Authors: Tarasenko S.O.1, Kashchenko M.V.2, Kreydich O.S. 2, Kuzmenko I.I. 2, Kulish I.O. 2, Yefimova O.O. 2, Kunatovskyi M.V. 2, Palamarchuk V.O. 2, Voitenko V.V. 2, Dashuk T.I. 2, Tsymbal I.A. 2, Maznichenko V.A. 1, Lishchynski P.O. 2, Rudenko V.L. 2, Kvitka D.O. 2, Smolyar V.A. 2
1 National Medical University named after O.O. Bogomolets
2 Ukrainian Scientific and Practical Center of Endocrine Surgery, Transplantation of Endocrine Organs and Tissues of the Ministry of Health of Ukraine
Background
Recently balanced analgesia (BA) has become the standard for postoperative (post-op) pain management. One of the most effective painkillers are ketoprofen and its derivatives, including dexketoprofen. Discussions on the clinical efficacy of generic drugs over the original molecules continue quite lively, especially, over cheaper generic drugs. But no direct clinical studies to compare original vs generic dexketoprofen molecules in clinical practice were found.
The Goal of Study
To investigate the therapeutic efficacy and safety of the use of original vs generic dexketoprofen in the complex of BA in patients with thyroidectomy. To assess a pharmacoeconomic comparison of the use of different dexketoprofen molecules.
Materials and Methods
440 patients with thyrotoxicosis syndrome were examined and then thyroidectomy was performed. 56 patients, who met the including/excluding criteria, were included in double-blinded study. By the method of adaptive randomization, patients were split on two groups: group D (n=27), who received original dexketoprofen (Dexalgin inject) and group S (n=29), who received generic dexketoprofen (Sertofen) from EU country. Complex BA included IV bolus dexketoprofen (DEX) 50 mg, IV lidocaine 1 mg/kg, IV dexamethasone 8 mg and bilateral blockade of superficial cervical plexus (BBSCP) by 0,5% bupivacaine 75-100 mg was used as pre-emptive analgesia 30 minutes before surgery in both groups. Maintenance anaesthesia was done by sevoflurane. According to study design in post-op preventive analgesia was done by DEX 50 mg every 8 hours (h) together with paracetamol (PAR) 1 g IV in the first 6h and following by oral 500 mg every 8 h. 100 mm NRS score was used for pain control. The laboratory markers of post-op stress (LMPOS), such as cortisol (CORT), prostaglandin E2 (PG E2), glucose (GLU) with NRS also were measured.
Results and Discussion
Gender distribution: women were 21 (88,9%) and 25 (86,2 %) respectively in group D and group S (not statistically differences, NS). Average age was 48,7±2,3 in group D and 49,6±2,5 in group S (NS). No differences were found between both groups according to ASA physical status score. Duration of surgery and anesthesia were 63,6±3,4 min and 84,7±3,7 min in group D, in group S these indicators were 62,9±3,9 min and 83,5±4,1 min respectively. Pain level according to NRS after 3h, 6h, 12h, 24 h was 18,9 ± 1,4 mm, 23,1 ± 1,7 mm, 24,1 ± 1,8 mm і 20,2 ± 1,2 mm respectively and was assessed as weak in group D. In group S according to NRS after 3h, 6h, 12h, 24 h pain level was 19,1 ± 1,6 mm, 23,1 ± 1,7 mm, 23,9 ± 1,9 mm і 20,3 ± 1,4 mm. Statistically difference (p<0,05, Wilcoxon test) was noted between all check-points in comparison with previous pain level by NRS, however no difference found between groups. Nobody needed more PAR doses or an addition of morphine. Dynamics of LMPOS were as follows: an increase in the GLU was noted at the end of operation in 6,2% (group D) and 7,3% (group S) (difference NS) due to surgical aggression and dexamethasone usage in the BA complex. CORT level was grown before premedication from 387,9 ± 21,2 nmol/l to 406,5 ± 36,1 nmol/l at the end of operation in group D, in group S from 390,7 ± 24,5 nmol/l to 410,3 ± 38,1 nmol/l respectively. No statistically difference was noted between groups neither before nor after the operation. However, after 24 hours CORT level was broken down till 38,4 ± 7,8 nmol/l (group D) and 41,1 ± 8,1 nmol/l (group S) (glucocorticosteroid suppression by dexamethasone). PG E2 level decreased from 281,2 ± 43,6 pg/ml till 192,1 ± 38,2 pg/ml after 24 hours in group D (p=0,018), from 288,5 ± 41,5 pg/ml till 186,8 ± 41,3 pg/ml in group S respectively without statistically differences between groups. No major bleeding complication were found in both groups, 2 cases in each group were erythematosis gastritis and erosis gastropathy. Safety level complex BA was assessed in 92,6% (group D) and 93,1% in group S (р=0,941, NS). Pharmacoeconomic analysis was shown, that using original DEX in scheme BA was more expensive by 48,2% (+additionally 58, 24 UAH per patient) vs generic DEX origin EU country.
Conclusions
In double-blind randomized study has shown the therapeutic equivalence of the generic dexketoprofen solution for injection to the original drug according to the NRS and the dynamics of LMPOS. High safety of use of dexketoprofen in the complex of balanced multimodal analgesia was established. No found significant difference between groups for efficacy and safety. Pharmacoeconomic analysis has shown that the use of generic drug dexketoprofen with confirmed clinically therapeutic equivalence has significant advantages.
Key Words: balanced analgesia, dexketoprofen, double-blinded randomized study, laboratory markers of post-operative stress.