Lack of Survival Benefit Found With Use of Intraaortic Balloon Pump in Extracorporeal Membrane Oxygenation: A Pooled Experience of 1517 Patients

Abstract: Objective. Intraaortic balloon pumps (IABPs) are frequently used as an adjunctive device to extracorporeal membrane oxygenation (ECMO) and are routinely placed at the initiation of ECMO at many institutions. Evidence for the additive benefit of IABP therapy is limited and conflicting in part due to small sample sizes. In the absence of large randomized trials, a meta-analysis would best elucidate potential benefit. Methods. A systematic PubMed/Medline search was performed. Studies reporting on survival to hospital discharge for cardiogenic shock and cardiac arrest requiring ECMO with an IABP subgroup were included. Concomitant IABP was compared with patients on ECMO alone. Secondary analyses included acute myocardial infarction (AMI) and postcardiotomy cardiogenic shock (PCS) subgroups, as well as timing of IABP insertion. Results. Sixteen studies were included in the main analysis, encompassing 1517 patients. The cumulative survival rate for patients on ECMO was 256/683 (37.5%) compared with 294/834 (35.3%) for patients with adjunctive IABP. Concomitant IABP was not associated with improved survival (risk ratio [RR], 1.143; 95% confidence interval [CI], 0.973-1.343; P=.10). IABP was not associated with improved survival in AMI patients (RR, 1.120; 95% CI, 0.772-1.624; P=.55), PCS (RR, 1.121; 95% CI, 0.826-1.520; P=.46) when placed prior to ECMO initiation (RR, 0.948; 95% CI, 0.718-1.252; P=.71), or when routinely inserted (RR, 1.102; 95% CI, 0.806-1.506; P=.54). Conclusion. Based on this observational analysis, the concomitant use of IABP with ECMO did not appear associated with a dramatic change in survival outcomes. The routine insertion of concomitant IABP with ECMO is not supported by our findings.

J INVASIVE CARDIOL 2015;27(10):453-458. Epub 2015 July 15

Key words: intraaortic balloon pump, outcomes

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Venoarterial extracorporeal membrane oxygenation (ECMO) has been widely employed for cardiogenic shock and cardiac arrest refractory to usual resuscitative techniques such as vasopressor and intraaortic balloon pump (IABP) use. To date, there have been no large randomized control trials of venoarterial ECMO, but an incremental survival benefit is generally accepted for “crashing and burning” patients who would otherwise have a diminutive chance of survival. IABPs are frequently used as an adjunctive device to ECMO and are routinely placed at the initiation of ECMO at many medical centers.^1-7 However, the evidence for the additive benefit of IABP therapy is limited, leaving clinicians uncertain on whether to remove previously inserted IABPs or to routinely place them at the time of ECMO initiation. 

Advocates of concomitant IABP and ECMO use note IABP’s theoretical benefit in left ventricular (LV) decompression, afterload reduction, improved diastolic pressures and coronary flow, and increased organ perfusion, and recommend routine concomitant placement with ECMO.^8,9 LV venting as an adjunct to ECMO especially has been widely reported with various techniques and devices.^10-17 However, despite their widespread use, none of these adjunctive techniques for LV venting has been established to have an incremental survival benefit compared with ECMO alone.

Moreover, studies conflict regarding the additive benefit of concomitant IABP support with centers that observe an increased survival with their use attributing the benefit to the aforementioned mechanisms.^9,18 However, these observations are in contrast with several other studies showing no additive survival benefit.^3,19-21 Small sample sizes may be partly to blame for the differences. Despite the lack of clarity, the practice of concomitant initiation of IABP with ECMO is already widespread, and at the expense of increased costs and vascular complications, including lower-extremity ischemia, compartment syndrome, fasciotomy, and amputation.²²

While large, prospective, randomized clinical trials would best elucidate the benefits of concomitant IABP with ECMO, in their absence, a pooled experience in the form of a meta-analysis represents the next best method. The purpose of this study was to determine whether concomitant use of IABP with ECMO associated with improved survival in patients with cardiogenic shock and arrest, and whether use in prespecified patient subgroups and placement strategies would demonstrate the most benefit.

Methods

Study selection and inclusion/exclusion criteria. A systematic PubMed/Medline search using the terms ECMO, ECLS, extracorporeal membrane oxygenation, and extracorporeal life support, cardiac shock, cardiogenic shock, cardiopulmonary resuscitation, cardiac arrest, myocardial infarction, IABP, and balloon pump was performed. Studies with n ≥10 reporting on venoarterial ECMO outcomes in adult patients for cardiogenic shock and cardiac arrest published in the year 2000 or later and reporting on the endpoint of survival to hospital discharge in an IABP subgroup were included. Studies reporting on non-human subjects or that were not accessible in English were excluded. Additionally, for studies that contained overlapping patient cohorts, those reporting on fewer patients were excluded. Study selection and reporting of statistics followed MOOSE and PRISMA systematic review and meta-analysis guidelines. The flow diagram for included and excluded studies is illustrated in Figure 1.

Planned analyses. The “main analysis” included all studies. Secondary analyses included concomitant IABP use with ECMO for cardiogenic shock or arrest due to acute myocardial infarction (AMI) and for postcardiotomy cardiogenic shock (PCS). The strategies of leaving previously placed IABP in place at ECMO initiation (“analysis prior”), and routine IABP placement at time of ECMO initiation (“analysis routine”) were also analyzed.

Statistical analysis. Cochran’s Q and I² values for heterogeneity are reported. The random effects model was utilized for all analyses. In the presence of low heterogeneity, fixed and random effects models would approximate the same point estimates and confidence intervals (CIs). Statistics were performed with a commercially available meta-analysis statistical software (Comprehensive Meta-Analysis version 2.2; Biostat, Inc).

Results

A systematic Medline search (Figure 1) resulted in 1361 articles as of April, 2014. Sixteen studies were included in the main analysis, encompassing 1517 patients.

Of the 16 studies, a total of 14 were explicit in their inclusion criteria for initiation of ECMO, which included inability to maintain systolic blood pressure >70-90 mm Hg or a mean blood pressure >65 mm Hg despite vasopressors and IABP, along with signs of organ hypoperfusion, or in the presence of cardiopulmonary arrest or malignant ventricular arrhythmias.^{1-5,9,20,23-29} The remaining 2 studies did not define the severity of cardiogenic shock that necessitated ECMO.^19,21

Nine out of 16 studies described post-discharge outcomes. Mean follow-up for patients who survived to discharge ranged from 1.0-3.5 years, with conditional survival ranging from 87%-100% in 7 studies.^{9,20,21,23,25,26,29} New York Heart Association heart failure class was described in 2 studies as I-II in 83%-100% of patients,^21,25 and in 1 study as class 1.5 ± 0.6.²⁰ In 2 studies with actuarial 5-year outcomes, conditional survival was 55.8% and 67.5%. Both studies were of PCS cohorts.^3,5

The cumulative survival rate for ECMO-only patients was 256/683 (37.5%), compared with 294/834 (35.3%) for patients with ECMO plus IABP. Concomitant IABP use was not associated with improved survival (risk ratio [RR], 1.143; 95% CI, 0.973-1.343; P=.10), as summarized in Figure 2 and Table 1. P-value for heterogeneity was not significant (P=.50) and the heterogeneity variable I² was 0.

A funnel plot was generated that showed one extreme outlier study (Figure 3). After removing this outlying study, reanalysis of 15 studies and 1430 patients demonstrated a cumulative survival for ECMO-only patients of 241/637 (37.8%) as compared with 266/793 (33.5%) for patients with IABP support. Concomitant IABP use was not associated with improved survival (RR, 1.052; 95% CI, 0.886-1.249; P=.56).

Baseline characteristics of studies and included patients are summarized in Table 2. Only 1 study reported separate demographic information for the 2 subgroups of ECMO-only (55 patients) and ECMO + IABP (41 patients). It found no differences in age, male gender, type of myocardial infarction, systolic and diastolic blood pressures, heart rate, hemoglobin, creatinine, lactate, and ejection fraction, among other factors.¹⁹ Cardiopulmonary resuscitation was more common in the ECMO-only group (74.5%) when compared with the ECMO + IABP group (48.8%), with a reported P=.01.

Subanalysis by etiology of cardiac failure. Five out of 16 studies reported on clinical outcomes for cardiogenic shock and cardiac arrest due to AMI requiring ECMO,^1,4,19,25,26 5/16 reported on PCS requiring ECMO,^2,3,5,9,27 and 5/16 reported on mixed cohorts.^{20,21,24,28,29} A final study reported on fulminant myocarditis.²³

Acute myocardial infarction. Five studies encompassing 288 patients were included in the analysis of AMI. Two out of 5 studies described the diagnosis of MI as symptoms, history, electrocardiographic, and serological findings consistent with ischemia.^1,4 The remaining 3 studies implied its appropriate diagnosis.^19,25,26 Percutaneous coronary intervention was attempted in 222/288 cases (77.1%), and was the preferred approach in 3/5 studies,^1,4,19 while coronary artery bypass graft (CABG) surgery was cumulatively employed in 57/288 cases (19.8%), and was the preferred approach in the remaining 2 studies.^25,26 The cumulative survival for ECMO-only patients was 29/73 (39.7%) compared with 84/215 (39.1%) for ECMO + IABP patients. Concomitant IABP use was not associated with improved survival (RR, 1.120; 95% CI, 0.772-1.624; P=.55).

Postcardiotomy cardiogenic shock. Four studies encompassing 811 patients were included in the analysis of PCS. All studies described inability to wean from cardiopulmonary bypass or refractory cardiogenic shock perioperatively as the indication for ECMO.^2,3,5,27 The cumulative survival for ECMO-only patients was 108/354 (30.5%) compared with 124/457 (27.1%) for ECMO + IABP patients. Concomitant IABP use was not associated with improved survival (RR, 1.121; 95% CI, 0.826-1.520; P=.46). 

Subanalysis by intraaortic balloon pump strategy. Five out of 16 studies employed IABP prior to initiation of ECMO and routinely continued IABP support during ECMO,^{19,20,23,25,28} 5/16 studies placed IABP routinely at initiation of ECMO for its potential benefit in decreasing afterload and increasing coronary perfusion,^1-5 and 5/16 studies did not describe their IABP strategy.^{9,21,24,27,29} A final study employed IABP after initiation of ECMO when the “arterial pulse wave disappeared.”²⁶ This study found no difference in survival between the two groups.

Intraaortic balloon pump initiation prior to extracorporeal membrane oxygenation. Five studies encompassing 301 patients were included in the analysis of IABP prior to initiation of ECMO (“analysis prior”), with a cumulative survival for ECMO-only patients of 91/185 (49.2%) compared with 51/116 (44.0%) for ECMO + IABP patients. Concomitant IABP use was not associated with improved survival (RR, 0.948; 95% CI, 0.718-1.252; P=.71).

Intraaortic balloon pump initiation routinely with extracorporeal membrane oxygenation. Five studies encompassing 714 patients were included in the analysis of routine IABP at initiation of ECMO (“analysis routine”), with a cumulative survival for ECMO-only patients of 32/150 (21.3%) compared with 162/564 (28.7%) for ECMO + IABP patients. Concomitant IABP use was not associated with improved survival (RR, 1.102; 95% CI, 0.806-1.506; P=.54). 

Discussion

IABPs are frequently used as an adjunctive device to ECMO and are routinely placed at the initiation of ECMO at many medical centers,^1-7 in spite of the limited and conflicting evidence for the additive benefit of IABP therapy. Small sample sizes may be partly to blame for the conflicting evidence. While large, prospective, randomized clinical trials would best elucidate the benefits of concomitant IABP with ECMO, in their absence, a pooled analysis represents the next best method. Our analysis encompassing 16 studies and 1517 patients revealed that concomitant IABP was not associated with improved survival regardless of the etiology of cardiogenic shock or arrest, and irrespective of the strategy of IABP implantation. Concomitant IABP was not associated with improved survival in patients with AMI or those with PCS, nor was it associated with improved survival in patients where IABP therapy was initiated before ECMO, at the same time as ECMO, or as bail-out for the absence of pulsatile flow after ECMO. 

The use of concomitant IABP with ECMO is widespread. In our systematic literature search, IABP was present in approximately 55% of all ECMO cases reviewed, stretching across all etiologies of cardiac failure beyond AMI. The rationale for concomitant IABP use is primarily for LV venting, but also for afterload reduction, improved diastolic pressures and coronary flow, and increased organ perfusion.^8,9 The incremental benefit of IABP support for afterload reduction and increasing organ perfusion in the presence of ECMO support is relatively minimal. With regard to improved diastolic pressures and coronary flow, despite the previously held belief of an estimated 11% survival benefit from pooled analyses of retrospective studies of IABP use in AMI, it is now known from the prospective and randomized IABP-SHOCK II study that the use of IABP in this cohort had no survival benefit.³⁰ Augmentation of diastolic pressures and coronary flow was thought to be the mechanism of an observed two-fold increase in survival to hospital discharge in 1 study when IABP was concomitantly used in post-CABG patients with PCS requiring ECMO.⁹ However, it is notable that this study was the outlier in our funnel plot analysis, and only had a CABG subgroup of 19.5%, and was a study predominantly of patients undergoing valve surgery. In contrast, there was no benefit in concomitant IABP use in the largest included study of 517 patients with PCS requiring ECMO with a larger CABG subgroup of 61.9%. This finding is in line with other studies with large CABG subgroups,^3,27 and along with our findings do not support a survival benefit from concomitant IABP and ECMO.

Significant LV distension occurs in 10%-60% of patients on ECMO.¹⁴ LV decompression, whether by balloon and blade atrial septostomy,¹⁵ left atrial decompression with a transseptal puncture and placement of a venous drain,¹⁰ direct apical LV venting,¹² pulmonary artery catheterization with a venous drain,¹¹ or right pulmonary upper vein venting,¹⁴ has been shown to decrease cardiac pressures, pulmonary edema, and LV distension. Additionally, transaortic LV venting with a non-pulsatile catheter or with a percutaneous microaxial flow pump has been described.¹⁶ Concomitant IABP use is thought to decompress the LV as well, and is widely used in part for this indication with ECMO therapy. However, none of these adjunctive techniques for LV venting, despite their frequent use, has been established as having an incremental survival benefit compared with ECMO alone. Nevertheless, the use of LV venting for select cases may still be beneficial. In fact, in a recent article, elective LV decompression with left atrial venting, blade septostomy, and LV cannulation in a pediatric cohort on ECMO resulted in decreased time on ECMO support of 128 hours vs 236 hours, although selection bias may have confounded these results.¹³ 

The optimal strategy for patient, device, and technique selection for LV decompression is left unanswered, although our findings suggest the hemodynamic improvements with IABP may not be sufficient. The absence of an observable survival benefit may be due to insufficient augmentation of cardiac output with IABP and inadequate LV decompression, and the use of devices with more cardiac output support such as percutaneous microaxial flow pumps may lead to a measurable survival benefit. However despite the many techniques for LV venting described, no survival benefit has yet been demonstrated. While it may be that IABP support is adequate for cardiac output and LV decompression, it may simply be that LV decompression does not improve survival or lead to better clinical outcomes. Additional studies are urgently needed to establish whether (and which type) of venting or support could improve outcomes, as LV venting including the use of percutaneous microaxial flow pumps is already gaining in use at many institutions.

In summary, despite limited and conflicting evidence regarding the benefit of IABP use when added to ECMO therapy,^3,9,18-21 many centers routinely insert IABP at ECMO initiation. In the absence of large clinical trials, this meta-analysis represents the best method to elucidate the potential benefit of concomitant IABP use, but showed no associated survival benefit.

Study limitations. As patients were not randomized to receive concomitant IABP use, selection bias is a limitation of the studies included in the analysis. Patient demographics were not routinely reported for the ECMO-only and ECMO + IABP subgroups. Despite small statistical heterogeneity, certainly the various studies that comprise this meta-analysis draw from different patient populations with intercenter variability of practice habits, patient selection, and reporting patterns. The judicial use of concomitant IABP in LV venting for LV distension was not routinely the reported strategy in studies included; therefore, this pooled analysis does not adequately illuminate the potential benefits of such a strategy. Finally, funnel plot analysis suggested a publication bias in favor of IABP use, the correction of which continued to demonstrate no survival benefit in the use of adjunctive IABP.

Conclusion

Based on this observational analysis, concomitant use of IABP with ECMO did not appear associated with a dramatic change in survival outcomes. The routine insertion of concomitant IABP with ECMO is not supported by our findings and should be undertaken with caution. Additional studies are urgently needed to establish whether and which type of venting or support could improve outcomes. 

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From the ¹Division of Cardiology, Cedars-Sinai Heart Institute, Los Angeles, California; ²Department of Cardiovascular Medicine, Heart and Vascular Institute, Cleveland Clinic, Cleveland, Ohio; and ³Division of Cardiothoracic Surgery, Cedars-Sinai Heart Institute, Los Angeles, California.

Disclosure: The authors have completed and returned the ICMJE Form for Disclosure of Potential Conflicts of Interest. Dr Makkar reports grants from St. Jude Medical, Edwards Lifesciences, Medtronic, and Capricor; personal fees from Edwards Lifesciences, Medtronic, Abbott Vascular, and Cordis Corporation. Dr Arabia reports personal fees from SynCardia, Inc. Dr Esmailian reports personal fees from SynCardia, Inc and Transmedics, Inc. The remaining authors report no conflicts of interest regarding the content herein.

Manuscript submitted March 13, 2015, provisional acceptance given April 28, 2015, final version accepted May 4, 2015.

Address for correspondence: Babak Azarbal, MD, 8536 Wilshire Blvd, #302, Los Angeles, CA 90211. Email: azarbalb@cshs.org