Sildenafil therapy in secondary pulmonary hypertension: Is there benefit in prolonged use?

BACKGROUND: Sildenafil is of benefit to selected patients with pulmonary hypertension due to parenchymal lung or cardiac disease. We present data from patients with secondary pulmonary hypertension, comparing their right heart catheter results and six minute walking distance to time on treatment. METHODS: 25 patients with symptomatic secondary pulmonary hypertension received sildenafil 50 mg tds in a 5-year period. Underlying causes were chronic inoperable thromboembolic disease (11), COPD (6), interstitial lung disease (5) and valvular heart disease (3). Their cardio-pulmonary haemodynamics were measured with right heart catheterization prior to treatment, post-treatment at 2, 6 and 12 months and subsequently depending upon clinical need. Six-minute walk distance was also measured. RESULTS: Patient age range was 40 to 83 (median 70.5) years. Time of treatment to latest right heart catheter was 2 to 60 (median 17) months and 8 to 61 (median 34) months to clinic follow-up or death. There was a significant reduction in six-minute walk distance from baseline to long term (>12 months) follow-up (p=0.002). Pulmonary vascular resistance was significantly reduced from baseline to 12 months (p=0.049). The mean pulmonary arterial (PA) pressure was significantly reduced at long-term follow-up (p=0.009). 20 patients had an improved PA pressure with treatment. In those with a worsening PA pressure, two had an improvement in cardiac output and six minute walk distance, two had stable cardiac output at 20 and 21 months, and one had measurements taken during a significant illness. Three patients, who had a reduction in PA pressure, subsequently died of progression of underlying illness at 8 months, from myocardial infarction at 34 months, and from aspergillus pneumonia at 59 months. CONCLUSION: Long-term use of sildenafil in patients with secondary forms of pulmonary hypertension is associated with a sustained improvement in cardio-pulmonary haemodynamics. Lack of improvement may be attributed to other factors apart from treatment failure, such as underlying disease progression or unrelated concurrent illness at time of assessment.

Pulmonary hypertension and pregnancy.

Pulmonary hypertension is defined by a mean pulmonary artery pressure of greater than 25 mmHg at rest or 30 mmHg with exercise. It can occur in association with a variety of medical conditions. The most serious elevation in pulmonary artery pressures are seen in a group of conditions that share the histological entity of plexogenic pulmonary arteriopathy. Pulmonary hypertension may be missed or diagnosed late in the course of the illness. It is associated with a poor prognosis. Pulmonary hypertension carries a significant risk to mother and child during pregnancy and pregnant women with pulmonary hypertension require careful monitoring within the framework of a multidisciplinary team. Specific targeted therapy for pulmonary hypertension may be required during pregnancy. Many agents are contraindicated because of risks of teratogenicity or secretion into breast milk. The optimum mode of delivery is not clear but early input from the high-risk obstetric anaesthesia team is essential.

Endobronchial stenting in the management of large airway pathology.

Endobronchial interventions including the deployment of endobronchial stents have a clear role in the management of central airway problems. The use of endobronchial stents has rapidly increased since the first airway stent was developed in the 1960s and with the subsequent manufacture of improved silicone and metallic stents. They provide effective relief for symptoms of intrinsic and extrinsic airway obstruction secondary to a wide range of pathologies including lung cancer, lymphoma, thyroid carcinoma and benign disease such as tracheal strictures and tracheobronchomalacia. Endobronchial stents can also seal defects within the airway including malignant broncho-oesophageal fistulae and posterior wall tracheal tears. They can be placed safely under conscious sedation at flexible bronchoscopy or under general anaesthetic at rigid bronchoscopy. Rigid bronchoscopy under general anaesthesia provided by a multidisciplinary team is safe with few contraindications. Complications of endobronchial stents include infection, granulation tissue formation and metallic stent fracture sometimes requiring removal, although serious life-threatening complications are very rare. Increasing numbers of patients are being referred to specialist centres for airway intervention. This article reviews the history of endobronchial stents, the different stents available, and the indications, outcomes and complications involved in deploying endobronchial stents.

A novel approach to the management of acute tracheal tear.

OBJECTIVE: We describe the emergency use of a covered, expandable, removable tracheal stent in a patient who developed a large posterior tracheal tear complicating endobronchial therapy for large airway obstruction. METHOD: Case report and review of the literature concerning management of acute tracheal tear. RESULTS AND CONCLUSION: Our patient demonstrates that endotracheal stenting is an option for managing acute large airway tear. Moreover, the use of a removable stent allows not only for rapid closure of the defect but also removal once the defect has healed, thus avoiding long-term complications of stent deployment.

Radiotherapy: a novel treatment for pneumothorax.

Pneumothorax is a relatively common condition that is usually managed either conservatively, by chest tube drainage or, if a refractory air leak persists, then with cardiothoracic intervention. However, there is a small group of patients with a persistent air leak in whom surgical intervention is felt to be inappropriate. This study looks at a novel management strategy in a patient presenting with this scenario. A male with underlying bullous lung disease presented with a right pneumothorax. Complete re-expansion was not achieved, despite chest tube drainage and suction. Cardiothoracic intervention was felt to be inappropriate and the air leak persisted despite prolonged conservative management. Ventilation scintigraphy was therefore used to localise the air leak prior to targeted radiotherapy in an attempt to seal the leak via radiation-induced fibrosis. Three weeks after the first fraction of radiotherapy, the air leak ceased. In complex cases of pneumothorax with persistent air leak where cardiothoracic intervention is deemed inappropriate, identification of the air leak site and localised radiotherapy could be considered.

Tracheal stenosis diagnosed on pulmonary ventilation/perfusion scan.

A 68-year-old woman, who had undergone coronary artery bypass surgery 5 months previously, was presented with cough, breathlessness and an elevated D-dimer. She was initially thought to have suffered a pulmonary embolus. A ventilation/perfusion scan demonstrated tracheal stenosis, which required dilation and endobronchial stent deployment. Tracheal stenosis is a well-recognised complication of endotracheal intubation; however, the onset of symptoms is often insidious and the diagnosis delayed.

Airway management of patients with tracheobronchial stents.

The use of tracheobronchial stents for compromised large airways is increasing. We provide a case series highlighting some of the complications of airway management in patients with tracheobronchial stents in situ and propose an approach for dealing with this potentially complicated situation.

Rigid bronchoscopy-guided percutaneous tracheostomy.

We describe a case series of seven patients that demonstrates the usefulness of rigid bronchoscopy in percutaneous tracheostomy. The technique was used in selected patients who had a previous tracheostomy, a difficult airway, high risk of bleeding, or a tracheal stent in place.

Novel approach to management of a posterior tracheal tear complicating percutaneous tracheostomy.

We treated a patient who developed a posterior tracheal wall perforation and severe respiratory compromise following percutaneous tracheostomy, using a covered expandable metallic stent. The stent was deployed under direct vision using rigid and fibreoptic bronchoscopy. The defect was sealed and the right lung, which had been collapsed, was re-expanded. The patient was subsequently weaned from mechanical ventilation. Late complications included halitosis, which was treated with nebulized colistin sulphate, and the development of intratracheal granulation tissue, which was cleared using low power (10 W) Nd:YAG laser.

Noninvasive ventilation in cystic fibrosis patients with acute or chronic respiratory failure.

The experience of using noninvasive ventilation (NIV) in 113 adult cystic fibrosis (CF) patients with chronic respiratory failure, during episodes of acute deterioration in respiratory function is reported. The patients aged 15-44 yrs were divided into three groups. Group A consisted of 65 patients (median forced expiratory volume in one second (FEV1)/forced vital capacity (FVC) 0.7/1.4 L) who were on a lung transplant waiting list. Group B consisted of 25 patients (median FEV1/FVC 0.7/1.4 L) who were being evaluated for lung transplantation. Group C consisted of 23 patients (median FEV1/FVC 0.6/1.2 L) who were not being considered for lung transplantation. The mean duration of NIV support for groups A, B and C was 61 (range: 1-600) days, 53 (1-279) days and 45 (0.5-379) days respectively. Twenty-three patients in group A subsequently received lung transplantation and 12 of these patients had a median survival of 39 months postsurgery. Thirty-nine patients died and three awaited transplantation. Five patients in group B received a transplant four of whom survived; thirteen patients died and seven awaited transplantation. Twenty patients in group C died. Noninvasive ventilation improved hypoxia but failed to correct hypercapnia in these cystic fibrosis patients. Noninvasive ventilation is useful in the treatment of acute episodes of respiratory failure in cystic fibrosis patients with end-stage lung disease who have been accepted, or are being evaluated, for lung transplantation. For these patients, there is a possibility of prolonging life if they are successfully treated for their acute episode of respiratory failure until transplantation. In this group, treatment is not merely prolonging the process of dying.

Tracheal granulation tissue after percutaneous tracheostomy treated with Nd:Yag laser: three cases.

Three adult patients who received percutaneous serial dilatational tracheostomy post-cardiac surgery developed histologically confirmed tracheal granulation tissue superior to the point of entry of the tracheostomy tube into the trachea. This tissue significantly occluded the trachea in all patients and, in two, led to serious haemorrhage. Each patient had serial dilatational percutaneous tracheostomy using the Cook/Ciaglia technique. On each patient fibre-optic bronchoscopy confirmed satisfactory position of the guidewire and tracheostomy tube. Nd:Yag laser therapy was applied to areas of tracheal granulation tissue and was also employed to secure haemostasis. In each patient endobronchial Nd:YAG laser therapy successfully cleared the granulation tissue and secured haemostasis. Follow-up bronchoscopy showed no recurrence. Fibre-optic bronchoscopy at the time of tracheal decannulation may identify granulation tissue requiring appropriate referral and intervention.

Nocardia asteroides abscess after heart transplantation.

We describe a patient who developed a primary, thigh adductor-muscle abscess caused by Nocardia asteroides 3 years after orthotopic cardiac transplantation. Nocardia was diagnosed by microbiologic culture and responded fully to a prolonged course of cotrimoxazole. The patient remains free of local or systemic disease at 2 years follow-up.

Low clinical utility of routine angiographic surveillance in the detection and management of cardiac allograft vasculopathy in transplant recipients.

BACKGROUND: Cardiac allograft vasculopathy (CAV), a form of accelerated atherosclerosis, is the major cause of late death in heart transplant recipients. Routine annual coronary angiography has been used as the standard surveillance technique for CAV in most transplant centers. HYPOTHESIS: The aim of this study was to investigate the clinical utility of routine angiographic surveillance in the detection and management of CAV in transplant recipients. METHODS: We reviewed the case notes and angiograms of 230 patients who underwent cardiac transplantation in our unit between January 1986 and January 1996 and survived beyond the first year post transplantation. RESULTS: Significant complications secondary to angiography arose in 19 patients (8.2%). Cardiac allograft vasculopathy was present on none of angiograms performed 3 weeks post transplantation, but was identified in 9 patients (4%) at the first annual angiogram and an additional 25 patients by the fifth annual angiogram. A target lesion suitable for angioplasty was only identified in two patients, and only limited procedural success was achieved in both cases. Twenty-five patients (11%) died during the study period, and the most common cause of late death was graft failure which occurred in 10 patients. All patients who died from graft failure had significant CAV at autopsy, but the most recent coronary angiogram had been normal in eight of these patients. CONCLUSIONS: These data clearly illustrate the limited clinical utility of routine angiographic surveillance for CAV in heart transplant recipients and prompted us to abandon this method of surveillance in our unit.

Successful treatment of endobronchial amyloidosis using Nd:YAG laser therapy as an alternative to lobectomy.

Endobronchial amyloidosis may cause local obstruction associated with a variety of clinical presentations including recurrent respiratory infection. Although some patients may require surgical intervention, encouraging experience with endobronchial Neodymium (Nd):YAG laser therapy in the management of this condition is reported. Two patients with localized endobronchial amyloidosis were treated with endobronchial Nd:YAG laser therapy. One patient received two treatments for right upper lobe amyloid and another patient received three treatments for right lower lobe amyloid. Excellent clearance of amyloid was achieved in each patient. The first patient remains well, 16 months post-treatment with full patency of the apical and posterior segments. Ten months post-treatment, the second patient has full patency of the right lower lobe. No complications occurred in association with Nd:YAG laser therapy. Endobronchial Neodymium:YAG laser treatment should be considered for selected patients with localized endobronchial obstruction due to amyloidosis.

Tacrolimus as a rescue immunosuppressant after heart transplantation.

OBJECTIVE: The purpose of this retrospective study is to review our experience with tacrolimus as a rescue immunosuppressant for heart transplant recipients with refractory rejection or cyclosporine intolerance. METHODS: From June 1995 to November 1998, 15 cardiac transplant recipients were converted from our standard cyclosporine-based immunosuppressive regimen to a tacrolimus-based treatment. Each patient had been treated with cyclosporine, azathioprine and steroids. Six were switched to tacrolimus for persistent rejection, four for recurrent acute rejection and five for severe debilitating side-effects attributed to cyclosporine. All ten patients converted to tacrolimus because of rejection had been treated with high-dose methylprednisolone intravenously and four had also received anti-lymphocyte globulin (ALG; one patient) or anti-thymocyte globulin (ATG; three patients) preparations. RESULTS: The time between transplantation and conversion to tacrolimus ranged from 44 to 1866 (median, 380) days. The range of follow-up after conversion was 84-1379 (median, 806) days. Eleven patients are alive with a follow-up period of 764+/-435 (median, 820) days. Four patients died between 90 and 930 (median, 464) days after conversion. The average number of episodes of acute rejection/recipient decreased from 2.1+/-1.6 on the cyclosporine regimen to 0.2+/-0.4 on the tacrolimus regimen (P<0.001). When the incidence of acute rejection was normalized for follow-up times (episodes/100 patient-days), the results were 1.1+/-1.4 and 0.07+/-0.2, respectively (P<0.01). The persistent/recurrent rejection resolved in all ten patients who were converted to tacrolimus. None of the five cyclosporine intolerant patients converted to tacrolimus experienced rejection after the changeover. CONCLUSIONS: In our experience, conversion from a cyclosporine-based to a tacrolimus-based maintenance immunosuppression has been shown to be an effective and safe approach to the management of patients with persistent or recurrent cardiac allograft rejection or those with cyclosporine intolerance.

Tracheal stenosis due to brachiocephalic artery aneurysm successfully treated with stenting.

Tracheal stenosis secondary to an aneurysm of the great vessels is a rare presentation, previously thought to be unremediable to tracheal stenting. The introduction of covered, expandable, metallic stents has led to the successful treatment of a patient with tracheal stenosis secondary to an aneurysmal brachiocephalic artery without resorting to major cardiothoracic surgery.

Covered expandable tracheal stents in the management of benign tracheal granulation tissue formation.

BACKGROUND: Tracheal obstruction secondary to benign proliferation of granulation tissue is a difficult problem to address if tracheal resection is contraindicated. Some patients may benefit from Nd:YAG (neodymium: yttritium-aluminum garnet) laser fulguration or tracheal stenting. If uncovered expandable metallic stents are employed granulation tissue can regrow and proliferate through the mesh, thereby obstructing the lumen once again. Covered metallic stents confer the advantage of preventing granulation tissue proliferation and therefore maintain patency of the tracheal lumen. METHODS: Two patients who developed tracheal obstruction secondary to proliferating granulation tissue formation after tracheostomy and who were medically unfit for prolonged general anesthesia were successfully treated using covered expandable metallic tracheal stents. RESULTS: Each patient demonstrated a significant improvement in respiratory status, and in both patients, at 6 and 9 months' follow-up, stent position has not changed, tracheal lumen remains patent, and there has been no proliferation of granulation tissue through the stent. CONCLUSIONS: Covered expandable metallic stents should be considered in the management of patients with proliferating tracheal granulation tissue when tracheal resection is contraindicated.