A 50-year-old male sushi chef who had never traveled outside Japan presented with a 2-day history of fever and muscle pain. Laboratory investigation yielded the following results: white blood cells (WBC): 7780/microL; platelets: 89000/microL; C-reactive protein (CRP): 36.4 mg/dL; blood urea nitrogen (BUN): 47 mg/dL; creatinine: 2.41 mg/dL; and total bilirubin (T-Bil): 2.0 mg/dL. The day after he was admitted to the hospital, the patient's condition worsened, as indicated by the laboratory data: WBC: 6700/muL; platelets: 50000/microL; CRP: 32.49 mg/dL; BUN: 66 mg/dL; creatinine: 2.81 mg/dL; and T-Bil: 5.6 mg/dL. He was presumptively diagnosed with bacterial pneumonia, atypical pneumonia, and miliary tuberculosis. He was also diagnosed with leptospirosis on the basis of jaundice, renal failure, and thrombocytopenia. He was administered the broad-spectrum antibiotics ceftriaxone, levofloxacin, and minocycline on the first day of admission to the referral hospital. Vancomycin and meropenem were administered on the second day. He was also given the antitubercular agents:isoniazid, rifampicin, pyrazinamide, and ethambutol:even though the results of a tuberculosis screening test were negative. Despite these treatments, his systolic blood pressure dropped to 70 mmHg, and his respiratory condition deteriorated; he was intubated 5 days after the onset of symptoms, which is three days after admission to the previous hospital. An X-ray showed bilateral alveolar infiltrates, and blood gas analysis revealed the following: pH: 7.390; partial pressure of arterial carbon dioxide (PaCO2): 28.3 mmHg; and partial pressure of arterial oxygen (PaO2): 70.4 mmHg HCO3- 16.8 mmol/L with fraction of inspired oxygen (FIO2) of 1.0 as well as positive end-expiratory pressure (PEEP) of 10 cm H2O. The patient developed a life-threatening condition with septic shock and severe acute respiratory failure, despite optimal medical treatment. He was referred to our center for ECMO. Our ECMO team decided to initiate V-V ECMO at the previous hospital and transport the patient on V-V ECMO because the patient was severely hypoxic and needed maximal doses of norepinephrine, epinephrine, and vasopressin to stabilize his cardiac condition. Cannulation was performed via the right femoral vein with 25-French drainage cannulae (HLS Cannulae Maquet Cardiopulmonary, Hirrlingen, Germany) for access and via the right internal jugular vein with 23-French cannulae for return. The ECMO circuit was an adult ECMO bypass custom tubing pack consisting of a Rotaflow  centrifugal pump (Maquet Cardiopulmonary GmbH, Hirrlingen, Germany) and gas exchanger (MERA NHP Excelung NSH-R HPO-23WH-C , Senko Medical Inc., Tokyo, Japan). V-V ECMO was initiated at a blood flow rate of 4.0 L/min, with sweep gas flow through the oxygenator at 4.0 L/min of 100% oxygen. After the procedure, the patient's SpO2 was 94%, heart rate was 131 beats/min, and blood pressure was 142/74 mmHg on 0.1 mug/kg/min of epinephrine and 0.3 mug/kg/min of norepinephrine. He was transported to our center via ground ambulance.
After he was transported to our ICU, we maintained the ECMO blood flow at >3.0 L/min during the first 3 days of ECMO because his activated partial thromboplastin time was maintained at around 40-50 s, which was lower than normal because of bleeding (Table 1). After bleeding was controlled, we decreased the ECMO blood flow gradually to 1.5 L/min when peripheral capillary oxygen saturation (SpO2) was over 90%. During V-V ECMO the mechanical ventilation was set at the lung rest setting, which consisted of a driving pressure of 5 cm of water, PEEP of 12 cm of water, and FIO2 of 0.4. Fiber-optic bronchoscopy showed diffuse endobronchial bleeding. The patient was systemically heparinized to maintain an activated partial thromboplastin time of 40-50 seconds, which was lower than the normal value for V-V ECMO. Dobutamine was initiated at 3 microg/kg/min because transthoracic echocardiography showed that the ejection fraction was 30%, mitral regurgitation was moderate, and tricuspid regurgitation was severe. After initiation of dobutamine, his cardiac function improved, epinephrine was stopped the next day, and norepinephrine was stopped the day after that. He remained oliguric and needed renal replacement therapy for 7 days. At the time of presentation to our center, his WBC count was 18,000/microL, CRP level was 24.52 mg/dL, and procalcitonin level was > 100 ng/mL. Although we thought of a wide variety of infections as differential diagnoses, we strongly suspected leptospirosis on the basis of severe acute respiratory failure, myocardial pericarditis, renal failure, jaundice, and thrombocytopenia, which made us continue the broad-spectrum antibiotics, levofloxacin, vancomycin, meropenem, antitubercular agents, and add benzylpenicillin. Because of pulmonary hemorrhage, he was given a platelet transfusion (20 units) for the first 3 days of V-V ECMO therapy. Even though his pulmonary hemorrhage improved on day 8 of V-V ECMO, computed tomography scans showed bilateral ground-glass opacities, bilateral pleural effusion, and atelectasis. Rehabilitation, including sitting on the edge of the bed and standing, was initiated. On day 6 of ECMO therapy, polymerase chain reaction analysis of urine samples collected at the previous hospital confirmed the presence of leptospiral DNA. The tests for tuberculosis, Legionella urinary antigen, pneumococcal antigen, serum Mycoplasma antibody, and Chlamydia pneumoniae antibody all yielded negative results. We switched the intravenous antibiotics from broad-spectrum antibiotics to benzylpenicillin (12 million units/day).
On day 11 of ECMO therapy, blood tests showed improvements in platelet count and serum CRP, creatinine, and T-Bil levels (Figure 1). In addition, the amount of sputum decreased, and improvements were observed in his chest X-ray (Figure 2), compliance, and oxygenation (Figure 3); therefore, we performed a 2-hour trial off-test. The patient tolerated the trial without O2 flow to the oxygenator; therefore, we decided to wean him off ECMO. He was extubated 2 days after being taken off ECMO and transferred back to the previous hospital 2 days after extubation. His last blood gas analysis revealed the following results: pH: 7.468; PaCO2: 36.6 mmHg; PaO2: 67.2 mmHg; and HCO3-: 26.2 mmol/L on room air. Laboratory investigation revealed the following results: WBC: 7400/microL; platelets: 256000/microL; CRP: 1.13 mg/dL; BUN: 29.1 mg/dL; creatinine: 1.36 mg/dL; and T-Bil: 7.9 mg/dL. Finally, paired serum antibody titer testing (on days 5 and 19 after the onset of symptoms) showed a fourfold or higher increase in antibody titers for Leptospira interrogans serovar Copenhageni and Leptospira interrogans serovar Icterohaemorrhagiae, confirming the diagnosis of leptospirosis.