Norepinephrine/phenylephrine/vasopressin

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An event is serious (based on the ICH definition) when the patient outcome is:

• * death

• * life-threatening

• * hospitalisation

• * disability

• * congenital anomaly

• * other medically important event

In a series of 3 cases, a 75-year-old man was described, who exhibited lack of efficacy during treatment with norepinephrine, phenylephrine and vasopressin for hypotension.

The man, who had type 2 diabetes mellitus, hypertension, coronary artery disease and hyperlipidaemia, was referred to the hospital with 1 week of fatigue, cough and fevers. A diagnosis of coronavirus disease-19 (COVID-19) was suspected, and off-label treatment with azithromycin and hydroxychloroquine was initiated (scheduled to be administered for 5 days). On day 6 of admission, he was intubated due to persisting hypoxaemia. His D-dimer levels were found to be consistently >50000 ng/mL for 4 days after intubation, and his fibrinogen levels were between 375 and 541 mg/dL. On day 8 of hospitalisation, his partial pressure of oxygen/FiO2 (P/F) ratio ranged between 140 and 240. A diagnosis of COVID-19 associated acute respiratory distress syndrome (ARDS) and respiratory failure was considered. He became anuric. Therefore, he was started on continuous renal replacement therapy (CRRT); that combined with persistently increased D-dimer. Thus, it was decided to initiate off-label treatment with a tissue plasminogen activator (tPA) for the COVID-19 associated acute respiratory distress syndrome (ARDS) considering a possibility of thromboembolism. Therefore, IV infusion of alteplase (a tPA therapy) was initiated at 25mg over 2 hours of infusion, followed by a 25mg infusion over the subsequent 22 hours. He tolerated tPA therapy with no bleeding or any other apparent complications. His P/F ratio also found to be improved. After completion of tPA therapy, he was initiated on heparin with a partial thromboplastin time goal of 60 to 80. An hour into the heparin infusion, the P/F ratio worsened. There was a concern for pulmonary oedema and fluid overload given he was 1L positive on his fluid balance for the previous 24 hours and remained anuric on CRRT; however, efforts to remove volume via CRRT were complicated by the development of hypotension and rapid atrial fibrillation. These complications made it difficult to attain a negative fluid balance. His vasopressor requirements increased from 1 to 3; and started receiving vasopressin, norepinephrine and phenylephrine [dosages and routes not stated]. At 48 hours after-tPA, his P/F was similar to his pre-tPA status. His D-dimer also decreased and fibrinogen levels remained similar. However, by day 11 of hospitalisation, he continued to descend into multiple organ failure with refractory hypotension despite treatment with vasopressor therapy. A superimposed bacterial infection and arrhythmia were also noted [aetiology not stated]. He died eventually [immediate cause of death not stated].