Efficacy of diclofenac transdermal patch versus injection as post-cesarean analgesia: A clinical, comparative, single-blind randomized control trial

INTRODUCTION

Cesarean deliveries are quite common in obstetric practice. The procedure does cause severe acute tissue injury and results in unbearable pain. An adequate pain relief after cesarean section encourages early movement and will help provide better care of the baby.^[1]

Lower segment cesarean section (LSCS) is a class one surgical procedure, where surgical incision, cutting, separation, and access to the surgical site are cleaner with no bacterial contamination. The procedure involves opening the tissues, retracting the layers, clamping the cut blood vessels, tying the knots, and suturing the cut layers, and all these events damage the cells, stimulate the nerve endings, trigger liberation of leukotrienes, and signal the formation of prostaglandins to mitigate the tissue injury. In this scenario, natural physiological response is the unpleasant feeling of pain at the site of operation.

The intensity of pain is influenced by age, personality, cultural background, and current health status of the mother.

The management of post-operative pain is a critical component in patient care activity and we now know the pain biology better and appreciate the pain cascade of injury like, cellular damage, leukotrienes, cyclooxygenase and formation of prostacyclin, prostaglandins and accordingly suitable pharmacologic agents to block this pathway, have heralded the innovation of non-steroidal anti-inflammatory drugs (NSAIDs). The drug diclofenac is an NSAID. The routine use of intravenous infusion of paracetamol for post-operative analgesia is also well known.

It is agreed that the choice of analgesia should be effective and safe, without interfering the mothers’ ability to take care of her baby along with no adverse effects to the baby.

The drug diclofenac is one such NSAIDs. Oral and injectable diclofenac has been used widely for postoperative pain relief.^[2-4] Oral administration is the preferred choice in daily practice, but becomes impractical before and soon after surgery. The drug acts primarily by blocking the cyclooxygenase and lipoxygenase enzymes, thus halting the inflammatory pathway and providing relief from pain. When given orally, the drug is readily absorbed, however, only 50% reaches the circulation due to first-pass metabolism. However, when given intramuscular/intravenous, the drug quickly reaches the optimum blood levels. However, these are invasive routes. Newer modes of drug delivery systems are now available with the understanding of pain pathophysiology and treatment, and new routes of drug delivery are being used, with the objective of attempting to block pain at peripheral sites, with maximum active drug and minimal systemic effects. The result is availability topical (transdermal) preparations. The topical preparations being non-invasive in nature, simple to use, assuring steady plasma concentration, and giving therapeutic effect are an added benefit. During transdermal drug delivery system, the drug passes through intercellular spaces at the epidermis by its amiable physical, chemical, pharmacological, and drug dynamic characters, absorbed into the circulation through dermal capillaries. The absorption is steady, reaches optimum therapeutic level by a few hours, and lasts 24 h. Finally, the drug is eliminated by oxidative metabolism in the urine.

The use of transdermal diclofenac patch for pain relief in acute tissue injury following tooth extraction, dental implants, and dental surgeries is well studied and documented.^[5-13] There is also good number of studies showing efficacy of transdermal diclofenac patch in osteoarthritis, acute injuries, abdominal laparoscopic surgeries, and herniorrhaphy procedure.

However, there is not enough literature available on the application of transdermal patch as post-operative analgesia in LSCS cases.

This is the focus of our study. We evaluated and compared the analgesia obtained between transdermal diclofenac patch with intramuscular diclofenac injection in patients undergoing LSCS.

MATERIAL AND METHODS

We obtained approval from our Institutional Ethical Committee (Ref: USM KLE/01 20/Oct 3, 2022), for our study and registered with Clinical Trial Registry India (CTRI/2022/12/048088). This is a hospital-based, prospective, randomized, comparative study conducted in the Obstetric Gynaecology department of a Teaching hospital. The CONSORT guidelines are adopted for reporting the study.

RESULTS

Enrolled 95 participants, 5 participants excluded for short of inclusion criteria.

The “Flow Chart” [Figure 1]:

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Figure 1:

Flowchart.

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We finalized 45 symmetrical pairs of participants for the study, matching the demographic characters.

The mean age of participants is 27.20 ± 5.10 years. The participants are evenly distributed across the sociodemographic characters [Tables 2-4].

The clinical characters between the two study groups are equal and matching, summarized in Tables 5 and 6.

The pain scores assessed in both the groups, summarized in Figures 2-4.

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Figure 2:

Comparison of two groups with mean pain scores at different treatment times.

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Figure 3:

Trend of visual analog mean pain score of group A and group B.

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Figure 4:

Comparison of different time points with mean pain scores in group A and group B.

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The pain relief scores between Group A and Group B at 12 h was 3.10 ± 074, 3.04 ± 0.21 respectively and the difference was not statistically significant (p>0.05) but at 24 h was 2.48 ± 0.51, 2.09 ± 0.29 respectively which was significant (P = 0.0022).

The pain relief scores in both the groups was statistically significant at 24 h and 42 h (P = 0.0022, 0.0004).

The pain relief scores in both groups match and statistically significant at 6 h–24 h and 6 h–48 h (P = 0.0001, 0.0001).

There are no untoward events recorded in both the groups.

DISCUSSION

The diclofenac formulations are well understood, efficient, safe, and widely used products. However, oral and injectable products are commonly used; the transdermal patch is less commonly used. There is literature mentioning its use for post-operative pain relief.^[14-16] In our study, we found good post-operative pain relief using transdermal patch. The quality of pain relief was equal and comparable to injectable diclofenac. In Group A, 43 women the pain relief set in 4 h, lasted 16 h, tapered by 20 h, there was no need for extra analgesics. In two women, pain relief was good but needed extra analgesia after 16 h. In Group B, the pain relief was similar, 42 women had good analgesia, while three women needed extra analgesia after 12 h. The VAS scores in both the groups ranged between one and three in first 12 h. Then, two women in transdermal patch group and three women from injectable group, the score crossed three VAS score. The general condition, clinical parameters, post-operative recovery remained good. There were no untoward events.

There are many studies using transdermal diclofenac patch for cesarean post-operative pain relief. The study by Chawla et al., very systematic, in a sample of 200 mothers, showed excellent analgesia in all the patients. The VAS scores at 6 h, 12 h, 18 h, and 24 h in the 1^st post-operation day for both the groups matched evenly in both the groups. This finding is indicative of comparable pain relief action of transdermal patch.^[17] In another study, Rajeev and Harikrishnan used diclofenac suppository, transdermal diclofenac patch and control, in 150 women for post-cesarean pain relief, to find excellent analgesia in suppository group, good relief in transdermal patch compared to the control group.^[18] Dahl et al. found diclofenac suppository given twice daily, had good pain relief in a sample of 82 mothers.^[19] Lim et al., in a sample of 48 mothers, also found diclofenac suppository an excellent pain relief after cesarean delivery.^[20]

Both diclofenac suppository and diclofenac patch are locally absorbed and suppository has superior action. All these studies concur with our study results showing comparable pain relief with transdermal diclofenac patch. Perhaps, we need many more such studies from different geoclinical setting, so that the outcomes are really representative.

Further pain relief with diclofenac patch following gynecological procedures and major general surgeries have also showed promising results. The study by Alessandri et al., in a sample of 21 patients undergoing laparoscopic surgery found comparable pain relief with that of standard analgesic.^[13]

Kumar et al., in 200 patients found significant pain relief in 65% of patients in the first 24 h using diclofenac patch.^[21] In a study by Narzaree et al., also found good analgesic effect of diclofenac patch.^[22]

Besides these, numerous studies are using transdermal diclofenac patch in dentistry, orthopedics, and general surgical practice as a useful analgesic. Sharma et al. have found transdermal diclofenac patch useful in mandibular fracture surgery.^[23] Singh et al. have demonstrated that the use of transdermal diclofenac patch gives good analgesia in head-and-neck cancer surgery.^[24] Samal et al. too have shown transdermal diclofenac providing good post-operative analgesia.^[25]

In conclusion, we mention one more study by Bhargava et al., who used transdermal diclofenac patch and injectable diclofenac in 100 women during general surgical procedures, to find excellent analgesia and recommend for routine use of transdermal diclofenac patch.^[26]

CONCLUSION

We find that diclofenac transdermal patch gives equal and good pain relief in post-operative period following cesarean delivery.