Tourniquets are used to decrease blood loss, enhance operating conditions, and shorten surgical time while performing lower extremity surgeries. However, tourniquet application often causes inflammation, which may lead to severe ischemia and reperfusion injury, causing acute lung injury and other organ damage. This research seeks to evaluate the impact of various intra-venous sedatives (propofol, Dexmedetomidine, or midazolam) in terms of preconditioning prior to tourniquet application, with respect to post-tourniquet ischemia-reperfusion damage under spinal anaesthesia. Methods: The four groups receiving spinal anaesthesia split into 80 knee surgery patients under spinal anaesthesia into 4 identical groups: Group C: Only spinal anaesthetic was administered to them (control group). Group M: This group was sedated with midazolam, with the sedative 0.05 mg/kg/h being administered to them throughout the surgery. Group P: The members of this group were sedated with propofol infusion, and in this group propofol (n = 20) was given as a 0.2 mg/kg bolus dosage and as a 2 mg/kg/min infusion during the operation. Group D: Dexmedetomidine was administered to Group D members (n = 20), who were sedated with dexmedetomidine; they were first given a 10-minute intravenous infusion of dexmedetomidine (1 μg/kg), followed by a continuous infusion of 0.5 μg/kg/h throughout the operation for sedation. Conclusions and results: Contrary to our expectations, the use of midazolam in preconditioning did not show an advantage in the IRI, perhaps possibly worsening acidosis in the control group. Propofol pre-conditioning, according to the controversy, has an antioxidant effect and reduces the negative side effects of IRI.