The past, present, and future

CHAPTER

The past, present, and future

25

Jonathan E. Millar*,†, Shaun D. Gregory†,‡,§, Michael C. Stevens‡,¶,k, Robert H. Bartlett**, John F. Fraser†,‡ Critical Care Research Group, The Prince Charles Hospital, Brisbane, QLD, Australia* School of Medicine, The University of Queensland, St Lucia, QLD, Australia† Innovative Cardiovascular Engineering and Technology Laboratory, Critical Care Research Group, Adult Intensive Care Service, The Prince Charles Hospital, Brisbane, QLD, Australia‡ School of Engineering, Griffith University, Southport, QLD, Australia§ Graduate School of Biomedical Engineering, University of New South Wales, Sydney, NSW, Australia¶ Central Clinical School, University of Sydney, Sydney, NSW, Australiak General and Thoracic Surgery, University of Michigan, Ann Arbor, MI, United States**

INTRODUCTION In the last 20 years, mechanical circulatory and respiratory support (MCRS) technologies have become firmly established in the management of a wide range of conditions. These indications span the continuum of critical care: from the hyperacute use of extracorporeal membrane oxygenation (ECMO) in patients suffering cardiac arrest to the use of destination mechanical circulatory support (MCS) for those with end-stage heart failure. The increasing use of ECMO and MCS technologies is largely a result of the improvements in device design and manufacture over the last two decades. The heavy physiological burden of complications associated with earlier iterations has been minimized, making MCRS more acceptable and accessible to a wider range of pathologies, clinicians, and centers. As the use of these technologies becomes more widespread, its research should reflect this. Growing attention must be paid to the organization and design of services for MCRS, to the long-term outcomes of patients receiving it, and to the interaction of devices and novel disease-modifying therapies. In this chapter, we consider the near future of MCRS and develop a research agenda that reflects it. This is not a comprehensive list of future research in the field and is aimed to promote discussion on strategies for future MCRS development.

Mechanical Circulatory and Respiratory Support. https://doi.org/10.1016/B978-0-12-810491-0.00025-4 Copyright # 2018 Elsevier Inc. All rights reserved.

775

776

CHAPTER 25 The past, present, and future

HOW TECHNOLOGY WILL CHANGE MECHANICAL CIRCULATORY AND RESPIRATORY SUPPORT? ECMO Recent growth in the use of ECMO is related to technological advances made in the latter half of the last decade. Around 2008, several companies marketed modern ECMO devices that are associated with lower rates of complication and increased ease of use [1]. Since then, sequential improvements in design have produced further gains. The use of coated tubing, such as covalently bonded heparin circuits (Bioline, Maquet, Carmeda, and Medtronic), has reduced the requirement for systemic anticoagulation during ECMO [2], while the miniaturization of control systems has resulted in improved portability and the opportunity to ambulate patients [3]. Further advances can be anticipated in the near future. Several areas of ongoing research and innovation are worth considering in detail. Circuit design—Advances in circuit biomaterial composition promise to remove several limitations of contemporary ECMO (Fig. 25.1). While heparin bonded circuits have reduced the need for systemic anticoagulation during ECMO, their short half-life limits their efficacy, particularly when the duration of ECMO is extended [4]. Contemporary circuits also fail to replicate the effects of an intact endothelium and as a result are potent activators of host inflammatory pathways [5]. The introduction of surface coatings capable of mimicking the abilities of the intact endothelium, the so-called “smart” coatings, may entirely abolish the need for anticoagulation and open the means by which the extracorporeal circulation (ECC) can become an antiinflammatory or antibacterial intervention [6].

pH T° ABG Coagulation

Contemporary ECMO circuits fail to replicate the intact human endothelium. This leads to protein absorption, platelet activation and an innate inflammatory response.

Advanced circuit designs will include in-vivo sensors. These will deliver real-time information about conditions within the extracorporeal circulation.

Advances in ecmo circuitry In future, “endothelialised” circuits, which secrete anti-coagulant compounds, will remove the need for systematic anticoagulation. Circuit polymers will be coated with bloodcompatible hydrogels or even human endothelial cells.

NO Antibiotic release anti-FXII anti-FXII

Novel anti-coagulant compounds will be incorporated into circuit coatings, such as Nitric Oxide (NO) and factor XII inhibitor.

NO

Bacteraemia

In certain clinical circumstances, circuits may be selected to release antiinflammatory drugs or even immune regulatory stem cells. Circuit coatings will incorporate pH or enzyme responsive triggers. Future circuits will be impregnated with antibiotic compounds, which are released when bacteria are detected.

FIG. 25.1 Advances in ECMO circuitry.

Of the candidate circuit coating materials under evaluation in this area, nitric oxide (NO)-releasing polymers are the most advanced. NO is an endogenous platelet inhibitor and has been shown to maintain platelets in a quiescent state during ECC [7]. Its use is limited by the fact that NO cannot prevent the absorption of

How technology will change mechanical circulatory and respiratory support? procoagulant proteins onto the surface of the polymer, a way in which platelets may still become activated. This problem may be overcome by the addition of a protein absorption resistant coating, such as polycarboxybetaine (pCB) [8]. Coatings with properties that go beyond simple thromboresistance are also under development. These include bacterial-triggered antimicrobial release coatings and coatings that can store and release various antiinflammatory drug compounds [9]. ECMO circuitry in the future may not be inert or simply thromboresistant but may become an intervention. In patients with sepsis, such as those with bacterial pneumonia leading to severe acute respiratory distress syndrome (ARDS), ECMO circuitry that releases antibiotic or antimicrobial compounds may be selected based on knowledge of the underlying pathogen. Likewise, in patients with hyperinflammatory states supported with ECMO, circuitry containing immobilized antiinflammatory mesenchymal stromal cells may be used as a therapy. Bio-active filters—The concept of extracorporeal blood purification as a treatment for sepsis has existed for some time, although practical technologies have so far failed to find widespread clinical application [10]. Of the differing means by which extracorporeal blood purification can be performed, hemoadsorptive devices appear to have the most promise. Hemoadsorption devices are placed in series with the ECC and can bind a range of molecules including cytokines, chemokines, endotoxins, and activated leukocytes [11,12]. The best studied hemoadsorption technologies are polymyxin B (PMX)-immobilized fiber column hemoperfusion (Toraymyxin, Toray Industries, Tokyo, Japan) and the CytoSorb system (CytoSorbents Corporation, New Jersey, the United States). The Toraymyxin device uses PMX, an antibiotic bound to polystyrene fibers, to filter endotoxin. Evidence for its use in patients supported with ECMO is limited to case reports, although successful integration with both venovenous (VV) and venoarterial (VA) ECMO has been achieved [13–15]. The CytoSorb unit consists of porous adsorbent polymerized beads, capable of filtering cytokines with molecular weights in the range of 10–55 kDa. Its use alongside ECMO has also been described in several case reports [16,17]. CytoSorb has been studied more extensively in a setting analogous to ECMO and cardiopulmonary bypass (CPB) [18]. Several randomized trials are currently recruiting, including the REFRESH trial (NCT02566525), which will examine the ability of CytoSorb to remove plasma-free hemaglobin (PFHb) during CPB, and the RECCAS study (DRKS00007928), which will evaluate interleukin-6 removal. At present, the evidence supporting hemoadsorptive extracorporeal blood purification is limited. Clinical trials, particularly those using polymyxin B, have produced conflicting results [19,20]. Despite the uncertain early development of hemoadsorption devices, the concept of extracorporeal filters used in conjunction with ECMO remains attractive. Future work should address the effects of PFHb removal during ECMO, given that elevated levels have been associated with an increased risk of renal failure and death [21–23]. Improvements in technology, especially in devices capable of isolating activated leukocytes, may present new options when treating patients with sepsis on ECMO. In the future, clinicians may be able to select individually tailored bioactive filters, placed in series with ECMO, to address hemolysis, cytokine storm, and endotoxemia.

777

778

CHAPTER 25 The past, present, and future

Microfluidic oxygenators and artificial lungs—Membrane oxygenators (MO) in current clinical use are almost all based on a hollow-fiber design. These devices can provide gas exchange rates of between 250 and 400 mL min1 [24]. This is clearly inferior to the performance of human lungs, with which even patients with chronic heart failure may still achieve a peak VO2 in excess of 25 mL kg1 min1 [25]. Ultimately, hollow-fiber MOs are limited by their relatively small surface area and the thickness of the blood-gas membrane. The production of microfluidic oxygenation systems may overcome these limitations. Here, microfabrication techniques are used to create branching vascular networks from materials such as polydimethylsiloxane (PDMS), with proportions similar to those found in the native lung [26]. Equally, microfluidic manufacturing techniques can be used to create extremely thin, nonporous, hollow fibers for gas transmission. These features confer microfluidic oxygenators with hugely superior surface area-to-volume ratios and more efficient gas exchange properties. An additional benefit of microfluidic devices is the substantial reduction in priming volume that would be achievable. Early versions have been successfully developed and tested in both ex vivo and animal models [27,28]. Rapid translation is limited by two key factors. Firstly, given the exceedingly thin diameter of the blood channels, there is a significant risk of thrombosis. This requires the design of nonthrombogenic coatings that exceed the performance of those currently in use. Secondly, novel manufacturing processes, which can scale sufficiently to allow commercial manufacture of microfluidic membranes, have yet to be developed. As research in this area matures, microfluidic oxygenators (MOs) may permit at least two fundamental shifts in the paradigm of ECMO provision. Firstly, in the acute setting, miniaturized MOs that permit near physiological gas exchange rates would allow patients on ECMO for cardiorespiratory failure to become truly ambulatory, freeing individuals to participate in strenuous rehabilitation programs. This would reduce the risk of physical deconditioning and postcritical care myopathy, which are associated with current management options. It is even conceivable to imagine that highly efficient MOs could remove the need for mechanical ventilation in a wide range of conditions. Secondly, novel MOs could pave the way for artificial lungs that are more analogous to contemporary MCS devices. This would see patients with chronic irreversible lung failure fitted with paracorporeal “destination” lung support devices, allowing them to lead extended active lives outside of a health care facility.

MECHANICAL CIRCULATORY SUPPORT The use of MCS continues to expand due to improved devices, medical management, and clinical acceptance. The rise in MCS use has been dramatic over the past decade, with the seventh Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) report demonstrating an increase in all device implants (ventricular assist devices (VAD) and total artificial heart (TAH)) from 95 in 2006 to 2738 in 2013 (Fig. 25.2) [29]. Improved device design has contributed significantly, evident by the increase in implanted rotary blood pumps (RBPs) from 0 in 2006 to 2642 in 2013. Survival with MCS has followed a similar path to implantation numbers, with recent data from the HeartWare ADVANCE trial demonstrating 84% 1-year survival [30]

How technology will change mechanical circulatory and respiratory support? Implants: June 2006–December 2014, n = 13286

3000

Continuous flow intracorporeal LVAD pump - axial Continuous flow intracorporeal LVAD pump - centrifugal

Implants per year

2500

Pulsatile flow intracoporeal TAH Pulsatile flow intracorporeal LVAD pump Pulsatile flow paracorporeal LVAD pump

2000 1500 1000 500 0 2006 CF intra pump/axial 0 CF intra pump/centrif 0 1 PF intra TAH PF intra pump 76 PF para pump 18

2007

2008

2009

2010

2011

2012

2013

0 0 22 260 55

459 0 30 180 72

867 0 24 54 65

1580 0 29 13 29

1838 0 26 2 54

2183 38 41 0 31

2044 598 74 1 21

2014 1695 728 54 0 24

FIG. 25.2 Implant numbers from mechanical circulatory support devices implanted between 2006 and 2014, reported in the INTERMACS database. Reprinted with permission from Kirklin JK, Naftel DC, Pagani FD, Kormos RL, Stevenson LW, Blume ED, et al. Seventh INTERMACS annual report: 15,000 patients and counting. J Heart Lung Transplant 2015;34 (12):1495–1504.

compared with 52% in the Randomized Evaluation of Mechanical Assistance for the Treatment of Congestive Heart Failure (REMATCH) trial [31]. In fact, the 1-year survival reported in the HeartWare ADVANCE trial is similar to that of the gold standard treatment of heart failure—heart transplant (85% 1-year survival) [32]. To continue the increasing trend of MCS implants and improved survival, device design must continue to be improved. Attention should be given to factors leading to the most common adverse events (such as bleeding and infection) and influences on poor quality of life (wearable systems and physiological control). Miniaturized devices that can be implanted less invasively should be given high priority, with the HeartWare MVAD being a potential solution with further development (Fig. 25.3). However, as discussed in Chapter 5, the shortcomings of the current miniaturized devices must be overcome. The same priority should also apply to total artificial hearts, with the only device currently used clinically being the large, pulsatile Syncardia TAH [33]. There are several devices under development that employ similar technology to that seen in rotary VADs to support the systemic and pulmonary circulations with a single rotating hub [34]. Progression of these devices to the clinical arena promises to be a game changer in this field and will see the relatively low TAH implant numbers increase significantly.

779

780

CHAPTER 25 The past, present, and future

FIG. 25.3 Computer-aided design of the less-invasive miniaturized ventricular assist device (MVAD), including an anchor for ventricular apex attachment and an outflow cannula to progress across the aortic valve. Reprinted with permission from Slaughter MS, Giridharan GA, Tamez D, LaRose JA, Sobieski M, Sherwood L, et al. Transapical miniaturized ventricular assist device: design and initial testing. J Thorac Cardiovasc Surg 2011;142(3):668–74.

Device designers must continue to optimize the blood-device interaction to reduce the effects on red blood cells, platelets, von Willebrand factors, etc. Interestingly, two of the more commonly implanted devices use different blood-contacting surface topologies, with the HeartWare HVAD employing a smooth, polished surface, while the HeartMate 3 employs textured surfaces. Another key difference between these devices is their output flow profile, with the HVAD operating at a relatively continuous speed (minor changes are prevalent when operated in the Lavare cycle) compared with the pulsatile speed profile of the HeartMate 3. Pulsatility may influence pump and vessel washout, aortic valve opening, arterial vascular function, blood trauma, end-organ perfusion, and more. Although the MOMENTUM 3 trial that compared the continuous flow HeartMate II and the pulsatile flow HeartMate 3 provides a useful comparison between those devices [35], the short- and long-term effects of pulsatility must be evaluated through a randomized, multicenter clinical trial comparing the same device in both continuous and pulsatile modes. Automatic RBP speed control based on patient cardiac demand (physiological control) should be implemented to reduce postoperative complications and improve quality of life. There has been significant research on RBP physiological control [36]; however, it is limited by only short-term clinical implementation [37]. While engineers continue to develop more advanced, robust but often complicated systems, clinicians argue over whether physiological control is even required. If even the smallest improvement in quality of life or reduction in complications can be implemented with a reliable system, then physiological control should be further explored. Perhaps a return to a basic control system, which is easily understood by clinicians, is the best way forward until clinical acceptance leads to implementation of more advanced systems. The advancement of physiological control systems does depend on the development of low-drift and high-accuracy pressure and/or flow sensors. There have been significant developments in this area recently [38], including the first report of a long-term pressure transducer implanted in the left atrium of patients with a HeartMate II [39].

Emerging applications for mechanical circulatory and respiratory support

Additional patient-device interactions to reduce complications and improve quality of life must also be explored. Less-invasive implantation techniques, particularly those which can be achieved without the use of cardiopulmonary bypass (associated with many postoperative complications), should be considered. Several sutureless inflow cannula designs have been proposed [40–42], and further development of these devices could dramatically improve patient outcomes. Wearable systems must be improved and battery life increased for improved patient comfort. HeartWare has seen the need for improved wearables, with data presented at the 2016 Congress of the International Society for Rotary Blood Pumps of a new system to be implemented in the near future. Tied to the wearable systems is the power and data transfer connections, which are currently limited by infection-prone percutaneous drivelines. Although transcutaneous energy transfer systems (TETS) are under development and would potentially solve this problem, cost and reliability (component and coil alignment) may limit worldwide clinical acceptance. Novel driveline coatings that reduce biofilm infiltration should be further explored as an alternative avenue. One exciting and untapped area of LVAD development is the harnessing of the Internet of things (IoT) for remote monitoring (RM) of LVAD patients. RM systems have been integrated into pacemakers for a long time; however, these systems have only been applied to LVADs recently. The HeartAssist 5 (ReliantHeart Inc., Houston, TX, the United States), at time of print, is the only LVAD that incorporates RM into its system [43]. At an individual patient level, the use of IoT to transmit pump and motor data, as well as events such as ventricular suction and low battery alarms to a medical team remotely may reduce the number of unnecessary outpatient visits while also providing clinical staff an opportunity to intervene prior to a potential hazardous event. At a larger scale, the collection of many anonymized patient data, in conjunction with big data analysis techniques, will enable researchers to identify trends in device usage and issues. This will provide researchers with a greater understanding of the day-to-day life of LVAD patients.

EMERGING APPLICATIONS FOR MECHANICAL CIRCULATORY AND RESPIRATORY SUPPORT ECMO In the last 10 years, the use of ECMO has expanded from the traditional indications of cardiac and respiratory failure. The use of ECMO in novel areas is opening extracorporeal support to a wider medical audience and changing how we perceive the therapy and its future use. These newer indications are addressed below.

E-CPR Extracorporeal cardiopulmonary resuscitation (E-CPR) is the single most rapidly expanding indication for ECMO. In the years 2016–17, the Extracorporeal Life Support Organization (ELSO) registry recorded a 46% increase in the total number of adult E-CPR cases performed. Extracorporeal support for refractory cardiac arrest is not a

781

782

CHAPTER 25 The past, present, and future

recent phenomenon; cardiopulmonary bypass has been used in this setting since the 1960s, particularly in cases of accidental hypothermia [44]. The novelty is the ease with which E-CPR is now performed. Advances in percutaneous cannulation and ECMO device technology have made the technique accessible to a much broader audience. What was once the domain of the cardiothoracic surgeon is now routinely performed by emergency physicians, intensive care specialists, and cardiologists [45–47]. Recently, we have witnessed the advent of “prehospital” E-CPR, with one of the first described cases undertaken within the confines of the Louvre Museum in Paris [48]. Despite growing enthusiasm, high-level evidence for benefit is lacking [49]. The situation is further complicated by the absence of universally accepted criteria for the institution of E-CPR, for both in-hospital (IHCA) and out-of-hospital cardiac arrest (OHCA). Using data from the ELSO registry, a large, international, multicenter cohort study has examined trends in E-CPR between 2003 and 2014 [50]. While failing to show any improvement in survival over time, these data do describe an increase in the mean age of patients undergoing E-CPR and an expansion in the number of comorbidities associated with individual patients. These factors, coupled with a rise in the number of cases performed, demonstrate a willingness to accept the use of E-CPR before more conclusive evidence of benefit becomes available. Given the nature of cardiac arrest, particularly OHCA, a randomized controlled study is challenging. Despite this, there are several clinical trials of E-CPR currently open to recruitment. Two randomized controlled trials (NCT01605409 and NCT03065647) have been designed to study E-CPR, performed on arrival to hospital, for OHCA. Neither of these studies lists functional neurological outcome as a primary measure. Another trial (NCT02527031) will examine the effectiveness of “prehospital” E-CPR for OHCA. A large pseudo-randomized trial (NCT02832752), using a parallelgroup design, is currently recruiting patients in Canada. This study allocates patients to either E-CPR for refractory OHCA or usual treatment based on region. The primary outcome measure is favorable neurological outcome (Cerebral Performance Category 1 or 2) at hospital discharge or 6 months. The use of VA-ECMO to perform E-CPR is likely to expand in the coming years. While observational studies offer evidence of survivors who would otherwise seem likely to have died [51], expansion brings with it a number of challenges. Firstly, inclusion criteria for E-CPR are variable. Further research is needed to better define those patients who will benefit from E-CPR. This will involve studies that address longer-term functional outcomes. Accelerating the implementation of E-CPR, without an appreciation of the long-term results, risks creating a cohort of patients who achieve a return of spontaneous circulation (ROSC) but have limited (or no) functional recovery. Secondly, the optimal means of organizing an E-CPR service remain open to debate. As the use of E-CPR becomes more widespread, relationships between center volume and outcome may become apparent. These problems may be solved using dedicated “prehospital” E-CPR teams. E-CPR is an area of exciting and rapid development. As uptake in the technique increases and current challenges are addressed, new refinements of the technique may improve survival. The potential applications of cerebral selective deep hypothermia during E-CPR are of particular interest [52].

Emerging applications for mechanical circulatory and respiratory support

ECMO and organ transplantation Advances in technology and its clinical application have rendered ECMO an important tool in the care of the heart-lung transplant patient. In lung transplantation, the use of ECMO increasingly spans the phases of patient care: as a bridge to transplant (BTT), as an intraoperative support, and as a means of rescuing those who suffer primary graft failure. In keeping with other indications, ECMO was first used to bridge patients to lung transplant as long ago as the 1970s [53]. However, this did not result in long-term survival until the early 1990s [54]. ECMO, in bridge-to-transplant situations, is now establishing itself as a routine technique [55]. This evolution follows a period in which 1-year survival for those undergoing ECMO BTT improved from 25% (2000–22) to almost 75% (2009–11) [56]. Most supporting data associated with ECMO BTT are derived from case series or retrospective registry studies, largely due to the near impossibility of controlled study in this situation. While large contemporary series show continuous improvements in survival [57], there are several questions that warrant further study. The most important of these relate to the timing of ECMO initiation and patient selection. Patients who require lung transplantation are a heterogenous group. They have a wide range of etiologies of irreversible lung failure and a similarly wide range of ages. This makes developing definitive patient selection criteria difficult. Disregarding the complexities, in health-care systems that use organ allocation scores, such as the US lung allocation score (LAS) [58], standardizing criteria for therapies like ECMO BTT is important in ensuring equality of access among patients listed for transplant. Evidence derived from a large, prospective, international, multicenter registry will be of used in identifying patient factors associated with outcome after ECMO BTT. The timing of ECMO initiation is as important as patient selection. In a retrospective review of over 15,000 primary lung transplants performed in the United States, Mason et al. described a reduction in 1-year survival for those who required pretransplant mechanical ventilation [59]. Some of this difference can be explained by the significant physical deconditioning that occurs during periods of mechanical ventilation. This has led many centers to recognize the fundamental importance of pretransplant rehabilitation [60]. ECMO BTT can now facilitate the rehabilitation process with the advent of “awake and ambulatory” support strategies [61]. Future work should address the effect of early initiation of “awake” ECMO BTT in selected patients, as a means of improving conditioning before transplant. During lung transplantation surgery, between 20% and 40% of patients require extracorporeal circulatory support [62]. Traditionally, this has been with cardiopulmonary bypass. While often necessary, this is by no means desirable, as CPB has been associated with acute lung injury in other settings [63–65]. The limitations of CPB have led to a recent proliferation in the use of ECMO as a method of intraoperative circulatory support during lung transplantation. This has been accompanied by emerging evidence of benefit, including a reduction in the need for blood transfusion, a reduction in ICU length of stay, and a decrease in 90-day mortality [66,67]. When using intraoperative ECMO, it is easier to extend support to the early postoperative period in those at high risk of primary graft dysfunction (PGD). Large

783

784

CHAPTER 25 The past, present, and future

randomized studies are required to fully assess the benefit of ECMO over CPB. The Bypass versus ECMO in Lung Transplant (BELT) study (NCT03021538) will randomize 80 patients commencing in early 2017. The influence of ECMO support, initiated before heart transplantation, is complex. In those who find themselves supported by ECMO due to an acute deterioration, the decision to progress directly to heart transplant, or to transition to MCS, may not always be clear. Numerous studies have reported lower 1-year survival rates in those undergoing heart transplant after ECMO [68]. Some have suggested that this is an acceptable risk given the high transplant waiting list mortality [69]. However, improvements in MCS, coupled with currently available outcome data, would suggest that direct to heart transplant strategies after ECMO should not be a preferred option. International, multicenter data sets, such as the International Society for Heart and Lung Transplantation (ISHLT) Registry, should be used to identify patient cohorts with poor outcome after a direct to heart transplant procedure. ECMO use in primary graft dysfunction after heart transplant has also become an established technique. The ISHLT consensus statement on PGD after heart transplant now suggests that mechanical circulatory support of PGD such as ECMO is indicated when medical management is not sufficient to support the newly transplanted graft [70]. Even with the early application of ECMO in those suffering PGD, mortality is still significant [71], and survivors have been shown to have impaired physical function in the longer term [72]. Ongoing work should access the impact of posttransplant ECMO support on meaningful functional outcomes.

Other emerging indications for ECMO ECMO in Sepsis—Among adults, preexisting sepsis was once considered a relative contraindication to ECMO. But with the advent of modern device technology and increased familiarity with its use, many centers are turning to ECMO as an intervention in refractory septic shock. Intuitively, VA-ECMO is more likely to benefit those with sepsis-induced cardiac dysfunction than those with distributive shock. This has been partially confirmed by observational studies [73,74]. In a single-center prospective study, Park et al. described an association between higher peak troponin I measurements and survival [75]. Mortality rates for those with refractory septic shock treated with ECMO vary widely between series, with quoted figures ranging between 15% and 70% [73–76]. However, in their small series of adult males supported with VA-ECMO during bacterial septic shock, Br
echot et al. reported good long-term quality-of-life measures among survivors. With mortality rates in the low 20% range, VA-ECMO for septic shock has a survivability comparable with E-CPR. As the practicality of ECMO for the general intensivist increases, VA-ECMO may become a viable option to treat patients with septic shock who are refractory to medical management. Studies using standardized inclusion criteria are required. These should address both patient selection and the optimal timing of ECMO support. ECMO in Trauma—Historically, VV-ECMO has been used in cases of ARDS occurring after blunt chest trauma [77]. In fact, its first recorded use for adult respiratory failure was in a 24-year-old man who had sustained a thoracic aortic

Emerging applications for mechanical circulatory and respiratory support

transection and rib fractures after blunt injury [78]. A prerequisite was the ability to tolerate systemic anticoagulation, and thus, there was a requirement for hemostasis. This view has been challenged by more recent evidence. In a case series of 10 individuals with severe major trauma and hemorrhagic shock, Arlt et al. described the use of both VV- and VA-ECMO to treat cardiopulmonary failure [79]. Heparinization was omitted during treatment and several patients underwent damage control surgery while on ECMO. The successful use of ECMO in cases of traumatic brain injury and in spinal cord injury has since been described [80,81]. Work performed in a rabbit model of traumatic hemorrhage even suggests that the use of heparin-freeVA-ECMO may ameliorate acute traumatic coagulopathy [82]. In the future, emergent ECMO (VV or VA) may become an intervention used in the early period after major trauma, supporting patients during damage control surgery procedures and in the immediate postoperative phase. Additional preclinical work is required to evaluate the relationship between ECMO and acute traumatic coagulopathy and to better understand how ECMO can be integrated into existing resuscitation strategies. In the meantime, there have been a number of calls to include trauma as a distinct indication for ECMO within the ELSO registry [83].

MECHANICAL CIRCULATORY SUPPORT Device strategy for MCS implantation has evolved over the past decade, particularly with regulatory approval of devices for destination therapy. Used as the primary implant strategy in less than 30% of patients in the 2008–11 era, destination therapy has become a major strategy in recent times with over 45% of patients in 2014 according to the seventh INTERMACS database [29]. As expected, survival (at least up to 30 months post implant) is reduced in patients supported as destination therapy compared with those in the bridge-to-transplant group (Fig. 25.4). However, with continued device development, improved medical management, and continued trials of destination therapy for new devices (e.g., the HeartWare HVAD ENDURANCE trial), there should be an increase in long-term survival of patients with MCS. MCS implantation in less-sick patients is another avenue that has been partially explored but would benefit from additional research. The primary study to date, known as the ROADMAP study by Thoratec, evaluated the HeartMate II against optimal medical management in ambulatory New York Heart Association (NYHA) class IIIB/IV (INTERMACS profile 4–7) heart failure patients [84]. Survival was higher in the HeartMate II group at 1 year (80% vs 63%), while the primary end point of survival on the original therapy with at least a 75 m increase in 6 min walk test distance was achieved with 39% of patients in the HeartMate II group, compared with just 21% of patients on optimal medical management. Quality-of-life metrics favored the HeartMate II group, although adverse events were also higher in this group with bleeding the most frequent event. Although the 2-year followup study presented similar results (Fig. 25.5) with reduced adverse events in the HeartMate II group [85], additional long-term clinical data would assist with gaining clinical acceptance for MCS in this less-sick population.

785

Continuous flow LVAD/BiVAD implants: 2008–2014, n = 12030

Bridge to transplant listed and destination therapy by era 100 90

BTT listed: 2012 – 2014 N = 1761, deaths = 215

80 BTT listed: 2008 – 2011 n = 1529, Deaths = 344

% Survival

70 DT: 2012 – 2014

60

N = 3243, deaths = 863

50 40

DT: 2008 – 2011 N = 1355, deaths = 682

30 20

P < 0.0001

10 0

Event: Death (censored at transplant and recovery) 6

0

12

18 24 30 Months post implant

36

42

48

FIG. 25.4 Survival comparison between bridge to transplant and destination therapy strategies by era reported in the INTERMACS database. Reprinted with permission from Kirklin JK, Naftel DC, Pagani FD, Kormos RL, Stevenson LW, Blume ED, et al. Seventh INTERMACS annual report: 15,000 patients and counting. J Heart Lung Transplant 2015;34 (12):1495–1504.

100 80 ± 4%

Event-free survival (%)

80

70 ± 5% 63 ± 5%

60 P < 0.001 HR = 2.3 [1.5–3.7], OMM vs LVAD

41 ± 5%

40 LVAD arm free from death, urgent HTx, or urgent explant OMM arm free from death, delayed LVAD, or urgent HTx 20

0

97 103 0

60 35

74 58 6

12

18

24

Time post-enrollment (months)

FIG. 25.5 Survival as treated in the ROADMAP study, comparing LVAD support against optimal medical management (OMM). Htx, heart transplant; HR, hazard ratio. Reprinted with permission from Starling RC, Estep JD, Horstmanshof DA, Milano CA, Stehlik J, Shah KB, et al. Risk assessment and comparative effectiveness of left ventricular assist device and medical management in ambulatory heart failure patients: the ROADMAP study 2-year results. JACC Heart Fail 2017.

Emerging applications for mechanical circulatory and respiratory support

FIG. 25.6 The Infant Jarvik 2015 ventricular assist device. Reprinted with permission from Baldwin JT, Adachi I, Teal J, Almond CA, Jaquiss RD, Massicotte MP, et al. Closing in on the PumpKIN trial of the jarvik 2015 ventricular assist device. Semin Thorac Cardiovasc Surg Pediatr Card Surg Annu 2017;20:9–15.

The pediatric population will also benefit from additional development and clinical trials with MCS. Currently, the National Heart, Lung, and Blood Institute (NHLBI) Pumps for Kids, Infants, and Neonates (PumpKIN) program is seeking to develop pediatric-specific devices. The Infant Jarvik 2015 device (Fig. 25.6) is a promising option to support the pediatric population [86], with FDA approval for a clinical trial in infants and children [87]. It is vital that this research continues, while other pediatricspecific devices are developed as alternatives to support the smaller patient population. Right heart failure after left ventricular assist device (LVAD) implantation is a significant complication, exacerbated by the fact that there are no clinically approved long-term implantable right ventricular assist devices (RVADs) available. While the development of an implantable RVAD-specific device is required, clinicians are currently using approved LVADs for right-sided MCS [88]. Clinical experience with this configuration is still limited, with some centers opting to operate the RVAD in a reduced speed mode, while others band the outflow graft to match the lowerpressure pulmonary circulation. A multicenter trial comparing the two techniques would be of significant value, especially as the alternative modes may induce poor pump washout (reduced speed) or high shear and potential poor washout at the restriction (banded outflow graft). Another possible avenue for future development

787

788

CHAPTER 25 The past, present, and future

is a control system for biventricular assist devices to prevent flow imbalance caused by improper speed settings. However, this would require development of new controller hardware that allows operation of two LVADs from a single console. A future strategy for MCS should include the development of low-cost devices to support patients with advanced heart failure in lower socioeconomic environments. In 2001, it was estimated that there were 16 million deaths from cardiovascular disease, with only 3 million estimated deaths in high-income countries where optimal medical therapy including pharmaceuticals, ventricular assist devices, and transplants are available [89]. There is a clear need for improved cardiovascular support for the millions of patients dying each year in middle- or low-income countries. Meanwhile, age-specific rates of cardiovascular disease are increasing in middleor low-income countries, while developed countries report reductions due to optimal medical therapy [89,90]. For instance, 3%–7% of all hospital admissions in Africa are caused by heart failure [91], while cardiovascular disease is now the leading cause of death in South America [92]. Meanwhile, heart failure incidence throughout Asia and the Arab population is starting to record similar rates to Western countries [93,94]. While pharmaceutical treatments are becoming cheaper and available in most areas of the world, more expensive and often critical options such as MCS are simply unaffordable [95]. A global collaborative to develop a low-cost device (many aspects of the “device cost” must be reduced including development, regulatory, marketing, insurance, etc. costs) to support patients all over the world could be the most clinically significant step forward in the MCS field.

ORGANIZING THE PROVISION OF MECHANICAL CIRCULATORY AND RESPIRATORY SUPPORT IN THE FUTURE ECMO As the number of patients supported by ECMO and the number of centers offering it each continue to expand [96], the way in which services are organized will evolve. Current guidelines on service provision and arrangement are provided by ELSO and in a position statement published by ECMONet (http://www.internationalecmonetwork. org) [97]. The international ECMONet collaborative consensus statement offers specific advice in relation to the organization and design of ECMO services for severe acute respiratory failure. In their paper, they recommend the creation of ECMO tertiary referral centers, which provide services to peripheral hospitals as part of a network. In this scenario, peripheral hospitals refer cases to the tertiary center for consideration of ECMO, and if appropriate, the ECMO center dispatches a mobile team. This team may choose to retrieve the patient to the ECMO center where support is initiated or elect to establish the patient on ECMO at the peripheral hospital prior to transfer. Experiences with ECMO retrieval services are well documented [98–100]. This approach to system design has been formally established in several countries, including the United Kingdom [101]. This arrangement seems to apply equally to the provision of ECMO for cardiac failure. Tertiary centers should be capable of providing the full spectrum of ECMO and MCS support.

Organizing the provision of mechanical circulatory and respiratory support in the future The organizational structure outlined above is prudent, while ECMO remains a comparatively uncommon intervention. As its role expands in the care of critically ill patients, this model may require revision. This is especially true if E-CPR or the use of ECMO for refractory septic shock becomes a common practice. An illustration of how this may work can be found in the development of modern inclusive trauma systems. In many countries, major trauma patients are cared for as part of a trauma network [102]. These networks are based on a hub-and-spoke model, with a major trauma center at the core, interlinked with several smaller trauma units. The major trauma center can provide the full array of definitive interventions for the most severely injured, as well as coordinating training, research, and governance. Trauma units are hospitals that retain the ability to resuscitate and stabilize major trauma patients prior to transfer to the major trauma center, treat and retain the less severely injured, or receive patients repatriated from the major trauma center for ongoing acute care or rehabilitation. This system can be readily applied to the provision of ECMO (Fig. 25.7). In the future, the monopoly on the provision of ECMO currently held by tertiary referral centers could diffuse to a wider network of institutions. The tertiary center would remain the central focus of the network. Here, complex cases or those requiring more advanced support options would be treated. Smaller ECMO units would work with the tertiary center to provide short-term uncomplicated VV- or VA-ECMO in cardiorespiratory failure, E-CPR, or VA-ECMO for sepsis or poisoning. This would reduce the requirement for intrahospital transfer and expand the availability of a potentially life-saving intervention.

MECHANICAL CIRCULATORY SUPPORT MCS has come a long way over the last three decades, from keeping approximately 50% of patients alive after 1 year in the early trials (e.g., REMATCH) to matching the 1-year survival of heart transplant recipients. Patients have been supported by MCS for over 10 years now on a single device. With growing support durations and implant numbers, more data are being gathered, resulting in improved device development and medical management. This must continue to further reduce MCS-associated complications and improve patient quality of life. The US-based INTERMACS database is a fantastic but insular resource that can assist with directing future research; however, a combined database with other regions would add more data and lead to even more rapid evolution of this field. As seen in the INTERMACS reports, MCS devices are gaining clinical acceptance. It is vital this momentum is maintained, and that engineers and clinicians improve the technology and our medical management strategies to improve patient outcomes. Approximately half of the patients receiving MCS in the United States are aimed at destination therapy, often returning home to regular daily activities and an improved quality of life. Gathering pump and patient data during these activities is essential for the development of the next generation of MCS devices. As patients become more comfortable with their device, issues such as battery life, driveline complications, and need for physiological control will become more apparent.

789

790

- Provides 24/7 clinical leadership to the network

Repatriation when appropriate

H

- Takes the lead for governance, research and education

Peripheral ecmo unit - Capable of initiating E-CPR, VV-ECMO and VA-ECMO Referral for advanced care

FIG. 25.7 Relationships in an inclusive ECMO network.

- Retains straight forward ECMO cases locally

CHAPTER 25 The past, present, and future

Regional ecmo centre - Full spectrum of MCRS interventions

References

MCS in rural areas must also be considered. Most regions have large cardiac centers based in major cities; however, these centers can have massive geographic separation in large countries such as the United States, Canada, and Australia. Continued clinical experience and further development of the less-invasive devices such as the Abiomed Impella are critical to meet the demands for MCS in rural areas. Devices that can be rapidly implanted without the patient going to the surgical theater will save countless lives, even if they only provide short-term support until the patient can be transferred to a larger center. Additional clinical training and experience of rural centers for less-invasive device implantation will see MCS implant numbers dramatically increase.

CONCLUSION This book demonstrates the ever-broadening scope and importance of contemporary MCRS, and many chapters highlight the significant advances that have been made in the recent past. Looking to the future, the pace of advance seems set to continue. In the short to medium term, MCRS will become a much more routine feature of clinical medicine, transforming from a niche endeavor to a much more common set of interventions. This has been facilitated by dramatic improvements in technology over the last decade but will be sustained by improvements in clinical organization and an expanding evidence base. In the same time frame, sequential improvements in design will continue to improve the convenience and safety of MCRS. In the longer term, emerging technologies have the potential to revolutionize MCRS. While the common theme of miniaturization will continue to be worked upon, future technologies will also improve the biointegration of devices. MCRS devices will no longer be implanted foreign objects but will become biologically active. This will pave the way for MCRS to become a long-term ambulatory therapy for end-stage heart and lung failure, eliminating the need for organ transplantation. The last 20 years has been an era of remarkable progress in the fields of extracorporeal organ support and in implantable mechanical assist devices. The work of researchers and clinicians has brought these interventions to a point of consistent productivity. In the next 20 years, advancements will fundamentally alter the practice of medicine. Our hope is that this will result in not only longer lives for the patients that require such interventions but also a greater quality of life.

REFERENCES [1] Bartlett RH. ECMO: the next ten years. Egypt J Crit Care Med 2016;4(1):7–10. [2] Sy E, Sklar MC, Lequier L, Fan E, Kanji HD. Anticoagulation practices and the prevalence of major bleeding, thromboembolic events, and mortality in venoarterial extracorporeal membrane oxygenation (VA-ECMO): a systematic review and metaanalysis. J Crit Care 2017;39:87–96. [3] Alwardt CM, Wilson DS, Alore ML, Lanza LA, Devaleria PA, Pajaro OE. Performance and safety of an integrated portable extracorporeal life support system for adults. J Extra Corpor Technol 2015;47(1):38–43.

791

792

CHAPTER 25 The past, present, and future

[4] Kidane AG, Salacinski H, Tiwari A, Bruckdorfer KR, Seifalian AM. Anticoagulant and antiplatelet agents: their clinical and device application(s) together with usages to engineer surfaces. Biomacromolecules 2004;5(3):798–813. [5] Millar JE, Fanning JP, McDonald CI, McAuley DF, Fraser JF. The inflammatory response to extracorporeal membrane oxygenation (ECMO): a review of the pathophysiology. Crit Care 2016;20(1):387. [6] Wo Y, Brisbois EJ, Bartlett RH, Meyerhoff ME. Recent advances in thromboresistant and antimicrobial polymers for biomedical applications: just say yes to nitric oxide (NO). Biomater Sci 2016;4(8):1161–83. [7] Major TC, Brisbois EJ, Jones AM, Zanetti ME, Annich GM, Bartlett RH, et al. The effect of a polyurethane coating incorporating both a thrombin inhibitor and nitric oxide on hemocompatibility in extracorporeal circulation. Biomaterials 2014;35 (26):7271–85. [8] Amoako KA, Sundaram HS, Suhaib A, Jiang S, Cook KE. Multimodal, biomaterialfocused anticoagulation via superlow fouling zwitterionic functional groups coupled with anti-platelet nitric oxide release. Adv Mater Interfaces 2016;3(6):1500646. [9] Cloutier M, Mantovani D, Rosei F. Antibacterial coatings: challenges, perspectives, and opportunities. Trends Biotechnol 2015;33(11):637–52. [10] Shum HP, Yan WW, Chan TM. Extracorporeal blood purification for sepsis. Hong Kong Med J 2016;22(5):478–85. [11] Zhou F, Peng Z, Murugan R, Kellum JA. Blood purification and mortality in sepsis: a meta-analysis of randomized trials. Crit Care Med 2013;41(9):2209–20. [12] Rimmel
e T, Kaynar AM, McLaughlin JN, Bishop JV, Fedorchak MV, Chuasuwan A, et al. Leukocyte capture and modulation of cell-mediated immunity during human sepsis: an ex vivo study. Crit Care 2013;17(2):R59. [13] Shin SH, Lee H, Choi AJ, Chang KHJ, Suh GY, Chung CR. Use of polymyxin B hemoperfusion in a patient with septic shock and septic cardiomyopathy who was placed on extracorporeal membrane oxygen support. Korean J Crit Care Med 2016;31(2):123–8. [14] Lee YK, Ryu JA, Yang JH, Park C-M, Suh GY, Jeon K, et al. Refractory septic shock treated with nephrectomy under the support of extracorporeal membrane oxygenation. Korean J Crit Care Med 2015;30(3):176–9. [15] Itai J, Ohshimo S, Kida Y, Ota K, Iwasaki Y, Hirohashi N, et al. A pilot study: a combined therapy using polymyxin-B hemoperfusion and extracorporeal membrane oxygenation for acute exacerbation of interstitial pneumonia. Sarcoidosis Vasc Diffuse Lung Dis 2015;31(4):343–9. [16] Bruenger F, Kizner L, Weile J, Morshuis M, Gummert JF. First successful combination of ECMO with cytokine removal therapy in cardiogenic septic shock: a case report. Int J Artif Organs 2015;38(2):113–6. [17] Trager K, Schutz C, Fischer G, Schroder J, Skrabal C, Liebold A, et al. Cytokine reduction in the setting of an ARDS-associated inflammatory response with multiple organ failure. Case Rep Crit Care 2016;2016:9852073. [18] Bernardi MH, Rinoesl H, Dragosits K, Ristl R, Hoffelner F, Opfermann P, et al. Effect of hemoadsorption during cardiopulmonary bypass surgery—a blinded, randomized, controlled pilot study using a novel adsorbent. Crit Care 2016;20(1):96. [19] Cruz DN, Antonelli M, Fumagalli R, Foltran F, Brienza N, Donati A, et al. Early use of polymyxin B hemoperfusion in abdominal septic shock: the EUPHAS randomized controlled trial. JAMA 2009;301(23):2445–52.

References

[20] Payen DM, Guilhot J, Launey Y, Lukaszewicz AC, Kaaki M, Veber B, et al. Early use of polymyxin B hemoperfusion in patients with septic shock due to peritonitis: a multicenter randomized control trial. Intensive Care Med 2015;41(6):975–84. [21] Omar HR, Mirsaeidi M, Socias S, Sprenker C, Caldeira C, Camporesi EM, et al. Plasma free hemoglobin is an independent predictor of mortality among patients on extracorporeal membrane oxygenation support. PLoS ONE 2015;10(4). e0124034. [22] Lyu L, Long C, Hei F, Ji B, Liu J, Yu K, et al. Plasma free hemoglobin is a predictor of acute renal failure during adult venous-arterial extracorporeal membrane oxygenation support. J Cardiothorac Vasc Anesth 2016;30(4):891–5. [23] Pan KC, McKenzie DP, Pellegrino V, Murphy D, Butt W. The meaning of a high plasma free haemoglobin: retrospective review of the prevalence of haemolysis and circuit thrombosis in an adult ECMO centre over 5 years. Perfusion 2015;31(3):223–31. [24] Potkay JA. The promise of microfluidic artificial lungs. Lab Chip 2014;14 (21):4122–38. [25] Riley M, Po´rsza´sz J, Stanford CF, Nicholls DP. Gas exchange responses to constant work rate exercise in chronic cardiac failure. Br Heart J 1994;72(2):150. [26] Kniazeva T, Hsiao JC, Charest JL, Borenstein JT. A microfluidic respiratory assist device with high gas permeance for artificial lung applications. Biomed Microdevices 2011;13(2):315–23. [27] Rochow N, Manan A, Wu W-I, Fusch G, Monkman S, Leung J, et al. An integrated array of microfluidic oxygenators as a neonatal lung assist device: in vitro characterization and in vivo demonstration. Artif Organs 2014;38(10):856–66. [28] Hoganson DM, Pryor 2nd HI, Bassett EK, Spool ID, Vacanti JP. Lung assist device technology with physiologic blood flow developed on a tissue engineered scaffold platform. Lab Chip 2011;11(4):700–7. [29] Kirklin JK, Naftel DC, Pagani FD, Kormos RL, Stevenson LW, Blume ED, et al. Seventh INTERMACS annual report: 15,000 patients and counting. J Heart Lung Transplant 2015;34(12):1495–504. [30] Slaughter MS, Pagani FD, McGee EC, Birks EJ, Cotts WG, Gregoric I, et al. HeartWare ventricular assist system for bridge to transplant: combined results of the bridge to transplant and continued access protocol trial. J Heart Lung Transplant 2013;32(7):675–83. [31] Rose EA, Gelijns AC, Moskowitz AJ, Heitjan DF, Stevenson LW, Dembitsky W, et al. Long-term use of a left ventricular assist device for end-stage heart failure. N Engl J Med 2001;345(20):1435–43. [32] Lund LH, Edwards LB, Kucheryavaya AY, Benden C, Christie JD, Dipchand AI, et al. The registry of the international society for heart and lung transplantation: thirty-first official adult heart transplant report—2014; focus theme: retransplantation. J Heart Lung Transplant 2014;33(10):996–1008. [33] Torregrossa G, Anyanwu A, Zucchetta F, Gerosa G. SynCardia: the total artificial heart. Ann Card Surg 2014;3(6):612–20. [34] Cohn WE, Timms DL, Frazier OH. Total artificial hearts: past, present, and future. Nat Rev Cardiol 2015;12(10):609–17. [35] Mehra MR, Naka Y, Uriel N, Goldstein DJ, Cleveland JCJ, Colombo PC, et al. A fully magnetically levitated circulatory pump for advanced heart failure. N Engl J Med 2017;376(5):440–50. [36] AlOmari AHH, Savkin AV, Stevens M, Mason DG, Timms DL, Salamonsen RF, et al. Developments in control systems for rotary left ventricular assist devices for heart failure patients: a review. Physiol Meas 2013;34:R1–R27.

793

794

CHAPTER 25 The past, present, and future

[37] Moazami N, Fukamachi K, Kobayashi M, Smedira NG, Hoercher KJ, Massiello A, et al. Axial and centrifugal continuous-flow rotary pumps: a translation from pump mechanics to clinical practice. J Heart Lung Transplant 2013;32(1):1–11. [38] Poeggel S, Tosi D, Leen G, Lewis E. Low drift and high resolution miniature optical fiber combined pressure- and temperature sensor for cardio-vascular and other medical applications. Proc IEEE Sens 2013;9107:1–6. [39] Hubbert L, Baranowski J, Delshad B, Ahn H. Change of left atrial pressure, LAP measured with a wireless implantable pressure sensor (titan sensor) during echocardiographic RAMP-test in HeartMate II patients. J Heart Lung Transplant 2015;34: S218–9. [40] Koenig SC, Jimenez JH, West SD, Sobieski MA, Choi Y, Monreal G, et al. Early feasibility testing and engineering development of a sutureless beating heart (SBH) connector for left ventricular assist devices (LVAD). ASAIO J 2014;60(6):617–25. [41] Cohn W. Automated Surgical Connector. US 2008/0009887 A1, SEMMT, Houston; 2008. [42] Gregory SD, Liebhardt A, Pearcy M, Timms D. Cannula. BiVACOR Pty Ltd Queensland University of Technology; 2015. [43] Pektok E, Demirozu ZT, Arat N, Yildiz O, Oklu E, Eker D, et al. Remote monitoring of left ventricular assist device parameters after HeartAssist-5 implantation. Artif Organs 2013;37(9):820–5. [44] Kennedy JH. The role of assisted circulation in cardiac resuscitation. JAMA 1966;197 (8):615–8. [45] Tonna JE, Johnson NJ, Greenwood J, Gaieski DF, Shinar Z, Bellezo JM, et al. Practice characteristics of emergency department extracorporeal cardiopulmonary resuscitation (eCPR) programs in the United States: the current state of the art of emergency department extracorporeal membrane oxygenation (ED ECMO). Resuscitation 2016;107:38–46. [46] Stub D, Bernard S, Pellegrino V, Smith K, Walker T, Sheldrake J, et al. Refractory cardiac arrest treated with mechanical CPR, hypothermia, ECMO and early reperfusion (the CHEER trial). Resuscitation 2015;86:88–94. [47] Arlt M, Philipp A, Voelkel S, Schopka S, Husser O, Hengstenberg C, et al. Early experiences with miniaturized extracorporeal life-support in the catheterization laboratory. Eur J Cardiothorac Surg 2012;42(5):858–63. [48] Lamhaut L, Hutin A, Deutsch J, Raphalen J-H, Jouffroy R, Orsini J-P, et al. Extracorporeal cardiopulmonary resuscitation (ECPR) in the prehospital setting: an illustrative case of ECPR performed in the Louvre museum. Prehosp Emerg Care 2017;1–4. [49] Ortega-Deballon I, Hornby L, Shemie SD, Bhanji F, Guadagno E. Extracorporeal resuscitation for refractory out-of-hospital cardiac arrest in adults: a systematic review of international practices and outcomes. Resuscitation 2016;101:12–20. [50] Richardson AS, Schmidt M, Bailey M, Pellegrino VA, Rycus PT, Pilcher DV. ECMO cardio-pulmonary resuscitation (ECPR), trends in survival from an international multicentre cohort study over 12-years. Resuscitation 2017;112:34–40. [51] Kim SJ, Kim HJ, Lee HY, Ahn HS, Lee SW. Comparing extracorporeal cardiopulmonary resuscitation with conventional cardiopulmonary resuscitation: a meta-analysis. Resuscitation 2016;103:106–16. [52] Wang C-H, Lin Y-T, Chou H-W, Wang Y-C, Hwang J-J, Gilbert JR, et al. Novel approach for independent control of brain hypothermia and systemic normothermia: cerebral selective deep hypothermia for refractory cardiac arrest. J Neurointerv Surg 2017;9 (8):e32.

References

[53] Veith FJ. Lung transplantation. Transplant Proc 1977;9(1):203–8. [54] Jurmann MJ, Haverich A, Demertzis S, Schaefers HJ, Wagner TO, Borst HG. Extracorporeal membrane oxygenation as a bridge to lung transplantation. Eur J Cardiothorac Surg 1991;5(2):94–7. discussion 98. [55] Chiumello D, Coppola S, Froio S, Colombo A, Del Sorbo L. Extracorporeal life support as bridge to lung transplantation: a systematic review. Crit Care 2015;19(1):19. [56] Hayanga AJ, Aboagye J, Esper S, Shigemura N, Bermudez CA, D’Cunha J, et al. Extracorporeal membrane oxygenation as a bridge to lung transplantation in the United States: an evolving strategy in the management of rapidly advancing pulmonary disease. J Thorac Cardiovasc Surg 2015;149(1):291–6. [57] Biscotti M, Gannon WD, Agerstrand C, Abrams D, Sonett J, Brodie D, et al. Awake extracorporeal membrane oxygenation as bridge to lung transplantation: a 9-year experience. Ann Thorac Surg 2017;104(2):412–9. [58] Egan TM, Murray S, Bustami RT, Shearon TH, McCullough KP, Edwards LB, et al. Development of the new lung allocation system in the United States. Am J Transplant 2006;6(5p2):1212–27. [59] Mason DP, Thuita L, Nowicki ER, Murthy SC, Pettersson GB, Blackstone EH. Should lung transplantation be performed for patients on mechanical respiratory support? The US experience. J Thorac Cardiovasc Surg 2010;139(3):765–773.e1. [60] Lehr CJ, Zaas DW, Cheifetz IM, Turner DA. Ambulatory extracorporeal membrane oxygenation as a bridge to lung transplantation. Chest 2015;147(5):1213–8. [61] Biscotti M, Sonett J, Bacchetta M. ECMO as bridge to lung transplant. Thorac Surg Clin 2015;25(1):17–25. [62] Hoechter DJ, Shen Y-M, Kammerer T, G€unther S, Thomas W, Schramm R, et al. Extracorporeal circulation during lung transplantation procedures: a meta-analysis. ASAIO J 2017. Publish Ahead of Print. [63] Massoudy P, Zahler S, Becker BF, Braun SL, Barankay A, Meisner H. Evidence for inflammatory responses of the lungs during coronary artery bypass grafting with cardiopulmonary bypass. Chest 2001;119(1):31–6. [64] Kotani N, Hashimoto H, Sessler DI, Muraoka M, Wang JS, O’Connor MF, et al. Cardiopulmonary bypass produces greater pulmonary than systemic proinflammatory cytokines. Anesth Analg 2000;90(5):1039–45. [65] Kotani N, Hashimoto H, Sessler DI, Muraoka M, Wang JS, O’Connor MF, et al. Neutrophil number and interleukin-8 and elastase concentrations in bronchoalveolar lavage fluid correlate with decreased arterial oxygenation after cardiopulmonary bypass. Anesth Analg 2000;90(5):1046–51. [66] Biscotti M, Yang J, Sonett J, Bacchetta M. Comparison of extracorporeal membrane oxygenation versus cardiopulmonary bypass for lung transplantation. J Thorac Cardiovasc Surg 2014;148(5):2410–5. [67] Machuca TN, Collaud S, Mercier O, Cheung M, Cunningham V, Kim SJ, et al. Outcomes of intraoperative extracorporeal membrane oxygenation versus cardiopulmonary bypass for lung transplantation. J Thorac Cardiovasc Surg 2015;149(4):1152–7. [68] Zalawadiya S, Fudim M, Bhat G, Cotts W, Lindenfeld J. Extracorporeal membrane oxygenation support and post-heart transplant outcomes among United States adults. J Heart Lung Transplant 2017;36(1):77–81. [69] Jasseron C, Lebreton G, Cantrelle C, Legeai C, Leprince P, Flecher E, et al. Impact of heart transplantation on survival in patients on venoarterial extracorporeal membrane oxygenation at listing in France. Transplantation 2016;100(9):1979–87.

795

796

CHAPTER 25 The past, present, and future

[70] Kobashigawa J, Zuckermann A, Macdonald P, Leprince P, Esmailian F, Luu M, et al. Report from a consensus conference on primary graft dysfunction after cardiac transplantation. J Heart Lung Transplant 2014;33(4):327–40. [71] Chou N-K, Chi N-H, Yu H-Y, Lin J-W, Wang C-H, Wang S-S, et al. Extracorporeal rescue for early and late graft failure after cardiac transplantation: short result and long-term followup. Sci World J 2013;2013:8. [72] Hayes K, Holland AE, Pellegrino VA, Leet AS, Fuller LM, Hodgson CL. Physical function after extracorporeal membrane oxygenation in patients pre or post heart transplantation—an observational study. Heart Lung 2016;45(6):525–31. [73] Huang C-T, Tsai Y-J, Tsai P-R, Ko W-J. Extracorporeal membrane oxygenation resuscitation in adult patients with refractory septic shock. J Thorac Cardiovasc Surg 2013;146(5):1041–6. [74] Cheng A, Sun HY, Lee CW, Ko WJ, Tsai PR, Chuang YC, et al. Survival of septic adults compared with nonseptic adults receiving extracorporeal membrane oxygenation for cardiopulmonary failure: a propensity-matched analysis. J Crit Care 2013;28 (4):532.e1–532.e10. [75] Park TK, Yang JH, Jeon K, Choi SH, Choi JH, Gwon HC, et al. Extracorporeal membrane oxygenation for refractory septic shock in adults. Eur J Cardiothorac Surg 2015;47(2):e.68–74. [76] Br
echot N, Luyt C-E, Schmidt M, Leprince P, Trouillet J-L, L
eger P, et al. Venoarterial extracorporeal membrane oxygenation support for refractory cardiovascular dysfunction during severe bacterial septic shock. Crit Care Med 2013;41(7):1616–26. [77] Bosarge PL, Raff LA, McGwin Jr. G, Carroll SL, Bellot SC, Diaz-Guzman E, et al. Early initiation of extracorporeal membrane oxygenation improves survival in adult trauma patients with severe adult respiratory distress syndrome. J Trauma Acute Care Surg 2016;81(2):236–43. [78] Hill JD, O’Brien TG, Murray JJ, Dontigny L, Bramson ML, Osborn JJ, et al. Prolonged extracorporeal oxygenation for acute post-traumatic respiratory failure (shock-lung syndrome). Use of the Bramson membrane lung. N Engl J Med 1972;286(12):629–34. [79] Arlt M, Philipp A, Voelkel S, Rupprecht L, Mueller T, Hilker M, et al. Extracorporeal membrane oxygenation in severe trauma patients with bleeding shock. Resuscitation 2010;81(7):804–9. [80] Lotzien S, Schildhauer TA, Aach M, Strauch J, Swol J. Extracorporeal lung support in patients with spinal cord injury: single center experience. J Spinal Cord Med 2016;1–5. [81] Biscotti M, Gannon W, Abrams D, Agerstrand C, Claassen J, Brodie D, et al. Extracorporeal membrane oxygenation use in patients with traumatic brain injury. Perfusion 2015;30(5):407–9. € [82] Larsson M, Forsman P, Hedenqvist P, Ostlund A, Hultman J, Wikman A, et al. Extracorporeal membrane oxygenation improves coagulopathy in an experimental traumatic hemorrhagic model. Eur J Trauma Emerg Surg 2016;1–9. [83] Swol J, Cannon JW, Napolitano LM. ECMO in trauma: what are the outcomes? J Trauma Acute Care Surg 2017;82(4):819–20. [84] Estep JD, Starling RC, Horstmanshof DA, Milano CA, Selzman CH, Shah KB, et al. Risk assessment and comparative effectiveness of left ventricular assist device and medical management in ambulatory heart failure patients: results from the ROADMAP study. J Am Coll Cardiol 2015;66(16):1747–61. [85] Starling RC, Estep JD, Horstmanshof DA, Milano CA, Stehlik J, Shah KB, et al. Risk assessment and comparative effectiveness of left ventricular assist device and medical

References

[86]

[87]

[88]

[89]

[90] [91] [92] [93] [94]

[95] [96]

[97]

[98]

[99]

[100]

[101] [102]

management in ambulatory heart failure patients: the ROADMAP study 2-year results. JACC Heart Fail 2017;5(7):518–27. Wei X, Li T, Li S, Son HS, Sanchez P, Niu S, et al. Pre-clinical evaluation of the infant jarvik 2000 heart in a neonate piglet model. J Heart Lung Transplant 2013;32 (1):112–9. Heart J. Jarvik Heart Receives FDA Approval for Clinical Trial of Miniature Heart Assist Device for Infants and Children. http://www.jarvikheart.com/news/jarvik15mm-press/ [accessed 10.05]. Hetzer R, Krabatsch T, Stepanenko A, Hennig E, Potapov EV. Long-term biventricular support with the heartware implantable continuous flow pump. J Heart Lung Transplant 2010;29(7):822–4. Mathers C, Salomon J, Ezzati M, Begg S, Vander-Hoorn S, Lopez A. Global burden of disease and risk factors. Washington, DC: The International Bank for Reconstruction and Development/The World Bank; New York: Oxford University Press; 2006. Murray CJ, Lopez AD. Mortality by cause for eight regions of the world: global burden of disease study. Lancet 1997;349(9061):1269–76. Oyoo GO, Ogola EN. Clinical and socio demographic aspects of congestive heart failure patients at Kenyatta National Hospital, Nairobi. East Afr Med J 1999;76(1):23–7. Mendez GF, Cowie MR. The epidemiological features of heart failure in developing countries: a review of the literature. Int J Cardiol 2001;80(2–3):213–9. Agarwal AK, Venugopalan P, de Bono D. Prevalence and aetiology of heart failure in an Arab population. Eur J Heart Fail 2001;3(3):301–5. Sanderson JE, Chan SK, Chan WW, Hung YT, Woo KS. The aetiology of heart failure in the Chinese population of Hong Kong—a prospective study of 730 consecutive patients. Int J Cardiol 1995;51(1):29–35. Sanderson JE, Tse Tf. Heart failure: a global disease requiring a global response. Heart 2003;89(6):585–6. Thiagarajan RR, Barbaro RP, Rycus PT, McMullan DM, Conrad SA, Fortenberry JD, et al. Extracorporeal life support organization registry international report 2016. ASAIO J 2017;63(1):60–7. Combes A, Brodie D, Bartlett R, Brochard L, Brower R, Conrad S, et al. Position paper for the organization of extracorporeal membrane oxygenation programs for acute respiratory failure in adult patients. Am J Respir Crit Care Med 2014;190(5):488–96. Broman LM, Holzgraefe B, Palm
er K, Frenckner B. The Stockholm experience: interhospital transports on extracorporeal membrane oxygenation. Crit Care 2015;19 (1):278. Javidfar J, Brodie D, Takayama H, Mongero L, Zwischenberger J, Sonett J. Safe transport of critically ill adult patients on extracorporeal membrane oxygenation support to a regional extracorporeal membrane oxygenation center. ASAIO J 2011;57:421–5. Desebbe O, Rosamel P, Henaine R, Vergnat M, Farhat F, Dubien PY. Interhospital transport with extracorporeal life support: results and perspectives after 5 years experience. Ann Fr Anesth Reanim 2013;32:225–30. Peek GJ. Organization of extracorporeal membrane oxygenation for acute respiratory distress syndrome in the United Kingdom. Reanimation 2013;22(3):673–7. McCullough AL, Haycock JC, Forward DP, Moran II CG. Major trauma networks in England. Br J Anaesth 2014;113(2):202–6.

797

798

CHAPTER 25 The past, present, and future

FURTHER READING [1] Slaughter MS, Giridharan GA, Tamez D, LaRose JA, Sobieski M, Sherwood L, et al. Transapical miniaturized ventricular assist device: design and initial testing. J Thorac Cardiovasc Surg 2011;142(3):668–74. [2] Baldwin JT, Adachi I, Teal J, Almond CA, Jaquiss RD, Massicotte MP, et al. Closing in on the PumpKIN trial of the jarvik 2015 ventricular assist device. Semin Thorac Cardiovasc Surg Pediatr Card Surg Annu 2017;20:9–15.