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Access site complications of postcardiotomy extracorporeal life support

Open AccessPublished:November 24, 2021DOI:https://doi.org/10.1016/j.jtcvs.2021.09.074

      Abstract

      Objective

      To assess the influence of primary arterial access in patients receiving peripheral postcardiotomy extracorporeal life support on associated complications and outcome.

      Methods

      Of 573 consecutive patients requiring PC-ECLS between 2000 and 2019 at a single center, 436 were included in a retrospective analysis and grouped according to primary arterial extracorporeal life support access site. Survival and rate of access-site–related complications with special emphasis on fatal/disabling stroke were compared.

      Results

      The axillary artery was cannulated in 250 patients (57.3%), whereas the femoral artery was used as primary arterial access in 186 patients (42.6%). There was no significant difference in 30-day (axillary: 62%; femoral: 64.7%; P = .561) and 1-year survival (axillary: 42.5%; femoral: 44.8%; P = .657). Cerebral computed tomography-confirmed stroke with a modified ranking scale ≥4 was significantly more frequent in the axillary group (axillary: n = 28, 11.2%; femoral: n = 4, 2.2%; P = .0003). Stroke localization was right hemispheric (n = 20; 62.5%); left hemispheric (n = 5; 15.6%), bilateral (n = 5; 15.6%), or infratentorial (n = 2; 6.25%). Although no difference in major cannulation site bleeding was observed, cannulation site change for bleeding was more frequent in the axillary group (axillary: n = 13; 5.2%; femoral: n = 2; 1.1%; P = .03). Clinically apparent limb ischemia was significantly more frequent in the femoral group (axillary: n = 12, 4.8%; femoral: n = 31, 16.7%; P < .0001).

      Conclusions

      Although survival did not differ, surgeons should be aware of access–site-specific complications when choosing peripheral PC-ECLS access. Although lower rates of limb ischemia and the advantage of antegrade flow seem beneficial for axillary cannulation, the high incidence of right hemispheric strokes in axillary artery cannulation should be considered.

      Graphical abstract

      Key Words

      Abbreviations and Acronyms:

      aPTT (activated partial thromboplastin time), CCT (cerebral computed tomography), CPB (cardiopulmonary bypass), CPR (cardiopulmonary resuscitation), DPC (distal perfusion cannula), HTX (heart transplantation), LCOS (low cardiac output syndrome), MCS (mechanical circulatory support), MRS (modified ranking scale), PC-ECLS (postcardiotomy extracorporeal life support), VAD (ventricular assist device), Xclamp (aortic crossclamp time)
      Figure thumbnail fx2
      A, Axillary arterial cannulation. B, Femoral cannulation with distal perfusion cannula.
      Surgeons should be aware of specific access-site–related adverse events when choosing PC-ECLS access. The high incidence of right hemispheric strokes in axillary artery cannulation must be considered.
      PC-ECLS is a lifesaving bailout therapy for patients with postcardiotomy shock, but is associated with relevant mortality and morbidity. Several complications of PC-ECLS are related to the vascular access site. Knowledge of possible cannulation–site-related complications enables surgeons to choose the most suitable peripheral access site for individual patients.
      See Commentary on page 1559.
      Complexity of cardiac surgical procedures has risen during the past decades. Along with increasing age and morbidity of the patient population, the number of patients requiring postcardiotomy temporary extracorporeal life support (PC-ECLS) steadily increases.
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      Furthermore, PC-ECLS is associated with a number of potentially devastating complications that may arise during therapy and limit outcome, some of which are directly related to the site of cannulation, including limb ischemia and cannulation site bleeding. Cerebrovascular events are another frequent and often fatal complication.
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      With growing experience, peripheral vessel access has become the recommended strategy for PC-ECLS.
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      2020 EACTS/ELSO/STS/AATS expert consensus on post-cardiotomy extracorporeal life support in adult patients.
      Main advantages over central cannulation are the facilitated sternal closure, the lower risk for infection and mediastinal bleeding, as well as the easier intensive care unit handling and ECLS explantation. A recent meta-analysis also reported higher mortality in patients with central cannulation.
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      Peripheral versus central extracorporeal membrane oxygenation for postcardiotomy shock: multicenter registry, systematic review, and meta-analysis.
      Evidence on which peripheral access site is preferable is still scarce. Different peripheral arterial access sites have variable flow properties related to the location of the arterial cannula in the bloodstream. Cannulation of the axillary artery allows for predominantly antegrade body perfusion and proximal shift of the watershed, therefore preventing differential hypoxemia in patients with compromised pulmonary function.
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      Extracorporeal membrane oxygenation with right axillary artery perfusion.
      Another obvious advantage of axillary cannulation is the uncompromised leg perfusion, avoiding leg ischemia and related problems. For the stated reasons, indirect axillary artery cannulation via side graft has evolved to be the preferred access site for elective implantation at our center in recent years, whereas the femoral artery remains the access of choice in cases where rapid ECLS initiation is required.
      Despite all advantages, cerebral blood flow properties are more likely to be influenced in axillary artery cannulation because of the anatomic proximity of the cannulation site, which might represent a potential source of cerebral embolism. A possible relation of vascular ECLS access site and cerebrovascular adverse events is conceivable, but yet unclear. Furthermore, indirect axillary cannulation via an anastomosed side graft poses a risk of bleeding from the cannulation site.
      The aim of this study was to compare axillary and femoral artery cannulation in terms of outcome and the incidence of cannulation-site–related and cerebrovascular adverse events, as well as further assessment of the location of stroke in these patients.

      Methods

      Study Population

      The data of all patients undergoing PC-ECLS at the Department of Cardiac Surgery, Medical University of Vienna, were collected within an institutional database approved by the local ethics committee of the Medical University of Vienna (institutional review board No. 1086/2019), in compliance with the Declaration of Helsinki. Informed consent was waived due to the retrospective study design.
      All consecutive patients who received PC-ECLS from 2000 to 2019 (N = 573) at the Department of Cardiac Surgery at the Medical University of Vienna were screened for the inclusion and exclusion criteria stated below.

      Inclusion Criteria

      Patients aged 18 years or older who received ECLS after cardiopulmonary bypass (CPB) either intraoperatively or within 72 hours postoperatively for postcardiotomy low cardiac output syndrome (LCOS), cardiopulmonary resuscitation, or hemodynamic/respiratory instability of other etiologies necessitating initiation of ECLS.
      There is no defined age cutoff for PC-ECLS at our institution, and whenever a patient is determined to be a candidate for cardiac surgery, advanced age is not regarded a contraindication for ECLS if required to treat postcardiotomy shock. However, older patients are less likely to be eligible candidates for durable MCS or heart transplantation (HTX) and therapy may be withdrawn in the case the patient cannot be weaned from ECLS. In this case, a weaning attempt is made and ECLS explanted. HTX age cutoff is 70 years in our center, and although there is no absolute age cutoff for durable MCS, we are more restrictive with durable MCS implantation in patients aged 75 years or older. In cases when we anticipate that the patient will not be weanable from ECLS because of an underlying structural cardiac defect, we are more restrictive with ECLS implementation when the patient is no candidate for ventricular assist device (VAD)/HTX.

      Exclusion Criteria

      Patients were excluded in the case that 1 or more of the following criteria was met (Figure 1):
      • Central ECLS cannulation,
      • ECLS already installed before surgery/before CPB,
      • Patients who received ECLS for temporary right ventricular support at the time of left VAD implantation,
      • Patients undergoing thoracoabdominal aortic surgery,
      • Patients with a duration of ECLS <6 hours,
      • ECLS implanted >72 hours after the end of surgery,
      • Patients younger than age 18 years,
      • Missing data, and/or
      • Patients transferred on ECLS from another hospital.
      Figure thumbnail gr1
      Figure 1Study flowchart. Five hundred seventy-three consecutive patients undergoing postcardiotomy extracorporeal life support (PC-ECLS) from 2000 to 2019 were screened for inclusion and exclusion criteria. Four hundred thirty-six patients were included in a retrospective analysis and grouped by primary arterial cannulation site (axillary artery n = 250 or femoral artery n = 186). LVAD, Left ventricular assist device.
      Patients who received ECLS >72 hours after surgery were excluded to exclude patients with delayed complications of surgery that occurred after the patient has already been transferred to the regular ward, such as unexpected, brisk bleeding leading to tamponade and cardiopulmonary resuscitation and ECLS implantation under emergency conditions on a normal ward. These patients have unfavorable prognosis due to the unexpected and sudden deterioration in a less-controlled environment (ward vs intensive care unit), and we therefore believe these patients are not comparable to patients receiving ECLS during or shortly after cardiac surgery. However, because the majority of patients who required PC-ECLS at our center received ECLS intraoperatively or within 72 hours after surgery, using a cutoff of 72 hours, only a very low number of patients had to be excluded.

      Clinical Definitions and End Points

      Indication for ECLS implantation was:
      • Inability to separate from CPB because of LCOS, respiratory or metabolic instability with signs of anaerobic metabolism upon CPB weaning despite optimized supportive measures (ie, adequate vasopressor and inotropic support and fluid status), or
      • Postoperative LCOS or hemodynamic or respiratory instability of any cause not amenable to conservative measures and requiring the implantation of ECLS, or postoperative cardiac arrest.
      All-cause 30-day mortality was set as the primary end point. Incidence of cerebrovascular and access-site–related complications (stroke with modified ranking scale [MRS] ≥4, cannulation site bleeding requiring surgical revision and/or change of cannulation site, extremity ischemia and wound healing disorders), as well as all-cause long-term mortality were secondary end points.

      Peripheral ECLS Cannulation

      For axillary cannulation, the axillary artery is exposed and proximal and distal control is obtained. In the case that the patient is still on CPB at the time of implantation, an activated clotting time of >400 seconds is maintained. In the case that ECLS implantation is performed in a patient who is not on CPB, 5000 IU unfractionated heparin is administered before a side-biting clamp is applied to the vessel. An 8-mm polyethylene terephthalate graft is then anastomosed end-to-side. A 19F or 21F arterial cannula is inserted via the graft with the cannula tip placed 0.5 to 1 cm proximal to the anastomosis and secured to the graft with silk ligatures. A silicone vessel-loop is placed distally around the axillary artery, and a biradial invasive blood pressure monitoring is installed to enable regulation of the perfusion of the right arm. A venous drainage cannula is percutaneously inserted via the femoral vein.
      For femoral cannulation, the right or left common femoral artery is either percutaneously cannulated using the Seldinger technique or surgically exposed. A distal perfusion cannula (DPC) is used depending on vessel diameter and surgeon's preference. A representative video of axillary arterial cannulation is provided (Video 1).

      Patient Management on ECLS

      Anticoagulation on ECLS was performed with continuous intravenous administration of 7.5 to 20 IU/kg/h unfractionated heparin and monitored by activated partial thromboplastin time (aPTT) with a target therapeutic aPTT range of 1.5 to 2.5 × baseline. In case of confirmed or suspected heparin induced thrombocytopenia, argatroban was used instead of heparin with the same target aPTT. Anticoagulation was adapted or discontinued in case of severe mediastinal bleeding.
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      Anticoagulation in critically ill adults during extracorporeal circulation.
      Patients who receive ECLS during surgery are transferred to an intensive care unit specialized on the postoperative care of patients after cardiac surgery. The decision to initiate ECLS, irrespective of intraoperatively or postoperatively, is made with a multidisciplinary team approach involving anesthesiologists, intensivists as well as the surgeon who performed the surgery.
      Although a standardized weaning protocol has been developed at our institution within recent years, this was not available for the majority of the study period. In case of absent recovery, patients are evaluated for durable left ventricular assist device/HTX or ECLS is withdrawn after repeatedly unsuccessful ECLS weaning attempts if the patient is not eligible for left VAD/HTX, after thorough ethical consideration, interdisciplinary discussion of the case and involvement of the patient's family.

      Follow-up

      Survival data were retrieved from federal statistics (Statistics Austria, Vienna, Austria) and patient records. Hospital records were used to characterize intra- and postoperative course, as well as incidence of cerebral and access site related adverse events.
      Cerebral computed tomography (CCT) images were acquired during clinical routine in case of clinical suspicion of stroke and were retrospectively assessed for stroke location. Stroke severity was graded by clinical presentation and neurological assessment using MRS at the time of hospital discharge. Stroke with MRS ≥2 at the time of hospital discharge was classified as a disabling stroke according to the proposed definition for standardized neurological end points for cardiovascular clinical trials published by The Neurologic Academic Research Consortium,
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      Proposed standardized neurological endpoints for cardiovascular clinical trials: an Academic Research Consortium initiative.
      together with evidence of ischemic or hemorrhagic stroke on CCT. Additionally, the rate of patients with MRS ≥4 is reported.

      Statistical Analysis

      All statistical analyses were performed using Prism for Mac OS version 8.1.2 (GraphPad Software Inc, San Diego, Calif). Data are presented as median and interquartile range (IQR) for continuous variables, and absolute and relative frequencies for categorical variables. Survival was estimated using Kaplan-Meier curves and group comparisons of survival depending on primary arterial cannulation site performed by log rank test. For group comparisons of baseline characteristics, procedural variables, and adverse event rates, Fisher exact test was used for categorical variables, and Mann-Whitney U test for continuous variables. To identify risk factors of fatal/disabling stroke, a multivariable binary logistic regression model was used, including clinically relevant and statistically significant parameters from the bivariate analysis. Two-tailed P < .05 was considered statistically significant.

      Results

      Patients

      Between February 2000 and December 2019 a total of 573 patients required PC-ECLS at our center. After application of inclusion and exclusion criteria listed in Figure 1, 436 patients with primary peripheral ECLS cannulation were included in the analysis and divided into groups according to the primary arterial access site (axillary artery, n = 250 or femoral artery, n = 186).

      Baseline Characteristics

      Patients with primary axillary arterial cannulation were older, had a higher European System for Cardiac Operative Risk Evaluation II score (EuroSCORE II), higher prevalence of coronary artery disease, lower preoperative bilirubin level, aspartate aminotransferase level, and hemoglobin level, and a higher prevalence of peripheral arterial disease. There was no significant difference in the other studied baseline variables. Baseline characteristics are presented in Table 1.
      Table 1Baseline characteristics of the study cohort grouped by primary arterial extracorporeal life support (ECLS) access site
      CharacteristicTotal study population (N = 436)Indirect axillary (n = 250)Femoral (n = 186)P value
      Age (y)67.0 (57.2-73.8)68.7 (58.3-75.0)65 (55.8-71.5).0051
      Significantly different.
      Male sex287 (65.8)163 (65.2)124 (66.7).7605
      EuroSCORE II14.2 (5.9-30.9)15.0 (6.8-31.7)11.0 (3.9-28.1).0034
      Significantly different.
      BMI26.8 (24.0-30.0)26.8 (23.5-29.9)26.7 (24.3-30.1).5451
      Hypertension312 (71.6)186 (73.6)126 (67.7).1341
      Hypercholesterolemia236 (54.1)142 (56.8)94 (50.5).2074
      Insulin-dependent diabetes mellitus32 (7.3)21 (8.4)11 (5.9).3585
      Coronary artery disease243 (55.7)155 (62)88 (47.3).0025
      Significantly different.
      Left ventricular ejection fraction <15% or previous VAD78 (17.9)40 (16)38 (20.4).2564
      LVEF
       16%-30%88 (20.2)48 (19.2)40 (21.5).6296
       31%-50%105 (24.1)66 (26.4)39 (21).2134
       ≥51%147 (33.7)86 (34.4)61 (32.8).7592
      Creatinine (mg/dL)1.3 (1-1.8)1.3 (1-1.7)1.3 (1.1-1.8).0821
      Estimated glomerular filtration rate (mL/min/1.73 m2)57.4 (39.4-79)57.4 (39.3-75.9)56.7 (40.3-82.3).9479
      Blood urea nitrogen (mg/dL)24 (17-36.8)23 (16.4-34)25 (18.6-40.8).0644
      Total bilirubin (mg/dL)1 (0.6-1.2)1 (0.5-1.2)1 (1-1.1).0257
      Significantly different.
      ASAT (U/L)30 (22-52.3)28 (21-49)35 (23.5-60.5).0068
      Significantly different.
      ALAT (U/L)26 (18-43)26 (18-40)28 (18-48.5).2798
      Gamma-GT (U/L)59 (33-104)59.5 (32.8-98.3)54 (33-116.5).8644
      Hemoglobin (mg/dL)12 (10.3-13.9)11.9 (10.2-13.3)12.6 (11-14).0139
      Significantly different.
      C-reactive protein (mg/dL)1 (0.1-4)1 (0.2-4)1 (0.1-3.6).9597
      Peripheral arterial disease61 (14)45 (18)16 (8.6).0052
      Significantly different.
      Cerebrovascular disease62 (14.2)42 (16.8)20 (10.8).0956
      Previous stroke/TIA74 (17)46 (18.4)28 (15.1).3701
      Previous cardiac surgery139 (31.9)81 (32.4)58 (31.2).8356
      Previous VAD21 (4.8)10 (4)11 (5.9).3741
      Previous HTX1 (0.23)1 (0.4)0 (0)>.9999
      Active endocarditis46 (10.6)31 (12.4)15 (8.1).1586
      Values are presented as median (interquartile range) for continuous variables and absolute numbers (%) categorical variables. EuroSCORE, European System for Cardiac Operative Risk Evaluation score BMI, body mass index; VAD, ventricular assist device; LVEF, left ventricular ejection fraction; ASAT, aspartate aminotransferase; ALAT, alanine aminotransferase; gamma-GT, gamma-glutamyl transferase; TIA, transient ischemic attack; HTX, heart transplantation.
      Significantly different.

      Peripheral Arterial ECLS Access

      Of 436 patients with peripheral ECLS cannulation, the axillary artery was cannulated in 250 patients (57.3%), whereas the femoral artery was used as primary access site in 186 patients (42.6%). In case of axillary cannulation, the right axillary artery was used in the majority of patients (n = 242; 96.8%), whereas the left axillary artery was used infrequently (n = 8; 3.2%).

      Operative Data and ECLS Indication

      Procedure duration, CPB and aortic crossclamp (Xclamp) time were significantly longer in the axillary group, and the rate of surgery for type-A aortic dissection was higher in the axillary group. Periprocedural data are shown in Table 2. The rate of patients requiring cardiopulmonary resuscitation (CPR) before ECLS initiation, as well as the number of patients implanted under ongoing CPR was significantly higher in the group with primary femoral cannulation.
      Table 2Procedure data of the study cohort grouped by primary arterial extracorporeal life support (ECLS) access site
      Procedure detailsTotal study population (N = 436)Indirect axillary (n = 250)Femoral (n = 186)P value
      Isolated CABG51 (11.7)28 (11.2)23 (12.3).7639
      Valve repair/replacement131 (30)73 (29.2)58 (31.2).6737
      Combined CABG/valve surgery113 (25.9)72 (28.8)41 (22).1225
      Aortic aneurysm surgery13 (3)8 (3.2)5 (2.7)>.9999
      Acute type A aortic dissection24 (5.5)22 (8.8)2 (1.1).0004
      Significantly different.
      HTX81 (18.6)38 (15.2)43 (23.1).0460
      Significantly different.
      Congenital heart disease6 (1.4)2 (4)4 (2.2).4088
      Other17 (3.9)7 (2.8)10 (5.4).2125
      Procedure duration (hh:mm)8:08 (6:15-10:00)8:40 (6:45-10:15)7:27 (5:34-9:19)<.0001
      Significantly different.
      CPB (min)242 (175.3-321.8)262 (191-333)219 (155.0-296.0).0002
      Significantly different.
      Xclamp (min)102 (71.3-154)114 (80-162.5)94.5 (65.8-135.8).0010
      Significantly different.
      IABP37 (8.5)13 (5.2)24 (12.9).0052
      Significantly different.
      Values are presented as median (interquartile range) for continuous variables and absolute numbers (n) for categorical variables. CABG, Coronary artery bypass graft; HTX, heart transplantation; CPB, cardiopulmonary bypass time; Xclamp, aortic crossclamp time; IABP, intra-aortic balloon pump.
      Significantly different.
      Indication for ECLS was intraoperative failure to separate from CPB (73.6%), or postoperative LCOS or hemodynamic/metabolic instability/cardiopulmonary resuscitation within 72 hours from surgery (26.4%). The duration of ECLS was significantly longer in the axillary group (4.6 days [IQR, 2.9-7.1 days] vs 4 days [IQR, 2.5-6.1 days]; P = .044) (Table 3).
      Table 3Extracorporeal life support (ECLS) indications, run details, and adverse event rates of the study cohort grouped by primary arterial ECLS access site
      VariableTotal study cohort (N = 436)Indirect axillary (n = 250)Femoral (n = 186)P value
      ECMO indication
       CPB weaning failure (implanted during initial surgery)321 (73.6)188 (75.2)133 (71.5).4419
       Hemodynamic decline/CPR/respiratory failure after cardiac surgery (implanted within 72 h after end of surgery)115 (26.4)62 (24.8)53 (28.5).4419
      ECLS run details
       CPR before implant92 (21.1)42 (16.8)50 (26.9).0126
      Significantly different.
       Implant during ongoing CPR25 (5.7)5 (2)20 (10.8).0001
      Significantly different.
       Duration of support (d)4.31 (2.71-6.7)4.64 (2.91-7.09)4 (2.52-6.13).0442
      Significantly different.
       Reimplantation after weaning25 (5.7)15 (6)10 (5.4).8377
      Outcome
       In-hospital mortality219 (50.2)128 (51.2)91 (48.9)
       Length of hospital stay (d)39.2 (28.4-69.4)39.9 (29.1-77.1)36.7 (27.9-63.3).3340
      ECLS-related complications
       Any stroke48 (11)41 (16.4)7 (3.8)<.0001
      Significantly different.
      MRS 19 (18.8)7 (17.1)2 (28.6)
      MRS 23 (6.3)3 (7.3)0 (0)
      MRS 34 (8.3)3 (7.3)1 (14.3)
      MRS 411 (22.9)10 (24.4)1 (14.3)
      MRS 53 (6.3)3 (7.3)0 (0)
      MRS 618 (37.5)15 (36.6)3 (42.9)
       Stroke MRS ≥ 239 (8.9)34 (13.6)5 (2.7)<.0001
      Significantly different.
       Stroke MRS ≥ 432 (7.3)28 (11.2)4 (2.2).0003
      Significantly different.
      Ischemic23 (5.3)19 (7.6)4 (2.2).0155
      Significantly different.
      Hemorrhagic9 (2.1)9 (3.6)0 (0).0120
      Significantly different.
       Major cannulation site bleeding59 (13.5)34 (13.6)25 (13.4)>.9999
       Limb ischemia43 (9.9)12 (4.8)31 (16.7)<.0001
      Significantly different.
      Fasciotomy21 (4.8)8 (3.2)13 (7).0743
      Limb amputation5 (1.1)2 (0.8)3 (1.6).6550
       Arm hyperperfusion5 (1.1)5 (2)0 (0).0746
       Wound healing disorder/lymphocele (cannulation site)44 (10.1)10 (4)34 (18.2)<.0001
      Significantly different.
       Change of cannulation site36 (8.3)19 (7.6)17 (9.1).6002
       Change of cannulation site for bleeding15 (3.4)13 (5.2)2 (1.1).0301
      Significantly different.
       Change of cannulation site for limb ischemia10 (2.3)3 (1.2)7 (3.8).1059
       Arterial cannula accidentally displaced5 (1.1)2 (0.8)3 (1.6).6550
       Cannula/device thrombosis15 (3.4)11 (4.4)4 (2.2).2891
       Leg cannula displaced/obstructed38 (8.7)3 (1.2)35 (18.8)<.0001
      Significantly different.
       Aortic dissection2 (0.5)0 (0)2 (1.1).1814
      Values are presented as median (interquartile range) for continuous variables and absolute numbers (%) for categorical variables. ECMO, Extracorporeal membrane oxygenation; CPB, cardiopulmonary bypass time; CPR, cardiopulmonary resuscitation; ECLS, extracorporeal life support; MRS, modified ranking scale.
      Significantly different.

      Survival

      There was no significant difference in survival after 30 days (axillary: 62%; femoral: 64.7%; P = .561) and 1 year (axillary: 42.5%; femoral: 44.8%; P = .657) after ECLS initiation between patients with primary arterial ECLS cannulation of the axillary artery and femoral artery. There also was no difference in overall survival (P = .766) (Figure 2).
      Figure thumbnail gr2
      Figure 2Kaplan-Meier estimates of survival. Survival in patients with axillary (ax) and femoral (fem) arterial extracorporeal life support (ECLS) cannulation is visualized by Kaplan-Meier curves, and survival compared between the groups by log rank test. There was no significant difference in survival between patients with ax and fem primary arterial ECLS access site (ax vs fem P = .766). The shaded areas represent the 95% CI.
      Older age, lower preoperative glomerular filtration rate, longer duration of ECLS support, and performed procedure were significantly associated with mortality in a Cox proportional hazards model for mortality (Tables E1 and E2).

      Cerebral and Access-Site–Related Adverse Events

      Incidence of CCT-confirmed stroke with an MRS ≥4 was significantly higher in the axillary group (axillary: n = 28, 11.2% vs femoral: n = 4, 2.2%; P = .0003). Although there was no significant difference in major cannulation site bleeding requiring surgical revision, change of cannulation site because of bleeding was significantly more frequent in the axillary group (axillary: n = 13; 5.2% vs femoral: n = 2; 1.1%; P = .03).
      Clinically apparent limb ischemia (axillary: n = 12, 4.8%; femoral: n = 31, 16.7%; P < .0001) was significantly more frequent in the femoral group. The rate of complications arising from limb ischemia in patients with femoral arterial cannulation were reduced with use of a DPC; however, this reduction lacked statistical significance (Table E3). Of 12 patients with limb ischemia in the axillary group, the right arm was affected in 8 patients and leg ischemia occurred in 4 patients. The likely origin/pathomechanism of limb ischemia in patients with axillary arterial cannulation, as well as resulting morbidity, is described in detail in Table E4. Moreover, wound healing disorders requiring surgical intervention were significantly more frequent in the femoral group (Table 3).
      Of a total of 32 cases of stroke with MRS ≥4 in the study cohort, localization was right hemispheric in the majority of cases (n = 20; 62.5%), left hemispheric (n = 5; 15.6%), bilateral (n = 5; 15.6%), and infratentorial (n = 2; 6.25%) (see Table 4 and Figure 3).
      Table 4Stroke localization
      Primary arterial cannulation siteTotal No. of patients with stroke MRS ≥4Right hemisphericLeft hemisphericBilateralInfratentorial
      Total study population (N = 436)32 (7.3)20 (62.5)5 (15.6)5 (15.6)2 (6.25)
      Axillary artery (n = 250)28 (11.2)18 (64.3)4 (14.3)4 (14.3)2 (7.1)
      Femoral artery (n = 186)4 (2.2)2 (50)1 (25)1 (25)0 (0)
      Values are presented as absolute numbers (%). MRS, Modified ranking scale.
      Figure thumbnail gr3
      Figure 3The aim of the present study (), the definition of the study cohort and end points (), as well as the main results and conclusion of the study ( and ). Although no difference in survival between patients with femoral (fem) and axillary (ax) arterial extracorporeal life support (ECLS) cannulation was observed, the rate of stroke and cannulation site change for bleeding was significantly higher in the axillary group, whereas the incidence of limb ischemia and cannulation site wound healing disorders was significantly higher in the femoral group. The distribution of stroke localization in 32 patients with stroke with a modified ranking scale (MRS) ≥4 is shown. PC-ECLS, Postcardiotomy extracorporeal life support.
      Comparing baseline and periprocedural data of patients with (n = 32) and without (n = 404) fatal/disabling stroke, patients with severe stroke had significantly longer ECLS run duration (P = .034), longer aortic Xclamp time during main surgery (P = .004), higher rates of primary axillary arterial cannulation (P = .0003), aortic surgery (P = .043), and CPR before implantation (P = .174). All results of the bivariate analysis are depicted in Table E5. To identify risk factors for fatal/disabling stroke, the following variables were included in a multivariable binary logistic regression model: ECLS run duration, aortic Xclamp time, initial arterial cannulation site, and aortic surgery.
      Primary axillary arterial ECLS cannulation was identified as the strongest risk factor for severe stroke with an adjusted odds ratio of 4.51. Additionally, ECLS duration and aortic Xclamp time were identified as risk factors (Table 5).
      Table 5Risk factors for stroke modified ranking scale (MRS) ≥4 were identified using a binary logistic regression model, including clinically relevant and significant parameters from the bivariate analysis
      Risk factorAdjusted odds ratio (95% CI)P value
      Duration of ECLS (d)1.08 (1.00-1.15).0332
      Xclamp (min)1.00 (1.00-1.01).0323
      Initial cannulation site = axillary4.51 (1.69-15.63).0064
      Aortic surgery1.67 (0.55-4.41).3305
      ECLS, Extracorporeal membrane oxygenation; Xclamp, aortic crossclamp time.

      Discussion

      PC-ECLS is often a rescue therapy for patients with cardiopulmonary failure after cardiac surgery not amenable to conservative measures, which is reflected by a tremendously high mortality. Previous studies report in-hospital survival rates after PC-ECLS ranging from 25% to 46%.
      • Biancari F.
      • Perotti A.
      • Ruggieri V.G.
      • Mariscaloco G.
      • Dalen M.
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      • et al.
      Five-year survival after post-cardiotomy veno-arterial extracorporeal membrane oxygenation.
      • Biancari F.
      • Dalen M.
      • Fiore A.
      • Ruggieri V.G.
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      • Johsson K.
      • et al.
      Multicenter study on postcardiotomy venoarterial extracorporeal membrane oxygenation.
      • Khorsandi M.
      • Dougherty S.
      • Bouamra O.
      • Pai V.
      • Curry P.
      • Tsui S.
      • et al.
      Extra-corporeal membrane oxygenation for refractory cardiogenic shock after adult cardiac surgery: a systematic review and meta-analysis.
      • Rastan A.J.
      • Dege A.
      • Mohr M.
      • Doll N.
      • Falk V.
      • Walther T.
      • et al.
      Early and late outcomes of 517 consecutive adult patients treated with extracorporeal membrane oxygenation for refractory postcardiotomy cardiogenic shock.
      • Meani P.
      • Matteucci M.
      • Jiritano F.
      • Fina D.
      • Panzeri F.
      • Raffa G.M.
      • et al.
      Long-term survival and major outcomes in post-cardiotomy extracorporeal membrane oxygenation for adult patients in cardiogenic shock.
      • Chen F.
      • Wang L.
      • Shao J.
      • Wang H.
      • Hou X.
      • Jia M.
      Survival following venoarterial extracorporeal membrane oxygenation in postcardiotomy cardiogenic shock adults.
      In our study cohort, survival after 1 year from PC-ECLS implantation was 42.5% in patients with primary axillary cannulation, and 44.8% in patients with primary femoral cannulation.
      Although patients requiring PC-ECLS may have little or no chance to survive without temporary circulatory support, ECLS itself poses a considerable source of related complications that for themselves carry a high burden of morbidity and mortality.
      • Wong J.K.
      • Melvin A.L.
      • Joshi D.J.
      • Lee C.Y.
      • Archibald Wj
      • Angona R.E.
      • et al.
      Cannulation-related complications on veno-arterial extracorporeal membrane oxygenation: prevalence and effect on mortality.
      ,
      • Ohman J.W.
      • Vemuri C.
      • Prasad S.
      • Silvestri S.C.
      • Jim J.
      • Geraghty P.J.
      The effect of extremity vascular complications on the outcomes of cardiac support device recipients.
      These ECLS-related complications might be partly related to general and often inevitable circumstances of ECLS such as increased risk of surgical site bleeding under systemic anticoagulation, but others might be preventable and represent a vantage point for improving the outcome of patients on PC-ECLS, such as complications related to the choice of cannulation site.
      In the present study we evaluated 2 different peripheral arterial cannulation strategies for PC-ECLS in a cohort of 436 patients treated at a single center in terms of survival and incidence of cerebral and access-site–related adverse events. Although femoral arterial cannulation is a commonly used access site at many centers, indirect axillary artery cannulation has evolved to be a preferred arterial access site for PC-ECLS at our center for the benefit of predominantly antegrade body perfusion, avoidance of lower limb ischemia, as well as reduction of differential hypoxemia (ie, Harlequin effect) in patients with impaired pulmonary function.
      • Buchtele N.
      • Staudinger T.
      • Schwameis M.
      • Schorgenhofer C.
      • Herkner H.
      • Hermann A.
      • et al.
      Feasibility and safety of watershed detection by contrast-enhanced ultrasound in patients receiving peripheral venoarterial extracorporeal membrane oxygenation: a prospective observational study.
      ,
      • Honore P.M.
      • Gutierrez L.B.
      • Kugener L.
      • Redant S.
      • Attou R.
      • Gallerani A.
      • et al.
      Risk of harlequin syndrome during bi-femoral peripheral VA-ECMO: should we pay more attention to the watershed or try to change the venous cannulation site?.
      ,
      • Javidfar J.
      • Brodie D.
      • Costa J.
      • Miller J.
      • Jurrado J.
      • LaVelle M.
      • et al.
      Subclavian artery cannulation for venoarterial extracorporeal membrane oxygenation.
      A reported high rate of hyperperfusion syndrome in axillary cannulation
      • Chamogeorgakis T.
      • Lima B.
      • Shafii A.E.
      • Nagpal D.
      • Pokersnik J.A.
      • Navia J.L.
      • et al.
      Outcomes of axillary artery side graft cannulation for extracorporeal membrane oxygenation.
      can be addressed easily by application of a silicone vessel loop distal to the cannulation site and biradial invasive blood pressure monitoring to enable regulation of distal blood flow.
      In the setting of CPB weaning failure where a direct switch from CPB to ECLS is conducted, there is usually enough time to allow the more time-consuming indirect axillary artery cannulation. In emergency situations or whenever rapid initiation of ECLS is required, the femoral artery is still the preferred access site.
      Although survival did not differ between axillary and femoral arterial cannulation in our study (30-day survival: axillary: 62% vs femoral: 64.7%) we found a different spectrum and incidence of access-site–related adverse events. In particular, we observed a significantly higher rate of severe stroke in patients cannulated via the right axillary artery (axillary: 11.2% vs femoral: 2.2%), predominantly these strokes were located in the right hemisphere. Pisani and colleagues
      • Pisani A.
      • Braham W.
      • Bregga C.
      • Lajmi M.
      • Provenchere S.
      • Danial P.
      • et al.
      Right axillary artery cannulation for venoarterial extracorporeal membrane oxygenation: a retrospective single centre observational study.
      described a low incidence of local complications in axillary arterial cannulation in a mixed cohort of PC and non-PC ECLS patients; however, cerebral complications were not assessed. Toivonen and colleagues
      • Toivonen F.
      • Biancari F.
      • Dalen M.
      • Dell'Aquila A.M.
      • Jonsson K.
      • Fiore A.
      • et al.
      Neurologic injury in patients treated with extracorporeal membrane oxygenation for postcardiotomy cardiogenic shock.
      found that neurologic injury (ischemic or hemorrhagic stroke) is a common complication in PC-ECLS patients with a reported incidence as high as 19% and associated with adverse outcome in a multicenter meta-analysis of 781 PC-ECLS patients; however, the influence of the arterial access site was not addressed.
      Hypotheses for the high incidence of right hemispheric strokes are the anatomical proximity of the cannulation site together with flow turbulences at the anastomosis site. Especially in patients with smaller subclavian arteries and higher flow requirements, this might play an underestimated role.
      On the other hand, in some cases there is a chronological relation between ECLS weaning and onset of stroke (Table E6), although due to the retrospective design of the study, we could not prove this point. Nevertheless, it is recommended not to keep the patient on lower flow for a too-long time period.
      Measures to avoid thromboembolism during explant include proximal clamping of the subclavian/axillary artery during the explant procedure; however, this does not protect against thromboembolism from the cannulation site during the ECLS run. Based on the results of the present analysis, we consider it important to implement a standard operating procedure for axillary ECLS explant because a relevant proportion of major strokes seem to be in relation to the explant procedure. However, we emphasize that we cannot yet tell whether or not these measures are able to mitigate the occurrence of stroke in any way, and this must be subject of future studies. We suggest achieving proximal and distal control of the axillary artery before stopping ECLS and excluding the vessel from circulation. The cannula should then be removed, and the graft inspected for any thrombus formation, which is removed carefully. If a thrombus is present in the graft, a thrombectomy should then be performed from distally and proximally, before the artery is unclamped, the graft flushed in a retrograde fashion and ligated. To avoid thrombus formation at the cannulation site, adequate anticoagulation should be maintained, especially during the weaning phase, and a structured weaning protocol followed to avoid prolonged low-flow promoting thrombus formation during this phase. Because ECLS duration was also identified as a risk factor for stroke in this study, another important conclusion is that explantation of ECLS should never be unnecessarily delayed (eg, for logistic reasons) because longer ECLS run duration may increase the risk for adverse events and also for mortality, which has already been suggested by the results of previous studies,
      • Distelmaier K.
      • Wiedemann D.
      • Binder C.
      • Haberl T.
      • Zimpfer D.
      • Heinz G.
      • et al.
      Duration of extracorporeal membrane oxygenation support and survival in cardiovascular surgery patients.
      ,
      • Mariscalco G.
      • El-Dean Z.
      • Yusuff H.
      • Fux T.
      • Dell'Aquila A.M.
      • Jonsson K.
      • et al.
      Duration of venoarterial extracorporeal membrane oxygenation and mortality in postcardiotomy cardiogenic shock.
      and was also confirmed in the present study. Explantation of indirect axillary cannulated ECLS following the abovementioned standard operating procedure is uncomplicated and can be performed in the intensive care unit in most cases, thus not requiring any operating room capacity. Potentially, stroke incidence can be reduced by strictly adhering to these measures; however, surgeons should be aware of the specific risk in axillary cannulation.
      We observed no significant difference in cannulation site bleeding requiring surgical revision; however, change of cannulation site for severe bleeding was significantly more frequent in the axillary group. This may suggest that bleeding at the axillary cannulation site can be more difficult to manage and treat with success, thus requiring change to another site more frequently. This finding is in line with the results of previous studies investigating axillary ECLS cannulation.
      • Chamogeorgakis T.
      • Lima B.
      • Shafii A.E.
      • Nagpal D.
      • Pokersnik J.A.
      • Navia J.L.
      • et al.
      Outcomes of axillary artery side graft cannulation for extracorporeal membrane oxygenation.
      Of note, bleeding at the axillary cannulation site and hematoma formation can lead to malperfusion of the right arm and a vicious circle causing further complications, and this was the cause of upper extremity ischemia in 5 of 12 patients with extremity ischemia in the axillary cannulation group in our study (Table 5).
      As expected, we saw a significantly higher rate of clinically apparent limb ischemia in the group with femoral cannulation, and the rate of limb ischemia necessitating cannulation site change was more frequent in the femoral group. This was to be expected; however, rates of severe associated complication such as fasciotomy and amputation were similar in both groups.
      There was a visible reduction of limb ischemia and associated complications with the use of a DPC in our study; however, these reductions missed statistical significance and the study was probably underpowered to prove a benefit of DPC utilization. Additionally, although it became standard to implant a DPC at the time of ECLS implantation within recent years, this was not the case in earlier years where DPCs were often only implanted with already apparent clinical limb ischemia (Table E3).
      We believe that DPC placement right at the time of femoral ECLS implantation, as well as close clinical monitoring of the extremity to detect limb ischemia before complications arise, is of paramount importance and may be able to reduce the problem of severe limb complications with femoral ECLS cannulation. Furthermore, it is important to understand that axillary cannulation likewise carries a risk of limb complications, often related to cannulation site bleeding and subsequent impaired perfusion of the arm (Table E4).
      Despite the higher incidence of stroke, survival in the axillary group was the same as in the femoral group. The reasons for this might be that the femoral cannulation strategy has other disadvantages like the higher incidence of leg ischemia and the higher left ventricular afterload together with poorer oxygenation of the upper body. Therefore, according to our data, we cannot clearly recommend one cannulation site over the other but obviously the occurrence of major stroke is a relevant obstacle of the right axillary artery as cannulation site. Limb complications occurring with femoral access can be reduced by DPC utilization and close clinical monitoring. Furthermore, it should be emphasized that limb complications are not limited to femoral access but also occur in axillary cannulation, often as a consequence of cannulation site bleeding and hematoma formation. Pros and cons of each cannulation site need to be taken into consideration for each individual patient. Additionally, the quality of cannulation in each technique is highly dependent on the ECLS implanting surgeon. Attention must be paid to every detail: appropriate cannula selection, meticulous performance of the anastomoses of the graft to the axillary artery, as well as protection of leg perfusion in case of femoral arterial cannulation are essential. Anastomosis site bleeding as well as thrombus formation within the system need to be avoided, because a technically not optimally implanted ECLS might be the source of severe complications regardless of the site of cannulation.
      Nevertheless, our study shows that the primary access site can significantly influence the outcome of an individual patient. In our eyes, a prospective randomized trial comparing arterial ECLS access would be justified and necessary. Moreover, other options for primary access site need to be addressed such as cannulation of the left instead of the right subclavian artery, indirect femoral cannulation with a site graft, and even direct cannulation of the axillary artery in comparison to the indirect option.

      Limitations

      The retrospective design and potential for a historical bias are inherent to the present study because indirect axillary cannulation evolved to be the preferred access site at out center within the recent years, whereas femoral cannulation was more common in earlier years (Figure E1). Axillary cannulation is mostly used for ECLS access in controlled situations, such as weaning failure from CPB, allowing for cannulation while the patient is still on CPB, whereas femoral access naturally is preferred in emergency settings. Also, the management of ECLS patients in an intensive care unit is likely to have changed over time. A randomized trial evaluating different peripheral ECLS access sites for postcardiotomy ECLS is justified. Whereas preceding ECLS related events leading to stroke were detectable in some of the patients, it is not possible in every case to differentiate between perioperative and ECLS related origin of strokes in a retrospective study, especially in patients undergoing procedures with a high risk of perioperative stroke, such as patients with aortic dissections. Furthermore, strokes without clinical neurological symptoms in sedated patients were not apprehended because no routine CCTs were performed in absence of clinical neurological deficits.

      Conclusions

      Surgeons should be aware of different complication profiles when choosing peripheral arterial access site for postcardiotomy ECLS. Although lower rates of limb ischemia and the advantage of antegrade flow seem beneficial for axillary cannulation, especially the high incidence of right hemispheric strokes in axillary artery cannulation should be considered.

      Webcast

      Conflict of Interest Statement

      Dr Wiedemann is a proctor for Abbott and Medtronic. All other authors reported no conflicts of interest.
      The Journal policy requires editors and reviewers to disclose conflicts of interest and to decline handling or reviewing manuscripts for which they may have a conflict of interest. The editors and reviewers of this article have no conflicts of interest.

      Supplementary Data

      • Video 1

        Representative video of axillary arterial cannulation for postcardiotomy extracorporeal life support (PC-ECLS) using an 8-mm polyethylene terephthalate side graft. Video available at: https://www.jtcvs.org/article/S0022-5223(21)01659-7/fulltext.

      Appendix E1

      Figure thumbnail fx5
      Figure E1Histogram showing the utilization of axillary and femoral arterial postcardiotomy extracorporeal life support (PC-ECLS) cannulation over the study period.
      Table E1Baseline and periprocedure data of patients who died (n = 219) and who survived until hospital discharge (n = 217)
      Periprocedure dataTotal study population (N = 436)Survivors (n = 217)Nonsurvivors (n = 219)P value
      Age (y)67.0 (57.2-73.8)64.3 (54.1-77.8)68.6 (60.7-76.3)<.0001
      Significantly different.
      Male287 (65.8)154 (71)133 (60.7).0265
      Significantly different.
      EuroSCORE II14.2 (5.9-30.9)10.5 (4.5-22.1)17 (7-35.9).0002
      Significantly different.
      BMI26.8 (24.0-30.0)26.6 (23.7-29.4)26.8 (24.2-30.8).1327
      Hypertension312 (71.6)154 (71)158 (72).8321
      Hypercholesterolemia236 (54.1)121 (55.8)115 (52.5).5028
      Insulin-dependent diabetes mellitus32 (7.3)14 (6.5)18 (8.2).5824
      Coronary artery disease243 (55.7)121 (55.8)122 (55.7)>.9999
      Creatinine (mg/dL)1.3 (1-1.8)1.2 (1-1.7)1.3 (1.1-1.8).0392
      Significantly different.
      Estimated glomerular filtration rate (mL/min/1.73 m2)57.4 (39.4-79)62.3 (46.1-84.9)52.1 (36-72).0003
      Significantly different.
      Blood urea nitrogen (mg/dL)24 (17-36.8)22 (16-32)25.8 (18.4-42).0066
      Significantly different.
      Total bilirubin (mg/dL)1 (0.6-1.2)1 (0.5-1.0)1 (0.7-1.7).0134
      Significantly different.
      ASAT (U/L)30 (22-52.3)29 (22-51.8)31 (22.3-52.8).2967
      ALAT (U/L)26 (18-43)27 (17-43)26 (18-43).9757
      Gamma-GT (U/L)59 (33-104)54 (29-97)61 (35-124.5).0739
      Hemoglobin (mg/dL)12 (10.3-13.9)12.4 (11-14)12 (10-13.2).0164
      Significantly different.
      C-reactive protein (mg/dL)1 (0.1-4)1 (0.1-2.7)1 (0.2-5).0598
      Peripheral arterial disease61 (14)27 (12.4)34 (15.5).4080
      Cerebrovascular disease62 (14.2)24 (11.1)38 (17.4).0742
      Previous stroke/TIA74 (17)32 (14.7)42 (19.2).2512
      Previous cardiac surgery139 (31.9)68 (31.3)71 (32.4).8375
      Active endocarditis46 (10.6)19 (8.8)27 (12.3).2753
      ECMO indication>.9999
       CPB weaning failure (implanted during initial surgery)321 (73.6)160 (73.7)161 (73.5)
       Hemodynamic decline/CPR/respiratory failure after cardiac surgery (implanted within 72 h after end of surgery)115 (26.4)57 (26.3)58 (26.5)
      Duration of support (d)4.31 (2.71-6.7)3.6 (2.52-5.51)5.2 (3.1-8.2)<.0001
      Initial arterial cannulation site.6986
       Axillary250 (57.3)122 (56.2)128 (58.4)
       Femoral186 (42.7)95 (43.8)91 (41.6)
      Procedure performed.0003
      Significantly different.
       Isolated CABG51 (11.7)32 (14.7)19 (8.7)
       Valve repair/replacement131 (30)55 (25.3)76 (34.7)
       Combined CABG/valve surgery113 (25.9)46 (21.2)67 (30.6)
       Aortic surgery37 (8.5)18 (8.3)19 (8.7)
       HTX81 (18.6)57 (26.3)24 (11)
       Congenital heart disease6 (1.4)2 (1)4 (1.8)
       Other17 (3.9)7 (3.2)10 (4.6)
      CPB (min)242 (175.3-321.8)221.5 (165.5-313)256 (185.3-322).0398
      Significantly different.
      Xclamp (min)102 (71.3-154)97 (68-139)117 (75-167).0057
      Significantly different.
      CPR before implant92 (21.1)42 (19.4)50 (22.8).4120
      Implant during ongoing CPR25 (5.7)13 (6)12 (5.5).8398
      IABP37 (8.5)16 (7.4)21 (9.6).4925
      Values are presented as median (interquartile range) for continuous variables and absolute numbers (%) for categorical variables. EuroSCORE, European System for Cardiac Operative Risk Evaluation score; BMI, body mass index; ASAT, aspartate amino transferase; ALAT, alanine amino transferase; gamma-GT, gamma-glutamyl transferase; TIA, transient ischemic attack; ECMO, extracorporeal membrane oxygenation; CPB, cardiopulmonary bypass time; CPR, cardiopulmonary resuscitation; CABG, coronary artery bypass graft; HTX, heart transplantation; Xclamp, aortic crossclamp time; IABP, intra-aortic balloon pump.
      Significantly different.
      Table E2Cox proportional hazards model for mortality in patients undergoing postcardiotomy extracorporeal life support (PC-ECLS) (N = 436)
      CharacteristicHazard ratio (95% CI)P value
      Age1.011 (1-1.02).044
      Significantly different.
      Male gender0.935 (0.73-1.2).601
      Total bilirubin1.011 (0.99-1.02).072
      Estimated glomerular filtration rate0.993 (0.98-0.99).006
      Significantly different.
      Hemoglobin0.964 (0.91-1.02).211
      Aortic crossclamp time1.001 (1-1.01).156
      Duration of ECLS support1.04 (1.01-1.07).006
      Significantly different.
       Initial arterial cannulation site1.12 (0.87-1.44).369
      Procedure
      Reference = isolated CABG.
      .015
      Significantly different.
       Valve repair/replacement1.265 (0.83-1.93).275
       Combined CABG/valve surgery1.3 (0.85-2).231
       Aortic aneurysm surgery1.176 (0.53-2.6).688
       Aortic dissection1.006 (0.49-2.1).988
      HTX0.612 (0.38-0.99).048
      Significantly different.
       Congenital heart disease2.09 (0.77-5.6).148
       Other1.41 (0.71-2.8).326
      CI, Confidence interval; ECLS, extracorporeal life support; CABG, coronary artery bypass graft; HTX, heart transplantation.
      Significantly different.
      Reference = isolated CABG.
      Table E3Distal perfusion cannula (DPC) utilization and complications related to extremity ischemia in patients with femoral arterial extracorporeal life support (ECLS) cannulation
      ComplicationAll patients (N = 186)DPC at implant (n = 121)No or delayed DPC (n = 65)P value
      Leg ischemia31 (16.7)17 (14)14 (21.5).2181
      Compartment syndrome14 (7.5)7 (5.8)7 (10.8).2500
      Fasciotomy13 (7)6 (5)7 (11).2256
      Amputation3 (1.6)2 (1.7)1 (1.5)>.9999
      Cannulation site change due to leg ischemia7 (3.8)2 (1.7)5 (7.7).0518
      Values are presented as absolute numbers (%). DPC, Distal perfusion cannula.
      Table E4Origin/pathomechanism and resulting morbidity of extremity ischemia in patients with axillary arterial cannulation and limb ischemia (n = 12)
      PatientAffected limbLikely origin/pathomechanismMorbidity
      1Left legPrior left femoral arterial implant attempted, venous cannula in left femoral vein, known peripheral arterial diseaseFasciotomy of left thigh and lower leg
      2Right armSevere bleeding and hematoma formation at axillary cannulation siteFasciotomy of right arm
      3Right legOccurred after change of cannulation site to right femoralNone
      4Right armHyperperfusion and severe bleeding and hematoma at axillary arterial cannulation siteCompartment syndrome
      5Right armThrombotic occlusion of right subclavian and brachial arteryThrombectomy of right upper extremity and change of cannulation site to the left axillary artery, amputation
      6Left legKnown left atrial thrombus, cardioembolismFasciotomy and amputation of left leg, patient also had an ischemic stroke (MRS 2)
      7Right armSevere bleeding and hematoma formation at axillary cannulation siteFasciotomy and change of cannulation site to left axillary artery
      8Right armSevere bleeding and hematoma formation at axillary cannulation siteFasciotomy of right arm, change of cannulation site to right femoral artery
      9Right armHematoma formation and malperfusion, after revision hyperperfusionFasciotomy of right arm
      10Right armUnknownFasciotomy of right arm
      11Right armThromboembolic occlusion of right ulnar and radial artery, prior thrombus in arterial line describedIschemia of right hand
      12Right legPopliteal artery occlusion, venous cannula in right femoral veinFasciotomy right lower leg
      MRS, Modified ranking scale.
      Table E5Baseline and periprocedural data of patients with (n = 32) and without (n = 404) fatal/disabling stroke
      Patient dataTotal study population (N = 436)No fatal/disabling stroke (n = 404)Fatal/disabling stroke (n = 32)P value
      Age (y)67.0 (57.2-73.8)67.2 (57.1-74)67 (60.1-74.5).6737
      Male287 (65.8)268 (66.3)19 (59.4).4423
      EuroSCORE II14.2 (5.9-30.9)14.1 (5.9-31.6)14.2 (5.5.-21.7).7362
      BMI26.8 (24.0-30.0)26.7 (24.1-30)28.2 (23.1-30).8798
      Hypertension312 (71.6)288 (71.3)24 (75).8389
      Hypercholesterolemia236 (54.1)215 (53.2)21 (65.6).1999
      Insulin-dependent diabetes mellitus32 (7.3)29 (7.2)3 (9.4).7202
      Coronary artery disease243 (55.7)229 (56.7)14 (43.8).1956
      Creatinine (mg/dL)1.3 (1-1.8)1.3 (1-1.8)1.1 (0.9-1.6).0584
      Estimated glomerular filtration rate (mL/min/1,73 m2)57.4 (39.4-79)56.8 (39.3-77.7)66.6 (41.2-90.7).2292
      Blood urea nitrogen (mg/dL)24 (17-36.8)24 (17.4-37)21.9 (14.8-29.6).1587
      Total bilirubin (mg/dL)1 (0.6-1.2)1 (0.6-1.2)1 (0.4-1.4).9089
      ASAT (U/L)30 (22-52.3)30 (22-53)29 (22.8-43.8).6225
      ALAT (U/L)26 (18-43)26 (17.8-43)33 (20-44.5).3760
      Gamma-GT (U/L)59 (33-104)59 (33-106.5)54.5 (35.8-89.3).7018
      Hemoglobin (mg/dL)12 (10.3-13.9)12 (10.3-14)12 (10.5-13).3362
      C-reactive protein (mg/dL)1 (0.1-4)1 (0.2-4)0.9 (0.1-2.1).5026
      Peripheral arterial disease61 (14)55 (13.6)6 (18.8).4265
      Cerebrovascular disease62 (14.2)59 (14.6)3 (9.4).5995
      Previous stroke/TIA74 (17)67 (16.6)7 (21.9).4626
      Previous cardiac surgery139 (31.9)128 (31.7)11 (34.4).8440
      Active endocarditis46 (10.6)43 (10.6)3 (9.4)>.9999
      ECMO indication
       CPB weaning failure (implanted during initial surgery)321 (73.6)297 (73.5)24 (75)>.9999
       Hemodynamic decline/CPR/respiratory failure after cardiac surgery (implanted within 72 h after end of surgery)115 (26.4)107 (26.5)8 (25)>.9999
      Duration of support (d)4.31 (2.71-6.7)4.22 (2.68-6.67)5.1 (3.6-10.2).0336
      Significant difference.
      Initial cannulation site = axillary250 (57.3)222 (55)28 (87.5).0003
      Significant difference.
      Procedure details
       Isolated CABG51 (11.7)50 (12.4)1 (3.1).1547
       Valve repair/replacement131 (30)118 (29.2)13 (40.6).2281
       Combined CABG/valve surgery113 (25.9)104 (25.7)9 (28.1).8341
      Aortic surgery37 (8.5)31 (7.7)6 (18.8).0431
      Significant difference.
      Type A aortic dissection24 (5.5)22 (5.4)2 (6.25)
      Aortic aneurysm surgery13 (3.2)9 (2.2)4 (12.5)
       HTX81 (18.6)79 (19.6)2 (7.1).0942
       Congenital heart disease6 (1.4)6 (1.5)0 (0)>.9999
       Other17 (3.9)16 (4)1 (3.1)>.9999
      CPB (min)242 (175.3-321.8)242 (175.3-316)270 (174.5-338.3).4299
      Xclamp (min)102 (71.3-154)101 (70-153)133 (96.5-200.5).0044
      Significant difference.
      CPR before implant92 (21.1)82 (20.3)10 (31.25).1746
      Implant during ongoing CPR25 (5.7)24 (5.9)1 (3.1)>.9999
      IABP37 (8.5)37 (9.2)0 (0).0955
      Values are presented as median (interquartile range) for continuous variables and absolute numbers (%) for categorical variables. EuroSCORE, European System for Cardiac Operative Risk Evaluation score; BMI, body mass index; ASAT, aspartate amino transferase; ALAT, alanine amino transferase; gamma-GT, gamma-glutamyl transferase; TIA, transient ischemic attack; ECMO, extracorporeal membrane oxygenation; CPB, cardiopulmonary bypass time; CPR, cardiopulmonary resuscitation; CABG, coronary artery bypass graft; HTX, heart transplantation; Xclamp, aortic crossclamp time; IABP, intra-aortic balloon pump.
      Significant difference.
      Table E6Characterization of all strokes (N = 48) with timing and clinical indication for cerebral computed tomography (CCT), preceding extracorporeal life support (ECLS)–related events, and possible causes
      Cannulation site groupPatientTiming of CCTIndication for CCTHemorrhagic/ischemicMRS at dischargeLikely cause of stroke
      Axillary artery1Respiratory weaning/after explantReduced vigilanceHemorrhagic1Unknown
      2Respiratory weaning/after explantLeft-sided hemiplegiaIschemic4ECLS
      3Respiratory weaning/after explantLeft-sided hemiparesisIschemic4ECLS
      4Respiratory weaning/after explantComaHemorrhagic6ECLS
      5Directly after explantSudden onset fixed dilated pupilsHemorrhagic6ECLS explant
      62 d after explantLeft-sided hemiplegia, decrease of right-sided near-infrared spectroscopy to 29% directly after ECLS explantIschemic4ECLS explant
      7Respiratory weaning/after explantReduced vigilanceIschemic2ECLS
      8Respiratory weaning/after explantComaIschemic4ECLS
      9After extubationParesis of right armIschemic2ECLS or surgery related (type a aortic dissection)
      102 wk after ECLS explant, on regular ward before dischargeVisual field lossIschemic1Unknown/patient also had type a dissection
      11During ECLS run (day 6)Sudden onset fixed dilated pupils on day 6 during ECLS runHemorrhagic6ECLS
      12Respiratory weaning/after explantReduced vigilanceIschemic1Unknown, patient also underwent perioperative CPR
      13Respiratory weaning/after explantLeft-sided hemiplegiaIschemic4Patient also had mechanical mitral valve thrombosis
      14During ECLS run (day 3)Sudden onset anisocoria at day 3 of ECLSIschemic6ECLS
      15Respiratory weaning/after explantComa, leftsided hemiplegia, embolectomy of right brachial artery after ECLS explantischemic6ECLS related: CCT at beginning of ECLS normal, embolectomy right brachial artery after explant
      16Respiratory weaning/after explantTetraparesisIschemic5ECLS
      17Respiratory weaning/after explantTetraplegia and comaIschemic6Known left atrial thrombus and systemic embolism, also to left leg
      18Respiratory weaning/after explantUnknownIschemic3Unknown
      19Before hospital dischargeVisual field lossIschemic1Unknown, patient underwent concomitant right-sided carotid endarterectomy
      20During ECLS run (day 3)Sudden onset fixed dilated pupils at day 3 of ECLSHemorrhagic6On ECLS
      21Respiratory weaning/after explantHemiplegiaIschemic4ECLS
      22During ECLS run (day 4)Sudden onset anisocoria on day 4 of ECLSHemorrhagic6On ECLS
      23Respiratory weaning/after explantNCSEIschemic5Unknown, also underwent CPR
      24Respiratory weaning/after explantAphasia, leftsided HemiparesisIschemic3ECLS explanted because of device thrombosis despite adequate anticoagulation
      25Respiratory weaning/after explantHemiplegiaIschemic4ECLS, arterial cannula was changed due to thrombus formation
      26During ECLS runSeizureIschemic2ECLS
      27Respiratory weaning/after explantReduced vigilanceIschemic1Unknown
      28Respiratory weaning/after explantLeft-sided hemiplegia and dysphagiaIschemic4Patient had normal CCT 2 d before ECLS explant, large right sided ischemic stroke in CCT 3 d after ECLS explant
      29After arterial cannula change (same day)Sudden onset anisocoria after cannula exchangeHemorrhagic6Normal CCT 2 d prior to explant, onset of anisocoria after arterial cannula change due to thrombus formation
      30Respiratory weaning/after explantMyocloniaIschemic5Unknown, potentially ECLS related
      31Respiratory weaning/after explantReduced vigilance, positive Babinski right sideIschemic4ECLS
      32Directly after explantfixed dilated pupils after explant, thrombus in arterial cannulaIschemic62 d after explant, occlusion of the right internal carotid artery was diagnosed and patient underwent thrombectomy; however, patient developed a fatal stroke. Thrombotic material in the arterial cannula was noted at the time of explant
      33On ECLS (day 3)Sudden onset fixed dilated pupilsHemorrhagic6ECLS
      34Respiratory weaning/after explantComaIschemic6Unknown, 30 min CPR
      35During ECLS (day 5)SeizureIschemic1ECLS
      36On ECLS (day 3), after revision for mediastinal bleedingSudden onset fixed dilated pupilsHemorrhagic6Hypertensive phase during revision for bleeding; fixed unresponsive pupils after revision→CCT
      37Respiratory weaning/after explantReduced vigilance and seizureIschemic3Unknown
      38During ECLS run (day 24)UnknownIschemic6ECLS
      39Respiratory weaning/after explantHemiparesis and aphasia after extubationIschemic4ECLS
      40During ECLS (day 17)Seizures, dilated pupilsHemorrhagic6ECLS
      41Respiratory weaning/after explantUnknownIschemic1Unknown, also had aortic dissection
      Femoral artery1Respiratory weaning/after explantReduced vigilanceIschemic1ECLS
      2Respiratory weaning/after explantReduced vigilanceIschemic4Embolic? Patient also underwent CPR before implant
      3Respiratory weaning/after explantUnknownIschemic1Watershed infarct, CPR before implant
      4During ECLS run (day 6)AnisocoriaIschemic6On ECLS, cannulation site was changed from femoral to axillary artery 4 d before the event
      5Respiratory weaning/after explantHemiparesisIschemic3Unknown, perioperative CPR
      6On ECLS (day 8)Anisocoria during ECLS runIschemic6ECLS, Cannulation site was changed from femoral to axillary artery on day 4 after implant
      7On ECLS (day 7)Evaluation for durable left ventricular assist device implantationIschemic6Mechanical mitral valve thrombosis
      CCT, Cerebral computed tomography; MRS, modified ranking scale; ECLS, extracorporeal life support; CPR, cardiopulmonary resuscitation; NCSE, nonconvulsive status epilepticus.

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      Linked Article

      • Mechanism of stroke in the setting of postcardiotomy venoarterial extracorporeal membrane oxygenation support
        JTCVS OpenVol. 11
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          With great interest we read the study by Schaefer and colleauges,1 who conducted a detailed analysis of the outcomes of postcardiotomy venoarterial extracorporeal membrane oxygenation (VA-ECMO) support focusing on stroke and cannulation-related complications. The stroke rate of right axillary (RAX) VA-ECMO was greater than that of femoral cannulation. In both axillary and femoral VA-ECMO, the right hemisphere was the most common stroke location (64.5% in RAX and 50% in femoral). This stroke laterality trend in RAX cannulation was similar in our experiences.
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        Open Access
      • Commentary: Peripheral cannulation for postcardiotomy extracorporeal life support: An important piece of a much larger puzzle
        The Journal of Thoracic and Cardiovascular SurgeryVol. 164Issue 5
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          Postcardiotomy extracorporeal life support (PC-ECLS) is an essential component of contemporary cardiac surgical care. Temporary PC-ECLS can permit recovery of native myocardial or pulmonary function, correction of underlying derangements precluding the same, or allow time for bridging to more durable forms of support, as needed. The recent seminal European Association for Cardio-Thoracic Surgery, the Extracorporeal Life Support Organization, the Society of Thoracic Surgeons, and the American Association for Thoracic Surgery expert consensus statement provided recommendations on several aspects for PC-ECLS; however, detailed discussion of cannulation strategies was less granular in detail.
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