RA-UK Project Grant

The Problem
Inadvertent hypothermia (unintended core temperature reduction to ≤ 35°C) is common in patients administered with local anaesthetic. This is a serious concern because it makes patients five times more likely to develop cardiac (heart) complications and six times more likely to develop a postsurgical wound infection. Interestingly, although the use of pain relievers during surgery (preemptive analgesia) reduces pain during the post-operative period, their use may contribute to the onset of hypothermia.

The class of pain medications in question are known as "cyclooxygenase inhibitors", because they relieve pain by blocking the biological activity of a molecule called cyclooxygenase (COX). This molecule has two forms (COX-1 and COX-2), but it is currently unclear which one is involved in regulating core temperature. Recently, our research group discovered a novel side effect of paracetamol (which inhibits both COX isoforms), in that it reduces core temperature by up to 1°C in healthy individuals exposed to cold conditions. These effects are pertinent because paracetamol may cause hypothermia to occur in a shorter amount of time in surgical patients, compared with non COX-inhibiting medications. Additionally, the use of COX inhibitors may interfere with normal blood flow and contribute to total blood loss during surgery by deactivating clotting mechanisms (a common use of aspirin). Hypothermia alone has been shown to increase blood loss by 500 ml during hip replacement surgery, so it is vital to ascertain if COX inhibitors used in preemptive analgesia contributes to this response.

It is currently unclear if COX inhibition alters core temperature or blood (hemodynamic) responses to prolonged exposure to operating room temperature. Thus, the aim of this study is to identify how inhibition of COX-1 (aspirin administration) and COX-2 (celecoxib administration) alters the core temperature and hemodynamic responses to an operative environment (18 - 20°C).

Methods
Ten males will be recruited for this study. Participants will be exposed to operating room temperature (18 - 20°C) in surgical gown for two hours. This will simulate the environmental conditions experienced by patients during surgery. Participants will visit the laboratory on three occasions, where they will be exposed to this environment having ingested aspirin (COX-1 inhibitor), celecoxib (COX-2 inhibitor) or nothing (control trial). Each trial will be separated by at-least one week. During each trial we will monitor core temperature and shivering intensity (by a technique called electromyography). We will also analyse concentrations of molecules involved in blood thickening/thinning before, during, and immediately after the cold exposure (i.e. pre, 60 and 120 min).

Conclusion
The results of this study will help elucidate if the use of COX inhibitors in pre-emptive analgesia contribute to the occurrence of hypothermia and blood loss in patients. This will allow anaesthetists to make more accurate judgements in regards to what type of pain reliever is administered to the patient during surgery. This information may increase patient safety and potentially decrease hospital stay duration.