Extracorporeal life support in adults in the intensive care unit: Vascular complications

INTRODUCTION — As a treatment modality for cardiopulmonary failure, the use of extracorporeal membrane oxygenation (ECMO) has increased substantially [1]. From 2001 to 2021, the number of centers performing ECMO and reporting their data increased more than fivefold, while case volume increased approximately tenfold [2]. This growth in the use of ECMO has been driven in part by improvements in technique and instrumentation, and also by a greater clinical need for ECMO in association with expanding indications [3-5].

Factors inherent to the use of ECMO lead to vascular complications such as bleeding, thrombosis, and acute limb ischemia. Because of their link to increased mortality, these complications are among the most devastating associated with ECMO. A high index of clinical suspicion helps ensure an early diagnosis, which is paramount to avoid poor outcomes.

Vascular complications associated with ECMO are reviewed. The implementation, management, and indications for ECMO are reviewed separately. (See "Extracorporeal life support in adults in the intensive care unit: Overview" and "Extracorporeal life support in adults: Management of venovenous extracorporeal membrane oxygenation (V-V ECMO)" and "Extracorporeal life support in adults: Management of venoarterial extracorporeal membrane oxygenation (V-A ECMO)".)

GENERAL INFORMATION — As experience with the use of extracorporeal membrane oxygenation (ECMO) has grown and outcomes improve, indications have expanded to include a group of patients in whom treatment would have previously been considered futile. It should be emphasized that suitable candidates for ECMO must have a reversible or surgically correctable cause of respiratory failure or cardiogenic shock and have failed standard treatment. Extracorporeal Life Support Organization (ELSO) guidelines include the following as indications for ECMO: acute myocardial infarction, massive pulmonary embolus, postcardiotomy syndrome, heart transplant failure, postpartum cardiomyopathy, sepsis, hypothermia, drug intoxication, nonviral pneumonia, viral pneumonia, acute respiratory distress syndrome, and respiratory failure from various etiologies including coronavirus disease 2019 (COVID-19) [3-5]. They also recommend ECMO use before the onset of multiorgan failure and the use of prognostic scores to predict mortality risk in an attempt to improve patient outcomes.

The use of ECMO in an increasingly older and sicker population is supported by a growing body of literature demonstrating improved survival in high-risk patients with pulmonary or cardiopulmonary failure. The conventional ventilatory support versus extracorporeal membrane oxygenation for severe adult respiratory failure (CESAR) trial was among the first to establish a survival advantage for patients with pulmonary failure treated with ECMO compared with conventional treatment, with an absolute difference of 16 percent (63 versus 47 percent) [6]. This trial fueled the explosive growth of ECMO use seen since. One review reported a 646 percent increase in ECMO utilization in the United States over a ten-year period, with a significant increase in use subsequent to the publication of the CESAR trial [7]. In the later years of the trial, patients were older and had more comorbidities, but there were no differences in hospital mortality when comparing the older and younger groups. In a separate report, the use of ECMO in patients over the age of 70 increased by 280 percent from 2005 to 2015 [8]. By comparison, ECMO use in younger patients increased only by 190 percent during this same time frame. Although the authors of this report noted that older age was associated with increased mortality when compared with younger cohorts, older age alone was not considered a contraindication to ECMO use. These results suggested the benefit of using ECMO in sicker, older, or debilitated patients. In fact, ECMO is now well established as a treatment modality for pulmonary or cardiopulmonary failure, which is refractory to standard therapy including low-tidal volume, low positive end-expiratory pressure, prone ventilation, or oscillatory ventilation, irrespective of age. Complications associated with ECMO are increased in these older populations.

ECMO modes and cannulation — In its most basic form, the ECMO circuit requires an outflow cannula, plastic tubing, a centrifugal pump, a membrane oxygenator that also removes carbon dioxide, and a return cannula. As previously noted, significant improvements in technique and instrumentation have occurred since ECMO was first implemented in the 1970s, and these have been associated with a decrease in the incidence of vascular complications over time [9,10]. These advancements include heparin-coated circuits that are less thrombogenic and silicone-based membrane oxygenators that are less prone to hemolysis and consumption of clotting factors and platelets [3,11].

There are two distinct types of ECMO: veno-venous (V-V) and veno-arterial (V-A). Both provide temporary support and are used in the cardiac intensive care unit by a specialized team of physicians that includes critical care intensivists, interventional cardiologists, and cardiothoracic and vascular surgeons.

●V-V ECMO is used for pulmonary failure when hemodynamic support is unnecessary (image 1). (See "Extracorporeal life support in adults: Management of venovenous extracorporeal membrane oxygenation (V-V ECMO)".)

●V-A ECMO is used in cardiogenic shock when both pulmonary and hemodynamic support are required (figure 1). (See "Extracorporeal life support in adults: Management of venoarterial extracorporeal membrane oxygenation (V-A ECMO)".)

With both types of ECMO, large-bore cannulas are needed to move an adequate volume of blood through an extracorporeal circuit for oxygenation and carbon dioxide removal. The size of these cannulas in adults varies from 15 to 31 Fr. Cannula placement can be either central or peripheral. Central cannulation involves access to the ascending aorta, right atrium, or left atrium, and is used mostly in postcardiotomy patients since it requires a median sternotomy. Peripheral cannulation can use the internal jugular vein, femoral, axillary, or subclavian vessels. Compared with central cannulation, peripheral cannulation has been associated with decreased incidence of bleeding, infection, and neurologic complications [3,4]. Peripheral cannulation using the femoral vessels can also be established relatively quickly through a percutaneous route and has become the preferred cannulation approach with ECMO [4].

For V-A ECMO, ELSO guidelines recommend placement of the arterial and venous cannulas in separate limbs to reduce vascular complications and facilitate decannulation [4]. If possible, the venous cannula should be placed in the right common femoral vein, which is a more direct route to the inferior vena cava and right atrium, and the arterial cannula is placed in the left common femoral artery. For V-V ECMO, using a single, double-lumen cannula is preferred [4]. An image-guided approach to percutaneous cannula placement and protocolized anticoagulation management can help prevent bleeding and thrombosis related to ECMO [4]. Data suggest that ultrasound and fluoroscopy can be helpful at the time of cannulation to avoid complications and optimize cannula positioning [12-16]. When needed, open surgical cannula placement may be used.

Incidence and related mortality — Despite documented benefits [17,18], the rate of complications and mortality in patients undergoing ECMO is high [4]. Poor outcomes are driven in part by the underlying disease processes but are also related to the requirements for ECMO use, which include an extracorporeal circuit, the use of large-bore cannulas, and systemic anticoagulation. Vascular complications, such as bleeding, resulting from a consumptive coagulopathy and the use of systemic heparin; thrombosis, related to the presence of an extracorporeal circuit or the use of intravascular cannulas; and acute limb ischemia from femoral cannulation are commonly seen, and an overall survival of only approximately 50 percent is reported in the literature. Combined improvements in technique and instrumentation have undoubtedly contributed to better outcomes and a lower incidence of vascular complications when compared with earlier ECMO experience [9,10]. (See 'ECMO modes and cannulation' above.)

It should be noted that the incidence of vascular complications reported in the literature varies widely in part due to variable patient cohorts, variable definitions of vascular complications, and a lack of uniform reporting standards. The true incidence of these complications is best derived by analyzing data from the ELSO registry. This registry includes data collected from over 540 centers with more than 172,000 cases reported since 1990 from than 50 countries [2]. The data are voluntarily reported and consist of clinical variables, circuit mode and cannulation details, complications, and clinical outcomes. Importantly though, the ELSO registry only reports in-hospital outcomes, which prevents long-term analysis. In addition, it lacks data on venous thromboembolism, including deep vein thrombosis and pulmonary embolism, which an important cause of ECMO-related morbidity and mortality. (See 'Venous thromboembolism' below.)

Data collected from this registry on 14,580 V-A ECMO patients from 2014 to 2018 and reported in 2021 established the incidence of surgical site bleeding at 14.5 percent. Bleeding from the cannulation site was reported in an additional 12.5 percent of cases. Pulmonary hemorrhage was seen in 2.3 percent, and intracranial hemorrhage in 1.4 percent. Thrombosis with circuit component clots was reported in 9.2 percent. Acute limb ischemia was less common and occurred in 5.3 percent of patients, with 0.7 percent requiring amputation. In a separate report from the ELSO registry, which analyzed data on 7579 patients undergoing V-V ECMO from 2010 to 2017, surgical site bleeding occurred in 460 (6.1 percent) of patients, cannulation site bleeding was seen in 743 (9.8 percent), and thrombosis with circuit component clots in 1276 (16.8 percent). Pulmonary bleeding was seen in 291 (3.8 percent) and intracranial hemorrhage in 216 (2.8 percent). From these reports, the incidence of vascular complications varies with the mode of ECMO. Bleeding is the most common vascular complication reported with V-A ECMO, with thrombosis and acute limb ischemia seen less frequently. For V-V ECMO, thrombosis is more common than bleeding, with less impact on patient survival, and acute limb ischemia is rarely if ever seen [19].

Importantly, vascular complications have been correlated with increased mortality [20-24], and approximately 50 percent of those with vascular complications require operative intervention [12,25].

●One study reported a significant increase in mortality for bleeding (odds ratio [OR] 1.69, 95% CI 1.49-1.93) and for thrombotic complications (OR 1.23, 95% CI 1.08-1.41), although the association between thrombosis and mortality was not as strong [9]. Bleeding in this study was mostly driven by events such as intracranial bleeding, gastrointestinal bleeding, and pulmonary bleeding. Another analysis of the ELSO registry reported significantly decreased hospital survival in those who developed bleeding complications compared with those who did not (V-A ECMO: 33.9 versus 44.9 percent; V-V ECMO: 49.6 versus 66.6 percent) [10].

●Acute limb ischemia (ALI) is less commonly reported than bleeding or thrombosis and seen mostly with V-A ECMO, but has also been strongly linked with mortality by numerous observational studies [20,24-26]. In a retrospective review of 235 patients, ALI increased mortality threefold (OR 3.18, 95% CI 1.02-9.92) [26]. Likewise, another retrospective review of 229 patients in which the rate of acute limb ischemia was 16.5 percent, the reported hospital survival was significantly decreased for those with versus without ALI (32.6 versus 54 percent) [25].

ARTERIAL COMPLICATIONS

Bleeding — After initiation of extracorporeal membrane oxygenation (ECMO), bleeding is the most prevalent arterial complication, with bleeding reported more commonly in association with veno-arterial (V-A) ECMO when compared with veno-venous (V-V) ECMO, as previously mentioned. In fact, bleeding with V-V ECMO is unlikely arterial in origin and more likely related to cannula placement or to intracranial, gastrointestinal, or pulmonary hemorrhage.

Incidence of bleeding — Extracorporeal Life Support Organization (ELSO) registry data have reported overall bleeding rates of 30 percent for V-A ECMO [10]. In one report of V-A ECMO patients, surgical site bleeding was seen in 14.5 percent, bleeding from the cannulation site occurred in 12.5 percent, and retroperitoneal bleeding was reported in 7 percent, likely related to arterial trauma following cannula placement [19] In a meta-analysis of 47 studies that included 6124 patients undergoing V-A ECMO, significant bleeding and cannula site bleeding occurred in 15.4 and 12.6 percent, respectively [27]. Other reviews have reported a high incidence of bleeding associated with V-A ECMO ranging from 23 to 40 percent [12,17,28].

Etiology and risk factors for bleeding — The etiology of bleeding associated with V-A ECMO is often multifactorial. Arterial cannula placement can result in vascular trauma and is an important source of bleeding. Anticoagulation can cause surgical site bleeding in postcardiotomy, heart transplant patients, postpartum patients, or bleeding from other sites. Bleeding can also occur at the venous cannula site. As blood circulates through the ECMO circuit, the consumption of clotting factors and platelets with continuous thrombin deposition and fibrinogen consumption also predisposes to bleeding complications. Platelet dysfunction also occurs because of the shearing forces of the ECMO pump itself. Other factors that can exacerbate bleeding including hypothermia, liver dysfunction, and renal failure. In a report by Willers et al, risk factors for bleeding in V-A ECMO included female sex, ECMO duration, pre-ECMO arrest, hypothermia, and surgical cannulation.

Detection and management of bleeding — Recognition of bleeding from surgical sites, cannulation sites, or from the retroperitoneum is usually clinical and is supplemented by routine monitoring of hemoglobin levels and coagulation parameters and by appropriate imaging studies, as indicated. Bleeding is addressed based on severity and etiology. Holding or stopping anticoagulation altogether for those with excessive anticoagulation or life-threatening bleeding is appropriate, although decisions regarding anticoagulation in these patients are often difficult [29]. Blood transfusion and supplementation of clotting factors or infusion of cryoprecipitate or antifibrinolytic drugs such as aminocaproic acid or tranexamic acid may also be necessary [11]. A standard protocol for anticoagulation is critically important, and this has been described in detail [30,31]. ELSO guidelines recommend adequate anticoagulation and regular monitoring of activated partial thromboplastin time, platelets, and fibrinogen, and stopping or holding anticoagulation in cases of excessive or life-threatening bleeding [31].

Surgical site bleeding in postcardiotomy patients will often require reoperation. Access site bleeding can sometimes be controlled by local compression and adjusting anticoagulation. If this fails, surgical intervention may be required. Arterial repair and moving the cannula to another site such as the contralateral limb or axillary or subclavian arteries may be necessary. Aortic cannulation is seldom indicated because of its higher risk of bleeding and continued need for anticoagulation. (See "Access-related complications of percutaneous access for diagnostic or interventional procedures", section on 'Access site bleeding'.)

Retroperitoneal bleeding can often be managed conservatively, if limited, and may require withholding anticoagulation. Other patients may require endovascular or open surgical management (coil embolization, evacuation hematoma). (See "Access-related complications of percutaneous access for diagnostic or interventional procedures", section on 'Retroperitoneal hematoma' and "Spontaneous retroperitoneal hematoma and rectus sheath hematoma".)

Acute limb ischemia — Acute limb ischemia (ALI) is usually associated with V-A ECMO and rarely with V-V ECMO.

Incidence of ALI — An update from the ELSO registry on V-A ECMO, which included 14,580 patients, reported a 5.3 percent incidence of ALI, with 0.7 percent of patients requiring amputation [4]. In other reviews, the incidence of ALI has ranged from 10 to 17 percent [17,27,28].

Etiology and risk factors for ALI — ALI can occur at different time points in the care of ECMO patients and can present during cannulation, during ECMO support, after decannulation, or after hospital discharge.

●ALI is seen mostly with V-A ECMO when the femoral artery is used for placement of the arterial cannula. The principal mechanism of ischemia in this case is reduced arterial perfusion distal to the cannula site secondary to a large diameter, occluding cannula. Selective perfusion of the deep femoral artery (rather than the superficial femoral artery) due to misplacement of a distal perfusion catheter (DPC) has also been reported.

●Other potential mechanisms of ALI include injury or dissection of the femoral or iliac arteries during cannula insertion, distal embolization, elevated levels of vasopressors, complications related to preexisting peripheral artery disease (PAD), or venous obstruction leading to venous gangrene from an obstructing venous cannula. (See 'Venous thromboembolism' below.)

Risk factors correlated with ECMO-related ALI, although not consistently across reports [13,22], include lack of a prophylactic DPC [32,33], younger age [13,22,24], diabetes [22], pulmonary disease [22], PAD [22,33,34], percutaneous cannulation [12,35], large cannulas (>20 Fr) [33,36], female sex [37], vasopressors [34], and small femoral vessels (<6 mm) [13,34,37]. Heparin-induced thrombocytopenia can lead to arterial thrombosis and should be considered in patients with falling platelet counts. Other hypercoagulable states (eg, factor V Leiden, antithrombin III deficiency, protein C or S deficiency) can also result in thrombosis and ALI. Diabetes and respiratory diseases have also been independently correlated with limb ischemia during peripheral V-A ECMO. Diabetes is known to cause a proinflammatory state, with macrovascular and microvascular changes that contribute to limb hypoperfusion during low flow states [22,38]. Pulmonary conditions are characterized by a state of chronic hypoxia which induces endothelial damage, an inflammatory state, and development of atherosclerotic disease [39].

Prophylactic (nonselective) DPC (typically 6 Fr sheath) placement at the time of initial femoral artery cannulation is one strategy to prevent ischemic vascular complications [3,4,20,24,33,34,40,41]. In a meta-analysis, the risk of developing ALI was increased when patients did not have a DPC (odds ratio 1.93, 95% CI 1.17–2.47) [27]. In this study, using a DPC was also associated with decreased mortality. Similarly, a retrospective review showed that not using a DPC was significantly associated with ALI [32]. However, not all studies have reported significant reductions in ALI with DPC use [22,42]. One study noted a similar rate of ischemic vascular complication for patents with a DPC in place [42].

Larger cannulas are more likely to cause ALI due to obstruction [32,33,36]. In a retrospective review, cannula diameter greater than 20 Fr was significantly associated with ALI [32]. Young patients and female patients have smaller diameter femoral arteries and therefore may have a higher incidence of ischemic complications when undergoing V-A ECMO [24,30]. For patients with underlying PAD, baseline arterial flow may be reduced and there is an increased risk of arterial injury with manipulation of diseased vessels [14,24,33]. On the other hand, patients with PAD may better tolerate a certain level of ischemia due to the preexistent collateral circulation, whereas young, otherwise healthy patients usually have no collateral circulation. Also, placement of a large-bore venous cannula can increase venous pressure, which reduces perfusion pressure, further contributing to tissue hypoxia and potentially the development of compartment syndrome [31].

Detection of limb ischemia — Detection of ALI in patients undergoing V-A ECMO relies on frequent physical examination and assessment of perfusion pressure, supplemented by duplex ultrasound. Duplex ultrasonography can be used to measure peak systolic velocity of the dorsalis pedis and posterior tibial arteries [43]. (See "Clinical features and diagnosis of acute lower extremity ischemia", section on 'Physical examination'.)

Perfusion pressure in the limb can be measured once V-A ECMO is established and followed over time. A systolic pressure below 50 mmHg may indicate limb ischemia [44]. The adjunctive use of near-infrared spectroscopy (NIRS) may also aid the early recognition of ischemia in patients on ECMO and improve outcomes [32,42,45-48]. A drop in oxygen tissue saturation (StO₂) below 40 percent or a drop of more than 25 percent from baseline strongly correlated with ischemic events in one study [48]. Another study looked at differences in StO₂ between the cannulated and noncannulated extremity [45]. All patients with clinically significant limb ischemia had StO₂ below 50 percent, and all patients with cannula-related obstruction of flow had StO₂ difference greater than 15 percent between the extremities. ELSO guidelines recommend monitoring oxygen tissue saturation by NIRS and maintaining StO2 of greater than 50 percent, preferably 60 percent, and difference of less than 20 percent between limbs to facilitate the diagnosis of ALI [4].

Management of limb ischemia

Steps to reverse ischemia — The management of ALI involves maneuvers to improve lower extremity perfusion while maintaining ECMO. The patient's condition typically doesn't allow for discontinuing ECMO and as such, if efforts including revascularization do not resolve ischemia, amputation may be the only option, but this is overall uncommon. In various reviews, the rate of amputation has ranged from 0 to 5 percent [4,12,17,25,35].

Once ECMO-related ALI is identified, the following steps should be taken to reverse it:

●Increase the level of systemic anticoagulation.

●Evaluate for and treat reversible conditions contributing to ECMO-related ALI (hypotension, elevated level of vasopressors).

●Assess existing cannulas and catheters including any existing DPC for proper placement or thrombus. Improve blood flow to the limb by placing a DPC if one is not present. Other options include downsizing the arterial cannula, moving the arterial cannula to another site, retrograde limb perfusion thru distal tibial catheters, or using a venous drainage catheter. (See 'ECMO cannula/catheter management' below.)

●If ALI does not resolve, evaluate and treat other conditions (arterial dissection, distal thromboembolism, acute extremity compartment syndrome). If all else fails, thromboembolectomy, arterial repair, or distal revascularization using open surgical or endovascular techniques may be necessary. (See 'Recognize and treat acute compartment syndrome' below and "Embolism to the lower extremities", section on 'Open embolectomy' and "Lower extremity surgical bypass techniques" and "Endovascular techniques for lower extremity revascularization".)

ECMO cannula/catheter management — For patients with a DPC in place, the position of the catheter should be evaluated, and if malpositioned, the catheter should be repositioned or replaced. If a DPC was not used, we suggest proximal (superficial femoral artery) DPC placement as the initial measure to improve perfusion [24,49-52].

DPC placement into the superficial femoral artery is mostly performed percutaneously using ultrasound guidance, although an open surgical cut down can also be done. When possible, target flow through the DPC should be at least 100 mL/min to ensure adequate tissue perfusion [4]. While the catheter is typically placed into the superficial femoral artery, occasionally, retrograde limb perfusion can be also considered using the dorsalis pedis artery or the posterior tibial artery [4]. Placement of a distal venous drainage catheter attached to the vent port of the venous cannula can improve drainage and prevent venous thrombosis and venous ischemia [53,54].

In one registry on selective DPC placement, correct placement of DPC reversed all ischemic complications, however, there were several cases in which ischemia progressed due to the presence of occlusive disease in the superficial femoral artery, which limited distal flow [55]. It should be noted that persistent ischemia despite ultrasound-guided placement into the target vessel can be related to inadvertent advancement into the deep femoral artery rather than the superficial femoral artery. If ischemia persists despite correct placement of a DPC, another option to consider is downsizing the arterial cannula by replacing it with a smaller caliber cannula to improve antegrade flow or moving the arterial cannula to another site such as the contralateral limb, axillary artery, or subclavian artery. Aortic (central) cannulation is seldom done because of its higher risk of bleeding, infection, and neurologic injury, and this option is usually reserved for postcardiotomy patients because it requires an open chest [4]. (See 'ECMO modes and cannulation' above.)

When a DPC is in place, there is a risk of clot formation in the superficial femoral artery between the return cannula and the DPC, where flow is stagnant. As such, the approach to cannula removal becomes important for preventing additional vascular complications [4,41]. In a review of 814 patients with V-A ECMO, a higher rate of complications was reported after percutaneous decannulation compared with the surgical cutdown to remove the cannula (14.7 versus 3.4 percent) [35]. An open surgical approach also allows repair of the femoral puncture site with patch angioplasty, as necessary. In addition, if thromboembolism has occurred, a Fogarty balloon catheter can be used to clear thrombus. Intraoperative angiogram can be used to confirm adequate limb perfusion.

Recognize and treat acute compartment syndrome — If there has been a delay in management or if ALI persists despite the maneuvers discussed above (eg, DPC, cannula downsizing or replacement), compartment syndrome can develop and contribute to worsening ischemia. Reported rates of fasciotomy for compartment syndrome range from 4.5 to 10.8 percent [12,20,25,35], with major amputation rates of 0 to 4.7 percent [12,17,25,35].

Clinical manifestations of extremity compartment syndrome include an edematous, tense calf, pain on dorsiflexion of the foot, paresthesias, or paralysis. Increased compartment pressures may necessitate decompression of the leg compartments via a four-compartment fasciotomy or major amputation if irreversible ischemia has developed. (See "Pathophysiology, classification, and causes of acute extremity compartment syndrome" and "Acute compartment syndrome of the extremities" and "Lower extremity fasciotomy techniques".)

In addition, it is important to monitor for rhabdomyolysis, which may lead to renal failure or cardiac arrythmias. (See "Rhabdomyolysis: Clinical manifestations and diagnosis" and "Prevention and treatment of heme pigment-induced acute kidney injury (including rhabdomyolysis)".)

Other arterial complications — Other ECMO-related arterial complications include retrograde aortic or iliac artery dissection, pseudoaneurysm, and arteriovenous fistula formation. These complications can occur at the time of cannulation, during the ECMO run, or after decannulation. In the above-mentioned review, retrograde aortic dissection occurred in 5 of 320 patients (1.6 percent) [17].

●Most aortic dissections associated with ECMO are asymptomatic. When arterial occlusion results from dissection, differentiation from thromboembolic occlusion is important. Management of asymptomatic dissections is usually conservative, while symptomatic dissection can be treated endovascularly or by relocating the arterial cannula to a different site. (See "Access-related complications of percutaneous access for diagnostic or interventional procedures", section on 'Arterial dissection'.)

●Pseudoaneurysms have also been reported with incidence of 1.3 to 14 percent [27]. Pseudoaneurysms can be treated with ultrasound-guided thrombin injection if the neck is narrow or by placement of a covered stent [56]. Large pseudoaneurysms require surgical intervention. (See "Femoral artery pseudoaneurysm following percutaneous intervention", section on 'Management'.)

●Arteriovenous fistula. (See "Acquired arteriovenous fistula of the lower extremity".)

VENOUS COMPLICATIONS

Venous thromboembolism — Thrombosis is a common complication of extracorporeal membrane oxygenation (ECMO), more so with veno-venous (V-V) compared with veno-arterial (V-A) ECMO [4,8-10,17]. In a meta-analysis, among patients who underwent V-V ECMO, three studies reported thromboembolism encompassing 161 patients and the pooled prevalence was 58.2 percent (95% CI 5.2–100) [27]. One author attributed the predominance of thrombotic events in V-V ECMO to the longer duration of V-V ECMO, less aggressive anticoagulation, and lack of arterial cannulation [9]. Thrombus deposition within the ECMO circuit, and especially the oxygenator, is a common problem [4,9]. This can occur from the activation of clotting factors and platelets as blood is exposed to the circuit components. ECMO circuit malfunction and troubleshooting are reviewed separately. (See "Extracorporeal life support in adults: Management of venovenous extracorporeal membrane oxygenation (V-V ECMO)", section on 'Troubleshooting circuit dysfunction'.)

Thrombosis occurs because of stasis, vascular trauma, or hypercoagulability in the setting of insufficient anticoagulation. Infection also increases the risk of thrombosis. Collapse of the inferior vena cava from excessive suction on the outflow cannula in the presence of hypovolemia can also predispose to thrombosis. Particularly concerning are pulmonary thrombosis or thrombosis of the left ventricular outflow tract due to impaired ventricular contractility and stasis. Heparin-induced thrombocytopenia can lead to venous thrombosis and should be considered in patients with falling platelet counts. Other hypercoagulable states such as factor V Leiden, antithrombin III deficiency, and protein C and S deficiencies can also cause venous thrombosis.

In a study of 107 patients undergoing V-A ECMO, the most important determinant of cannula-associated thrombosis was infection on ECMO (odds ratio [OR] 3.03, 95% CI 1.14-8.03) [57]. Infection induces an acute phase reaction and may lead to a rise in fibrinogen levels. Interestingly, cannula diameter was not a risk factor for thrombosis in this report. Longer duration of ECMO support was also a risk factor for cannula associated thrombosis (OR 1.12, 95% CI 1.02-1.22), while anticoagulation (OR 0.21, 95% CI 0.06-0.68) and older age (OR 0.97, 95% CI 0.94-0.99) were protective. Other authors have reported similar findings, with duration of ECMO as an important risk factor for thrombosis and anticoagulation having a protective effect [9].

Venous thromboembolism can involve cannula site or inferior vena cava [27,58,59]. In a review of 67 V-V ECMO patients, half of identified thrombus occurred in the inferior vena cava [59]. Pulmonary embolism occurred in 7 patients (11.1 percent). Pulmonary embolism was observed more often in nonsurviving (autopsy) versus surviving patients (5 of 21 versus 2 of 42).

Venous thrombosis can also occur following decannulation, also commonly occurring in the inferior vena cava, followed by the femoral vein and the internal jugular vein in one review [57]. All cases of jugular and vena cava thrombus were asymptomatic, whereas femoral deep vein thrombosis (DVT) was associated with lower extremity edema. Interestingly, postcannulation DVT did not correlate with increased mortality, and only two patients with postdecannulation DVT were later diagnosed with pulmonary embolism.

Thrombotic complications are usually addressed by adjusting anticoagulation.

Venous injury and bleeding — Overall venous bleeding is less common than arterial bleeding. In a meta-analysis of 47 studies, among the 459 patients undergoing V-V ECMO, cannula site bleeding was reported in only one study with an incidence of 6.4 percent [27]. However, among 7579 patients undergoing V-V ECMO from 2010 to 2017, surgical site bleeding occurred in 6.1 percent of patients and cannulation site bleeding in 9.8 percent [9].

In an Extracorporeal Life Support Organization (ELSO) registry review, the bleeding rate for V-V ECMO was 22 percent [10]. Significant risk factors associated with bleeding on multivariate regression analysis included older age, ECMO duration, surgical cannulation, renal replacement therapy, and prone positioning.

Injury to the inferior vena cava has also been reported, likely resulting from cannula placement. In the above-mentioned reviews, inferior vena cava tear was reported in 2 out of 92 patients (2.2 percent) [17]. (See "Traumatic and iatrogenic injury to the inferior vena cava".)

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Acute extremity ischemia".)

SUMMARY AND RECOMMENDATIONS

●General principles – The use of extracorporeal membrane oxygenation (ECMO), either veno-venous (V-V) or veno-arterial (V-A) ECMO, has increased. ECMO requires the placement of large-bore cannulas (percutaneous, open surgical), which can be placed either centrally or peripherally. For peripheral cannulation, using the common femoral vessels has become a typical approach. For V-A ECMO, the arterial and venous cannulas are placed in opposite limbs, while for V-V ECMO, the use of a single cannula is preferred. (See 'ECMO modes and cannulation' above.)

●Vascular complications – Vascular complications such as bleeding, thrombosis, and acute limb ischemia (ALI) occur frequently and are associated with increased mortality. A high index of clinical suspicion is important for early recognition of vascular complications, which is paramount to avoiding poor outcomes. Factors inherent to the use of ECMO cause these complications, including the need for vascular cannulation, anticoagulation, other factors contributing to coagulopathy, and the potential for vascular stasis. (See 'Incidence and related mortality' above.)

●Arterial complications

•Bleeding – Recognition of bleeding from surgical sites, cannula sites, or the retroperitoneum is predominantly clinical, supplemented by routine laboratory monitoring and appropriate imaging studies. Transfusion of blood and blood products and withholding anticoagulation may be necessary, as may arterial repair and repositioning of the cannula if bleeding persists. (See 'Bleeding' above.)

•ALI – Early recognition of ALI in patients on V-A ECMO is based on frequent assessment of limb perfusion. (See 'Acute limb ischemia' above.)

-In addition to clinical symptoms and signs, the following parameters are suggestive of limb ischemia on ECMO: limb pressure below 50 mmHg and tissue oxygen saturation (StO₂) below 50 percent or a drop of more than 20 percent from the cannulated to the noncannulated limb.

-For patients identified with ALI, we adjust the level of anticoagulation and evaluate for possible acute compartment syndrome.

-For patients with a distal perfusion catheter (DPC) already in place, we evaluate the position of catheter, and if malpositioned, reposition or replaced it.

-For patients without a DPC in place (nonselective DPC), we suggest placement of a superficial femoral artery catheter as an initial measure to improve perfusion (Grade 2C). Other catheter management strategies may be to place a DPC more distally in the leg, downsize the arterial cannula, or placement of a distal venous drainage catheter.

-If ischemia persists, removing and repositioning the cannula or revascularization may be necessary. If revascularization is unsuccessful, amputation may be required, but this is uncommon.

•Others – Other arterial complications include aortic dissection, pseudoaneurysm formation, and arteriovenous fistula. (See 'Other arterial complications' above.)

●Venous complications – Thrombosis, which is more common with V-V ECMO, can occur because of stasis, vascular trauma, or hypercoagulability in the setting of insufficient anticoagulation. Venous thrombosis can involve the cannula site or inferior vena cava. Risk factors for thrombosis include infection and increasing number of days of ECMO support. Venous thrombosis also commonly occurs following decannulation. Venous thrombosis is usually managed by adjusting anticoagulation. (See 'Venous complications' above.)