A 31-year-old woman at 17 weeks of gestation was admitted to the emergency department for cough, expectoration for 1 month, and dyspnea and fever for 3 days. A previous hospital administered empirical anti-infection therapy with ceftriaxone, but the effects were unsatisfactory. Furthermore, two days later, non-invasive mechanical ventilation failed due to ARDS. Consequently, endotracheal intubation and invasive mechanical ventilation were performed, and the patient was admitted to the medical intensive care unit (MICU). The patient had a history of chronic hepatitis B, long-term oral antiviral treatment, three pregnancies, and two induced abortions.
 Table 1 summarizes the vital signs and general laboratory test results. At admission, the vital signs were: temperature, 39.5 C; blood pressure, 97/43 mm Hg (continuous intravenous pumping of norepinephrine 1.0 mug/kg/min); respiratory rate, 40 bpm; heart rate, 145 bpm; hemoglobin oxygen saturation, 80%; and a fraction of inspired oxygen (FiO2), 100%. The patient was 159 cm tall and weighed 52.5 kg. Physical examination revealed shortness of breath, wet voice, wheezing of both lungs, and tachycardia. Gastrointestinal decompression drained a small amount of dark red blood cells.
We also performed laboratory tests; smears and cultures for acid-fast bacilli, TB-DNA, and TB-Xpert of bronchoalveolar lavage fluid (BALF) tests were positive. In addition, TB interferon-gamma release assay, purified protein derivative skin test, and hepatitis B surface antigen and core antibody results were positive. Next-generation sequencing (NGS) of BALF and peripheral blood revealed 235 and 75 sequences of Mycobacterium tuberculosis complex, respectively. However, blood cultures for aerobic and anaerobic bacteria were negative, as tested for G and GM, human immunodeficiency virus, hepatitis C, Epstein-Barr virus, cytomegalovirus, Mycoplasma pneumoniae, and TORCH (i.e., toxoplasmosis, other, rubella, cytomegalovirus, and herpes) toxoplasma. Also, the HBV DNA levels were below the lower limit of detection.
Nevertheless, high-resolution computed tomography (CT) showed multiple miliary nodular lesions partially clustered and diffusely consolidated in both lungs (Figures 1A, B). Moreover, obstetric ultrasonography revealed a normal fetal heart rate. Finally, head CT, echocardiography, and limb vascular ultrasound findings were normal.
The initial VV-ECMO treatment, which began after conventional therapies for ARDS, failed. The initial ECMO parameters were: blood flow, 5.5 L/min; centrifugal pump speed, 4,010 circles/min; water temperature, 37 C; the fraction of delivered oxygen, 100%; oxygen flow 3.5 L/min; invasive mechanical ventilation, A/C (VC); respiratory rate, 12 times/min; tidal volume, 280 ml; positive end-expiratory pressure (PEEP), 5 cmH2O; and FiO2, 60%. UFH was initially selected for anticoagulant therapy; 12,500 units of UFH were administered via bolus at the cannulation time, followed by a continuous infusion of 10 units/kg/h. The active partial thromboplastin time (APTT) and activated clotting time (ACT) therapeutic targets were 40-60 s and 200-240 s, respectively. APTT and ACT were initially checked every 2 h, followed by every 4 h after reaching the therapeutic target. If these two indicators were inconsistent, the APTT value was preferentially considered.
After 3 days of VV-ECMO, the patient's platelet count and antithrombin III (AT-III) level decreased to 27 x 103 cells/muL and 26.9%, respectively, and the 4T (the pretest probability of heparin-induced thrombocytopenia) score was 5. However, the platelet antibody test results were negative. Therefore, we initiated argatroban as an alternative therapy on ECMO day 3, administering argatroban by an infusion of 0.06 mug/kg/min without a bolus. The APTT and ACT therapeutic targets and checks were identical to those for the UFH therapy.
After platelet infusion and alternative anticoagulant therapy, the patient's platelet count increased to 66 x 103 cells/muL on day 8. Thus, UFH was resumed. However, we reverted to argatroban on day 11 due to a decreased platelet count and unsatisfactory APTT with UFH. The APTT and ACT ranged from 43 to 58 s and 220-260 s, respectively, and the argatroban infusion varied from 0.9 to 1.2 mug/kg/min. However, the platelet count and AT-III level were within the normal range in the subsequent therapy. In addition, hematuria appeared during argatroban therapy but improved without additional treatment. Notably, the patient met the therapeutic targets during argatroban therapy without circuit thrombosis, severe bleeding, infection, hemolysis, or thrombocytopenia. In addition, continuous ultrasound monitoring did not find fetal distress. Figure 2 presents the APTT, ACT, AT-III, and platelet count variations throughout the anticoagulant treatments.
Moreover, we prescribed the isoniazid, rifampicin, pyrazinamide, ethambutol (HRZE) regimen and dexamethasone as anti-TB therapies. However, on day 7 of the HRZE regimen, the patient developed a systemic skin rash and liver damage (alanine aminotransferase 143 U/L, total bilirubin 88 mumol/L). Consequently, we changed to the ethambutol, levofloxacin, amikacin, cycloserine, and linezolid regimen based on liver protection and anti-allergy treatments and decreased then ceased dexamethasone for 1 month. We also prescribed meropenem empiric antibacterial treatment and sedation, analgesia, muscle relaxation therapy, functional vascular medicine, liver protection therapy, proton-pump inhibitors, and enteral nutrition after MICU admission.
Under the above treatments, the patient's temperature and oxygenation gradually improved. However, on day 23, the patient developed a fever. In addition, blood and BALF NGS revealed Klebsiella pneumoniae, and a drug-sensitivity test determined that the organism was multidrug-resistant. Therefore, 2.5 g q8h of Zavicefta was prescribed based on the drug susceptibility results. However, after eight days of initiating Zavicefta treatment, the patient's temperature did not decrease; hence, we had to administer tigecycline. Later, the patient's temperature gradually returned to normal after the combined drug therapy.
Adequate oxygenation and ventilation were provided to the patient during the downregulation of ECMO parameters, and on day 27, the patient was weaned off VV-ECMO successfully along with administration of low-molecular-weight heparin, followed by argatroban for hypercoagulability. Finally, on day 32, we performed a tracheotomy. However, on day 38, after oxygenation, we weaned the patient off mechanical ventilation and observed an improvement in the chest images (Figures 1C,D).
After anti-TB and other treatments, the patient and family members decided to terminate the pregnancy. However, on day 42, the patient underwent labor induction, delivering a dead fetus, and on day 45, the patient experienced a sudden twitch and disturbance of consciousness, which continued for 1 minute. However, emergency head CT showed no signs of hemorrhage or infarction. Additional tests conducted included a lumbar puncture for cerebrospinal fluid (CSF; 123 mmH2O of pressure), routine CSF analyses (identifying no nucleated cells or erythrocytes), and CSF biochemical analysis (protein 0.66 g/L, glucose 3.88 mmol/L, and chlorine 120 mmol/L). Besides, synchronous blood glucose and chlorine were 5.36 mmol/L and 117 mmol/L, respectively, and the immunoglobulin G synthesis rate was 4.205 mg/day. At the same time, smears and cultures of acid-fast bacilli and other bacteria and ink stains, cryptococcal antigens, TB-DNA, and TB-Xpert tests were negative. However, head magnetic resonance imaging indicated multiple demyelinating brain white matter lesions. Therefore, we prescribed levetiracetam (0.5 g) twice daily, and consequently, the patient did not experience more twitches.
On day 49, the patient was transferred to the TB ward without respiratory support or active vascular drugs. The anti-TB treatment regimen was changed to the ethambutol, rifapentine, amikacin, and linezolid regimen to account for potential nervous system adverse reactions to cycloserine and levofloxacin. The patient's symptoms and chest images improved significantly (Figures 1E,F), and she was discharged on day 59.