Therapeutic Effects of Rectal Diclofenac Sodium and Intramuscular Pethidine Injection in The Treatment of Acute Renal Colic: A randomized Clinical Trial
Mohammad Mehdi Hosseini, Abdoul-Rasoul Ebrahimi
Renal colic is a type of abdominal pain commonly caused by obstructive stones. The aims of this study were to evaluate safety and efficacy of rectal diclofenac sodium ( RD ) in acute renal colic and compare it with intramuscular pethidine (IMP) injection. In an interventional prospective double blind randomized control trial with 541 patients, which referred to Emergency Department due to acute renal colic, RD and IMP were administrated to 266 patient (as group I) and 275 patients (as group II), respectively. Pain relief was measured through asking the patient by the physician at 10, 20 and 30 min after using of respective drugs in each group. In group I, analgesic effects of RD were appeared in 121 patients (45.5%) after 10 min, 191 patients (71.9%) after 20 min and 233 patients (87.5%) after 30 min. 33 patients (12.5%) had no response to RDS . In group II, analgesic effects of IMP were appeared in 123 patients (44.7%) after 10 min, 191 patients (69.5%) after 20 min and 254 patients (92.3%) after 30 min. 21 patients (7.7%) had no response to IMP. Our results demonstrated that although, there were no significant differences in analgesic effects between two drugs (P=0.06), but, due to availability, cheapness, safety and self administration properties, use of sodium diclofenac in suppository form is highly recommended in renal colic.
Keywords: Renal colic; diclofenac sodium; pethidine; analgesia.
Renal colic is a common urological emergency at the emergency department, often caused by the movement of ureteral stones and characterized by severe pain. Patients describe this pain as the most severe and excruciating situation ever experienced (Ay et al. 2013). This condition afflicts 5aˆ?12% of the population in industrial societies at least once in their life time and its recurrence rate is approximately 50% (Esmailian and Keshavarz 2014). The pain is usually attributed to contraction of ureter soft muscles in response to the presence of stone (Holdgate and Pollock 2004). Therefore, the most important consideration in the emergency management of renal colics is pain control/relief (Esmailian and Keshavarz 2014).
Both parenteral opioids and nonsteroidal anti-inflammatory drugs (NSAIDs) are commonly used to provide relief from renal colic (Bektas et al. 2009). For relieving this pain, morphine and pethidine in the traditional approach were used, but, due to their side effects such as addictive effects, constipation, respiratory depression, and mental changes,, using of them is reduced and replaced by NSAIDs (Kalb et al. 2010; Muslumanoglu and Tepeler 2008). Experimental works suggest that prostaglandins (PGs) play an important role in producing pain in renal colic and therefore, antiprostaglandins can eliminate or diminish this type of pain (Hetherington and Philp 1986; Thompson et al. 1989).
Diclofenac, 2-(2-(2,6-dichlorophenylamino)phenyl)acetic acid, is an NSAID taken or applied to reduce inflammation and as an analgesic reducing pain in certain conditions such as renal colic. The exact mechanism of action is not entirely known, but the primary mechanism responsible for its analgesic action is thought to be inhibition of PG synthesis by inhibition of cyclooxygenase, one of the basic enzymes in the PG synthesis pathway (Dutta et al. 2000). On the other hand, pethidine is a once popular synthetic opioid analgesic of the phenylpiperidine class (MacPherson and Duguid 2008). The specific adverse event of vomiting showed a clear association with opioids, in particular pethidine. Although no studies reported serious adverse events, the short follow-up period and failure to specifically record renal dysfunction and gastrointestinal bleeding means these results should be interpreted cautiously (Holdgate and Pollock 2004). Given these findings, when a single bolus of analgesia is used, an NSAID rather than an opioids was recommended. However, in some condition such as severe pain using of opioids is inevitable. Therefore, in this study, we compared the efficacy of analgesic therapy of rectal diclofenac sodium (RD) and intramuscular pethidine (IMP), commonly preferred in emergency departments in our country in patients with renal colic.
Participants and Methods
A. Patients and study design
An interventional prospective multicenter double blind randomized control trial (RCT) with five hundred forty one eligible patients which had renal colic and referred to Motahhary and Peymanieh Hospitals of Jahrom and Faghihi and Nemazee Hospitals of Shiraz between Dec 2005 to Apr 2007 was done. The study protocol and informed consent were approved by the Ethics Committee at Jahrom University of Medical Sciences. All patients who enrolled in this study, were read, accepted and signed the consent form. Participant, with age between 17 to 52 years, randomly allocated in two parallel groups, RD (single dose of 100 mg) and IMP (single dose of 50 mg) in the approximately ratio of 1:1 (266 and 275 patients, respectively). Randomization was performed using a computer-generated random permuted block method. Patients with history of allergy to NSAIDs, hemorrhoids and anal fissures, peptic ulcers, coagulopathy, inflammatory bowel disease, pregnancy, ischemic coronary diseases, chronic obstructive pulmonary disease, and liver or renal failure were excluded from the study.
B. Method of measurement
Subjects reported pain and its decline at 10, 20 and 30 min after drug receiving and according to significant decrease in pain intensity at each time (decrease in pain intensity more than 50%), the patient was placed in the respected groups. Subjects were blind to their previous reports. Our outcome measure was the change in pain intensity at 10, 20, 30 and more than 30 min. The participants that enrolled in group 3 (significant decrease in pain after 30 min) were composed from patient in group 1 (significant decrease in pain after 10 min) and 2 (significant decrease in pain after 20 min) and there was similar pattern between group 2 and 1.
C. Statistical analysis
SPSS for Windows version 16 package program was used for statistical analysis of the data.
t test and analysis of variance were used for analysis of variables. Results were expressed as n (number of patients), and percentage (%). According to the results, a P value <0.05 was considered statistically significant.
Our patient consisted of 351 men (64.9%) and 190 women (35.1%) that devided between two treatment groups. Percentage of patients which responded to each drug are presented in Figure 1. Although, the number of patients which responded to IMP were higher than RD, but, this difference was no significant (P>0.05). Distribution of patients according to time of responding to analgesic effects of RD and IMP is displayed in Figure 2. According to these data, the percentage of patients that showed defined decline in pain at 10 and 20 min after using of drug in RD was higher than IMP. However these differences were not significant (P=0.06).
In this study, the analgesic efficacy of rectal sodium diclofenac and intramuscular pethidine administration in patients which suffered from renal colic were evaluated. Our results demonstrated that although, the percent of patients with diminished pain in 10 and 20 min after using of RD was higher than IMP but, this difference was not significant. Therefore, the efficacy of these two drugs is similar. However, due to availability, cheapness, safety and self administration properties, use of RD is highly recommended in renal colic in compare to IMP. In two previously studies, the efficacy of using of sodium diclofenac versus pethidine in acute renal colic were evaluated and reported. In the study of Hetherington and Philp (1986) on 58 renal colic patients, it has been concluded that 75 mg of sodium diclofenac, IM, was more effective than 100 mg of Pethdine, IM, in the management of acute renal colic and has fewer side effects (Hetherington and Philp 1986). Also, Thompson et al (1989) reported that diclofenac suppositories provided potent, specific analgesia in renal colic. They also concluded that, diclofenac is superior to pethidine, because its effect starting at a similar time but lasting longer (Thompson et al. 1989).
On the other hand, this fact that diclofenac can be self administered and is not an opiate makes it a useful drug in general practice, especially for patients with recurrent renal colic. Pethidine as a synthetic opioids, is about one tenth as potent as morphine and due to having more lipid solubility than morphine, elimination half life of two to four hours and duration of action of only two to three hours were considered for it (Foley 1985). At 2000, in a double blind RCT, analgesic efficacy, patient satisfaction and side effects of morphine and pethidine in patients with clinically suspected renal colic were evaluated. Although, their data demonstrated that there was no significant difference between morphine and pethidine with respect to any of the parameters measured, but they concluded that because of the well known adverse effects that may be associated with pethidine use, morphine should be the preferred agent in suspected renal colic, when an opioid analgesic is to be used (O’Connor et al. 2000). In addition, it has been reported that norpethidine, the predominant metabolite of pethidine, is potentially toxic and causing central nervous system excitability such as tremors, myoclonus or seizures. Also, accumulation of norpethidine has also been seen in patients with normal kidneys, particularly with large doses or frequent dosing intervals (Marinella 1997).
Finally, due to adverse effects of pethidine and its metabolite, norpethidine and also due to possibility of pethidine addiction, we believe that diclofenac suppositories should be considered as the first line treatment of renal colic, both in hospital and in general practice.
The authors thank the staff physians and nursing team of the Emergency Department of the Motahhary and Peymanieh Hospitals of Jahrom and Faghihi and Nemazee Hospitals of Shiraz and all other people who help in this study.
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Figure 1. Number and percentage of patients which response/non response to rectal sodium diclofenac and intramuscular pethidine.
Figure 2. Comparison on the efficacy of rectal sodium diclofenac and intramuscular pethidine in attenuating of renal colic pain.