Methemoglobinemia due to incorrect use of benzocaine sprays

[Ridryder 911]

Methemoglobinemia due to incorrect use of benzocaine sprays

By

Feb 22, 2006, 07:28

Courtesy the EMS House of DeFrance http://www.defrance.org

Benzocaine sprays are used in medical practice for locally numbing mucous membranes of the mouth and throat for minor surgical procedures or when a tube must be inserted into the stomach or airways. Their use is known to be occasionally associated with methemoglobinemia. However, cases of methemoglobinemia have also resulted from medication errors due to incorrect use of benzocaine sprays (e.g., longer duration or more frequent sprays than recommended.). On February 8, 2006, the Veterans Health Administration (VA) announced the decision to stop using benzocaine sprays for these purposes. The FDA is aware of the reported adverse events and is reviewing all available safety data, but at this time is not planning action to remove the drugs from the market. Up until now, the FDA has concluded that the number of reported adverse events with these sprays has been low and, when properly used, these products can help make important procedures less uncomfortable for patients. This advisory applies only to benzocaine sprays used in the mouth and throat, not to other benzocaine products or to benzocaine sprays applied to exterior skin.

The FDA is again highlighting here safety information previously addressed by the Agency (see http://www.accessdata.fda.gov/scripts/cdrh...inter.cfm?id=40 ), and will make further announcements or take action as warranted by the ongoing review. At present, the FDA suggests considering the following points about the use of benzocaine sprays in procedures requiring that a tube be inserted in the larynx or pharynx (down the throat, windpipe, or gullet) or in minor surgical procedures performed in these locations.

Considerations

Benzocaine sprays used in the mouth and throat can result in potentially dangerous levels of methemoglobinemia.

Patients who have breathing problems such as asthma, bronchitis, or emphysema, patients with heart disease, and patients who smoke are at greater risk for complications related to methemoglobinemia and may be candidates for other forms of therapy.

Patients who may have greater tendency for elevated levels of methemoglobinemia, such as all children less than 4 months of age and older patients with certain in-born defects (such as glucose-6-phosphodiesterase (G-6-PD) deficiency, hemoglobin-M disease, NADH-methemoglobin reductase (diaphorase 1) deficiency, and pyruvate-kinase deficiency) may benefit from products with different active ingredients such as lidocaine.

Patients who receive benzocaine sprays should be given the minimum amount needed, to reduce the risks associated with methemoglobinemia.

Patients who receive benzocaine sprays should be carefully observed for signs of methemoglobinemia including pale, gray or blue colored skin, headache, lightheadedness, shortness of breath, anxiety, fatigue and tachycardia (rapid heart rate).

Methemoglobinemia makes a standard device used to assess the amount of oxygen bound to hemoglobin (2-wavelength pulse oximetry) unreliable. If blood is drawn to check for the condition, a co-oximeter is needed to reliably detect methemoglobinemia.

A characteristic color of the blood (chocolate-brown rather than blood-red) can be a danger sign, but these changes are a late sign of the condition.

Patients suspected of having high levels of methemoglobinemia should be promptly treated.

Methemoglobinemia is a condition where too much of the hemoglobin in red blood cells becomes unable to bind and carry oxygen. While there is treatment available, until the condition is reversed, oxygen is not effectively delivered throughout the patient’s body. Patients with methemoglobinemia can suffer effects ranging from headache to cyanosis (turning blue due to lack of oxygen) that can be life-threatening in the most severe cases. Patients with underlying breathing problems, such as asthma or emphysema, patients with heart disease, and those who smoke may be more susceptible to the problems from methemoglobinemia and may suffer from bad effects from this condition at lower levels of methemoglobin than healthy individuals. Similarly, some patients may lack or have reduced level of enzymes that help reverse the methemoglobinemia, and they are also more susceptible to risks associated with benzocaine sprays.

The VA health system has announced its decision to remove benzocaine sprays from their practice because they believe other topical anesthetics are less likely to cause methemoglobinemia and because the procedures themselves might cause similar signs, suggesting that methemoglobinemia may occur but go unrecognized in some cases. The FDA has received adverse event reports involving benzocaine sprays together with symptoms that probably indicated methemoglobinemia in the patients. It is important to note also that these cases were received over a period of many years and this is an uncommon adverse event. The FDA is continuing to review all available safety information for these affected products.

1 In addition to benzocaine, Cetacaine® also contains butyl aminobenzoate and tetracaine as active ingredients.

The contents, unless otherwise specified, are copyrighted by © EMS House of DeFrance.

http://www.defrance.org and/or http://www.emshouse.com

[Eydawn]

So how does one treat methemoglobinemia? I assume that it needs some sort of chemical intervention because the problem lies in having too high a ratio of inactive hemoglobin (methemoglobin) and subsequent hypoxia; how would one reverse that?

Wendy

NREMT-B

[AZCEP]

From eMedicine:

Pathophysiology: Oxidation of iron to the ferric state reduces the oxygen-carrying capacity of hemoglobin and produces a functional anemia. In addition, a ferric heme group affects nearby ferrous heme groups. Ferric heme groups impair the release of oxygen from nearby ferrous heme groups on the same hemoglobin tetramer. The result of methemoglobinemia is that oxygen delivery to tissues is impaired and the oxygen hemoglobin dissociation curve shifts to the left.

Organs with high oxygen demands (ie, CNS, cardiovascular system) usually are the first systems to manifest toxicity. Oxygenated blood is red, deoxygenated blood is blue, and blood-containing methemoglobin is a dark reddish brown color. This dark hue imparts clinical cyanosis when methemoglobin levels are at 1.5 g/dL (approximately 10-15% methemoglobin concentration); however, a level of 5 g/dL of deoxygenated blood is required for similar effects. Therefore, when methemoglobin levels are relatively low, cyanosis may be observed without cardiopulmonary symptoms.

Removal of the patient from the offending environment must be attempted by properly trained and equipped personnel

Methylene blue is the first-line antidotal therapy.

Methylene blue accelerates the enzymatic reduction of methemoglobin by NADPH-methemoglobin reductase and also reduces to leucomethylene blue that, in turn, reduces methemoglobin. The initial dose is 1-2 mg/kg IV over 5 min. Its effects should be seen in approximately 20 min to 1 h. Patients who are exposed may require repeated dosing, but high doses of methylene blue may actually induce a paradoxical methemoglobinemia.

Treatment failure may occur in patients with ongoing exposure, patients exposed to sulfhemoglobinemia, and patients who have deficient NADPH-methemoglobin reductase enzymatic pathways. Methylene blue should be avoided in patients with G-6-PD deficiency, if possible, because case reports and in vitro models suggest that this antidote may induce hemolysis in this patient population.

Hyperbaric oxygen and exchange transfusion should be considered for patients who are not candidates for methylene blue treatment or when methylene blue is ineffective.

Because of the disparity of HBO facilities, high concentrations of oxygen should be administered as early as possible.

Methylene blue is also popular at parties. You can readily identify if someone is using your pool as a community urinal with a few drops in their drink.

[medic429]

While there is treatment available' date=' until the condition is reversed, oxygen is not effectively delivered throughout the patient’s body. Patients with methemoglobinemia can suffer effects ranging from headache to cyanosis (turning blue due to lack of oxygen) that can be life-threatening in the most severe cases. Patients with underlying breathing problems, such as asthma or emphysema, patients with heart disease, and those who smoke may be more susceptible to the problems from methemoglobinemia and may suffer from bad effects from this condition at lower levels of methemoglobin than healthy individuals.

[als_medic_uk]

Methaemoglobinaemia is treated with the use of methylene blue, which reintroduces haemoglobin to its normal oxygen-distributing state.