Introduction:

Laparoscopic surgeries are minimally invasive surgeries that are safe and advantageous because they reduce the hospital stay and lead to better convalescence after surgery. They are increasingly being termed as outpatient procedures.The most crucial step in the postoperative recovery period is the optimal control of early postoperative pain and postoperative nausea and vomiting. Effective perioperative pain management poses a significant challenge for healthcare practitioners. ¹

Since time immemorial, opioids have been the mainstay drugs for management of postoperative pain, despite their manifold adverse effects such as respiratory depression, PONV and physical dependence. So a multimodal approach using combination of opioid and non- opioid analgesics or a mixture of non-opioid analgesics given as pre-emptive analgesic improve pain relief, minimize opioid consumption and opioid associated side effect. ² Pre-emptive analgesia is an anti-nociceptive treatment, which prevents central hyperexcitability, central sensitization evoked by the incisional and inflammatory injuries occurring during surgery and early postoperative period via altering the afferent input involved in pain. ³

Etoricoxib is a selective inhibitor of cyclooxygenase-2 (COX-2),an enzyme involved in pain and inflammation. Its extensively used because of its wide safety profile (GI, CVS, renal), good oral bioavailability, rapid onset of action and long plasma half life. ⁴ Along with its opioid sparing analgesic effect it has its proven benefits in acute (postoperative) and chronic(arthritis) pain management. Laparoscopic surgeries have remarkably high incidence of PONV .Glucocorticoids likemethylprednisolone have shown to decrease pain, PONV and postoperative fatigue. They have also shown to have opioid sparing analgesic effect similar to NSAIDs. ^{4, 5, 6} Hence etoricoxib was combined with methylprednisolone in our study to attenuate pain and PONV.

Material and Methods:

A prospective, double-blind clinical study was initiated after clearance from institutional ethical committee. Sample size was calculated to be 35 patients to be randomly allocated in each group keeping a power of 0.8, α error of 0.05 and allowing for study error and attrition. A total of 70 patients were assigned to either test group(A) receiving combination of tab etoricoxib 120 mg and iv methylprednisolone 125 mg or control group(B) receiving placebo tablet with sterile water iv using computer generated table of random numbers. Patients were given either a combination of tab etoricoxib 120 mg (1 hour prior to induction) and iv methylprednisolone 125 mg (just before induction)in Group A while control Group B received a placebo tablet and sterile water iv. All patients included in the study were kept nil per oral for 8 hrs. ⁷ Routine vital parameters including pulse oximeter, NIBP, ECG were attached and monitored intraoperatively. The anesthesia technique was standardized for both groups. Patients were induced with 3 μg/kg of fentanyl IV and 2 mg/kg of propofol IV; orotracheal intubation was facilitated by 0.08 mg/kg of vecuronium IV. Anaesthesia was maintained by inhalational sevoflurane with oxygen and nitrous oxide. At the end of the surgery, residual neuromuscular paralysis was antagonized with neostigmine at 0.04 mg/kg and glycopyrrolate at 0.01 mg/kg IV. Following reversal, the patients were extubated and shifted to the post-anesthesia care unit (PACU). Pain was assessed perioperatively using standard 10 cm visual analog scale with 0 corresponding to no pain and 10 worst possible pain. ⁸

VAS score was noted subsequently after every 2 hrs at wards. The time in minutes from the end of surgery to the first analgesia request was noted together with total analgesia consumed in the first 24 hrs. In addition, the incidence of PONV(using four-point ordinal scale),sedation (assessed using Ramsey Sedation Scale),total number of rescue analgesic (inj fentanyl 50μg) doses.Haemodynamic parameterswere recorded both intra and post-operatively for first 24 hours. ^{9, 10}

Statistical analysis was done using the SPSS version 20 software. Standard qualitative and quantitative tests were used to compare the data. (e.g. unpaired student — t test, Chi-square test etc). A p value < 0.05 with a power of 80% was considered statistically significant.

Results:

Both groups were comparable in terms of demographic profile such age, sex, height, weight, ASA physical status, site of surgery with no statistical significant difference between two groups.

The duration of analgesia was longer (7.57 ± 1.04 hrs) in Group A than Group B (3.05 ± 0.9 hrs) and the difference was statistically significant (p=0.02). Table 1

Mean VAS scores were significantly low in group A than group B at postoperative time, 2 hrs (0 vs 1.4); 4 hrs (1.28 vs 2.8) and 6 hrs (2.2 vs 3.42); after which the difference became insignificant. Figure 1 Mean number of analgesic doses required in Group A was 1.31 ± 0.50, were as in Group B was 1.771±0.6897 for first 24 hours. There was statistically significant difference between two groups (p value = 0.0203).Table 2 Table 3

22.85% of patients in Group A complained PONV compared to 51.42% in Group B which was statistically significant. (p<0.001).All the patients remained haemodynamically stable throughout the period of study. There was no statistically significant difference between the groups.Hypotension and sedation was noted in some patients of both the groups and was statistically insignificant.

Discussion

Pain is a subjective sensation, however its undertreatment can lead to various physical, emotional and psychological sequelae. Inadequate treatment of postoperative pain leads to prolonged hospital stay, delayed recovery and more economic burden to patient. ¹¹

As part of pre-emptive multimodal analgesia, use of opioid and non-opioid analgesics that act at different sites within the central and peripheral nervous systems has found to prevent postoperative pain. ^{11, 12, 13} Opioids are associated with emesis, risk of respiratory depression and addiction. NSAID’s are the most commonly used analgesics for acute pain control. COX-2 inhibitors like etoricoxib are associated with fewer adverse effects than conventional NSAIDs and hence more preferred. ^{14, 15} Celik EC et al used NSAIDs as along with general anesthesia and found total reduction in post op analgesic consumption but their study was limited by unsatisfactory VAS score and various side effect.Bisgaard used dexamethasone with selective COX-2 inhibitors where as Gautam S et al and Romundstad et al used methylprednisolone with etoricoxib all noticed good analgesia with opioid sparing effect. ^{16, 17, 18, 19}

Use of methylprednisolone along with etoricoxib significantly prolonged duration of action with reduce number of rescue analgesic doses in present study as seen by Boonriong et al and others. ^{18, 19, 20} Lierz et al and Ko-iam et al used etoricoxib as preemptive analgesia in therapeutic knee arthroscopy surgeries and abdominal surgeries respectively and showed reduced VAS score at different time intervals as seen in our study.As very less number of studies have noted VAS score at different time interval,there is scope for future studies to note the same. ^{21, 22}

Glucocorticoids like methylprednisolone are well known for their analgesic(membrane stabilization),anti-inflammatory, immune modulating and antiemetic effects. ¹⁸ Potential side effects of glucocorticoids include gastrointestinal bleeding, impaired wound healing, susceptibility of wound site infection, but with 125mg single dose many studies have ruled out the same. ^{18, 19, 20} Present study showed combining methylprednisolone with etoricoxib not only prolongs analgesia but also reduces PONV. Hence this combination can be used as multimodal approach to attenuate pain and PONV.

World is behind laparoscopic surgeries because of its wide variety of advantages over open surgeries but at the same time pain from port site, peritoneal stretch is associated with PONV. ¹⁸ To combat this, the concept of multimodal analgesia and preemptive analgesia is vast developing rather than single analgesic technique for better pain relief.

Nausea often accompanies pain so drug which reduces pain and PONV together would be a boon to pain physicians in post op patients. Gautam et al, Lunn et al concluded from their studies that a single dose of methylprednisolone decreases the incidence of PONV and reduces the consumption of ondansetron. ^{18, 23} Whereas Konuganti et al conducted their study using dexamethasone and concluded that the glucocorticoid played an important role in alleviating patient discomfort related to nausea and vomiting. ^{23, 24} All the patients of both groups remained haemodynamically stable throughout the study period. It was in accordance with other studies like Lierz et al, Shuying et al and Ko-iam et al. ^{21, 22, 25} This is evident by the fact that there was good analgesia throughout the period of study. The concept of multi modal analgesia is well-established for management of pain and has to be used regularly in order to provide speedy recovery of patients at hospital

Conclusion

Single dose of intravenous methylprednisolone and oral etoricoxib combination used as preemptive analgesic significantly reduces postoperative pain and PONV in patients undergoing laparoscopic surgeries.

Limitation:

Single dose etoricoxib does not infer the long term benefits to the patients. Although both the drugs are safely used there is lack of evidence for drugs interaction between them and assessment of visual analog scale score is subjective.