Study population
We investigated 257 consecutive patients who underwent VA-ECMO from a retrospective multicenter registry at Samsung Medical Center, Seoul, South Korea, and Samsung Changwon Hospital, Gyeongnam, South Korea, from August 2014 through July 2017. Of these, we included only patients who were placed on peripheral VA-ECMO via femoral cannulation and excluded patients who were under 18 years of age or who underwent ECMO using central aortic or axilla-arterial cannulation. Ultimately, 230 patients were enrolled in this study and were divided into two groups according to timing of DPC insertion: patients who underwent DPC insertion at the time of the primary cannulation (DPC group) and patients who did not undergo DPC insertion at the primary femoral cannulation including provisional DPC insertion after the onset of distal limb ischemia (No-DPC group) (Fig. 1). The local institutional review board of each participating hospital approved this study and waived the requirement for informed consent.
Extracorporeal membrane oxygenation implantation and management
The decision to implant ECMO was made by an experienced team, and the ECMO was placed by either cardiovascular surgeons or interventional cardiologists. The Capiox Emergency Bypass System (Capiox EBS™; Terumo, Inc., Tokyo, Japan) and Permanent Life Support (PLS) System (MAQUET, Rastatt, Germany) were used. Heparin was intravenously administered as a bolus of 5000 units, followed by continuous intravenous infusion to maintain an activated clotting time between 150 and 180 s. After initiation of ECMO, the pump blood flow rate was initially set above 2.2 L/min/body surface area (m2) and subsequently adjusted to maintain a mean arterial pressure above 65 mmHg. Blood pressure was continuously monitored through an arterial catheter, and arterial blood gas analysis was performed in the artery of the right arm to estimate cerebral oxygenation. Additional fluids, blood transfusion, and/or catecholamines (i.e., norepinephrine, epinephrine, or dobutamine) were supplied to maintain intravascular volume and/or to achieve a mean arterial pressure above 65 mmHg if necessary [8].
Cannulation of extracorporeal membrane oxygenation and distal perfusion catheter
Percutaneous cannulation of the femoral artery and vein was mainly performed by the attending staff interventional cardiologist or cardiovascular surgeon using the Seldinger technique. The femoral vessels (either unilateral, one-side arterial, or one-side venous) were accessed retrograde using an angiogram needle. The venous cannula was either 55 or 68 cm in length and from 21 to 28 Fr.; the arterial cannula was 24 cm and from 14 to 21 Fr. The final selection of cannula was based on manufacturer pressure–flow curves for each cannula size and patient size. Femoral cut-down procedures were performed when it was difficult to puncture the femoral artery percutaneously, for example, in patients with peripheral artery disease or severe obesity. At bedside, the DPC placement site was accessed antegrade using a micropuncture needle followed by a 0.018-inch nitinol wire (Cook Medical Inc, Bloomington, IN, USA) at the proximal SFA ipsilateral to the arterial cannula. A 6- or 7-Fr. sheath was then advanced into the mid-SFA. In the catheterization laboratory, we first inserted another sheath at the common femoral artery (CFA) contralateral to the arterial ECMO cannula and advanced a hydrophilic wire from the CFA sheath (through the aortic bifurcation and the ipsilateral common iliac artery, then between the arterial ECMO cannula and the vessel wall of the ipsilateral common iliac artery) to the distal portion of the ipsilateral SFA. The DPC was then safely inserted into the distal portion of the arterial cannula (ipsilateral to the SFA) using a micropuncture needle as the reference point of the previously placed hydrophilic wire. The catheter was attached to the side port of the arterial cannula using 6-inch extension tubing with an intervening three-way stopcock (Fig. 2).
Data collection, definitions, and study outcomes
Baseline characteristics, procedural characteristics, laboratory data, and clinical outcome data were obtained by reviewing medical records or by telephone contact, if necessary. Laboratory findings, including creatinine and lactate, were collected just before VA-ECMO insertion. The primary outcome was limb ischemia, which was defined as cases requiring surgical management or involving neurologic sequelae. In-hospital mortality, successful weaning rate of ECMO, thrombotic events, major bleeding, and catheter-related complications (defined as a composite of limb ischemia, major bleeding, and thrombotic events) were assessed in addition to the primary outcome. Major bleeding was defined as cases involving hemodynamic instability or those that occurred in a critical area or organ such as intracranial, retroperitoneal, pericardial, or intramuscular with compartment syndrome.
Statistical analysis
Continuous variables were compared using Student’s t test or the Wilcoxon rank-sum test. The results were presented as mean ± standard deviation or median with interquartile range. Categorical data were tested using Fisher’s exact test or the Chi-square test. Multivariable logistic regression analysis was performed via a stepwise backward selection process to determine the independent predictors of limb ischemia. Clinical variables (i.e., fluoroscopy-guided simultaneous DPC, age ≥ 65 years, gender, duration of ECMO > 5 days, and large arterial cannula) were included in the regression models. All variables associated with limb ischemia were analyzed using univariate analysis. Factors with p < 0.2 and those that were clinically relevant were included in the multivariable analysis. All tests were two-tailed, and p value < 0.05 was considered statistically significant. Statistical analyses were performed using SPSS software, version 23 (IBM, Armonk, New York, USA).
