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http:/ Emergency Treatment of Endobronchial Stents Placement in Serious Main Bronchial Stenosis Following High-risk Orthotopic Heart Allotransplantation1Yongxiang Zhao1,Lingling Zhao1,Bo Yi1,Zhonggui Shan2,Qinming Fan2,Mingyao Ke2,Chongxian Liao2,Qifa Ye1,Zufa Huang1,Yue Zhu3 1The National Ministry of Health Transplantation Engineering and Technical Reseach Center,The Third Xiangya Hospital,Central South University,Changsha,Hunan 410013,PR China 2The Affiliated Zhongshan Hospital,Xiamen University,Xiamen,Fujian 361003,PR China 3Organ Transplantation Institute,University of Pittsburgh,200 Lothrop Street C-700,Pittsburgh,PA 15213,USA*Correspondence to:Yongxiang Zhao,MD,The Third Xiangya Hospital,Central South University,Changsha,Hunan 410013 P.R.China,Tel:+86 731 861 8316,Fax:+86-863 8327,Email:yongxiang_ Abstract Objective:To investigate the curative effect of emergency stent placement for left main bronchial malacia,stenosis and collapse after orthotopic heart allotransplantation.Methods:To evaluate the risk and efficacy of treatment of bronchus stent placement after orthotopic heart allotransplantation in one dilated cardiomyopathy patient complicated with left main bronchial malacia,stenosis and collapse resulting in left pulmonary ventilation dysfunction,and other multi-diseases,such as severe pulmonary artery hypertension and mixed(mainly central)sleep apnea syndrome.Results:After treatment of stent placement,patient was relieved from left pulmonary ventilation dysfunction with obviously improved hypercapnia,hypoxemia,pulmonary hypertension and the function of transplanting heart recovered.Conclusions:Emergency treatment with stent placement for bronchial malacia,stenosis and collapse occurring after orthotopic heart allotransplantation could improve ventilation dysfunction caused by bronchial malacia and stenosis,and increase the survival rate of heart transplantation.Keywords:orthotopic cardiac transplantation,bronchial malacia,stenosis,stent placement Heart transplantation is now an established technique for the effective treatment of end-stage heart diseases,including dilated cardiomyopathy,rheumatic heart diseases and ischemic heart diseases(1,2,3,4).Tracheobronchial obstruction from either benign or malignant disease is associated with high morbidity and possible early death by asphyxia1(5).Even in the absence of parenchymal lung disease,ventilation failure frequently occurs if the obstruction is not relieved(6).A variety of benign etiologies can underly airway obstruction,including tracheomalacia,tracheal stricture,inflammatory diseases such as Wegeners granulomatosis and relapsing polychondritis,and anastomotic stricture following lung 1 This work was supported by central south university key subject project of transplantation foundation of China.No 2004-24。-1-http:/ transplantation(7).Central airway obstruction can result in dyspnea,cough,and impaired clearance of respiratory secretions.Surgical tracheal sleeve resection and reconstruction remains the“gold standard”treatment for most benign airway strictures.However,the management of patients with tracheobronchial strictures of benign etiology can be quite challenging(8).There are a large number of patients with lesions not amenable to surgery,or who are considered medically inoperable(9).Endoscopic implantation of airway prostheses(stents)in these patients has gained increasing popularity over the last decade.Up till now,it is demonstrated that stenting has shown efficacy in such benign airway conditions such as relapsing polychondritis(10),tuberculosis(11)and post-lung transplant stenoses(12).In these patients,airway stenting may represent the only possible treatment.Currently,various inoperable benign airway disorders are considered indications for airway stenting(8,9).The goal of stent placement is to relieve airflow obstruction(6).The indication for stent placement is significant extraluminal compression causing severe symptoms such as dyspnea and stridor in patients with tracheobronchial malacia.Advances in techniques to insert airway prostheses have provided clinicians with a variety of pneumatic dilators,and expandable metallic and silicone stents(13).Ventilation dysfunction caused by bronchostenosis following high-risk heart transplantation is an acute clinical disease,which seriously impairs the function of transplant heart,and increases the death possibility of patients.The case of high-risk multi-complication bronchial stent placement following heart transplantation has not been reported yet.We applied a nickel-titanium shape memory alloy stent for emergency placement to rescue a patient with severe bronchostenosis following high-risk heart transplantation,and acquired a satisfied result.1.Clinical data and methods.1.1 General information An eighteen years old female patient with dilated cardiomyopathy,moderate-severe pulmonary artery hypertension,left main bronchial malacia/stenosis/collapse,mixed(mainly central-)sleep apnea syndrome,left inferior pulmonary sequestration,right emphysema,and rheumatoid arthritis was carried out the orthotopic heart allotransplantation in our hospital in April,2005.Before operation,the enlargement heart of patient long-term compressed the left main bronchus,and caused bronchus dysplasia,left inferior pulmonary separation(see Figure A).Bronchus inflammation,-2-http:/ congestion,edema accompanied with tracheomalacia,collapse and stenosis(see,Figure B)occurring after heart transplantation led to obstructive type of ventilation,carbon dioxide retention,hypercapnia,hypoxemia,and secondary severe pulmonary hypertension,which seriously impaired the function recovery of patient after heart transplantation.In the post-operation,patient complicated with supraventricular tachycardia(heart rate130-140bpm),ventricular extrasystole(5-7bpm),and hypofunction of transplant cardiac systolic function(peak Epeak A,EF 70%,FS 41%).The vital sign of patient was stable,the blood pressure fluctuated at about 120/70mmHg,and the heart rate fluctuated at 100-110 beats/min.Post-operation chest-radiography and CT indicated changes of bronchial stent placement after heart transplantation,relief of left main bronchial stenosis.When ventilation function of patient improved,the parameters of breathing machine were reduced gradually,and replaced by low-flow oxygen.There was no obstructive ventilatory disorder reoccurred.However,patient was found that carbon dioxide partial pressure(average PCO2,88mmHg)and oxygen partial pressure(average PO2,172mmHg)both are increased during sleep.Patient was orderly treated with BIPAP non-invasive Ventilation to assist spontaneous ventilation(respiration parameter:IP：9mmHg，EP：4mmHg，FIO2：21%)and American Stars 425 portable bi-level sleep apnea instrument.At the same time,Duxil was administered to reinforce the sensitivity of peripheral chemoreceptor to carbon dioxide partial pressure,and excite respiratory center.The sleep apnea syndrome of patient was correct,and the increased carbon dioxide partial pressure was also corrected(PO2 is controlled between 35 and 50mmHg).2.2 Treatment of complication after stent placement Patient was suffered the left main bronchial stenosis,left lower atelectasis,and right lung compensatory emphysema in the pre-operation,in addition,flushing dose of immunodeppressant were used for heart transplantation,thus bronchus mesh stent as a extraneous matter increase the risk of pulmonary infection.Alpha hemolytic streptococcus，staphylococcus aureus(MRSA)and enterobacter cloacae were found in the patients sputum,and patching-shape blurred shadow was found in double lung field through chest-radiography;the patient appeared to fever(body temperature up to 40.8C),accompanied with cough and expectoration(white color sputum crudum),but no hemoptysis and respiratory embarrassment.Hemoculture found staphylococcus aureus(MRSA)and enterobacter cloacae.The hemogram heightened,of which WBC20109,N 94%.According to susceptibility test and antibiotics serum bactericidal test to choose antibiotics,alternatively treated with teicoplanin plus -4-http:/ imipenem plus fosfomycin,polymyxin E plus vancomycin plus meropenem,and fosfomycin plus polymyxin E.Dual infection was precluded through administrated itraconazole for mycotic infection,and acyclovir for viral infection.Meanwhile,the dose of immunosuppressant was adjusted:FK506 maintained at 0.15mg/kg/d,prednisone reduced from 30mg/d to 5mg/d,and Cellcept(MMF)discontinued.To enhance turn-over,back-patting and postural drainage,to encourage patient to cough and expectorate,and to reinforce the disinfection and isolation of ward.Through effective therapy,the infections caused by bacteria,virus,and mycetes were under the control,and body temperature recovered,symptom of cough and expectoration disappeared,and hemogram normalized.Re-check of chest-radiography showed that focus of infection had been absorbed.After continuous culture for 7 days,there was no microorganism found in sputum culture.3.Discussion Orthotopic heart allotransplantation has always been a very high-risk surgery for those patients who suffered dilated cardiomyopathy,complicating with severe pulmonary artery hypertension,left pulmonary ventilation dysfunction caused by left main bronchial malacia,stenosis and collapse,and mixed(mainly central)sleep apnea syndrome.Life-threatening risk is more increased by impairment of pulmonary ventilation function caused by serious left bronchostenosis during peri-operation.At present,stent placement is the most useful emergency measures for managing dyspnea or respiratory failure caused by tracheobronchial stenosis,as well as recurrent obstructive pneumonia and pulmonary atelectasis when other common measures are ineffective(14,15,16,17).In this case,bronchus inflammation,congestion and edema occurring after heart transplantation aggravated the severity of preoperative tracheobronchial stenosis of patient,and led to carbon dioxide retention,hypercapnia,hypoxemia,aggravating pulmonary hypertension,and finally to cardiac function and respiratory failure,which seriously jeopardized patients life.Emergency treatment of bronchus stent placement can relieve the lung hypoventilation caused by bronchiostenosis,improve the state of carbon dioxide retention,and lower pulmonary artery hypertension.All these results produce a significant efficacy on salvaging of transplant heart,improving of prognosis,and diminishing of the risk of postoperative death.Despite stent placement relieved the pulmonary ventilation dysfunction,this patient was found that carbon dioxide partial pressure(average PCO2,88mmHg)and oxygen partial pressure(average PO2,172mmHg)are both increased during nighttime sleep.As for this current sleep apnea syndrome,simply improvement of ventilation function -5-http:/ would not achieve remarkable clinical effect.Considering a preoperative complication of mixed sleep apnea syndrome,mainly as central sleep apnea syndrome,suffered,and long-term dys-ventilating,carbon dioxide retention,respiratory acidosis,as well as insensitivity of respiration central chemoreceptor for CO2 simultaneously existed,such phenomenon were believed to be induced by the lowering of respiratory central excitability of patient(18,19).By orderly treatment with BIPAP non-invasive ventilation to assist spontaneous ventilation and American Stars 425 portable bi-level sleep apnea instrument,and in combination with“Duxil”to enhance sensitivity of peripheral chemoreceptor to CO2 and to excite respiratory center,the symptoms of patient were obviously relieved.Meanwhile,it is proven that BIPAP portable bi-level sleep apnea instrument is an effective means for the treatment of central sleep apnea syndrome.Moreover,because the placement of bronchus mesh stent increases the risk of pulmonary infection,the postoperative monitoring of sputum culture and hemoculture should be performed to discover and diagnose infection,and to adjust antibiotics in terms of the result of susceptibility test.In addition,regular turnover,body-patting,and postural drainage play a positive role on precaution and control of pulmonary infection.So far,the patient has survived more than one year,who is in good clinical and functional condition,i.e.,cardiac function class I,smooth respiration,and able to manage daily living herself.Acknowledgment We thank Bracker G.Hattler,MD,Artificial Lung Program,University of Pittsburgh,for providing consultation of posttransplantation complications.Reference 1.Barnard CN.What we have learned about heart transplants.J Thorac Cardiovasc Surg,1968,56:457-468 2.Keon WJ.Heart transplantation in perspective.J Card Surg,1999,14:147-151 3.Cardiac transplantation has become an accepted treatment for end-stage or inoperable heart disease.Ann Thorac Surg 2004;78:644-649 4.Hosenpud JD,Bennet LE,Keck BM,Boucek MM,Novick RJ.The registry of the International Society of Heart and Lung Transplantation:eighteenth official report-2001.J Heart Lung Transplant 2001;20:805815.5.Shin JH,Song HY,Shim TS.Management of tracheobronchial strictures Cardiovasc Intervent Radiol 2004;27:314324 6.Rafanan AL,Mehta AC.Stenting of the tracheobronchial tree.Radiol Clin North Am,2000;38:395408 7.Colt HG,Dumon JF.Airway stents:present and future.Clin Chest Med 1995;16:465478 8.Noppen M,Stratakos G,Haese JD,Meysman M,Vinken W.Removal of covered self-expandable metallic airway stents in benign disorders:indications,technique,and outcomes.Chest,2005;127:482-487 9.Wood DE,Liu YH,Vallie res E,et al.Airway stenting for malignant and benign tracheobronchial stenosis.Ann Thorac Surg 2003;76:167174 10.Faul J,Kee S,Norman W.Endobronchial stenting for severe airway obstruction in relapsing polychondritis.Chest 1999;116:825827 -6-http:/ 11.Lee KW,Im JG,Han JK,et al.Tuberculous stenosis of the left main bronchus:results of treatment with balloons and metallic stents.J Vasc Interv Radiol 1999;10:352835.12.Sonett JR,Keenan RJ,Ferson PF,et al.Endobronchial management of benign,malignant,and lung transplantation airway stenoses.Ann Thorac Surg 1995;59:14171422.13.Vonk-Noordegraaf A,Postmus PE,Sutedja TG.Tracheobronchial stenting in the terminal care of cancer patients with central airways obstruction.Chest 2001;120:1811-1814 14.Eisner MD,Gordon RL,Webb WR,Gold WM,et al.Benign Airway Obstruction Pulmonary Function Improves After Expandable Metal Stent Placement for Benign Airway Obstruction Chest 1999;115:1006-1011 15.Belleguic C,Lena H,Briens K,et al.Tracheobronchial stenting in patients with esophageal cancer involving the central airways.Endoscopy,2000,12(1):24-26 16.Noppen M,Stratakos G,DHaese J,et al.Removal of covered self-expandable metallic airway stents in benign disorders:indications,technique,and outcomes.Chest.2005,127(2):482-487.17.Saad CP,Murthy S,Krizmanich G,Mehta AC.Self-expandable metallic airway stents and flexible bronchoscopy:long-term outcomes analysis.Chest.2003,124(5):1993-1999.18.Bradley TD,Floras JS.Sleep apne
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