The 56 year- old male patient was administered to our tertiary care hospital due to severe ARDS following infection with COVID-19. Previously, he had been treated in another hospital. At the time point of arrival, he was under controlled ventilation. The pre- existing conditions documented for the patient were asthma and obesity. On admission, he was under controlled ventilation with an FiO2 of 1,0. PEEP was 16 mbar.
Chest x- ray at admission showed bilateral infiltrates. Blood sampling was done immediately after arrival. In addition, urine was checked for infection with legionella, pneumococcus and chlamydia, too. Also, tracheal suctioning was performed to look for bacterial superinfection.
Blood count at administration showed leukocytosis (12.700/µl) and anemia (Hb 13,1 g/dl). D- dimers were highly increased (> 33 mg/l). Na+ was slightly reduced (133 mmol/l). Chloride and Calcium were also reduced (95 mmol/l and 1,99 mmol/l, respectively). Phosphate was increased (1,53 mmol/l). Renal function appeared normal (creatinine 94 µmol/l). Creatinine- kinase was not elevated (163 U/l), LDH was highly increased (636 U/l). GOT and GPT both were slightly increased (92 U/l and 90 U/l, respectively) as was GGT (88 U/l). CHE was decreased (3,4 kU/l). Troponin levels were slightly increased (16 ng/l). CRP was highly increased (319 mg/l). Protein and albumin levels were decreased (56 g/l and 26 g/l, respectively).
Adequate blood pressure could be achieved through administration of norepinephrine (0,48 µg/h). Initially, MAP was 72 mmHg. Heart rate was 103/min. SpO2 was 94%, Horowitz- index was 76 mmHg. Body temperature, which was measured via the transurethral catheter was 37°C, but increased in the following hours, finally reaching 38,8°C. Fever could be controlled via administration of acetaminophen and metamizole. At the ventilator, pressure-controlled ventilation was performed. PEEP was set to 14 mbar, initially, but had to be increased to 16 mbar the following hours due to inadequate oxygenation. Peak pressure was set to 30 mbar, breathing rate 30/min and inspiration time was 1,1 sec. Tidal voluminal were between 425 ml and 550 ml. Since FiO2 could not be reduced the following hours below 0,9 despite repeated relaxation through administration of rocuronium, we decided to begin prone positioning. In addition, sedation that was initially performed with propofol and remifentanil was switched to sevoflurane and sufentanil. Prone positioning was done for 16 hours daily followed by supine positioning for additional 8 hours. With prone positioning, slowly, improvement of respiratory function was visible and FiO2 could be gradually decreased to 0,4. After 7 days, prone positioning could be stopped after we observed sustained improvement of respiratory function also in supine position.
The next days, the patient developed progressive renal failure. Creatinine level increased to 423 µmol/l and urine output almost completely suspended. Therefore, we started continuous renal replacement therapy (CRRT). Here, GeniusÒ 90 system (Fresenius Medical Care, Bad Homburg Germany), was used. Both PCT and IL-6 level shortly after administration were elevated to 3,7 µg/l and 800 ng/l, respectively. Therefore, a CytosorbÒ filter was added to CRRT (Fig. 2). Treatment with a CytosorbÒ filter was performed for a total of three days. After that, blood sampling revealed a significant drop of IL-6, from 800 ng/l to 113 ng/l (Fig 1). Before admission to our university hospital, the colleagues had already started an antibiotic therapy with Ampicillin/Sulbactam and Clarithromycin. We went on with this antibiotic therapy for further 12 days (Ampicillin/Sulbactam) and 8 days (Clarithromycin). Circulation continuously improved, reflected through decreasing doses of Norepinephrine, necessary. We started another antibiotic treatment with Piperacillin/Tazobactam when inflammatory markers, again, began to increase. Diagnostics could exclude infection with legionella and pneumococcus. We could only find staphylococcus epidermidis in one blood culture drawn from the arterial catheter line, which we considered contamination.
Disease course was complicated by pneumothorax that was successfully treated with drainage, which we could remove later on. We finally tried extubation after a total of 23 days of ventilator support. However, intubation became necessary again after three days, due to progressive respiratory failure. After intubation, severe respiratory acidosis was seen in blood gas sampling, despite FiO2 of 1,0. Tidal volume was 280 ml only, although inspiratory pressure was as high as 40 mbar and PEEP was 14 mbar, too. Both, incorrect position of the endotracheal tube and de novo pneumothorax were excluded. We quickly decided to implant VV- ECMO (Maquet Cardiohelp, Rastatt, Germany). Implantation was done through the right internal jugular vein and right femoral vein. Blood was drawn from the right femoral vein and returned after oxygenation to the right internal jugular vein (Fig. 3). After implantation, respiratory acidosis slowly improved. Both, high norepinephrine support (4,8 µg/h) and intensive fluid therapy were necessary, to achieve sufficient mean arterial pressure. Since blood sampling showed high levels of the inflammatory cytokines IL-6 and soluble IL-2 receptor, we decided to integrate Biosky® filter into the ECMO circuit for cytokine removal (Fig. 3). In addition, antibiotic therapy was first escalated to Vancomycin and Meropenem, finally changed to Caspofungin, Linezolid and Meropenem. With the combination of a changed antibiotic regimen and Biosky® filter all markers of inflammation, e.g. leukocytes, CRP, PCT, IL-6, soluble interleukin 2- receptor started to decrease (Fig. 1). Interestingly, neither blood and urine cultures nor tracheal suctioning could reveal microbial infection. Finally, weaning from VV- ECMO was possible. However, after weaning from VV- ECMO had been done, the patient again deteriorated and unfortunately, finally died.