Acquired Methemoglobinemia in the Surgical Intensive Care Unit.

Acquired methemoglobinemia is a potentially lethal medical condition caused by exposure to oxidizing xenobiotics, including antibiotics such as dapsone and inhaled anesthetics such as benzocaine. In this case report, we describe two presentations of acquired methemoglobinemia which presented to our surgical intensive care unit within one month. This highlights the potential connection between an emergent surgery or procedure and the development of methemoglobinemia in an environment where it is presumed that this condition would be extremely rare. High clinical suspicion for methemoglobinemia is warranted if the patient develops cyanosis or a decreased oxygen saturation unresponsive to supplemental oxygen when another etiology is not identifiable. If methemoglobinemia is suspected, a direct measurement of blood methemoglobin levels can be obtained to confirm the diagnosis. Prompt treatment with intravenous methylene blue is highly effective.

Asymptomatic benzocaine spray-induced methaemoglobinaemia in preoperative sedation for oesophagogastroduodenoscopy.

Methaemoglobinaemia is defined as elevated methaemoglobin in the blood which is characterised by conversion of some of the reduced ferrous iron elements [Fe2+] to the oxidised ferric [Fe3+] form which does not have capacity to bind and transport oxygen resulting in functional anaemia. Causes can be genetic mutations or acquired by medications such as dapsone, nitrates or benzocaine. Benzocaine is currently being used as a topical anaesthetic agent before certain procedures. We report a case of benzocaine spray-induced methaemoglobinaemia in a patient who underwent oesophagogastroduodenoscopy for evaluation of upper gastrointestinal bleeding.

A Case Report of Benzocaine-Induced Methemoglobinemia.

Methemoglobinemia is a serious medical condition characterized by the disrupted binding of oxygen to iron on hemoglobin, with a consequent impaired oxygen delivery to body tissues. Various drugs including the local anesthetics such as benzocaine can cause acquired methemoglobinemia. The reported case describes methemoglobinemia that occurred in association with the use of topical benzocaine spray and lozenges in a previously healthy 51-year-old female who had undergone colon surgery to remove a bleeding polyp. Pulse oximetry revealed the patient was hypoxic and a measured methemoglobin (MetHB) serum concentration was 32.4%, well above the normal of less than 2%. Treatment with intravenous methylene blue resulted in a rapid improvement in the patient's respiratory status. The case emphasizes the need for practitioners to appreciate that topical benzocaine products can cause potentially fatal methemoglobinemia.

Topical Benzocaine and Methemoglobinemia.

Methemoglobinemia can cause life-threatening hypoxia associated with cyanosis and dyspnea not responsive to oxygen. We present a case of recurrent methemoglobinemia because of occult use of topical benzocaine to the vulva. A 47-year-old female with medical history of vulvar cancer and HIV undergoing chemoradiation was sent by the oncology clinic to the emergency department for worsening dyspnea, fatigue, hypoxia to 78% on room air, and gradual onset of cyanosis over the past week. A methemoglobin (MetHb) level was 49%. She received methylene blue, and repeat MetHb levels initially decreased but later increased to 56% despite continued treatment. Additional interviews with the patient revealed she was applying vagicaine (20% benzocaine), an over the counter preparation to the vulvar area for analgesia, and she continued application while hospitalized. She received a total of 6 mg/kg methylene blue and underwent vaginal lavage with 60 mL of sterile saline and cleansed with soapy water. Cyanosis, hypoxia, and dyspnea resolved, and the MetHb level decreased to 5.4% on the day of discharge. Benzocaine is a frequent cause of iatrogenic methemoglobinemia. In this case, additional medication inquiries were helpful in making the diagnosis. Many patients do not consider over-the-counter medications to be potentially harmful. Methemoglobinemia from occult topical benzocaine administration to the vulva is an uncommon exposure route. Occult medication use can be a source of methemoglobinemia.

Lidocaine contact allergy is becoming more prevalent.

BACKGROUND: Allergic contact dermatitis (ACD) to lidocaine is rising in prevalence. This is due to a growing number of over-the-counter (OTC) products containing topical amide and ester anesthetics. The phenomenon poses a real threat to the authors' surgical anesthetic options. OBJECTIVE: To investigate the epidemiology of topical anesthetic ACD in British Columbia, Canada and provide an approach for clinicians to deal with this problem. MATERIALS AND METHODS: A retrospective chart review of 1,819 patients who underwent patch testing at the University of British Columbia Contact Dermatitis Clinic between January 2009 and June 2013 was completed. The authors also performed a detailed review of Canadian OTC preparations containing lidocaine in 2013. RESULTS: The prevalence of ACD to local anesthetics is significant at 2.4%. The most common allergen is benzocaine (45%) followed by lidocaine (32%) and dibucaine (23%). CONCLUSION: The proportion of ACD caused by lidocaine is higher than expected. This is likely secondary to an increase in OTC medicaments containing lidocaine. Patients who are patch test-positive to a local anesthetic should be challenged intradermally to confirm clinical relevance. Because ACD is a delayed Type IV hypersensitivity reaction (localized dermatitis), the risk of anaphylaxis is not a concern.

The effect of oral topical anesthesia on the characteristics of voice.

OBJECTIVES/HYPOTHESIS: Although oral topical anesthesia is used routinely before rigid laryngeal endoscopy, no study has determined whether oral topical anesthesia changes voice quality. Our goal was to determine the effects of topical anesthesia on voice. STUDY DESIGN: Prospective cohort study. METHODS: Adult patients presenting to a laryngology practice who required rigid laryngeal endoscopy as part of the routine clinical visit were eligible for the study. Voices were recorded before and after oral topical benzocaine (14%)/butamben (2%)/tetracaine (2%) (ie, cetacaine) spray. Consensus auditory perceptual evaluation of voice (CAPE-V) protocol was used for the voice recordings and was the primary outcome measure. Recordings were presented randomly to two blinded speech-language pathologists specialized in voice. Secondary outcome measures were fundamental frequency (F0), jitter, shimmer, and noise-to-harmonics ratio (N/H) on sustained /i/ and speaking F0. RESULTS: One hundred two patients participated in the study. There was no significant difference in CAPE-V measurements before and after topical anesthesia for all six attributes: overall severity (P = 0.145), roughness (P = 0.214), breathiness (P = 0.761), strain (P = 0.053), pitch (P = 0.301), and loudness (P = 0.320). There was no significant difference in jitter (P = 0.315), shimmer (P = 0.942), N/H (P = 0.128), and speaking F0 (P = 0.320). F0 /i/ decreased by a mean of 4.8Hz, which was statistically significant (P = 0.003), but probably not clinically significant. CONCLUSION: There was no clinically significant voice change after oral topical anesthesia.

Occupational contact dermatitis in hairdressers: an analysis of patch test data from the Danish contact dermatitis group, 2002-2011.

BACKGROUND: Occupational contact dermatitis among hairdressers is frequent, owing to daily exposure to irritants and allergens. OBJECTIVES: To identify sensitization to the most common allergens associated with the occupation of hairdressing. METHODS: Patch test results of 399 hairdressers and 1995 matched controls with contact dermatitis, registered by the Danish Contact Dermatitis Group between January 2002 and December 2011, were analysed. All patients were patch tested with the European baseline series, and hairdressers were additionally tested with the hairdressing series. RESULTS: Occupational contact dermatitis (p < 0.001) and hand eczema (p < 0.001) were observed significantly more often among hairdressers than among controls. Atopic dermatitis was less commonly observed among hairdressers (21.3%) than among controls (29.4%) (p < 0.01). Allergens from the European baseline series with a statistically significant association with the occupation of hairdressing were p-phenylenediamine, thiuram mix, and benzocaine. Frequent sensitizers from the hairdressing series were ammonium persulfate, toluene-2,5-diamine, 3-aminophenol, and 4-aminophenol. Cysteamine hydrochloride and chloroacetamide emerged as new sensitizers. CONCLUSIONS: These results indicate a healthy worker effect among hairdressers diagnosed with eczema. Ammonium persulfate and p-phenylenediamine remain frequent sensitizers in hairdressers with contact dermatitis. Cysteamine hydrochloride and chloroacetamide should be included in future surveillance studies.

Benzocaine and clove oil as anesthetics for pejerrey (Odontesthes bonariensis) fingerlings / Benzocaina e óleo de cravo como anestésicos para alevinos de peixe-rei (Odontesthes bonariensis)

Pejerrey (Odontesthes bonariensis) is a native species from Rio Grande do Sul, Uruguay and Argentina where it is of great economic importance for artisanal fishing. One difficulty in laboratory research with pejerrey is related to its sensitivity, as it presents higher basal cortisol levels than other freshwater species. For this reason, the aim of this work was to evaluate the efficiency of benzocaine and clove oil as anesthetics for pejerrey fingerlings. Two experiments were done where fingerlings (57±7.8mm and 1.1±0.44g) were exposed to benzocaine with concentrations between 40mgL-1 and 120mgL-1 and to clove oil with concentrations between 12mgL-1 and 75mgL-1. Survival, anesthesia induction time and recovery time for each pharmaceutics were evaluated. Both benzocaine and clove oil pharmaceutics showed efficiency as anesthetics for pejerrey fingerlings, with negative correlation between the dose of anesthetics and the anesthesia induction time. For benzocaine, the concentrations between 80mgL-1 and 100mgL-1 showed better results, as for clove oil the optimal concentrations were between 25mgL-1 and 50mgL-1. On the other hand, the anesthesia recovery time did not present significant variation on the different concentrations of the tested products. The tested products are highly metabolizable by pejerrey.

O peixe-rei (Odontesthes bonariensis) é uma espécie nativa do Rio Grande do Sul, Uruguai e Argentina, onde tem grande importância econômica para a pesca artesanal. Uma dificuldade da pesquisa em laboratório com peixe-rei está relacionada à sua sensibilidade, pois apresenta níveis basais de cortisol mais elevados que outras espécies de água doce. Este trabalho avaliou a eficiência da benzocaína e do óleo de cravo como anestésicos para alevinos de peixe-rei. Foram realizados dois experimentos em que alevinos (57±7,08mm e 1,1±0,44g) foram expostos à concentração entre 40mg-1 e 120mgL-1 de benzocaína e entre 12mgL-1 e 75mgL-1 de óleo de cravo. Avaliaram-se a sobrevivência, o tempo de anestesia e o tempo de recuperação para cada um dos fármacos. Ambos os fármacos, benzocaína e óleo de cravo, mostraram eficiência para anestesiar peixe-rei, com correlação negativa entre a dose e o tempo de indução de anestesia. Para benzocaína, concentrações entre 80mgL-1 e 100mgL-1 mostraram melhor resultado, enquanto para óleo de cravo as melhores concentrações ficaram entre 25mgL-1 e 50mgL-1. Por outro lado, o tempo de recuperação do estado de anestesia não apresentou variação significativa nas diferentes concentrações testadas. O peixe-rei tem elevada capacidade de metabolização dos produtos testados.

Methemoglobinemia in bronchoscopy: a case series and a review of the literature.

BACKGROUND: Methemoglobinemia results from oxidation of ferrous iron to ferric iron within the hemoglobin molecule. This molecule cannot bind oxygen and increases the affinity of normal hemoglobin for oxygen, which results in decreased oxygen offloading in peripheral tissues. At elevated levels, methemoglobinemia can cause dyspnea, cyanosis, and even death. Common local anesthesia agents have been correlated with methemoglobinemia. Bronchoscopy is a commonly performed clinical procedure which uses topical application of these anesthetics to provide patient comfort. Methylene blue is an agent thought to help reverse the effects of methemoglobinemia by facilitating the methemoglobin reductase system. METHODS: Using multiple search engines including PubMed and the Cochrane Database, available data on cases of methemoglobinemia after bronchoscopy were pooled. Adult and pediatric cases were considered. RESULTS: Eleven cases were identified. Cases occurred from 1977 until present. Data gathering was complicated by the fact that a consistent reporting system was not used across cases. Arterial blood gas data and CO-oximetry reported levels of methemoglobin were reported where available. No patients died from methemoglobinemia. The most common finding across all patients was decreased peripheral oxygen saturation. Cyanosis was also frequently reported. There was a disparity between the low peripheral oxygen saturation which was reported and the pO(2) on the arterial blood gas. Dose and type of anesthetic agent varied widely across studies. CONCLUSIONS: Using topical anesthetic during bronchoscopy appears relatively safe. No fatalities from methemoglobinemia after bronchoscopy have been reported. A high suspicion for methemoglobinemia is required in patients who develop hypoxia or cyanosis postprocedurally. Access to CO-oximetry can confirm the diagnosis but the clinical picture is often sufficient to proceed with methylene blue treatment or observation, based on how severely the patient is affected. Patients who return to baseline can be considered for discharge home.

Methemoglobinemia in patients undergoing esophagogastroduodenoscopy: a randomized controlled trial.

BACKGROUND: Methemoglobinemia is a potentially life-threatening complication of local anesthetic sprays employed in upper endoscopy. There is limited information available on the incidence of this complication, and no prospective trial has ever undertaken to evaluate subclinical levels of methemoglobinemia. OBJECTIVE: To evaluate the incidence of subclinical methemoglobinemia in patients exposed to anesthetic spray. METHODS: Subjects were randomized to a "spray" or "no-spray" group. Subjects in the "spray" group received a 1-second benzocaine spray before upper endoscopy. All subjects in both groups were monitored with a noninvasive co-oximetry device capable of detecting methemoglobin levels in real time. RESULTS: 401 subjects were enrolled (209 in the study group, 192 in the control group); mean peak methemoglobin concentrations were 0.82% (CI 0.74-0.90%, SD 0.57%) and 0.80% (CI 0.73-0.86%, SD 0.46%) respectively. There was no statistically significant difference between the two groups (p = 0.69). Only 3 (1.4%) subjects in the study group and 2 (1%) subjects in the control group had a peak methemoglobin concentration >2%. CONCLUSIONS: In this randomized clinical trial, no significant elevation of methemoglobin concentration was observed in any subject. Final analysis failed to demonstrate any statistically significant difference between the two groups.

Risk of topical anesthetic-induced methemoglobinemia: a 10-year retrospective case-control study.

IMPORTANCE: Methemoglobinemia is a rare but serious disorder, defined as an increase in oxidized hemoglobin resulting in a reduction of oxygen-carrying capacity. Although methemoglobinemia is a known complication of topical anesthetic use, few data exist on the incidence of and risk factors for this potentially life-threatening disorder. OBJECTIVE: To examine the incidence of and risk factors for procedure-related methemoglobinemia to identify patient populations at high risk for this complication. DESIGN AND SETTING: Retrospective study in an academic research setting. PARTICIPANTS: Medical records for all patients diagnosed as having methemoglobinemia during a 10-year period were reviewed. EXPOSURES: All cases of methemoglobinemia that occurred after the following procedures were included in the analysis: bronchoscopy, nasogastric tube placement, esophagogastroduodenoscopy, transesophageal echocardiography, and endoscopic retrograde cholangiopancreatography. MAIN OUTCOMES AND MEASURES: Comorbidities, demographics, concurrent laboratory values, and specific topical anesthetic used were recorded for all cases. Each case was compared with matched inpatient and outpatient cases. RESULTS: In total, 33 cases of methemoglobinemia were identified during the 10-year period among 94,694 total procedures. The mean (SD) methemoglobin concentration was 32.0% (12.4%). The methemoglobinemia prevalence rates were 0.160% for bronchoscopy, 0.005% for esophagogastroduodenoscopy, 0.250% for transesophageal echocardiogram, and 0.030% for endoscopic retrograde cholangiopancreatography. Hospitalization at the time of the procedure was a major risk factor for the development of methemoglobinemia (0.14 cases per 10,000 outpatient procedures vs 13.7 cases per 10,000 inpatient procedures, P < .001). CONCLUSIONS AND RELEVANCE: The overall prevalence of methemoglobinemia is low at 0.035%; however, an increased risk was seen in hospitalized patients and with benzocaine-based anesthetics. Given the potential severity of methemoglobinemia, the risks and benefits of the use of topical anesthetics should be carefully considered in inpatient populations.

Methemoglobinemia in postchemotherapy stomatitis topical treatment: 2 pediatric cases.

Methemoglobinemia is a rare congenital or acquired disease of increased blood methemoglobin concentration. We documented 2 cases of children suffering from neuroblastoma whose postchemotherapy anemia, leucopenia, and stomatitis were complicated by methemoglobinemia after using a formulary oral gel (7.5% benzocaine, doxycycline, nystatin, glycerin). The complication resulted in hospital treatment. Percutaneous oxygen saturation remained at 85% and 87% despite administration of 100% oxygen through a nonrebreather mask. Arterial blood gas analysis showed an oxygen saturation of 98% and 97%, respectively. Spectroscopic measurement showed methemoglobin concentration of 42% and 35.5%, respectively. After red blood cell transfusion and oral ascorbic acid in case 1 and methylene blue in case 2, the patients' condition improved. Although the benzocaine gel is not in use in several medical systems, it should be considered as a possible reason for methemoglobinemia.

Benzocaine-induced methaemoglobinaemia: a case study.

Benzocaine is a widely used topical anaesthetic and has been reported to cause toxic methaemoglobinaemia in otherwise healthy individuals with no predisposing risk factors. This article reports on a rare case of benzocaine-induced methaemoglobinaemia following adenotonsillectomy in a 5-year-old girl. Topical benzocaine was applied orally for the relief of postoperative wound pain on the eighth postoperative day. Two hours after application, generalized cyanosis, mild dyspnoea and some degree of agitation developed. The methaemoglobin level was 38.5%. Treatment with methylene blue was initiated immediately. Symptoms completely disappeared 4 hours after initiation of methylene blue therapy. The further course was uneventful. Therefore, all health professionals should be aware that topical anaesthetics after surgery can induce methaemoglobinaemia in children, even after a prolonged interval, and especially when applied on wound surfaces.

Methemoglobinemia secondary to over-the-counter Anbesol.

BACKGROUND: Methemoglobinemia is a potentially lethal condition which may result from exposure to benzocaine. It must be treated promptly, because it may cause a significant decrease in oxygen delivery to tissues and organs. CASE DESCRIPTION: A 39-year-old caucasian man presented to the emergency department (ED) with dental pain. After a review of systems and a dental exam, an oxygen saturation of 90% was noted. The patient reported no previous cardiac or pulmonary pathology, but did report using a large amount of over-the-counter Anbesol. A second oxygen saturation measurement had fallen to 87%. An arterial blood gas sample was taken, and the patient was found to have high levels of methemoglobin. He was transferred to the critical care ED and treated with 2 mg/kg intravenous methylene blue. CLINICAL IMPLICATIONS: Dentists must be aware of the possible lethal effects of benzocaine toxicity, including methemoglobinemia. It is important to recognize the signs and symptoms and act in a judicious manner.

Infection and the risk of topical anesthetic induced clinically significant methemoglobinemia after transesophageal echocardiography.

BACKGROUND: Methemoglobinemia is a recognized complication of topical anesthesia with benzocaine during transesophageal echocardiography (TEE). Though several risk factors have been described, the importance of individual factors is not known. We performed a retrospective study to identify determinants of the risk of methemoglobinemia. MATERIALS AND METHODS: All patients who underwent TEE with benzocaine topical anesthesia between June 2005 and June 2007 were included in this retrospective study. RESULTS: Of the 886 patients who were included in the study, 140 had active infection (15.8%). The incidence of methemoglobinemia in this group was 2.9% (vs. 0%, P < 0.001). Compared to those without infection, patients in the active infection group were more likely to have a lower hemoglobin (P < 0.001), serum albumin level (P < 0.001), glomerular filtration rate less than 60 ml/min per 1.73 m(2) (P < 0.001), higher rates of dialysis (P < 0.001), a higher incidence of malignancy (P = 0.01), and increased use of acetaminophen and sulfa drugs (P < 0.001). However, multivariate logistic regression analysis did not identify any statistically significant covariates. CONCLUSION: In conclusion, patients with an active systemic infection who undergo TEE are at a higher risk of methemoglobinemia. However, none of the risk factors for methemoglobinemia including active infection reached statistical significance in the regression analysis which has to be interpreted with caution in view of the low event rate.

Severe methemoglobinemia detected by pulse oximetry.

An elderly surgical patient acquired a life-threatening methemoglobinemia as a result of topical benzocaine spray to the oropharynx in preparation for awake endotracheal intubation. A new multiwavelength pulse oximeter, the Masimo Rad-57, detected this methemoglobinemia an hour before it was confirmed by laboratory CO-oximetry. The Rad-57 monitored the patient's methemoglobin levels during diagnosis and treatment with methylene blue, and the values it provided (as high as 33%) were very close to those of the laboratory CO-oximeter. The new pulse oximeter gave continuous readings of methemoglobin level at the bedside, whereas the laboratory values were delayed by up to an hour. This case demonstrates the clinical application of a multiwavelength pulse oximeter in the diagnosis and treatment of a life-threatening dyshemoglobinemia.

Intraoperative detection of methemoglobinemia in a patient given benzocaine spray to relieve discomfort from a nasogastric tube: a case report.

A 27-year-old man who had 2 admissions 1 month apart for abdominal surgery had a high methemoglobin (MHb) level secondary to liberal use of benzocaine oral spray. A co-oximetry level for MHb of greater than 0.30 proportion of total hemoglobin (30.1%) was detected intraoperatively. The patient was successfully treated with methylene blue intravenously and recovered uneventfully. When 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, methemoglobinemia should be considered as a differential diagnosis. This case illustrates the acquired form of methemoglobinemia. Adequate oxygen delivery to the tissues in the body is compromised when MHb overwhelms the capacity of the red blood cells to carry oxygen. If methemoglobinemia is left untreated, it may be fatal.