Abstract
Background:
Simple and efficient way of pain management after Coronary Artery Bypass Graft (CABG) surgery is an important aspect of patients' care.Objectives:
This study aimed to compare the effects of morphine and diclofenac suppositories on postoperative pain management.Patients and Methods:
In this double-blinded clinical trial study, 120 patients aged 30-65 years old, undergone CABG, were equally divided into two groups of A (morphine) and B (diclofenac). All patients were anesthetized with intravenous fentanyl 10 μg/kg, etomidate 0.2 mg/kg and cisatracurium 0.2 mg/kg. Anesthesia was maintained with oxygen 50% and air 50%, propofol 50 μg/kg/min, fentanyl 1-2 μg/kg/h and atracurium 0.6 mg/kg/h. Analgesics were administered after the operation at intensive care unit (ICU) and Visual Analogue Score (VAS) was evaluated in both groups in 4-hour intervals after extubation for 24 hours. After extubation in case of VAS > 3, morphine suppository 10 mg (group A) or diclofenac suppository 50 mg (group B) was administered for patients.Results:
No significant statistical relationship was found between the two groups regarding gender, age, BMI, paracetamol consumption, length of operation time, cardiopulmonary bypass pump (CPB) time, and stay time at ICU (P Value ≥ 0.05). Total dosage of used morphine was 22 ± 8.3 mg in each patient and total dosage of used diclofenac was 94 ± 32.01 mg. Average variation of VAS at measured intervals was significant (P Value ≤ 0.0001), but these variations were not significantly different when comparing the two groups (P Value = 0.023).Conclusions:
Both morphine and diclofenac suppositories reduced pain significantly and similarly after CABG surgery.Keywords
1. Background
Coronary artery bypass graft (CABG) is a common procedure in cardiac surgery. Pain management is one of the most important aspects of postoperative management (1-3). Opening the chest in most patients for CABG requires mid sternotomy. Surgical instruments that expand the chest put pressure on muscles and bones in the operation site. Separating the left internal mammary artery (LIMA) can be extremely painful. Postoperation pain is due to pulling the skeleton muscles or manipulation of parietal pleura, cartilages and periosteum of sternum. In addition, placement of chest tubes at the end of operation can cause postoperative pain. Pain after CABG usually lasts for three days (4). Postoperative pain can stimulate autonomic nervous system resulting in physiological reactions such as increased oxygen consumption of myocardium and myocardial ischemia. Inadequate pain management in ICU can cause restriction of physical movement leading to decreased respiratory activities and undesirable consequences such as pulmonary complication and thrombotic events (5). Pain management not only provides patient satisfaction, but also is important for physicians because of extra physiological benefits. To control postoperative pain, various nonsteroidal anti-inflammatory drugs (NSAID) and opioids are commonly used. Several routes of drug delivery are used including oral, intramuscular or intravenous injection, transdermal patch, patient control analgesia (PCA) or rectal (5-7). Opioids are generally used during and immediately after the operation. Although, opioids are relatively effective, prescribing high dosages of opioids can cause a series of adverse effects such as itching, sedation, nausea, vomiting, respiratory depression and constipation (8). Some surgical centers prescribe NSAIDs as analgesic agent. Immediately after the operation, short-term prescription of NSAIDs in selected patients has been demonstrated to be effective with relatively low adverse effects (5, 7, 8). Diclofenac sodium as a NSAID agent has anti-rheumatic, anti-inflammatory, pain control and some other properties. Despite the fact, it causes platelet, renal and gastrointestinal dysfunction (9). Diclofenac reduces pain and inflammation in surgical site. Diclofenac can be prescribed as 50-100 mg suppository with the maximum dosage of 150 mg per day in two or three divided doses in adults. Quick absorption through rectum has been shown (10, 11).
2. Objectives
Considering the nothing per oral (NPO) restriction for oral medications in early post extubated patients, and since “Epidural Thoracic Catheter” contradicts anticoagulant medications, it is impossible to use invasive pain control measures. Due to unavailability of intravenous forms of certain medications, specifically NSAIDs, and less “first pass effect” of the suppository form of medications compared to the oral form (3), it was decided to compare suppository forms of morphine sulphate and diclofenac to study and compare their efficacy in controlling patients’ pain. In addition to compare pain reduction properties in the both groups, this study aimed to assess undesirable adverse effects in post CABG patients in ICU in the two groups (12, 13).
4. Results
This study was performed on two groups of 60 patients. One group received morphine suppository, and the other diclofenac suppository. Of all patients, 52.5% were male and 47.5% were female. Using Fisher’s exact test, there were no significant statistical differences between male and female patients who received morphine suppository or diclofenac suppository (P < 0.855) (Table 1). Patients’ demographic information was presented in Table 1. Among all patients, 76.7% had CBP time over 60 minutes and 23.3% of the patients had CBP time less than 60 minutes. By using Fisher’s exact test, no significant differences in CBP time were seen between the two groups (P = 0.829) (Table 2). Duration of operation in 48.3% of patients was less than 2.5 hours and in 51.7% was more than 2.5 hours. Fisher’s exact test showed no significant differences in the duration of operation between the two groups who received morphine and diclofenac suppository (P > 0.05) (Table 2). In total, 65% of patients were intubated for less than 8 hours and 35% more than 8 hours in ICU. By using fisher’s exact test, no significant differences in intubation time at ICU were found between the two groups (P = 0.848) (Table 2).
At first in morphine and diclofenac groups, mean values of VAS were 5.85 and 5.18, respectively. These amounts gradually decreased to 2.45 and 2.43, respectively after 24 hours of VAS measurement. Changes in VAS values were approximately similar in the both groups in each time. By using General linear model and repeated measurement, there were significant statistical differences between measured VAS (P < 0.0001, F = 39.32) in the group A. Likewise, there were significant statistical differences between the values of measured VAS in the group B (P < 0.0001, F = 33.43) (Figure 1). In the both groups, significant variations were found in the values of VAS in different periods (intra-group) (Table 3). Variations in VAS averages at different periods did not show significant statistical results (P = 0.203, F = 1.45) in the both groups using general linear model and repeated measurement. It means that average VAS variations in different periods in both groups were not noticeably different and approximately similar (Table 3, indicator 1).
Paracetamol was used once in some patients and 2 or 3 times in some other patients. A small group of patients did not receive paracetamol to relief pain (Table 4). In all patients, pain did not persist after administration of intravenous paracetamol. Therefore, no one needed intravenous morphine in addition to paracetamol. By using Chi-square test, no significant statistical association was found between the groups of A and B when Paracetamol was administered after the removal of chest tube (P = 0.595). In morphine group, 14 (9%) patients experienced some adverse effects. Two patents (3%) had pruritus, treated with chlorpheniramine 10 mg, and four patients (6%) had nausea treated with ondansetron 4 mg IV. There was no adverse effect in diclofenac group. Considering the limitations of using these drugs within a 24-hour period, supplementary use of Paracetamol injection with the dosage of 1000 mg every 8 hours could help manage patients’ pain, between suppository prescription intervals. Statistical results indicated no meaningful differences in the number of times that Paracetamol was administered to the both groups.
Demographic Data of Patientsa
| Group | Morphine | Diclofenac | Total | P Value |
|---|---|---|---|---|
| Gender | 0.855 | |||
| Male | 31 (51.7) | 32 (53.3) | 63 (52.5) | |
| Female | 29 (48.3) | 28 (46.7) | 57 (47.5) | |
| Age, y | 0.917 | |||
| Younger than 50 | 13 (21.7) | 12 (20) | 25 (20.8) | |
| 50-60 | 31 (51.7) | 30 (50) | 61 (50.8) | |
| Older than 60 | 16 (26.7) | 18 (30) | 34 (28.2) | |
| BMI, kg/m2 | 0.431 | |||
| Less than 19 | 2 (3.3) | 0 (0) | 2 (1.7) | |
| 19-25 | 17 (28.3) | 22 (36.7) | 39 (32.5) | |
| 25-30 | 29 (48.3) | 27 (45) | 56 (46.7) | |
| More than 30 | 12 (20) | 11 (18.3) | 23 (19.2) | |
| Total | 60 (100) | 60 (100) | 120 (100) |
Relative Frequency Rate of Cardiopulmonary Bypass Time, Duration of Operation and Intubation Time in ICU Patients in the Two Groups (Morphine and Diclofenac)a
| Group | Morphine | Diclofenac | Total | P Value |
|---|---|---|---|---|
| CPB time | 0.829 | |||
| Less than 60 min | 13 (21.7) | 15 (25) | 28 (23.3) | |
| More than 60 min | 47 (78.3) | 45 (75) | 92 (76.7) | |
| Duration of operation | 1.0 | |||
| Less than 2.5 h | 29 (48.3) | 29 (48.3) | 58 (48.3) | |
| More than2.5 h | 31 (51.7) | 31 (51.7) | 62 (51.7) | |
| Intubation time In ICU | 0.848 | |||
| Less than 8 h | 40 (66.7) | 38 (63.3) | 78 (65) | |
| More than 8 h | 20 (33.3) | 22 (36.7) | 42 (35) | |
| Total in each Group | 60 (100) | 60 (100) | 120 (100) |
Comparison of Visual Analogue Score Changes, Measured in Different Times, in Morphine and Diclofenac Groups
Comparing Mean Values of Visual Analogue Score at Different Times in the Two Groups
| Time | Number of Patients | Mean ± SD | F | P value in Each group | F | P value Between groups |
|---|---|---|---|---|---|---|
| Morphine | 0.0001 | 1.45 | 0.203 | |||
| After extubation | 60 | 5.58 ± 1.8 | 35.13 | |||
| 4th hour | 60 | 3.38 ± 1.71 | ||||
| 8th hour | 60 | 3.18 ± 1.55 | ||||
| 12th hour | 60 | 3.06 ± 1.42 | ||||
| 16th hour | 60 | 3.23 ± 1.33 | ||||
| 20th hour | 60 | 2.66 ± 1.08 | ||||
| 24th hour | 60 | 2.45 ± 0.92 | ||||
| Diclofenac | 37.74 | 0.0001 | ||||
| After extubation | 60 | 5.18 ± 1.83 | ||||
| 4th hour | 60 | 3.16 ± 1.32 | ||||
| 8th hour | 60 | 2.46 ± 0.87 | ||||
| 12th hour | 60 | 2.55 ± 0.99 | ||||
| 16th hour | 60 | 2.85 ± 1.16 | ||||
| 20th hour | 60 | 2.63 ± 1.04 | ||||
| 24th hour | 60 | 2.43 ± 0.85 |
Times of Paracetamol Administration in Morphine and Diclofenac Groups
| Times of Paracetamole Administration | Morphin Supp., No. (%) | Diclofenac Supp., No. (%) | Total, No. (%) | P value |
|---|---|---|---|---|
| No need | 9 (15) | 6 (10) | 15 (12.5) | 0.595 |
| Once | 28 (46.7) | 32 (53.3) | 60 (50) | 0.595 |
| Twice | 20 (33.3) | 21 (35) | 41 (34.2) | 0.595 |
| Three times | 3 (5) | 1 (1.7) | 4 (3.3) | 0.595 |
| Total | 60 (100) | 60 (100) | 120 (100) | 0.595 |
5. Discussion
Effective pain management is necessary to help stimulating adequate breathing efforts and to reduce myocardial ischemic events in post CABG patients. This is essential for patients’ comfort, also warrants physicians' achievement for better physiological outcome (4, 5, 7). Effective pain management is especially important for post CABG patients in ICU, because it can prevent a number of adverse effects, resulting in a shorter stay in ICU, patients' satisfaction, and a smaller economic burden (1, 14). Morphine Sulfate is a narcotic analgesic for controlling moderate to severe pain. Diclofenac sodium, as an NSAID, can also decrease inflammation and alleviate moderate to severe pain due to surgical manipulation (8, 12, 15, 16). In this study, these two drugs were compared to determine their efficacy on post CABG surgery pain. In sonography guided study conducted by Haswir et al. effects of oral morphine and diclofenac suppository on pain management in prostatic biopsy were compared; no meaningful differences were found between the two drugs for pain alleviation (3), which is similar to our study. It could be concluded that morphine and diclofenac reduce pain similarly regardless of the route of administration. In the study conducted by Kulik and colleagues, effectiveness of Naproxen was examined to reduce pain in post CABG patients in ICU. Ninety-eight patients were divided into two groups. One group received Naproxen and the other group placebo. The study showed that Naproxen reduced pain during four postoperative days. They also reported some adverse effects such as nausea, emesis and dyspepsia in diclofenac suppository group (P = 0.034) (15). In our study, no adverse effects were found in diclofenac suppository group. This difference could be due to the duration of using naproxen in Kulik’s study. We used diclofenac for 24 hours. In the study conducted by Khan, diclofenac efficacy was assessed to manage pain and reduce narcotic dosage in post cardiac surgery. Their result indicated that diclofenac suppository together with Tramadol was ideal for post cardiac surgery (6). Besides, use of diclofenac and Tramadol together, reduced the dosage of used Tramadol resulting in less narcotic adverse effects. Goushe et al. conducted a study comparing paracetamol and opioids for reducing pain after laparoscopic cholecystectomy. They mentioned that paracetamol caused better pain relief than opioid in case of mild pain, but paracetamol could not control pain as well as opioid in acute phase after the operation (17). We had similar results in morphine and diclofenac groups. Paracetamol is a weak analgesic compared to diclofenac (morphine was common in the both studies). In Jazayeri et al. study, the effect of intraarticular administration of morphine and tramadol was assessed after arthroscopic knee surgery. They found that these two drugs significantly decreased pain with the maximum effect at six-hour postinjection. Based on the results of our study, morphine suppository could relief pain after CABG. It seems that morphine can reduce postoperative pain effectively regardless of the route of administration (11). This study showed that using either of the suppository drugs, morphine sulfate or diclofenac sodium, in post-surgery CABG patients in ICU, can be effective in pain control. No meaningful differences were found between the two groups. Given the facts, both of these drugs could be prescribed for pain management, and if one group is contraindicated or accompanied with undesirable adverse effects, the other one can be substituted.
5.1. Limitations
Most patients with coronary artery disease have concurrent illnesses, and some of them consume opioids regularly to reduce chest pain. Besides, some patients need emergency CABG surgery. Therefore, all issues mentioned above took time for allocating samples needed for this study.
Acknowledgements
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