Methemoglobinemia-induced cardio-respiratory failure secondary to topical anesthesia

Acute toxic methemoglobinemia is an infrequent complication of the use of topical anesthetics, most notably benzocaine. The clinical picture is characterized by sudden development of tissue hypoxia without underlying cardiac or respiratory dysfunction, and deceptively normal oxygen saturation on conventional arterial blood gas analysis. This condition may be rapidly fatal and management depends upon prompt recognition, confirmation of clinical suspicion using cooximetry of arterial blood, and quick institution of therapy. We describe the first reported case of cardio-respiratory failure associated with acute toxic methemoglobinemia, which was initially misconstrued as an evolving acute coronary event and rapidly responded to methylene blue therapy.     

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.     

Mechanisms of methylene blue stimulation of the hexose monophosphate shunt in erythrocytes.

The response of the hexose monophosphate shunt in erythrocytes was studied with the ionization chamber-electrometer apparatus to measure continuously 14CO2 derived from 14C-labeled substrates. The effect of methylene blue at high (0.1 mM) and low (1 muM) concentrations was evaluated under different gas mixtures; air, carbon monoxide, and 6% carbon monoxide in air. The latter gas mixture results in nearly 100% carboxyhemoglobin but provides a physiologic partial pressure of oxygen. The extent to which pentose is recycled through the shunt in response to methylene blue stimulation was examined with radioactive glucose substrates labeled on the first, second, and third carbon positions. Generation of hydrogen peroxide after stimulation of erythrocytes with methylene blue was evaluated by the catalase-aminotriazole trapping technique, [14C]formate oxidation, and oxidation of reduced glutatione. Stimulation of the shunt with 1 muM methylene blue was markedly impaired in the absence of oxyhemoglobin, but stimulation with 0.1 mM methylene blue was only slightly impaired under the carbon monoxide-air mixture. The higher concentration of methylene blue produced evidence of hydrogen peroxide generation of all three techniques. Despite the evidence for the involvement of oxygen, oxyhemoglobin, and hydrogen peroxide in the response to methylene blue, cells containing methemoglobin induced by sodium nitrite or from a patient with congenital methemoglobinemia responded normally to methylene blue in the absence of oxygen. These experiments indicate that the reactions induced by methylene blue in erythrocytes are more complex than generally thought and that high concentrations are associated with production of peroxide.     

Cyanosis in a compulsive urine drinker

An 18-year-old gentleman with a habit of compulsive urine drinking was admitted because of repeated vomiting and was noted to be cyanotic. His oxygen saturation was 84% on pulse oximeter but arterial blood gas was normal. He was subsequently confirmed to have methemoglobinemia. He was successfully treated with methylene blue followed by behavioral therapy for his compulsive urine drinking and there was no recurrence of methaemoglobinaemia.     

Local Anesthetic−Induced Methemoglobinemia During Pregnancy: A Case Report and Evaluation of Treatment Options

Background

Methemoglobinemia is a well-recognized adverse drug reaction related to the use of certain local anesthetic agents. The mainstay of treatment for methemoglobinemia is i.v. methylene blue, along with provision of supplemental oxygen; however, methylene blue is listed as a category X teratogen. This poses an issue should methemoglobinemia develop during pregnancy.

Hyperoxia in lethal methemoglobinemia: effects on oxygen transport, tissue oxygenation, and survival in pigs

BACKGROUND: Treatment of severe methemoglobinemia includes the avoidance of methemoglobin-inducing drugs, the application of methylene blue, and the administration of supplementary oxygen. However, the efficacy of the latter on oxygen transport, tissue oxygenation, and survival in the treatment of extreme methemoglobinemia is ambiguous. The objective was to assess whether using hyperoxic ventilation as the sole therapeutic intervention (i.e., ventilation with pure oxygen, Fio2 1.0) improves the short-term (6-hr) survival rate during otherwise lethal methemoglobinemia. DESIGN: Prospective, randomized, controlled study. SETTING: Experimental animal laboratory of a university hospital. SUBJECTS: Fourteen anesthetized, mechanically ventilated pigs. INTERVENTIONS: After induction of profound methemoglobinemia (60 +/- 2%) by the injection of 15 mg/kg 4-dimethylaminophenol, artificial ventilation either was continued with room air (G 0.21, n = 7) or was changed over to hyperoxic ventilation (G 1.0, n = 7). A constant level of methemoglobinemia was maintained by continuous infusion of 4-dimethylaminophenol throughout a 6-hr follow-up period. MEASUREMENTS AND MAIN RESULTS: All animals died within the 6-hr follow-up period, but survival time was prolonged in animals ventilated with pure oxygen (G 0.21, 105 +/- 30 mins; G 1.0, 210 +/- 64 mins, p < .05). No differences were encountered between G 0.21 and G 1.0 with respect to the investigated variables of macrohemodynamics, oxygen transport, and tissue oxygenation. CONCLUSIONS: Hyperoxic ventilation has negligible effects on oxygen transport and tissue oxygenation during lethal methemoglobinemia; nevertheless, survival was increased without severe adverse reactions provoked by hyperoxic ventilation.     

Toxic methemoglobinemia caused by topical anesthetic given before transesophageal echocardiography.

Transesophageal echocardiography was performed on a patient with critical aortic stenosis and severe three-vessel coronary artery disease. Immediately after the procedure the patient experienced marked cyanosis (oxygen saturation of 53%) secondary to methemoglobinemia (methemoglobin saturation of 45%). Toxic methemoglobinemia was thought to be caused by topical anesthetic. He responded dramatically to treatment with intravenous methylene blue. Toxic methemoglobinemia should be suspected in unexplained cyanosis occurring after transesophageal echocardiography and other endoscopic procedures during which potentially causative agents have been used.     

Methemoglobinemia: pathogenesis, diagnosis, and management

The diagnosis of methemoglobinemia should be considered in patients presenting with cyanosis and hypoxia. A variety of frequently used medications are capable of inducing methemoglobinemia, with dapsone and benzocaine being common culprits. Unique features, such as a saturation gap and chocolate-brown-colored blood, can raise suspicion for methemoglobinemia. Typically, symptoms correlate with the methemoglobin level, and treatment with methylene blue is reserved for patients with significantly elevated methemoglobin levels. In the presence of comorbid conditions that impair oxygen transport, however, low-grade methemoglobinemia can become symptomatic and may warrant treatment.     

Severe Methemoglobinemia Linked to Gel-Type Topical Benzocaine Use: A Case Report

Background: Methemoglobinemia is an uncommon cause of tissue hypoxia, but it can be life threatening if it is not identified and treated promptly. Objectives: To highlight the importance of understanding the potential risks of over-the-counter medications, especially in unsupervised use. Topical benzocaine must be used with caution, even in the healthy population. Case report: We report a case of methemoglobinemia secondary to topical benzocaine gel. A 6-year-old boy presented to our Pediatric Emergency Department with cyanosis, vomiting, and lethargy after using a gel-type, 7.5% benzocaine (Baby Orajel®) for a toothache. Physical examination revealed dusky blue skin, tachycardia, tachypnea, and a normal neurologic examination. His percutaneous oxygen saturation remained 77–83% despite the administration of 100% oxygen. His arterial blood sample had a dark chocolate color appearance, and methemoglobinemia was suspected. His methemoglobin level was 69.9%, which is considered a lethal level. After a single dose of methylene blue (1 mg/kg/dose), cyanosis was reduced and oxygenation improved. Conclusion: Over-the-counter topical benzocaine should be used with caution, and the presence of methemoglobinemia must be promptly identified and treated.     

Methemoglobinemia secondary to topical benzocaine use in a lung transplant patient

OBJECTIVE: To report a case of methemoglobinemia secondary to the administration of topical benzocaine spray in an anemic patient who had previously undergone a lung transplant. CASE SUMMARY: A 40-year-old white man with a past medical history significant for lung transplant acutely decompensated following oropharyngeal administration of topical benzocaine spray. Subsequent blood analysis revealed a methemoglobin concentration of 51.2%. Following the administration of a single dose of methylene blue 2 mg/kg intravenously, the patient's respiratory status dramatically improved and stabilized. DISCUSSION: Methemoglobinemia is a rare but potentially fatal condition that may be either acquired or congenital; however, the disorder is most commonly acquired secondary to exposure to oxidizing chemicals, which are often routinely prescribed medications, including benzocaine. Benzocaine can react with hemoglobin to form methemoglobin at a rate that exceeds reduction capabilities, which may result in oxygenation difficulty and respiratory distress. In severe or symptomatic methemoglobinemia, the treatment of choice is methylene blue. CONCLUSIONS: Application of the Naranjo probability scale established a highly probable relationship between topical benzocaine spray and methemoglobinemia and associated respiratory compromise. The risks of palliative use of topical benzocaine in patients with preexisting disorders that compromise oxygen delivery may outweigh any benefit. In our patient, anemia and lung disease increased his risk for clinically significant adverse respiratory events secondary to deficiencies or interferences in oxygen delivery. Topical benzocaine should be administered with caution and careful monitoring in such patient populations.     

Treatment of high-risk,refractory acquired methemoglobinemia with automated red blood cell exchange

Ingestion of strong oxidant substances may result in acquired methemoglobinemia, a clinical condition in which the oxidized blood hemoglobin is incapable of delivering oxygen to the tissues, and the patient becomes cyanotic. Traditional first-line therapy consists of infusion of methylene blue, whose action depends on the availability of reduced nicotinamide adenine nucleotide phosphate (NADPH) within the red blood cell (RBC). Some patients, particularly those who are deficient in glucose-6-phosphate dehydrogenase (G6PD), will not benefit from methylene blue. In these patients, and in some patients who have ingested very strong oxidants, methylene blue may also precipitate Heinz body hemolytic anemia. We present a case of severe, acquired methemoglobinemia in a 26-month-old, 9.8-kg boy with G6PD deficiency. He was cyanotic, in respiratory failure, intubated in a pediatric intensive care unit. In typical fashion, he did not respond to methylene blue. Manual exchange of two whole blood volumes, performed over 4 hr, also failed to resolve his severe methemoglobinemia. An automated RBC exchange (1.3 RBC volume), lowered his methemoglobin content from 31.8% to 7% in a single 40-min procedure. Thereafter his methemoglobin level continued to decrease rapidly and spontaneously. He was discharged home 2 days later, with 0.4% methemoglobin. To our knowledge, this is the first report to demonstrate the (potentially superior) effectiveness of automated RBC exchange for treatment of patients with high-risk acquired methemoglobinemia, that is, those with G6PD deficiency or who have ingested strong oxidants. J. Clin. Apheresis 13:28–31, 1998. © 1998 Wiley-Liss, Inc.     

Methemoglobinemia in a patient undergoing gastrointestinal endoscopy.

OBJECTIVE: To report a case of methemoglobinemia induced by benzocaine in a patient undergoing gastrointestinal endoscopy. CASE SUMMARY: Before undergoing an upper gastrointestinal endoscopy, a 15-year-old girl received 20% benzocaine as a spray, to locally anesthetize the pharyngeal mucosa. Thirty minutes after the endoscopy, the patient suddenly became cyanotic, short of breath, and comatose. She was intubated and transferred to the intensive care unit. Her blood methemoglobin concentration was 54 percent. The patient was treated with intravenous methylene blue. Four hours later she was extubated. She was alert, awake, and asymptomatic. DISCUSSION: This is the fourth reported case of methemoglobinemia induced by benzocaine spray in patients undergoing gastrointestinal endoscopy. Pathways for the formation of methemoglobin in the body are reviewed. Intravenous methylene blue is the drug of choice for this condition, and produces rapid and dramatic reversal of methemoglobinemia. CONCLUSIONS: It is common to use benzocaine spray prior to upper gastrointestinal endoscopy. Benzocaine rarely induces methemoglobinemia in these patients. Prompt diagnosis and treatment with intravenous methylene blue is warranted in such cases.     

Methemoglobinemia induced by indoxacarb intoxication

Indoxacarb is a recently introduced insecticide whose mode of action is blockage of voltage-gated sodium channels. There are limited data on human ingestion. A case of 68-year-old healthy male who presented with general cyanosis because of methemoglobinemia following the ingestion of indoxacarb is presented. After receiving a methylene blue injection, the patient recovered without sequelae.     

Severe Chlorate Poisoning Successfully Treated with Methylene Blue

Background

Chlorate poisoning as a cause of methemoglobinemia is regarded in current literature to be resistant to treatment by methylene blue due to the oxidizing and denaturing properties of the chlorate anion, and often leads to severe renal and hematological complications with a high mortality rate. Recent case studies suggest practitioners have eschewed the use of methylene blue in such situations.

Objectives

This report describes a case of chlorate poisoning presenting as severe methemoglobinemia successfully treated with methylene blue alone, believed to be a first in reported literature.

Case Report

A 34-year-old male construction worker presented 4 h after accidental ingestion of an industrial chemical, with giddiness and breathlessness. Physical examination did not reveal any abnormal cardiorespiratory findings, although arterial blood gas analysis and pulse oximetry revealed an “oxygen saturation gap.” Methemoglobin levels were found to be severely elevated at 66.8% 6 h after ingestion, and the patient was promptly treated with methylene blue. Clinical examination and laboratory tests suggested the absence of hemolysis at the time of treatment. The patient was discharged after a brief and uneventful hospital stay. Subsequent tests revealed the chemical ingested to be sodium chlorate.

Conclusion

The successful outcome in our case suggests that a window of opportunity as long as 6 h may exist during which treatment of chlorate poisoning with methylene blue may be of clinical value. We postulate that the absence of significant hemolysis and hematological alterations at the time of antidote administration may be a necessary prerequisite for treatment success.     

The Acute Treatment of Methemoglobinemia in Pregnancy

Background

Methemoglobinemia can be a potentially lethal condition due to the hypoxic stress placed on the body. In pregnancy, the deleterious effects can be even more catastrophic. The benefits of treatment in all patients, especially in those who are pregnant, must outweigh the inherent risks of the therapies used to treat methemoglobinemia.

Plasmapheresis in severe methemoglobinemia following occupational exposure

Ferrous iron can be converted to ferric iron by oxidative stress which results in the formation of methemoglobin. Consequently, the oxygen dissociation curve is shifted to the left, which leads to tissue hypoxia and ultimately may cause death. Acquired methemoglobinemia can be due to a host of offending agents and chemicals including nitrites, local anesthetics, aniline and antimalarial drugs.There are several approaches to the management of methemoglobinemia. The first step is to stop the offending agent and initiate supportive measures. Methylene blue can be used successfully provided the patient has no evidence of glucose 6 phosphate deficiency. Hyperbaric oxygen and intravenous ascorbic acid are other treatment options.We present a case of unusually severe methemoglobinemia (82% methemoglobin) secondary to occupational exposure that failed to respond to several lines of management including methylene blue, red cell exchange, intravenous ascorbic acid, and hyperbaric oxygen. However, the patient responded swiftly to plasmapheresis started upon suspicion of concomitant thrombotic thrombocytopenic purpura, and he subsequently recovered completely.Thus, plasmapheresis may have a role in severe methemoglonbinemia unresponsive to standard treatment options.     

Difference of the clinical course and outcome between dapsone-induced methemoglobinemia and other toxic-agent-induced methemoglobinemia

Context: Acquired methemoglobinemia is a potentially fatal condition that leads to tissue hypoxia. Although the clinical features of methemoglobinemia depend on the methemoglobin levels, the clinical course would differ depending on the causative agents.

Objective: We attempted to clarify this issue by comparing the clinical course of methemoglobinemia caused by dapsone and that caused by other toxic agents.

Materials and methods: A retrospective case–control study was performed. All patients with methemoglobinemia and who were admitted to the emergency department (ED) of our hospital from 1 January 2002 to 31 December 2014 were included.

Results: Of the 34 patients with methemoglobinemia, 15 ingested dapsone (14 with acute overdose and one with chronic therapeutic use) and 19 had been exposed to other toxic agents, such as sodium nitrites, indoxacarb, primaquine, and lidocaine. The clinical characteristics and the course of dapsone-induced and other toxic-agent-induced methemoglobinemia were compared. There was no significant difference in clinical presentation and methemoglobin level (38.5% vs. 35.0%, p?=?0.456) upon their ED arrival between the two groups. However, the methemoglobin level after use of methylene blue and the total dose of methylene blue were higher in patients with dapsone-induced methemoglobinemia than in those with other agent-induced methemoglobinemia (11.9% vs. 1.7%, p?=?0.001, 455?mg vs. 144?mg, p?=?0.006). The majority of dapsone-induced methemoglobinemia (93.3%) required more than 72?h for normalization of the methemoglobin level, despite the use of methylene blue. Five of the study patients died due to multiorgan failure, and all of whom were inpatients with dapsone-induced methemoglobinemia.

Conclusion: The clinical course of dapsone-induced methemoglobinemia was worse than that of other toxic-agent-induced methemoglobinemia despite no significant difference in their initial clinical presentation. Continuous treatment with serial monitoring of the serum methemoglobin is necessary for patients with dapsone-induced methemoglobinemia.     

Methemoglobinemia in a Case of Paint Thinner Intoxication,Treated Successfully with Vitamin C

Background

Methemoglobin (MetHb) is an oxidized form of hemoglobin. It is a poor transporter of oxygen and is unable to deliver oxygen to the tissue. Globally, drug & toxin induced methemoglobinemia is more common as compared with the congenital form. Methemoglobinemia caused by paint thinner intoxication is rare. Methylene blue is well established as the first-line therapy for severe methemoglobinemia.

Center for Human Toxicology

Abstract

Acquired methemoglobinemia results from the exposure to various chemicals and drugs able to oxidize hemoglobin at a rate exceeding the normal enzymatic capacity for hemoglobin reduction. Levels of methemoglobin exceeding 60–70% may be associated with coma and death. We describe a case of complete, uneventful recovery involving a 10 week-old infant who presented to the Emergency Department with profound sudden onset of cyanosis, irritability, metabolic acidosis, and a lethal methemoglobin level of 71.4%. Intravenous administration of 12?mg methylene blue resulted in immediate resolution of the cyanosis and reduction of measured methemoglobin to 1.3%. The carboxyhemoglobin was negative. Sodium bicarbonate successfully corrected the acidosis. RBC reductase measurement was within normal limits, ruling out congenital methemoglobinemia. Family history revealed a wood-burning stove which emitted pine tar fumes as the potential environmental methemoglobin-producing source. The infant's cradle was situated five feet from the stove. The infant was discharged on day three of hospitalization with a methemoglobin level of 0.2%.     

Application of GLC-AFID and GLC-MS Procedures to Analysis of Plasma in Suspected Cases of Psychotropic Drug Overdose

Abstract

Metobromuron, a substituted urea herbicide, is widely used for control of grasses and broad-leaved weeds in Taiwan. Major systemic toxicity has not been reported following poisoning. A 22-year-old woman at 36 weeks of gestation was admitted to the emergency department three hours after ingestion of a mixture of 25% metobromuron and 25% metolachlor. Though stable initially, she developed central cyanosis 12 hours later. Emergent cesarean section was considered but administration of intravenous methylene blue readily reversed the cyanosis and prevented the operation. Recurrent cyanosis did not develop. Normal vaginal delivery occurred 17 days after the poisoning. Follow-up for four years revealed normal growth of the child. Metobromuron poisoning, like other urea herbicides, may cause methemoglobinemia via its hydrolysis products. Administration of methylene blue is effective treatment and should be considered in the treatment of methemoglobinemia following urea herbicide poisoning.