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Comparative study of fentanyl versus tramadol as adjuvant with low dose local anaesthetic ropivacaine (0.1%) for epidural labour analgesia

Background: Toxonomy committee of International Association defined pain as an unpleasant emotional and sensory experience associated with potential tissue damage. The present study was conducted to evaluate the effect of a combination of low dose ropivacaine with fentanyl and tramadol in epidural labour analgesia. Methods: This prospective randomized double blinded clinical study was conducted in 100 patients in labour after ethical committee approval. Inclusion criteria was patients who had ASA I and ASA II (American society of anesthesiologists physical status classification system), age above 18 years, height more than 150 cm, weight less than 110 kg, either primigravidae or gravid 2. Patients were allocated into two groups Group F (ropivacaine with fentanyl) and group T (ropivacaine with tramadol) by computer generated randomisation technique. Results: In the present study, mean age in group F (ropivacaine with fentanyl) was 22.54±2.5, mean age in group T (ropivacaine with tramadol) was 22.86±2.17, and weight in group F was 56.68±2.75 and group T was 56.58±2.58. Duration of labour in group F was 3.39±1.01 hrs and in group T was 3.42±0.70 hrs. There was no significant difference between the two groups at any time points for mean VAS score. There was no significant difference in the mean heart rate and arterial blood pressure among both the groups statistically (p>0.05). More side effects were seen in group F. Conclusions: Both fentanyl and tramadol in combination with ropivacaine provide similar analgesia with minimal motor block. Both have no adverse effects on cardiotocographic parameters. However side effects were relatively more common in fentanyl group. Thus tramadol is a safer alternative to fentanyl as an adjunct to epidural labour analgesia.


INTRODUCTION
The delivery of the infant into the arms of a conscious and pain free mother is one of the most exciting and rewarding moments in medicine. Severe labour pain can have neuropsychological consequences, postnatal depression and it has also been correlated with the development of post-traumatic stress disorder. 1,2 Pathophysiological responses occur in the body during pain. In the respiratory system there is hyperventilation during contraction, increasing the work of breathing and oxygen consumption. 3 Effective pain relief reduces plasma noradrenaline, prevents the rise during first and second stage of labour, prevents metabolic acidosis by reducing the rate of rise of lactate and pyruvate. 4,5 Bupivacaine and ropivacaine are widely used to provide efficient epidural analgesia in labour. Ropivacaine, an amide local anaesthetic is less cardiotoxic as well as it may also be more selective for sensory fibers when compared to other local anaesthetics, producing less motor block.
Epidural opioids ensure analgesia without a motor block; however, when they are used alone, they do not lead to a satisfactory analgesia throughout labour. When the two drugs are combined, both the local anaesthetic and opioids can be administered at low concentrations, resulting in increased maternal satisfaction and most importantly, a decrease in the incidence of adverse effects such as hypotension and drug toxicity. 6 The absence of the neuronal toxicity of tramadol and fentanyl allowed its use in neuraxial analgesia. 7 The current study was planned to compare epidural analgesia using low dose ropivacaine with fentanyl and tramadol as adjuvant for labour with respect to maternal and foetal parameters.

METHODS
This was a prospective randomized double blinded clinical study conducted after institutional ethical committee approval at SNMC, Jodhpur from January 2015 to December 2015. The study compromised of 100 patients in labour. Inclusion criteria was patients who had ASA I and ASA II (American society of anesthesiologists physical status classification system), age above 18 years, height more than 150 cm, weight less than 110 kg, either primigravidae or gravid 2. An informed consent was obtained from all patients. 100 patients were allocated into two groups Group F (ropivacaine with fentanyl) and group T (ropivacaine with tramadol) by computer generated randomisation technique.
A detailed history was taken and a complete general physical examination including airway assessment, spine and systemic examination was done to confirm the inclusion and exclusion criteria. The parturients were evaluated by the obstetrician for cervical dilatation, effacement, position, station, integrity of membranes and adequacy of pelvis.
Baseline recording of heart rate, blood pressure and oxygen saturation and fetal heart rate (FHR) were noted. An intravenous (IV) line was accessed and maintenance fluid started. The patient was positioned in a sitting position. Under aseptic conditions the back was prepared was 5% povidone iodine solution and spirit. The L2-L3/L3-L4 interspace was identified by palpation and overlying skin was infiltrated with 2-3 ml of xylocaine (1%). Epidural space was identified with the help of 18 G tuohy needle using loss of resistance (LOR) to air technique and then 20 G epidural catheter was threaded through the epidural needle into the epidural space in cephalic direction, the catheter about 3 to 5 cm was left in epidural space.
10 ml epidural bolus dose was administered according to the group selected viz group F-ropivacaine 0.1% and 2 mcg/ml of fentanyl and group T-ropivacaine 0.1% and 5 mg/ml of tramadol. After the administration of bolus dose, an epidural infusion of ropivacaine/fentanyl (0.1%/2 mcg/ml) was started at the rate of 5 ml/hr by syringe pump in group F. Similarly, group T received a 5 ml/hr continuous infusion of ropivacaine/tramadol (0.1%/5 ml). Supplemental doses of 5 ml ropivacaine (0.1%) were administered on demand in each group. Epidural infusion was continued till the completion of second stage of labour.
Demographic data, haemodynamic effects, sensory block, motor block, onset of analgesia, duration of labour, mode of delivery, pain relief maternal satisfaction, side effects and foetal outcome were noted in both the groups. All the data was expressed as frequency, percentages and mean ± standard deviation. Qualitative data between the two groups was compared using a chi-square test. Continuous variables between the groups were compared using an independent t-test. P values <0.05 were considered significant.

RESULTS
Mean age, height, weight, cervical dilatation during epidural placement and gestational age in both the group were similar and non-significant. Group F and group T were similar with respect with to age of the parturient. (p>0.05) The mean age in group F was 22.54±2.5 years and group T was 22.86±2.17 years ( Table 1).
Height of parturient in this study ranged from 152 cm to 163 cm in both the groups. The mean height in group F was 157.22±2.63 cm and 156.76±3.05 cm in group T. The p value was >0.05. The results were not statistically significant. Most of the parturient weighed between 50-60 kgs in the two groups. The P value was >0.05 which was not significant.
Around half (48%) of parturient in group F and 38% of parturient in group T had cervical dilatation of 5 cm while 36% in group F and 42% in group T had cervical dilatation of 4 cm. P value was >0.05 and was not statistically significant.
Duration of labour in group F the mean duration of first stage of labour was 2.60±0.87 hours while in group T the mean was 2.67±0.56 hours. The difference between the two groups was not statistically insignificant ( Table 2).
Basal visual analogue scale (VAS) of parturient was comparable in the two groups with p value >0.05 which was statistically not significant. There was no significant difference between the two groups at any time points (Table 3).
Side effects between the two groups showed that more side effects were seen in group F i.e. fentanyl along with ropivacaine (Table 4).
There was no significant difference in the mean heart rate and mean arterial blood pressure at any time interval among both the groups (p>0.05) (Figure 1 and 2).

DISCUSSION
Epidural analgesia for painless labour was given to 100 parturient belonging to ASA grade I and II admitted to hospital. The parturient were randomly allocated by computer generated system into 2 groups. Group F (n=50) received ropivacaine (0.1%) with fentanyl (2 mcg/ml) and group T (n=50) received ropivacaine (0.1%) with tramadol (5 mg/ml) given as an initial bolus of 10 ml followed by continuous epidural infusion of 5 ml/hour continued until the delivery. Extra top ups of 5 ml ropivacaine (0.1%) were given on patient demand (VAS>3).
Finegold et al also conducted a similar type of randomized double blind study comparing ropivacaine (0.1%) fentanyl and bupivacaine (0.125%) fentanyl infusions for epidural labour analgesia. 8 Rao et al also carried out a similar study on walking epidural with low dose bupivacaine plus tramadol on normal labour in primipara patients. 9 Gupta et al conducted a study on painless labour by epidural analgesia and its effects on cardiotocographic parameters and labour. 10 Dostbil et al compared maternal and neonatal effects of adding morphine with fentanyl to low dose bupivacaine for epidural labour analgesia. 6 In our study after giving a bolus dose we used the same drug concentration as a continuous epidural infusion till the completion of second stage of labour, top-up doses were given in supine position. The dose used for subsequent top-ups was 5 ml ropivacaine (0.1%) in both the groups.
Demographic variables and obstetric characteristics were similar between the two groups. There was no statistically significant difference between the two groups. Demographic and obstetric data were similar with the Indian studies by Kalra et al and Tomar et al. 11,12 The baseline mean arterial blood pressure (MAP) and maternal heart rate (HR), VAS score were comparable in both the groups. For study purpose data were recorded for the first 60 minutes. These parameters were in accordance with the study carried out by Fan et al. 13 Many studies have reported sensory loss up-to T10 to cold, pain and warmth sensation. Tomar et al and Fan et al studied the analgesic effects of fentanyl and tramadol in combination with bupivacaine and ropivacaine for extradural labour analgesia and found that the height level of sensory block was T8 in 16 and T10 level in 10 parturient. 12,13 In our study we used pinprick method to test the level of sensory blockade 54% in group F versus 56% in group T achieved the sensory level up to T10 which was comparable between the two groups. In our study the mean duration of first stage of labour was 2.60 hours in group F and 2.67 hours in group T. As far as the duration of labour was considered, there was no statistically significant difference between the two groups. Tomar et al in a study using fentanyl 2 mcg/ml with bupivacaine 0.125% for epidural labour analgesia found the mean duration of first stage of labour to be 2.87 hours. 12 The mean duration of second stage of labour was 47.08 min in group F and 45.34 min in group T in this study. There was no statistically significant difference between the two groups. Rao et al also found similar results in a study using tramadol 5 mg/ml with 0.1% bupivacaine. 9 Total amount of drug used from bolus till the completion of second stage was calculated. Total average dose of ropivacaine used was 40.05±8.47 mg and 42.07±7.77 mg in group F and T respectively. Total average dose of fentanyl used in group F was 53.77±10.08 mcg. Total average dose of tramadol used in group T was 135.96±17.67 mg.
In our study no significant difference in maternal men arterial pressure (MAP), heart rate (HR) and visual analogue scale (VAS) score seen in both groups at any time points. Similar finding were seen in a study conducted by Fan et al. 13 In our study, spontaneous vaginal delivery occurred in 94% of the parturient in group F and 96% in group T. Three patients in group F and 2 patients in group T underwent caesarean. There was no stastically significant difference between the two groups. Fan et al in a comparative study of epidural tramadol/ropivacaine and fentanyl/ropivacaine for labour analgesia found that caesarean was done in 2 patients in both groups. 13 Kalra et al in a study comparing efficacy of bupivacaine/fentanyl with bupivacaine/sufentanyl for epidural labour analgesia found the similar results where one patients in each group had undergone caesarean. 12 In our study FHR were comparable in both the groups throughout the study. Gupta et al found no significant effect on cardiotocographic parameters in epidural and control group. 10 Fan et al found neonatal HR comparable between both groups at any time points. 13 Reynold et al in their study did not report any change in the neurobehavioural or appearance, pulse, grimace, activity, and respiration (APGAR) score when up to 80 mcg fentanyl was given for first stage of labour for pain relief. 16 In our study APGAR score was employed to assess the newborns. At 1-minute interval only 10% of the newborns in group F, 4% in group T had an APGAR score of less than 7. Although no significant difference was seen, there was a tendency that the incidence of side-effects (pruritus, shivering and urinary retention) was higher in group F. No significant difference was observed in other side effects such as nausea, vomiting, motor block, respiratory depression and hypotension between the two groups. Furthermore, none of the parturient in any group required specific treatment during labour. Chestnut et al found pruritus (7%), nausea (14%), emesis (14%) and urinary retention (41%) when bupivacaine (0.0625%)/fentanyl (0.0002%) was used as continuous infusion. 17 Cohen et al reported pruritus in 26%, drowsiness in 11% and urinary retention 21% of the patients when bupivacaine (0.068%) with fentanyl 10 mcg was used. 18 Fan et al in a comparative study of tramadol/ropivacaine and fentanyl/ropivacaine for epidural labour analgesia found the similar results. 13 In our study 40 in group F and 38 patients in group T had good satisfaction score while 7 patients in group F and 10 patients in group T had excellent satisfaction scores. There was no statistically significant difference between the two groups. Tomar et al in a study using fentanyl 2 mcg/ml with bupivacaine 0.125% for epidural labour analgesia found 7 patients reporting good satisfaction level and 20 reporting excellent satisfaction levels. 12

CONCLUSION
Epidural analgesia is a safe and excellent method of relieving pain in labour with excellent satisfaction in parturient. Both fentanyl and tramadol in combination with ropivacaine provide similar analgesia with minimal motor block. Both have no adverse effects on cardiotocographic parameters. However side effects were relatively more common in fentanyl group. Thus tramadol is a safer alternative to fentanyl as an adjunct to epidural labour analgesia.