Last Updated

27 Nov 2002

Source: Mina B et al. Fata inhalational Anthrax with unknown source of exposure in 61-year-old woman in New York City. JAMA 287(7), 858-862, 2002 (Feb. 20, 2002).

October 28, 2001

On October 28, 2001, a 61-year-old Vietnamese woman was brought into the emergency department of Lenox Hill Hospital in New York City complaining of weakness, chest heaviness, dyspnea, malaise, cough, and chills for the preceding 3 days. On the day prior to admission, the cough was associated with pink-tinged sputum. The patient previously had been in her usual state of health and had worked until 2 days prior to admission. The patient denied headache, neck pain, fever, sore throat, or skin rash. The patient had a medical history of hypertension controlled with amlodipine and fosinopril. The patient was a nonsmoker and denied alcohol use or recreational drug use. She had immigrated to the United States from Vietnam 20 years earlier but had no recent travel. She worked in the central supply room of a Manhattan hospital in a space shared with a mail receiving and sorting room.

On physical examination, the patient had a respiratory rate of 38/min and was in respiratory distress. Blood pressure was 128/60 mm Hg, pulse was 86/min, and temperature was 97°F (36°C). Head examination results were normal without scleral icterus or oral thrush. The neck was supple with no bruits or jugular venous distension, and the trachea was midline. There was no evidence of cervical or axillary adenopathy. Chest examination revealed inspiratory rales and decreased breath sounds bilaterally. Heart examination revealed regular rate and rhythm, with normal S₁ and S₂ and no S₃, S₄, or murmurs. The abdomen was soft, nontender, and nondistended, and no organomegaly was evident. There were no neurological deficits. No skin lesions were detected.

The initial portable view of the chest obtained shortly after presentation demonstrated marked widening of the superior mediastinum, with moderate bilateral pleural effusions, fluid in the minor fissure, and bilateral perihilar infiltrates (see Figure 1A).

Figure 1A. Chest radiograph on admission.

Chest radiograph shows marked widening of the paratracheal stripe and superior mediastinum. There are moderate bilateral effusions with fluid in the minor fissure and bilater perihilar infiltrates.

An electrocardiogram showed sinus tachycardia at a rate of 101/min without any signs of myocardial ischemia. Arterial blood gas values obtained while the patient was receiving supplemental oxygen (100% nonrebreather face mask) were: pH, 7.41; partial pressure of carbon dioxide, 40 mm Hg; partial pressure of oxygen, 122 mm Hg; and oxygen saturation, 99%. Laboratory values on hospital admission are shown in Table 1 (see below).

A bedside echocardiogram showed normal left ventricular function and wall motion, slight aortic regurgitation, a small pericardial effusion, and an aneurysm of the ascending aorta. Blood cultures were drawn and were submitted in aerobic and anaerobic culture bottles (BioMerieux, Raleigh-Durham, NC). The patient was initially treated presumptively for congestive heart failure with 20 mg of intravenous furosemide. Empirical intravenous levofloxacin, 500 mg/d, was administered for community-acquired pneumonia and the possibility of inhalational anthrax.

The patient was admitted to the medical intensive care unit. Her respiratory and hemodynamic status deteriorated rapidly, and she was immediately intubated because of tachypnea, respiratory distress, and oxygen desaturation. Frothy pink secretions were suctioned from the endotracheal tube. Pulmonary artery catheterization revealed right atrial pressure of 4 mm Hg (reference range, 0-6 mm Hg), right ventricular pressure of 17/5 mm Hg (reference range, 20-30/0-5 mm Hg), and pulmonary artery pressure of 20/10 mm Hg (reference range, 20-30/5-15 mm Hg), but pulmonary artery wedge pressures could not be measured. After unsuccessful crystalloid resuscitation, vasopressor therapy (norepinephrine, phenylephrine, and, later, vasopressin) was initiated. The differential diagnosis included dissecting ascending aortic aneurysm with leakage, severe community-acquired pneumonia, vasculitis (Wegener granulomatosis), and inhalational anthrax. Rifampin, 300 mg intravenously every 8 hours, and clindamycin, 800 mg every 8 hours, were added to the antibiotic regimen, and the levofloxacin dosage was increased to 500 mg every 12 hours.

Figure 2A. Spiral computed tomography of the chest and 20-minute delayed image.

Computed tomographic image demonstrates large bilateral pleural effusion (white arrowheads) with a small amount of hemorrhagic debris (black arrrowhead) in the dependent portion of the right pleural space.  There is a large amount of edema and high-density soft tissue surrounding the trachea, bronchi, and hilar regions bilaterally, with obliteration of the mediastinal fat planes. There is marked bronchial mucosal edema and compression of the hilar vessels.

Repeat chest radiograph revealed progressive widening of the mediastinum, and the tip of the pulmonary artery catheter was positioned in the main pulmonary artery trunk. Spiral computed tomography of the chest demonstrated large bilateral pleural effusions, a small amount of blood layering in the dependent portion of the right pleural space, and a large amount of edema and hemorrhage in the soft tissues surrounding the trachea, bronchi, and hilar regions bilaterally, with complete infiltration of the mediastinal fat planes, bronchial mucosal thickening, encasement and compression of the hilar vessels (see Figure 2A). An intact 4.2-cm aneurysm of the ascending aorta was incidentally noted. Delayed images at 20 minutes demonstrated multiple confluent ringlike areas of enhancement with hypodense centers compatible with hemorrhagic lymph node necrosis involving the subcarinal, paratracheal, subaortic, and azygoesophageal recess nodes (see Figure 2B). A high-density pericardial effusion, suggesting hemorrhage, was also present.

Figure 2B. Spiral computed tomography of the chest and 20-minute delayed image.

This image demonstrates multiple confluent ringlike areas of enhancement with hypodense centers, consistent with subcarinal and mediastinal hemorrhagic lymphadenopathy (white arrowhead).  There is additional involvement of the paratracheal, subaortic, and azygoesophageal recess nodes.  A high-density hemorrhagic pericardial effusion is also present.

Bilateral chest tubes were inserted and each drained more than 1 L of serosanguinous fluid. Pleural fluid analysis produced the following values: glucose, 147 mg/dL (8.2 mmol/L); total protein, 4.2 g/dL; lactic dehydrogenase, 1264 U/L; white blood cell count, 3.0 - 10³/µL; and red blood cell count, 0.073 - 10⁶/µL. At the time of admission to the intensive care unit, the patient had an Acute Physiology and Chronic Health Evaluation III score of 143, with predicted intensive care unit and hospital mortality of 80% and 89%, respectively.

October 29, 2001

On the second hospital day, fiberoptic bronchoscopy revealed severe hemorrhagic tracheobronchitis with oozing of bloody fluid from the mucosal surfaces and easy sloughing of the mucosa. The patient developed worsening hepatic function with increasing aminotransferases, nonoliguric renal failure with creatinine level increasing to 1.9 mg/dL (168 µmol/L), lactic acidosis (lactate, 75 mg/dL), leukocytosis (23.9 - 10³/µL), and disseminated intravascular coagulopathy (see Table 1 above).  A continuous infusion of furosemide was initiated and multiple blood products were transfused. Blood cultures obtained on admission became positive for large gram-positive bacilli after 20 hours of incubation (see Figure 1B).  

Figure 1B. Blood culture obtained on admission.

Gram stain of blood culture shows gram-positive bacilli (original magnification x 1000).

Smears of the broth were Gram stained and revealed gram-positive rods in extremely long chains. Examination of a wet preparation of the blood culture broth demonstrated that the organism was nonmotile. Blood, pleural fluid, and bronchial wash specimens were sent for DNA amplification by polymerase chain reaction (PCR). A repeat echocardiogram confirmed a slight increase in the amount of pericardial fluid.

October 30, 2001

On the third hospital day, phenylephrine was tapered off and the norepinephrine dose was decreased by 50%. The patient's respiratory status deteriorated, with worsening oxygenation and ventilation. The blood culture isolate was confirmed as B anthracis by gamma phage lysis and direct fluorescent antibody testing against capsular and cell wall antigens at the New York City Department of Health and the CDC. Blood, pleural fluid, and bronchial washings were also positive by PCR for B anthracis at the same laboratories. Levofloxacin was discontinued and ciprofloxacin, 400 mg every 12 hours, was initiated. Repeat echocardiogram confirmed an increase in the size of the pericardial effusion and mild-to-moderate right atrial and ventricular collapse during early diastole. Cardiac index was 2.6 L/(min/m²) (reference range, 2.4-4.0 L/[min/m²]), systemic vascular resistance was 1131 (dynes.s.m²)/cm⁵ (reference range, 900-1400 [dynes.s.m²]/cm⁵), and a pulmonary capillary wedge pressure was 13 mm Hg (reference range, 6-12 mm Hg), with no evidence of equalization of pressures. A follow-up echocardiogram 5 hours later documented further increase in the pericardial fluid with evidence of collapse of the right atrium and ventricle.

The patient's respiratory status deteriorated further, and blood gas analysis revealed a pH of 7.49, a partial pressure of carbon dioxide of 37 mm Hg, a partial pressure of oxygen of 59 mm Hg, and an oxygen saturation of 92% with pressure-control ventilation, with pressure control of 20 cm H₂O, 100% oxygen, and positive end-expiratory pressure of 5 cm H₂O. Because of her deteriorating hemodynamic status and inability to maintain adequate oxygenation, a bedside echocardiographically guided pericardiocentesis was attempted unsuccessfully by the interventional cardiology service. The patient decompensated further, with worsening oxygenation and refractory hypotension with vasopressors, and she became bradycardic and pulseless. Cardiopulmonary resuscitation was unsuccessful and the patient died on the fourth hospital day (October 31, 2001). Repeat blood cultures from the second and fourth hospital days were negative for any pathogens.

An autopsy performed at the office of the chief medical examiner of the city of New York confirmed marked hemorrhagic mediastinitis. The hilar and peribronchial lymph nodes were enlarged, necrotic, and replaced by hematoma. Touch prep revealed few scattered gram-positive bacilli. There was a large hemorrhagic pericardial effusion and extensive pulmonary edema. There was no meningitis, bronchopneumonia, splenomegaly, or mesenteric lymphadenopathy. There were no hemorrhagic lesions of the liver or kidney. The cause of death was inhalational anthrax and the manner of death was homicide (oral communication, James Gill, MD, New York City Medical Examiner Office, January 14, 2002).

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