Outcomes of early versus delayed initiation of extracorporeal life support in cardiac surgery

The incidence of postcardiotomy myocardial dysfunction is approximately 3–5% after cardiac surgical procedures [1]. Extracorporeal membrane oxygenation (ECMO) is the most potent form of acute cardiorespiratory support available and enables complete relief of cardiac workload. ECMO, first introduced clinically in 1972, has been applied as a means of cardiopulmonary support in patients with potential reversible cardiac or respiratory failure when conventional medical strategies have been exhausted [2, 3]. Recently, studies have documented the successful use of ECMO for temporary circulatory support in patients with heart failure [4‐6].

However, the Extracorporeal Life Support Organization reports a 31% survival in patients with hypoplastic left heart syndrome (HLHS) undergoing stage I Norwood repair who require mechanical support [7]. Moreover, the survival statistics after ECMO support following cardiac surgery (approximately 50% for infants and 15% for adults) have not been very encouraging and have remained static since its inception in 1973 [8‐10]. It has become a major topic in the study of improving the survival rate of patients who need ECMO support after cardiac surgery with postoperative heart failure. There have been reports of higher survival rate comparing patients undergoing cardiac surgery whose ECMO support was initiated in the operating room with those initiated in an emergency situation in the postoperative period [11, 12]. However, the optimal time and indications of ECMO initiation in the operating room are not yet clear.

The most common indications of ECMO in patients after cardiovascular surgery include low cardiac output syndrome, inability to be weaned off from cardiopulmonary bypass (CPB), refractory arrhythmias, pulmonary hypertension, refractory cardiogenic shock, bridge to heart transplant, and extracorporeal cardiopulmonary resuscitation [3, 13, 14]. While these indications and/or criterias are well-established and reliable measurements, there may be a lag between what happens during clinical diagnosis and ECMO initiation. An empirical practice has been developed since 2015 in our hospital, which is used to identify patients at a high risk of refractory cardiogenic shock based on the CPB findings, vasoactive-inotropic score (VIS) [15], cardiac index (CI), and arterial lactate level. The ECMO was early initiated in the operating room in those patients at a high risk of developing postoperative refractory cardiogenic shock. Therefore, we compared the outcomes between patients who were delayed initiating of ECMO (delayed ECMO group) and propensity-matched patients who underwent similar surgical procedures but initiated ECMO early (early ECMO group) to determine if early ECMO, based on the present empirical practice was associated with an improved clinical prognosis.

There were 173 patients participated in this study. After propensity match, 72 patients with similar risk profile (age, EuroSCORE [16], CPB and surgical procedure) were enrolled in this study (36 in the delayed ECMO group and 36 in the early ECMO group). The baseline and demographic variables were not significantly different between the early ECMO group and delayed ECMO group (Table 1). In matched groups, the early ECMO group had the same age (57.31 ± 16.90 years vs 61.17 ± 12.22 years, P = 0.27), EuroSCORE (6.94 ± 1.94 vs 7.11 ± 1.14, P = 0.53), and CPB time (median: 262 min, IQR: 223–306 min vs median: 264 min, IQR: 220–320 min, P = 0.87) as the delayed ECMO group. In addition, the sex, preoperative left ventricular ejection fraction, preoperative left ventricular end-diastolic diameter, New York Heart Association class, and medical history were also similar between the early ECMO group and delayed ECMO group. The detailed variables are presented in Table 1.

As shown in Table 2, the early ECMO group had a significantly decreased mortality compared with the delayed ECMO group (69.44% vs 41.67%, P = 0.03). The early ECMO group also had decreased rates of CRRT use (88.89% vs 66.67%, P = 0.04) and pulmonary infection (86.11% vs 55.56%, P < 0.01). The rate of successful ECMO weaning was higher (30.56% vs 63.89%, P < 0.01), and the ECMO duration for the survivors was shorter (median: 7 days, IQR: 4–10 days vs median: 5 days, IQR: 4–8 days, P = 0.03) in the early ECMO group than in the delayed ECMO group. The early ECMO group also had shorter mechanical ventilation time (median: 11 days, IQR: 9–14 days vs median: 9 days, IQR: 7–12 days, P = 0.01) and ICU stay for the survivors (median: 31 days, IQR: 21–42 days vs median: 16 days, IQR: 13–54 days, P = 0.04). Compared with delayed ECMO group, early ECMO group had lower frequency of pulmonary infections (31, 86.11% vs 20, 55.56%, P < 0.01). There were 16 patients who met the same criteria as the early ECMO group but did not receive ECMO from 2010 to 2017. They all died within 7 days after surgery. These 16 patients were implemented Intra-aortic ballon pump (IABP) support (n = 9) or IABP+CRRT (n = 4). Additionally, no patients had axillary bleeding; no patients were bridged to durable ventricular assist device or transplant in each category; no patient had any paravalvular leak in propensity matched cohort.

From admission to the ICU (T0) to 72 h after surgery (T72), the early ECMO group had a higher rate of arterial lactate clearance (Fig. 1, P < 0.01), higher CI (P = 0.01), and lower VIS (P = 0.03) than the delayed ECMO group. In addition, the ECMO flow and hemoglobin and indirect bilirubin levels had no significant differences between the two groups from T0 to T72. The detailed variables associated with the postoperative hemodynamic variables in the matched patients are presented in Table 3.

The main difference in the timing of initiation of ECMO between the early ECMO group and delayed ECMO group is the failed CPB wean-off for three times (27 patients in the delayed ECMO group, 75%) and once-failed CPB wean-off (31 patients in the early ECMO group, 86.11%). To determine whether the “failed CPB wean-off for three times or once-failed CPB wean-off,” as the main effects between the early ECMO group and delayed ECMO group, could reduce poor outcomes, we investigated the outcomes between the “failed CPB wean-off for three times” in the delayed ECMO group (α group, n = 27) and “once-failed CPB wean-off” in the early ECMO group (β group, n = 31). The results showed that the β group had significantly decreased rates of mortality (92.59% vs 48.39%, P < 0.01), CRRT use (92.59% vs 64.52%, P = 0.01), and pulmonary infection (85.18% vs 58.06%, P = 0.02) compared with the α group. The detailed variables between the α group and β group are shown in Table 4.

It is well known that the aim of ECMO is to unload the heart and decrease its work profoundly. Although ECMO allows a finite time interval for the myocardium to recover from injury, the mortality associated with its use is high. However, a number of recent reports on the initiation of ECMO in the operating room for refractory cardiogenic shock have shown encouraging results [11, 12, 17]. Similarly, our study indicated an association of ECMO initiation in the operating room with less vasoactive-inotropic agent requirement, better heart function recovery, low rate of pulmonary infection, and decreased CRRT use. Thus, the initiation of ECMO, based on our empirical risk evaluation practice, could decrease patient mortality.

ECMO after repair of heart diseases can often reverse profound myocardial dysfunction and correct the severe metabolic consequences of a prolonged low cardiac output. The timing of ECMO support directly impacts survival [17‐19]. In the past, patients had to be transferred directly from CPB to ECMO, as they could not be weaned off from the bypass despite multiple attempts over an extended period of observation in the theater. Many reports have identified initiation of ECMO in the operating room as an independent predictor for early mortality. A multi-institutional analysis reported that lengthening the time from surgery to ECMO initiation was not associated with worsening mortality [20]. However, Chaturvedi et al. reported that the higher survival of patients cannulated in the operating room than of patients cannulated in the ICU is because of the early effective support preventing prolonged hypoperfusion and the avoidance of a catastrophic cardiac arrest [17]. The Duke University experience similarly did not find the initiation of ECMO in the operating room to impact survival adversely [21]. Therefore, the optimal timing of ECMO initiation remains controversial.

While it is generally accepted that early institution of VA ECMO support in the context of postcardiotomy cardiogenic shock is preferred before multiorgan failure sets in, VA ECMO is an invasive modality and carries complications, such as bleeding, dissection, stroke, etc. Furthermore, prophylactically use of VA ECMO support can pose immense pressure on health care systems, especial socialist health care systems. Hence every case should be considered on the individual merits and multidisciplinary, including advanced patients’ directives and/or wishes, opinion should be taken into consideration prior to institution of such invasive and costly modalities. That was why an early warning system of ECMO initiation was important and necessary to decrease postoperative mortality and hospitalized cost. We found a significant correlation between early initiation of ECMO and promotion of survival in adult patients with acquired heart diseases after cardiovascular surgery. Thus, the initiation of ECMO, based on our empirical risk evaluation practice, might be useful and eligible for clinicians to advance patients’ wishes if such invasive and costly modalities should be implemented.

Second, the population of their studies contained a large proportion of unplanned ECMO. They lacked data related to the decision-making process prior to initiation of ECMO as well as on the adult patients with acquired cardiovascular diseases. In other words, the conditions of the patients prior to ECMO in this study might be better than those of their patients, which could also influence the postoperative outcomes. What demand add is, sharpening the axe will not interfere with the cutting of firewood, explaining the importance of the preparation. Based on our empirical risk evaluation practice, we methodically implemented ECMO for high-risk patients. This study proved that our risk evaluation practice was useful and effective in improving the survival of patients by initiating early ECMO after cardiovascular surgery. To our best knowledge, no study has attempted to deliver criteria for early ECMO interventions in adult patients after cardiovascular surgery. Therefore, this study may be the first to provide the optimal timing of initiation of ECMO for patients with cardiovascular diseases useful as a basis for cardiac surgeons, anesthetists, and intensive specialists worldwide.

Finally, Swan-Ganz catheters were used in all patients to monitor the CI in the operating room. During ECMO, the net cardiac output is the combination of the patients’ cardiac output and the ECMO output. However, the arterial lactate level, VIS, and ECMO flow decreased more rapidly in the early ECMO group than in the delayed ECMO group from T0 to T72. Meanwhile, the CI increased more rapidly in the early ECMO group than in the delayed ECMO group. Patients who receive early initiation of ECMO, which promotes lactate clearance and decreases the dosage of vasoactive-inotropic agents and ECMO flow, may benefit from an improved cardiac output, thus increasing their survival after cardiovascular surgery. It is possible that a proportion of patients in this study who were “electively” placed on ECMO never needed this form of support and IABP support was enough. However, inotropic and vasoactive drugs were routinely used in intraoperative and postoperative management. Additionally, there were 16 patients who met the same criteria as the early ECMO group but did not receive ECMO from 2010 to 2017. They all died within 7 days after surgery. These 16 patients were implemented IABP support or IABP+CRRT. It may be because of the serious preoperative condition of these patients (mean LVEF 42% ± 8%). The ECMO may be prior to IABP for patients with preoperative left ventricular dysfunction. Compared with preoperative echo-variables, the intraoperative LVEF (43.99 ± 8.21% vs 43.67 ± 7.57%, P = 0.16) and LVDd (59.49 ± 13.05 mm vs 59.36 ± 12.49 mm, P = 0.43) had not significantly changed in propensity matched patients. Therefore, the cardiogenic shock before going on VA ECMO may be resulted from the poor preoperative condition, such as preoperative left ventricular dysfunction and high risk of the surgery (high EuroSCORE), rather than the selectivity of the procedure. Moreover, Alph and beta group comparison was used to illustrate the high mortality of delayed ECMO. In α group, “failed CPB wean-off for three times” means artificially prolonged timing of ECMO initiation. In β group, “once-failed CPB wean-off” means early timing of ECMO initiation. The biggest difference between α and β groups was whether timing of ECMO initiation had been deliberately prolonged. That is to say, as the variables shown in Table 4, deliberately prolonged ECMO initiation could significantly morbidity and mortality. Thus, we suggested that ECMO should be initiated as early as possible.

Notably, several limitations of our study still exist. This study involved the experience in a single center with a relatively small sample size. This observational study could be influenced by potential biases. We used propensity score matching to avoid these biases. However, we cannot account for the factors that affect assignment to treatment and outcomes but cannot be observed in the matching procedure. Any hidden bias due to latent variables might remain after matching, which could lead to some statistical faults. Furthermore, with this analysis, we remove a large number of patients from the analysis, which may have elevated statistical errors. Some limitations are also inherent in non-randomized studies. Thus, randomized controlled studies are needed to re-confirm our conclusion.

Extracorporeal membrane oxygenation provides effective support for cardiogenic failure refractory to medical management; early initiation improves cardiac output and promotes lactate clearance, thus increasing survival in patients with cardiogenic shock after cardiovascular surgery.