Pain is an emotional experience and discomfort the patient feels due to organ or tissue damage. There are two types of pain- somatic and visceral. Somatic pain originates from the musculoskeletal system or skin. Visceral pain originates from internal organs and blood vessels. Pain causes poor wound healing and leads to several complications causing chronic pain syndrome.  Even though every individual has a similar pain pathway, the pain tolerance is not up to the same degree. Pain tolerance is affected by age, gender, socioeconomic life, and past experiences. Poorly controlled acute postoperative pain may result in significant complications due to substantial clinical and psychological changes like anxiety, depression, deep vein thrombosis, infections, shock, pulmonary embolism, urinary retention, cardiac problems, pneumonia, etc.1,2,3

Treatment of acute postoperative pain, before it turns into chronic postoperative pain, is necessary for improved outcomes. To provide better pain management, a comparison of different analgesics can show how they work to decrease pain levels.  The first choice of analgesics are opioids and nonsteroidal anti-inflammatory medications. The most commonly used analgesics are Tramadol, Aceclofenac, and Paracetamol, and combinations of different analgesics are known for their effectiveness in reducing pain.  Ideal pain management in the postoperative period is based on dose frequency, route of administration, and type of analgesia.4,5

Opioid analgesics include alkaloids, semisynthetic and synthetic derivatives. Among all morphine and tramadol are mostly used analgesics. Tramadol is mostly preferred to morphine due to its dependence properties.6,7 Tramadol is a centrally acting, atypical opioid analgesic with a dual mechanism of action. It is an opioid agonist and inhibitor of norepinephrine and serotonin reuptake and increase in serotonin release. Thus, tramadol activates monoaminergic spinal inhibition of pain. The analgesic effect of tramadol is believed to be due to both binding to μ-opioid receptors and weak inhibition of re-uptake of norepinephrine and serotonin.8   Tramadol is indicated for mild-to-moderate short-lasting pain due to diagnostic procedures, injury, surgery, etc, and for chronic pain. Tramadol is useful in patients with poor cardiopulmonary function, including the elderly, the obese, smokers, in patients with impaired hepatic or renal function, and in patients in whom nonsteroidal anti-inflammatory drugs are not recommended or need to be used with caution.9 Adverse effects of Tramadol are insignificant respiratory depression, constipation, or urinary retention. Side effects are sleepiness, dry mouth, adrenal insufficiency, mania, sweating, and lowering of seizure threshold, therefore contraindicated in epileptics.10-14

Paracetamol is a synthetic, non-opioid, centrally acting analgesic. It is the most commonly used and safest analgesic medicine. Paracetamol is most frequently taken for self-medication, because of its low cost and availability without a prescription. It may avoid the use and undesirable side effects of opioids. Paracetamol is also a good and promptly acting antipyretic without significant anti-inflammatory action. A4nalgesic action of paracetamol has been attributed to its inhibition of the cyclooxygenase (COX) pathway in the central nervous system, reducing the production of pain-mediating prostaglandins.15 Paracetamol selectively inhibits COX-2 in the central nervous system, unlike non-steroidal anti-inflammatory drugs that inhibit both COX-1 and COX-2. It also modulates descending serotonergic inhibitory pathways enhancing cannabinoid transmission.  It is metabolized to N-arachidonoylphenolamine (AM404), that acts on the transient receptor potential vanilloid 1 (TRPV1) and cannabinoid 1 receptors in the brain, leading to analgesia.16 the onset and duration of the analgesic action of paracetamol varies with the route of administration. Paracetamol can be used in all age groups (infants to elderly), pregnant/lactating women, and in the presence of other disease states as it has no drug interactions. It is also used in combination with other medications such as opioids and non-steroidal anti-inflammatory drugs for managing pain and inflammation associated with various conditions. Paracetamol is not recommended in premature infants for fear of hepatotoxicity. Adverse events caused by paracetamol are usually mild, transient, and comparable in frequency to placebo. Acute paracetamol poisoning occurs especially in small children who have low hepatic glucuronide conjugating ability.17

Multimodal analgesia helps to achieve an effective analgesic action by limiting the dosage and minimizing side effects.18-21 It also beneficial for decreases the dose of the drug. Co-administration of drugs helps increase in safety and efficacy of drugs. Tramadol–Paracetamol coadministration is one of the proposed methods in postoperative multimodal analgesia in the era of the opioid epidemic. In postoperative pain management, Tramadol monotherapy does not usually provide adequate analgesia, but in coadministration with Paracetamol, it can be highly effective. Tramadol–Paracetamol coadministration has a supra-additive efficacy in preventing hyperalgesia, and as Tramadol and Paracetamol doses in the commercial combination products are relatively low, they are commonly well tolerated. The Tramadol–Paracetamol combination product has analgesic efficacy in patients with both subacute and chronic pain and is effective in sustaining these patient’s physical functioning and quality of life. Aceclofenac-Paracetamol coadministration is presence of the two most popular and effective medicines making these drugs effective in lowering body temperature as well. It works on the same principle inhibiting enzymes causing pain, inflammation, and fever. The dose of this multimodal analgesia should follow the prescription and people with pre-existing medical conditions should be careful with the intake of this combination of drugs. The Aceclofenac-Paracetamol combination product is beneficial in reducing and subsiding some side effects.22,23

Synergic and Additive effects are produced by administration of opioid and non-opioid substances that act on distinct sites. These strategies decrease postoperative morbidity and mortality. Rational postoperative pain management is beneficial to achieve satisfaction in patients who are in the hospital or at home and unable to carry out normal activities for a minimal amount of time.

In our study, we adapted multimodal analgesia in the combination of opioid and non-opioid analgesics (Tramadol with Paracetamol and Aceclofenac with Paracetamol), to compare the safety and efficacy of the combination of analgesics among patients who are in postoperative period.

AIM & OBJECTIVES

 AIM:

• To compare the safety and efficacy of Aceclofenac with Paracetamol versus Tramadol with Paracetamol.

OBJECTIVES

To study:

• Safety of Aceclofenac with Paracetamol.
• Safety of Tramadol with Paracetamol.
• Efficacy of Aceclofenac with Paracetamol.
• Efficacy of Tramadol with Paracetamol.

This is a comparative study in which postoperative patients in the Department of General Surgery were included from October 1st, 2024, to November 10th, 2024. This study was done according to the declaration of Helsinki. The patients are enrolled after obtaining the informed consent. Patients who gave consent were randomized into 2 groups based on a simple randomization sampling. Group A patients were given Aceclofenac (100mg) and Paracetamol (325mg) orally. Group B patients were given Tramadol (37.5mg) and Paracetamol (325mg) orally. For both Groups of patients, Paracetamol is commonly administered after surgery. Patients of Group A received Aceclofenac immediately after recovery from anesthesia. Patients of Group B received Tramadol immediately after recovery from anesthesia (5-6 hrs).

Pain was assessed using Visual analogue scale (VAS).  Patients are evaluated after 5-6 hours after post-operation. The first dose of prescribed analgesic is usually given at the 6^th hour after surgery. Further, pain readings are taken every hour up to the 12^th hour. Next, pain readings are taken every third hour up to the 24^th hour after surgery. The decrease in the severity of pain with the use of medications was analyzed using a visual analogue scale. Vitals were monitored simultaneously. Adverse effects were documented and analyzed using the World Health Organization's causality assessment scale. Readings for pain severity on the visual analogue scale range from 0 to 10.

STATISTICAL ANALYSIS:

It was done after entering data into Microsoft Excel. Analysis was done using SPSS 17.0

ETHICAL ASPECTS:

Institutional ethics approval (IEC- GMC-ONG/232/2024) dated 19 OCT 2024, was taken before starting the study. Informed consent was taken from every participant.

87 patients participated in the study, out of them males were 70.11% and females were 29.89%.

DEMOGRAPHY AND HEMODYNAMIC PARAMETERS

Patients of the age group from 18 to 90 were taken into the study.

Patients belonging to Group A had a mean heart rate (HR) of 76.48 bpm and patients belonging to Group B patients had a mean HR of 76.20 bpm. No significant difference was seen between groups(p>0.05). Patients of Group A had a mean systolic blood pressure (SBP) of 126.7 mm of Hg and patients of Group B had a mean SBP of 124.3mm of Hg. No significant difference was seen between groups(p>0.05).

 Group A patients had a mean diastolic blood pressure (DBP) of 83 mm of Hg and patients of Group B had a mean DBP of 81.3 mm of Hg. No significant difference was seen between groups(p>0.05).

 Patients of Group A had a mean respiratory rate (RR) of 17.7 per minute and patients of Group B had a mean RR of 17.9 per minute. No significant difference was seen between groups(p>0.05).

A comparison was done between groups as follows:

Table 1: Comparison of demography and hemodynamic parameters

SURGERIES:

4 Anal surgeries were done which include Anal fistula (3) and Internal anal sphincterotomy (1).  10 Bowel surgeries were done which include Ileostomy closure (2), Small bowel obstruction (3), Large bowel obstruction (1), Distal gastrectomy (1), and Exploratory laparotomy (3). 2 Diabetic foot surgeries were done including Diabetic foot with wet gangrene (2).  6 Fracture surgeries were done which included Discectomy (3) corpectomy & fixation (1), C5-C6 dislocation (1), and C7 transverse process fracture (1).  5 Gall bladder surgeries were done which include Cholecystectomy (3) and Cholelithiasis (2).  9 Inguinal hernia surgeries were done which include Direct inguinal hernia (5), Indirect inguinal hernia (3) and Obstructive inguinal hernia (1).

Table no.2: Diabetes Mellitus & Hypertension

SOCIAL HABITS: Smoking was seen in 12.64%, Alcohol consumption in 13.79%, and Betal nut chewing in 2.30% of patients.

VISUAL ANALOGUE SCALE READINGS:

In all 87 patients after administrating of respective drugs, their mean values of pain readings for respective hours were calculated using the Visual Analogue Scale.

Table no.3: Mean values of Visual Analog Scale

At every time point, pain scores were assessed by a visual analog scale the mean VAS scores were numerically lesser in Group A (Aceclofenac + Paracetamol) but the difference was not found to be statistically significant.

87 patients participated in the study and out of them males were 70.11% and females were 29.89%. Out of the patients belonging to Group A are 43 and patients belonging to Group B are 44 in the current study.

According to the study done by Kamtane et.al on the safety and efficacy of tramadol compared to diclofenac in relieving postoperative pain, males had a predominant predisposition of 72.5% and females were 27.5%.24 According to the study done by Chandanwale et.al, males had a predominant predisposition of 61.76% and females had 38.24%.6

According to the study done by Sharma et.al on the tramadol-paracetamol combination for postoperative pain, males and females are almost equal in distribution.25

Patients of the age group 41 to 60 have undergone the most surgeries in the current study.

According to the study done by Kamtane et.al, most of the surgeries were done in the age group was 35 to 45 years. 24

According to the study done by Uztüre et.al on tramadol versus tramadol with paracetamol for the efficacy of postoperative pain management, most surgeries were done in the age group 32 to 58 years.26

According to the study done by Chandanwale et.al, most of the surgeries were done in the age group 40 to 60 years.6

 According to the study done by Sharma et.al, most of the surgeries were done in the age group 35 to 60 years.25

There is no significant difference in HR and RR between groups in the current study.  According to the study done by Chandanwale et.al, the mean heart rate was 78.52 ± 6.98 for the tramadol-diclofenac group and 77.24 ± 6.17 for the tramadol-paracetamol group.6

 Patients belonging to Group A have a Mean respiratory rate of 17.790 and patients belonging to Group B have a Mean respiratory rate of 17.97. No significant difference in the Mean Respiratory Rate was observed in the current study.

In the study of Chandanwale et.al, the mean SBP was 119.49 ± 11.86 for the tramadol-diclofenac group and 118.50 ± 12.77 for the tramadol-paracetamol group.6

 This study showed there is not much difference of both drugs in decreasing pain score during the first 24 hours of the postoperative period. There is a gradual decrease in pain statistically similar in both groups. At every time point, pain scores were assessed by a visual analogue scale the mean VAS scores were numerically lesser in Group A (Aceclofenac + Paracetamol) but the difference was not found to be statistically significant.  This infers that both the treatments Aceclofenac + Paracetamol and Tramadol + Paracetamol were equally efficacious in treating post-operative pain. Many studies of a combination of analgesics showed a statistically insignificant reduction of pain.

According to the study done by Kamtane et.al, the mean pain score at baseline was comparable in both the drug groups. The pain score decreased significantly in both the study groups over the postoperative period up to the 7th postoperative day.25

 In the present study, pain scores were evaluated only 24 hrs postoperatively and a decrease in the mean VAS scores was observed among both groups during the first 24 hours of the postoperative period.

In the study by Uztüre et.al, mean NRS scores in both groups were low and statistically different beyond postoperative 2 hours.27

 In the present study, VAS scale was utilized to evaluate pain scores, and there was statistically insignificant difference among two groups.

According to the study done by Shukla AK et.al on a comparison between tramadol and diclofenac as analgesics for postoperative pain, based on the VAS scale the mean value of the VAS scores at 24 hours using tramadol is 2.5 ± 0.24, and using diclofenac is 2.01 ± 0.10.27

According to the study done by Sharma et.al, based on the VAS scale the mean value of the VAS scores using tramadol-paracetamol combination at one minute was 0.30 ± 0.83, at 30 minutes 0.13 ± 0.51, at 1 hour 0.07 ± 0.25, at 2 hours 0.17 ± 0.64, at 3 hours 1.43 ± 1.01, and at 4 hours 3.50 ± 0.57. The observer compared the use of the tramadol alone and in combination with the paracetamol 30 minutes before the end of surgery.25

According to the study done by Rama Paudel et.al, based on the VAS scale, the mean value of the VAS scores using tramadol at baseline value is 6.90 ± 0.49, at 24 hours is 3.85 ± 0.47, and using diclofenac at baseline value is 6.70 ± 0.53, at 24 hours is 4.17 ± 0.47.28

According to Chandanwale et.al, the adverse effects were mild to moderate, with self-limiting nausea and vomiting being the most common. In the present study, no adverse drug events were experienced.6

According to a study done by Kamtane et.al. in the Diclofenac group, only one patient experienced the adverse effect of epigastric pain, whereas, in the Tramadol group, two patients complained of vomiting and one patient complained of vomiting associated with headache. 24 In the study done by Sunita Sharma et.al, The combination of low-dose tramadol and paracetamol was found to provide comparable analgesia and decreased incidence of nausea and vomiting compared with the higher dose of tramadol and paracetamol combination.25 In the study done by Rama Paudel et.al, no serious adverse effects were observed in either of the treatment groups in their study. Only a few minor side effects noted may be due to an assessment of adverse effects over a short period of our study time.28

Limitations of the study:

• Small sample size due to less span of the study duration.
• Only the VAS scale is used to assess pain, by comparing it with other pain scoring scales like the NRS scale, VRS scale, and McGill Pain Questionnaire, etc., can be used for assessment of pain.
• Quality of sleep among the drugs is not evaluated.
• This study was single-blinded, double-blind or triple-blinded comparisons would give more appropriate results.
• Use of analgesics 30 minutes before surgery was not done, which might affect the study results.

Aceclofenac + Paracetamol (100/325mg) orally and Tramadol + Paracetamol (37.5/325mg) orally were used to evaluate pain by using the visual analog scale in this study. The mean VAS scores were lesser in Group A (Aceclofenac + Paracetamol) but the difference was not found to be statistically significant.  This infers that both the treatments Aceclofenac + Paracetamol (100/325mg) orally and Tramadol + Paracetamol (37.5/325mg) orally were equally efficacious in treating post-operative pain. Postoperative pain should be managed effectively and quickly to reduce the patient’s discomfort by providing early recovery and quality postoperative period by avoiding complications. Along with better emergency surgical care, qualitative perioperative care must be provided.

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