key: cord-0069201-nq0h7wcx authors: Tatooles, Antone J.; Mustafa, Asif K.; Joshi, Devang J.; Pappas, Pat S. title: Extracorporeal Membrane Oxygenation with Right Ventricular Support in COVID-19 patients with severe ARDS date: 2021-11-02 journal: JTCVS Open DOI: 10.1016/j.xjon.2021.10.054 sha: 24b5c74b7b3af6de3af1960f347436a49233fa31 doc_id: 69201 cord_uid: nq0h7wcx nan Rare cases of COVID-19 infection can lead to life-threatening respiratory failure. 1 Despite attempts to control the disease with social distancing and mass vaccination, 2% of patients continue to succumb to lung injury related to infection with this virus. 2 Mechanical ventilatory support is the primary intervention for patients with worsening respiratory failure progressing to Acute Respiratory Distress Syndrome (ARDS). 3, 4 Barotrauma, prolonged sedation, and nosocomial pneumonia in patients requiring mechanical support further lead to secondary complications and potentially limit recovery. 5 Veno-venous Extracorporeal Membrane Oxygenation (ECMO) has been used in severe cases of respiratory failure. [6] [7] [8] The international Extracorporeal Life Support Organization (ELSO) reports a 51% survival in patients with COVID-19 respiratory failure supported on ECMO. 9 The largest U.S. multi-center study reports a survival of 42%. 10 Several cannulation strategies can be applied, and no randomized clinical trial has evaluated the superiority of one technique over another. Our practice has applied veno-venous ECMO with right ventricular support using a dual-stage right atrium to pulmonary artery cannula, the Protek-Duo, for COVID-19 infected patients with respiratory failure who have failed conventional mechanical ventilatory support throughout the pandemic. The rationale for adopting this system was based on inadequate support observed in patients supported with two venous cannulas. Recirculation using two venous cannulas for support and difficulty mobilizing the patient provided the impetus for change. Conversion to a single access site with right atrial to pulmonary artery catheter provided several advantages: stable platform with rare catheter malposition, adequate flows, and decreased recirculation of drainage blood. Ambulation with this system was simplified. Catheter J o u r n a l P r e -p r o o f malposition was uncommon even in limited patient access with patients in quarantine and during subsequent prolonged support with ambulation. Moreover, pulmonary artery pressure measurements were conducted during catheter implantation, demonstrating severe pulmonary hypertension in all patients. Acute cor pulmonale in COVID-19 patients carries significantly higher mortality, 11, 12 , and obesity and ARDS are independent risk factors for right ventricular failure. 13, 14 As such, the Protek-Duo was chosen over other single access dual lumen catheters due to the additional potential for right ventricular support, with flow directly into the pulmonary circulation. Although the limitation of this cannula has not been evaluated, the durability of this system has been observed in a patient maintained on support for ten months on a single cannula. Over the past year and a half, 150 patients were supported with ECMO using the single access, dual-stage right atrium to pulmonary artery cannula. Early results of our first 40 patients were published in JAMA Surgery. 15, 16 Survival to discharge was 82.5%. 16 As the care of patients with COVID-19 infection requiring ECMO has evolved, we describe our approach, patient selection, institutional requirements, cannulation strategy, management, and the results of our experience. onwards. Waiver of the need for consent was obtained. The data was de-identified during analysis and publication to protect patient privacy. Of the 136 patients who have completed their hospital course, 75% were extubated from the ventilator, and 67% decannulated from ECMO and discharged alive. Only 3% required longterm rehabilitation, and 24% needed supplemental oxygen at discharge. The average time on the J o u r n a l P r e -p r o o f mechanical ventilator was 23.5 ± 5.4 days, and on ECMO was 48.4 ± 4.9 days. The average age was 46.9 ± 1.1 (SEM) years; 71% were men and 52% Hispanic. The average BMI was 34.3 ± 0.6 kg/m 2 , with obesity noted in 68% of the patients. More than 80% were prone, chemically paralyzed, and on vasopressors before ECMO initiation. Major complications such as stroke, as well as acute kidney or liver injuries, were limited. Tracheostomy was performed in 13% of patients. Mortality was 95% in this subgroup. Criteria for ECMO were based on ELSO principles. Patients supported were less than 70 years old with single organ dysfunction suffering from severe hypoxia or hypercarbia despite maximum ventilatory support similar to the stringent criteria described by the EOLIA trial group. 7 Although most patients supported are obese, absolute body mass index (BMI) weighed into the decision to offer ECMO support. BMI less than 50 kg/m 2 was preferred. Extreme obesity provides additional challenges, and these include difficulty ambulating patients and assuring adequate ECMO flows. The limitations of institutional resources such as critical care hospital beds and nursing staff were additional factors in our decision-making. Some of the absolute contraindications to ECMO placement were outlined in our previous publication. 15 Briefly, they include patients who have suffered a cardiac arrest without return of spontaneous circulation, those with severe acidosis or significantly elevated lactate levels, patients in multi-system organ failure, those with projected life expectancy less than five years prior to COVID-19 infection, as well as patients with known severe pre-existing chronic, life-threatening conditions. Patients on the mechanical ventilator for over two weeks were not considered for support. Successful application of ECMO requires a dedicated, experienced team with coordinated care of physicians, allied health professionals, perfusionists, respiratory, physical, occupational, and speech therapists, pharmacists, and nutritionists. Critical care nursing is paramount. Cardiothoracic surgeons are core team members whose expertise provides leadership and guidance in the management of these patients. Institutional limitations due to physical space and staffed beds dictate capacity. Focused units provide consistent adherence to principles of ECMO support. 17 Recovery is slow, often requiring months of in-hospital care. Veno-venous ECMO works parallel to the native circulation, so there will always be a mixing of oxygenated ECMO blood with desaturated native venous blood. Therefore, no veno-venous support system will thoroughly oxygenate all blood entering the arterial system. If desaturated native venous flow (i.e., the cardiac output) increases while the ECMO flow is constant, the arterial saturation will decrease. 17 Extreme oxygen extraction also leads to a reduction in native venous saturation, which decreases arterial saturation at constant ECMO flow. As such, optimizing oxygen delivery and evaluating oxygen consumption are important principles of ECMO management. The goal is to maintain oxygen delivery (DO2) at least three times oxygen consumption (VO2). 17 This requires a calculation of the arterial blood oxygen content, which is based on the partial pressure of oxygen, oxygen saturation, and hemoglobin levels. Despite single access, veno-venous ECMO, patients with extreme BMI, high cardiac output, and J o u r n a l P r e -p r o o f significant oxygen extraction may still be hypoxemic. Assessment of arterial lactate in these patients is also critical to the determination of adequate support. As long as DO2/VO2 is over 3, aerobic metabolism is assured, and lactate will typically be within normal limits. Although a variety of cannulation strategies are feasible, a single access, dual-stage right atrium to pulmonary artery cannula with access through the internal jugular vein was primarily used in the majority of our patients. Properly secured cannula placement is critical (Figure 1) . Placement requires fluoroscopy, and is best performed in an operative or hybrid suite where imaging is optimal; however, bedside insertion with portable imaging has been required for patients unable to tolerate any movement. Access most commonly is performed through the right internal jugular vein, although left internal jugular or subclavian vein approaches are equally successful. A balloon-tipped catheter is floated into the pulmonary artery and exchanged over a stiff wire. The access site is dilated, and the catheter is advanced to the main pulmonary artery. Not uncommonly, the distal tip of the catheter extends to the left or right main pulmonary artery due to the length of the catheter as the inflow is best positioned to the right atrium. Small patients are not appropriate for cannulation with the Protek-Duo due to the length of the catheter. Patients with estimated distance from the right atrium to pulmonary artery less than 17 centimeters or restricted vascular access unable to accommodate 29 French cannula are supported with alternative strategies. Two venous cannulas without right ventricular support are the initial strategy in pediatric patients who have required ECMO support. Alternative approaches are applied in rare patients who require greater flow or pediatric patients requiring ventricular support. Direct cannulation of J o u r n a l P r e -p r o o f the pulmonary artery or aorta is performed through a sternotomy. An eight or ten-millimeter vascular graft is sewn to the main pulmonary artery or ascending aorta. These grafts are tunneled subcutaneously and connected to the outflow circuit. Percutaneous cannulation of the right atrium provides inflow with conversion to veno-arterial or veno-venous ECMO. Decannulation is performed with ligation of the graft and burying of the residual stump subcutaneously without re-operative sternotomy. Rapidly declining patients who are intolerant of transfer to the operating room are initially supported with femoral-femoral or internal jugular-femoral cannulation. With ongoing support, the majority of these patients are converted to the Protek-Duo. The rationale for conversion is primarily to simplify access, avoid recirculation, maintain efficient gas exchange, and provide long-term catheter stability without malposition. Right ventricular failure is a devastating consequence in many patients with severe COVID-19 respiratory failure. 11, 12 Elevated central venous and right ventricular pressures as well as significant pulmonary hypertension at the time of ECMO initiation were routinely noted. As such, supporting the right heart under these circumstances has potential benefits. We also routinely employ pulmonary vasodilators such as inhaled nitric oxide. Initial management involves discontinuation of paralytics and minimizing ventilatory barotrauma Relative hypoxemia must be tolerated when there is no evidence of end-organ malperfusion. Blood transfusion is required to increase oxygen content and improve delivery. Experience has shown that titrating sweep with increased CO2 removal during episodes of symptomatic increased work of breathing has decreased the air hunger patients manifest and facilitated the ability to get patients off the ventilator. Most patients will require polypharmacy while weaning, including narcotics, anxiolytics, and antipsychotics. No single combination of drugs can be applied to all patients as clinical response varies and individual tailoring of sedation is required. Patients with prolonged pre-ECMO mechanical ventilatory support with high-dose sedatives require longer weaning periods; several weeks may be required. Anticoagulation with direct thrombin inhibitors was initiated with titration of prothrombin time (PTT) between 50 to 70 seconds. Hypercoagulability is also detrimental to the ECMO circuit as clots can hamper flow and damage the oxygenator. 18 Choice of anticoagulation was initiated due to early heparin resistance and avoidance of heparin-associated antibodies. Extubation requires an awake, cooperative patient able to follow simple commands with stable hemodynamics without maximal flow or sweep. Arterial saturation over 70% with normal lactic acid was targeted. Transfusion may be required to maintain normal oxygen content and prevent the elevation of lactic acid. Tracheostomy is not favorable in this group of patients. Our goal is to remove the endotracheal tube, limit airway instrumentation, and provide lung recruitment over time with incentive spirometry and physical activity. With patients off ventilator support, sedatives are minimized, physical therapy is maximized, and most patients will rehabilitate on ECMO. Rehabilitation is initiated on ECMO. Once extubated, aggressive physical, occupational, and speech therapy with nutritional supplementations are the mainstays of treatment (Figure 2) . Ambulation on ECMO is critical for clinical improvement (Video 1). Not uncommonly, patients have complete opacification of lung fields that do not improve until they ambulate. Once patients demonstrate increased activity and subsequent radiographic improvement, ECMO support is gradually weaned. With patients ambulating on ECMO, long-term care is uncommon following lung recovery and discontinuation of ECMO support. Limiting the number and duration of intravenous lines helps avoid bacteremia and fungemia, as overt sepsis with renal failure is associated with a poor prognosis. ECMO in COVID-19 patients has led to promising outcomes. Using single access, dual-stage veno-venous cannula with right ventricular support provides a stable support platform to J o u r n a l P r e -p r o o f facilitate ECMO. Alternative cannulation strategies may be required to achieve successful outcomes. Liberating the patient from sedation and mechanical ventilation, early extubation, and emphasis on physical and respiratory rehabilitation on ECMO are critical components of our treatment protocol. With this approach, patients with the most severely affected lungs with complete opacification on their chest radiographs were able to make a meaningful recovery Typical chest radiographs of a patient at different phases of treatment with significant improvement noted from complete airspace opacification to return to baseline. Video 1 -Ambulating on ECMO. 44-year-old gentleman with COVID-19 was supported on ECMO for 143 days. The video was taken on the day of decannulation. 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We would like to thank Dr. Robert Bartlett, Professor Emeritus of Surgery and Director of the ECMO research laboratories at the University of Michigan, for his insight in revising the manuscript. We would also like to thank all our brave medical staff including the intensivists, nurses, physician assistants, nurse practitioners, respiratory therapists, perfusionists, physical therapists, and speech and occupational therapists among others who selflessly took care of the patients.J o u r n a l P r e -p r o o f