Download Hannah Allegretto Elk Regional Health Center Block 3 07/27/2012

Hannah Allegretto
Elk Regional Health Center
Block 3
07/27/2012
Drug Information Question 2
Question: Which medication has a side effect of cyanide toxicity and how can the toxicity be managed?
Answer:
Sodium nitroprusside is the most common medication seen in practice that can cause cyanide
poisoning in individuals receiving the drug. Sodium nitroprusside is often used in the treatment of
hypertensive emergencies in the ER. A hypertensive emergency is defined as having a systolic pressure of
greater than or equal to 180 mmHg and/or a diastolic pressure of greater than or equal to 120 mmHg. End
organ damage also has to be present to characterize an episode as a hypertensive emergency. Treating
individuals as quickly as possible is crucial for limiting morbidity and mortality. Although patients need
to be treated quickly, it is important that the medical team does not try and reduce the blood pressure too
quickly, as the patient could suffer from ischemia. Currently, the guidelines recommend reducing the
mean arterial blood pressure (MAP) by no more than 25% in the first hour, then If stable, to 160/100-110
mmHg within the next two to six hours. After the patient is clinically stable, the blood pressure can
continue to drop towards a normal blood pressure in the next 24-28 hours.
Sodium nitroprusside is the drug of choice for several patients presenting with a hypertensive
emergency for a few reasons. First, the onset of action is immediate. Several of the other agents can take
upwards of 30 minutes to exert an effect. Secondly, the duration of action is very short, lasting only two
minutes. This can be beneficial if the blood pressure would drop too quickly, as the dose would be able to
be adjusted/discontinued accordingly. The typical starting dose for patients in a hypertensive emergency
is 0.25 – 10 µg/kg/min as an IV infusion. Although it is a reasonable option for several patients, the side
effects of the medication also have to be taken into consideration. Some adverse effects include nausea,
vomiting, muscle spasms, sweating, and thiocynate and cyanide intoxication after prolonged use.
Five cyanide groups are contained on every nitroprusside molecule. Most of the cyanide reacts
with thiosulfate to form thiocyanate, which will be eliminated in the urine. Infusion rates of <2 µg/kg/min
should lead to successful hepatic clearance of cyanide by converting the cyanide to thiocyanate. Infusion
rates of >4 µg/kg/min can produce toxic cyanide concentrations in as quickly as 5 to 10 hours. Symptoms
of cyanide toxicity include headache, tachypnea, convulsions, dizziness, and lactic acidosis.
Currently, there are a few different ways to treat cyanide toxicity. Eli Lilly has a “Cyanide
Antidote Kit” containing amyl nitrite and sodium nitrite. This helps convert hemoglobin to
methemoglobin, which has a greater affinity for cyanide than cytochrome oxidase. Although this method
is effective, rapid infusions of sodium nitrite can lead to hypotension. Along with the cyanide antidote kit,
subsequent thiosulfate infusions can also be used clinically to treat cyanide poisoning. This helps convert
cyanate to thiocyanate. Although thiosulfate infusions at a 10:1 ratio with nitroprusside helps decrease
cyanide toxicity, it may lead to toxic thiocyanate at high infusion rates or in those individuals with renal
insufficiency. Lastly, vitamin B12a, hydroxocobalamin, has been shown safe and effective at preventing
and treating cyanide poisoning. Nitroprusside releases a cyanide group which replaces the hydroxyl group
of vitamin B12a, which forms vitamin B12. Vitamin B12 is excreted unchanged in the urine. In one study, a
60% reduction of cyanide concentrations was observed in patients receiving a combination of
nitroprusside and hydroxocobalamin therapy. It is also recommended that hydroxocobalamin infusions be
continued for 10 hours after the end of the nitroprusside infusion. Hydroxocobalamin is approximately
$14/mg, therefore, cost could limit its use in therapy. The recommended dosage is 25mg/hr for 10 hrs
after the end of the nitroprusside infusion.
Sodium nitroprusside should be used in caution and monitored closely due to the adverse side
effects and potential for cyanide toxicity. Currently, options to manage/prevent cyanide toxicity include
amyl nitrite and sodium nitrite, thiosulfate infusions, and hydroxocobalamin. Each method has both
advantages and disadvantages, therefore, different institutions have different methods put in place for this
small subset of patients that will encounter nitroprusside.
References:
1. Zerbe NF, Wagner BKJ. Use of vitamin B12 in the treatment and prevention of nitroprussideinduced cyanide toxicity. Crit Care Med. 1993; 21: 465-66.
2. Cummings TF. The treatment of cyanide poisoning. Occ Med.2004 ; 54: 82-5.
3. National Heart, Lung, and Blood Institute. The seventh report of the Joint National Committee on
the prevention, detection, evaluation, and treatment of high blood pressure. Washington, DC:
U.S. Department of Health and Human Services, 2004; NIH publication no. 04-5230.
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