Your patient presents with an ocular burn after accidentally splashing an industrial acid on his face. You, however, can not seem to find the ever elusive eye pH paper to track her initial and serial pH’s during copious ocular irrigation. Now what?
Case: An 84 year old female presents with five days of a diffuse rash. She had a seizure and was started on phenytoin 2 weeks ago. Her mouth, labia, and medial canthi are involved. There are scattered areas of desquamation comprising less than a tenth of her total body surface area. She is tachycardic and febrile. Her complete blood count differential is normal. What is the diagnosis?
On a Friday night shift, an ambulance brings you a 52 year-old man who had an episode of syncope at a local club. EMS found him confused and hypoxic with poor skin color. The patient was placed on oxygen via face mask en route to your ED without clinical improvement. On exam, you note a blue discoloration of his extremities, and his chest x-ray and ECG are unremarkable. You draw blood, which appears very dark, and an ABG demonstrates pH 7.39, PCO2 41, and PO2 176.
Figure 1. Blue foot
Figure 2. Dark arterial blood
You suspect that your patient has methemoglobinemia, so you order a methemoglobin level which comes back at 37%. The patient receives antidotal therapy, and, on further interviewing, ultimately explains that he had been using amyl nitrate “poppers” at the club prior to arrival.
Hemoglobin is a protein tetramer, with each subunit consisting of an iron-containing heme group. Normally, the iron in heme exists in a reduced state as ferrous iron (Fe 2+). Methemoglobinemia occurs when some proportion of this ferrous iron is oxidized to produce ferric iron (Fe 3+). 1 This oxidation renders the effected heme groups unable to carry oxygen. Even though not every heme group is oxidized, every heme group in the same hemoglobin tetramer is affected by so-called cooperative binding: oxidized heme molecules induce conformational changes in hemoglobin which increase the un-oxidized heme’s affinity for oxygen. As a result, the oxygen–hemoglobin dissociation curve shifts to the left, and oxygen is less readily released to tissues.
Methemoglobinemia is essentially a functional anemia with normal cardiopulmonary function. Because the cardiovascular system must still circulate these inactivated hemoglobin containing red blood cells, a methemoglobin level of 34% has more effects than if the patient had lost 34% of their blood. The resulting cellular hypoxia leads to a range of end organ dysfunction and clinical signs: gray discoloration, dyspnea, fatigue, acidosis, dysrhythmia, seizure, coma, and ultimately death. Co-morbid anemia as well as cardiopulmonary disease will exacerbate symptoms.
Methemoglobinemia is not always the result of exogenous substances. Normal oxidative metabolism results in a small amount of endogenously produced methemoglobin (usually < 1%). This process is kept in check by NADH methemoglobin reductase, which uses NADH to reduce methemoglobin back to hemoglobin. Genetic deficiencies in this enzyme, as well as alterations in hemoglobin, can lead to congenital methemoglobinemia. 2,3 Infants under 4 months of age are also at increased risk of methemoglobinemia due to immature activity levels of this enzyme. When oxidative stress overwhelms the NADH reduction pathway, methemoglobin levels rise and patients turn blue.
| Aniline dyes | Nitrates, Nitrites | Sulfa drugs |
| Benzocaine, Lidocaine | Phenazopyridine | Trinitrotoluene |
| Dapsone | Prilocaine | Quinones |
| Naphthalene |
Additionally, extremes of age, anemia, diarrhea, hospitalization, malnutrition, renal failure, and sepsis are predisposing factors.
Methemoglobinemia should be suspected in patients with low pulse oximetry who do not respond to supplemental oxygen. Low SpO2 readings occur because pulse oximeters utilize light absorption at 660 and 940 nm to calculate the ratio of oxy-hemoglobin to deoxy-hemoglobin in blood. Methemoglobin absorbs light at both of those wavelengths, thus the presence of these additional hemoglobin species makes SpO2 calculation inaccurate. 4 Arterial blood gas measurement of PO2 is not affected by methemoglobin, resulting in a normal (and often elevated due to supplemental oxygen) calculated SaO2. Whenever there is dissociation between the PO2 and the SpO2, a hemoglobinopathy should be suspected. Additionally, arterial blood has been described as “chocolate brown” with degree of color change correlating to methemoglobin level. 5
Asymptomatic patients with low levels of methemoglobinemia (10% or less) may be managed conservatively by removing oxidizing drugs and arranging follow up. 1 In patients with dapsone-associated methemoglobinemia, administration of cimetidine has been associated with reduced methemoglobin levels. 6 Symptomatic patients or patients with elevated levels of methemoglobin (25% or more) usually require antidotal treatment with methylene blue.
Methylene blue is reduced by NADPH reductase to leukomethylene blue in RBCs, which subsequently reduces methemoglobin to hemoglobin. In this way, though stores of NADH are exhausted, NADPH functions as a reducing agent. Dosing is 1-2 mg/kg of methylene blue administered intravenously over 5 minutes. Though an initial drop in pulse oximeter reading (due to the blue color of the antidote) is expected, cyanosis and methemoglobinemia should improve over the following hour.
Figure 3. Methylene blue antidote
Figure 3. Intravenous administration of methylene blue
While conflicting data exist, many consider G6PD-deficiency (and resulting low levels of NADPH) to be a relative contraindication to methylene blue therapy; treatment failures and hemolysis have been reported in patients with G6PD-deficiency who received high doses of methylene blue. 7 Where methylene blue is not available or contra-indicated, ascorbic acid 0.5 g IV every six hours has been described, but clinical relevance remains uncertain. 8 If treatment fails, consider decontamination to remove remaining oxidant drugs, repeat administration of methylene blue, exchange transfusion, and/or hyperbaric oxygen therapy.
Blunt chest trauma from falls or motor vehicle collisions are a common reason for ED visits and a common source of rib fractures. While many patients with rib fractures can be discharged home with oral analgesics and an incentive spirometer, certain patients are at much higher risk for morbidity and mortality. This post will look at which patients are at risk, what factors predict increased mortality, and inpatient interventions that can reduce mortality, with a focus on the risks in older adults.
Currently, guidelines recommend therapeutic hypothermia for comatose adults with out-of-hospital cardiac arrest (OHCA). A recent trial of adults with OHCA showed that therapeutic hypothermia with the use of a targeted temperature of 33°C vs maintained therapeutic normothermia of 36°C, did not improve outcomes. There is a paucity of randomized trials of therapeutic hypothermia in children with OHCA, but sometimes adult trials get extrapolated to pediatrics. There are differences between adult and pediatric populations with OHCA, which makes it difficult to extrapolate the results of the adult trials to a pediatric population.
Welcome to another ultrasound-based case, part of the “Ultrasound For The Win” (#US4TW) Case Series. In this peer-reviewed case series, we focus on real clinical cases where bedside ultrasound changed management or aided in diagnoses. In this case, a 101-year-old man presents after being found down with altered mental status.
Excited delirium syndrome is defined as “a syndrome of uncertain etiology characterized by delirium, agitation, and hyperadrenergic autonomic dysfunction”.1 You may have encountered a patient like this in the ED or prehospital setting. Although the etiology is impossible to determine in many cases, stimulant abuse and other drugs are involved in a majority of cases. An 8% mortality has been ascribed to Excited Delirium Syndrome, resulting from hyperthermia, severe metabolic acidosis, and cardiovascular collapse.