European Journal of Cardiovascular Medicine

Pain relief in the postoperative period is to be considered a basic human right. Pain is the commonest reason for admission to the emergency department. Acute pain following surgery constitutes a major distress experienced by the patient. It is thought that pain is inadequately treated in half of all surgical procedures.¹ Surgical trauma induces sensitization of both central and peripheral nociceptors and hyperalgesia.² Inadequately treated acute postoperative pain has many negative consequences on patients both physiological and psychological life. It not only affects the patient’s well-being and surgical outcome but also has various systemic complications like the development of tachycardia, hypertension, inadequate ventilation, poor wound healing, impaired sleep and development of chronic pain.^3,4 In fact, postoperative pain is one of the most common reasons for the delay in discharge after ambulatory surgeries, followed by drowsiness and nausea/vomiting.² Laparoscopic surgery is a day-care surgery. Although it is a minimally invasive procedure, pain in the early postoperative period is the most common complaint. It gives rise to three types of pain: parietal pain caused by incision, visceral pain, and shoulder pain (referred).⁵ Chronic pain like post laparoscopic cholecystectomy syndrome might develop from severe acute pain following laparoscopic cholecystectomy if it’s not adequately treated.⁶ Hence, adequate postoperative pain management forms an integral part of patient’s postsurgical care. The main aim of postoperative pain management is to provide adequate analgesia with an optimal dose of drugs and with minimum side effects. This can be accomplished through a multimodal pain management approach, in which pain is effectively managed by combining several analgesics, each of which targets all the processes in the sensory pathways.⁵ The concept of multimodal analgesia technique was described by Kehlet and Dahl in 1993, in order to improve outcomes following surgery.⁷ Newer postoperative pain management agents are being developed, allowing for better multimodal analgesic combinations.

Aim:

To determine and compare the analgesic properties of pregabalin versus paracetamol on postoperative pain after laparoscopic cholecystectomy.

Primary Objective:

To compare the effectiveness of pregabalin and paracetamol on immediate postoperative pain relief after laparoscopic cholecystectomy.

 Secondary Objective:

 To determine the time interval for the requirement of first dose of rescue analgesic.

All patients posted for elective laparoscopic cholecystectomy who fulfilled the inclusion criteria were taken for the study. Allocation of groups: 100 patients of either sex were randomly allocated into two study groups- Group I and Group II (50 in each group). Group I: Patients received 150 mg pregabalin capsule orally with sips of water 2 hrs before surgery. Group II: Patients received 15 mg/kg paracetamol tablet orally with sips of water 2 hrs before surgery. In the operation theatre intravenous line was secured with 18G cannula and IV fluid ringer lactate was connected. A multichannel monitor consisting of pulse oximeter, electrocardiogram, non-invasive blood pressure, temperature and capnography was connected. The base line pre-induction heart rate, oxygen saturation, systolic, diastolic blood pressure, mean arterial pressure values were recorded. Premedication was given with injection ondansetron 0.15 mg/kg IV, injection glycopyrrolate 0.04 mg/kg IV and injection fentanyl 2 mcg /kg IV was given prior to induction. Pre-oxygenation with 100% oxygen with 10L/min was done for 3 minutes. Then the patient was induced with injection Propofol 2 mg/kg followed by rocuronium (0.6 mg/kg) to facilitate orotracheal intubation. Endotracheal intubation was performed using an appropriate sized Macintosh blade and with an appropriate sized cuffed endotracheal tube. The timing of the events was noted. Endotracheal tube placement was confirmed by bilateral air entry, bilateral chest rise and capnography and then the tube was firmly secured. Anaesthesia was maintained with 50% oxygen, 50% nitrous oxide and sevoflurane (0.6%-1%) and intermittent doses of one fifth (1/5th) of the intubating dose of IV rocuronium when required. Ventilation was controlled by using Drager Fabius Plus ventilator. Tidal volume, respiratory rate and PEEP were adjusted to maintain the EtCO2 between 35-40 mmHg. At the end of the surgery, sevoflurane was discontinued. Then oropharyngeal suctioning was done. Nitrous oxide and oxygen were continued till the return of respiratory efforts. After returning of respiratory efforts, nitrous oxide was discontinued and residual neuromuscular blockade was reversed by injection neostigmine 0.05 mg/kg and injection glycopyrrolate 0.01 mg/kg intravenously. When the criteria for extubation were fulfilled, after suctioning of the oral cavity extubation was done. After extubation patients were oxygenated with 100% oxygen for 5 minutes and then shifted to post anaesthetic care unit. Upon arrival to postoperative ward, postoperative pain (on Visual Analogue Scale), sedation level (Ramsay sedation score), haemodynamic changes (Heart rate, SBP, DBP and MAP) and any side effects like nausea and vomiting, dizziness and blurring of vision was assessed and recorded at 0 min, 30 min, 1 hr, 2 hr, 3 hr and at 6 hrs postoperatively.

The present study was a hospital based observational study comparing the effect of oral pre-emptive pregabalin and paracetamol on acute postoperative pain relief in patients undergoing laparoscopic cholecystectomy. In the present comparative study 100 patients of ASA grade I and II of either sex and age between 18-60 years were selected after obtaining written and informed consent and were divided into 2 groups. Group I received 150 mg pregabalin capsule and Group II received 15 mg/kg paracetamol tablet orally with sips of water 2 hrs before surgery. The parameters which were compared between the two groups included age, sex, weight, ASA status, duration of surgery, visual analogue scale, ramsay sedation score, hemodynamic variables, any adverse effects and time for the requirement of first rescue analgesic dose. The result and observation of all these different parameters are shown in the following tables and graphs.

TABLE–1: POSTOPERATIVE VISUAL ANALOGUE SCALE (VAS)

                              FIG–1: POSTOPERATIVE VISUAL ANALOGUE SCALE

      Table- 1 and above graph showing the mean VAS scores during the postoperative period at 0 min, 30 min, 1hr, 2hr and 3hr in group I was 1.48, 2.18, 2.48, 2.86 and 3.34 and in group II was 1.94, 2.46, 2.88, 3.22 and 3.72 respectively.

TABLE–2: POSTOPERATIVE RAMSAY SEDATION SCORE

                          FIG–2: POSTOPERATIVE RAMSAY SEDATION SCORE

            Table-2 and the above graph showing the postoperative mean Ramsay sedation score at 0min,30 min,1hr,2hr and 3hr in group I was 2.60, 2.16, 1.90, 1.70 and 1.34 in group I and 2.06, 1.84, 1.60, 1.30 and 1.12 in group II respectively.

TABLE–3 : INCIDENCE OF ADVERSE EFFECTS

FIG–3: INCIDENCE OF ADVERSE EFFECTS

               Table - 3 and above graph showing the postoperative nausea and vomiting in 6 % and in 4% of patients in group I and II respectively.

TABLE– 4 :  TIME FOR THE REQUIREMENT OF FIRST DOSE OF  RESCUE  ANALGESIC (TRAMADOL)

FIG–4: TIME FOR THE REQUIREMENT OF FIRST DOSE OF RESCUE ANALGESIC (TRAMADOL))

 Table- 4 and above graph showing the mean time for the requirement of first dose of rescue analgesic in group I and group II was 211.00±40.92 and 80.50±27.93 mins respectively.

The most common complaint and the primary cause of prolonged recovery after elective laparoscopic cholecystectomy is early postoperative pain. Inadequately treated postoperative pain is the reason for several complications like delayed recovery, metabolic alterations, anxiety and stress to the patients. 3,4 Hence, several studies have been conducted to determine the most effective methods of providing postoperative pain relief. The concept of pre-emptive analgesia introduced by Crile and further developed by Wall and Woolf revolutionized postoperative pain relief.  Pre-emptive analgesia reduces postoperative pain by causing inhibition of central nervous system sensitization before the surgery-induced nociception stimulus. Effective postoperative pain management increases patient satisfaction, early mobilization, and reduces hospital stay. Postoperative pain management can be improved by multimodal analgesic techniques. The main aim of multimodal analgesia is to reduce the dosage and side effects of opioids by replacing them with the drugs that act by different mechanisms. Gabapentinoids (gabapentin and pregabalin) have been found to be very effective in this role. Hence several studies have been conducted and proved that the use of pre-emptive gabapentinoids was effective in providing postoperative pain relief. But there are limited studies conducted comparing pre-emptive oral pregabalin and paracetamol on postoperative pain control. This was the basis of the present study. The aim of the present study was to assess and compare the analgesic properties of pre-emptive oral pregabalin 150 mg versus paracetamol 15mg/kg on postoperative pain after laparoscopic cholecystectomy. We also assessed and compared the demographic data, ASA status, duration of surgery, severity of pain using VAS score, level of sedation by Ramsay sedation score, haemodynamic variables, any adverse effect like nausea and vomiting, dizziness and blurring of vision and the time interval for requirement of first dose of rescue analgesic up to 6 hrs after surgery.

Based on the present comparative study, it has been observed that a pre-emptive oral dose of pregabalin 150 mg is an effective analgesic for the control of acute postoperative pain in patients undergoing laparoscopic cholecystectomy compared to oral paracetamol 15mg/kg in the early postoperative period. Hemodynamic variables like heart rate, systolic blood pressure and mean arterial pressure was significantly reduced in pregabalin group up to 3 hrs after surgery. The VAS score was significantly reduced in pregabalin group in comparison to paracetamol group up to 3 hrs after surgery and the time for the requirement for first dose of rescue analgesic was prolonged in pregabalin group compared to paracetamol group. However, there was no significant difference between the two groups in terms of Ramsay sedation score and adverse effects. Hence, we conclude that single pre-emptive oral dose of pregabalin 150 mg is a safe and effective analgesic with significant opioid sparing effect in acute postoperative pain relief following laparoscopic cholecystectomy compared to paracetamol 15 mg/kg.

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