**2. Prevention of limb ischemia**

#### **2.1 Prophylactic distal perfusion cannula**

Several authors highlight the role of concurrent, prophylactic, selective distal limb perfusion from the time of femoral arterial cannulation for systemic perfusion in the prevention of limb ischemia. In one series, the authors claim no occurrence of limb ischemia in patients with prophylactic distal perfusion via selective cannulation (DPC) compared to a 21% incidence of ischemia in patients without DPC [21]. Tanaka *et al.* demonstrated that the absence of DPC was a significant predisposing factor for vascular complications, while other factors including medical history or risk factors like peripheral vascular disease and severity of baseline condition were not significantly associated with vascular complications [19]. However, from the review of published literature it is difficult to ascertain whether the elective avoidance of DPC or the presence of factors preventing its use (e.g. peripheral artery disease, vessel spasm, vessel injury due to attempted cannulation) are the underlying cause of the vascular complication.

In a comparative study, no limb ischemia was encountered in patients undergoing pro-active DPC in contrast to 9.3% incidence of limb ischemia in patients who underwent re-active DPC as a rescue strategy. They concluded that the delayed distal cannulation not only increased the extent of cannulation site bleeding, but also failed as a rescue therapy as it failed to improve the ischemia [23] whereas proactive DPC prevented its occurrence. In addition, patients in the pro-active group demonstrated a significantly better weaning rate as well as survival.

However, despite extensive literature advocating DPC as being preventive to limb ischemia, there is no class I evidence about its efficacy. Understandably, it is difficult to design a randomised trial to identify actual protection offered by prophylactic DPC given the multiple factors responsible for mortality and morbidity and grave condition of patients supported on VA-ECMO.

Although DPC offers incessant perfusion to the distal limb, its insertion and maintenance are not always smooth, and it is not devoid of complications. The DPC due to their small calibre, slow and low flow, acute angles, multiple connections are prone to bending, thrombogenesis, and peripheral embolization. It is important to note that DPC blockage due to thrombosis may go unnoticed in absence of continuous

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*DOI: http://dx.doi.org/10.5772/intechopen.86391*

monitoring of its flow and result in complete thrombo-embolism and obstruction of the femoral artery. In order to avoid this scenario and assess whether limb perfusion remains adequate in the absence of DCP, Huang *et al.* measured the pressure in the superficial femoral artery distal to the systemic cannula and introduced the DPC only when this pressure was less than 50 mmHg [24]. In their cohort of 26 patients, only 9 patients fulfilling this criterion required the DPC and authors report no limb ischemia in any patients, with or without DPC. These findings are interesting and warrant further evaluation of their technique and confirmation by other study groups.

Compared to open cut-down DPC related complications are more common after

percutaneous cannulation, often due to multiple cannulation attempts causing vessel injury, extravasation, hematoma and inadvertent cannulation of the *profunda femoris*. In contrast, while not ubiquitously feasible, technically more challenging and more time consuming, the open cut-down allows visualisation of the artery to ensure an adequate size of the cannula, proper placement, good haemostasis and the abandonment of the site without failed attempts in case of arterial calcifications [15]. Not surprisingly, a significantly higher incidence of limb ischemia was found in patients with a percutaneous DPC compared to patients with no DPC and open cut-down DPC in a series published by the Philadelphia group [25]. In this context, it is worth mentioning the 'chimney graft construction' approach on the femoral artery in which a small vascular graft is placed end-to side onto the main femoral artery, thus allowing for bi-directional perfusion without obstruction of the vessel. This avoids the more complex V-A-DPC-ECLS circuit, the DPC itself and its complications [26]. However, while avoiding ischemia and advocated for small femoral arteries, in bigger vessels it may lead to distal limb hyper-perfusion [15] (**Table 1**). A generalised and enthusiastic approach for prophylactic DPC should be carefully reviewed and implemented only in cases with high risk for limb ischemia. These include patients with a history and signs of peripheral vascular disease, atherosclerosis, previous utilisation of groin vessels for access and female gender due to smaller vessel size as they are more prone to develop limb ischemia. In addition, young age may be an independent risk factor due to the absence of collateral vascularisation [21]. Also, there are several variables influencing the of risk of development of limb ischemia which can be addressed separately. These include low or no cardiac output resulting in loss of the pulse wave, although in patients with failure to oxygenate blood via the lung a low or absent biological output may be intended to prevent a watershed phenomenon and ensure cerebral oxygenation. High vasopressor support, peripheral shut-down and big calibre flow-occlusive systemic femoral cannulation are other factors influencing

perfusion to distal limb and the development of limb ischemia.

As the principal role of the ECLS is temporary cardio-pulmonary support and preservation of organ perfusion, sufficient 'biomechanical' output can be provided often at a reasonable mechanical flow rate without complete replacement of the biological cardiac output. Cannulation with a small calibre systemic cannula may therefore provide enough flow and preserve a pulse wave allowing for sufficient perfusion of the distal limb. A 17F systemic cannula easily provides 4–5 L/min flow with a driving pressure of around 100 mmHg. Takayama *et al.* compared outcome in patients based on the size of the systemic cannula and showed that a 15F size cannula, while allowing for significantly less blood flow when compared to bigger (17–24F) cannulas, resulted in no difference in use of vasoactive medication, hemodynamic parameters or laboratory values measured [27]. On the other hand, significantly less cannulation-related adverse events were observed in the 15F group.

Patients on ECLS support may develop severe vasoplegia requiring high dose vasopressor support to sustain arterial blood pressure for satisfactory end-organ perfusion. Efforts to maintain a negative fluid balance to reabsorb peripheral and pulmonary oedema in a bid to wean ECLS may intensify vasopressor requirement

#### *Isn't Limb as Precious as Life? DOI: http://dx.doi.org/10.5772/intechopen.86391*

monitoring of its flow and result in complete thrombo-embolism and obstruction of the femoral artery. In order to avoid this scenario and assess whether limb perfusion remains adequate in the absence of DCP, Huang *et al.* measured the pressure in the superficial femoral artery distal to the systemic cannula and introduced the DPC only when this pressure was less than 50 mmHg [24]. In their cohort of 26 patients, only 9 patients fulfilling this criterion required the DPC and authors report no limb ischemia in any patients, with or without DPC. These findings are interesting and warrant further evaluation of their technique and confirmation by other study groups.

Compared to open cut-down DPC related complications are more common after percutaneous cannulation, often due to multiple cannulation attempts causing vessel injury, extravasation, hematoma and inadvertent cannulation of the *profunda femoris*. In contrast, while not ubiquitously feasible, technically more challenging and more time consuming, the open cut-down allows visualisation of the artery to ensure an adequate size of the cannula, proper placement, good haemostasis and the abandonment of the site without failed attempts in case of arterial calcifications [15]. Not surprisingly, a significantly higher incidence of limb ischemia was found in patients with a percutaneous DPC compared to patients with no DPC and open cut-down DPC in a series published by the Philadelphia group [25]. In this context, it is worth mentioning the 'chimney graft construction' approach on the femoral artery in which a small vascular graft is placed end-to side onto the main femoral artery, thus allowing for bi-directional perfusion without obstruction of the vessel. This avoids the more complex V-A-DPC-ECLS circuit, the DPC itself and its complications [26]. However, while avoiding ischemia and advocated for small femoral arteries, in bigger vessels it may lead to distal limb hyper-perfusion [15] (**Table 1**).

A generalised and enthusiastic approach for prophylactic DPC should be carefully reviewed and implemented only in cases with high risk for limb ischemia. These include patients with a history and signs of peripheral vascular disease, atherosclerosis, previous utilisation of groin vessels for access and female gender due to smaller vessel size as they are more prone to develop limb ischemia. In addition, young age may be an independent risk factor due to the absence of collateral vascularisation [21]. Also, there are several variables influencing the of risk of development of limb ischemia which can be addressed separately. These include low or no cardiac output resulting in loss of the pulse wave, although in patients with failure to oxygenate blood via the lung a low or absent biological output may be intended to prevent a watershed phenomenon and ensure cerebral oxygenation. High vasopressor support, peripheral shut-down and big calibre flow-occlusive systemic femoral cannulation are other factors influencing perfusion to distal limb and the development of limb ischemia.

As the principal role of the ECLS is temporary cardio-pulmonary support and preservation of organ perfusion, sufficient 'biomechanical' output can be provided often at a reasonable mechanical flow rate without complete replacement of the biological cardiac output. Cannulation with a small calibre systemic cannula may therefore provide enough flow and preserve a pulse wave allowing for sufficient perfusion of the distal limb. A 17F systemic cannula easily provides 4–5 L/min flow with a driving pressure of around 100 mmHg. Takayama *et al.* compared outcome in patients based on the size of the systemic cannula and showed that a 15F size cannula, while allowing for significantly less blood flow when compared to bigger (17–24F) cannulas, resulted in no difference in use of vasoactive medication, hemodynamic parameters or laboratory values measured [27]. On the other hand, significantly less cannulation-related adverse events were observed in the 15F group.

Patients on ECLS support may develop severe vasoplegia requiring high dose vasopressor support to sustain arterial blood pressure for satisfactory end-organ perfusion. Efforts to maintain a negative fluid balance to reabsorb peripheral and pulmonary oedema in a bid to wean ECLS may intensify vasopressor requirement

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*Advances in Extracorporeal Membrane Oxygenation - Volume 3*

including four compartment fasciotomies [17].

patient supported on ECLS.

**2. Prevention of limb ischemia**

**2.1 Prophylactic distal perfusion cannula**

ing cause of the vascular complication.

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

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

Several authors highlight the role of concurrent, prophylactic, selective distal limb perfusion from the time of femoral arterial cannulation for systemic perfusion in the prevention of limb ischemia. In one series, the authors claim no occurrence of limb ischemia in patients with prophylactic distal perfusion via selective cannulation (DPC) compared to a 21% incidence of ischemia in patients without DPC [21]. Tanaka *et al.* demonstrated that the absence of DPC was a significant predisposing factor for vascular complications, while other factors including medical history or risk factors like peripheral vascular disease and severity of baseline condition were not significantly associated with vascular complications [19]. However, from the review of published literature it is difficult to ascertain whether the elective avoidance of DPC or the presence of factors preventing its use (e.g. peripheral artery disease, vessel spasm, vessel injury due to attempted cannulation) are the underly-

In a comparative study, no limb ischemia was encountered in patients undergoing pro-active DPC in contrast to 9.3% incidence of limb ischemia in patients who underwent re-active DPC as a rescue strategy. They concluded that the delayed distal cannulation not only increased the extent of cannulation site bleeding, but also failed as a rescue therapy as it failed to improve the ischemia [23] whereas proactive DPC prevented its occurrence. In addition, patients in the pro-active group

However, despite extensive literature advocating DPC as being preventive to limb ischemia, there is no class I evidence about its efficacy. Understandably, it is difficult to design a randomised trial to identify actual protection offered by prophylactic DPC given the multiple factors responsible for mortality and morbid-

Although DPC offers incessant perfusion to the distal limb, its insertion and maintenance are not always smooth, and it is not devoid of complications. The DPC due to their small calibre, slow and low flow, acute angles, multiple connections are prone to bending, thrombogenesis, and peripheral embolization. It is important to note that DPC blockage due to thrombosis may go unnoticed in absence of continuous

demonstrated a significantly better weaning rate as well as survival.

ity and grave condition of patients supported on VA-ECMO.


#### **Table 1.**

*Prevention of limb ischemia.*

further. While maintaining central blood pressure levels, capillary perfusion of end organs, specifically the intestine as well as the limbs may be significantly reduced in such a scenario. Therefore, it is important to strike a balance between vasopressor delivery dependent blood pressure management, maintenance of fluid balance, arterio-venous perfusion pressure delta and capillary delivery, prioritising vasopressor weaning over 'drying up the lungs'. Maintenance of good intravascular volume also allows better ECLS flow and cardiac output along with pulsatility.

In essence, utilisation of a small calibre systemic femoral cannula, when possible, acceptance a biomechanical output with low ECLS flow, continued pulsatile flow and avoidance of high dose vasopressors obviate the need for prophylactic DPC insertion in patients, potentially protecting them from DPC related complications. With this conservative management and a protocol of continuous, diligent monitoring, patients that develop limb ischemia can then be detected at an early stage and treated with subsequent DPC, if necessary.

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**Figure 1.**

*Percutaneous cannulation.*

*Isn't Limb as Precious as Life?*

*DOI: http://dx.doi.org/10.5772/intechopen.86391*

**2.2 ECLS and DPC implantation strategies**

The individual approach of ECLS implantation heavily depends upon the place (out of the hospital, floor, bedside or operation theatre), urgency (elective or emergency), and aetiology (PCCS, post-PCI, primary graft failure or bridge to transplant) of the cardio-respiratory failure. In patients with cardiopulmonary arrest under resuscitation or peri-arrest patients, quick introduction of ECLS through is of utmost importance in order to sustain the patient's life. In this situation, the primary goal is the insertion of systemic arterial and venous cannulas and there may not be time for simultaneous DPC insertion. Such emergency bedside ECLS implantation in the intensive therapy unit is a scenario that usually does not offer facilities of an operation theatre making percutaneous insertion of peripheral cannulas necessary (**Figure 1**), often without availability of sonography to appropriately size for the smallest cannulae or fluoroscopy for intravascular positioning. In this context, it is important to note that percutaneous insertion of the DPC can be challenging in the presence of a systemic arterial cannula already in place, either due to the reduction or even absence of blood flow distal to the cannulation site or vasospasm and vessel injury during primary cannulation. Nevertheless, if it is attempted, ultrasound guidance during insertion is helpful and angiographic confirmation of DPC tip

position in the superficial femoral artery should be obtained [25, 28].

well as the patient a reasonable chance to recover.

PCCS is a scenario usually encountered after complex and long operations and has an extreme mortality. While ECLS is the only treatment option for these patients, it is important to make the decision to use it as early as possible and avoid repeated and prolonged attempts to wean the patient of CPB as these cause considerable collateral damage. ECLS should not be viewed as a last resort after all else has failed and the patient is in a catastrophic state but rather as a tool to be proactively used to ensure protection of organ function, continuous, uninterrupted sufficient perfusion and maintenance of a functioning coagulation system, thus preventing the well-known ICU exsanguination of these patients and offering both the heart as

For this, CPB can be converted directly to central ECLS, using the established cannulation or to peripheral ECLS. Peripheral ECLS allows the chest to be fully closed and no re-opening is needed for explantation of the ECLS system or for cannula-site bleeding especially in these patients on anti-coagulation therapy. With the patient stable on CPB it is safe and easy to perform a cut down to the groin vessels and placement of the cannulas under direct vision (**Figure 2**). If necessary, DPC can be introduced simultaneously. If the myocardial function is somewhat preserved, ECLS flows should be kept at a level allowing for blood flow through the heart to maintain left ventricular ejection in order to prevent its dilatation, stasis of
