High dose subcutaneous Anakinra to treat acute respiratory distress syndrome secondary to cytokine storm syndrome among severely ill COVID-19 patients.

OBJECTIVE: Severely ill COVID-19 patients may end in acute respiratory distress syndrome (ARDS) and multi-organ failure. Some of them develop a systemic hyperinflammatory state produced by the massive release of inflammatory agents, known as cytokine storm syndrome (CSS). Inhibition of IL-1 by Anakinra (ANK) is a potential life-saving therapy for severe CSS cases. We propose a rationale for the use of subcutaneous ANK and review our initial experience in a small cohort of severe COVID-19 CSS patients. METHODS: Retrospective cohort study of COVID-19 patients developing ARDS (PaO2/FiO2 <300) and exhibiting signs of hyperinflammation (ferritin >1000 ng/mL and/or d-dimers > 1.5 µg/mL, plus IL-6 < 40 mg/mL) that received ANK. For comparison, a propensity score matched historical cohort of patients treated with IL-6 inhibitor Tocilizumab (TCZ) was used. Patients had previously received combinations of azithromycin, hydroxy-chloroquine, and methyl-prednisolone. Laboratory findings, respiratory function and adverse effects were monitored. Resolution of ARDS within the first 7 days of treatment was considered a favorable outcome. RESULTS: Subcutaneous ANK (100 mg every 6 h) was given to 9 COVID-19 ARDS CSS patients (77.8% males). Median age was 62 years (range, 42 to 87). A TCZ cohort of 18 patients was selected by propensity score matching and treated with intravenous single dose of 600 mg for patients weighing >75 Kg, or 400 mg if < 75 Kg. Prior to treatment, median PaO2/FiO2 ratio of the ANK and TCZ cohorts were 193 and 249, respectively (p = 0.131). After 7 days of treatment, PaO2/FiO2 ratio improved in both groups to 279 (104-335) and 331 (140-476, p = 0.099) respectively. On day 7, there was significant reduction of ferritin (p = 0.046), CRP (p = 0.043), and IL-6 (p = 0.043) levels in the ANK cohort but only of CRP (p = 0.001) in the TCZ group. Favorable outcome was achieved in 55.6% and 88.9% of the ANK and TCZ cohorts, respectively (p = 0.281). Two patients that failed to respond to TCZ improved after ANK treatment. Aminotransferase levels significantly increased between day 1 and day 7 (p = 0.004) in the TCZ group. Mortality was the same in both groups (11%). There were not any opportunistic infection in the groups nor other adverse effects attributable to treatment. CONCLUSION: Overall, 55.6% of COVID-19 ARDS CSS patients treated with ANK exhibited favorable outcome, not inferior to a TCZ treated matched cohort. ANK may be a potential alternative to TCZ for patients with elevated aminotransferases, and may be useful in non-responders to TCZ.

Necrosis cutánea secundaria a terlipresina, un raro pero grave efecto secundario. Reporte de un caso y revisión de la literatura / Cutaneous necrosis secondary to terlipressin therapy. A rare but serious side effect. Case report and literature review

La terlipresina es un análogo de la vasopresina, utilizado tanto en el tratamiento de la hemorragia por varices esofágicas como en el síndrome hepatorrenal. En general es un fármaco seguro, con efectos secundarios leves. Sin embargo, en ocasiones pueden ocurrir complicaciones isquémicas potencialmente graves, como la necrosis cutánea, que es necesario reconocer de forma precoz para realizar la retirada inmediata del fármaco. Presentamos el caso de una paciente que presentó necrosis cutánea extensa secundaria a la administración de terlipresina, y realizamos una revisión de los casos publicados, describiendo sus características, posibles factores de riesgo, localización de las lesiones, dosis recibida, forma de administración y posibles tratamientos (AU)

Terlipressin is a vasopressin analogue used in esophageal variceal bleeding and hepatorenal syndrome management. It is a safe drug with mild secondary effects. However, potentially serious ischemic complications may occur, such as cutaneous necrosis. It is useful to recognize these events early, in order to withdraw terlipressin and introduce other adjuvant drugs if needed. We report a detailed case of cutaneous necrosis secondary to terlipressin administration and present a case review of patients, describing their characteristics, risk factors, lesion locations, doses, methods of administration and possible treatments (AU)

Cutaneous necrosis secondary to terlipressin therapy. A rare but serious side effect. Case report and literature review.

Terlipressin is a vasopressin analogue used in esophageal variceal bleeding and hepatorenal syndrome management. It is a safe drug with mild secondary effects. However, potentially serious ischemic complications may occur, such as cutaneous necrosis. It is useful to recognize these events early, in order to withdraw terlipressin and introduce other adjuvant drugs if needed. We report a detailed case of cutaneous necrosis secondary to terlipressin administration and present a case review of patients, describing their characteristics, risk factors, lesion locations, doses, methods of administration and possible treatments.