We found an enormous amount of posts on respiratory topics and thus have divided the content into two modules. This first module will focus on general respiratory issues with airway and pulmonary embolism covered in the second module. Below we have listed our selection of the 15 highest quality blog posts within the past 12 months (current as of April 2015) related to respiratory, curated and approved for residency training by the AIR Series Board. In this module we have 4 AIRs and 11 Honorable Mentions. We strive for comprehensiveness by selecting from a broad spectrum of blogs from the top 50 listing per the Social Media Index.
I was recently the author of a PV card for management of Salicylate Toxicity, which had some discrepancy with expert opinion. The point of contention was in regards to measurement of urine pH vs serum pH for alkalinization. In preparing the first version of the card, I began with notes from a recent toxicology rotation, and expanded by examining textbooks and review articles. Although there was mention of serum pH measurement, numerous sources emphasized urine alkalinization as the primary endpoint for the treatment of aspirin toxicity. Therefore I choose to include this on the size-limited PV card.
Despite review by numerous peers and colleagues, not long after publication we were met with concern from prominent toxicologists regarding an oversight in mentioning serum alkalinization. Utilizing the strengths of our blog and social media we were immediately able to initiate a discussion with experts on the topic.
Expert Peer Review Comments
Dr. Lewis Nelson of NYU was able to clarify that by prioritizing serum alkalinization, we will avoid the cerebral toxicity that is the primary etiology of mortality. Serum alkalinization should also facilitate urine alkalinization as well as allow time to arrange for hemodialysis. Dr. Bram Dolcourt from Detroit expanded that serum alkalinization and normokalemia alone do not guarantee an optimal urine pH and suggest measurement of both urine and serum. From Twitter, Dr. David Juurlink from Toronto also recommended measurement of both, stating his forthcoming publication will expand on the topic. Our own ALiEM clinical pharmacist Dr. Bryan Hayes also assisted with expert insight as I was revising the PV card.
As the ALiEM-CORD virtual fellow, I have had the challenging task of collaborating with experts in my field, while still very much in a learner role myself. I was fortunate enough to have been featured on a site that has a robust commenting system and pride in peer review, even if it is post-publication. There is certainly content on the web that may be inaccurate or ‘less-accurate’, and consumers of both FOAM and conventional publications, as always, should remain critical and review multiple sources. There is a broad range in teaching and practice based on region, and when we work together we can identify what is truly best practice. Hopefully this conversation and the forthcoming publication on the topic will translate into changes in practice and in the textbooks in the coming years. Luckily, utilizing the strengths of our medium, we are able to publish these corrections today.
PV Card: Acute Salicylate Toxicity
For those curious, here was the original version 1.
Application of fluorescein is a vital part of the workup of ocular complaints. Despite some studies showing questionable support, the typical cited clinical concern for stored fluorescein solutions is contimination with Pseudomonas and risk for iatrogenic infection with associated ulcer formation. 1–4 Subsequently, single dose sterile strips have become the standard agent stocked in most EDs. Many patients, especially children, can be apprehensive of the application of the physical strip directly to the eye, and are more comfortable with the concept of eye drops. In this post, we review multiple technique to create fluorescein solutions and additional tips for utilization that may be integrated into your practice, depending on the supplies available to you.
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.
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.
Many agents have been associated with methemoglobinemia.
|Aniline dyes||Nitrates, Nitrites||Sulfa drugs|
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.
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.
- Be aware of medications that can lead to methemoglobinemia, especially nitrates/nitrities, local anesthetics, dapsone, phenazopyridine, and aniline dyes.
- Consider hemoglobinopathy when SpO2 doesn’t improve with supplemental oxygen and when the SpO2 doesn’t correlate with SaO2.
- In patients with symptoms or elevated levels of methemoglobinemia, consider antidotal therapy with methylene blue 1-2 mg/kg intravenously.
- Consider consultation with poison control and/or medical toxicology.
Hoffman R, Howland M Ann, Lewin N, Nelson L, Goldfrank L. Goldfrank’s Toxicologic Emergencies, Tenth Edition. McGraw-Hill Education / Medical; 2014.
Hall A, Kulig K, Rumack B. Drug- and chemical-induced methaemoglobinaemia. Clinical features and management. Med Toxicol. 1986;1(4):253-260. [PubMed]
James SD. Fugates of Kentucky: Skin Bluer than Lake Louise. ABC News. http://abcnews.go.com/Health/blue-skinned-people-kentucky-reveal-todays-genetic-lesson/story?id=15759819. Accessed February 22, 2012. [Source]
Barker S, Tremper K, Hyatt J. Effects of methemoglobinemia on pulse oximetry and mixed venous oximetry. Anesthesiology. 1989;70(1):112-117. [PubMed]
Shihana F, Dissanayake D, Buckley N, Dawson A. A simple quantitative bedside test to determine methemoglobin. Ann Emerg Med. 2010;55(2):184-189. [PubMed]
Barclay J, Ziemba S, Ibrahim R. Dapsone-induced methemoglobinemia: a primer for clinicians. Ann Pharmacother. 2011;45(9):1103-1115. [PubMed]
Youngster I, Arcavi L, Schechmaster R, et al. Medications and glucose-6-phosphate dehydrogenase deficiency: an evidence-based review. Drug Saf. 2010;33(9):713-726. [PubMed]
Rino P, Scolnik D, Fustiñana A, Mitelpunkt A, Glatstein M. Ascorbic acid for the treatment of methemoglobinemia: the experience of a large tertiary care pediatric hospital. Am J Ther. 2014;21(4):240-243. [PubMed]
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.