Comparison of efficacy of fentanyl and tramadol as adjuvants to intrathecal hyperbaric bupivacaine 0.5% in elective caesarean section - A prospective randomised double blinded study

 

 

Abstract               Background: Spinal anaesthesia is the technique of choice for elective caesarean section all over the world. It offers excellent operating conditions like dense analgesia and adequate muscle relaxation. However it suffers from certain inherent disadvantages like fixed duration of anaesthesia and haemodynamic instability. Aim: To compare the efficacy of intrathecal fentanyl and intrathecal tramadol as adjuvants to hyperbaric bupivacaine 0.5% in elective caesarean section patients in terms of duration of analgesia and intra-operative hemodynamic stability Materials And Methods: A single centered randomized, double – blinded study conducted between May 2017 to October 2018 in 60 patients undergoing elective caesarean section with 30 patients in each group. Group I received 0.5% hyperbaric bupivacaine 9 mg (1.8ml) + 0.2 ml i.e. 10 micrograms of fentanyl intrathecally (2ml). Group II received 0.5% hyperbaric bupivacaine 9 mg (1.8 ml) + 10 mg (0.2 ml) of tramadol intrathecally (2ml). Results: Duration of analgesia in Fentanyl was 9.47 ± 2.08 hours compared to 6.40 ± 1.25 hours in Tramadol group. Differences between groups are statistically significant with a P value of 0.03. The onset of sensory block in Fentanyl group is 1.37 ± 0.49 minutes compared to 2 ± 0.69 minutes in Tramadol group and the difference is statistically significant with a P – value of 0.001. The onset of motor block in Fentanyl is 1.73 ± 0.45 minutes compared to 2.3 ± 0.65 minutes in Tramadol group and difference is statistically significant with a P – value of 0.001. The time for maximum sensory level in Fentanyl group is 3.7 ± 0.65 minutes compared to 4.3 ± 0.70 minutes in Tramadol group and the difference is statistically significant with a P - value of 0.001. Conclusion: Both the groups were effective in providing adequate surgical anaesthesia and hemodynamic stability, but fentanyl is the better alternative to tramadol as an adjuvant to spinal bupivacaine in elective caesarean section.

Key Word: Fentanyl, Tramadol, Spinal anaesthesia, Caesarean section, Analgesia, Muscle relaxation

 

 

 

 

INTRODUCTION

Subarachnoid block is the preferred technique for caesarean section. It is easy to perform, rapid onset of action, involves lesser drug doses, produces minimal neonatal depression and gives lesser incidence of chemical pneumonitis.¹ However, it also has disadvantages which include producing only a fixed duration of anaesthesia, causing intra-operative hypotension and difficulty in controlling the height of block.² Hyperbaric bupivacaine is the most common drug used in spinal anaesthesia for caesarean section. Bupivacaine belongs to amide group of local anaesthetics with high potency, slow onset (5-8 minutes) and long duration of action. For caesarean section intrathecal dose of hyperbaric bupivacaine is 12 to 15 mg.³ Addition of opioids to local anaesthetics is routinely done in central neuraxial blockade as it provides better intra-operative and early postoperative analgesia.⁴ Spinal anaesthesia is often used for both emergency and elective caesarean section. The advantages of spinal anaesthesia are its rapidity in onset, safety and reliability. Caesarean delivery requires traction of peritoneum and handling of intraperitoneal organs, resulting in intraoperative visceral pain. With higher doses of hyperbaric bupivacaine, incidence of intraoperative visceral pain associated with organ manipulation is reduced.^5,6 Although intrathecal bupivacaine alone offers good sensory blockade, a substantial number of patients experience haemodynamic instability, pain and discomfort and may require analgesic supplementation in early postoperative period.⁷ To overcome these drawbacks, opioids are administered intrathecally along with bupivacaine. Numerous benefits like stable hemodynamics, denser analgesia, lesser pulmonary complications, earlier ambulation of patients and prompt return of bowel function and reduced stress response. Mixing other drugs with local anaesthetics might help decrease the dosage of local anaesthetics, attenuate adverse effects and increase the duration of anaesthesia.⁸ Fentanyl, a lipophilic opioid, has rapid onset of action following intrathecal injection. It is less likely to migrate to the fourth ventricle when administered intrathecally in concentrations significant enough to cause delayed respiratory depression.⁹ The addition of fentanyl 10 micrograms to hyperbaric bupivacaine 10.5-12.5 mg enhances the intraoperative and early postoperative quality of subarachnoid block.¹⁰ Intrathecal opioids are prone to cause side effects such as pruritus, nausea, vomiting, respiratory depression. Tramadol is a synthetic analgesic drug which acts centrally having 2 distinct, synergistic mechanisms of action, one being a weak opioid agonist and another as a monoamine neurotransmitter reuptake inhibitor. The racemic mixture of tramadol has 2 enantiomers which compliment each other and enhance the efficacy of analgesia and improve its tolerability profile. Unlike centrally acting opioids, tramadol has a much lesser depressing effect on respiration because it has 6000 fold less affinity for μ receptors compared to morphine. Tramadol can provide effective postoperative pain relief, with almost no risk of respiratory depression when given via central neuraxial route. But, pruritus, nausea, vomiting, urinary retention, activation of herpes labialis and risk of unpredictable respiratory depression compel clinicians to administer lesser dose of tramadol that can be used intrathecally to provide effective and prolonged analgesia without these complications. It also inhibits serotonin and norepinephrine reuptake in the spinal cord providing prolonged post-operative analgesia and does not cause neural toxicity.¹¹ any studies have been done on the efficacy of either fentanyl with bupivacaine or tramadol with bupivacaine. Very few studies are available on tramadol as the sole adjuvant to bupivacaine. Only few studies are available in the literature, which had tested the same combination of drugs as our study, out of which one study was done in pregnant patients and remaining in non-pregnant patients. Hence the present study.

MATERIALS AND METHODS

This prospective, randomised, double blinded study was done over a period of 18 months. All the patients who underwent elective lower segment caesarean section under subarachnoid block between the age of 18-35yrs, body mass index between 18.5 to 24.9 Kg/m2 and belonging to ASA (American society of Anesthesiologists) Physical status II in Shri Sathya Sai Medical College and Research Institute, Ammapettai were included in the study. Patients who refused spinal anaesthesia, those who belonged to ASA class III and above, allergic to local anaesthetics and adjuvants, infection at needle site, any contraindications to subarachnoid block like bleeding tendencies, gross spinal deformities were excluded from the study. After obtaining institutional ethics committee approval and written informed consent in patient’s own language, 60 patients were randomly allocated into two groups (n=30 each) by computer generated list of random numbers and were given adjuvants to 1.8ml of 0.5% hyperbaric Bupivacaine according to the groups: Group I - Fentanyl 0.2ml (10mcg), Group II- Tramadol 0.2ml (10mg). The patients as well as the anaesthetist involved in the assessment of the block were blinded to the drug used for spinal anaesthesia. Separate independent investigator prepared the syringes with drugs and handed them over to the performing anaesthetist. Both drugs were taken in identical 5ml syringes. Patients, anaesthesiologists involved in intra-operative and postoperative care of the patient and investigator collecting the data were unaware of the group allocation. Pre anaesthetic checkup was done for all the patients. Patients were kept nil per oral 8 hours before surgery and given tablet Ranitidine 150mg and tablet Metoclopramide 10mg night before surgery as well as the morning of surgery at 7 AM with small sip of water. Patients were shifted to Operation Theatre (OT). Prior to shifting the patient, the operation theatre underwent routine inspection which included checking of Boyle’s machine for any leaks, availability of emergency drugs, all necessary equipment for difficult airway and working standard monitors. Any deficiencies from standard requirements were rectified before shifting patient to the theatre. Standard monitors like pulse oximeter, electrocardiography and non invasive blood pressure were connected. An IV access was established with 18 gauge intravenous cannula. Patients were preloaded with 15ml/kg of lactated ringer’s solution. Patients were positioned in left lateral position. Under strict aseptic precautions, L3-L4 intervertebral space was identified. Skin was infiltrated with 2ml of 2% Lidocaine. 25G Quincke’s needle was inserted into the intervertebral space till subarachnoid space was reached which was confirmed by free flow of CSF on removing stylet. The labeled syringe which contained the corresponding drug as per which study group the patient belonged to was attached to the needle, aspirated for CSF and then entire volume of drug was injected. Time of injection of local anaesthetic solution was considered as 0 minutes. Patient was put in supine position and sensory level was checked by pin prick method. Level was checked every 2 minutes in first 20 minutes. Two consecutively same readings of 2 minute intervals were taken as maximum sensory level. Degree of motor blockade was assessed using Bromage scale (0 - able to lift legs, 1 - able to flex knees but not hips, 2 - unable to flex knees but can move ankle, 3 - no movement in legs). It was checked every 2 minutes till grade 3 is reached. Intraoperative parameters such as heart rate, blood pressure, and SpO2 were monitored every 5 minutes for 20 minutes, then every 10 minutes till the end of surgery. Duration of surgery and duration for rescue analgesia (Injection Diclofenac 75mg Intramuscularly on demand when patient complains of pain) was also monitored. Total analgesics required over 24 hours was also noted. Patients were monitored postoperatively for complications like nausea (treated with injection metoclopramide 10mg intravenously), pruritis (treated with injection chlorpheniramine 20mg intravenously), shivering, respiratory depression, hypotension (MAP fall > 20% treated with injection Ephedrine), bradycardia (heart rate < 50 beats/min, treated with Injection Atropine 0.6mg intravenously). Primary outcome of the study was duration of analgesia. Secondary outcomes were onset of sensory and motor block, intra-operative hemodynamic stability.

Sample size calculation: Sample size calculation was done based on previous study with difference of 66 minutes and SD of 61 minutes - 25 patients / each group were taken with 90% of power and 5% significance. So 30 patients were included in each group to avoid possible dropouts.

Statistical methods: Data was analyzed using statistical package for social sciences (SPSS) VERSION 23, Microsoft USA, Armonk, NY: IBM Corporation and its licensors 2015. Continuous variables were expressed in standard deviation and mean. Data was analyzed by independent T-test, Mann Whitney U test or chi square tests whichever is applicable. Demographic parameters were assessed with analysis of variance between the groups and are expressed as Mean and standard deviation (SD). P value < 0.05 was taken as statistically significant.

 

OBSERVATIONS AND RESULTS

All the 60 patients randomized were analysed for the study and there were no dropouts. The demographic profile were comparable in both the groups in terms of age, height and weight (Table 1). Duration of analgesia in Fentanyl is 9.47 ± 2.08 hours compared to 6.40 ± 2.25 hours in Tramadol group. Difference between groups are statistically significant with a P value of 0.001(Table 2). The onset of sensory blockade in Fentanyl group is 1.37 ± 0.49 minutes compared to 2 ± 0.69 minutes in Tramadol group and the difference is statistically significant with a P – value of 0.001. The onset of motor blockade in Fentanyl group is 1.73 ± 0.45 minutes compared to 2.3 ± 0.65 minutes in Tramadol group and the difference is statistically significant with a P – value of 0.001(Table 3). The time for maximum sensory level in Fentanyl group is 3.7 ± 0.65 minutes compared to 4.3 ± 0.70 minutes in Tramadol group and the difference is statistically significant with a P – value of 0.001. The time for bromage 3 in Fentanyl group is 3.13 ± 0.51 minutes compared to 3.33 ± 0.61 minutes in Tramadol group but the difference is not statistically significant (Table4). The mean and standard deviation of the pulse rate of the fentanyl and tramadol group at various time intervals during the intra operative period was analysed. The statistically significant difference was assessed by using independent ‘t’ test. P-value <0.05 was considered significant. P value for pulse rate at various intervals were insignificant(Table 5). The mean and standard deviation of the mean arterial pressure of the fentanyl and tramadol group at various time intervals during the intra operative period was analysed. The mean arterial pressure in Fentanyl group is 80.06 ± 8.22 mm Hg compared to 69.83 ± 10.76 mm Hg in Tramadol group at 50 minutes and the difference is statistically significant with p value of 0.007(Table 6).

Table 1: Distribution of height, weight and BMI in study population

 

Table 2: Distribution of time for analgesia duration in the subjects of the study population

 

Table 3: Distribution of time for onset of sensory and motor blockade in the subjects of the study population study population

	GROUP	N	MEAN	STD. DEVIATION	P VALUE BY ‘T’ TEST
Onset of Sensory	Fentanyl	30	1.37	0.49	< 0.001*
	Tramadol	30	2.00	0.69
Onset of Motor	Fentanyl	30	1.73	0.45	< 0.001*
	Tramadol	30	2.30	0.65

Table 4: Distribution of Time for maximum sensory level and time for bromage 3 of the subjects in the study population

Table 5: Pulse rate of the fentanyl and tramadol group at various time intervals during the intra operative period.

 

Table 6: Mean arterial pressure of the fentanyl and tramadol group at various time intervals during the intra-operative period.

Adverse effects of opioids like nausea, vomiting, pruritus and shivering were monitored intraoperatively and postoperatively in Fentanyl and Tramadol group. There is no incidence of adverse effects.