Preconditioning Shields Against Vascular Events in Surgery

Major vascular surgery involves operations to repair swollen blood vessels, clear debris from blocked arteries or bypass blocked blood vessels. Patients with these problems are a high-risk surgical group as they have generalized blood vessel disease. These puts them at risk of major complications around the time of surgery such as heart attacks , strokes and death. The mortality following repair of a swollen main artery in the abdomen is about 1 in 20. This contrasts poorly with the 1 per 100 risk of death following a heart bypass. Simple and cost-effective methods are needed to reduce the risks of major vascular surgery. Remote ischaemic preconditioning (RIPC) may be such a technique. To induce RIPC, the blood supply to muscle in the patient's arm is interrupted for about 5 minutes. It is then restored for a further five minutes. This cycle is repeated three more times. The blood supply is interrupted simply by inflating a blood pressure cuff to maximum pressure. This repeated brief interruption of the muscular blood supply sends signals to critical organs such as the brain and heart, which are rendered temporarily resistant to damage from reduced blood supply. Several small randomized clinical trials in patients undergoing different types of major vascular surgery have demonstrated a potential benefit. This large, multi-centre trial aims to determine whether RIPC can reduce complications in routine practice.

The demand for major vascular surgery is increasing \[1\]. Patients requiring procedures such as aortic aneurysm repair, carotid endarterectomy, lower limb surgical re-vascularisation and major lower limb amputation for end-stage vascular disease constitute a high-risk surgical cohort. Peri-operative complications such as myocardial infarction, cerebrovascular accident, renal failure and death are common \[2,3\]. Multiple potential mechanisms may result in these complications. For example, myocardial injury may result from systemic hypotension leading to reduced flow across a tight coronary artery stenosis or, alternatively, it may arise due to acute occlusion when an unstable plaque ruptures. Most strategies aimed at peri-operative risk reduction target a single potential mechanism. For example, beta-blockade may prevent myocardial injury due to overwork, but cannot prevent acute coronary occlusion. There is a requirement for a simple, effective intervention that protects tissues against injury via multiple different mechanisms. Remote ischemic preconditioning (RIPC) may be suitable.

Ischemic preconditioning is a phenomenon whereby a brief period of non-lethal ischemia in a tissue renders it resistant to the effects of a subsequent much longer ischaemic insult. It was first described in the canine heart \[4\]. Subsequent clinical trials showed that ischemic preconditioning reduced heart muscle damage following coronary artery bypass grafting \[5\] and liver dysfunction following hepatic resection \[6\]. Following cardiac surgery, it is associated with a reduction in critical care stay, arrhythmias and inotrope use \[7\]. However, ischemic preconditioning requires direct interference with the target tissues' blood supply, limiting its clinical utility. Further experimental work suggested that brief ischemia in one tissue, such as the kidneys, could confer protection on distant organs such as the heart \[8\]. A similar effect was observed after transient skeletal muscle ischemia \[9-11\]. This effect is referred to as 'preconditioning at a distance' or 'remote ischemic preconditioning' (RIPC).

Eligibility Criteria:
Inclusion Criteria:

* Age greater than 18 years
* Patient willing to give full informed consent for participation
* Patients undergoing elective carotid endarterectomy or
* Patients undergoing open abdominal aortic aneurysm repair or
* Patients undergoing endovascular abdominal aneurysm repair or
* Patients undergoing surgical lower limb revascularisation (suprainguinal or infrainguinal)

Exclusion Criteria:

* Pregnancy
* Significant upper limb peripheral arterial disease
* Previous history of upper limb deep vein thrombosis
* Patients on glibenclamide or nicorandil (these medications may interfere with RIPC) Patients with an estimated pre-operative glomerular filtration rate \< 30mls/min/1.73m2
* Patients with a known history of myocarditis, pericarditis or amyloidosis
* Patients with an estimated pre-operative glomerular filtration rate \< 30mls/min/1.73m2.
* Patients with severe hepatic disease defined as an international normalised ratio \>2 in the absence of systemic anticoagulation
* Patients with severe respiratory disease (for the trial, defined as patients requiring home oxygen therapy)
* Patients previously enrolled in the trial representing for a further procedure
* Patients with previous axillary surgery