Use,of,veno-arterial,extracorporeal,membrane,oxygenation,in,the,first,successful,combined,lung-liver,transplantation,patient,in,China

Man Huang ,Yong-shan Xu ,Sheng Yan ,Yan-jun Shi ,Sai-bo Pan ,Yi-bing Chen ,Chen-yang Gao,Jing-yu Chen,Wei-lin Wang

1 Department of General Intensive Care Unit,the Second Affiliated Hospital of Zhejiang University School of Medicine,Hangzhou 310009,China

2 Department of Hepatobiliary and Pancreatic Surgery,the Second Affiliated Hospital,Zhejiang University School of Medicine,Hangzhou 310009,China

3 Department of Lung Transplantation,the Second Affiliated Hospital of Zhejiang University School of Medicine,Hangzhou 310009,China

Extracorporeal membrane oxygenation (ECMO) is a modality of extracorporeal life support that allows for temporary support in pulmonary and/or cardiac failure refractory to conventional therapy.ECMO use has been exponentially increasing over the last decade and is now considered a mainstream lifesaving treatment modality in critical care medicine.Many studies report ECMO use in patients with acute respiratory distress syndrome refractory to conventional clinical support,in-hospital cardiac arrest,and cardiogenic refractory shock.Herein,we report the use of veno-arterial ECMO (VA-ECMO) in the first successful combined lung-liver transplantation (CLLT)patient in China.

A 41-year-old man (height 170 cm,weight 54 kg)with pulmonary fibrosis presented with severe respiratory insufficiency.He also had liver cirrhosis,and the classification of liver function (Child-Pugh) was grade III.The donor was a middle-aged woman whose blood type matched that of the recipient.The methods of acquisition and preservation of organs were based on Chinese lung donation standard and procurement guideline.After assessment by a multidisciplinary team,this case was discussed by the Organ Transplant Evaluation Committee of our hospital.

The procedure for bilateral lung transplantation was performed first by our lung team as described previously.After intubation with a double-lumen tube and induction of general anesthesia,the patient was placed supine.Our lung transplantation group selected a“clamshell” incision,followed by catheterization of the right atrium and ascending aorta to operate VA-ECMO.Meanwhile,the lungs and liver from the donor were prepared in another operating room.

The right diseased lung was removed.The donor lung was implanted,after which the pulmonary artery,pulmonary vein and bronchus were inosculated successively.Resection of the left diseased lung and implantation of the donor lung were performed using the same procedure as that employed for the right lung.Ventilation of the implanted lung revealed good respiratory and circulatory functions.The lung transplantation group covered the chest incision with sterile gauze and retained ECMO.The liver transplantation group then substituted the lung team.The liver transplantation group carried out an inverted-Y incision into the abdomen as described previously by this group.Due to portal venous thrombosis,the liver transplantation group dissected the thrombosis into the splenic venous opening.The diseased liver was removed,and the donor liver was implanted into the abdomen.Then,anastomosis of the upper lumen and lower lumen was completed without blocking blood flow.Ultrasonography revealed a slow blood flow in the implanted liver.A huge varicosity in the splenic vein and renal vein was found.After ligation of collateral vessels,the blood flow in the implanted liver improved.The liver transplantation group then closed the abdomen in layers in a standard manner.

In the final step,the lung team re-evaluated the implanted lung,and closed the chest after confirming that it was in good condition.Before the end of the procedure,the lung team weaned the patient from VAECMO.After that,the recipient was returned safely to the intensive care unit (ICU).The tracheal cannula was removed on postoperative day (POD)-1,and the patient could undertake off-bed activity on POD-3.Oxygenation status,liver function,and ultrasound of the allograft liver were close to normal before hospital discharge.Postoperative immunosuppression was based on tacrolimus,mycophenolate mofetil tablets (180 mg,b.d.),and prednisone.We titrated the tacrolimus dose according to a target range of 8-10 ng/mL.We initiated the prednisone at 40 mg and reduced the dose gradually to 15 mg in 6 months.Early postoperative outcome was uneventful and discharge occurred on POD-28.At the 1-and 3-month follow-ups,the two allografts exhibited good function,and the patient had improved countenance and functional status (Figure 1).

Figure 1. A: the diseased lung and diseased liver of the recipient;B:preoperative chest radiography;C: computed tomography of abdomen one month after CLLT;D: computed tomography of the chest one month after CLLT;E: patient after CLLT;F: the lung transplantation group and liver transplantation group of the Second Affiliated Hospital of Zhejiang University School of Medicine.CLLT: combined lung-liver transplantation.

The challenges of CLLT include anesthesia,cooperation between teams,and the change in pulmonary arterial pressure in donor-liver implantation.In general,in cases with cystic fibrosis-induced end-stage liver disease and lung disease,liver transplantation is often performed before lung transplantation.This strategy reduces the risk of pulmonary edema,hemorrhage,and liver ischemia.

In our case,the lung reserve of the recipient meant that he could not tolerate a liver-first strategy;thus,we adopted a lung-first procedure.Intraoperatively,we used central VA-ECMO,which guaranteed sufficient blood flow through vital organs and maintained oxygenation saturation.The other benefit of centralarterial catheterization is the lower anticoagulation intensity;intraoperatively,the activated clotting time is about 160 s,which reduces the risk of bleeding.In our case,intraoperative blood loss was only 500 mL.Immunosuppression was necessary because the patient had been implanted with two types of allografts,but a standard method of immunosuppression prophylaxis is not available for CLLT.Based on a previous study,our patient was administered tacrolimus,mycophenolate mofetil,and prednisone as immunosuppressors.At the 3-month follow-up,the blood concentrations of immune markers were stable.Perioperatively,the lung transplantation group,liver transplantation group,ICU physicians,and physical therapists worked in close collaboration.According to the rapid-recovery principle,we established a detailed recovery plan so that the patient could be off -bed active on POD-3 and discharged within 28 d.Goldfarb et alreported that the mean duration of hospitalization after CLLT was 40-50 d,which is much longer than that of our case.

None.

This study was approved by the Ethics Committee of the Second Affiliated Hospital of Zhejiang University School of Medicine,and informed consent and permission to use the illustrations were obtained from the patient.

The authors report no conflicts of interest.

WLW and JYC contributed to the conception and design of the study.SY,MH,and YJS organized the database.HM wrote the first draft of the manuscript.MH,SBP,YBC,and CYG wrote sections of the manuscript.All authors contributed to manuscript revision,read,and approved the final version.

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