Naproxen-induced methemoglobinemia in an alcohol-dependent patient
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American Journal of Emergency Medicine
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Naproxen-induced methemoglobinemia in an alcohol-dependent patient
Abstract
The authors report a case of acute methemoglobinemia in a patient treated with naproxen for the common cold. A 42-year-old Asian woman began taking naproxen sodium and methocarbamol for mylagia, chills, and coughing. On the day prior to her emergency department (ED) admission, the patient was taking lorazepam, trazodon, and paroxetine in addition to the naproxen and methocarbamol prescribed for the cold symptoms, and she also ingested approximately 300 mL of 20% alcohol. Upon awakening the next morning, the patient experienced dyspnea and dizziness. At the hospital, she was diagnosed with severe methemoglobinemia. After initiation of Methylene blue therapy, the patient’s symptoms improved substantially and her serum metHemoglobin levels decreased. After 10 days in the hospital, the patient was discharged without any complications. Naproxen is known to cause oxidative stress. Alcohol is known to reduce G6PD activity, and thus it is hypothesized that the administration of naproxen in an alcohol-dependent patient caused methemoglobinemia.
Naproxen, or (S)-6-methoxy-?-methyl-2-naphthalene Acetic acid, is a fairly effective and clinically safe non-steroidal anti-inflammatory drug that is broadly used as a treatment for rheumatoid arthritis. Naproxen’s known side effects are gastrointestinal problems, neph- rotoxicity, hepatotoxicity and hemolytic anemia [1-4]. However, there are no reports of methemoglobinemia occurring after admin- istration of naproxen in the literature. We report a case of successful treatment of methemoglobinemia in a patient who received naproxen as treatment for a general upper respiratory infection.
A 42-year-old Asian woman visited the ED after First visiting another medical institution; the patient’s chief complaints being were symptoms of dyspnea and dizziness, which had begun 2 hours prior. The patient had been taking 333 mg of acamprosate for 6 months for alcohol dependence. The patient had begun taking 275 mg of naproxen sodium and 250 mg of methocarbamol for myalgia, chills and coughing 3 days prior to her ED admission. The patient reported drinking 300 to 600 mL of 20% alcohol daily for the past 6 months prior to the ED visit. On the evening before the ED visit, the patient went to bed after ingesting the prescribed lorazepam, trazodon and paroxetine, as well as naproxen and methocarbamol for the cold symptoms, and approximately 300 mL of 20% alcohol.
Upon visiting the ED, the patient’s vital signs were as follows: blood pressure 121/81 mmHg, heart rate 107 bpm, respiratory rate 20 bpm, body temperature 37.6?C and 88% O2 saturation. The patient complained of general weakness, chest discomfort, nausea, and vomiting. Upon exami- nation, the patient exhibited cyanosis and was utilizing accessory muscles for respiration. However, upon auscultation, her breathing sounds were clear. The patient’s arterial blood gas analysis results during administration
of oxygen via a reservoir mask with an oxygen flow of 15 L/min were pH 7.51, pCO2 25 mmHg, pO2 231 mmHg, and HCO- 19.9 mmHg. Laboratory results showed a white blood cell count of 10110/mm3, Hb of 13.4 g/dL and platelet count of 169000/mm3. Blood chemistry results showed the following: BUN, 10 mg/dL; creatinine, 0.71 mg/dL; AST, 59 IU/L; ALT, 70 IU/L. Blood electrolyte results and chest PA results showed no abnormalities, and an electrocardiogram displayed normal sinus rhythm. Prior to the patient’s visit to our ED, her laboratory results from another medical facility reported her methemoglobin (metHb) volume percent at 46.8%, and her metHb volume percentage decreased to 4.1% in our ED after administration of 140 mg of methylene blue. The patient’s metHb volume percent then rose to 13.1% by the third hospital day but decreased afterwards.
The patient was initially treated with 140 mg of methylene blue to treat methemoglobinemia due to drug administration. Two hours following admission to the ED, the patient was treated with an additional 60 mg of methylene blue and sent to the intensive care unit, where she received two units of 400 mL of Packed red blood cells at 8 hours after admission to the ED. At 12 hours, the patient showed worsening dyspnea and cyanosis, and she was therefore given an additional 70 mg of methylene blue. On the third hospital day, the patient received treatment for an alcohol withdrawal seizure; the patient’s electroencephalogram results were normal. On the fourth hospital day, the patient’s dyspnea improved. The patient was discharged without complications on the tenth hospital day.
3
Methemoglobin is hemoglobin in which the heme has been oxidized from the ferrous (Fe2+) to the ferric state (Fe3+), rendering it incapable of binding and transporting oxygen [5]. The condition may arise as a result of a genetic defect in red blood cell metabolism or hemoglobin structure, or it may be acquired following exposure to various oxidant drugs or toxins [6]. The patient reported here drank alcohol daily. Alcohol decreases the level of antioxidants, and the by-products of alcohol metabolism, such as acetaldehyde, react with proteins and lipids, resulting in radical formation. This results in oxidative stress that causes cell damage. In erythrocytes, radical formation is known to reduce G6PD activity [7,8].
Naproxen is a non-selective nonsteroidal anti-inflammatory drugs that increases the expression of nicotinamide adenine dinucleotide phosphate oxidase mRNA. This increases levels of Reactive oxygen species, which causes oxidative stress to the cardiovascular system. Non-selective inhibitors such as naproxen and diclofenac increase the amount of superoxide more than cyclooxygenase 2-selective inhibitors [9]. Further- more, there are numerous case reports of methemoglobinemia in G6PD- deficient patients who were treated with anticancer drugs or other drugs that cause oxidative stress. There has also been a report of methemoglo- binemia occurring after administration of celecoxib [10].
Although the specific mechanism is unknown, this information
implies that the patient’s methemoglobinemia was caused by the
0735-6757/(C) 2014
combined action of naproxen and alcohol as oxidative stressors in a reduced G6PD activity state induced by alcohol consumption. Thus, care must be taken when administrating naproxen, as it may cause oxidative stress in an alcohol-dependent patient, resulting in a serious complication such as methemoglobinemia.
Won Suk Lee, MD Jang Young Lee, MD? Won Young Sung, MD Sang Won Seo, MD
Department of Emergency Medicine
College of Medicine Eulji University
Daejeon, Republic of Korea
?Corresponding author. Eulji University Hospital
1306 dunsan-dong, Seo-gu Daejeon, Republic of Korea
E-mail address: [email protected] http://dx.doi.org/10.1016/j.ajem.2014.04.027
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