local anesthesia“>Case Report

Contents lists available at ScienceDirect

American Journal of Emergency Medicine

journal homepage: www. elsevier. com/ locate/ajem

Methemoglobinemia after local anesthesia with prilocaine: a case report

Abstract

local anesthetics are drugs that are commonly used by physicians in simple interventional procedures. O-toluidine, a degradation product of the local Anesthetic agent prilocaine, oxidizes hemoglobin and may cause methemoglobinemia. Normally, hemoglobin is comprised of 1% to 2% methemoglobin in the human body [1]. In this study, we present- ed a case of methemoglobinemia after local anesthesia with prilocaine, including clinical findings of respiratory distress in the early period.

Catheters and subcutaneous venous ports that are implanted under local anesthesia provide safe and easy venous access. They are placed under the skin during minor surgery and can be used for long-term medication administration for approximately 25 years [2]. Local anes- thetics are widely used by physicians in such simple interventional pro- cedures. Local anesthetics are used to eliminate sensory conduction in a part of the body without inducing loss of consciousness. According to their intermediate chain structure, local anesthetics are divided into 2 groups: esters and amides. The amide-structure group (eg, lidocaine, prilocaine, mepivacaine, bupivacaine, and etidocaine) is hydrolyzed in the liver by microsomal enzymes. O-toluidine, a degradation product of prilocaine, oxidizes hemoglobin (Hb) and may cause methemoglobi- nemia. Methemoglobin is a form of Hb that is normally kept below 1% to 2% by regulatory systems (ie, cytochrome b5 reductase) in the human body [1]. In this study, we presented a case of methemoglobinemia after local anesthesia with prilocaine that revealed clinical findings, in- cluding respiratory distress in the early period.

A 40-year-old female patient was brought to our emergency depart- ment complaining of a rash on her face, bruised fingers, and shortness of breath. Her relatives said that she had a Hepatocellular carcinoma diag- nosis and had received chemotherapy. We learned that approximately 2 hours before arriving at our clinic, she underwent placement of an im- planted catheter (port). Prilocaine (30 mL) was applied as a local anes- thetic (citanes 2%, R); approximately 20 to 30 minutes after treatment, she had clinical complaints. We found the following upon physical ex- amination: blood pressure, 140/90 mm Hg; pulse, 96/min; body temperature, 36.4?C; respiratory rate, 27/min; and sO₂, 90%. We initiat- ed 100% oxygen treatment with a mask (10 L/min) and saline infu- sion (100 mL/h). The patient was restless, exhibited tachypneic respiration, and had a normal cardiac examination; and her fingertips appeared cyanotic.

The patient’s electrocardiogram and chest radiograph results were normal. Laboratory analysis revealed the following: Hb, 13.1 g/dL; leukocyte count, 12,860/mm³; thrombocyte count, 474,000/mm³; Blood sugar, 245 mg/dL; Na, 135 mmol/L; and K, 4.1 mmol/L. Arterial blood gas analysis showed the following: pH, 7.46; pCO₂, 28.1 mm Hg; pO₂, 55.7 mm Hg; HCO₃, 20 mEq/L; lactate, 3.6 mmol/L; and methemo- globin, 13.3%. The patient, whose complaints were relatively regressive

with oxygen treatment, was admitted to the emergency intensive care unit for continuation of the methemoglobinemia diagnosis, follow-up, and treatment. In addition to oxygen and saline treatments, vitamin C (2 x 500 mg) and N-acetylcysteine (3 x 300 mg) were administered in- travenously. In the fourth hour, the patient’s circulating blood gas met- hemoglobin concentration was 12%. The patient was seamlessly followed up in the intensive care unit ;and after 8 hours, her blood gas methemoglobin level was 3.8%.

Hemoglobin, found in erythrocytes, is a molecule that contains iron in its ferrous (Fe++) form and is responsible for carrying oxygen to the tissues. Under normal conditions, iron that is present in Hb is diva- lent. Methemoglobin occurs as a result of Hb ferric iron oxidation. Under normal conditions, peripheral cyanosis is 35%, a finding encountered as 2% of circulating Hb. Methemoglobin accumulation is limited to the re- duction speed of ferric iron to ferrous iron by a nicotinamide adenine di- nucleotide methemoglobin reductase enzyme (ie, cytochrome b5 reductase) available in erythrocytes. Methemoglobinemia may occur because of hereditary or acquired reasons. The acquired form, which is more common than the congenital form, occurs as a result of exposure to an agent that causes Hb oxidation in healthy individuals. Many chem- ical substances or drugs that cause methemoglobinemia have been re- ported, such as sulfonamides, dapsone, phenacetin, primaquine, benzocaine, and some local anesthetics [3]. Prilocaine is an anesthetic agent that is known to cause methemoglobinemia and is commonly used as a local anesthetic. Prilocaine’s half-life is 55 minutes; methemo- globin starts to appear 20 to 60 minutes after application [4]. Prilocaine is hydrolyzed in the liver by microsomal enzymes. In Liver failure, elim- ination half-life may be increased. Prilocaine-induced methemoglobine- mia is rather rare, depending on treatment dosage [5]. However, development of methemoglobinemia due to prilocaine use at therapeu- tic doses has also been reported in the literature [6]. The Therapeutic dose of prilocaine 1 to 2 mg/kg; the maximum safe prilocaine dose in adults is 8 mg/kg or 600 mg per application [7,8]. In our case, 600 mg prilocaine was applied and cyanosis developed about an hour after appli- cation. Our patient had known hepatocellular carcinoma, and we believe that methemoglobinemia may have developed because of increased prilocaine half-life elimination. Methemoglobinemia may cause hypoxia by disrupting Tissue oxygenation, which is an emergency in terms of di- agnosis and treatment. When the methemoglobin level exceeds 10%, pe- ripheral cyanosis is observed as the most common manifestation. When methemoglobin concentration exceeds 35%, systemic symptoms occur, such as fatigue, tachycardia, tachypnea, nausea, and vomiting. When methemoglobin concentration exceeds 55%, arrhythmia, acidosis, lethar- gy, stupor, and syncope occur. The blood methemoglobin level in our pa- tient was 13.3%, and there were findings of tachypnea and finger cyanosis. Primary treatment should include oxidant agent removal, and supplemental oxygen should be provided. If the methemoglobin level is less than 20%, then application of the agent responsible for

0735-6757/(C) 2014

methemoglobinemia should be ended; removing the responsible agent is sufficient for treatment. At higher concentrations, intravenous methy- lene blue is the first drug of choice. At a 1- to 2-mg/kg dosage, Methylene blue is given intravenously for at least 5 minutes; and if sufficient clinical improvement does not ensue, the same intravenous dose is administered again an hour later [9]. We did not administer methylene blue because our patient’s methemoglobin level did not exceed 20%.

Prilocaine is a commonly used agent that may cause methemoglobi- nemia. Methemoglobinemia may occur even at therapeutic prilocaine doses; thus, illnesses that may prolong drug elimination should be con- sidered and questioned in detail. In addition, after prilocaine applica- tion, patients should be observed for at least an hour for the emergence of methemoglobinemia clinical findings, as they typically appear between 20 and 60 minutes following prilocaine administration. Our patient’s methemoglobin level was 13.3%. We supplied 100% oxy- gen therapy, saline infusion, and antioxidant therapy to relieve clinical discomfort, shortness of breath, and tachypnea. We then followed our patient closely. Our patient’s methemoglobin level decreased after 4 hours and returned to normal at 12 hours.

Mansur Kursad Erkuran, MD

Arif Duran, MD^? Bekir Baris Kurt, MD Tarik Ocak, MD

Abant Izzet Baysal University Medical Faculty, Department of Emergency

Medicine, Bolu, Turkey

?Corresponding author. Emergency Medicine Abant Izzet Baysal University Medical Faculty Department of Emergency Medicine 14280 Golkoy-Bolu, Turkey

Tel.: +90 374 2534656; fax: +90 374 2534615

E-mail address: [email protected] http://dx.doi.org/10.1016/j.ajem.2014.09.021

References

1. Turkmen E, Kocabay G, Yavuz AS, Ozturk S, Vatansever S, Akkaya V, et al. A case of methemoglobinemia induced by the administration of prilocaine prior to an epilation procedure. J Ist Faculty Med 2005;68:19-21.
2. John TC, Jeffrey PL, MMc Todd, Livingston Sheryl, Joseph AK. A prospective random- ized trial demonstrating valved implantable ports have fewer complications and lower overall cost than nonvalved implantable ports. Am J Surg 2004;188:722-7.
3. Guay J. Methemoglobinemia related to local anesthetics: a summary of 242 episodes.

   Anesth Analg 2009;108:837-45.

   Lunenfeld E, Kane GC. Methemoglobinemia: sudden dyspnea and oxyhemoglobin desaturation after esophagoduodenoscopy. Respir Care 2004;49(8):940-2.

4. Coleman MD, Coleman NA. Drug-induced methaemoglobinaemia. Treatment issues. Drug Saf 1996;14:394-405.
5. Kumar AR, Dunn N, Naqvi M. Methemoglobinemia associated with a prilocainelidocaine cream. Clin Pediatr 1997;36:239-40.
6. Aygencel SG, Akinci E, Pamukcu G. Prilocaine induced methemoglobinemia. Saudi Med J 2006;27:111-3.
7. Karahan MA, Aydogan H, Nacar H, Yucel T, Yalcin G. Methemoglobinemia after

   prilocaine: a case report. J Harran Univ Med Fac 2011;8(3):123-4.

   Ryoo S, Sohn Ch, Oh B, Kim W, Lim K. A case of severe methemoglobinemia caused by Hair dye poisoning. Hum Exp Toxicol 2014;33:103-5.