Methylene blue treatment for cytokine release syndrome-associated vasoplegia following a renal transplant with rATG infusion: A case report and literature review

Abstract

Rabbit anti-thymocyte globulin (rATG) is an infusion of polyclonal rabbit-derived antibodies against human thymocyte markers, which can be used to prevent and treat acute rejection following organ transplantation. However, the product monograph issued by the manufacturer (Sanofi Canada) reports that serious immune-mediated reactions have been observed following the use of rATG, consisting of anaphylaxis or severe cytokine release syndrome (CRS), which is a form of vasoplegic syndrome (VS), in which distributive shock occurs refractory to norepinephrine (NE) and vasopressin (VP). Severe infusion-associated reactions are consistent with CRS and can cause serious cardiac or respiratory problems, or in certain cases, mortality. CRS is a form of systemic inflammatory response syndrome (SIRS). In SIRS, the substantial activation of endothelial inducible nitric oxide synthase (iNOS) and smooth muscle guanylate cyclase (GC) is observed, which can produce severe hypotension that is unresponsive to conventional vasopressors. Methylene blue (MB) is a direct inhibitor of iNOS and GC and has been used as an effective treatment for VS following cardiothoracic surgery. In the present study, the successful use of MB as a rescue therapy for CRS in a patient receiving rATG following a renal transplant was reported. Following an uneventful cadaveric kidney transplant involving the intravenous (IV) administration of rATG for the induction of immunological tolerance, the patient became markedly hypotensive and tachycardic. The patient required high doses of VP and NE infusions. Following the protocol described for treating refractory VS in post-cardiac surgery patients, the decision was made to initiate the patient on an IV MB infusion. This treatment protocol was shown to improve the hemodynamic status of the patient, which enabled the withdrawal of vasopressors and suggests an important role for methylene blue in the management of refractory VS.