OBOA Journal

8. Comparison of rescue analgesic requirement in two study groups

4 patients (10%) in parecoxib group and 8 patients (20%) in tramadol group needed rescue analgesic (ketorolac injection). In parecoxib group, number of patients who needed rescue analgesic were fewer than that of tramadol group. But it is not statistically significant difference.

9. Comparison of mean time to rescue analgesia between two groups

Patients in the parecoxib group needed rescue analgesics at mean

(SD) time in minute of 540±207.8 and that of tramadol needed at 405±127.3. It showed that duration of analgesic effect was longer in parecoxib group than in tramadol group (p=0.176).

10.  Comparison of mean duration of CS between two groups

There was statistically significant difference between duration of caesarean section in parecoxib and tramadol groups with the mean (SD) of 56.4±12.8 and 50.9±11,5 respectively (p=0.046).

Discussion

Background characteristics of two study groups

Pre-existing pain, anxiety, age and type of surgery are the four significant predictors for post operative pain intensity. The type of surgery, age and psychological distress are the three most important predictive factors for post operative analgesic consumption [4].

There is evidence that advancing age appears to reduce the influence of specific genes on the experience of pain [5]. In the present study, majority of patients (65%) in parecoxib and (75%) in tramadol groups were less than 35 years and then the rest were elderly mother. There were no statistically significant differences between two groups.

Regarding the parity, [6] showed that total post operative parecoxib consumption in low-risk term pregnancies. Mean parity was 2.4±0.7 in study group and 2.2±0.7 in control group. Result was not significantly different between groups. In the present study, 72.5% in both parecoxib and tramadol groups were primigravidae. Gravida distributions were similar between group and no significant difference (p=0.525).

An American study proved that Latin America and Asia women usually perceive less pain than European women [7]. Race distribution was also studied in this study, 77.5% in parecoxib group and 65% in tramadol group were Myanmar and other ethnicity comprised nearly half of the proportion. But there was no significant ethnicity on pian in this study.

In the present study, more than half of women in both groups were higher education and above. All women were properly counselled about detailed procedure before operation to reduce anxiety. Therefore, educational status was not shown to influence on post operative pain.

Regarding occupational status among study population, ³95% of patients in both groups were non-manual workers and minority were working as manual workers. Occupation did not have significant effects on post operative pain relief in this study.

All participants were low risk pregnancy and were scheduled for elective surgery. Therefore, type and indication of surgery were mostly similar between groups. In this study, 55% of patients in both groups had previous uterine scar [2]. observed that there was no statistically significant difference in post operative pain whether it was repeat or primary caesarean section.

Pain score at different follow-up periods of study population

The onset of analgesic of parecoxib was 7-14 minutes and reached a peak effect within 2 hours. Whereas analgesic effect of tramadol is induced one hour after administration and peaks occurred after 2 to 3 hours.

The mean VAS after injection of parecoxib ranged from 2.76 to

3.02 with the mean (SD) of 2.89±0.07. Tramadol had the range between 2.91 and 3.17 with the mean (SD) of 3.04±0.07. It showed that parecoxib had lower pain score and more satisfactory pain relief than tramadol.

After 2 hours of caesarean section, the mean VAS of parecoxib was 0.9±0.55 and that of tramadol was 1.05±0.55. The mean VAS of parecoxib was slightly lower than tramadol at 2 hours VAS because of rapid onset of action of parecoxib.

The distribution of VAS at 4 hours after caesarean section in the parecoxib group was 1.72±0.6 and that in the tramadol group was 1.9±1.03. It revealed that VAS of parecoxib was still lower than tramadol at 4 hours after operation.

In parecoxib group, the mean VAS of 4.15±0.74 and 4.68±0.97 were 6 hours and 12 hours after caesarean section respectively. On the other side, it was 4.68±0.97 and 4.55±0.85 in tramadol. It meant that 6- and 12-hours VAS scores of both groups were higher than 2- and 4-hours VAS scores. This suggested that the effects of both analgesics start weaning off by 6 hours after caesarean section. When contrasting VAS scoring of time on a linear graph (Figure 1), pain control of parecoxib was better than tramadol in 2, 4 and 6 hours of caesarean section. When comparing VAS score at 12 hours, it showed that parecoxib was slightly higher pain score than tramadol. 10% of patients in parecoxib group and 20% from the rest required rescue analgesic for pain relief at 6- and 12-hours follow-ups because VAS was ³6 at that time. It was observed that most of the patients in parecoxib group had lower VAS score after operation and received less extra analgesic than patients in tramadol group.

Therefore, the level of pain relief in terms of VAS after injection of analgesics was comparable in both groups at 2 and 4 hours after caesarean section. But analgesic efficacy and rescue analgesic requirement were different in 6 and 12 hours. Analgesic efficacy of parecoxib seemed to be longer than tramadol according to this study.

Figure 1: Comparison of mean time to rescue analgesia between two groups

Level of pain relief with time after drug administration

According to present study, the mean VAS of parecoxib at 2 and 4 hours after surgery were comparable with that of tramadol. The mean VAS was significantly reduced at 6 hours in parecoxib than that in tramadol. It was statistically significant. At 12 hours followup, mean VAS seemed to be slightly higher in parecoxib than tramadol. It was because patients in the parecoxib group had less rescue analgesic requirements at 6-hour follow-up than tramadol. Therefore, VAS score of parecoxib group at next follow-up (twelve hours) was slightly increased than tramadol.

Adverse effects of drugs in the study population

The goal of post operative management is to reduce or eliminate pain and discomfort with a minimum side effect. Opioids have been the mainstay of post operative pain control for decades. However, opioid analgesics are associated with several limitations. Gastrointestinal side effects such as nausea and vomiting, respiratory side effects, sedation and abuse potentially limit their usage. Parecoxib is a water soluble pro-drug of non-steroidal antiinflammatory drug, and a potent and selective inhibitor of cyclooxygenase 2 (COX 2) isoenzyme. Despite some adverse effects like cutaneous reactions and thromboembolic events, they are useful alternative to opioids in managing surgical patients.

According to the study of [8], incidence of nausea (45%) and vomiting (45%) were reported by the patients in the group of tramadol which were higher than that of parecoxib. This was the study which compared the post operative analgesic effects of buterophenol, parecoxib and tramadol in patients undergoing major surgeries. In the present study, no patients suffered nausea in parecoxib but 20% suffered nausea in tramadol group. It was statistically significant difference between two groups. Whereas 20% and 17.5% of patients in tramadol group reported drowsiness and headache respectively. But no patients in parecoxib group suffered those symptoms which showed statistically significant difference. Vomiting was reported by 5% of patients in parecoxib group and 7.5% in tramadol group. This finding was like the study conducted by [8]. In contrast to findings of two studies, side effects were more experienced in patients of tramadol group because of centrally acting analgesic effect of tramadol on serotonergic and noradrenergic nociception.

In this study, there was no patients who had significant blood pressure and pulse rate changes after administration of both drugs. However, significant respiratory rate changes were noted between the drugs. Mean respiratory rate changes of parecoxib was 0.1±0.8 and that of tramadol was -0.63±1.2. Slightly increased respiratory rate was found in patients of tramadol group. It may be due to fact that patients in tramadol group suffered more pain than that of parecoxib.

In this study, it was found that patients in the parecoxib group experienced less nausea, vomiting, drowsiness and headache than tramadol group. There was no significant change in vital parameters of both women in both groups. From these findings, parecoxib is an analgesic with better side effect profile than tramadol.

Rescue analgesic requirement in the study population

In the present study, only 10% of patients in the parecoxib group required rescue analgesic. But in the tramadol group, it doubled. The mean time to first administration of rescue analgesic was 540±4 min in parecoxib group and 405±8 min in tramadol group. According to above data, pre-emptive parecoxib provided longer duration of post operative analgesia and reduced requirement for rescue analgesic compared with tramadol. This was provided by mean duration of caesarean section between two groups. It was found that mean duration of surgery was longer in parecoxib group (56.4 min) than that of tramadol (50.9 min). In parecoxib group, even though duration of surgery was prolonged, it provided more effective analgesia than tramadol.

Conclusion

Caesarean section rates are increasing worldwide, and effective pain relief is a key priority. Pain management in women after caesarean section is almost exclusively neuraxial, pre-emptive analgesic use is limited by fetal drug transfer, and postoperative analgesic given to the mother have the potential for transfer to the breastfeeding neonate. In addition to pain relief, optimal management of patients after caesarean delivery should address the goals of maximizing maternal mobility and rapid recovery. Therefore, the need for analgesia to overcome post operative pain is highly requested by women today. In developing countries, parentral single dose analgesics such as parecoxib and tramadol can be considered for relieving acute pain.

This was hospital-based study carried out in Central Women Hospital (Yangon). In this study, either intravenous parecoxib 40 mg or intravenous tramadol 1mg/kg was given randomly to 80 women who underwent caesarean section. The level of pain relief was noted by visual analog scale at 2, 4, 6 and 12 hours after caesarean section. Adverse effects of drugs and total numbers of rescue analgesic requirement were noted.

The mean VAS of parecoxib group was 2.89±0.07 and that of tramadol group was 3.04±0.07. According to side effects profile, only two patients in parecoxib group suffered vomiting. But nausea, vomiting, drowsiness and headache occurred in 8, 3, 8 and 7 patients respectively in tramadol group. On comparing rescue analgesic requirement, 10% of patients in parecoxib and 20% in tramadol required injection ketorolac for pain relief.

According to this study, pain score was reduced in parecoxib group. It meant that level of pain relief was better in parecoxib than that of tramadol. Nausea, vomiting and drowsiness were found only in tramadol. Parecoxib showed significant opioids sparing side effects in this study. No life-threatening side effects were found in both groups. Moreover, rescue analgesic requirement in parecoxib was less than that of tramadol.

To be concluded, both drugs can be used as effective post operative analgesia. However, parecoxib not only has slightly better analgesic efficacy than that of tramadol but also avoids opioids side effects of tramadol. Therefore, the use of parecoxib should be recommended instead of opioids to achieve optimal pain management with tolerable side effects profile after caesarean delivery. Moreover, this study is helpful in obstetric practice for post operative pain control after elective caesarean section.

Acknowledgements

I would like to express my sincere thanks to Professor Zaw Wai Soe, Rector of University of Medicine 1, Yangon, for his kind permission to do this study and Post Graduate Ethical Board of Committee, University of Medicine 1, Yangon for giving me opportunity to submit this dissertation.

I am immensely grateful to my supervisors, Professor San San

Myint, Consultant Ms Ei Shwe Syn, and Consultant Mr Shwe Kyaw for their enthusiastic guidance, careful supervision and their patience in helping me to complete this study.

My gratitude is extended to Professor Nu Nu Aye, Department of Pharmacology, University of Medicine 1, Yangon, for her advice in using drugs.

My grateful thanks to Ms Khin Pyone Kyi, Senior Medical Superintendent, Central Women’s Hospital, Yangon, for allowing me to conduct the study at post Caesarean Section Ward in Central Women’s Hospital, Yangon.

I would like to express my gratitude to all my senior and junior colleagues and all the staffs of operation theatre and post caesarean section ward at Central Women’s Hospital, Yangon for helping me throughout this study to complete.

Last, but not least, my sincere thanks to all pregnant women who gave consent, accepted the giving drugs and willingly participated in this study. This study would not finalize without their cooperation and participation.

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