The choice of analgesia affects the clinical worsening in a classic rat model of sepsis: Tramadol vs.Dexketoprofen

Abstract

Opioids and non-steroidal anti-inflammatory drugs (NSAIDs) are widely used to treat acute and chronic pain. Their effects on the immune system and possible interference with experimental results are widely discussed. The aim of this study was to evaluate the effects of tramadol (synthetic opioid) and dexketoptophen (NSAID COX-2) in the gold-standard model of sepsis in rats by ligation and cecal puncture (CLP). Mortality, microbiological changes in bronchoalveolar lavage fluid (BALF), peritoneal lavage fluid (PLF) and urine, biochemical alterations in serum and urine, as well as haematological alterations were analysed. 30 male Sprague-Dawley rats, 12-14 weeks old, were randomised into 3 groups: Septic control (CON) without analgesia, septic treated with dexketoprofen (DEX) (8µg/100gr)/12h sc, and septic treated with tramadol (TRA) (2.5mg/100gr)/12h sc (n=10 per treatment). All animals were subjected to CLP under an anaesthetic protocol with medetomidine/fentanyl (0.3/0.3 mg/kg sc). Every 12 hours, mortality, temperature, degree of hydration and welfare indicators (piloerection, response to stimuli, cyanosis, cryodacryorrhea) were measured. At 42 hours, the animals were euthanised and the following samples were taken: Venous blood from the external jugular vein, for haemogram and biochemistry; urine by puncture of the bladder, for biochemistry and urine culture; PLF and BALF for microbiological culture; cardiac blood for blood culture. Both protocols provided good analgesic coverage. Dexketoprofen offers an analgesic coverage similar to tramadol in the rat CLP model, but with lower mortalities, ALT values, urea, cytokines and CFU/ml of E. coli, being more similar to the control group