Anesth Analg 2004;99:1205-1207
© 2004 International Anesthesia Research Society
doi: 10.1213/01.ANE.0000130615.28893.52
CRITICAL CARE AND TRAUMA
Rapid Development of Severe Interstitial Pneumonia Caused by Epoprostenol in a Patient with Primary Pulmonary Hypertension
Hiroshi Morimatsu, MD*,
Keiji Goto, MD*,
Takashi Matsusaki, MD*,
Hiroshi Katayama, MD PhD*,
Hiromi Matsubara, MD PhD
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Tohru Ohe, MD PhD, and
Kiyoshi Morita, MD PhD
Departments of *Anesthesiology and Intensive Care and
Cardiology, Okayama University Medical School, Okayama, Japan
Address correspondence and reprint requests to Hiroshi Morimatsu, MD, Department of Anesthesiology and Intensive Care, Okayama University Medical School, 2-5-1, Shikata-cho, Okayama 700-8558, Japan. Address e-mail to morimatu{at}pop21.odn.ne.jp
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Abstract
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A young woman with primary pulmonary hypertension developed severe interstitial pneumonia (IP) 5 days after induction of epoprostenol infusion. Although the pathogen involved was not identified, her IP was initially responsive to steroids, and discontinuation of steroid therapy caused the redevelopment of IP. After intensive treatment, including steroid therapy and inhaled nitric oxide, epoprostenol was successfully switched to prostaglandin E1 infusion and she recovered. Epoprostenol infusion can cause a rapid severe IP, even soon after the induction of therapy. Clinicians should keep this syndrome in mind, especially when treating a severe case of IP.
IMPLICATIONS: Epoprostenol infusion can cause a rapid, severe interstitial pneumonia (IP), even soon after the induction of therapy. Clinicians should keep this syndrome in mind, especially when treating a severe case of IP.
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Introduction
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Primary pulmonary hypertension (PPH) is a disease characterized by the progressive increase of pulmonary artery pressure (PAP) and vascular resistance, producing right ventricular failure and death (1–3). Several randomized controlled trials showed that epoprostenol could improve exercise capacity, quality of life, and mortality in this disease (4–6). Generally, epoprostenol is well tolerated, although continuous infusion is essential because of its short half-life (1–3).
Although epoprostenol has some side effects, including jaw pain, headaches, flushing, diarrhea, and nausea (3), serious adverse effects have been relatively rare. Herein, we report the clinical course of a PPH patient treated with epoprostenol who experienced rapid and serious interstitial pneumonia (IP).
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Case Report
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A 25-yr-old woman who had been diagnosed with PPH 3 yr earlier was transferred to our coronary care unit with dyspnea and exacerbation of edema. On electrocardiography, right ventricular hypertrophy was observed and echocardiography showed a dilated right ventricle with a small and excluded left ventricle. A Swan-Ganz catheter was then inserted, and showed a PAP of 95/35 mm Hg and central venous pressure of 25 mm Hg. On her chest radiograph (Fig. 1A) at admission, only cardiomegaly was observed, and the patient’s white blood cell (WBC) count and serum C-reactive protein (CRP) were normal (WBC: 8.2*103/µL, CRP: 1.3 mg/dL). Her SpO2 was 98% on oxygen mask.
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Figure 1. Chest radiograph on admission showed almost no abnormal shadow (A). Chest radiograph on the fifth day after admission showed a diffuse bilateral reticulonodular change (B). Chest radiograph in the recovery phase had been improved significantly (C).
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On the day after admission, we decided to start epoprostenol infusion at a rate of 0.5 ng · kg–1 · min–1 with incremental increases of 0.5 ng · kg–1 · min–1 every 12 h. After the initiation of epoprostenol, the patient’s hemodynamics were stable, her arterial blood pressure was 120/63 mm Hg, PAP was 96/41 mm Hg, central venous pressure was 23 mm Hg, and SpO2 was 98%.
Five days after commencement of epoprostenol, the patient was receiving 4.5 ng · kg–1 · min–1. However, her chest radiograph showed rapid changes in bilateral infiltrate (Fig. 1B), and her respiration gradually deteriorated so that she required tracheal intubation. After intubation, we started inhaled nitric oxide (NO) administration at a concentration of 10–20 ppm. Because of the patient’s rapid deterioration, acute infection was suspected. Despite the intensive antibiotic therapy, her oxygenation did not improve and we had to increase the flow rate of NO. We administered methylprednisolone at 500 mg per day for 3 days and then weaned to 40 mg of prednisolone daily.
The patient’s oxygenation improved and the steroid dose was weaned to 20 mg of oral prednisolone. Ten days after intubation, she experienced massive bleeding from a gastric ulcer, which required a blood transfusion and endoscopic hemostasis. Steroid administration was stopped at that time.
One week later, the patient’s chest radiograph began to show a bilateral infiltrate and computed tomography showed diffuse nodular interstitial changes, consistent with a finding of IP (Fig. 2A). She then received a 3-day course of 500 mg of methylprednisolone followed by 40 mg of prednisolone daily. This resulted in significant improvement in her chest radiograph findings and oxygenation.
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Figure 2. Computed tomography scan on day 31 after admission showed diffuse reticulonodular interstitial changes (A). After 2 wk of steroid treatment, interstitial findings were improving (B).
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Because of the unknown cause of her respiratory failure, we conducted a drug lymphocyte stimulate test for epoprostenol, which was positive (273% compared with control). We decided to substitute prostaglandin E1 (PGE1) for the epoprostenol and successfully switched to the equivalent dose of PGE1 (9 ng · kg–1 · min–1) in 3 days. Thereafter, her oxygenation, chest radiograph (Fig. 1C), and computed tomography (Fig. 2B) were stable.
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Discussion
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Our patient with PPH developed severe IP caused by epoprostenol infusion, requiring mechanical ventilation and NO inhalation. Deterioration occurred only five days after commencement of epoprostenol infusion. Steroid therapy was effective in controlling the IP, and we successfully switched from epoprostenol to PGE1.
Ahearn et al. (7) reported a patient with severe erythroderma as a complication of continuous epoprostenol therapy. They suggested that severe allergic reactions may occur after epoprostenol therapy has begun. Furthermore, Kesten et al. (8) reported development of nonspecific IP associated with five years’ treatment of PPH with prostacyclin. They also speculated that further cases of this syndrome would be reported, as more patients are living beyond five years with prostacyclin.
Our patient experienced IP after a five-day course of epoprostenol. This is the first report to show a rapid onset of severe IP caused by epoprostenol infusion.
Some differential diagnoses should be considered. At the first deterioration, laboratory tests showed that the patient’s WBC count was 27.4*103/µL, with neutrophilia (87%) and CRP 26.3 mg/dL, which suggested infection had affected her deterioration. However, we were unable to detect any organisms from the intensive culture and serum test, including bacteria, viruses, or parasites.
We believe infection was not the only cause of the patient’s deterioration. Although the pathogen involved was not identified, her IP was initially responsive to steroids, and discontinuation of steroid therapy caused the redevelopment of IP. The result of the drug lymphocyte stimulate test was also positive for epoprostenol. Thus, it is likely that epoprostenol was the primary cause of her IP. Unfortunately, we did not conduct a bronchoalveolar lavage. This procedure might have made the patient’s diagnosis clear.
In our patient with severe IP caused by epoprostenol infusion, steroid therapy was effective at controlling this adverse effect, and we successfully switched from epoprostenol to PGE1. Epoprostenol infusion can cause a rapid severe IP even shortly after the induction of therapy. Clinicians should keep this syndrome in mind, especially when treating a severe case of IP.
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References
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- Barst RJ, Rubin LJ, McGoon MD, et al. Survival in primary pulmonary hypertension with long-term continuous intravenous prostacyclin. Ann Intern Med 1994; 121: 409–15.[Abstract/Free Full Text]
- Barst RJ, Rubin LJ, Long WA, et al. A comparison of continuous intravenous epoprostenol (prostacyclin) with conventional therapy for primary pulmonary hypertension. N Engl J Med 1996; 334: 296–301.[Abstract/Free Full Text]
- McLaughlin VV, Genthner DE, Panella MM, et al. Reduction in pulmonary vascular resistance with long-term epoprostenol (prostacyclin) therapy in primary pulmonary hypertension. N Engl J Med 1998; 338: 273–7.[Abstract/Free Full Text]
- Ahearn GS, Selim MA, Tapson VF. Severe erythroderma as a complication of continuous epoprostenol therapy. Chest 2002; 122: 378–80.[Abstract/Free Full Text]
- Kesten S, Dainauskas J, McLaughlin V, et al. Development of nonspecific interstitial pneumonitis associated with long-term treatment of primary pulmonary hypertension with prostacyclin. Chest 1999; 116: 566–9.[Abstract/Free Full Text]
Accepted for publication April 14, 2004.
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Abstract
Introduction
