Sodium nitroprusside-associated cyanide toxicity in adult patients – fact or fiction? A critical review of the evidence and clinical relevance

Abstract

Sodium nitroprusside-associated cyanide toxicity in adult patients – fact or fiction? A critical review of the evidence and clinical relevance Alissa Lockwood1, John Patka2, Marina Rabinovich2, Katleen Wyatt2, Prasad Abraham21Department of Pharmacy, Parkland Health System, Dallas, TX, USA; 2Department of Pharmacy and Drug Information, Grady Health System, Atlanta, GA, USAAbstract: Since its US Food and Drug Administration (FDA) approval in 1974, sodium nitroprusside (SNP) has been fraught with controversy in regards to its safety. Over the years, a growing concern related to SNPs propensity to cause cyanide (CN) toxicity culminated into a series of case reports that led the FDA to develop a black-box warning with dose limitations of <2 µg/kg/min. These recommendations stemmed also from the reality of the difficulty of obtaining CN levels in a timely manner, as well as the presumed poor correlation of metabolic markers (lactate levels and pH) as it related to the severity of CN toxicity. All these issues have driven practitioners to the use of alternative agents. In this paper, we critically review the cases and the data that led to the development of these restrictive dosing recommendations and reveal several limitations of the data and assumptions that led to these recommendations. We conclude that SNP is still a reasonable agent to use in the management of patients with hypertension today and can safely be used beyond doses of 2 µg/kg/min. Furthermore, in lieu of CN levels, monitoring of lactic acid levels is also a reasonable measure to ensure safety.Keywords: dose limits, monitoring, controversy, thiosulfate stores, cyanide levels