A 40-year-old woman (height, 156 cm; body weight, 43 kg; body surface area, 1.38 m2) had undergone simultaneous pancreas-kidney transplantation for type 1 diabetes mellitus 8 years previously and had been receiving immunosuppressive therapy using prednisolone, tacrolimus, and everolimus. The patient was diagnosed with COVID-19 in September 2022; on the 18th day after disease onset, the patient was admitted to our hospital owing of hypoxia and worsening general malaise. Computed tomography (CT) showed ground-glass opacities in bilateral lungs, and oxygen, remdesivir, and dexamethasone were administered. On the 14th day of hospitalization, the patient did not require oxygen therapy and showed improved ground-glass opacities in the bilateral lungs. However, since she still had a slight fever and forearm and hand pain, a bacterial infection was suspected. On the 24th day of hospitalization, the patient developed hypoxemia, and CT revealed ground-glass opacities in both lungs again (Fig. 1). The patient’s respiratory condition rapidly deteriorated, and she was intubated in the intensive care unit (ICU). Her arterial blood gas (ABG) showed the following: pH 7.42, PaCO2 37 mmHg, PaO2 79 mmHg on pressure-controlled ventilation (PCV), fraction of inspiratory oxygen (FIO2) 0.35, pressure control (PC) 15 cmH2O, positive end expiratory pressure (PEEP) 10 cmH2O, and respiration rate (RR) 15/min. The PaO2/FIO2 ratio (PFR) was 201, and compliance of the total respiratory system (Crs) was 21 mL/cmH2O. Several chest radiographs within the ICU stay are shown in Fig. 2. Blood tests on ICU admission revealed the following results: white blood cell count, 21,000/µL; platelet count, 4.9 × 104/µL; blood urea nitrogen level, 106 mg/dL; creatinine level, 4.6 mg/dL; C-reactive protein level, 22 mg/dL; and procalcitonin level, 1.3 mg/dL. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antigen test results were negative. Piperacillin-tazobactam were administered as empirical antibiotics to assess bacterial infection. Immunosuppressive therapy after simultaneous pancreas-kidney transplantation was continued combined with only steroids concerning that bacterial infection would worsen. As the patient had anuria, kidney replacement therapy was administered for fluid correction to treat overhydration, thereby, hemodynamics was maintained. Although the etiologies of anuria might have included sepsis, side effects of medication, and acute rejection, none could be identified. On the 2nd day in the ICU, Corynebacterium striatum was detected in blood cultures, and vancomycin was administered. Transthoracic echocardiography showed mitral valve thickening, suspecting vegetation. On the 4th day in the ICU, transesophageal echocardiography (TEE) revealed vegetation on the aortic (Fig. 3A) and mitral valves, leading to a diagnosis of IE. All aortic valve leaflets had vegetation length of 4 mm. The mitral valve showed three contiguous papillary, irregularly shaped, and mobile vegetations extending 5–15 mm from the entire A2P2 junction. Valve dysfunction was mild, and the ejection fraction was normal. As the patient’s cardiac function was normal, ARDS was suspected to be the cause of respiratory failure rather than heart failure. After discussing the timing of the surgery with the team, it was decided to continue antimicrobial therapy to improve her general condition. Blood cultures were negative; however, the patient’s pulmonary function did not improve. The Crs of the patient’s lungs decreased to 15 mL/cmH2O, resulting in hypercapnia, and chest radiography showed mediastinal emphysema. Regarding mediastinal emphysema, we avoided excessive ventilation pressures using mechanical ventilation. Although we applied the prone position, it was discontinued due to hemodynamic instability. On the 11th day in the ICU, a follow-up TEE revealed progressive aortic valve regurgitation (Fig. 3B). The patient was scheduled to undergo aortic and mitral valve replacement and the removal of vegetation that causes of septic ARDS.
Fig. 1Computed tomography on admission: multiple frosted shadows are seen in the bilateral lung fields
Fig. 2Chest radiographs during the course of treatment. A: on admission to ICU, B: preoperative radiograph, C: postoperative radiograph, D: before prone positioning, E: after prone positioning, F: before extracorporeal membrane oxygenation (ECMO) withdrawal, G: after respiratory weaning
Fig. 3Comparison of aortic valve long-axis images. A: Post-ICU admission transesophageal echocardiography (TEE): verrucae adhered to the aortic valve and aortic regurgitation were observed. B: Preoperative TEE showing enlarged verrucae and worsened aortic regurgitation
After preoperative consultation with the team, a decision was made to initiate V-V ECMO after the patient was weaned from CPB, with concerns about further worsening of her respiratory status after surgery. The patient was transported from the ICU to the operating room under intubation and sedation. Hemodynamic evaluation was conducted via TEE and a Swan-Ganz pulmonary artery catheter. During induction of general anesthesia, anesthesiologists inserted a drainage cannula (19-Fr cannula for drainage, HLS Cannula®; Getinge, Gothenburg, Sweden) into the right atrium via the right internal jugular vein. After the loss of spontaneous breathing, mechanical ventilation could not provide effective ventilation and acidemia progressed rapidly. The patient’s hemodynamics became unstable because of acidemia, and surgery was promptly initiated. An inflow cannula was inserted into the ascending aorta, and a drainage cannula (23-Fr cannula for drainage, Bio-Medicus® Nextgen; Medtronic, Minneapolis, MN, USA) was inserted into the inferior vena cava via the right femoral vein to establish CPB. Aortic and mitral valve replacement was performed with mechanical valve in consideration of life expectancy. After valve replacement, TEE showed no abnormalities in the replaced valve; circulation was maintained with inotropic support at the time of weaning from the CPB. We temporarily stopped the pump and assessed ABG while the cannula remained in position without protamine infusion. ABG test showed severe hypoxemia (PFR, 70) and respiratory acidosis due to which there was a failure of ventilation and accumulation of carbon dioxide. Hemodynamic parameters rapidly deteriorated and the pump was restarted. Since the cause of hemodynamic instability was poor ventilation, we decided to initiate V-V ECMO. Therefore, the perfusionist primed ECMO circuit and the patient was promptly transitioned from CPB to V-V ECMO (Cardiohelp System; Getinge). A drainage cannula in the patient’s right internal jugular vein was used as the return cannula to establish V-V ECMO. After V-V ECMO administration, the patient’s hemodynamics stabilized. Protamine was administered to neutralize heparin after V-V ECMO conversion. Thereafter, the chest was closed. The patient was returned to the ICU under sedative intubation.
In the ICU, the ECMO settings were 2700 rpm, flow rate at 3 L/min, and a sweep gas flow of 3.5 L/min. Ventilation was set at PCV, FIO2 0.3, PC 5 cmH2O, PEEP 7 cmH2O, and RR 6/min. The peripheral capillary oxygen saturation (SpO2) was kept at > 95%. A heparin drip was used to prevent blood clots. On postoperative day 6, a brain CT scan revealed scattered subcortical brain hemorrhages complicating IE. After consultation with a neurosurgeon, it was determined that anticoagulation could be continued because the cerebral hemorrhage was mild. Originally targeting an activated partial thromboplastin time (aPTT) of 60–80 s in the patient receiving ECMO support, after cerebral hemorrhage we targeted the aPTT range of 60–70 s. Despite daily bronchoscopic clearance of the sputum, white viscous sputum obstructed the patient’s bilateral bronchi. For sputum excretion, prone positioning was initiated on postoperative day 12. Tracheostomy was performed on postoperative day 18. Chest radiography showed improvement in the lung field and Crs. On postoperative day 20, the patient exhibited no abnormal neurological findings, and her lung function improved (PFR: 493 and Crs: 30 mL/cmH20). Therefore, V-V ECMO was discontinued on postoperative day 33. Mechanical ventilation was discontinued on day 35 and the patient was discharged from the ICU on postoperative day 47. Function of the transplanted organ was preserved, and blood purification and insulin therapy were weaned. The patient was discharged without assistance on postoperative day 107.
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