Horizon Scanning Technology Prioritising Summary. Ultrasonic embolic protection device in cardiac surgery

Transcription

1 Horizon Scanning Technology Prioritising Summary Ultrasonic embolic protection device in cardiac surgery

2 Commonwealth of Australia 2010 ISBN Publications Approval Number: This work is copyright. You may download, display, print and reproduce this material in unaltered form only (retaining this notice) for your personal, non-commercial use or use within your organisation. Apart from any use as permitted under the Copyright Act 1968, all other rights are reserved. Requests and inquiries concerning reproduction and rights should be addressed to Commonwealth Copyright Administration, Attorney General s Department, Robert Garran Offices, National Circuit, Canberra ACT 2600 or posted at Electronic copies can be obtained from Enquiries about the content of the report should be directed to: HealthPACT Secretariat Department of Health and Ageing MDP 106 GPO Box 9848 Canberra ACT 2606 AUSTRALIA DISCLAIMER: This report is based on information available at the time of research cannot be expected to cover any developments arising from subsequent improvements health technologies. This report is based on a limited literature search and is not a definitive statement on the safety, effectiveness or cost-effectiveness of the health technology covered. The Commonwealth does not guarantee the accuracy, currency or completeness of the information in this report. This report is not intended to be used as medical advice and intended to be used to diagnose, treat, cure or prevent any disease, nor should it be used therapeutic purposes or as a substitute for a health professional's advice. The Commonwealth does not accept any liability for any injury, loss or damage incurred by use of or reliance the information. The production of these Horizon scanning prioritising summaries was overseen by the Health Policy Advisory Committee on Technology (HealthPACT). HealthPACT comprises representatives from health departments in all states and territories, the Australia and New Zealand governments; MSAC and ASERNIP-S. The Australian Health Ministers Advisory Council (AHMAC) supports HealthPACT through funding. This Horizon scanning prioritising summary was prepared by Deanne Leopardi from the Australian Safety and Efficacy Register of New Interventional Procedures Surgical (ASERNIP- S).

3 PRIORITISING SUMMARY REGISTER ID S NAME OF TECHNOLOGY EMBLOCKER TM (NEUROSONIX LTD., ISRAEL) ULTRASONIC EMBOLIC PROTECTION DEVICE PURPOSE AND TARGET GROUP PATIENTS WITH A CARDIAC CONDITION REQUIRING SURGICAL INTERVENTION AND CARDIOPULMONARY BYPASS STAGE OF DEVELOPMENT (IN AUSTRALIA) Yet to emerge Established Experimental Established but changed indication or modification of technique Investigational Should be taken out of use Nearly established AUSTRALIAN THERAPEUTIC GOODS ADMINISTRATION APPROVAL Yes No Not applicable INTERNATIONAL UTILISATION COUNTRY Netherlands Trials Underway or Completed LEVEL OF USE Limited Use Widely Diffused IMPACT SUMMARY The EmBlocker (ultrasonic embolic protection) device is used during cardiac surgery to divert emboli generated by surgical manipulations away from the innominate and left common carotid arteries and into the descending aorta. The aim is to reduce the occurrence of emboli within the brain and thereby lower the risk of postoperative neurological defects in patients undergoing cardiac surgery with cardiopulmonary bypass. BACKGROUND During cardiac surgery requiring cardiopulmonary bypass (CPB) a cardioplegic solution is used to achieve asystole (no cardiac activity). A cross-clamp is applied to the distal aorta of the heart to limit systemic perfusion of this cardioplegic solution, and 1

4 deoxygenated blood is diverted from the body to the CPB pump for oxygenation. This oxygenated blood is then pumped back into arterial circulation. Cardiac procedures which require CPB include coronary artery bypass surgery, cardiac valve repair and/or replacement, repair and/or palliation of cardiac defects, and transplantation. Several procedures commonly performed during cardiac surgery with CPB are associated with the formation of intraoperative cerebral emboli, foreign material that can cause the sudden blockage of an artery (embolism). The procedures that can cause emboli include cannulation, cardioplegia needle incision, cross-clamp placement, the start and stop of cardiopulmonary bypass and de-clamping (Sauren et al 2007). The manipulation of the heart vessels with catheters, wires, balloons, and stents during these procedures releases pieces of atherosclerotic plaque and blood clots (thrombus material) and causes the formation of air bubbles (Gruberg 2007). When emboli travel to the brain they can cause postoperative neurological complications such as cognitive decline, transient ischemic attack and stroke (Sauren et al 2009). EmBlocker works on the principle that an object with different acoustic impedance than its surroundings partly reflects/absorbs ultrasound energy (Sauren et al 2007). Acoustic radiation force (acoustic energy absorbed by an object) is the energy able to move an object or change the direction of its path, and this force depends on the extent of the difference between the acoustic impedance of the object and its surroundings (Sauren et al 2007). Red and white blood cells and their surrounding have very little acoustic difference whereas emboli have a greater acoustic difference with their surroundings; therefore, ultrasonic radiation power will have no affect on blood cells and a greater affect on emboli (the greater the difference in acoustic impedance the higher the acoustical force will be on the object) (Sauren et al 2007). Gaseous emboli have a greater difference in acoustic impedance with their surroundings compared with solid emboli; therefore, a lower ultrasonic energy level (0.5 W/cm 2 ) is sufficient to achieve the same acoustic radiation force on gaseous emboli as a higher ultrasonic energy level (1.5 W/cm 2 ) on a solid emboli (Sauren et al 2007). The EmBlocker device delivers ultrasonic energy which is absorbed by the emboli in the form of acoustic radiation force, which results in the diversion of the path of the emboli. In short, the EmBlocker device deflects embolic material flowing inside arteries (in a non-invasive manner) away from vessels supplying blood to vital and delicate organs such as the brain. The EmBlocker device consists of an oval shaped 2.2 MHz disposable transducer (measuring a maximum of 15.8mm x 25 mm x 14mm). After thoracotomy, the EmBlocker device is placed on the ascending aorta at the point where the innominate artery emerges (Sauren et al 2007). There is no need for additional incisions for the placement of EmBlocker and all surgical manoeuvres are unaffected by its presence (Sauren et al 2009). The device is kept in position with a cardiac stabiliser. A biocompatible dome filled with saline is placed over the transducer to keep it cool and to prevent air seeping between the device and the tissue (Sauren et al 2009). Temperature sensors ensure that the transducer does not overheat (Sauren et al 2009). 2

5 CLINICAL NEED AND BURDEN OF DISEASE According to the Australian Institute of Health and Welfare (AIHW) database 610,713 individuals underwent a cardiovascular procedure from 2007 to 2008 (AIHW 2009). Specific data for CPB was not available. The rate of neurological complication arising from cardiac surgery is remarkably high. Transient neuropsychological deficits may be reported in up to 50% of patients undergoing cardiac surgery with CPB, whilst persistent sequelae are reported in up to 30% of operated patients (Di Carlo et al 2001). Sauren et al 2007 also describes the rate of cognitive decline between 5% and 43% of patients. Major complications of cardiac surgery, such as stroke, may occur in 1% to 5% of patients (Di Carlo et al 2001). A similar stroke rate was reported at 2% to 8% of patients in the study by Sauren et al DIFFUSION EmBlocker appears to be the only ultrasonic embolic protection device currently in use worldwide, although its use does not appear to be widespread. A single group of researchers have undertaken two trials, one in animals (pigs) and the other in humans, in the Netherlands (Sauren et al 2007; Sauren et al 2009). EmBlocker received CE mark approval in Europe on 14 December 2007 (Peregrine Ventures 2007). The use of EmBlocker in Australia is yet to take place, thus the device is not listed on the Australian Register of Therapeutic Goods (ARTG). As well as this, EmBlocker does not have US Food and Drug Administration (FDA) approval (FDA 2009). COMPARATORS There are currently three types of cerebral embolic protection devices: filters, distal occlusion balloons and proximal occlusion balloons (Gruberg 2007). 1. Filters are tiny nets supported by expandable metal which are placed in a vessel downstream and distal to the area of treatment (Fornell 2008). The filters are put in place using a delivery sheath. Once in position, the expandable metal frame pops open and secures itself within the vessel (Fornell 2008). The pores of the filter allow blood to continue to flow whilst trapping any debris (Gruberg 2007). A filter pore size of 100 microns is useful as it allows white blood cells (which measure approximately 25 microns across) to pass (Fornell 2008). These filters can only be used for 5-10 minutes, after which time they are captured in a retrieval sheath and removed (Fornell 2008). 2. Distal occlusion balloons are used to temporarily block blood flow in a vessel while the cardiac procedure is carried out (Gruberg 2007). Following the procedure any debris collected in the stagnant column of blood behind the device can be removed using an aspiration catheter (Fornell 2008). Because antegrade flow is interrupted while the procedure is carried out, the procedure must take place rapidly (approximately 4-6 minutes) to reduce ischaemic damage to tissues that receive blood from the blocked vessel (Fornell 2008). 3. Proximal occlusion balloons interrupt the flow of blood upstream of the treatment area (Fornell 2008). These devices are placed before the actual surgical treatment 3

6 takes place and are therefore the only type of embolic protection that allows crossing of the stenosis under protection (Gruberg 2007). A previous Horizon Scanning Report was carried out on embolic protection devices (February 2009). The data collected for this report found the safety and efficacy of embolic protection devices to be inconclusive. Ultrasonic embolic protection devices are different to the devices included in the original report as they defer emboli from the path to the brain, rather than capturing them or stopping blood flow. In the trial carried out using EmBlocker, the outcomes of the device were compared with a control group, which received no embolic protection; therefore, another possible comparator for the EmBlocker device is no treatment (Sauren et al 2009). SAFETY AND EFFECTIVENESS ISSUES Searches identified two studies that used the EmBlocker device (Sauren et al 2007; Sauren et al 2009); only one of these studies reported its use in humans (Sauren et al 2009). Study description Twenty-one consecutive patients undergoing a heart valve procedure (with or without coronary artery bypass grafting) between February 2006 and August 2007 were enrolled in the non-randomised, single centre, comparative pilot study conducted by Sauren et al (2009). Eleven consecutive patients served as the experimental group where the EmBlocker device was positioned and activated for 1 minute at an intensity of 1.5 W/cm 2 during seven selected aortic manipulations and for 10 minutes at an intensity of 0.5 W/cm 2 intermittently after cross clamp removal. One patient in the experimental group was excluded due to technical problems with the EmBlocker device; therefore, a total of 10 patients (8 men, 2 women) with a mean age of 61.2 years (standard deviation, 7.8 years) remained. The other 10 patients (7 men, 3 women) with a mean age of 68.7 years (standard deviation, 5.4 years) served as the control group. In these patients the EmBlocker console was put in place to simulate use but was not activated. All patients were monitored intraoperatively for microembolic signals (MES) with bilateral transcranial Doppler of the middle cerebral arteries. Patients eligible for inclusion were men and women between 50 and 75 years of age. Exclusion criteria were extensive and included carotid atheroma higher than grade II, protruding ascending aortic atheroma > grade III, previous cardiac operation, uncontrolled diabetes, risk for surgery, Euroscore >8 1, left ventricular ejection fraction < 40% (35% for aortic stenosis), history of stroke, abnormal clotting activation with a prothrombin time > 60% and a partial thromboplastin time > 2 than the normal, emergency procedure, and a non-cardiac life-threatening disease. The transcranial Doppler readings obtained during the periods of EmBlocker activation were divided into 200 microsecond segments. The readings were manually examined for 1 European System for Cardiac Operative Risk Evaluation: 0-100%, the higher the percentage the higher the approximate predicted mortality. 4

7 the absence or presence of MES independently by two physicians who were blinded to treatment allocation. Any discrepancies between the physicians determinations were resolved through discussion until a consensus could be reached. Safety There were no safety data reported in this study. Effectiveness In all selected manipulations the number of MES was lower in patients in the EmBlocker group compared with the control group. During aortic manipulations, MES were 63% lower when the EmBlocker was used (P<0.05). The overall number of cerebral MES was also significantly lower in the EmBlocker group compared with the control group (53% reduction; P<0.05). There was no significant difference in the number of MES detected in the left and right middle cerebral arteries in either group. There was also no significant difference between the EmBlocker and control groups in terms of mean operative time (P=0.813), mean intensive care unit stay (p=0.093), or mean hospital stay (P=0.165). There were fewer MES detected during the air removal phase in the EmBlocker group (left artery 133 MES; right artery 119 MES) compared with the control group (left 252 MES; right 266 MES), although the difference was statistically significant. This may be due to the variation in the time between release of the cross clamp and decannulation, which would cause variation of the dissolving capacity of the remaining air in the heart and may contribute to a different number of emboli entering the circulatory system. The counting method used may underestimate the counted MES when the density of emboli is high because the size of the segments (200 ms) restricts the number of counted MES per second to five. In the EmBlocker group, the reduction of MES detected in the right middle cerebral artery was slightly higher than for the left artery (54% versus 49%). This may be due to some of the microemboli that were diverted away from the innominate artery appearing in the left common carotid artery. COST IMPACT There was no material retrieved in regards to the cost of the EmBlocker device, costeffectiveness studies were unavailable due to the early stages of diffusion of the procedure. Efforts to contact the device manufacturer in regards to cost were unsuccessful. Theoretically, the proposed reduction in neurological defects resulting from cardiac procedures could reduce subsequent costs to patients and their families as well as the healthcare system. According to the manufacturers website brain damage following cardiac surgery alone costs the US economy $2.5-4 billion in direct annual expenditure (Neurosonix Ltd. 2009) ETHICAL, CULTURAL OR RELIGIOUS CONSIDERATIONS No issues were identified from the retrieved material. 5

8 OTHER ISSUES One of the authors of the study disclosed that he had a financial relationship with the manufacturer of EmBlocker, Neurosonix Limited. Other study limitations include the use of MES as a surrogate marker to examine the efficacy of the EmBlocker device (Sauren et al 2009). The duration of follow-up did not extend past discharge; therefore, no correlation between lowered MES and improved neurological outcomes after surgery could be made. The patient population was highly selected, with extensive exclusion criteria eliminating high risk patients, so that the outcomes of EmBlocker are likely to be favourable. These results may not be representative of real life as not all patients undergoing a cardiac procedure with EmBlocker are likely to be as healthy (Sauren et al 2009). SUMMARY OF FINDINGS Results from one small pilot study indicate a significant reduction in cerebral MES when the EmBlocker device is activated during cardiac interventions (average reduction 53%) compared to patients in a sham control group in whom the EmBlocker was not activated. However, the study did not link the surrogate outcome measures with clinical benefits in the patients. Further studies, particularly randomised controlled trials, are needed to determine whether the EmBlocker technology has the potential to diminish the risk of postoperative neurological complications by reducing cerebral emboli during cardiac surgery. Studies that measure neurological damage may also be useful in supporting the use of ultrasonic embolic protection devices. HEALTHPACT ACTION Based on the limited available evidence and the potential benefit of this technology it is recommended that the Emblocker and all other potential ultrasonic embolic protective devices be monitored for 24 months. NUMBER OF STUDIES INCLUDED Total number of studies 1 Level III-2 evidence 1 REFERENCES Australian Institute of Health and Welfare (AIHW). Interactive National Hospital Morbidity Data: Count of procedures, all hospitals, by ACHI fifth edition, Asutralia, _0708_v2. (Accessed December 2009). Fornell D. Diagnostic and Invasive Cardiology: An introduction to embolic protection devices. Last Updated October (Accessed December 2009). 6

9 Gruberg L. Medscape Cardiology: Embolic protection in carotid artery stenting. Last Updated 31 st January (Accessed December 2009). Neurosonix Limited. The future of embolic protection: overview. Last Updated (Accessed January 2009). Peregrine Ventures. Neurosonix Ltd. announces receipt of CE mark certificate and ISO certification for EmBlocker, V2. Last Updated 14 December vc.com/news_item.asp?id=37 (Accessed December 2009). Sauren LDC, la Meir M, Bolotin G, van der Veen FH, Heijmans JH, Mess WH, Maessen JG. The EmBlocker: efficiency of a new ultrasonic embolic protection device adjunctive to heart valve surgery. The Annals of Thoracic Surgery 2009; 88(1): Sauren LDC, la Meir M, Palmen M, Severdija E, van der Veen FH, Mess WH Maessen JG. New ultrasonic radiation reduces cerebral emboli during extracorporeal circulation. European Journal of Cardio-Thoracic Surgery 2007; 32(2): (Animal study) US Food and Drug Administration. Medical Devices. Last Updated 17 December (Accessed December 2009). SOURCES OF FURTHER INFORMATION Sauren LDC, la Meir M, Palmen M, Severdija E, van der Veen FH, Mess WH Maessen JG. New ultrasonic radiation reduces cerebral emboli during extracorporeal circulation. European Journal of Cardio-Thoracic Surgery 2007; 32(2): (Animal study) SEARCH CRITERIA TO BE USED EmBlocker Ultrasonic embolic protection device/transducer Heart/cardiac/cardiac surgery Cerebral emboli/embolism 7