Comparing Duration of Analgesia after Intrathecal Administration of Opioids in Primary Paturients for Lower Segment Cesarean Section.

Background: A pain free post operative period is a boon to mother for caring the neonate. We compared injection butorphanol and fentanyl as an adjuvant to bupivacaine in primary parturients for LSCS (Lower Segment Caesarean Section) with respect to duration of analgesia. Aims and
Objectives: To study the effect of butorphanol vs fentanyl on duration of analgesia when added to bupivacaine for LSCS amongst primi parturients and to observe the block characteristics as secondary outcome. Materials and
Methods: Study was carried out in 90 patients divided equally into three groups which included 12mg(2 mL) of 0.5% hyperbaric bupivacaine with 0.5 mL NS, 12mg (2 mL) of 0.5% hyperbaric bupivacaine 25 μg butorphanol made upto 2.5 mL with NS and 12mg(2 mL) of 0.5% hyperbaric bupivacaine with 25μg fentanyl made upto 2.5mL with normal saline. All patients were observed for duration of analgesia. Also Heart Rate (HR), Systolic and Diastolic Blood Pressure (SBP, DBP), two segment regression time of sensory block, motor block were assessed. The results were compiled and statistically analyzed using Chi-square test for nonparametric data and ANOVA for parametric data.
Results: Two segment sensory regression is significantly prolonged in group with intrathecal administration of Bupivacaine with Butorphanol (190.33±15.86) than Bupivacaine with Fentanyl (170.67±20.83) and Bupivacaine with Normal saline (150.33±16.91). Duration of effective post operative analgesia was 349.67, 591.87 and 468.00 min in Group I, Group II and Group III respectively. There was no significant difference in onset of sensory and motor blockage in all three groups. HR, SBP and DBP were comparable among the groups. Conclusions: Intrathecal bupivacaine with 25 μg butorphanol mixture was clinically better as it provided longer duration of analgesia along with prolonged sensory block when compared to intrathecal bupivacaine with 25μg fentanyl mixture in primary parturients for LSCS. Copyright:

INTRODUCTION

In primigravida pain, threshold varies and their ability to take labor pains decreases causing more sensitivity toward postoperative pain whenever they undergo lower segment cesarean section (LSCS).[1] Pregnancy induces many anatomical, physiological, and hormonal changes which causes decreased requirement of local anesthetic (LA) drugs in spinal anesthesia for LSCS. The effect with lesser dose of LA wears off quickly. Hence, for synergistic effect, various adjuvants have been added to LA for LSCS.[2] This may reduce the dose of LA agents, but leading to improved intraoperative and postoperative analgesia.[3] Hence, we plan to study the effect of butorphanol versus fentanyl on the duration of analgesia when added to bupivacaine for LSCS among primi parturients and to observe the block characteristics as secondary outcome.

MATERIALS AND METHODS

A prospective, double blind, randomized controlled study was conducted after getting approval from the Institutional Ethical Committee. Ninety primi gravida females belonging to theAmerican Society of Anesthesiology physical status classes I and II, aged 18–35 years, scheduled for elective cesarean section, were included after written informed consent. Patients with preexisting hypertension or twin pregnancy or complicated pregnancy induced hypertension, those with renal/cardiac or other end organ disease, patients in active labor, placenta previa and those with contraindication to neuraxial block were excluded from this study. The patients selected were randomly allocated by computer-generated random numbers into three groups of 30 each using sealed envelope technique. The study was initiated after registration with central trial registry of Govt of India: CTRI/2020/07/026284.

Group I: 0.5% hyperbaric bupivacaine 12 mg (2.0 mL) with 0.5 mL normal saline (NS) (total volume 2.5 mL) (control group). Group II: 0.5% hyperbaric bupivacaine 12 mg (2.0 mL) with 25 μg butorphanol made up to 2.5 mL with NS. Group III: 0.5% hyperbaric bupivacaine 12 mg (2.0 mL) with 25 μg fentanyl made up to 2.5 mL with NS.

After the fasting period of 8 h, the intravenous (i.v.) infusion with ringer lactate was started as co-loading solution. All patients received acid prophylaxis premedication. Standard monitoring included pulse rate, oxygen saturation, noninvasive blood pressure, and electrocardiography (ECG).

Subarachnoid block was performed at the L2-L3 or L3-L4 interspace using a 26-G spinal needle in the left lateral position. After confirming the free flow of clear cerebrospinal fluid, the study drug was injected. It was prepared by an independent technician. The subject and accessor both were blinded to the drug solution injected. For further blinding of drug solution in a syringe, the volume was kept constant. After the intrathecal injection, the patient was made supine. All the three groups of patients received oxygen @6 L.min−1 through facemask. In the supine position, wedge was given to maintain leftward tilt of the uterus. The assessment of sensory block was performed by the pinprick method at every 2 min till the maximum level achieved. The maximum level considered when two readings taken 5 min apart did not change, and the time to two segments below the highest level and considered the duration of block. If the spinal anesthesia seemed ineffective or partial effect achieved, general anesthesia was administered and these patients excluded from the result analysis.

Motor block in the lower limb was assessed using a Modified Bromage Scale.[4]

Score 0: able to lift extended leg and hip, Score 1: able to flex the knee but not lift extended leg, Score 2: able to move the foot only, and Score 3: unable to move even the foot.

On achieving maximum sensory level, the surgery was allowed to proceed. Intraoperative monitoring included parameters such as pulse rate, SpO2, ECG, and respiratory rate recorded every 15 min till the end of the surgery. The complications such as hypotension, bradycardia, nausea, and vomiting were managed as per the requirement. Time to incision and delivery of baby were noted. After the delivery, APGAR score of neonate was recorded at 1 min, 5 min, and 10 min. Postdelivery injection syntocin, 10 units were given as bolus and 10 units added to infusion.

At the end of surgery, sensory or motor level was evaluated. Time for regression of two segments for sensory and one scale down for motor block was noted. In postanaesthesia care unit, Visual Analog Scale (VAS), sedations and hemodynamic parameters were observed at 1, 2, 4, 6, 8, 12, and 24 h. Sedation were observed as per Ramsay sedation Score [Table 1].[5]

Table 1

Postoperatively sedation was assessed as per Ramsay sedation Score

Sedation score	Response
1	Anxious and agitated or restless or both
2	Cooperative, oriented, and tranquil
3	Responding to commands only
4	Brisk response to light glabellar tap or loud auditory stimulus
5	Sluggish response to light glabellar tap or loud auditory stimulus
6	No response to stimulus

VAS (0–100 point scale) with 0 as no pain and 100 as maximum pain one can experience. The duration of absolute analgesia defined as the time from intrathecal drug administration until pain score = 30. At VAS ≥40 rescue analgesia was given in the form of bolus or infusion paracetamol (PCM) i.v. 10 mg.kg−1. If analgesia inadequate after PCM, then rescue analgesia given after 1 h in the form of intramuscular diclofenac sodium 75 mg. Total analgesic requirement in the postoperative period was noted for 24 h.

Postoperative complications such as hypotension, bradycardia, nausea and vomiting, shivering, respiratory depression, pruritis, urinary retention, and dry mouth were observed and managed.

The sample size was determined on the basis of duration of postoperative analgesia among the groups as a primary outcome and taking the alpha error of 0.05 and power of study 80% with effect size 0.5, the number needed to conduct the study came out to be 27 patients in each group.[67] Considering the dropout rate of 10%, 90 patients were taken with 30 patients in each group. Decoding of the study groups was done at the end of the study. After the completion of the study, the results were compiled and statistically analyzed using the Chi-square test for the nonparametric data and analysis of variance for the parametric data. Post hoc student's paired t-test was applied IBM Corp. Released 2019. IBM SPSS Statistics for Windows, Version 26.0. Armonk, NY: IBM Corp. P < 0.05 was considered statistically significant and > 0.001 as highly significant.

RESULTS

Consort diagram is showing patient recruitment and analysis is shown in Figure 1. The three groups were comparable with regard to age, weight, height, body mass index, and duration of surgery (P > 0.05) [Table 2].

Figure 1

CONSORT diagram

Table 2

Demographic characteristics

	Group I (n=30)	Group II (n=30)	Group III (n=30)	P
Age	25.5±2	26.37±2.57	26.27±1.84	0.240
Female/Male	12/18	11/19	14/16	0.712
ASA I/II	22/8	21/9	19/11	0.270
BMI (kg/m2)	20.57±2.06	19.93±1.41	20.53±1.46	0.261
Duration of surgery (mins)	103.17±7.008	104.67±5.074	105.83±7.081	0.281

Mean VAS score in all three groups is shown in Figure 2. The duration of analgesia was observed to be longer in Group II (591.87) than Group I (349.67) and Group III (468.00) (P < 0.001) [Figure 3]. Mean analgesic requirement postoperative was found to be more in Group I (P < 0.001) as compared to Groups II and III which was determined by the total number of doses given [Table 3].

Figure 2

Mean visual analogue scale score in all three groups

Figure 3

Mean duration of analgesia in all three groups

Table 3

Rescue analgesia

Number of rescue doses	Group I (n=30)	Group II (n=30)	Group III (n=30)	P
1	0	30	12	0.000
2	2	0	18
3	25	0	0

The characteristics of sensory block in all three groups are depicted in Table 4. Time from giving injection to reach maximum sensory level was comparable among the three groups (P = 0.319). Significantly slower block regression to two level lower than highest level achieved was observed in Group II (P = 0.000).

Table 4

Block Characteristics

Block Characterstics	Group I (n=30)	Group II (n=30)	Group III (n=30)	P
Time of onset of Sensory Block	2.5±0.51	2.9±0.92	2.57±0.5	0.053
Maximum level achieved	8±0	8.2±0.61	8±0	0.045
Time of maximum sensory block	5.9±0.71	5.77±1.13	5.57±0.62	0.319
Time to 2 segment regressions	150.33±16.91	190.33±15.86	170.67±20.83	0.000
Time to max motor	6.6±1.43	6.5±1.48	6.18±0.98	0.791
Time of 1 grade regression	140.17±7.00	144.67±6.00	140.83±9.10	0.057

The characteristics of motor blockade achieved in all three groups are depicted in Table 4. The time of onset of maximum motor blockade and time to reach Grade 1 motor blockade were similar among groups (P = 0.791). Mean postoperative analgesic requirement was found to be lower in Group II as compared to Group I and III.

The mean baseline values of heart rate, systolic blood pressure, diastolic blood pressure and SpO2 were comparable among the groups (P > 0.05) [Table 5]. Also depicted in line diagram as shown in Figure 4.

Table 5

Hemodynamic parameters

Baseline parameters	Group I (n=30)	Group II (n=30)	Group III (n=30)	P
Heart Rate (bpm)	76.1±4.9	78.53±7.81	77.67±6.27	0.337
Systolic Blood Pressure (mmHg)	123.1±5.8	122.73±9.22	122.6±4.75	0.958
Distolic Blood Pressure (mmHg)	75.5±7.28	75.2±8.92	78±6.02	0.289
Respiratory rate	15.7±1.512	15.8±2.058	15.07±2.803	0.376

Figure 4

Mean heart rate, systolic blood pressure and diastolic blood pressure in all three groups

The complications observed during the study are listed in Table 6.

Table 6

Side effects

Complication	Group I (n=30)	Group II (n=30)	Group III (n=30)
Hypotension	2	1	4
Bradycardia	0	0	0
Nausea	0	0	0
Vomiting	0	0	0
Respiratory depression	0	0	0
Pruritis	0	0	2
Urinary retention	0	0	0

DISCUSSION

Spinal anesthesia is the preferred method for elective cesarean section as being simple to perform, economical and producing rapid onset of anesthesia with complete muscle relaxation. It carries high efficiency, involves less drug doses, minimal neonatal depression, and lesser incidences of aspiration pneumonitis.

Local anesthesia such as bupivacaine act mainly by blockade of voltage-gated sodium channels in the axonal membrane and presynaptic inhibition of calcium channels. Both butorphanol and fentanyl exert their action by the opening of potassium channels and reducing the calcium influx, resulting in inhibition of transmitter release.[8] A combination of these effects may explain the observed synergism between bupivacaine and butorphanol, fentanyl. The synergism is characterized by enhanced somatic analgesia without the effect on the degree of LA-induced sympathetic or motor block.[9]

The principal findings of this study are that intrathecal butorphanol – bupivacaine mixture produces longer duration of analgesia (with lesser requirement of rescue analgesia) as compared to intrathecal fentanyl – bupivacaine mixture.

The use of opioids in conjunction with LA for spinal anesthesia has been associated with reduced analgesic requirement in the postoperative period. In our study, butorphanol with bupivacaine not only provided adequate anesthesia and analgesia but also prolong the duration which was observed to be longer in Group II (591.87 min) than in Group III (468.00 min) and in Group I (349.67 min). The time for the first request for analgesia was significantly delayed in Group III and Group II as compared to Group I strongly suggestion a synergism of action between intrathecal opioids and LAs.

Kim et al. have reported the duration of analgesia approximately 7 h after the use of 4 mg bupivacaine with 25 μg fentanyl for transurethral resection of the prostate.[9] Earlier studies report the duration of analgesia with intrathecal fentanyl ranging from one to 4 h. Singh et al. have also reported that lesser number of patients receiving intrathecal butorphanol requested for rescue analgesia as compared to those receiving intrathecal fentanyl.[10]

In our study, the time from giving injection to reach maximum sensory level was comparable among the three groups (P > 0.05) but significantly slower block regression to S2 level was observed in Group II (P = 0.000) which support the result obtained from Mukherjee et al. and Kumar et al. they concluded that though both butorphanol and fentanyl prolong the duration of sensory block, butorphanol is better in terms of long duration of action.[1112] These results were also comparable to study conducted by Parpaglioni et al. who found shorter onset time and long regression time in patients whom opioid was added to LA.[13]

In our study, the time of onset of maximum motor blockade and time to reach Grade I motor blockade were similar among all groups (P > 0.05). This was in accordance with the study conducted by Ali et al. who compared different doses of fentanyl (10, 15 and 25 μg) when used along with 10 mg of 0.5% bupivacaine heavy for spinal anesthesia in cesarean section and observed that the time of achieving sensory block and motor block was similar in all three groups.[14]

We observed that the baseline values of heart rate, systolic blood pressure, and diastolic blood pressure were comparable among the groups. This was in contrast of study by Venkata et al. in which the systolic and diastolic blood pressure were decreased significantly (P < 0.001) after 3 and 5 min of spinal anesthesia in the control group when compared to the study group, mostly due to more sympathetic blockade by the higher doses of bupivacaine in the control group.[15] Similar finding was observed by Bogra et al. and also by Segedhejazi and Madarek wherein they studied by using 8 mg of bupivacaine and 10 μg of fentanyl for spinal anesthesia in cesarean section.[16]

The analgesia requirement in the postoperative period (number of doses of rescue analgesia) was found to be more in Group I as compared to Group II and III. These results correlate with the study done by Purohit and Badami who observed that duration of analgesia was significantly better in butorphanol group than control group on addition of 25 μg of injection butorphanol to hyperbaric injection bupivacaine 0.5% in patients undergoing elective LSCS.[17]

In conclusion, both the 25 μg fentanyl and 25 μg butorphanol given intrathecally with 12 mg of hyperbaric bupivacaine provided safe anesthesia in primary parturient for LSCS, but intrathecal bupivacaine-butorphenol mixture provides longer duration of anesthesia than fentanyl bupivacaine mixture.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.