BJA/RCoA Project Grant
Feasibility and metabolic effects of carbohydrate loading in patients with fragility hip fracture - a randomized double blind pilot study
Dr Iain Moppett
Hip fracture is a common injury affecting predominantly older, frail people. The outcome for patients is often poor with a high mortality following operation and worsening of mobility and function when compared with that before the injury. It has long been recognized that trauma due to surgery or accident is associated with changes in the way muscles use fuels such as sugar (glucose). These changes come on soon after injury and persist for some time and may have harmful effects on recovery and muscle strength. We also know that poor muscle function is a predictor of poor outcome in the days and months following hip fracture. Researchers in the field of elective surgery have found that providing patients with special carbohydrate drinks before their operation can improve muscle sugar use and have beneficial effects in the postoperative period.
Patients feel better before their operation and several studies have shown a reduction in the length of time patients need to stay in hospital following their operation. However, due to the nature of hip fracture, which is operated on urgently, and in a frail population who are often in pain, providing pre-operative drinks may be difficult. Some small studies from other researchers suggest that it is feasible. The muscle of older people behaves differently to younger people so we don't know whether these drinks will have the same effect as in younger people coming for planned operations.
Potentially, if we can find out what effect these drinks have on the way muscles behave, this may provide avenues of future research into the optimal way to enhance muscle function following hip fracture, hopefully providing a better outcome for this important group of patients.
To do this, we wish to study a group of hip fracture patients as well as a matched group of patients undergoing planned major orthopaedic surgery. We wish to find out what happens to the way their bodies deal with sugar if they have these drinks or if they have normal care without the drinks. We would do this by simple blood tests, and by taking some small tissue samples from leg muscles before and after their operation. Part of the study will be looking at the practical issues around providing these sorts of drinks to an elderly patient group admitted as emergencies as this is something that is often overlooked in studies of this type.
A characteristic cytokine gene expression signature may predict the development of post-operative pneumonia following major gastrointestinal surgery
Dr Michael O'Dwyer
Infection is one of the most frequent complications following major surgery. This may occur both at the site of the procedure (wound infection) or in more distant organs, such as a chest infection (pneumonia). Pneumonia is particularly frequent in patients who undergo major abdominal surgery involving the gut (gastrointestinal surgery). We do not fully understand why this complication occurs but it seems likely to represent a problem with the immune system. Although gastrointestinal surgery may be considered low risk by some, the development of pneumonia following surgery is associated with a short-term mortality in excess of 20%. Surprisingly, even those patients that survive a postoperative pneumonia and are discharged home have a considerable reduction in life expectancy. Clearly, the early identification of a patient group at high-risk of acquiring a post-operative pneumonia and an increased understanding of the immune mechanisms that contribute to this increased risk may allow us to develop interventions that ensure we treat this potentially devastating condition more effectively or prevent it altogether.
During previous research the lead applicant has identified abnormalities in the human immune system which were strongly related to the development of pneumonia following surgery on the lung and chest cavity. Importantly, these immune system abnormalities, measured by blood sampling, occurred immediately following surgery and well before a doctor was able to diagnose pneumonia at the bedside. These findings have furthered our understanding of the mechanisms behind the increased susceptibility to pneumonia and also have clear potential as a useful predictive tool. If proven conclusively, these results may allow us in the future to treat a group of high-risk patients pre-emptively, at a time point before the infection becomes established. This has the potential to reduce the very high mortality associated with pneumonia following surgery. However, to achieve these ultimate aims firstly the lead applicant's previous results must be validated in a larger patient group where the site of infection (chest) is different to the site of surgery. The opportunity has now arisen to study a subset of patients currently being recruited to a large international investigation of complications occurring around the time of surgery (VISION). Investigators involved with the UK arm of this trial (VISION-UK) are collaborating on the proposed study. We will analyse a subset of 300 patients, recruited to VISION-UK, who undergo major gastrointestinal surgery. As per the VISION-UK protocol, bloods are taken before surgery and at 6-12, 24 and 72 hours following surgery. Patients are then assessed on a daily basis following surgery for the development of pneumonia. We hope that our findings will allow us to identify a group of patients undergoing major gastrointestinal surgery at high risk of subsequently developing a post-operative pneumonia.
Furthermore, analysing specific immune system pathways will progress our understanding of why some patients are more susceptible to infection following surgery. These findings can then be exploited in an effort to decrease the high mortality rate associated with pneumonia following surgery.
