Calcium Channel Blocker Overdose: What Role Does Extracorporeal Membrane Oxygenation Have in Support? A Systematic Review of the Literature.

Extracorporeal membrane oxygenation (ECMO) has had increasing prevalence and indications in the last decade. Calcium channel blocker overdose (CCBOD) can lead to significant cardiopulmonary dysfunction and has also increased in recent years. CCBOD results in cardiac depression, vasoplegia, and hyperglycemia. Expert consensus recommends treatment with calcium, high-dose insulin, inotropes, and vasopressors. Our systematic review evaluated when to initiate ECMO in the CCBOD population and the mortality rate associated with use. Electronic literature review identified all relevant studies for CCBOD and ECMO. PRISMA guidelines for systematic review were followed. Three independent authors reviewed abstracts and full texts, and only CCB ingestion without polypharmacy was included. Two authors independently collected data, which included demographics, current medical treatments, ECMO type, and survival. From 314 abstracts, 25 papers were included with a median publication year of 2019. Twenty-six patients were included with an average age of 32.7 years and 42%/58% male/female. Average time on ECMO 4.3 days. VA and VV ECMO use were 92.3% and 7.7%, respectively, and 84.6% of patients survived to hospital discharge. Before ECMO, most patients received 4-5 medical treatments (53.8%). Our systematic review demonstrates ECMO is a newly used, yet valuable therapy for CCBOD when medical treatment fails. Survival to discharge after ECMO for CCBOD is substantially higher than standard VV or VA ECMO. Medical management is still the mainstay therapy for CCBOD, but we show that a persistently unstable patient may benefit from prompt evaluation at an ECMO center for treatment.

IL-17 mediates neutrophil infiltration and renal fibrosis following recovery from ischemia reperfusion: compensatory role of natural killer cells in athymic rats.

T cells have been implicated in the pathogenesis of acute kidney injury (AKI) and its progression to chronic kidney disease (CKD). Previous studies suggest that Th17 cells participate during the AKI-to-CKD transition, and inhibition of T cell activity by mycophenolate mofetil (MMF) or losartan attenuates the development of fibrosis following AKI. We hypothesized that T cell-deficient rats may have reduced levels of IL-17 cytokine leading to decreased fibrosis following AKI. Renal ischemis-reperfusion (I/R) was performed on T cell-deficient athymic rats (Foxn1rnu-/rnu-) and control euthymic rats (Foxn1rnu-/+), and CKD progression was hastened by unilateral nephrectomy at day 33 and subsequent exposure to 4.0% sodium diet. Renal fibrosis developed in euthymic rats and was reduced by MMF treatment. Athymic rats exhibited a similar degree of fibrosis, but this was unaffected by MMF treatment. FACS analysis demonstrated that the number of IL-17+ cells was similar between postischemic athymic vs. euthymic rats. The source of IL-17 production in euthymic rats was predominately from conventional T cells (CD3+/CD161-). In the absence of conventional T cells in athymic rats, a compensatory pathway involving natural killer cells (CD3-/CD161+) was the primary source of IL-17. Blockade of IL-17 activity using IL-17Rc receptor significantly decreased fibrosis and neutrophil recruitment in both euthymic and athymic rats compared with vehicle-treated controls. Taken together, these data suggest that IL-17 secretion participates in the pathogenesis of AKI-induced fibrosis possibly via the recruitment of neutrophils and that the source of IL-17 may be from either conventional T cells or NK cells.