Journal of Cardiothoracic and Vascular Anesthesia 33 (2019) 11591162

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Journal of Cardiothoracic and Vascular Anesthesia

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Pro and Con Pro: Venoarterial Extracorporeal Membrane Oxygenation Should Always Include Placement of a Left Ventricular Vent

1 Meena Bhatia, MD*, , Priya A. Kumar, MD*,y

*Department of Anesthesiology, University of North Carolina School of Medicine, Chapel Hill, NC yOutcomes Research Consortium, Cleveland, OH

Key Words: venoarterial extracorporeal membrane oxygenation; left ventricular vent; left ventricular distention

THE USE OF VENOARTERIAL extracorporeal membrane common cannulation strategy for . Although oxygenation (VA-ECMO) for refractory cardiogenic shock there are no large, randomized controlled studies comparing has become increasingly common.1 The purpose of instituting unloading of the LV during VA-ECMO, it is the authors’ opin- VA-ECMO is 2-fold: first and foremost, to provide perfusion ion that an LV vent should always be placed. to vital organs, and secondly, to decrease myocardial oxygen Traditional cannulation for peripheral VA-ECMO involves a demand and potentially promote myocardial recovery.2,3 Sur- femoral venous cannula extending into the right atrium and femo- vival after VA-ECMO is reportedly low at 25% to 45% for a ral arterial cannulation. Venous blood, however, continues to number of reasons.4 A potential complication of both central flow through the native circulation and eventually reaches the and peripheral VA-ECMO is the development of left ventricu- LV, causing dilation. In the presence of severe LV dysfunction, lar distention. Because there is inevitable incomplete unload- the LV is unable to eject this blood forward, thereby increasing ing of the left ventricle (LV), a certain amount of distention is distention. If a patient has concomitant aortic regurgitation, this likely to occur in most adult patients on VA-ECMO. This cycle only worsens. Furthermore, as the arterial cannula delivers occurs regardless of cannulation strategy. Schiller et al.5 dem- oxygenated blood throughout the body, retrograde blood flow onstrated this concept in 10 pigs randomized to receive VA- from the cannula increases . A severely compromised ECMO either through peripheral or central cannulation. Left LV is unable to eject against this increased afterload, promoting ventricular performance was measured during the first 5 hours further LV distention. With continued distentionandworsening in both groups. The investigators found that both LV ejection volume overload, the LV potentially can suffer from myocardial fraction and stroke work decreased similarly in both groups. strain and increased oxygen demands.6 Myocardial recovery may Distention was seen universally, with comparable increases in become challenging in this scenario. The rates of unwanted LV LV end-diastolic volume (LVEDV) and LV end-systolic vol- distention during VA-ECMO range from 12% to 68%.7 Down- ume.5 The clinical significance of LV distention is somewhat stream effects of this vicious cycle go beyond myocardial strain. theoretical and often relates to the underlying cause of cardio- Left ventricular failure often is associated with the development genic shock and the severity of LV dysfunction. For the pur- of mitral annular dilatation and functional mitral regurgitation poses of this article, the authors will discuss LV distention in (MR). Worsening mitral valve incompetence in turn leads to the setting of peripheral ECMO, as it remains the most increased left atrial pressures and, potentially, pulmonary edema. Patients whose LV dysfunction is severe enough for the aortic 1Address reprint requests to Meena Bhatia, MD, University of North Caro- valve to remain closed, and patients with aortic regurgitation, lina School of Medicine, N2198 UNC Hospitals, CB 7010, Chapel Hill, NC have higher degrees of LV distention and MR.810 Furthermore, 27599-7010. E-mail address: [email protected] (M. Bhatia). the development of stagnant blood in a nonejecting LV can https://doi.org/10.1053/j.jvca.2018.11.004 1053-0770/Ó 2018 Elsevier Inc. All rights reserved. 1160 M. Bhatia and P.A. Kumar / Journal of Cardiothoracic and Vascular Anesthesia 33 (2019) 11591162 increase the risk for thrombus formation. Hireche-Chikaoui et al. retrograde into the LV across the aortic valve. There are differ- have described this phenomenon and reported on several cases in ent sizes and settings of the Impella that can allow various flow which reduced flow across the aortic valve during VA-ECMO rates and amounts of LV unloading.1719 Eliet et al. examined allowed for thrombus formation in the aortic root.11 Although the the impact of the Impella on hemodynamic markers, including true prevalence of this event is unknown, observational studies Doppler velocity-time integral (pVTI) and have quoted the incidence of intracardiac thrombus after VA- LV end-diastolic diameter (LVEDD). The authors assessed ECMO to be as high as 4% to 10%. Nearly half of thrombus for- 11 patients on VA-ECMO who subsequently had an Impella mation occurs within the aortic root,11,12 and the aftermath of this placed for LV venting. They compared pVTI and LVEDD dur- occurrence can be catastrophic. ing stepwise increases in Impella flow. They observed Multiple strategies may be used to unload the LV during increases in pVTI and decreases in LVEDD as Impella flows peripheral VA-ECMO. One of the easiest and least invasive were increased, suggesting that improvements in pulmonary methods is the use of an intra-aortic balloon pump (IABP). flow and LV decompression were occurring in a stepwise fash- The IABP not only decreases afterload during systole, but also ion. They also looked at end-tidal carbon dioxide monitoring facilitates unloading and decreases myocardial oxygen con- as a surrogate for pulmonary blood flow and noted increases sumption.13 Petroni et al. did a prospective observational study with increased Impella flow.20 These observations are particu- where they examined hemodynamic changes associated with larly interesting because they show that the adjustment of concomitant IABP and VA-ECMO support of patients in car- Impella flows based on individual patient LV size allows the diogenic shock. They evaluated 12 patients before and 30 achievement of desired amounts of decompression. minutes after discontinuing IABP support while on VA- In a recent study by Lim et al., Impella use in patients on ECMO. They found that when the IABP was paused, patients VA-ECMO had a favorable effect on pulmonary pressures had higher pulmonary artery occlusion pressures, increased and right ventricular (RV) . A cohort of 6 LV end-systolic volume and LVEDV, and decreased pulsatil- patients received an Impella plus VA-ECMO for cardio- ity. When the IABP was restarted, hemodynamics improved, genic shock. Pulmonary pressures were measured 2 hours and markers of LV distention decreased.14 There are essen- after initiation of Impella flows. A marked reduction in pul- tially no randomized controlled trials comparing clinical out- monary capillary wedge pressure and pulmonary vascular comes in patients on VA-ECMO with and without IABP resistance was noted. Pulmonary artery capacitance also support. However, in a retrospective review of Japanese data- increased, with reduced RV afterload resulting in increased bases, Aso et al. extracted data from a large number of patients RV stroke volume. With increasingly favorable RV hemo- who were placed on VA-ECMO with IABP counterpulsation dynamics, 4 of the 6 patients with an Impella plus VA- for cardiogenic shock. After propensity matching, the authors ECMO survived. Similar to previous studies, bleeding and examined 533 patients in the VA-ECMO only group and 533 hemolysis were the most common complications noted.21 patients in the IABP plus VA-ECMO group. They found that Cardiogenic shock can take many forms and often is not patients in the IABP plus VA-ECMO group had a statistically isolated to the LV. Pulmonary edema and increased RV significant lower in-hospital mortality (55% v 64%) and a afterload are well-known complications of cardiogenic reduced 28-day mortality (48% v 58%). Furthermore, 82% shock. The decompression seen with Impella support helps from the IABP plus VA-ECMO group were weaned success- not only to reduce the workload on the RV, but also to opti- fully from ECMO versus 73% in the VA-ECMO only group.15 mize hemodynamics and facilitate RV recovery. This study is in stark contrast to an observational analysis of Fiedler et al. retrospectively studied 59 patients at Massachu- 1,517 pooled patients by Cheng et al., where there was no sur- setts General Hospital who were placed on VA-ECMO from vival benefit (21% v 28%) between the VA-ECMO alone and 2015 to 2017. Twelve of these patients had concomitant Impella IABP plus VA-ECMO groups. In this analysis, however, placement for LV decompression. The survival rate in the IABP insertion at the time of initiation of VA-ECMO occurred Impella plus VA-ECMO group was 58%, including 5 patients in only 5 of 16 studies examined. It is important to note this who were bridged to myocardial recovery. The 5 nonsurvivors significant bias and the fact that the number of patients all had echocardiographic evidence of dilated and hypokinetic assessed and the study quality were inferior to the more recent LVs. Seven of the 12 patients with combined therapy had hemo- observations reported by Aso et al.16 Also noteworthy is the lysis and 5 had bleeding complications, which are the most relatively low rate of complications associated with IABP use common complications associated with the Impella. The use of in both studies. There are, however, scenarios where place- an Impella plus VA-ECMO did, however, result in improved ment of an IABP may be inappropriate, as in the case of LV function, LV decompression, and a trend toward increased patients who are coagulopathic or in the presence of significant survival compared with VA-ECMO alone.22 aortic regurgitation. Generally speaking, the IABP is mini- The scarcity of large randomized controlled trials comparing mally invasive and safe and can easily serve as a vent during the Impella plus VA-ECMO to ECMO alone makes it challeng- VA-ECMO. ing to draw conclusions about effectiveness; however, emerging Another method of decreasing LV distention associated small studies show promise. Cheng et al. found that Impella use with VA-ECMO is through the use of percutaneous axial flow with VA-ECMO resulted in LV decompression and reduced sta- devices such as the Impella (Abiomed U.S., Danvers, MA). sis.23 Koeckert et al. presented a case report of a 70-year-old This device is a catheter-mounted rotary pump that is placed man in cardiogenic shock who developed pulmonary edema M. Bhatia and P.A. Kumar / Journal of Cardiothoracic and Vascular Anesthesia 33 (2019) 11591162 1161 and respiratory failure on VA-ECMO. After placement of an References Impella, the LV was decompressed, and oxygen saturation improved. Both devices were removed after 5 days, at which 1 Karagiannidis C, Brodie D, Strassmann S, et al. Extracorporeal membrane time the patient demonstrated myocardial recovery.24 Perhaps oxygenation: Evolving epidemiology and mortality. Intensive Care Med one of the largest cohorts of patients with Impella plus VA- 2016;42:889–96. 2 Camboni D, Philipp A, Rottenkolber V, et al. Long-term survival and qual- ECMO support was from a retrospective study of 157 patients 25 ity of life after extracorporeal life support: A 10-year report. Eur J Car- on VA-ECMO reported by Pappalardo et al. In this cohort, 34 Thor Surg 2017;52:241–7. patients also had an Impella placed for decompression. The 3 Rihal CS, Naidu SS, Givertz MM. Society for Cardiovascular Angiography authors found a significantly lower hospital mortality in the and Interventions (SCAI). Failure Society of America (HFSA). Soci- VA-ECMO plus Impella group (47% v 80%) and a higher rate ety of Thoracic Surgeons (STS). American Heart Association (AHA). American College of Cardiology (ACC). 2015 SCAI/ACC/HFSA/STS of successful bridge to recovery or subsequent therapy (76% v clinical expert consensus statement on the use of percutaneous mechanical 20%). Because patients in the Impella plus VA-ECMO group circulatory support devices in cardiovascular care: Endorsed by the Ameri- had a higher survival rate, they did have prolonged ventilation can Heart Associaton, the Cardiological Society of India, and Sociedad times and higher rates of hemofiltration. Similar to previously Latino Americana de Cardiologia Intervencion; affirmation of value by the cited publications, the Impella plus VA-ECMO group had Canadian association of interventional cardiology-association Canadienne de Cardiologie d’intervention. J Am Coll Cardiol 2015;65:e7–26. higher rates of hemolysis (76% v 33%), but there was no signifi- 25 4 Truby LK, Takeda K, Mauro C, et al. Incidence and implications of left cant difference in bleeding between groups. ventricular distention during venoarterial extracorporeal membrane oxy- Although the IABP and Impella are 2 of the least invasive genation support. ASAIO J 2017;63:257–65. methods for venting the LV, numerous case reports have dem- 5 Schiller P, Vikholm P, Hellgren L. Experimental venoarterial extracorpo- onstrated success with more invasive techniques. Avalli et al. real membrane oxygenation induces left ventricular dysfunction. ASAIO J 2016;62:518–24. described percutaneous placement of a venous cannula into the 6 Truby LK, Takeda K, Mauro C, et al. Incidence and implications of left pulmonary artery via the right internal jugular vein to vent the ventricular distention during venoarterial extracorporeal membrane oxy- 26 LV. Aiyagari et al. published a large series of successful per- genation support. ASAIO J 2017;63:257–65. cutaneous decompressions with trans-septal puncture and left 7 Soleimani B, Pae WE. Management of left ventricular distention during atrial drainage.27 This is similar in concept to the venous out- peripheral extracorporeal membrane oxygenation for cardiogenic shock. Perfusion 2012;274:326–31. flow from the TandemHeart (Cardiac Assist, Inc., Pittsburgh, 8 Ostadal P, Mlcek M Kruger A, et al. Increasing venoarterial extracorporeal PA), where a long cannula placed trans-septally via the femoral membrane oxygenation flow negatively affects left ventricular performance vein decompresses the left heart. Several other case reports in a porcine model of cardiogenic shock. J Transl Med 2015;13:266. have described retrograde placement of a transaortic LV vent 9 Aissaoui N, Guerot E, Combes A, et al. Two-dimensional strain rate and Dopp- via the femoral or subclavian artery.2830 Each method, ler tissue myocardial velocities: Analysis by echocardiography of hemodynamic and functional changes of the failed left ventricle during different degrees of although not without risk, can help with appropriate decompres- extracorporeal life support. J Am Soc Echocardiogr 2012;25:632–40. sion of a damaged LV. Because of the paucity of literature on 10 Strunina S, Ostadal P. Left ventricle unloading during veno-arterial extra- this subject, there are limited studies looking at mortality and corporeal membrane oxygenation. Curr Res Card 2016;3:5–8. other primary outcomes. It does appear, however, that when LV 11 Hireche-Chikaou H, Grubler MR, Bloch A, et al. Nonejecting on distention is present, a multitude of approaches can accomplish femoral veno-arterial extracorporeal membrane oxygenation: Aortic root 31 blood stasis and thrombus formation. Crit Care Med 2018;46:459–64. similar levels of decompression. Large, randomized trials are 12 Williams B, Bernstein W. Review of venoarterial extracorporeal mem- needed to allow further comment on the effects of invasive brane oxygenation and development of intracardiac thrombosis in adult methods of LV decompression on mortality. cardiothoracic patients. J Extra Corpor Technol 2016;48:162–7. In conclusion, VA-ECMO is being used increasingly as a 13 Ma P, Zhang Z, Song T, et al. Combining ECMO with IABP for the form of rescue therapy in patients suffering from cardiogenic treatment of critically ill adult patients. Heart Lung Circ 2014;23:363–8. shock. When the LV is severely compromised, VA-ECMO 14 Petroni T, Harrois A, Amour J, et al. Intra-aortic balloon pump effects on can lead to a nonejecting state. Increased afterload from arte- macrocirculation and microcirculation in cardiogenic shock patients sup- rial cannula flow can result in LV distention that culminates in ported by venoarterial extracorporeal membrane oxygenation. Crit Care worsening MR, pulmonary edema, and stasis of flow.32 Med 2014;42:2075–82. Numerous case reports have shown that stasis in the LV can 15 Aso S, Matsui H, Fushimi K, et al. The effect of intraaortic balloon pump- 11,12 ing under venoarterial extracorporeal membrane oxygenation on mortality propagate clot formation. Furthermore, increases in of cardiogenic patients: An analysis using a nationwide inpatient database. LVEDV can lead to increased myocardial wall stress and oxy- Crit Care Med 2016;44:1974–9. 33 gen consumption, inhibiting potential myocardial recovery. 16 Cheng R, Hachamovitch R, Makkar R, et al. Lack of survival benefit As survival among patients on VA-ECMO remains dismal, it found with use of intraaortic balloon pump in extracorporeal membrane is important to attempt to minimize potential complications. oxygenation: A pooled experience of 1517 patients. J Invasive Cardiol 2015;10:453–8. The placement of an LV vent is not without risk, but the litera- 17 O’Neill WW, Kleiman NS, Moses J. A prospective, randomized clinical ture supports a variety of methods for accomplishing decom- trial of hemodynamic support with Impella 2.5 versus intra-aortic balloon pression. Supporting evidence is admittedly weak on both pump in patients undergoing high-risk percutaneous coronary intervention: sides of the argument, and despite the need for large, random- The PROTECT II study. Circulation 2012;126:1717–27. ized trials, it is the authors’ opinion that patients who are on 18 O’Neill WW, Schreibe T, Wohns DH. The current use of Impella 2.5 in acute complicated by cardiogenic shock: Results VA-ECMO should have an LV vent placed to prevent inevita- from the USpella Registry. J Interv Cardiol 2014;27:1–11. ble LV distention. 1162 M. Bhatia and P.A. Kumar / Journal of Cardiothoracic and Vascular Anesthesia 33 (2019) 11591162

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