**1.3 Causes and presentation spectrum of limb ischemia**

Limb ischemia has a broad spectrum of presentation ranging from hypothermia to muscle necrosis. In patients on ECLS it may occur for a number of reasons. Of these, the first and foremost is, of course, the simple complete obstruction of the femoral artery by the systemic perfusion cannula, which is inserted in a retrograde fashion, either percutaneously or open. The second is the requirement of extensive vasoconstrictor and inotropic support, which may restrict the 'residual' flow to the limb to the point of induction of clinically relevant ischemia. The third is the result of a deterioration of remaining cardiac output and loss of pulse wave, as the limb may be perfused—adequately—during the systolic ejection and be completely ischemic should pulse-wave be lost. Finally, insertion of the venous cannula on the ipsilateral side may result in clinically relevant venous congestion by itself and thus exacerbate any arterial perfusion deficit. Thus, careful monitoring and adjustment of several variables is essential in the prevention of ischemia and the treatment must be aimed at not only correcting the underlying causation but also to mitigate the resulting effects as in necrosis or reperfusion induced injury.

The signs and symptoms of acute limb ischemia are classically described with the 6 Ps- **P**ain, **P**allor, **P**ulselessness, **P**araesthesia, **P**oikilothermia, and **P**aralysis [16]. In this context, Rutherford's grading of acute limb ischemia depending upon the clinical examination namely viable, threatened (salvageable if promptly treated) and irreversible (major tissue loss or permanent nerve damage inevitable) is helpful to determine the timing and type of intervention. The onset of fixed mottling of the skin usually implies irreversible changes but does not allow for an estimation as to the extent. Compartment syndrome results from increased pressure (greater than 30–45 mmHg) in the muscle compartments often due to ischemia or reperfusion related swelling which further decreases blood supply leading to a vicious cycle of swelling-ischemia-swelling, rapidly progressing to irreversible

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on the situation and the presenting patient.

limited equipment available (e.g. fluoroscopy, surgical set).

[8, 9], can be achieved simply by switching back to an ECLS circuit.

In essence, peripheral access for the ECLS has become popular due to its flexibility of implantation outside operation theatre, reduced cannula site bleeding, the option of chest closure, avoidance of chest re-exploration and explantation without chest intervention. With the overall increase in the utilisation of ECLS in PCCS,

immediately.

**1.1 Indications**

Interestingly enough, this specific complication can be almost totally avoided with a protocol-based approach and precautions taken during the ECLS support; and if it occurs, it can be managed without significant consequences if detected and addressed

ECLS, although offered by specialised units only, is becoming more and more adopted for treatment of patients presenting with a variety of problems. Recent developments in technology have resulted in easier implantation and maintenance, ability to implement directly at the bedside, complete cardiopulmonary support and cost-effectiveness when compared to other mechanical circulatory support devices. In surgery, ECLS is utilised as a rescue in post-cardiotomy cardiogenic shock (PCCS) or as a temporary prolongation of cardiopulmonary bypass (CPB) to allow for an extensive weaning. Historically, the ECLS circuit was connected to the central CPB cannulation following unsuccessful weaning attempts of CPB. Recent years have seen a paradigm shift in preference to peripheral access. It is because peripheral cannulation allows for chest closure and avoids bleeding from high pressure aortic and thin-walled right atrial cannulation site and thus, multiple re-explorations for bleeding-temponade. Furthermore, the risk of formation of a positional thrombus on the intraluminal part of the aortic cannula, which may be dislodged at the time of decannulation and result in a catastrophic embolic event is avoided. And lastly, peripheral access obviates reopening of chest at the time of explantation of ECLS [2, 3]. Cannulation is either performed percutaneously or open, depending

A second group experiencing a significant increase in the utilisation of ECLS are patients during primary coronary intervention (PCI) [4, 5], although recent developments may lead to a shift in the technology used, such as Impella®. In this particular clinical setting, the expertise of interventional cardiologists and availability of fluoroscopy obviously lends itself to direct percutaneous implementation of ECLS. Bed-side, emergency direct ECLS implantation in intensive care units is a last and only resort to resuscitate patients after cardiopulmonary arrest undergoing prolonged efforts to re-establish life sustaining cardiac and pulmonary function (e-CPR) [6, 7]. In this situation, percutaneous peripheral access to the groin vessels is the preferable approach in view of the continuation of chest compressions and

In patients with advanced cardiac failure ECLS may be used as a bridge to decision, recovery or heart transplantation. In some of these patients, particularly those awaiting transplantation or long-term VAD implantation it is used in a 'semielective emergency situation' where patients are destabilising and showing signs of rapidly deteriorating end-organ function and impending cardiogenic shock. In this particular scenario ECLS is used to re-perfuse and stabilise end-organ function such as liver and kidney to allow for a non-emergency long-term VAD implantation at significantly less perioperative risk in a more stable patient. In this complex group of patients, peripheral access is favoured as it does not necessitate a sternotomy or thoracotomy leaving the chest 'virgin' or which may be complex due to previous, often multiple, surgical interventions. At the time of subsequent surgery ECLS can then easily be converted to CPB and continuation of ECLS post-surgery, if required

necrosis of the affected muscles. Diagnosis is essentially clinical with findings of swelling, stiffness, pain, and loss of pulse. It is a limb and life-threatening emergency and is usually fatal unless immediate action is undertaken, almost always including four compartment fasciotomies [17].

Limb ischemia compromises survival not only of the involved limb but also the patient. The ischemic process, multiple procedures, and transfusions exacerbate the systemic inflammatory response related to ECLS, resulting in increased risk of death [18]. Tanaka *et al.* report a higher number of procedures per patient and an increased frequency of disseminated intravascular coagulation in patients with vascular complications [19]. They also found the rate of survival to discharge as 18 vs. 49% in patients with and without vascular complications, respectively, demonstrating vascular complications as an independent factor of survival in patients on VA ECLS [19]. While some authors did not find any correlation between limb ischemia and patient mortality [20–22], it is widely accepted that apart from severity of the underlying condition, neurological uncertainty, and eligibility for substantive therapy, the limb ischemia plays a seminal role in deciding fate of the patient supported on ECLS.
