Abstract
Background
This study was conducted to avoid the pain of an intramuscular injection of diclofenac after a cesarean section, by modifying it to an intravenous infusion by diluting it with 5% dextrose in 100 mL of water.
Objective
The aim of this study was to determine the efficacy of a single-dose modified diclofenac being given intravenously, instead of intramuscularly, for pain relief after a cesarean section.
Study design
A double-blind, randomized controlled trial was conducted.
Participants
We enrolled 30 patients who underwent cesarean sections with Pfannenstiel skin incision.
Methods
All patients received 2.2–2.5 mL of 0.5% bupivacaine with 0.2 mg morphine for spinal anesthesia. The participants were equally and randomly allocated to two groups to receive intravenous diclofenac or placebo at 12 hours postoperatively. Both groups received the same regimen for postoperative pain control.
Main outcome measurements
The severity of postoperative pain was measured directly using a verbal numerical rating scale (0–10) and a pain-relief scale (1–4), and indirectly from the amount of tramadol used.
Results
The characteristics of the two groups of patients were similar. The mean postoperative pain relief at 24 hours in the study group was better than that in the control group (3.14 ± 0.66 vs. 2.13 ± 0.99; p < 0.05). The severity of postoperative pain at 24 hours and the amount of tramadol used were not different between groups.
Conclusion
Intramuscular diclofenac (75 mg), modified by diluting it with 5% dextrose in 100 mL of water, for intravenous administration in combination with spinal morphine (0.2 mg) provided good analgesia after a cesarean section within 24 hours when assessed by the pain-relief scale; however, the mean pain intensity was not different.
Keywords
cesarean section; diclofenac; injections, intravenous; pain, postoperative;
1. Introduction
Pain during and after a cesarean section is the greatest concern expressed by patients.1 Indeed, inadequate pain control after a cesarean section can significantly detract from the sense of well-being and joy of the mother in the immediate postpartum period, by affecting maternal activities such as the pleasure of breastfeeding.2 In our previous study, we found that the proportion of patients who experienced moderate to severe pain during the 24-hour postcesarean section period was high.3
Nonsteroidal anti-inflammatory drugs (NSAIDs), when combined with opioids, can help reduce opioid consumption and improve the quality of pain control.4, 5 Diclofenac is an NSAID widely used in various forms or preparations (e.g., intramuscular, intravenous, oral, and suppository preparation) for pain control. In our institute, only the intramuscular and oral forms are available; an oral diclofenac is not allowed during the nothing per oral or NPO period after a cesarean section. Since pain prevalence after the cesarean section in our institute remains high, we are trying to improve the status quo by including the use of diclofenac during this transition period. However, to avoid the painful intramuscular injection of diclofenac, the intramuscular preparation was modified for intravenous infusion by diluting it with 5% dextrose in 100 mL of water. A single dose of diclofenac was designed for this study because the authors wanted to make sure that the modified technique worked well prior to incorporating it into practical use. Therefore, the purpose of this study was to determine the efficacy of such a modified, single-dose diclofenac given intravenously instead of intramuscularly for pain relief after a cesarean section.
2. Materials and methods
The study was approved by the Khon Kaen University Ethics Committee. Enrolled in the study were 30 pregnant women who were to undergo lower segment cesarean section with Pfannenstiel skin incision under spinal anesthesia in July 2008. Written informed consent was obtained from each woman. Exclusion criteria for participation included patients in whom the use of NSAIDs was contraindicated, with a history of NSAIDs allergy and a midline skin incision or the surgery under general anesthesia.
Spinal anesthesia was performed by an anesthesiologist in the operating room with 2.2–2.5 mL of 0.5% bupivacaine plus 0.2 mg of morphine. All patients received standard care during the operation and in the recovery room, after which they were transferred to the postpartum ward. At the postpartum ward, 12 hours after the caesarean section, patients were randomly allocated (by computer randomization) to receive 75 mg diclofenac sodium diluted with 5% dextrose in 100 mL of water or placebo, in accordance with the order sealed in an envelope, coded by the investigator. The reason for starting the study medication at 12 hours after spinal anesthesia was to make sure that analgesic effect of bupivacaine had faded. Prior to starting the study medication, pain scores were recorded (to be the baseline data) using a verbal numerical rating scale (VNRS, a scale of 0–10: 0 = no pain and 10 = very severe pain). The trained ward nurses, who recorded pain scores at the postpartum ward, were ignorant of the study regimen, and the study solutions were prepared by the anesthesiologist who performed the spinal analgesia.
The study solution was then administered over a period of 10 minutes. Later, at 24 hours post operation, the patients were again evaluated for the severity of their pain and pain relief by a four-point pain-relief scale (1 = no pain relief, 2 = poor pain relief, 3 = good pain relief, and 4 = excellent pain relief) (Fig. 1).
Postoperative fever (>37.5 °C), nausea and vomiting (which needed treatment), abdominal discomfort (reported by patient as “yes” or “no”), and length of stays were also assessed. All the patients received the same regimen for postoperative pain control (in addition to the 0.2 mg single doses of spinal morphine), namely 50 mg intravenous tramadol every 6 hours as requested. The patients then had their pain scores reassessed within 15 minutes. If pain persisted (i.e., pain scores ≥5) a 25-mg intravenous rescue dose of tramadol was given.
The sample size was calculated based on a power analysis, using the mean pain score at rest (1.9 ± 1.1) from the previous study investigating the effectiveness of a single dose of 75 mg diclofenac for pain relief at 24 hours after a cesarean section.6 With a power of 80% for the detection of 50% difference, α = 0.05, and β = 0.2, we needed at least 14 participants in each group. We had 15 participants in each group.
The continuous data were presented as means ± standard deviation (SD). The Student t test was used to compare the continuous variables. Pain-relief scores were present as mean ± SD and analyzed by unpaired t test. Other categorical data (such as abdominal discomfort) were presented as frequency, while the Chi-square test was used to compare these variables where appropriate. A p value of <0.05 was considered statistically significant.
3. Results
The total number of patients in the study groups was 14 because one patient who had internal bleeding and needed re-exploration under general anesthesia was excluded from the study. The re-exploration was necessary due to a surgical problem caused by slippage of bilateral tubal resection stumps. The baseline characteristics of participants and operative factors were similar for both the groups, except that the operative time and gravida were longer (Table 1) and the pain score at rest appeared to be lower (Table 2) for the diclofenac group.
The mean pain score 24 hours after surgery was not statistically different between two groups, nor was the amount of tramadol used (Table 2). Pain relief after receiving diclofenac (measured at 24 hours postoperatively) was significantly different between the two groups (3.14 ± 0.66 vs. 2.13 ± 0.99; p = 0.003). There was no statistically significant difference between groups vis-à-vis postoperative fever, nausea, vomiting, abdominal discomfort, or length of hospital stay.
4. Discussion
The current study demonstrated that when a diclofenac intramuscular formula is modified to an intravenous infusion (by diluting it with 5% dextrose in 100 mL of water), it is effective for pain relief after a cesarean section, as rated by patients using 1–4 scales (3.14 ± 0.66 vs. 2.13 ± 0.99; p = 0.003), although pain intensity (measured by numerical rating scale) and tramadol used during the 12 hours after administration were not different. There were some uncontrolled factors in the baseline data, which were different between groups that had confounded pain relief, for example the number of gravidity as we know repeated incisions could be less painful, tubal resection, operation time, and pain intensity prior to the administration of study solution. The amount of tramadol used in 24 hours seemed to be higher in the placebo group, but data were not clear enough to demonstrate whether its use was higher in the first 12 hours. All these confounding factors made pain intensity inconsistent with pain relief.
Our results support the study by Bhuttarechval,6 in which it was reported that a single, intramuscular dose of 75 mg of diclofenac plus an additional 50 mg given orally every 8 hours could significantly decrease postoperative pain. In renal colic, intravenous diclofenac can more effectively reduce pain that it causes than intramuscular diclofenc.7 We are therefore interested in studying the effectiveness of an intravenous route because of its following two advantages: (1) it has a more rapid onset of action than other routes and (2) it is less painful. Moreover, due to the limitation on the availability of other formulations of diclofenac at our hospital, intravenous infusion is the best option and, although it is more expensive than oral or rectal route formulations, it can be affordable with our economy.
The most common side effect of NSAIDs is gastrointestinal irritation, which is associated with its long-term use. In case of its use for a short period of time (i.e., during an in-hospital postoperative period), this side effect is quite limited.2 Similarly and importantly, this side effect was not present in our study. Regarding breastfeeding, following a cesarean section and after the end of a 1-day infusion of 150 mg of diclofenac, no diclofenac was found in the colostrum. Breast milk of the mother who has been treated with diclofenac contains only small amounts of diclofenac; therefore, there is a low risk of any hazard to breastfed infants.8, 9 Moreover, the American Academy of Pediatrics states that diclofenac is considered compatible with breastfeeding.
Normally, diclofenac is recommended to be administered three times daily or once every 8 hours, but when combined with morphine its analgesic effect lasts longer. The limitation of the present study is that we did not evaluate the severity of pain at more than one point (i.e., at 3, 6, and 12 hours after being given the study drug), so we do not know the progression of pain relief. Multiple points (or at least one more point at 6 hours) would have provided valuable information. In addition, the small sample size is another limitation of this study.
5. Conclusion
Intramuscular diclofenac 75 mg (modified by diluting it in 5% dextrose in 100 mL of water) for intravenous route delivery, in combination with spinal morphine 0.2 mg, provided good analgesia within 24 hours after a cesarean section when assessed by the pain-relief scale; however, the mean pain intensity was not different.
Acknowledgments
The authors wish to thank the nurses of obstetrics and gynecology wards for data collection, residents and nurses of the anesthesiology department for preparing study solution, and Mr Bryan Roderick Hamman and Mrs Janice Loewen-Hamman for their assistance in the presentation of the manuscript in English.