None listed
Conditions
Brief summary
BACKGROUND: Transcatheter aortic valve implantation (TAVI) is a minimally invasive management option available to select patients suffering from severe aortic stenosis (AS). However, the incidence of cerebrovascular events (CVEs), such as stroke, have raised concern and have the potential to dramatically mitigate any benefits associated with the procedure. We have identified two promising physiological neuroprotective strategies that warrant investigation in this setting: 1) remote ischemic preconditioning (RIPC); and, 2) targeted temperature management (TTM). RATIONALE: (1) RIPC is a protective mechanism whereby a non-lethal ischemic insult, occurring at a site remote from the target organ, activates adaptive mechanisms that blunt tissue injury on subsequent challenge. Laboratory and animal studies have demonstrated this to be one of the most powerful anti-ischaemic strategies known; and yet translation from theory to clinical practice remains a largely unmet medical need. One reason for this has been the unpredictable nature of the timing of stroke, precluding pre-treatment. Cardiovascular procedures, such as TAVI, provide a unique opportunity to apply this technique to a setting of predictably high risk for cerebrovascular events. (2) TTM relies on the reduction in metabolic (e.g. oxygen and glucose) requirements of the brain that occurs with hypothermia. In addition to affecting oxygen consumption and glucose utilisation, hypothermia has other potential benefits including reducing waste products, inflammation, and preventing cell death. HYPOTHESIS: TTM and RIPC offer feasible neuroprotective strategies during TAVI and warrant further investigation. METHODS: This is a prospective, randomised, controlled pilot study. All patients planned to undergo TAVI at The Prince Charles Hospital and St. Andrew’s War Memorial Hospital will be considered. TAVI can be delivered in a number of ways including via blood vessels in the groin (transfemoral or TF approach) or directly through the chest wall (transaortic or TAo approach). Consecutive eligible participants undergoing implantation via a TAo approach will be randomised (1:1) to either control or TTM. Those for whom a Transfemoral (TF) approach is to be used will be randomised (1:1) to either control or RIPC. ASSESSMENT & DATA COLLECTION: A multi-disciplinary approach has been adopted to ensure that relevant experts address each assessment domain. Assessors will be blinded to treatment allocation.
Interventions
Participants randomised to the intervention group will receive one of the following interventions:
1. Remote Ischaemic Preconditioning - Under standard conditions, two blood pressure cuffs will be placed, one on the left lower limb distal to the femoral cannulation site and one on the upper limb contralateral to the arterial line. Two to four cycles of transient ischaemia/reperfusion will follow induction of anaesthesia with completion prior to insertion of the delivery catheter. Each cycle wi
Participants randomised to the intervention group will receive one of the following interventions: 1. Remote Ischaemic Preconditioning - Under standard conditions, two blood pressure cuffs will be placed, one on the left lower limb distal to the femoral cannulation site and one on the upper limb contralateral to the arterial line. Two to four cycles of transient ischaemia/reperfusion will follow induction of anaesthesia with completion prior to insertion of the delivery catheter. Each cycle will involve concurrent inflation of both upper and lower limb blood pressure cuffs to a pressure of greater than or equal to 200mmHg and at least 15mmHg greater than the systolic arterial pressure measured via the arterial line for 5 minutes, followed by 5 minutes of reperfusion (total 10 minutes). Patients will be sedated with intravenous propofol target controlled infusion and paralysed with intravenous rocuronium or cisatracurium. Doses will be initially calculated on a milligrams per kilogram basis at the induction of anaesthesia and titrated appropriately with ongoing administration for the duration of the procedure and extubation prior to transfer to the post anesthetic recovery unit. This intervention will be performed by dedicated research nurse or doctor with a minimum of 3 years clinical experience. All other researchers and clinicians will be blinded to randomization. 2. Targeted Temperature Management - Mild cerebral hypothermia, targeting a nasopharyngeal temperature of 34.5 degrees celsius, will be achieved as described below. Cerebral hypothermia will be induced following general anaesthetic induction and maintained until closure of the skin (last stage of the procedure). Continuous temperature monitoring will be performed and titrated using nasopharyngeal temperature probe. A urinary bladder temperature probe and intermittent tympanic measures will be used for comparison /analysis. Hypothermia will be achieved by withholding routine warming devices, administration of cooled fluids and with use of a cooling device (Cincinnati Sub-Zero Products Ltd, Cincinnati, OH, USA). Patients will be sedated with intravenous propofol target controlled infusion and paralysed with intravenous rocuronium or cisatracurium to prevent shivering. Doses will be initially calculated on a milligrams per kilogram basis at the induction of anaesthesia and titrated appropriately with ongoing administration for the duration of the procedure and in the intensive care unit, as required, until normothermia is achieved (36.5 degrees celsius to 37.5 degrees celsius). To avoid the deleterious effects of cerebral hyperthermia, slow re-warming, controlled at a rate of 0.5 degrees celsius/hour will occur in the intensive care unit, where required, following completion of the procedure until normothermia is attained, with ongoing monitoring to ensure the occurrence of rebound hyperpyrexia is managed rapidly. This will take approximately 4 hours if target temperature of 34.5 degrees celsius is achieved intraoperatively. This intervention will be performed by the treating anaesthetists, who will be the only person unblinded to randomisation.
Sponsors
The Prince Charles Hospital
Study design
Allocation
Randomised controlled trial
Intervention model
Parallel
Primary purpose
Prevention
Masking
Blinded (masking used) (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
All
Age
65 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1) Informed consent for participation; 2) severe aortic stenosis requiring management with isolated TAVI with an Edwards SAPIEN-XT prosthesis under general anaesthetic, as determined by the local 'heart team'; 3) Pre-procedural mini-mental state examination score greater than or equal to 24; 4) stable haemoglobin.
Exclusion criteria
1) <65 years of age; 2) pre-existing neurological impairment including previous clinical cerebrovascular event or cognitive dysfunction; 3) contraindication to MRI (including incompatible prostheses / foreign body, inability to lie flat, claustrophobic requiring sedation); 4) contraindication to proposed neuroprotective intervention (e.g., previous thromboembolic disease, peripheral vascular disease etc.); 5) non- or poor english speaking (due to the unknown validity of neuropsychiatric battery in such a population); 6) chronic kidney or liver disease; 7) Patients with diabetes.
Outcome results
None listed