Aptamer-based factor IXa inhibition preserves hemostasis and prevents thrombosis in a piglet model of ECMO.

Extracorporeal membrane oxygenation (ECMO) requires anticoagulation to prevent clotting when the patient's blood contacts the circuit. Unfractionated heparin (UFH) usually prevents clotting but can cause life-threatening bleeding. An anticoagulant that selectively inhibits the contact activation (intrinsic) pathway while sparing the tissue factor (extrinsic) pathway of coagulation might prevent clotting triggered by the circuit while permitting physiologic coagulation at surgical sites. DTRI-178 is an RNA anticoagulant aptamer conjugated to polyethylene glycol that increases its half-life in circulation. This aptamer is based on a previously described molecule (9.3t) that inhibits intrinsic tenase activity by binding to factor IXa on an exosite. Using a piglet model of pediatric venoarterial (VA) ECMO, we compared thromboprevention and blood loss using a single dose of DTRI-178 versus UFH. In each of five experiments, we subjected two litter-matched piglets, one anticoagulated with DTRI-178 and the other with UFH, to simultaneous 12-h periods of VA ECMO. Both anticoagulants achieved satisfactory and comparable thromboprotection. However, UFH piglets had increased surgical site bleeding and required significantly greater blood transfusion volumes than piglets anticoagulated with DTRI-178. Our results indicate that DTRI-178, an aptamer against factor IXa, may be feasible, safer, and result in fewer transfusions and clinical bleeding events in ECMO.

Perioperative Anesthetic and Transfusion Management of Veno-Venous Extracorporeal Membrane Oxygenation Patients Undergoing Noncardiac Surgery: A Case Series of 21 Procedures.

OBJECTIVES: To analyze the perioperative management of veno-venous extracorporeal membrane oxygenation (VV ECMO) in patients undergoing major noncardiac surgical procedures, which is poorly described in the literature. In doing so, perioperative challenges related to hemodynamic instability, impaired gas exchange, bleeding, and coagulopathy will be quantified. DESIGN: Retrospective, nonrandomized, observational study. SETTING: A single, university-affiliated, quaternary medical center. PARTICIPANTS: Fourteen patients who underwent 21 noncardiac surgical procedures during the period of January 1, 2014, through April 1, 2016. Approval for this study was obtained from the Duke University Medical Center Institutional Review Board (study Pro00072723). INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Fifty percent of subjects were alive at 1 year after ECMO cannulation. Anesthetic type was variable with an inhaled anesthetic utilized in 71.4% of events, a presurgical continuous sedative was continued in 81.0% of cases, fentanyl was utilized in 100% of encounters, and midazolam was utilized in 71.4% of encounters. Intraoperatively, 50% of encounters resulted in an oxygen desaturation with a peripheral oxygen saturation assessed by pulse oximetry (SpO2)<90%, and 15% of procedures resulted in a SpO2 <80%. A vasopressor, most commonly epinephrine, was used during 66.7% of procedures. Intraoperatively, blood was administered in 52.4% of procedures, fresh frozen plasma was administered in 23.8% of procedures, and platelets were administered in 28.6% of procedures. Hemoglobin levels remained stable throughout the perioperative period, averaging 9.5 g/dL preoperatively, 9.7 g/dL immediately postoperatively, and 9.5 g/dL 24 hours after surgery. CONCLUSIONS: VV ECMO patients can be anesthetized using either inhalational or intravenous anesthetics. Patient hemodynamics, oxygenation, and decarboxylation require frequent interventions, but can typically be optimized to meet clinically acceptable thresholds.

Interhospital ECMO Transport: Regional Focus.

Utilization of extracorporeal membrane oxygenation (ECMO) has increased dramatically over the last decade. Despite this trend, many medical centers have limited, if any, access to this technology or the resources necessary to manage these complex patients. In an effort to improve the current infrastructure of regional ECMO care, ECMO centers of excellence have an obligation to partner with facilities within their communities and regions to increase access to this potentially life-saving technology. While the need for this infrastructure is widely acknowledged in the ECMO community, few reports describe the actual mechanisms by which a successful interfacility transport program can operate. As such, the purpose of this document is to describe the elements of and methods for providing safe and efficient mobile ECMO services from the perspective of an experienced, high-volume tertiary ECMO center of excellence in the Southeastern United States.

Vascular Complications and Use of a Distal Perfusion Cannula in Femorally Cannulated Patients on Extracorporeal Membrane Oxygenation.

Femoral arterial cannulation in adult venoarterial (VA) extracorporeal membrane oxygenation (ECMO) predisposes patients to ipsilateral limb ischemia. Placement of a distal perfusion catheter (DPC) is one of few techniques available to prevent or manage this complication. Although frequently used, the indications for and timing of DPC placement are poorly characterized, and no guidelines are available to guide its use. The purpose of this study was to compare the incidences of vascular complications and limb ischemia between patients who did and did not receive a DPC at the time of primary ECMO cannulation. Between June 2009 and April 2015, 132 adults underwent VA ECMO cannulation at our institution. Of the 80 femoral cannulations comprising this retrospective single-center study cohort, 14 (17.5%) received a DPC at the time of primary cannulation. Demographics, indications for ECMO, and cardiovascular history and risk factors were not significantly different between comparison groups. Median arterial cannula size was 17 French in both groups. Vascular complications occurred in 2 of the 14 patients with initial DPC (14.3%) compared with 21 of 66 without initial DPC (31.8%; p = 0.188). Limb ischemia occurred in 2 of 14 patients in the DPC group (14.3%) and 15 of 66 in the non-DPC group (22.7%; p = 0.483). In-hospital mortality was comparable between groups. DPC placement at the time of primary cannulation may lower the incidence of limb ischemia. The benefit of DPC placement once evidence of limb ischemia is apparent remains unclear.

Central Cannulation as a Viable Alternative to Peripheral Cannulation in Extracorporeal Membrane Oxygenation.

Arterial cannulation for veno-arterial (VA) extracorporeal membrane oxygenation (ECMO) is most commonly established via the aorta, axillary, or femoral vessels, yet their inherent complications are not well characterized. The purpose of this study was to compare the outcomes and complication rates of central vs peripheral cannulation. Adult patients undergoing VA ECMO between June 2009 and April 2015 were reviewed in this retrospective single-center study. Patient characteristics, clinical outcomes, and details related to deployment were extracted from the medical record. Complications and survival rates were compared between patients by cannulation strategy. Of 131 VA ECMO patients, there were 36 aortic (27.5%), 16 axillary (12.2%), and 79 femoral (60.3%) cannulations. Other than a lower mean age with femoral cannulations (53.9 ± 13.9 years) vs aortic (60.3 ± 12.2 years) and axillary (59.8 ± 12.4 years) (P = 0.032), the baseline patient characteristics were not statistically different. Central cannulation was more common in patients transferred from outside facilities (74.3% central vs 51.6% peripheral) (P = 0.053). Seven of 36 aortic cannulations were via anterior thoracotomy (19.4%). Forty of 131 patients underwent extracorporeal cardiopulmonary resuscitation (30.5%), 33 of whom were femorally cannulated. Peripheral cannulation carried a 29.5% rate of vascular complications compared with an 11.1% rate of mediastinal bleeding with central cannulation. Incidence of stroke and overall survival between groups were not statistically different. Central cannulation is a viable alternative to peripheral cannulation. Central cannulation avoids high rates of extremity morbidity without causing significant risks of alternative morbidity or death.

Extracorporeal Membrane Oxygenation and Interfacility Transfer: A Regional Referral Experience.

BACKGROUND: The number of adults referred to high-volume centers for extracorporeal membrane oxygenation (ECMO) is increasing. Outcomes of patients requiring transport are not well characterized, and referral guidelines are lacking. This study describes the experience and outcomes of a single high-volume center. METHODS: A retrospective study was performed that included adults undergoing ECMO between June 2009 and December 2015. Patient characteristics and outcomes were acquired from the medical record. Logistic regression was used to identify predictors of survival to hospital discharge. The Kaplan-Meier method was used to depict rates of survival. RESULTS: Of 133 patients, 77 (57.9%) underwent venoarterial (VA) ECMO and 56 (42.1%) underwent venovenous (VV) ECMO. Median transport distance was 88.8 miles (range 0.2-1,434 miles). Median duration of support was 6 days (range, 1-32.5 days). Age older than 60 years, pulmonary hypertension, and body mass index (BMI) greater than 30 were associated with worse survival to discharge for VA ECMO; a history of hypertension and presence of left ventricular (LV) vent were associated with better survival. Age older than 60 years and diabetes were associated with worse survival to hospital discharge for VV ECMO. Survival to decannulation was 66.2% and 76.8%, and to hospital discharge it was 48.1% and 69.6% for VA and VV ECMO, respectively. Of hospital survivors, Kaplan-Meier estimates of 1-year survival were 82.4% and 95.5% for VA and VV, respectively. CONCLUSIONS: Outcomes are favorable after transport to high-volume ECMO centers. Guidelines and infrastructure for short- and long-distance ECMO transport is imperative for the efficient and successful management of these patients.

Elective Venovenous Extracorporeal Membrane Oxygenation for Resection of Endotracheal Tumor: A Case Report.

We present a case in which we electively used venovenous extracorporeal membrane oxygenation (VV-ECMO) to facilitate safe resection of a nearly obstructing airway tumor near the carina in a 37-year-old male. The patient was brought to the operating room and underwent bifemoral cannulation for VV-ECMO under light sedation while maintaining spontaneous ventilation. After VV-ECMO was initiated, general anesthesia was induced, and the tumor was resected via rigid bronchoscopy. After resection, the patient was intubated, weaned from ECMO, decannulated, awoken, extubated, and taken to the postanesthesia care unit for recovery.

Outcomes before and after implementation of a pediatric rapid-response extracorporeal membrane oxygenation program.

BACKGROUND: Rapid-response extracorporeal membrane oxygenation (RR-ECMO) has been implemented at select centers to expedite cannulation for patients placed on ECMO during extracorporeal cardiopulmonary resuscitation (ECPR). In 2008, we established such a program and used it for all pediatric venoarterial ECMO initiations. This study was designed to compare outcomes before and after program implementation. METHODS: Between 2003 and 2011, 144 pediatric patients were placed on venoarterial ECMO. Records of patients placed on ECMO before (17 ECPR and 62 non-ECPR) or after (14 ECPR and 51 non-ECPR) RR-ECMO program implementation were retrospectively compared. RESULTS: The peak performance of the ECMO team was assessed by measuring ECMO initiation times for the ECPR patient subgroup (n = 31). There was a shift toward more ECPR initiations achieved in less than 40 minutes (24% pre-RR-ECMO versus 43% RR-ECMO; p = 0.25) and fewer requiring more than 60 minutes (47% pre-RR-ECMO versus 21% RR-ECMO; p = 0.14) after program implementation, although these changes did not reach statistical significance. After multivariable risk adjustment, RR-ECMO was associated with a 52% reduction in neurologic complications for all patients (adjusted odds ratio, 0.48; 95% confidence interval, 0.23 to 0.98; p = 0.04), but the risk of in-hospital death remained unchanged (adjusted odds ratio, 0.99; 95% confidence interval, 0.50 to 1.99; p = 0.99). CONCLUSIONS: Implementation of a pediatric RR-ECMO program for venoarterial ECMO initiation was associated with reduced neurologic complications but not improved survival during the first 3 years of program implementation. These data suggest that development of a coordinated system for rapid ECMO deployment may benefit both ECPR and non-ECPR patients, but further efforts are required to improve survival.

Active rehabilitation during extracorporeal membrane oxygenation as a bridge to lung transplantation.

BACKGROUND: Patients with end-stage lung disease often progress to critical illness, which dramatically reduces their chance of survival following lung transplantation. Pre-transplant deconditioning has a significant impact on outcomes for all lung transplant patients, and is likely a major contributor to increased mortality in critically ill lung transplant recipients. The aim of this report is to describe a series of patients bridged to lung transplant with extracorporeal membrane oxygenation (ECMO) and to examine the potential impact of active rehabilitation and ambulation during pre-transplant ECMO. METHODS: This retrospective case series reviews all patients bridged to lung transplantation with ECMO at a single tertiary care lung transplant center. Pre-transplant ECMO patients receiving active rehabilitation and ambulation were compared to those patients who were bridged with ECMO but did not receive pre-transplant rehabilitation. RESULTS: Nine consecutive subjects between April 2007 and May 2012 were identified for inclusion. One-year survival for all subjects was 100%, with one subject alive at 4 months post-transplant. The 5 subjects participating in pre-transplant rehabilitation had shorter mean post-transplant mechanical ventilation (4 d vs 34 d, P = .01), ICU stay (11 d vs 45 d, P = .01), and hospital stay (26 d vs 80 d, P = .01). No subject who participated in active rehabilitation had post-transplant myopathy, compared to 3 of 4 subjects who did not participate in pre-transplant rehabilitation on ECMO. CONCLUSIONS: Bridging selected critically ill patients to transplant with ECMO is a viable treatment option, and active participation in physical therapy, including ambulation, may provide a more rapid post-transplantation recovery. This innovative strategy requires further study to fully evaluate potential benefits and risks.

Active rehabilitation and physical therapy during extracorporeal membrane oxygenation while awaiting lung transplantation: a practical approach.

OBJECTIVE: Extracorporeal membrane oxygenation as a bridge to lung transplantation has traditionally been associated with substantial morbidity and mortality. A major contributor to these complications may be weakness and overall deconditioning secondary to pretransplant critical illness and immobility. In an attempt to address this issue, we developed a collaborative program to allow for active rehabilitation and physical therapy for patients requiring life support with extracorporeal membrane oxygenation before lung transplantation. DESIGN: An interdisciplinary team responded to an acute need to develop a mechanism for active rehabilitation and physical therapy for patients awaiting lung transplantation while being managed with extracorporeal membrane oxygenation. We describe a series of three patients who benefited from this new approach. SETTING: A quaternary care pediatric intensive care unit in a children's hospital set within an 800-bed university academic hospital with an active lung transplantation program for adolescent and adult patients. PATIENTS, INTERVENTIONS, AND MAIN RESULTS: Three patients (ages 16, 20, and 24 yrs) with end-stage respiratory failure were rehabilitated while on extracorporeal membrane oxygenation awaiting lung transplantation. These patients were involved in active rehabilitation and physical therapy and, ultimately, were ambulatory on extracorporeal membrane oxygenation before successful transplantation. Following lung transplantation, the patients were liberated from mechanical ventilation, weaned to room air, transitioned out of the intensive care unit, and ambulatory less than 1 wk posttransplant. CONCLUSIONS: A comprehensive, multidisciplinary system can be developed to safely allow for active rehabilitation, physical therapy, and ambulation of patients being managed with extracorporeal membrane oxygenation. Such programs may lead to a decreased threshold for the utilization of extracorporeal membrane oxygenation before transplant and have the potential to improve conditioning, decrease resource utilization, and lead to better outcomes in patients who require extracorporeal membrane oxygenation before lung transplantation.