Extracorporeal membrane oxygenation (ECMO) for severe acute respiratory distress syndrome (ARDS) in fulminant blastomycosis in Germany

Abstract

In fulminant blastomycosis with multiorgan failure, the earliest diagnosis possible is crucial for successful treatment. If severe acute respiratory distress syndrome (ARDS) develops, miniaturised veno-venous extracorporeal membrane oxygenation (ECMO) might provide a unique and efficacious possibility to prolong the time frame for diagnosis and the beginning of treatment. This is the first report on a case of fatal blastomycosis in Germany. It reminds us to add exotic infections to the differential diagnosis in patients with refractory pneumonia in the era of worldwide tourism.

BACKGROUND

To the best of our knowledge, this is the first report of a fulminant blastomycosis with acute respiratory distress syndrome (ARDS) and multiorgan failure in Germany. The case demonstrates that in patients with severe ARDS, extracorporeal membrane oxygenation (ECMO) can provide temporary pulmonary assistance to prolong the time frame for diagnosis and specific treatment. This case reminds us again to add exotic fungal infection to the list of differential diagnoses in patients with refractory pneumonia in the era of worldwide tourism.

CASE PRESENTATION

A previously healthy 33-year-old man became symptomatic with visual disturbance, tunnel vision, retrobulbar ocular pain, a mild form of apraxia of the right hand and holocephalic headache. A cMRT scan revealed a 0.8 cm mass with perifocal oedema in the left mesencephalon close to the nucleus ruber. An abdominal ultrasound and chest x ray showed no pathological findings. The cerebrospinal fluid revealed a granulocytic pleocytosis with 44 white cells/μl, 53 mg/dl protein, and 10 000 red cells/μl. There were no oligoclonal bands and glucose concentration was normal. A stereotactic biopsy yielded an infiltration with lymphocytes (B and T type). Immunohistochemically, the lymphocytes in the vessel walls and perivascular region were classified as CD8 cytotoxic and CD 20 positive B cells without clonal proliferation. The diagnosis of an inflammatory central nervous system (CNS) syndrome was made and corticosteroid therapy with 4 mg/day dexamethasone was initiated to reduce perifocal oedema. Within 2 weeks, the neurological symptoms improved, but an attempt to reduce the corticoid dose failed and resulted in a relapse of symptoms with progressive apraxia of the right hand. As a consequence corticoid therapy was resumed. One month later, in January 2007, a non-productive cough, chills and fever up to 39°C developed. A chest radiograph and computed tomography (CT) scan yielded pulmonary infiltrates in the right upper lobe and the patient was started on amoxicillin and clavulanic acid (3×500+125 mg/day for 4 days). Despite this treatment his condition deteriorated and he was admitted to a local hospital. The patient had to be intubated and mechanically ventilated because of rapidly developing respiratory failure and sepsis. One day later, he was transferred to our institution with severe ARDS.

Upon arrival he was febrile with a temperature of 39.5 °C. There was no skin rash. He had a regular tachycardia of 140/min and was normotonic (130/80 mm Hg) with vasopressors (norepinephrine 1.0 mg/h). Invasive blood pressure monitoring was initiated. There were no signs of congestive heart failure and no murmur was present. Abdominal ultrasound was normal without splenomegaly. Widespread inspiratory crackles were audible throughout both lung fields and a chest radiograph demonstrated widespread bilateral interstitial infiltrates (fig 1). The laboratory findings showed a C reactive protein (CRP) value of 396 mg/l (normal <5 mg/l), a white cell count of 15.9/nl (normal <10.8/nl), lactate concentration of 1.5 mmol/l, and lactate dehydrogenase (LDH) of 543 U/l (normal <247 U/l). Na⁺ (148 mmol/l), K⁺ (5.27 mmol/l), urea (7.3 mmol/l), creatinine (95.4 µmol/l), glutamic oxaloacetic transaminase (GOT) (39 U/l), glutamic pyruvic transaminase (GPT) (26 U/l), platelet counts (183/nl), and international normalised ratio (INR) (1.08) were normal. HIV or infective hepatitis were excluded. Infective endocarditis was excluded by transoesophageal echocardiography. Upon fundoscopy no Roth spots were identified.

Figure 1.

Chest x ray at admission, showing widespread bilateral infiltrates.

Despite intensive mechanical ventilation (FiO₂ of 1.0, peak inspiratory pressure (PIP)/peak end expiratory pressure (PEEP) 35/16 cm H₂O, AF 20/min, tidal volume 560 ml, I:E 1:1) gas exchange was marginal (Pao₂ 65 mm Hg, Paco₂ 80 mm Hg) and the patient was in severe respiratory acidosis (pH 7.20).

Subsequently, the patient was switched to high frequency oscillatory ventilation (HFOV) (Paw 31 cm H₂O, oscillatory rate 6 Hz, amplitude 98 cm H₂O, Fio₂ 1.0) with continuously inhaled nitric oxide (NO) (15 ppm) to reduce intrapulmonary shunting. Bronchoscopy showed massive purulent secretion in both lungs, which made daily bronchoscopic suction necessary. An expansive microbiological workup detected Candida albicans only in tracheal aspirate; no other pathological agent could be isolated from bronchoalveolar lavage (BAL) samples or multiple sets of blood cultures. Treatment was continued with broad spectrum antibiotics (piperacillin, sulbactam, ciprofloxacin, fluconazole intravenously, oseltamivir) and hydrocortisone (10 mg/h) for septic shock. Under these measures, a temporary respiratory and haemodynamic stabilisation with reduced need of vasopressors could be achieved.

However, despite further switches of antibiotic and antimycotic treatment including meropenem, doxycyclin and voriconazole, the pulmonary infection could not be controlled and oxygenation deteriorated.

To ensure a sufficient gas exchange, an extracorporeal lung assist device was established on day 4 (veno-venous ECMO) with a 23 French cannula (Stöckert) in the femoral vein, and a 17 French cannula (Novalung) in the subclavian vein. A Rotaflow pump (Jostra) and a heparin coated oxygenator (PLS – System Maquet) were used. With a blood flow of 3 l/min and a sweepgas flow of initially 6 l/min, we were able to reach a rapid reduction in Paco₂ (from 60 to 29 mm Hg) associated with a rise in Pao₂ (from 59.5 to 112 mm Hg). Ventilator settings could be reduced markedly, and a stable gas exchange was possible for the next 14 days.

Veno-venous ECMO drains desaturated central venous blood via a long cannula and can support gas transfer effectively. According to our measurements about 50% of total oxygen consumption can be provided. More than half of the body’s carbon dioxide production is eliminated by the membrane oxygenator (unpublished data). A veno-arterial ECMO, which is used in combined pulmonary and circulatory failure, can temporarily support near total gas exchange, but is prone to a higher complication rate due to arterial cannulation. Pumpless extracorporeal lung assist (PECLA, also interventional lung assist, iLA), which uses the arterio-venous pressure difference as the driving force, is well suited for carbon dioxide removal, but can provide only small amounts of oxygen.¹ Therefore, it is not adequate in severe hypoxaemic lung failure.

Subsequent CT scans showed signs of progressive destruction of both lungs (fig 2) and relapsing pneumothorax, which necessitated bilateral chest drainage. On day 17 the patient’s condition deteriorated rapidly and, despite high dose vasopressors, progressive multiorgan failure including renal and coagulation failure developed. The laboratory values on this day showed: CRP 61 mg/l (normal <5 mg/l), white cell count 24.4/nl (normal <10.8/nl), lactate 8·4 mmol/l, LDH 733 U/l (normal <247 U/), K⁺ 6.5 mmol/l, urea 13.9 mmol/l, creatinine 83 µmol/l on dialysis, GOT 135 U/l, and INR of 1.5. After 18 days on mechanical ventilation (15 days HFOV, 14 days NO, 14 days on pulmonary assist by ECMO) the patient died.

Figure 2.

Computed tomography scan on day 10, showing progressive destruction of both lungs.

The autopsy showed massively destroyed and haemorrhagic lytic lungs with infiltrates of Grocott-positive fungus (figs 3 and 4). Further histological evaluation also detected mycotic material in the coronary arteries, the liver and the kidneys, and was finally identified as Blastomyces dermatitidis by light cycler polymerase chain reaction (PCR). Retrospectively, blastomycotic infection of the mid brain was also confirmed by PCR from brain tissue initially obtained by stereotactic biopsy.

Figure 3.

Macroscopic view at autopsy, showing destroyed and haemorrhagic lungs with multiple air leaks.

Figure 4.

Histological view (20×), showing massive pulmonary infiltration with blastomyces.

DISCUSSION

Blastomycosis is a systemic pyogranulomatous disease caused by the thermally dimorphic fungus B dermatitidis. This disease occurs in defined geographic regions, hence its designation as an endemic mycosis. In North America, blastomycis occurs in the southeastern and south central states that border the Mississippi and Ohio rivers, the midwestern states, the Canadian provinces bordering the Great Lakes, and a small area of New York and Canada adjacent to the St Lawrence River.² Primary infection generally results from inhalation of conidia into the lungs, although primary cutaneous blastomycosis has infrequently been reported after dog bites. The clinical spectrum of blastomycosis varies, including asymptomatic infection, acute or chronic pneumonia, and disseminated disease.³ Acute pulmonary blastomycosis mimics influenza or bacterial pneumonia. Diffuse pulmonary infiltrates associated with ARDS occur infrequently but are associated with a very high mortality rate.⁴ In patients with blastomycosis and ARDS, broad based budding yeasts on microscopical examination can be detected. This results in a diffuse pyogranulomatous inflammation with massive infiltration of alveolar spaces by large numbers of B dermatitidis organisms. Hyaline membranes and other histopathological changes characteristic of ARDS can be seen. Haematogenous dissemination occurs frequently and almost any organ can be infected resulting in multiorgan failure. CNS involvement is rare, except in immunocompromised patients.⁵ Amphotericin B is the treatment of choice for patients who are immunocompromised, have life threatening disease or central nervous involvement.⁶ Recently voriconazole was also successfully used for the treatment of cerebral blastomycosis.⁷ According to published sepsis guidelines,⁸ we treated our patient with 10 mg/h hydrocortisone, which, in retrospective, may be counterproductive in severe fungal infection. Prednisolone is not implemented routinely in our institution for severe persistent ARDS, as a recent randomised clinical trial did not support its use.⁹

In summary, our patient suffered from severe blastomycosis with CNS infection and dissemination and development of ARDS after steroid treatment. The patient worked as a security officer at an international airport in Southern Germany. Contact with blastomycosis at an airport is very unlikely. Five years ago he had travelled to Kenya for a holiday. Although there are no documented cases of infections with blastomycosis in Kenya, blastomycosis has been described in surrounding countries such as Uganda. For Europe there are only a few documented reports of blastomycosis infection.^10,11 To our knowledge, a genuine case of blastomycosis has never been diagnosed in Germany. Even if we are not able to exclude exposure to blastomycosis in Europe, we consider it more likely that the primary contact occurred in Africa and the infection remained latent for 5 years as has been described before in the literature in blastomycosis.^12,13

To the best of our knowledge, this is the first report of a fulminant blastomycosis with ARDS and multiorgan failure in Germany. The case demonstrates that in patients with severe ARDS, ECMO can provide temporary pulmonary assistance to prolong the time frame for diagnosis and specific treatment. This case serves as a reminder to add exotic fungal infection to the list of differential diagnoses in patients with refractory pneumonia in the era of worldwide tourism.

LEARNING POINTS

• ECMO can provide temporary pulmonary assist to prolong the time frame for diagnosis and specific treatment.

• This case reminds us to add exotic fungal infection to the list of differential diagnoses in patients with refractory pneumonia in the era of worldwide tourism.