressure, pulse rate, respiratory rate, and SpO2 were recorded. Patients were randomly allocated into three groups in equal numbers.

Group I(n = 30) received bupivacaine 0.5% heavy 2.0 mL diluted up to 2.5 mL with normal saline.

Group II (n = 30) received bupivacaine 0.5% heavy 2.0 mL and fentanyl 20 μg diluted up to 2.5 mL with normal saline.

Group III (n = 30) received bupivacaine 0.5% heavy 2.0 mL and fentanyl 50 μg diluted up to 2.5 mL with normal saline.

Randomization was done using a computer-generated random number and sealed in an envelope. The slip was taken out by the consultant on duty not involved in the study and the drug prepared according to the coded slip. Both an assessor and the patients were blinded.

All the patients were shifted to the operation theater. Baseline blood pressure, pulse rate, respiratory rate, and SpO2 were recorded in the OT. Under all aseptic precautions, lumbar puncture was performed using 25G spinal needle in sitting position. After obtaining a clear and free flow of cerebrospinal fluid, 2.5 mL of the study drug was injected and the patient was turned in supine position. All the patients receive supplemental oxygen at the rate of 4 L.min-1 via venturi mask.

The assessment of sensory block by a pinprick was performed at every minute until the maximum level was achieved. It was the level which did not change in between two readings taken 5 min apart. The time required for a sensory block to reach T10 dermatome level was considered as the sensory onset. The time required for two-segment regression from the highest level achieved was considered as the duration of anesthesia.

Motor block was assessed using a modified Bromage scale every 5 min before incision and then after completion of surgery. The time for the motor block to the Bromage scale of 2 was considered as the motor onset, and this was considered the point where surgery was allowed to start. The time to achieve one grade lower motor regression was also noted.

Modified Bromage scale

Complete block (unable to move feet or knees)

Almost complete block (able to move feet only)

Partial block (just able to move knees)

The detectable weakness of hip flexion while supine (full flexion of knees)

No detectable weakness of hip flexion while supine

Able to perform partial knee bend.

Vitals were recorded initially every 5 min for the first 20 min and then every 10 min till the end of surgery. During surgery, if bradycardia occurs then it was treated with injection atropine 0.01 mg/kg and if hypertension occurs then it was treated with injection mephentermine 6 mg intravenously. Total doses of atropine and vasopressors were also recorded.

Pain intensity was measured using Visual Analog Score every 4, 8, and 12 hourly and at 24 h postoperatively. The duration of spinal analgesia is defined as the time from intrathecal injection until pain score ≤4. When VAS >4, rescue analgesia was given in the form of intramuscular diclofenac sodium 75 mg. The total analgesic requirement in the postoperative period was also noted. Complications such as nausea, vomiting, bradycardia, hypotension, and pruritus were noted and treated accordingly.

The sample size of the study determined by considering the alpha error of 0.05 and power of study 80% was calculated to be 26 in each group with a total sample size of 78. With 8%–10% dropout rate, the sample size increased to 90 with 30 patients in each group.

Statistical analysis

At the end of the study, data compiled were decoded and statistically analyzed using the Statistical Package for the Social Sciences (SPSS) version 20.0.0 (SPSS Inc., Chicago, IL, USA). The continuous variables (quantitative data) were expressed as mean and standard deviation. The categorical variables (qualitative data) were presented in frequency and percentage. Nominal data were analyzed with Chi-square test. P < 0.05 was considered statistically significant and P > 0.05 as insignificant in all the analyses.

RESULTS

The age, weight, height, and duration of surgery were comparable in all the three groups and statistically insignificant (P > 0.05) [Table 1].

Table 1

A Comparison of Demographic Profile

	Group I (n=30)	Group II (n=30)	Group III (n=30)	P
Age (years)	41.50±9.26	42.37±11.29	41.67±11.37	0.640
Weight (Kg)	55.68±5.03	54.32±7.01	56.27±4.98	0.880
Height (cm)	156±6.9	159±7.4	158.00±8.6	0.560
Duration of surgery (min)	55.00±14.19	51.50±10.01	56.00±11.32	0.230

Data is presented as mean±SD, SD: standard deviation, *significant, †highly significant.

The characteristics of sensory block in all three groups, as depicted in Table 2, showed a significant increase in median sensory level in Group III in comparison to Group I and Group II. The meantime to achieve maximum sensory blockade was comparable in all three groups (P = 0.001). The time to two-segment regression was prolonged in Group III (145.16 ± 5.64) when compared to Group I (105.50 ± 9.6) and Group II (120.66 ± 4.68) (P = 0.002). However, the regression time between Groups II and III was comparable (P = 0.002).

Table 2

Characteristics of sensory block

	Group I (n=30)	Group II (n=30)	Group III (n=30)	P
Highest sensory level (median range)	T10 (8 10)	T10 (8 10)	T8 (8 10)
Time from injection to the highest sensory level (minutes)	5.80±0.92	4.60±0.49	3.86±0.81	0.001†
Time of two segment regression from highest sensory level (min)	105.50±9.6	120.66±4.68	145.16±5.64	0.002†
Duration of analgesia (in hours)	1.12±0.5	3.86±1.04	4.8±1.12	0.002†

Data is presented as mean±SD, SD: standard deviation, *significant, †highly significant.

The characteristics of motor blockade achieved in all three groups is depicted in Table 3. The time of onset of the motor blockade is comparable among all the three groups (P = 0.024). The mean duration of motor block was more in Group III (156.66 ± 5.62), followed by Group II (139.16 ± 4.16) and Group I (124.50 ± 8.34), which was statistically highly significant (P = 0.002).

Table 3

Characteristics of motor block

Parameter	Group I	Group II	Group III	P
Time to onset of Bromage grade 3	5.70±0.91	6.50±1.47	6.23±0.89	0.024*
Time to reach grade 1 Bromage score	124.50±8.34	139.16±4.16	156.66±5.62	0.001†

Data is presented as mean±SD, SD: standard deviation, *significant, †highly significant.

There was a decrease in HR in Group I which was settled after 15 min, whereas in Groups II and III, the HR decreased gradually till the end of surgery but was stable in both the groups. On intergroup comparison, there was no significant difference, as depicted in Figure 1.

Figure 1

Consort diagram

There was a decrease in systolic blood pressure for 10 min in Group I and 15 min in Group II and Group III for 30 min. On the intergroup comparison between Groups I and II, there was no statistically significant difference (P > 0.05), and in Group I versus III, there was a statistically significant difference in systolic blood pressure at 15, 20, and 30 min (P < 0.001). On the intergroup comparison between Groups II and III, there was a statistical difference at 10, 15, and 20 min, respectively (P < 0.05), as depicted in Figure 2. There was a decrease in diastolic blood pressure for 10 min in Group I, and in Group II, diastolic blood pressure remained stable. In contrast, in Group III, there was a decrease in blood pressure for 15–20 min; however, on intergroup comparison, the difference was not statistically significant (P > 0.05), as depicted in Figure 3.

Figure 2

Intraoperative heart rate (bpm) in study groups at various time intervals

Figure 3

Intraoperative systolic blood pressure (mmHg) in study groups at various time intervals

The mean duration of analgesia in Groups I, II, and III was 1.12 ± 0.5, 3.86 ± 1.04, and 4.8 ± 1.12, h, respectively. The duration of analgesia was significantly longest in Group III (P = 0.002), followed by Group II (P < 0.05), and least in Group I, as depicted in Table 2. The mean requirement of rescue analgesia was more in Group I as compared to Group II and Group III, similar to the total number of doses given (P < 0.001). Furthermore, Group II required more number of rescue analgesia as compared to Group III (P < 0.05) [Figure 4].

Figure 4

Intraoperative diastolic blood pressure (mmHg) in study groups at various time intervals

In our study, none of the patients in Group I and Group II had any complications such as hypotension, nausea, vomiting, bradycardia, and pruritus, as depicted in Table 4. However, in Group III, four patients had hypotension and were treated with mephentermine 6 mg intravenously. Three patients had nausea and were treated by metoclopramide 10 mg intravenously. Seven patients had pruritus and were relieved with hydrocortisone 100 mg intravenously.

Table 4

Complications

Complications	Group I	Group II	Group III
Hypotension	0	0	4
Nausea	0	0	3
Vomiting	0	0	0
Bradycardia	0	0	0
Pruritus	0	0	7
Respiratory depression	0	0	0

DISCUSSION

Spinal anesthesia with opioids like fentanyl prolongs analgesia into the postoperative period and is the off-label use of it. This combination of opioids and local anesthetics administered intrathecally has a synergistic analgesic effect.[3] Opioids, in conjunction with local anesthetics, improve the quality of intraoperative analgesia and prolong the duration of postoperative analgesia. Although morphine was the first opioid used intrathecally, a wide variety of clinically relevant side effects, especially respiratory depression, limited its utility. In contrast, a favorable pharmacokinetic and pharmacodynamic profile of lipophilic opiates (fentanyl) proved to be a better alternative as their lipophilicity leads to rapid uptake and faster clinical onset of action and short duration of action.[4] They also minimize the rostral migration of drugs to the respiratory center, thereby avoiding delayed respiratory depression.

As in this study, the early onset of sensory block was also observed by Bano et al. and Peng and Sandler who reported that the addition of fentanyl fastened the onset of block.[56] Even the mean duration of sensory block was more with bupivacaine–fentanyl combination, as observed by Atallah et al.[7] The underlying mechanism by which intrathecally administered fentanyl and bupivacaine interact to produce synergism remains to be determined. Previously, it has been suggested that the interaction between drugs that are agonist at the same receptor is expected to be additive, whereas drugs that act at different receptors are more likely to show a synergistic interaction.

We also observed that the level of sensory block in Group III was higher than Group II, suggesting that the dose of fentanyl also affected the level of sensory block. Hooda et al., also found that there was an increase in sensory level when a higher dose of fentanyl was added to hyperbaric bupivacaine.[8]

Hemodynamically, fall in systolic blood pressure was statistically significant at 10, 15, and 20 min with fentanyl 50 μg (P < 0.001). However, diastolic blood pressure, the mean HR was comparable in all three groups. Kumar et al. also observed that seven patients in the fentanyl-treated group and two patients in the butorphanol-treated group had hypotension in the perioperative period (P = 0.077) with statistically significant fall in diastolic blood pressure and mean HR when using 25 μg fentanyl intrathecally with hyperbaric bupivacaine.[3]

These findings were also supported by Ben-David et al. and Jain et al. The intrathecal fentanyl with low-dose bupivacaine provides excellent surgical anesthesia and prolongs the duration of analgesia without hemodynamic or neonatal compromise in patients with pregnancy-induced hypertension undergoing cesarean delivery.[910]

In a dose-finding study by Celeski et al., they compared the difference in the duration of adequate analgesia and adverse effects produced by 25 μg, 37.5 μg and 50 μg of intrathecal fentanyl through a combined spinal-epidural technique in laboring patients. Their study demonstrated that there is no real advantage of using intrathecal fentanyl >25 μg in quality and duration of labor analgesia.[11]

Katiyar et al. demonstrated that intraoperative hemodynamics showed the incidence of hypotension and bradycardia was more in the fentanyl group (25 μg) as compared to magnesium groups.[12]

No significant changes were observed in SpO2 in our study [Figure 5]. Varrassi et al. who found that subarachnoid administration of 25 μg fentanyl during spinal anesthesia did not alter the respiratory rate and ventilator response to carbon dioxide in contrast to 50 μg of subarachnoid fentanyl could cause early respiratory depression in elderly patients.[13] We did not observe any such effect, probably due to more younger healthy and climate-adapted patients.

Figure 5

Intraoperative oxygen saturation in study groups at various time intervals

The mean requirement and the number of doses of rescue analgesia were more in Group I, followed by Group II and Group III (P < 0.05) [Figure 6]. Similarly, Weigl et al. reported that patients in the 25 μg fentanyl group had significantly reduced opioid consumption compared to the controls during the postoperative period along with decreased requirement of rescue analgesia.[14]

Figure 6

Comparison between number of doses of rescue analgesia in study groups

CONCLUSIONS

Thus, to conclude, the optimum conditions for improved spinal block were observed with a combination of intrathecal bupivacaine 0.5% hyperbaric 2 mL and fentanyl 20 μg. However, a combination of bupivacaine 0.5% hyperbaric 2 mL and 50 μg fentanyl provided early onset of sensory and motor block and prolonged the duration of analgesia but has a greater potential of producing complications such as hypotension, nausea, and pruritus. Hence, there seems no additional advantage of using a high dose of fentanyl.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.