**6.2 Weaning trials**

*Advances in Extracorporeal Membrane Oxygenation - Volume 3*

**5.3 Post VA-ECMO wean**

**6. Weaning strategies**

**6.1 Pharmacological agents**

with VA-ECMO weaning [35, 36].

at time of VA-ECMO cannulation may be more specific than hemodynamic measures for identifying successful VA-ECMO weaning and survival. This discordance between the micro and macro-circulation has been described previously as a loss of hemodynamic coherence in part due to heterogeneous flow the organs receive during support, alterations in capillary density and presence of tissue edema [31]. Specifically, one study which assessed microcirculation serially, found that even in the presence of preserved lactate, tissue perfusion as estimated by parameters of microcirculation did not improve on VA-ECMO and those with compromised microcirculation—measured as perfused capillary density and proportion of perfused vessels—could not be weaned from VA-ECMO [32]. A separate study looking specifically at 28-day survival in cardiogenic shock patients placed on VA-ECMO, found that while MAP, pressor requirement and lactate did not differ, microcirculation was better preserved in survivors compared to non-survivors within 12 hours of VA-ECMO support [33]. However, further research is needed to determine if microcirculatory assessment can help guide timing of VA-ECMO weaning.

Survival post VA-ECMO is predicated on correcting the underlying cause for shock or cardiac arrest, ultimately allowing device removal. However, weaning does not always signify that individuals will survive. Individual factors have to be considered to predict long term survival such as age, comorbidities, complications arising during circulatory support, underlying ventricular function and end organ function. On the latter, renal failure (signified by elevated creatinine level) or hepatic failure (marked by elevated total bilirubin and elevated INR) at the time of wean can impact short-term and long-term survival with multiorgan failure being the predominant mode of death after weaning [22]. If myocardial recovery is unlikely but other factors have been controlled and improved (including renal and hepatic function, lactate and resolution of pulmonary edema), durable VAD or heart transplantation should be taken into consideration, as longer duration on VA-ECMO can reduce the likelihood of survival to discharge or success towards a bridging option. In a small observational study, survival to discharge was higher for those transitioned within 14 days from VA-ECMO support to a VAD compared to

those transitioned longer than 14 days (92 vs. 25%, *p* < 0.05) [34].

The pharmacologic agents that have been used to assist with weaning trials have primarily been inotropic agents including dobutamine, epinephrine, dopamine, milrinone and levosimendan. Epinephrine, dopamine and dobutamine are catecholamines, with epinephrine and dopamine having alpha-1 activity and thus some crossover with norepinephrine as vasoconstrictors. Dobutamine acts predominantly on beta-1 and beta-2 receptors. Milrinone and levosimendan on the other hand are inotropes without direct adrenergic receptor targets. Milrinone is a type-3 phosphodiesterase inhibitor and augments myocardial contraction by increasing intracellular concentrations of cAMP and calcium. Levosimendan on the other hand is a calcium sensitizer and is postulated to augment myocardial contractility without increasing intracellular calcium and myocardial oxygen consumption. Current evidence supports the use of both milrinone and levosimendan to assist

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Protocols for weaning VA-ECMO include:


In addition to requiring full anticoagulation during weaning trials, flows cannot be turned down below 1–1.5 L/min because of concerns for thrombus formation within the VA-ECMO circuit. Thus, clinicians must monitor changes in hemodynamic and echocardiographic parameters as VA-ECMO flows are decreased and terminate weaning if evidence of hemodynamic compromise or intolerance to preload changes such as loss of pulsatility, ventricular dysfunction or increases in filling pressures are seen. Hemodynamic tolerance during the weaning trial is extrapolated to imply myocardial recovery has occurred and that decannulation will be tolerated by the patient. In order to allow clinical assessments off VA-ECMO support entirely, some centers are using arteriovenous cannula bridging strategies that form a circuit that bypasses the patient [41], or a separate technique pioneered in neonates that reduces pump flow until the circuit runs retrograde [42, 43].
