- Open Access
Extracorporeal membrane oxygenation for overwhelming Blastomyces dermatitidis pneumonia
© Current Science Ltd 1999
- Received: 29 October 1998
- Accepted: 28 June 1999
- Published: 19 July 1999
- fungal infection
- respiratory failure
- extracorporeal life support
Blastomyces dermatitidis is a fungus that is found primarily in endemic areas of the midwestern and southcentral USA. Blastomycosis pneumonia may develop after the inhalation of spores. While blastomycosis may lead to acute or chronic pneumonitis, it will rarely result in the development of the acute respiratory distress syndrome (ARDS). In this situation, mortality rates are 50–80%. Patients who survive, however, commonly show good recovery of pulmonary function. Extracorporeal membrane oxygenation (ECMO), a modified form of cardiopulmonary bypass that allows systemic perfusion, oxygenation, and carbon dioxide removal, may be used to support patients with cardiorespiratory failure that is refractory to conventional therapies. The use of ECMO allows the reduction of high levels of mechanical ventilatory support that may cause iatrogenic injury to the diseased lung. Fungal diseases are often contraindications for ECMO use, since systemic fungal organisms may bind to the ECMO circuit and be difficult to eradicate. It may be reasonable to utilize ECMO, however, if the fungal infection is isolated to the respiratory system. We report the case of a patient with ARDS secondary to blastomycosis pneumonia who was treated with ECMO due to the failure of conventional cardiorespiratory supports. To our knowledge, this is the first report of the use of ECMO for this condition.
Blastomyces dermatitidis, a fungus that is endemic to the midwestern and southcentral USA, is a relatively common cause of pulmonary and cutaneous mycosis in these areas. Both respiratory and extrapulmonary infections are commonly initiated with the inhalation of fungal spores. Following the introduction of amphotericin B, the fatality rate has fallen from 78% to between 21–28%. If a total dose of 2 g amphotericin B is given, the cure rate may rise to 97% . However, if blastomycosis pneumonia is associated with the development of the acute respiratory distress syndrome (ARDS), the mortality rate rises to 50%–80% .
Extracorporeal membrane oxygenation (ECMO) has been used successfully to support newborn, pediatric and adult patients with cardiac and respiratory diseases that are refractory to conventional therapy. Survival rates of 80% have been achieved in the 13000 neonates who have been supported with ECMO, while survival in the 1500 pediatric patients listed in the International Extracorporeal Life Support Registry who have received ECMO for respiratory failure is 53%. Of the 547 adults listed in the registry, 47% have survived .
In general, a primary fungal infection, especially when the infection is hematogenous, is a contraindication to the use of ECMO. Historically, patients with hematogenous fungal infections do poorly on ECMO, primarily because the mycosis cannot be eradicated from the synthetic surfaces of the ECMO circuit. The restriction against ECMO support for cardiorespiratory failure secondary to fungal pneumonia without hematogenous spread is less certain. In theory, this condition should not preclude the use of ECMO, but no reports about the use of ECMO in this situation are available.
We report our experience with the use of ECMO to support a previously healthy adolescent with respiratory failure secondary to blastomycosis pneumonia to raise awareness of this disease as a cause of pneumonia and better understand the use and limitation of extracorporeal support in this condition.
A 15-year-old, 100kg black male developed fever, cough, and headache 12 days prior to admission to Georgetown University Hospital. Prior to this, the patient had been in good health with no evidence of immunodeficiency. There was no history of unusual travel or exposure to unusual environments. He was treated with amoxicillin for presumed sinusitis but his symptoms persisted and he was hospitalized for 2 days with erythromycin treatment for presumed atypical pneumonia. His chest radiograph revealed a left lower lobe infiltrate. After hospital discharge, the patient's private physician prescribed amantadine after his condition failure to improve. The patient was readmitted to the hospital 3 days later with respiratory distress and complete opacification of the right hemithorax and left lower hemithorax on chest radiograph (Fig. 1). Emergent intubation and institution of mechanical ventilatory support was performed.
Despite supportive care and the institution of broad-spectrum antibiotic therapy, the patient's respiratory failure progressed. Mean airway pressures of 30–40 cmH2O 48 h after his readmission were required to maintain arterial partial pressure of carbon dioxide (PaCO2) 70torr and oxygen (PaO2) 50torr. Calculation of the oxygenation index (OI), a measure that relates airway pressure and PaO2 to presumed mortality, revealed that his OI was 36. OI is the product of mean airway pressure (MAP) and fraction of inspired oxygen concentration (FiO2) divided by the PaO2 [OI=(MAP × FiO2 × 100)/PaO2]. Treatment with inverse ratio ventilation, permissive hypercapnia, prone positioning and pulmonary surfactant instillation failed to improve oxygenation.
A tracheal aspirate and subsequent bronchoscopy specimen revealed broad-based fungal elements consistent with Blastomyces dermatitidis. No other organ involvement with blastomycosis was evident. Amphotericin B was added to the treatment regimen. By day 5 of readmission (day 11 of illness), continued deterioration in respiratory function led to referral for ECMO rescue.
The patient was transported to Georgetown University Hospital without complication. Despite multiple manipulations of mechanical ventilatory support (peak inspiratory pressure to 54 cmH2O, peak end-expiratory pressure to 18cm H2O) and a trial of inhaled nitric oxide, the OI remained >40, PaCO2 >99torr, PaO2 50–75torr and pulmonary artery pressure more than one-half systemic. Hemodynamic instability developed, requiring treatment with dopamine and dobutamine infusions. Progressive renal insufficiency, as demonstrated by rising creatinine and the development of anuria, was also present.
In an attempt to provide cardiorespiratory support while treatment for blastomycosis pneumonia was completed, and to allow time for potential lung recovery, ECMO was instituted. Modified venoarterial ECMO was chosen because of the cardiopulmonary instability of the patient. Cannulation was achieved using a 29 F catheter introduced into the right femoral vein and a 19F catheter placed into the right femoral artery. The ECMO circuit has been previously described . Since adequate ventilation and oxygenation can be maintained by the ECMO circuit, the peak inspiratory pressure, rate, and inspired oxygen concentration can be reduced to lessen iatrogenic lung injury and to provide a better environment for potential lung healing.
Initial ECMO flows of 50–60 cm3/kg per min maintained mixed venous oxygen saturations of >70% and allowed a reduction in ventilator settings. After 24 h stabilization, the patient underwent bronchoscopy, which revealed denuded airway mucosa and purulent material filling the airways. Over the next few days, repeat bronchoscopy was performed to remove debris. On ECMO day 3, the patient became hyperdynamic and developed leukocytosis and decreasing mixed venous oxygen saturations. Sepsis was presumed, although cultures remained sterile. Membrane oxygenators on the ECMO circuit were changed without complication. The patient continued to have episodes of decreased mixed venous oxygen saturation despite increased ECMO circuit flow. Restriction of additional increases in circuit flow over the next few days led to the placement of a right internal jugular venous cannula and right carotid arterial cannula on ECMO day 10. All other organ systems remained intact and all cultures (blood, bronchial washing and tissue, urine) remained sterile. The patient was responsive to commands and questions while pharmacologic sedation was maintained. By ECMO day 14, minimal clearing of right and left lung fields was noted with concurrent increases in exhaled tidal volumes. Bronchoscopy was performed to remove airway debris with good results over the next few days and efforts to slowly re-expand the lungs were initiated. On ECMO day 18, bilateral tension pneumothoraces developed and the patient suffered cardiac arrest. Despite prompt resuscitation and continued support with ECMO, the patient deteriorated over the next 24h and ECMO support was electively withdrawn. Native pulmonary function was insufficient and the patient expired.
Despite systemic antifungal therapy and extracorporeal life support, postmortem examination revealed almost complete replacement of normal lung parenchyma with fungal elements and chronic inflammatory reaction. Extensive necrosis, acute and chronic inflammatory cells, abscesses, fibrin deposition and hemorrhage were seen (Fig. 2). Broad-based budding fungal organisms consistent with Blastomyces dermatitidis are seen in Figure 2 throughout the lung parenchyma. They are not seen in association with vascular structures. The left lung had regions of interstitial fibrosis. The central nervous system showed multiple areas of acute infarction and global ischemic encephalopathy. No evidence of invasion by Blastomyces dermatitidis was noted in the bloodstream or in any other organs outside of the lungs. The final pathologic cause of death was listed as fungal pneumonia with extensive destruction of lung tissue.
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