The study was a prospective, randomized (simple randomization, computer generated) controlled trial and carried out in the Department of Anaesthesiology between January 2011 to December 2011 at Era’s Lucknow Medical College and Hospital, Lucknow, India.

A total number of 60 adult patients between 18-55 years of age ASA I or ASA II who were scheduled for elective laparoscopic cholecystectomy under general anaesthesia and who were ready to stay in hospital for 24 hours after surgery were enrolled. Pregnant and lactating patients, patients with known allergy to Tramadol or Paracetamol, patients on chronic analgesic medications, patients with significant coronary artery disease or ischemic myocardial disease, drug or alcohol abuse, chronic pulmonary disease, renal failure, hepatic dysfunction, haemorrhagic disorder were excluded from the study.

Necessary approval and clearance for study was obtained from Institutional ethics committee. Informed consent was obtained from all the participants. The patients were randomly divided into two groups, group A (n=30): Comprised of patients who received intravenous Paracetamol (1g in 100 ml solution) and group B (n=30): Comprised of patients who received intravenous Tramadol (100 mg in 100 ml NS)

All the patients were visited the night before surgery. They were kept nil orally overnight. The patients were given Tab. Alprazolam (Alprax) 0.25 mg a night before surgery and two hours prior to surgery with a sip of water.

On arrival of patients to the operation theatre, intravenous line was initiated with 18G cannula. Preoperative recording of Heart Rate (HR), non invasive blood pressure (SBP, DBP, MAP) and arterial oxygen saturation (SpO₂) was carried out. All patients were premedicated with inj. Metoclopromide 10 mg and inj. Fentanyl (2 μg/kg) intravenously. All the patients were preoxygenated with 100% oxygen for 3 minutes. Induction of anaesthesia was carried out with inj. Propofol 2 mg/kg intravenously. Endotracheal intubation was facilitated with a paralyzing dose of inj Atracurium 0.5 mg/kg intravenously. Anaesthesia was maintained with oxygen-40%, nitrous oxide- 60% delivered through Bain’s circuit using IPPV and a continuous infusion of inj Propofol (150 mcg/kg/min).

Muscle relaxation was maintained with intermittent doses of atracurium in aliquots of 0.1 mg/kg intravenously. At the conclusion of surgery residual muscle paralysis was reversed with inj. Neostigmine 50 μg/kg and inj. Glycopyrrolate 10 μg/kg intravenously. The patients were extubated following return of regular, rhythmic respiration when reasonably awake, after a gentle oral suction.

The parameter recordings included Etco₂, Heart Rate (HR), oxygen saturation (SpO₂), Systolic Blood Pressure (SBP), Diastolic Blood Pressure (DBP) and Mean Arterial Pressure (MAP) perioperatively.

Initial dose of analgesic (either Tramadol 100 mg intravenous or Paracetamol 1g intravenous) was given to the patients in the postoperative period when the pain intensity, as observed on the VAS, showed a score >5. Thereafter, Tramadol 100 mg or Paracetamol 1g intravenous infusion was given at 6, 12 and 18 hours.

Pain intensity was measured based on a 10 point Visual Analogue Scale (VAS; 0-10 cm; 0= no pain and 10= worst imaginable pain).

VAS pain scores were obtained postoperatively at: just before analgesic administration (T0), 0.5 hours (T1), 1.5 hours (T2), 3 hours (T3), 6 hours (T4), 12 hours (T5), 18 hours (T6) and 24 hours (T7).

Any pain score above 5 on VAS was considered a breakthrough pain. It was managed by rescue analgesia with intravenous Diclofenac sodium 1.5 mg/kg, repeated as required. The patient having breakthrough pain were not included in the study but records were kept for comparison.

The observations made during above study were recorded on a proforma and the results obtained were analysed by appropriate statistical tests such as Chi-square test, Student’s t-test and p <0.05 was considered significant.

Baseline data of both the groups were matched for age, weight, height, BMI and gender [Table/Fig-1].

At baseline (T0), mean SBP in Group A was 131.60±8.46 mm of Hg as compared to 131.73±9.20 mm of Hg in Group B, showing the ‘between group’ difference not to be significant statistically (p=0.954). At T1, mean SBP in Group A was 126.40±10.92 mm of Hg as compared to 126.00±10.69 mm of Hg in Group B. At T2, both the groups showed a slight decrease in mean SBP, 123.17±7.92 (Group A) and 124.20±8.76 (Group B). This was followed by an increase in both the groups at T3 and T4 intervals. At T5 interval, both the groups showed the mean SBP values close to baseline values, followed by a slight increase at T6 interval which remained almost stabilized at T7. At T7, mean SBP in Group A was 127.47±6.26 mm of Hg as compared to 128.87±9.16 mm of Hg in Group B. At none of the time intervals, the difference between two groups was significant statistically (p>0.05) [Table/Fig-2].

For DBP- At baseline (T0), mean DBP in Group A was 79.40±6.83 mm Hg as compared to 78.83±8.31 mm Hg in Group B. At T1 mean DBP in Group A was 78.13±5.74 mm of Hg as compared to 78.03±5.60 mm of Hg in Group B. At T2, both the groups showed a slight decrease in mean DBP to reach at 75.37±7.62 (Group A) and 75.40±7.75 (Group B). At T3, a further decrease in mean DBP was observed, taking the mean value in Group A to 71.38±10.72 mm of Hg as compared to 73.97±8.12 mm of Hg in Group B. This was followed by an increase in both the groups at T4 interval followed by a decrease at T5 and T6 intervals. At T6 interval, both the groups showed the mean DBP values close to baseline values followed by a slight increase at T6 interval which remained almost stabilized at T7. At none of the time intervals, the difference between two groups was significant statistically (p>0.05) [Table/Fig-3].

As compared to baseline, mean change in heart rate was maximum at T4 interval in Group A and T5 interval in Group B. In Group A, at all time intervals, except at T4 and T5, mean heart rate was lower as compared to baseline but it was significant statistically only at T1. At T4 and T5 intervals, in both the groups, mean heart rate was significantly higher as compared to baseline. In Group B, mean heart rate was lower than baseline only at T1 interval and the difference was significant (p=0.005). At all the other intervals, mean heart rate was higher than baseline, but the increase was significant statistically only at T4, T5 and T7 intervals [Table/Fig-4].

At baseline (T0), mean VAS score in Group A was 6.30±0.99 as compared to 6.20±1.30 in Group B, thus showing no significant difference between the two groups (p=0.738). However, at T1 and T2, mean VAS score in Group A (3.10±0.61 and 2.53±0.63 respectively) was significantly lower as compared to that in Group B (3.47±0.51 and 3.03±0.93 respectively). At T3, mean VAS score in Group A (3.03±0.67) was lower as compared to that in Group B (3.23±0.77) yet the difference was not significant statistically (p=0.289). At all the other time intervals, Group A had mean VAS scores lower than Group B, but the difference was not significant statistically at T6 and T7 intervals (p>0.05) [Table/Fig-5].

None of the patients in either group required rescue analgesic. Only one (3.3%) case in Group B complained of nausea and vomiting. The patient was managed with inj Ondansetron 4 mg i.v. No other side effect was noticed in either of the two groups.

Postoperative pain management is one of the most important and an ever challenging task for an anaesthesiologist. Postoperative pain is variable in duration, intensity and character and is the main factor delaying discharge of patients undergoing day-care procedures including laparoscopy and hence adding to the hospital cost. Pain after laparoscopic surgery may vary in quality and localization and is reported in several trials to be incisional, intra-abdominal, or referred (shoulder tip). The aetiology is complex, it could be due to damage to abdominal wall structures, visceral trauma, inflammation [4,11] or peritoneal irritation because of carbon dioxide entrapment beneath the haemidiaphragms [12].

Generally, NSAIDs and opioids are administered for postoperative pain management, however, owing to their controversial results [5,13] they are losing their value as a drugs of choice. Paracetamol, a non-opioid has emerged to be effective, which leads to faster recovery in patients undergoing laparoscopic cholecystectomy [6,8,9] while tramadol which has agonist actions at μ- opioid receptors also gained momentum owing to its central analgesic effect and weak opioid agonistic properties [14].

In the present study, a comparison of analgesic effect and side effects of intravenous infusion of paracetamol and intravenous infusion of tramadol was carried out for postoperative pain relief in patients undergoing laparoscopic cholecystectomy under general anaesthesia.

Blood pressure levels as well as heart rate in both the groups were comparable throughout the study period, though a decrease in blood pressure levels and heart rate was observed in early follow up intervals at 30 min, 1.5 hour and 3 hour time intervals. The initial high scores of haemodynamic parameters could be a result of post-surgical stress response. Although operative stress response is much reduced in laparoscopic cholecystectomy, yet postoperative pain itself is accompanied with a stress response [15].

Although tramadol has been reported to reduce blood pressure and increase heart rate in some cases [16] yet in present study though the blood pressure lowering effect of tramadol was observed in the early intervals itself, the increase in heart rate was observed from 1.5 hour interval only. However, the increase in haemodynamic parameters at 6 and 12 hours intervals could be attributed to return of pain as the blood levels of the drugs decline with time.

Studied done earlier on postoperative pain management using Tramadol and Paracetamol have not reported any significant clinical impact of these two drugs on haemodynamics [17–20].

In a study conducted by Shabir et al., one group received Bupivacaine (0.5%) 20ml, instilled in gallbladder bed and the undersurface of diaphragm and infiltration of port wounds [21]. In other group, Tramadol (100mg) was given Intramuscularly (IM) at the completion of elective laparoscopic cholecystectomy. The assessment of postoperative analgesia was done using Visual Analogue Scale (VAS) at hourly intervals for first four hours and then 24 hours also. Vital signs like Spo₂, HR, NIBP, RR were recorded six hourly for 24 hours postoperatively. Tramadol group had better analgesic effect as compared to Bupivacaine group.

In the present study, both the drugs showed effective control on pain scores in short time only. It was observed that mean scores indicative of acute pain (VAS score ≥5) were brought down to mild or bearable pain (VAS score ~3) within 30 minutes of administration showing a significant change from baseline. However, paracetamol group showed a better efficacy as compared to tramadol group for most of the follow-up intervals being studied. By 18 hour and 24 hour both the groups had pain scores indicative of mild nature of pain (VAS scores ~ 2).

Study done on oral acetaminophen plus IV propacetamol and oral Tramadol plus IV Tramadol, when compared pain management after tonsillectomy [22] found that the side effects of nausea and vomiting were comparable between the two groups, pain relief was higher and need for rescue medication was less in the Tramadol group. In our study only one episode of nausea and vomiting was noticed in Tramadol group and this was not statistically significant.

Given below in the table are the studies comparing different drugs as pain relief measure in patients undergoing surgeries and their outcome [Table/Fig-6].

In our study, paracetamol proved to be having superior pain control as compared to tramadol in terms of difference in mean VAS scores, however, as far as rescue analgesia was concerned, none of the patients in either group required rescue analgesic. Thus both tramadol and paracetamol were comparable and could be effectively used as postoperative pain management measures in laparoscopic cholecystectomy.

During postoperative follow-up intervals, paracetamol showed significantly lower VAS scores as compared to Tramadol at 1.5 hour, 3 hour, 6 hour, 12 hour and 24 hour follow up intervals, patient’s satisfaction was also found more in Paracetamol group.

Paracetamol is antipyretic and analgesic but has little, if any, anti-inflammatory action. Its analgesic efficacy is not more than that of traditional analgesics; however, it has fewer side effects. It has been seen to inhibit COX-3 and at spinal cord level it antagonize neurotransmission by NMDA, substance P, and nitric oxide pathways [29]. Optimal analgesia for moderate to severe postoperative pain cannot be achieved using a single agent alone, but a balanced approach in combination with non-steroidal agents can result in up to a 40 to 50 percent reduction in opioid requirements.

Paracetalmol with its safety profile can prove to be an asset in managing perioperative pain, especially of mild to moderate severity [29].

IV Propacetamol (1g), a prodrug of acetaminophen, has been shown to be as efficacious as intramuscular morphine (10 mg) following dental extractions [30] and as effective as intramuscular Ketorolac (30 mg) following lower limb arthroplasty [31].

Given the mild to moderate profile of laparoscopic cholecystectomy pain after 24 hours, the utility of analgesics capable of controlling the postoperative pain to that level and up to the required period of time, but with fewer side effects is a promising finding. In the present study, except three cases, none of the cases had VAS pain score above 3 after initial dose of analgesia with either of the two drugs in the 24 hour interval and no side effect was reported in Paracetamol group.

The findings in the present study will pave way for further work on the issue. More studies on use of drugs with less side effects and optimum analgesic efficacy are recommended.

Limitations of our study was small sample size, lack of placebo arm, and these were reasons we could not draw further conclusion.

On the basis of present study both Paracetamol and Tramadol were found to be safe and comparable in postoperative pain management though Paracetamol showed better results in terms of significantly lower mean VAS pain scores for most of the postoperative follow-up intervals. Thus intravenous infusion of Paracetamol can safely and effectively be recommended for postoperative pain relief in patients undergoing laparoscopic cholecystectomy.