Which skin color alteration may be observed in a client diagnosed with methemoglobinemia?

Hematologic

Methemoglobin concentrations of 10–15% can cause dark-colored blood and cyanosis. Concentrations of 20–45% can cause lethargy, dizziness, headache, and collapse. Higher concentrations [50–70%] can cause seizures, dysrhythmias, coma, and death. The EIDOS and DoTS descriptions are shown inFigure 1.

Of 28 478 patients undergoing transesophageal echocardiography at the Mayo Clinic under topical local anesthesia with benzocaine there were 19 patients with methemoglobinemia [1 in 1500], 18 of whom were treated with methylthioninium chloride; all had a good outcome [2]. Susceptibility factors were sepsis, anemia, and hospitalization; the authors recommended avoidance of benzocaine in such patients.

There have been other reports of methemoglobinemia after the use of a topical anesthetic spray containing benzocaine [3], including oral spray [4]. The authors of the latter report suggested that the suspicion of methemoglobinemia should be raised if the arterial blood gas with a normal partial pressure of oxygen is inconsistent with a low pulse oximeter reading and with the physical appearance of the patient. The appropriateness of this has been confirmed in another case [5].

A 23-year-old woman with temporomandibular joint pain had fiberoptic intubation while awake for intermedullary maxillary fixation using benzocaine topical anesthesia. Her oxygen saturation on pulse oximetry remained in the range of 91–93% despite ventilation with 100% oxygen and cyanosis of the lips and nail beds. Based on the clinical signs and blood gas analysis, methemoglobinemia was diagnosed.

Cases of methemoglobinemia have been reported after the use of benzocaine in many different settings, including endoscopy [6], transesophageal echocardiography [7,8], percutaneous gastrostomy tube placement [9], and intubation [10–12]. There were no deaths and all the patients recovered fully when treated with methylthioninium chloride [methylene blue] 1–2 mg/kg. The problem arises in both adults and children [13–16], and the risk has led to criticism of its free availability. It has, amongst other things, been suggested that it should be eliminated from products for use in children, that concentrations in over-the-counter products should be limited, and that there should be explicit label warnings of the hematological risk [13,17]. Early diagnosis and treatment are crucial, as the condition is potentially fatal, particularly in neonates.

Five cases of benzocaine-induced methemoglobinemia were reported in 1998, following its use for transesophageal echocardiography [18–21]. Methemoglobin concentrations over 15% can lead to cyanosis, while concentrations over 70% lead to circulatory collapse and death [20,21]. The degree of methemoglobinemia depends on the total dose of drug and any factors that enhance systemic absorption. The elderly and neonates are particularly susceptible to methemoglobinemia, as are those with inherited methemoglobin reductase deficiency or the abnormal hemoglobin M. Adequate monitoring and observation of patients both during and after transesophageal echocardiography is essential, as this rare complication of benzocaine and other local anesthetics, such as prilocaine, is both potentially fatal and eminently treatable.

Severe methemoglobinemia was suspected in a 1-year-old infant after topical application of 10% benzocaine ointment around an enterostomy; on postoperative day 3 the SpO2 was 90% and arterial blood was dark red in color [22].

General information

Benzocaine is a poorly soluble local anesthetic, an ester of para-aminobenzoic acid. It is used in many countries as a component of some free-sale formulations for topical use, for example in skin creams, as a dry powder for skin ulcers, as throat lozenges, and as teething formulations for young children. It is also used in aerosol sprays when anesthetizing the oropharynx. Relatively high concentrations of local anesthetic are required to be effective topically, increasing tissue penetration and the risk of subsequent toxicity. Benzocaine formulations are available in concentrations of 1–20%.

Lidocaine [Xylocaine], Benzocaine, Tetracaine [Mucous Membranes]

Wolfe and colleagues reported in 2000 that atomized lidocaine 4% solution decreased the discomfort of nasogastric tube placement.The combination of 1.5 mL atomized lidocaine applied intranasally plus 3.0 mL applied oropharyngeally plus 5 mL 2% lidocaine jelly applied intranasally is superior to jelly alone. Caution should be used because of impaired swallowing after use. Patients should expectorate excess anesthetic to avoid systemic absorption and toxicity. Plasma levels are similar to those obtained with intravenous injection. For viscous solution, do not exceed one tablespoon [15 mL] every 3 hours or one teaspoon [5 mL] of 5% liquid in an adult [seeChapters 5 and 6Chapter 5Chapter 6 for maximum doses]. Ingestion of food should be avoided for at least 1 hour after oral use to prevent aspiration.

Magic mouthwash contains diphenhydramine elixir, Maalox, and 2% viscous lidocaine and is often used for aphthous ulcers or stomatitis. Anbesol is a popular over-the-counter benzocaine preparation used for dental pain. HurriCaine/Americaine/Cetacaine spray is useful for many oral procedures. It is available in various flavors, requires a prescription, and contains benzocaine. Another compounded formula used for mucous membranes contains lidocaine, prilocaine, and tetracaine [Profound, Steven’s Pharmacy].

Benzocaine

Benzocaine is a derivative of procaine in which the amino terminus is lacking. Poorly soluble in aqueous fluid, benzocaine tends to remain at the site of application and is not readily absorbed into the systemic circulation. Because of its low toxic potential, benzocaine is especially useful for anesthesia of large surface areas within the oral cavity. Benzocaine is not totally innocuous, however; cases of methemoglobinemia have been reported after the administration of very large doses, especially in unmetered spray form. Benzocaine is available in a variety of preparations; a 20% concentration in the form of an aerosol spray, gel, ointment, paste, and solution is most commonly advocated for intraoral use. A mucosal gel patch [containing 36 mg per 2-cm-long × 1-cm-wide patch] is also available.

Benzocaine

Unlike lidocaine, benzocaine can be given to children in lozenge and spray formulations. Lozenges are available and can be given to children age 3 years and older [Tyrozets, one lozenge, 5 mg every 3 hours when needed; maximum of six in 24 hours]; adults can take up to eight in 24 hours every 2 to 3 hours when needed [e.g., Tyrozets, Boots anaesthetic and antibiotic throat lozenges]. Additionally, children over the age of 6 can also use a spray formulation [Ultra Chloraseptic, 0.71%, or AAA Spray, 1.5%], for which the dose is one spray every 2 to 3 hours, up to a maximum of eight doses per day. The adult dose is up to three sprays [Ultra Chloraseptic] and two sprays [AAA Sore Throat Spray] repeated every 2 to 3 hours.

C Other Local Anesthetics

Benzocaine is a water-insoluble ester-type local anesthetic agent that is mainly useful for topical application. The onset of action is rapid [