European Journal of Cardiovascular Medicine

In India, cesarean sections (C-sections) have become increasingly common, with a significant rise in both elective and emergency procedures. Regional anesthesia, particularly spinal or epidural blocks, is the most preferred method of anesthesia for cesarean deliveries. Bupivacaine, a long-acting local anesthetic, is commonly used for spinal and epidural anesthesia due to its effectiveness in providing both sensory and motor blockade. However, the addition of clonidine (an alpha-2 adrenergic agonist) and fentanyl (an opioid analgesic) to bupivacaine has been a subject of interest in enhancing pain management during and after surgery. This article aims to analyze the benefits and risks of incorporating clonidine and fentanyl with bupivacaine for cesarean sections, with a focus on the context of Indian clinical practices and patient population.Relief of Pain is purchased always at a price – Ralph Waters. “For allthe happiness mankind can gain is not in pleasure but in rest frompain”. – John Dyrden. The aim of anesthesiology as a science is theremoval of pain temporarily started initially with pain relief forsurgeries, extending now to post operative pain relief, relief of chronicpain and cancer pain. Spinalanesthesia plays in important role ofalleviating painintraoperatively, extending sometime intopostoperative period also. The entry of Corning's needle in 1885-intothe subarachnoid space paved the way for the greatest leap into spinalanaesthesia. His words “Be the density of this observation, what it mayhave seemed to me on the whole, worth recording. This opened theprologue for the word “spinal anaesthesia”. Cocaine was the drug firstused experimentally in dogs. In men the first spinal anaesthesia wasconducted by “August Bier” on 16.8.1898 with cocaine 3 ml as 0.5%solution followed by Matas in America and Tuffier in France.Spinal anesthesia for caesarean section has always enjoyed popularityas it eliminates the complication of pulmonary aspiration and avoidsthe problem of difficult tracheal intubation observed with generalanaesthesia. Other advantages of this technique are its simplicity, rapidonset and dependability.The demonstration of opiate receptors in substantia gelatinosa ofspinal cord (Yaksh and Rudy 1976) has created interest in theintrathecal administration of opiates. The use of intrathecal morphinefor providing postoperative pain relief in caesarean section was startedin the year 1988 by EzzazAboulesish et.al. The advantages ofneuraxial opioids over neuraxial local anesthetics are that it producesprolonged, intense, 2 selective, segmental analgesia without motorblockade and sympathetic dysfunction.Opiods and local anesthetics administered together have a potentsynergistic analgesic effect. Intrathecal opiods enhance analgesia fromsubtherapeutic dose of local anesthetic and make it possible to achievesuccessful spinal anaesthesia using otherwise inadequate doses oflocal anesthetic. The α2 adrenergicmechanism have been exploited formore than 100 yrs. Vetenarians have used α2 agonist for many years forregional analgesia, but the experience with these agents in humans,dates back only slightly more than 10 years.In 1984 Tamsen, Gordh after testing neurotoxicity in animals and theninjected a parenteral preparation of α2 agonist clonidine, epidurallyIntwo patients with chronic pain. Since then the complete toxicologicassessment in animal studies has suggested that clonidine is safe forIntrathecal use.

AIM OF THE STUDY

• To evaluate the effects of fentanyl and clonidineadded toBupivacaine, for caesarean section in spinal Anaesthesia
• To evaluate the duration of analgesia by comparing two groups.
• To evaluate the hemodynamic effects, post-operative sedation andneonatal outcome between the two groups.generate graphs, tables etc.

Following approval by the institutions ethical committee, thisprospective study was done at The Oxford Medical College, Hospital & Research Centre, Bangalore ,Karnataka, India in 120 patients undergoing elective or emergency caesarean sectionafter getting informed consent from each patient and explaining theprocedure. This is a randomized prospective comparative study.

Inclusion Exclusion Criteria

Term, parturient, ASA I an ASA IE who were fit to undergo spinalanaesthesia for caesarean section, age between 18-35 yrs., are selected. Patients with medical and obstetrical complications and impairedplacental function were excluded; patients who were converted togeneral Anaesthesia were also excluded from the study.

Preoperative Preparation

Preoperatively all patients were seen by the anesthetist. The procedurewas explained in detail and informed consent was obtained. Nopremedication was given. Patients were randomly allocated into 3groups of 40 each.

A- Control Group - Injection (0.5%) Bupivacaine 1.8 ml + 0.4 ml NS

B- B- Study group 1 inj. (0.5%) Bupivacaine 1.8 ml + Clonidine 30 μg)+ 0.2 ml NS.

C- C- Study group 2 Inj (0.5%) Bupivacaine 1.8 ml + Clonidine (30 μg)+fentanyl (10μg)

Procedure

> On arrival to operation theatre, basic monitoring was applied to allpatients and basic pulse rate, blood pressure, oxygen saturation andrespiratory rate were recorded.

>™ Intravenous line with 18 g canula was established and preload of 250-300 ml of crystalloid was given to all patients. ™

> Following resuscitative measures were kept ready before the start ofthe procedure: Boyles machine with oxygen source, laryngoscope andappropriate size blades, suction apparatus, vasopressors (Ephedrine),naloxone and other emergency drugs.

> The subarachnoid block was performed in right lateral position with23 G spinal needle through L3, 4 space. Free flow of CSF was ensuredbefore introducing the drug. The drug injected was according to thegroup assigned.

A- Injection (0.5%) Bupivacaine 1.8 ml + 0.4 ml NS .

B- inj. (0.5%) Bupivacaine 1.8 ml + Clonidine 30 μg) + 0.2 ml NS.

C-Inj (0.5%) Bupivacaine 1.8 ml + Clonidine (30 μg) + fentanyl(10μg)

Drugs were measured in a sterile tuberculin syringe. Thorough asepticprecautions were taken during the addition of injection and making the final injection.Immediately after the intrathecal injection the patients were gentlyturned to supine position with leftward tilt by a wedge under rightbuttock 100% oxygen was given through Magills breathing system till the delivery of baby.

Assessment Of Patient And Recording Of Data

Time of subarachnoid block was noted, following observations were made

1. Time of onset of analgesia
2. Time of maximum cephalic spread
3. Upper level of sensory block
4. Grade of motor block obtained according to bromage motor scale.

Bromage Motor Scale

0-No paralysis

1- Inability to raise extended legs.

2- Inability to flex the knee joint

3- inability to flex the ankle joint

After the establishment of an adequate level of analgesia, the surgeonswere allowed to operate and the time of beginning of surgery wasnoted.Blood pressure, pulse rate, respiratory rate and Spo2 were monitoredintraoperatively every 2 minutes for the first 10 minutes and every 5minutes till the end of surgery. Patients were watched for side effectslike hypotension, bradycardia, and vomiting, itching and respiratorydepression.Any hypotension (30 % fall from base line) was treated with oxygen, intravenous fluid and inj. ephedrine.Any hypotension (30 % fall from base line) was treated with oxygen,intravenous fluid and inj. ephedrine. Any bradycardia (pulse rate<60) treated withinj.atropine0.6mgTwo segment regression time: Time to decrease from maximumsensory level to 2 segments below that level was noted.

Sedation state was assessed by Brain and Ready sedation score

1. Awake and alert
2. Drowsy
3. Sleepy but easily arousable on call.
4. Sleepy but difficult to arouse.

In the postoperative period, any complications to the mother and baby, especially that is attributed to opioids like respiratory depression,nausea, vomiting, pruritus were noted (one of the expectedcomplication i.e., urinary retention could not be studied as all thepatients were invariably catheterized).Total duration of analgesia was taken as the period from the time ofgiving subarachnoid block till the patient's first requirement ofanalgesic medication. Pain was evaluated using 10 cm linear visualanalogue scale (VAS) with 0 for no pain and 10 for worst pain. If VASwas more than 6, supplementary analgesia was given and the study wasassumed to be concluded at that poin.

Statistical Method

Results were expressed as mean ± standard deviation. Statisticalsignificance was determined by Anova table

Statistical Analysis:

The Randomization of three groups was done by matching their age, height, and weight of their demographic factors and base Physiologicalfactors such as pulse rate, SBP, respiration rate and SPO2 by ANOVA(Analysis of Variance). The differences between them were interpretedby the Post hoc test of Bonferroni. Similarly, the time for maximumloss of sensation, the 2 segment regression time, pain free time andApgar score at 1 minute and 5 minutes were compared between groupsby ANOVA. The intra and post-operative pulse rate and SBP atdifferent intervals were compared between groups by ANOVA andinterpreted the difference by Post hoc test of Bonferroni. The abovestatistical procedures were performed by the statistical package IBMSPSS statistics 20. The P - values less than 0.05 (P< 0.05) were treatedas significant in two tail condition.

Randomization By Group Matching:

The three groups were namely A (Bupivacaine only), B (Bupivacaine+ intrathecal clonidine) and C (Bupivacaine + intrathecal fentanyl +Clonidine). Each group 40 Caesarean Sections were selected and datawere collected before during and after surgery.For Randomization the three groups were matched according to theirselected and related demographic characteristics and base levelPhysiological characteristics.

Maximum Sensory level, Time and 2 Segment regression time:

The maximum sensory level and maximum time taken to reach thelevel were compared between three groups. The 2 segment regressiontime was also compared between the three groups.

Table-1 Comparison Of Sensory Level Between Three Groups.

The above table-1 associates the maximum sensory level of threegroups.The group A was associated with T , B was associated with T 7 6and C was associated with T . The above associations were statistically 5very highly significant (P<0.001)

Table-2 Duration Of Time (Minutes) To Attain Sensory BlockadeOr Level Between Groups.

The sensory time between the groups were compared in the table-2.The mean time of A was 3.8±0.8 minutes with mean time of B(3.6±0.7) and C (4.3±0.8) not differed significantly (P>0.05). But themeans of B (3.6±0.7) and C (4.3±0.8) were differed significantly(P<0.01).

Table -3 Two Segment Regression Time (minutes) To AttainSensory Level Between Groups.

The two segment regression time between the groups were compared in the above table 3. The means of three groups were differed significantly between them (P<0.001).

Table-4 Comparison Of Pulse Rates Between Groups At DifferentIntervals.

The above table -4 shows the pulse rate at different intervals like at 5minutes 15minutes and 30 minutes. The group A was significantlydiffered with group B (P<0.05) and C was not significantly differedwith groups A and C (P>0.05) at 5 minutes. At 15 minutes nosignificant difference was observed between the three groups(P>0.05). At 30 minutes B significantly differed with C (P<0.01) and atthe same time A&B and A&C were not significantly differed (P>0.05).

Table-5 Comparison Of SBP Between Groups At DifferentIntervals.

The SBP at different interval between the groups were shown in the above table-5. At 5 minutes, three groups were not significantly differed between them (P>0.05). At 15 minutes A significantly differed with the groups B and C (P<0.001). But B&C was not significantly differed between them (P>0.05). At 30 minutes A&B differed significantly (P<0.05). But A vs C and B vs. C were not significantly differed (P>0.05).

Table 6 Comparison Of APGAR Scores At 1 Minute And 5minutes.

The Apgar score at 1 minute and 5 minutes were compared between the three groups in table-6. At 1 minute the Apgar were not significant between groups (P>0.05). At the Apgar scores of groups A&B was significantly differed (P<0.05). The others A&C and B&C were not statistically significant (P>0.05).

Intra-operative Complications

Nausea and vomiting occurred in 7.5% of all three groups. All were treated with inj. Metaclopromide. Pruitus developed in only one patient i.e. 2.5% of group A patients. In group B, 7.5% of patients developed pruitus. In group C, 12.5% of patients developed pruritus All were treated with inj. Chlorpheniramine maleate.

Post-Operative Complications

Nausea and vomiting occurred in 5% of patients in group A and group B and 2.5% in group C and they were treated with inj. Metaclopromide. Pruritus occurred in 2.5% of patients in group B and 7.5% of patients in group C and they were treated with inj. chlorpheniramine maleate.

For Randomization, the three groups were matched with their age, height, weight, pulse, SBP, respiration and SPO2 and found that there +was no significant difference between them (P>0.05). Hence, there groups were comparable groups. The sensory level T4 was obtained by A group 1(2.5%), B group 2(5%) and C group 10 (25%). The above attainment by C group was significantly greater than the other A& B groups (P<0.001). The mean time of C was significantly greater than B (4.3±0.8 > 3.6±0.7) and A and C were equal (4.3±0.8 = 3.8±0.8). The two segment regression time for C group was significantly more than B and the same for B was significantly more than A.(101.1±8.1 > 89.5 ± 5.7 > 69.4 ±8.6 and P<0.001). The Pulse rate at 5 minutes of B group was significantly greater than A and C groups. (93.5 ±7.6 > 88.2±7.6 &90.6 ±7.5) and A group C group was equal (88.2±7.6 = 90.6 ±7.5). At 15 minutes, the pulse rates of three groups were more or less equal. (92.5±9.1 = 95.5±8.5 = 91.8=8.3 and P>0.05). At 30 minutes the pulse rate of C group was lesser than B group (89.4 ±6.1<94.2 ±7.6 and P<.0.01).

The same of A vs. B and A vs. C were more or less equal (91.2±6.7 = 94.2 ±7.6 and 91.2 ±6.7 = 89.4±6.1 and P>0.05).

The SBP at 5 minutes of three groups were 120.6 ±11.4, 116.2, ±13.5 and 120.9 ± 8.8 minutes respectively. The means were not significantly differed (P>0.05). At 15 minutes, the mean SBP of A group was 102.4 ± 12.4 and the same was significantly lower than B and C groups (102.4 ± 12.4 < 115.8 ± 9.9 & 112.2 ±12.0 and P<0.01). At 30 minutes, the mean SBP of B group was significantly higher than B group (115.1± 9.7 > 105.9 ±12.5 and P<0.01). The mean SBP of A vs. C and B vs. C were not significant (P>0.05).

The Apgar score between the three groups was not significant at 1 Minute, But at 5 minutes, A group was significantly improved than B (9.1±0.5 > 8.8 ±0.5 and P<0.05). The A vs. C (9.1±0.5 = 9.0±0.3)and B vs.C (8.8 ±0.5= 9.0±0.3) were not significant (P>0.05).

From the above results and discussions the C group administration is better than the above two groups namely A and B groups.

• Evidences to conclude, improved quality of analgesia is the postoperative Period
• There is not of much difference in the onset of analgesia
• Two segment regression took longer time (C>B>A)
• Duration of analgesia increased (C>B>A)

Hemodynamics

• There is less incidence of hypotension and Bradycardia.

Complications

• No respiratory depression occurred in any of these patients
• Pruritus developed in 12.5% in Group C

Fetal Outcome

• Low dose opiods do not have adverse effects on fetus and neonates.

The above study bears out the following facts.

1. Intrathecal clonidine and the clonidine fentanyl combination, both improved quality of Intra Operative analgesia.
2. Combination of clonidine with fentanyl increased the intra operative analgesic efficacy and significantly prolonged post- operative analgesia compared with clonidine alone.
3. Stable Intra Operative hemodynamics was obtained.
4. Duration of analgesia was prolonged.
5. The incidence of side effects due to additive effects of the drugs was minimal.
6. Fetal outcome was not altered.

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