Post-operative management of inflammation after orthopaedic surgeries using trypsin, bromelain and rutoside combination: a single-centre prospective observational study
Keywords:Orthopaedic surgery, Enzymes, Inflammation, Pain, Swelling
Background: Post-operative management of inflammation plays an important role in orthopaedic surgeries, as delay in wound healing may lead to extended hospital stay. Proteases like trypsin and bromelain combined with the bioflavonoid rutoside are often used to reduce post-operative pain and swelling. The present study aimed to evaluate the efficacy and safety of oral administration of a fixed dose combination of trypsin-bromelain-rutoside in the post-operative management after orthopaedic surgeries.
Methods: The study was a prospective, observational data collection exercise. Hundred subjects undergoing orthopaedic surgeries, who were administered trypsin-bromelain-rutoside combination, were observed over a period of 8 days post-surgery. Verbal rating scales were used for grading the pain intensity and extent of swelling, while a 5-point Likert scale was used to evaluate patient- and investigator-reported global assessment of improvement in pain and swelling. Scores at day 3 and day 8 were analysed using paired t test.
Results: At day 3 and day 8, the mean scores of pain and swelling were significantly reduced from baseline (all p<0.0001). By day 8, 74% of the patients achieved complete resolution of pain, while 50% reported complete resolution of swelling. By day 8, 54% patients reported excellent/ very good global improvement in pain and swelling, while the investigator reported excellent/ very good global improvement in 81% of the patients. No adverse event was reported in any of the patients.
Conclusions: The combination of trypsin-bromelain-rutoside was safe and effective in reducing the post-operative pain and swelling after orthopaedic surgeries. An 8-day treatment led to complete resolution of pain in three-fourths of the patients and complete resolution of swelling in half the patients. The use of this combination has the potential to reduce hospital stay and pill burden.
Daftary G, Shah A, Divekar G, John J, Patil N, Khemnar B. Systemic therapy with bromelain- trypsin-rutoside combination in inflammation: A narrative review of the pharmacodynamics. Natl J Physiol Pharm Pharmacol. 2022;12(11):1.
Kerkhoffs GM, Struijs PA, De Wit C, Rahlfs VW, Zwipp H, Van Dijk CN. A double blind, randomised, parallel group study on the efficacy and safety of treating acute lateral ankle sprain with oral hydrolytic enzymes. Br J Sports Med. 2004;38:431-5.
Singer F, Singer C, Oberleitner H. Phlogenzym® versus diclofenac in the treatment of activated osteoarthritis of the knee. A double-blind prospective randomized study. Int J Immunother. 2001;17:135-42.
Klein G, Kullich W. Short-term treatment of painful osteoarthritis of the knee with oral enzymes. Clin Drug Investig. 2000;19:15-23.
Akhtar NM, Naseer R, Farooqi AZ, Aziz W, Nazir M. Oral enzyme combination versus diclofenac in the treatment of osteoarthritis of the knee a double-blind prospective randomized study. Clin Rheumatol. 2004;23:410-5.
Tilwe G, Beria S, Turakhia N, Daftary G, Schiess W. Efficacy and tolerability of oral enzyme therapy as compared to diclofenac in active osteoarthrosis of knee joint: An open randomized controlled clinical trial. J Assoc Physicians India. 2001;49:617-21.
Klein G, Kullich W, Schnitker J, Schwann H. Efficacy and tolerance of an oral enzyme combination in painful osteoarthritis of the hip. A double-blind, randomised study comparing oral enzymes with non-steroidal anti-inflammatory drugs. Clin Exp Rheumatol. 2006;24:25.
Nanda MS, Kaur M. Role of oral enzymes in post-operative septoplasty cases. Indian J Otolaryngol Head Neck Surg. 2019;71(3):1663-7.
Kamenicek V, Holan P, Franĕk P. Systemic enzyme therapy in the treatment and prevention of post-traumatic and postoperative swelling. Acta Chir Orthop Traumatol Cech. 2001;68:45-9.
Singh T, More V, Fatima U, Karpe T, Aleem MA, Prameela J. Effect of proteolytic enzyme bromelain on pain and swelling after removal of third molars. J Int Soc Prev Community Dent. 2016;6:S197.
Dockery GL, Crawford ME. Lower extremity soft tissue and cutaneous plastic surgery. Elsevier Health Sci. 2012;26.
Hess CT. Checklist for factors affecting wound healing. Adv Skin Wound Care. 2011;24(4):192.
Conaghan P. A turbulent decade for NSAIDs: update on current concepts of classification, epidemiology, comparative efficacy, and toxicity. Rheumatol Int. 2011;32(6):1491-502.
Marcum Z, Hanlon J. Recognizing the risks of chronic nonsteroidal anti-inflammatory drug use in older adults. Ann Longterm Care. 2010;18(9):24-7.
Anderson K, Hamm RL. Factors that impair wound healing. J Am Coll Clin Wound Spec. 2012;4(4):84-91.
Yasir M, Goyal A, Sonthalia S. Corticosteroid Adverse Effects. In: StatPearls. Treasure Island (FL): StatPearls Publishing. 2022.
Fowler C. Do nonsteroidal anti-inflammatory drugs impair tissue healing? JAAPA. 2018;31(8):1-5.
Kamenicek V, Holan P, Franĕk P. Systemic enzyme therapy in the treatment and prevention of post-traumatic and postoperative swelling. Acta Chir. Orthop. Traumatol. Cechoslov. 2001;68(1):45-9.
Bakhshi GD, Tiwari S, Prajapati RK, Rudrappa GH, Uppin MI, Vinchhi PJ et al. Systemic Enzyme Therapy with Trypsin-Bromelain-Rutoside combination to counter post-operative wound inflammation-a randomized active-controlled multi-centre trial. Eur J Pharm Med Res. 2019;6(8):493-500.
Dhadiwal R, Tiwari S, Jauhari RK. Management of post-surgical inflammation with proteolytic enzyme-bioflavonoid combination. Int J Sci Res. 2021;10(9):34-7.