WBR283

Author	PageAuthor::Gerald Chi (Reviewed by Serge Korjian)
Exam Type	ExamType::USMLE Step 1
Main Category	MainCategory::Pharmacology
Sub Category	SubCategory::Cardiology
Prompt	[[Prompt::A 32-year-old woman delivers a newborn at 33 weeks gestation. The newborn is found to have persistent pulmonary hypertension and is promptly administered high frequency ventilation and inhaled nitric oxide therapy. Six hours later, the newborn becomes cyanotic and lethargic and develops a seizure. What is the most appropriate initial therapy for this patient?]]
Answer A	AnswerA::N-Acetylcysteine
Answer A Explanation	[[AnswerAExp::N-Acetylcysteine replenishes the reduced form of glutathione, which neutralizes the oxidative stress associated with acetaminophen overdose. It is also used in reducing the mucus viscosity in patients with cystic fibrosis by isolating disulfide bonds.]]
Answer B	AnswerB::EDTA
Answer B Explanation	AnswerBExp::EDTA is a chelating agent for treating heavy metal poisoning. It is also an anticoagulant for keeping blood samples.
Answer C	AnswerC::Methylene blue
Answer C Explanation	AnswerCExp::Methylene blue and ascorbic acid (Vitamin C) have the ability to convert ferric ion into ferrous ion in hemoglobin and restores its oxygen-binding capacity to the proper state.
Answer D	AnswerD::Amyl nitrite
Answer D Explanation	AnswerDExp::Amyl nitrite is used in cyanide poisoning. It oxidizes iron to the ferric state and actually causes methemoglobinemia to decrease the binding of cyanide to hemoglobin.
Answer E	AnswerE::Vitamin K
Answer E Explanation	AnswerEExp::Vitamin K is required for gamma carboxylation of glutamate residues and is used in warfarin overdose.
Right Answer	RightAnswer::C
Explanation	[[Explanation::Persistent pulmonary hypertension in the newborn may be either idiopathic or associated with prematurity, pulmonary hypoplasia, or premature closure of the ductus arteriosus. In hypoxemic newborns with pulmonary hypertension, inhaled nitric oxide reduces pulmonary vascular resistance and decreases the need for extracorporeal membrane oxygenation therapy. However, nitric oxide inhalation may result in elevations in methemoglobin leading to methemoglobinemia. In infants with PPH receiving nitric oxide, methemoglobin levels should be monitored every 4 hours and maintained below 5%. Infants with methemoglobinemia have signifcant cyanosis. Methemoglobin interferes with the regular pulse oximetry often giving a reading higher than the true available oxygen, and not in proportion to the level of cyanosis. A co-oximeter, able to differentiate oxyhemoglobin, methemoglobin, and deoxyhemoglobin, is the best way to monitor methemoglobin levels. Treatment should be initiated promptly in patients with elevated methemoglobin with or without clinical manifestations. Methylene blue is the optimal initial agent. Exchange transfusions are recommended when methylene blue is contraindicated (E.g.: G6PD deficiency). Methylene blue increases the rate of reduction of methemoglobin into hemoglobin by converting the iron moeity from a ferric ion (Fe3+) into a ferrous ion (Fe2+). Educational Objective: Methylene blue is the treatment of choice in methemoglobinemia. It increases the rate of reduction of methemoglobin into hemoglobin by converting the iron moeity from a ferric ion (Fe3+) into a ferrous ion (Fe2+). References: Jaffe ER, Neurmann G. A comparision of the effect of menadione, methylene blue and ascorbic acid on the reduction of methemoglobin in vivo. Nature. 1964;202:607-8. Bizzarro M, Gross I, Barbosa FT. Inhaled nitric oxide for the postoperative management of pulmonary hypertension in infants and children with congenital heart disease. Cochrane Database Syst Rev. 2014;7:CD005055. Hamon I, Gauthier-moulinier H, Grelet-dessioux E, Storme L, Fresson J, Hascoet JM. Methaemoglobinaemia risk factors with inhaled nitric oxide therapy in newborn infants. Acta Paediatr. 2010;99(10):1467-73.]]
Approved	Approved::Yes
Keyword	WBRKeyword::Pulmonary hypertension, WBRKeyword::Methylene blue, WBRKeyword::Methemoglobinemia
Linked Question	Linked::
Order in Linked Questions	LinkedOrder::