All posts by Patrick Ng

Toxcards: Sympathomimetic vs. Anticholinergic Toxidromes

Author: Patrick C Ng, MD (Chief Resident, San Antonio Military Medical Center) // Edited by: Cynthia Santos, MD (Senior Medical Toxicology Fellow, Emory University School of Medicine), Alex Koyfman, MD (@EMHighAK, EM Attending Physician, UTSW / Parkland Memorial Hospital) and Brit Long, MD (@long_brit)


Case Presentation

An 18 year old female is brought in by EMS after an unknown suicidal ingestion. She is confused, her pupils are dilated, and she is tachycardic. She has no tremors or rigidity. She has no history of chronic substance abuse or withdrawal.


How can you distinguish an anticholinergic vs sympathomimetic toxidrome?


There are overlapping signs and symptoms in both toxidromes; historical clues and a physical exam targeting the pupils, skin, GI and GU systems can reveal the toxidrome.

anticholinergic sympathomimetic toxidromes

-Antihistamines, antidepressants, scopolamine, hyoscyamine, atropine, and plants containing anticholinergic alkaloids (Datura, Belladonna) can precipitate an anticholinergic syndrome.1

-Treatment for anticholinergic syndrome is mainly supportive. Benzodiazepines are the mainstay treatment. Physostigmine is given to diagnose and treat anticholinergic delirium. A widely followed recommendation is that Physostigmine should not be given if there are signs of sodium channel blockade on the EKG.2 However newer research is challenging this notion.3

-TCA overdose can present with an anticholinergic toxidrome. Physostigmine is contraindicated in TCA overdose due to the concern for Na channel blockade causing myocardial depression.4

-Amphetamines, synthetic cannabinoids and methylxanthines like caffeine, nicotine, and theophylline can precipitate a sympathomimetic syndrome.5

-Treatment for sympathomimetic syndrome is mainly supportive with IV fluids and benzodiazapines. Beta blockers should be avoided in patients presenting with sympathomimetic syndrome secondary to cocaine use secondary to the possible effect of unopposed alpha-stimulation.

-The differential diagnosis for sympathomimetic syndrome include anticholinergic syndrome, sedative-hypnotic withdrawal, alcohol withdrawal, neuroleptic malignant syndrome, opioid withdrawal, and serotonin syndrome. Medical conditions like hypoglycemia, heat stroke, encephalitis, pheochromocytoma, thyoid storm, and sepsis can also mimic sympathomimetic syndrome.5


Table source: Santos C, Olmedo R. Sedative-Hypnotic Drug Withdrawal Syndrome: Recognition and Treatment. Emergency Medicine Practice Guidelines. Evidence Based Medicine Journal. March 2017;19(7):1-20

Main Point:

The clinical picture of sympathomimetic and anticholinergic can appear similar. Both may have agitation, confusion, delirium, seizures, tachycardia, hypertension, fever, and mydriasis. Distinguishing characteristics for anticholinergic syndrome are dry skin, absent bowel sounds, and urinary retention. Remember the colloquial description for anticholinergic toxicity; “Blind as a bat, mad as a hatter, red as a beet, hot as Hades (or hot as a hare), dry as a bone, the bowel and bladder lose their tone, and the heart runs alone.” Both sympathomimetic and anticholinergic syndrome respond well to benzodiazepines. Physostigmine can be used to treat delirium associated with anticholinergic syndrome after checking the EKG for signs of Na channel blockade.


  1. Curry S, et al. Chapter 14: Neurotransmitters and Neuromodulators. Chapter in Goldfrank’s Toxicologic Emergencies, 10th edition. New York: McGraw-Hill Education, 2015, p173-201
  2. Burns MJ, Linden CH, Graudins A et al. A comparison of physostigmine and benzodiazepines for the treatment of anticholinergic poisoning. Ann Emerg Med. 2000;35:374-81.
  3. Rasimas JJ, Sachdeva KK, Donovan JW. Revival of an antidote: bedside experience with physostigmine. J Amer Acad Emerg Psychiatr. 2014;12:5–24.
  4. Suchard JR: Assessing physostigmine’s contraindication in cyclic antidepressant ingestions. J Emerg Med. 2003; 25:185-91.
  5. Santos C, Olmedo R. Sedative-Hypnotic Drug Withdrawal Syndrome: Recognition and Treatment. Emergency Medicine Practice Guidelines. Evidence Based Medicine Journal. March 2017;19(7):1-20

Tox Cards: CO Poisoning

Author: Patrick C. Ng (Chief Resident, San Antonio Military Medical Center) // Edited by: Cynthia Santos, MD (Senior Medical Toxicology Fellow, Emory University School of Medicine), Alex Koyfman, MD (@EMHighAK, EM Attending Physician, UTSW / Parkland Memorial Hospital), and Brit Long, MD (@long_brit, EM Attending Physician, San Antonio Military Medical Center)
Case Presentation:
It is a cold day in the middle of December. A 56 yo female and her 29 yo daughter who is 8 months pregnant present to your ED with a chief complaint of generalized weakness and headache for 2 days. They mention that they think they both caught the flu due to the cold temperatures despite turning their heater on high and using oil lamps for extra heat in their apartment. Their vital signs are normal.
What are the most common signs/symptoms of carbon monoxide (CO) poisoning, and what are the general management plans?

CO poisoning presents with nonspecific symptoms that can be mistaken for other diagnosis such as the flu. Initial treatment includes high-flow supplemental O2. Hyperbaric oxygen therapy (HBOT) may or may not be the “standard of care” (controversial).

  • CO poisoning can be an elusive diagnosis, as non-specific symptoms such as headache, dizziness, nausea, fatigue, and chest pain are non-specific and can be consistent with many other disease processes.(1,2)
  • Key historical clues include people from the same household presenting with symptoms of headache and flu-like symptoms that improve throughout the course of the day (i.e. when patients leave their dwellings for work, school, etc.) and history of exposure to CO sources such as heaters and enclosed garages.(1,2)
  • A co-oximetry is a spectrophotometer that uses many different wavelengths to measure oxygenated hemoglobin (oxyHb), deoxygenated hemoglobin (deoxyHb), as well as carboxyhemoglobin (COHb) and methemoglobin (MetHb) concentrations.(3)
  • The use of greater number of wavelengths in a co-oximeter as compared to a standard pulse oximeter allows the co-oximeter to distinguish between other types of hemoglobin,  whereas a standard pulse oximetry can only distinguish between oxyHb and deoxyHb.(3)
  • Blood COHg levels commonly reaches a level of 10 % in smokers and may even exceed 15 %, as compared with 1 to 3 % in nonsmokers.(2)
  • Standard treatment includes  high-flow O2  via NRB mask (or intubation in severe cases) until symptoms resolve and CO levels return to baseline; pregnant patients should continue for at least 24 hours with fetal wellbeing assessment. Patients also require follow up at 1-2 months for neuropsychiatric assessment.(1,2)
  • Normal half life of Hb-CO is 4-6 hrs with room air oxygen, 40- min with high-flow O2, and 15-30 min with HBOT.(2)
  • Although the indications for HBO are controversial, some recommend HBO for any CO-poisoned patient with mental status change or history of syncope, signs of cardiac ischemia or arrhythmia, history of ischemic heart disease and CO level > 20%, symptoms that do not resolve with normobaric O2 therapy after 4-6 hours, or any pregnant patient with CO > 15%. Coma is generally an undisputed indication for hyperbaric-oxygen therapy.(2)
  • The use of HBO has been reported to reduce the risk of neurological/cognitive sequelae thought to be associated with carbon monoxide poisoning.(4,5)
Main Point:
Carbon monoxide poisoning can be a deadly diagnosis associated with significant morbidity and long-term permanent neurological damage. It can present with very non-specific symptoms. Specific historical clues as well as co-oximetry can help the emergency physician quickly make the diagnosis. High-flow O2 therapy is the initial standard therapy with some advocating HBOT for select severe or at risk cases.
1. Piantadosi CA. Diagnosis and treatment of carbon monoxide poisoning. Respir Care Clin N Am. 1999;5:183-202.
2. Ernst A, Zibrak JD. Carbon Monoxide Poisoning. N Engl J Med 1998;339:1603-1608.
3. Hampson NB. Noninvasive pulse CO-oximetry expedites evaluation and management of patients with carbon monoxide poisoning. Am J Emerg Med. 2012 Nov;30(9):2021-4.

4. Tibbles PM, Perrotta PL. Treatment of carbon monoxide poisoning: a critical review of human outcome studies comparing normobaric oxygen with hyperbaric oxygen. Ann Emerg Med. 1994;24:269-276.
5. Weaver LK, Hopkins RO, Chan KJ, et al. Hyperbaric oxygen for acute carbon monoxide poisoning. N Engl J Med 2002;347:1057–1067

An Approach to Bradycardia in the Emergency Department

Authors: Patrick C Ng, MD (EM Chief Resident, SAUSHEC Emergency Medicine Department) and Brit Long, MD (@long_brit, EM Attending Physician, SAUSHEC Emergency Medicine Department) // Edited by: Jennifer Robertson, MD, MSEd and Alex Koyfman, MD (@EMHighAK, EM Attending Physician, UTSW Medical Center / Parkland Memorial Hospital)


A 15-year-old male is brought to the emergency department (ED) via ambulance with a chief complaint of syncope. He reports that he was washing his hands in the bathroom at approximately 4:00 AM and the next thing he remembers, he was waking up to paramedics putting him on a stretcher. He denies preceding symptoms and does not report any relieving or exacerbating features. This has never happened to him before.

His review of systems is positive for recent rhinorrhea, cough, mild chest discomfort, and a low grade fever. His primary care physician was treating him symptomatically with a working diagnosis of an upper respiratory infection. The patient states that his symptoms had been improving.

Emergency medical services (EMS) reports the following vital signs on scene: blood pressure of 70/40 mm Hg, a heart rate of 36 beats per minute (bpm), a respiratory rate (RR) of 16/minute, a temperature of 100.6°Fahrenheit (F), an oxygen saturation of 98% on room air (RA), and a glucose level of 120. The patient’s vital signs upon arrival to your ED were similar and did not change despite intravenous (IV) fluids. A STAT echocardiogram was ordered and revealed decreased cardiac function. Laboratory tests were significant for an elevated troponin and white blood cell (WBC) count. A respiratory viral panel is positive for Coxsackie virus.

The patient’s electrocardiogram (EKG) is as follows:


(Image reproduced from:; last accessed 10/19/2016)

You place pacing pads on the patient and start him on a dobutamine drip. He gets admitted to the pediatric intensive care unit and receives IV immunoglobulin (IVIG) for 3 days. He is downgraded to the floor and is discharged a week later with a discharge diagnosis of bradycardia and sick sinus syndrome, likely secondary to viral myocarditis.

This article will evaluate the ED approach to bradycardia. Before we get to the evaluation and management of the sick bradycardic patient, a little background in conduction is necessary…


The cardiac conduction system consists of the His-Purkinje system. Electrical impulses are generated in the sinoatrial (SA) node, conducted down to the atrioventricular (AV) node, and then conducted down to the ventricles via the left and right bundle branches (Figure 1). A normal heart rate is typically between 60-100 bpm. Bradycardia is defined according to some sources as a heart rate below 60 bpm1.


Figure 1: Electrical conduction system of the heart. Image reproduced from: ( – Last Accessed 10/19/2016.

Bradycardia can be organized into two main categories: symptomatic and asymptomatic. Bradycardia can be normal in various individuals, particularly in children and well-conditioned athletes2,3. Some reports describe asymptomatic individuals with profound bradycardia defined as a HR <35 bpm. Findings of bradycardia in these individuals may not require any intervention, as long as the patient does not experience symptoms.

This is the opposite of patients with symptomatic bradycardia. The signs and symptoms of bradycardia are not specific and may include syncope, dizziness, chest pain, shortness of breath, and fatigue4. A slow heart rate can lead to heart failure and/or hemodynamic instability 5. Upon initial presentation, it is imperative the ED provider focus the history on determining if the patient is symptomatic.

The differential for symptomatic bradycardia is broad. One way to look at the differential is by broad categories which includes but is not limited to: structural/electrophysiological, infectious, endocrine, toxicology/iatrogenic, and other (Table 1).

Table 1 – Etiologies of Bradycardia

Category Possible Etiologies
Structural/Electrophysiological -Sick Sinus Syndrome

-AV Block


-Congenital Heart Disease

-Prior Cardiac Surgery


-Arterial Dissection (Aorta, Coronary, Carotid)

Infectious -Myocarditis

-Lyme Disease



-Typhoid Fever*

-Legionnaires disease*





-Q fever*

-Yellow Fever*

-Rocky Mountain Spotted Fever*

Endocrine -Hypothyroidism/Myxedema coma

-Bamforth syndrome

-Hypothalamic dysfunction

-Electrolyte Abnormalities/Malnutrition

-Hashimoto’s thyroiditis

Toxicology/Iatrogenic -Beta blocker**

-Calcium channel blocker**






-Organophosphate poisoning


-Carbamate insecticide poisoning


-Tricyclic Antidepressant Poisoning


-Levetiracetam overdose


Other -Heat exhaustion/stroke



-Increased Intracranial Pressure

-Spinal Cord Injury

-Carotid hypersensitivity syndrome

-Chromosome 19p duplication syndrome

-Fleisher syndrome

-Young Simpson syndrome

-Asphyxia neonatorum


-Lupus Carditis

-Oculocardiac Reflex



Table 1: Causes of bradycardia8-20 (Not an all-inclusive list)

*Can cause relative bradycardia i.e. not in proportion to fever

** In overdose, and also at therapeutic dose

What are the key ED studies?

An EKG should be one of the first diagnostic tests obtained when bradycardia is recognized. Additionally, depending on the suspected etiology, a troponin, brain natriuretic peptide (BNP), electrolytes, infectious labs, chest x-ray, neuroimaging, and echocardiogram should be considered.  The workup should be tailored to the initial clinical assessment. Not all patients warrant these tests.

The EKG is imperative, and examples of various heart blocks are shown below:


1st degree heart block- Image reproduced from:; last accessed 10/25/2016.


2nd degree block-Type I, Image reproduced from:; last accessed 10/25/2016.


2nd degree block-Type II, Image reproduced from:; last accessed 10/25/2016


3rd degree block Image reproduced from:; last accessed 10/25/2016.


Sick Sinus-Alternating patterns of tachy- and bradyarrhythmia which can be seen with sick sinus syndrome. Image reproduced from:; last accessed 10/25/2016.


As mentioned in the introduction, not all bradycardic rhythms require intervention, especially in the otherwise healthy, asymptomatic patients. If the ED provider is presented with a patient with symptomatic bradycardia, one of the first things to consider is the placement of transcutaneous pacer pads. Preparation for transvenous pacing (which requires a central line) should also be considered. Specific discussion of management plans for the different etiologies listed in Table 1 is too lengthy and out the scope of this post. General categories are mentioned below.

Structural/Electrophysiological (EP): A general way to approach potential structural/EP causes of bradycardia is to consider an abnormality that hinders the normal conduction of the heart. To address this, the emergency provider should consider transcutaneous/transvenous pacing to temporize the patient until definitive treatment can be obtained, such as percutaneous coronary intervention (PCI) for a ST elevation myocardial infarction (STEMI) or a permanent pacemaker for conduction abnormalities.  An echocardiogram can assist in evaluation if a structural cause is suspected.

Infectious: Viral myocarditis is a more common cause of bradycardia in the infectious category. Myocarditis leading to hemodynamic compromise is important to consider, particular in the febrile, crashing child. Vasopressors, IVIG, and extracorporeal membrane oxygenation (ECMO) therapy have been reported in treating cardiogenic shock secondary to infectious etiologies. For further reading, consider reviewing: Antibiotic therapy should be considered, particularly with tick-borne diseases such as Lyme disease.

Endocrine: Specific electrolyte and hormone abnormalities should be corrected. Thyroid disorders are a commonly reviewed topic for the emergency medicine inservice/board exam. For further management on myxedema coma, please review: An abnormal thyroid stimulating hormone can drastically change your management pathway. However, disorders such as thyrotoxicosis and myxedema coma are clinical diagnoses. The patient with myxedema coma should be given IV T4. IV T3 is an option as well, though it carries a higher risk of dysrhythmias.

Toxicology: The specific management plans for each potential toxin listed is out of the scope of this post. Beta blocker and calcium channel blocker toxicity is commonly seen in review books and examinations. Treatment includes glucagon, calcium supplementation, high dose insulin/glucose therapy, and potentially lipid emulsion therapy. For further reading on this topic, one can consider reviewing:

For cholinergic and hypnotic/sedative management, please review:

When reviewing medications and drug toxicity, it is vital to obtain a detailed medication reconciliation on patients with bradycardia, as a myriad of medications can cause a low heart rate.

Other: For etiologies listed in this category, there are a few management principles to consider for specific etiologies. For example, the emergency provider should understand the increased susceptibility of arrhythmias in the hypothermic patient.  Warming these patients should take precedence over other interventions such as introducing a transvenous pacer. This is because without warming, hardware can cause a deadly arrhythmia.

For neurogenic/traumatic etiologies of bradycardia such as head trauma, specific interventions to decrease intracranial pressure (ICP) (head elevation, mannitol, hyperventilation, 3% saline) should be considered.


As seen, the differential for bradycardia is broad, and management depends on the suspected etiology. Not all bradycardia can be fixed with atropine and pacing. The emergency provider must focus his or her history and physical to narrow the differential to address the underlying pathology to effectively treat symptomatic bradycardia.

Overall remember that: 

-Bradycardia is defined as a HR <60bpm

-Bradycardia can be benign and asymptomatic

-An EKG is essential to obtain as early as possible

-There is a broad differential for symptomatic bradycardia, and one can organize some of the causes into 5 categories: Structural/EP, Infectious, Endocrine, Toxicology/Iatrogenic, and Other

-Temporizing measures such as vasoactive drugs and pacing should be considered, but may not be effective in certain patients

References/Further Reading

  1. Spodick DH. Normal sinus heart rate: sinus tachycardia and sinus bradycardia redefined. Am Heart J. 1992 Oct;124(4):1119-21.
  2. Northcote RJ, Canning GP, Ballantyne D. Electrocardiographic findings in male veteran endurance athletes. Br Heart J. 1989 Feb; 61(2):155-60.
  3. Talan DA, Bauernfeind RA, Ashley WW, Kanakis C Jr, Rosen KM. Twenty-four hour continuous ECG recordings in long-distance runners. Chest 1982;82(1):19.
  4. Eraut D, Shaw DB. Sick sinus syndrome. Br Med J. 1973 Aug 4;3(5874):295.
  5. Tresch DD, Fleg JL. Unexplained sinus bradycardia: clinical significance and long-term prognosis in apparently healthy persons older than 40 years. Am J Cardiol. 1986 Nov 1;58(10):1009-13.
  6. Lateef A, Fisher DA, Tambyah PA. Dengue and Relative Bradycardia. Emerg Infec Dis. 2007 Apr;13(4):650-651.
  7. Ostergaard L, Huniche B, Andersen PL. Relative bradycardia in infectious diseases. J infect 1996;33:185-91.
  8. Tanriverdi S, Ulger Z, Siyah BB, Kultursay N, Yalaz M, Koroglu OA. Treatment of Congenital Complete Atrioventricular Heart Block With Permanent Epicardial Pacemaker in Neonatal Lupus Syndrome. Iran Red Crescent Med J. 2015 Sep 1;17(9):e16200
  9. Skog A, Lagnefeldt L, Conner P, Wahren-Herlenius M, Sonesson SE. Outcome in 212 anti-Ro/SSA-positive pregnancies and population-based incidence of congenital heart block. Acta Obstet Gynecol Scand. 2016 Jan;95(1):98-105.
  10. St-Onge M, Anseeuw K, Cantrell FL. Gilchrist IC, Hantson P, Bailey B, et al. Experts Consensus Recommendations for the Management of Calcium Channel Blocker Poisoning in Adults. Crit Care Med. 2016 Oct 3.
  11. Wong LY, Wong A, Robertson T, Burns K, Roberts M, Isbister GK. J Med Toxicol. 2016 Jul 4.
  12. Page CB, Mostafa A, Saiao A, Grice JE, Roberts MS, Isbister GK. Cardiovascular toxicity with levetiracetam overdose. Clin Toxicol. 2016;54(2):152-4.
  13. Roberts DM, Gallapatthy G, Dunuwille A, Chan BS. Pharmacological treatment of cardiac glycoside poisoning. Br J Clin Pharmacol. 2016 Mar;81(3):488-95.
  14. Dhooria S, Behera D, Agarwal R. Amitraz: a mimicker of organophosphate poisoning. BMJ Case Rep. 2015 Oct 1;2016.
  15. Graudins A, Lee HM, Druda D. Calcium channel antagonist and beta-blocker overdose: antidotes and adjunct therapies. Br J Clin Pharmacol. 2016 Mar;81(3):453-61.
  16. Leung AM. Thyroid Emergencies. J Infus Nurs. 2016 Sep-Oct;39(5):281-6.
  17. Wang FF, Xu L, Chen BX, Cui M, Zhang Y. Anorexia with sinus bradycardia: a case report. Beijing Da Xue Xue Bao. 2016 Feb 18;48(1):180-2.
  18. Alhussin W, Verklan MT. Complications of Long-Term Prostaglandin E1 Use in Newborns with Ductal-Dependent Critical Congenital Heart Disease. J Perinat Neonatal Nurs. 2016 Jan-Mar;30(1):73-9.
  19. Partida E, Mironets E, Hou S, Tom VJ. Cardiovascular dysfunction following spinal cord injury. Neural Regen Res. 2016 Feb;11(2):189-94.
  20. Thomsen JH, Nielsen N, Hassager C, Wanscher M, Pehrson S, Kober L, et al. Bradycardia During Targeted Temperature Management: An Early Marker of Lower Mortality and Favorable Neurologic Outcome in Comatose Out-of-Hospital Cardiac Arrest Patients. Crit Care Med. 2016 Jan;50(1):51-4.

Hemoptysis: Key principles and management

Authors: Patrick C Ng, MD (EM Chief Resident, SAUSHEC Emergency Medicine Department) and Brit Long, MD (@long_brit, EM Attending Physician, SAUSHEC Emergency Medicine Department) // Edited by: Jennifer Robertson, MD, MSEd and Alex Koyfman, MD (@EMHighAK, EM Attending Physician, UTSW Medical Center / Parkland Memorial Hospital)

Case 1

After being discharged from your hospital after a three-day stay for a bowel obstruction, a 76- year old male presents with two days of cough productive of green sputum with red streaks. He reports no relief with the use of his inhalers that he normally uses for his chronic obstructive pulmonary disease (COPD). Upon reviewing his chart, you notice that he had no cough during his hospital stay. His review of systems is positive for chills, intermittent nausea, and chest discomfort when actively coughing.

On examination, his vital signs are blood pressure (BP) 170/90, heart rate (HR) 110 beats per minute (bpm), respiratory rate (RR) 30 per minute, oxygen saturation (Sat) of 92% on room air (RA), and temperature (temp) of 101.6°Farenheit (F). He is actively coughing and is in mild distress. He coughs up about 1 cc of purulent material with red streaks in it. His right lower lung fields have significant crackles. Cardiac examination reveals tachycardia. Laboratory tests are significant for a white blood cell count of 16 x 109/L, a creatinine of 1.5mg/dL, and lactate of 2.5. Chest x-ray reveals a right lower lobe (RLL) infiltrate.

You make the diagnosis of hospital acquired pneumonia, start antibiotics and intravenous (IV) fluids and admit the patient for further management.

Case 2

An 80-year-old female presents to your emergency department (ED) with a sudden onset of shortness of breath. She recently completed a trans-Atlantic flight from London. Upon arrival to her room, you notice that she is in respiratory distress. She has never had anything like this before, and has no relief with oxygen supplementation. Her review of systems is positive for cough productive of reddish sputum.

Physical examination is significant for a swollen right calf. Her vital signs are: BP 80/60, HR 140, RR 46, Sat 88% on room air, and a Temp 100.3°F. Her EKG shows sinus tachycardia, and a bedside echocardiogram shows a dilated right ventricle (RV).

Suddenly, the patient goes into cardiac arrest. You start standard advanced cardiac life support (ACLS) protocol, intubate the patient, and call for tissue plasminogen activator (tPA) because you suspect a massive pulmonary embolism (PE) as the diagnosis. After rounds of chest compressions and a dose of tPA, you achieve return of spontaneous circulation (ROSC). You start post arrest hypothermia protocol and admit the patient to the medical intensive care unit (MICU).


Hemoptysis is defined as the expectoration of blood originating from the tracheobronchial tree or lung parenchyma1. A common source of the bleeding is the bronchial artery1,2. Blood coming from other sources, including but not limited to the oral cavity, upper gastrointestinal (GI) tract, or esophagus can sometimes be mistaken for hemoptysis and is categorized as pseudohemoptysis. There are numerous causes of hemoptysis. Ong et al divides such etiologies into 5 main categories: infective, neoplastic, vascular, autoimmune, and drug/other related.

Examples of infectious causes include tuberculosis, lung abscesses, and pneumonia. Primary and metastatic cancer are examples of neoplastic causes. Pulmonary embolism is a vascular cause of hemoptysis. Lupus and various vasculitic diseases are examples of autoimmune causes of hemoptysis. Anticoagulants and trauma can cause hemoptysis as well1. According to a retrospective population based study conducted by Abdulmalak et al from 2008-2012, 15,000 adults were admitted for hemoptysis each year. The investigators found hemoptysis is associated with a 27% mortality at three years2.

There are two main categories of hemoptysis: massive and non-massive. The initial evaluation should try to focus on this differentiation. Most cases of hemoptysis are non-massive (95%) and self-limited3. Massive hemoptysis is described as a large enough volume of blood expectorated to cause hemodynamic instability, abnormal gas exchange, or a significant threat to life. According to Yoon et al, most deaths that occur secondary to massive hemoptysis are due to asphyxiation, rather than exanguination4. There is no consensus on the volume of blood that needs to be expectorated to be categorized as massive hemoptysis. Some reports define massive hemoptysis as expectorating >300 cc of blood in 24 hours5. Other sources have described massive hemoptysis as expectorating >100 to >1000 cc of blood in 24 hours4-6. With no clear definition on what volume of blood must be lost to meet the diagnosis of massive hemoptysis, the emergency physician must target his/her evaluation to determine the risk of death with the patient’s clinical presentation, regardless of how much blood is expectorated.

Key ED Work Up

For patients presenting with hemoptysis, the emergency medicine (EM) provider must determine whether it is massive or not and what etiology (infectious, vascular, etc) to suspect by history and physical examination. Laboratory work including a complete blood count, a basic metabolic panel, a type and screen (with cross if massive hemoptysis suspected), coagulation studies (particularly important in patients on anticoagulation) and a lactate level should be considered. Since patients with massive hemoptysis can decompensate quickly, the EM provider should not fall into a false sense of assurance if initial laboratory work and evaluation are normal. These patients should be monitored closely and labs repeated if there are signs of clinical deterioration.

Important imaging to consider includes chest radiograph and computed tomography (CT)7. Chest CT is needed in patients with history of tobacco use, age greater than 40 years, massive hemoptysis, and mass or infiltrate on radiograph. Bronchoscopy should be considered, as it can help to localize and control the source of bleeding by infusion of vasoactive drugs at the site of the bleeding. However, the performance of this procedure can be challenging secondary to a blood filled airway6-8.

Radiographs and CT can help locate the bleeding and possibly characterize an infectious, neoplastic, or other cause of the bleeding8-11. Table 1 summarizes a set of guidelines for imaging patients that present with hemoptysis.


Table 1: Imaging recommendations (Reproduced from Earwood et al. Am Fam Physician 2015)

Key ED Work Up: Non-Massive Hemoptysis

In patients determined to have pseudohemoptysis and/or non-massive hemoptysis, it may be appropriate to discharge these patients with follow up testing/imaging if indicated according to their history and physical (Figure 1). Patients should be hemodynamically stable with normal vital signs, have normal chest radiographs, possess no comorbidities, and have adequate follow-up. Repeat chest radiograph may be needed. Any concern for massive hemoptysis warrants admission for further evaluation and management.


Figure 1: Evaluation of non-massive hemoptysis (Table reproduced from Ong et al. Singapore Med J 2015)

Key ED Work Up: Massive Hemoptysis

Massive hemoptysis requires immediate resuscitation with blood products, interventional radiology consultation (for bronchial artery embolization), and cardiothoracic surgery consultation. As mentioned in the introduction, asphyxiation is a cause of death in patients with hemoptysis. Early and aggressive airway management should be considered. When intubating, large (8.0) ET tubes are preferred, as smaller tubes, as well as double lumen tubes, can make bronchoscopy difficult. One should also consider the utility of selective mainstem bronchus intubation to isolate the side that is bleeding. One can accomplish this by placing the tube past the cords and then rotating the tube 90 degrees toward the side that one is trying to intubate13.

In patients on anticoagulation, reversal may be needed. Some medications to consider, depending on the specific anticoagulant, include prothrombin complex concentrate (PCC), TXA (tranexamic acid) vitamin K, fresh frozen plasma (FFP), and recombinant Factor VII14. For further information on reversal of anticoagulation please visit: Blood products may be required.

In patients with massive hemoptysis, hemodynamic instability, or significant comorbidities, the emergency provider should consider admission for further workup. Inpatient workup may involve bronchoscopy, endovascular embolization, and/or surgery (Figure 2).


Figure 2: A management approach to massive hemoptysis (Image reproduced from Larici et al. Diagn Interv Radiol 2014)


-Hemoptysis is defined as expectoration of blood originating from the tracheobronchial tree or lung parenchyma and must be distinguished from pseudohemoptysis

-Hemoptysis is categorized as Massive or Non-massive

-There are many causes of hemoptysis and broad categories of these causes include: Infection, Autoimmune, Trauma, Drugs, and Neoplastic

-There is no consensus on the volume of expectorant that one must have to meet the diagnosis of massive hemoptysis

-Massive hemoptysis is life threatening, and, after securing the airway with intubation and maximizing hemodynamic stability with transfusion and reversal of anticoagulation, the patient should be admitted.

-Depending on the suspected etiology, definitive care may come in the form of bronchoscopy, bronchial artery embolization, and/or surgery

References / Further Reading

  1. Ong Z, Chai H, How C, Koh J, Low TB. A simplified approach to haemoptysis. Singapore Med J 2015; 57(8): 415-418.
  2. Abdulmalak C, Cottenet J, Beltramo G, Georges M, Camus P, Bonniaud P, et al. Haemoptysis in adults: a 5-year study using the French nationwide hospital administrative database. Eur Respir J 2015 Aug;46(2):50311.
  3. Larici AR, Franchi P, Occhipinti M, Contegiacomo A, Ciello A, Calandriello L, et al. Diagnosis and management of hemoptysis. Diagn Intervn Radiol 2014 Jul-Aug; 20(4):299-309.
  4. Yoon Woong, Kim JK, Kim YH, Chung TW, Kang HK. Bronchial and Nonbronchial Systemic Artery Embolization for Life-threatening Hemoptysis: A Comprehensive Review. Radiographics 2002 Nov-Dec;22(6):1395-409.
  5. Andersen PE. Imaging and interventional radiological treatment of hemoptysis. Acta Radiol 20016 Oct;47(8):780-92.
  6. Jean-Baptiste E. Clinical assessment and management of massive hemoptysis. Crit Care Med 2000;28:1642-1647.
  7. McGuinness G, Beacher JR, Harkin TJ, Garay SM, Rom WN, Naidich DP. Hemoptysis: 30 prospective high-resolution CT/bronchoscopic correlation. Chest 1994:105:1155-1162.
  8. Cahill BC, Ingabar DH. Massive hemoptysis: assessment and management. Clin Chest Med 1994; 15:147-167.
  9. Nadich DP, Funt S, Ettenger NA, Arranda C. Hemoptysis: CT—bronchoscopic correlations in 58 cases. Radiology 1990:357-362.
  10. Abal AT, Nair PC, Cherian J. Haemoptysis: aetiology, evaluation, and outcome—a prospective study in a third-world county. Respir Med 2001;95:548-552.
  11. Tak S, Ahluwalia G, Sharma SK, Mukhopadhya S, Pande JN. Haemoptysis in patients with a normal chest radiograph: bronchoscopy-CT correlation. Australas Radiol 1999; 43:451-455.
  12. Earwood JS, Thompson TD. Hemoptysis: Evaluation and Management. Am Fam Physician 2015 Feb 15;91(4):243-249.
  13. Bair AE, Doherty MJ, Harper R, Albertoson TE. An evaluation of a blond rotational technique for selective mainstem intubation. Acad Emerg Med 2004;11(10):1105-7.
  14. Sakr L, Dutau H. Massive Hemoptysis: An Update on the Role of Bronchoscopy in Diagnosis and Management. Respiration 2010;80:38-58.

Hydrogen Sulfide Toxicity: More than just a rotten egg smell

Authors: Patrick C Ng, MD (EM Chief Resident, SAUSHEC Emergency Medicine Department) and Brit Long, MD (@long_brit, EM Attending Physician, SAUSHEC Emergency Medicine Department) // Edited by: Alex Koyfman, MD (@EMHighAK, EM Attending Physician, UTSW / Parkland Memorial Hospital) and Stephen Alerhand, MD (@SAlerhand)


Case 1

You get a call from EMS that they are en route to your ED with a 37-year-old male who was found down in a sewer, with a current CGS of 3. The patient is being ventilated with a BVM. ETA 2 minutes!

The patient arrives to your ED. You immediately set up your safety net of bilateral IVs, oxygen, and get the patient on the cardiac monitor. As you begin your resuscitation, EMS repeats that the patient was found down in a sewer. His colleagues report that he was working in there alone and was radio silent for approximately 30 minutes before EMS arrived. EMS reports a strong odor at the scene resembling rotten eggs. The patient had been found without any PPE or respirators on.

Vitals: BP 170/80, HR 100, RR 0, Temp 100.0°F, Sat 86% with 15L of oxygen via BVM

Recognizing that this patient is apneic and unresponsive, you prepare for intubation. Upon inserting the laryngoscope, copious amounts of a pink, frothy substance emerge from the airway. With suctioning, you get a grade 1 view and intubate successfully. In consultation with the poison control center for suspected hydrogen sulfide toxicity, you resuscitate the patient with fluids and administer sodium nitrite to induce methemoglobinemia.

Resulting labs are significant for a white blood cell count of 12.1 x 109, pH of 7.23, PaCO2 72 mm Hg, PaO2 51, and Lactate of 5.6 mmol/L. Troponin was normal.

CXR revealed bilateral pulmonary infiltrates and an ET tube 1 cm above the carina.

Head CT was negative for sign of trauma or CVA.

The patient was admitted to the MICU for respiratory failure and lactic acidosis likely secondary to hydrogen sulfide toxicity.


Hydrogen sulfide is a triatomic molecule that is typically found as a gas (Figure 1). It is a natural substance that is formed by the digestion of organic material by prokaryotes in the environment. Typically, hydrogen sulfide is found in sewers, wells, volcanoes, and hot springs1. Additionally, hydrogen sulfide is a major occupational hazard in the oil and gas industry. It is a component of natural gas, and a significant amount of the gas can be released in the extraction and refining of natural gas through hydraulic fracturing aka ‘fracking’2. Fracking is a process of drilling where a mixture containing water, chemicals, and sand is directed at rock at a high pressure causing fractures in the rock to allow the natural gas to flow out to the well head3.


Figure 1: Molecular structure of H2S

Permissible OSHA exposure is 20ppm during an 8-hour shift

Over the past decade, particularly in Japan, there has been an increase in reports of “detergent suicides”, where individuals have been mixing household products such as toilet bowl cleaners and insecticides, which serve as a proton donor and sulfur source respectively, to commit suicide. The combination of these products can form H2S gas in toxic concentrations leading to toxicity, particularly when in an enclosed environment4. This also poses a threat to neighbors and first responders who can also be exposed to the gas6.

There are varying degrees of H2S toxicity. Variables such as length of exposure and concentration of exposure have direct effects on the level of toxicity (Table 1). Exposures to the gas can cause intense upper airway irritation, conjunctivitis, coughing, seizure, and dyspnea1,7. At higher concentrations, cardiac arrest, myocardial infarction, and death can occur1,7-9. The “knockdown” effect is described as a sudden loss of consciousness when exposed to high concentrations of H2S; the exact pathophysiology of this is not well known1. H2S has also been reported to cause olfactory fatigue, which can result from prolonged exposure as the classic rotten egg smell dissipates5.

In the body, hydrogen sulfide hinders aerobic respiration by inhibiting cytochrome c oxidase in the mitochondria. This inhibits mitochondrial ATP production. This mechanism of toxicity is similar to cyanide toxicity. Additionally, H2S is thought to poison the brain, particularly in the respiratory centers leading to central apnea11. Also, it affects the L-type calcium channels in the heart causing arrythmia13. Hydrogen sulfide toxicity can result in coma, apnea, shock, and eventually cardiac arrest.


Table 1: Effects of H2S at various concentrations (Table reproduced from Morii et al)5

Key ED Work Up

For suspected H2S toxicity and with the understanding of complications such as pulmonary edema, apnea, and cardiac arrhythmia, it is important to monitor these patients very closely. Initial workup should include: VBG to assess respiratory status, lactate level as H2S can precipitate a profound lactic acidosis, a chest x-ray to assess for presence of pulmonary symptoms/edema, an ECG to assess for arrhythmias, and continuous cardiac monitoring as H2S toxic patients are at risk for cardiac arrhythmia. Since there is no diagnostic test to diagnose H2S toxicity, the ED provider must have a high clinical suspicion for this diagnosis based on history and physical. Consider basic labs such as CBC and Chem 8 as well as further imaging to assess for trauma in patients found unconscious. Co-oximetry should be considered as well in these inhalation injuries, particularly if sodium nitrite is used as therapy, as it causes a methemoglobinemia which can be monitored with co-oximetry. The EM provider must consider other gases that may have also been inhaled including but not limited to cyanide and carbon monoxide. Additionally, ophthalmologic complications have been reported and must be considered.

Key Management Principles

The first step in managing a patient exposed to H2S is to remove them from the exposure and to be aware of possible secondary exposure to bystanders and first responders. Rapid assessment of the ABCs is warranted and aggressive supportive care should take place. Sodium nitrite (0.33mL/kg of 3% solution) has been reported to treat hydrogen sulfide poisoning 1,17. There is no consensus on the proper dosing of sodium nitrite. Sodium nitrite induces a methemoglobinemia which increases hemoglobin’s ability to bind H2S. Sodium nitrite can cause hypotension, and induction of a methemoglobinemia in an apneic patient can worsen tissue hypoxia and end organ damage. Thus, aggressive supportive care with IV fluids and mechanical ventilation in a patient poisoned with H2S is of paramount importance. Close monitoring of methemoglobin is important, and co-oximetry should be obtained to measure methemoglobin levels 30 minutes after administration of sodium nitrite. There are several reports of using hyperbaric oxygen to treat H2S toxicity as well 13-14. Recently, there have been animal models that have demonstrated that the use of cobinamide, a vitamin b12 analog, may be effective in treating H2S toxicity, but this is still in the nascent stages of development18. Hydroxocobalamin and methylene blue have also been reported to be used for H2S toxicity19,20. Management of H2S exposures should take place with toxicology consultation.


-Hydrogen sulfide exposures can be deadly.
-Hydrogen sulfide exposures can happen in various industrial settings as well as in the home as a suicide attempt.
Removal of the patient from the exposure as soon and as safely as possible is a key initial step.
Aggressive supportive care is the mainstay of treatment.
Sodium nitrite and other nitrite formulations can be used to induce a methemoglobinemia to treat H2S toxicity. Hyperbaric oxygen, methylene blue, and hydroxocobalamin have also been used.
-There is no consensus on dosing of sodium nitrite, and one must consider the drug’s side effects including hypotension.
Cobinamide, a hydroxocobalamin derivative, may serve as an effective intramuscular antidote for H2S toxicity in the future.


References/Further Reading

  1. Yalamanchili C, Smith MD. Acute hydrogen sulfide toxicity due to sewer gas exposure. Am J Emerg Med 2008 May;26(4):518.
  2. The Process of Hydraulic Fracturing.; last accessed 15July2016.
  3. Carpenter DO. Hydraulic fracturing for natural gas: impact on health and environment. Rev Environ Health 2016 Mar;31(1):47-51.
  4. Reedy SJ, Schwartz MD, Morgan BW. Suicide Fads: Frequency and Characteristics of Hydrogen Sulfide Suicides in the United States. West J Emerg Med 2011 Jul;12(3):300-304.
  5. Morii D, Miyagatani Y, Nakamae N, Murao M, Taniyama K. Japanese experience of hydrogen sulfide: the suicide craze in 2008. J Occup Med Toxicol 2010;5:28.
  6. Knight LD, Presnell SE. Death by sewer gas: case report of a double fatality and review of the literature. Am J Forensic Med Pathol 2005 Jun;26(2):181-5.
  7. Truscott A. Suicide fad threatens neighbours, rescuers. CMAJ 2008 Aug 12;179(4):312-313.
  8. Lewis RJ, Copley GB. Chronic low-level hydrogen sulfide exposure and potential effects on human health: a review of the epidemiological evidence. Crit Rev Toxicol 2015 Feb;45(2):93-123.
  9. Wu N, Du X, Wang D, Hao F. Myocardial and lung injuries induced by hydrogen sulfide and effectiveness of oxygen therapy in rats. Clin Toxicol (Phila). 2011 Mar;49(3):161-6.
  10. Fiedler N, Kipen H, Ohman-Strickland P, Zhang J, Weisel C, Laumbach R et al. Sensory and cognitive effects of acute exposure to hydrogen sulfide. Environ Health Perspect 2008 Jan;116(1):78-85.
  11. Warenycia MW, Goodwin LR, Benishin CG, Reiffenstein RJ, Francom DM, Taylor JD et al. Acute hydrogen sulfide poisoning. Demonstration of selective uptake of sulfide by the brainstem by measurement of brain sulfide levels. Biochem Pharmacol 1989 Mar 15;38(6):973-81.
  12. Chenuel B, Sonobe T, Haouzi P. Effects of infusion of human methemoglobin solution following hydrogen sulfide poisoning. Clin Toxicol (Phila) 2015 Feb;53(2):93-101.
  13. Chen J, Chen S, Mao W. A Case of Survival: Myocardial Infarction and Ventricular Arrhythmia Induced by Severe Hydrogen Sulfide Poisoning. Cardiology. 2016 May 19;135(1):43-47.
  14. Asif MJ, Exline MC. Utilization of hyperbaric oxygen therapy and induced hypothermia after hydrogen sulfide exposure. Respir Care 2012 Feb;57(2):307-10.
  15. Belley R, Bernard N, Cote M, Paquet F, Poitras J. Hyperbaric oxygen therapy in the management of two cases of hydrogen sulfide toxicity from liquid manure. CJEM 2005 Jul;7(4):257-61.
  16. Smilkstein MJ, Bronstein AC, Pickett HM, Rumack BH. Hyperbaric oxygen therapy for severe hydrogen sulfide poisoning. J Emerg Med 1985;3(1):27-30.
  17. Fujino Y, Inoue Y, Onodera M, Kikuchi S, Endo J, Endo S et al. Case followed by delayed loss of consciousness after exposure to hydrogen sulfide that was treated with intermittent administration of sodium nitrite. Chudoku Kenkyu 2010 Dec;23(4):297-302.
  18. Jiang J, Chan A, Ali S, Saha A, Haushalter KJ, Lam WL et al. Hydrogen Sulfide—Mechanisms of Toxicity and Development of an Antidote. Sci Rep 2016 Feb 15;6:20831.
  19. Judenherc-Haouzi A, Zhang XQ, Sonobe T, Song J, Rannals MD, Wang J et al. Methylene blue counteracts H2S toxicity-induced cardiac depression by restoring L-type Ca channel activity. Am J Physiol Regul Integr Comp Physiol 2016 Jun 1;310(11):R1030-44.
  20. Haouzi P, Sonobe T, Judenherc-Haouzi A. Developing effective countermeasures against acute hydrogen sulfide intoxication: challenges and limitations. Ann N Y Acad Sci 2016 Jun;1374(1):29-40.

Thank you to Dr. Daniel Sessions, Dr. Joseph K Maddry, and Dr. Vikhyat S Bebarta, Medical Toxicologists and EM physicians for their meaningful feedback while producing this document.

Blast Crisis: ED-focused management

Authors: Patrick C Ng, MD (EM Chief Resident, SAUSHEC Emergency Medicine Department) and Brit Long, MD (@long_brit, EM Attending Physician, SAUSHEC Emergency Medicine Department) // Editors: Jennifer Robertson, MD, MSEd and Alex Koyfman, MD (@EMHighAK, EM Attending Physician, UTSW / Parkland Memorial Hospital)

Case 1

A 66-year-old male, recently diagnosed with chronic myelogenous leukemia (CML) presents with a sudden onset of pain and loss of vision in the left eye while eating lunch. He had been previously asymptomatic. He reports no relieving or exacerbating features. Labs were at baseline two weeks prior to this visit.

On exam, he has normal vital signs. His visual acuity reveals 20/200 OS and 20/40 OD with his corrective lenses. His exam is otherwise unremarkable.

Some standard labs are ordered, and his white blood cell count returns at 50 x 109/L. With progression of his symptoms despite supportive care, the patient is admitted for further management. MRI reveals enhancement of soft tissue are around the orbit and optic nerve of the left eye. He undergoes enucleation of the left eye. Histopathology reveals thickening of the choroid and infiltration of the choroid by blast cells. The working diagnosis of extramedullary blast crisis in CML is made and induction therapy is started1.

Case 2

A 58 year old female, with a history of hypertension and CML, on imatinib, presents to your ED with 2 weeks of generalized fatigue and a 10lb weight loss.  For the past 24 hours, she has started to experience left upper quadrant abdominal pain with decreased appetite. Her review of systems is positive for bilateral knee pain and fever with a Tmax of 101°F. She has never experienced this constellation of symptoms in the past and reports minimal relief with OTC antipyretics.

Vitals: T101°F, HR 100, BP 170/90, RR 18, Sat 100% on RA

Exam is positive for a palpable spleen approximately 3cm below the costal margin, tachycardia, and suprapubic pain.

Labs are significant for a white blood cell count of 40.4 x 109/L with 25% blasts, platelet count of 110 x 103/µL, Hb of 8g/dL, and a normal chemistry.  UA is positive for nitrite, leukocyte esterase and 2+bacteria.

The patient is started on IV fluids, antipyretics, and broad spectrum antibiotics. Hematology/Oncology service is consulted, and the patient is started on ponatinib for the suspected progression of her CML despite first generation tyrosine-kinase inhibitor therapy. She is admitted with continued treatment to the hematology/oncology service. While in the hospital, she underwent a bone marrow biopsy which revealed hypercellularity with a predominance of neutrophils, eosinophils, and basophils with many megakaryocytes. Peripheral smear revealed a myeloid cell predominance.

During her hospital stay, she showed improvement with continued antibiotic and tyrosine kinase inhibitor therapy. She underwent a hematopoietic cell transplant by hematology/oncology and was discharged from the hospital with continued outpatient therapy.


Chronic myeloid leukemia (CML) is a hematological malignancy that affects the leukocyte cell linage. In essence, malignancies occur when cells have a reproductive advantage over others, with disruption in the balance of cell proliferation and cell death2. In CML, this balance of cell proliferation and cell death is disrupted secondary to a reciprocal translocation between chromosome 9 and 22, t(9:22)(q34;q11), also known as the Philadelphia (Ph) chromosome. These chromosomes contain the BCR and ABL genes. The translocation forms a BCR-ABL gene which is a tyrosine kinase. This ultimately leads to an increase in myeloid cells in the blood3.

There are three phases of CML: Chronic, Accelerated and Blast, shown below in Figure 1. Approximately 90% of patients present in the chronic phase3. Blast phase is a poor prognostic marker. According to some reports, the median survival after diagnosis of blast crisis ranges from 7-11 months and that patients with 20%-29% blasts at diagnosis have a better prognosis than those with >30%4. Typically, patients present in the chronic phase and are diagnosed with routine blood testing. CML can progress to the accelerated phase, followed by the blast phase. The disease is on a continuum and nonspecific characteristics of each phase are summarized in Table 1. Many of the symptoms are nonspecific, especially in the chronic and accelerated phases. The blast phase may present with signs/symptoms similar to infection.



CML Phase Chronic Accelerated Blast
Onset Indolent <1 year <6months
Signs/Symptoms Often asymptomatic, Fatigue, Decreased Appetite, Abdominal Pain/Fullness Same as Chronic Phase +/-Bone pain Same as accelerated phase+/- symptoms consistent with infection
Characteristic Clinical Findings Hepato/Splenomegaly Hepato/Splenomegaly unresponsive to treatment


Fever not otherwise explained




Same as accelerated phase +/- Bleeding, Infection


Symptoms refractory to treatment

Laboratory Abnormalities Including Peripheral Smear Leukocytosis, Anemia, Thrombocytosis Leukocytosis(>50 x 109/L)

Anemia (Hct <25%)

Thrombocytopenia (<100 x 109/L) or

Thrombocytosis (>1,000 x 109/L)

Blasts (≥10%)

Basophils (≥20%)

Thrombocytopenia(<100 x 109/L)


≥20% Blasts


Bone Marrow Aspirate Characteristics Hypercellular Hypercellular

≥10% Blasts


Same as accelerated +/-Megakaryocytes

≥20% Blasts


Table 1: Characteristics of CML phases,4,5,6,7,8

What are the key ED studies?

When the progression of CML is suspected in the ED, key studies to obtain include the CBC with differential, peripheral smear, chemistry, magnesium, coags, LFTs, lactate, uric acid, LDH, and phosphorous. As seen in Table 1, the diagnosis can be difficult due to the often vague symptoms, and lab abnormalities that are required for diagnosis confirmation. Patients that carry a diagnosis of CML can progress to the accelerated/blast phase despite being on treatment. CBC and differential with smear are important to obtain to determine whether or not a leukocytosis with a left shift is present, which can help you and your consultants narrow in on the diagnosis. Additionally, patients can present with varying degrees of platelet abnormalities and anemia, both of which may require specific interventions. It is important to consider these possible abnormalities as procedures such as bone marrow aspiration/biopsy can pose a significant bleeding risk.

The response to treatment and progression of CML is monitored by three different responses: hematologic, cytogenic, and molecular. In the ED, we can assess the hematologic changes in these patients with the labs mentioned above. Cytogenic and molecular testing are out of the scope of the ED provider and will be assessed by our consultants.

Additionally, infection can accompany progression of this disease. Based on the patient’s presentation and lab results, further workup (CXR, Blood cultures, UA, etc) and treatment with appropriate fluid resuscitation and antibiotics should be considered and discussed with the oncology team. Patients with documented fever will likely warrant broad-spectrum antibiotics. The ED provider must have a high degree of suspicion for infection in febrile patients presenting in blast crisis, as patients can be functionally asplenic. The proliferation of malignant cells in CML, particularly in the accelerated/blast phases, can lead to damage of the spleen secondary to splenic congestion and even splenic rupture5.

With the rapid proliferation of cell lines, patients may present with signs of end organ damage, likely secondary to hyperviscosity6-7, which can lead to end organ dysfunction and electrolyte abnormalities. Symptoms include but are not limited to bleeding, ocular, neurological, and cardiovascular problems8.

On a case by case basis, targeted diagnostics including labs and imaging may be indicated. There are rare presentations of blast crisis, particularly when there is an infiltration of leukemic blasts in areas other than the bone marrow, called extramedullary blast crisis9-12. Various case reports that describe extramedullary blast crisis include: presenting in the scalp, in the paravertebral area causing spinal cord compression, as leukemic ascites with liver disease and coagulopathy, in the eye with pain and vision changes eventually leading to enucleation, as an initial presentation with lymphadenopathy, with palpitations and dyspnea, with an osteolytic lesion presenting with leg pain, and as an osteolytic bone lesion leading to a pathologic fracture12-17. Although rare, extramedullary blast crisis can occur. However, this form is difficult to diagnose and requires oncology consultation.


As seen, the clinical presentation of CML can vary widely; however, the treatment is relatively consistent. The ED management requires initial resuscitation and stabilization. Assessment for infection and hyperviscosity syndrome is required, as these account for significant mortality. Hyperviscosity syndrome can be treated with plasmapheresis, plateletpheresis, or phlebotomy. For a further read on this dangerous manifestation, please see

The mainstay of oncologic therapy is with tyrosine-kinase inhibitors, with imatinib traditionally serving as the first line18. Patients not responding to initial dosing may be given a trial of an increased dose of imatinib. According to a recent survey, due to improved methods of disease monitoring and new generation tyrosine-kinase inhibitors, the use of imatinib as a first line agent has decreased. The use of newer generation tyrosine kinase inhibitors such as nilotinib/dasatinib has replaced imatinib as a first line agent according to several reports19-20. In patients that progress to blast crisis despite therapy, initial stabilization and resuscitation depending on the clinical presentation is indicated. Early consultation with a hematologist/oncologist is indicated as many of these patients with go on to combination chemotherapy with tyrosine-kinase therapy, and/or hematopoetic cell transplantation18-20.


-CML is a myeloproliferative disorder that can present at any age, but typically presents in the 6th decade of life

-CML has three phases: Chronic(most common), Accelerated, and Blast

-Blast phase is a poor prognostic factor

-Blast phase can present in a variety of ways including but not limited to eye pain, vision changes, neurologic complaints, joint pain, and bleeding. The emergency provider must maintain a high suspicion for this diagnosis, particularly in patients that carry a diagnosis of CML, although these can serve as initial presentations of the disease as well

-Blast phase can present in conjunction with other pathology including but not limited to fractures and infections. The emergency provider must be aware of this key point to properly address these pathologies in the initial resuscitation and management of the patient.

-Tyrosine kinase inhibitors serve as the first line of treatment for CML, those progressing to later phases may require other specialized therapy such as combination therapy or cell transplantation that will require expert consultation with a hematologist/oncologist.


References/Further Reading

  1. Gulati R, Alkhatib Y, Donthireddy V, Felicella MM, Menon MP, Inamdar KV. Isolated Ocular Manifestation of Relapsed Chronic Myelogenous Leukemia Presenting as Myeloid Blast Crisis in a Patient on Imatinib Therapy: A Case Report and Review of the Literature. Case Rep Pathol 2015:380451.
  2. Ferlay J, Bray F, Pisani P, Parkin DM. GLOBOCAN 2002: Cancer incidence, mortality and prevalence worldwide. IARC Cancerbase no.5, version 2.0. Available at: Last accessed 14July2016.
  3. Thora NK, Gundeti S, Linga VG, Coca P, Tara RP, Raghunadharao. Imatinib mesylate as first-line therapy in patients with chronic myeloid leukemia in accelerated phase and blast phase: A retrospective analysis. Indian Journal of Cancer 2014 51(1):5-9.
  4. Hehlmann R. How I treat CML blast crisis. Blood 2012 120:737-747.
  5. Jafferbhoy S, Chantry A, Atkey N, Turner D, Wyld L. Spontaneous splenic rupture: an unusual presentation of CML. BMJ Case Rep 2011 Mar 24;2011.
  6. Druker, BJ. Translation of the Philadelphia chromosome into therapy of CML. Blood 2008 112:4808-4817.
  7. Faderl S, Kantarjian HM, Talpaz M. Chronic Myelogenous Leukemia: Update of Biology and Treatment. Oncology 1999 Feb;13(2):169-80.
  8. Mehta J, Singhal S. Hyperviscosity syndrome in plasma cell dyscrasias. Semin Thromb Hemost 2003 Oct;29(5):467-71.
  9. Jabbour E, Kantarjian H, O’Brien S, Rios MB, Abruzzo L, Verstovsek S et al. Sudden blastic transformation in patients with chronic myeloid leukemia treated with imatinib mesylate. Blood 2006 107:480-482.
  10. Besa E. Chronic Myelogenous Leukemia. Medscape. Available at: Last accessed: 14July2016
  11. Granatowicz A, Piatek C, Moschiano E, El-Hemaidi I, Armitage JD, Akhtari M. An Overview and Update of Chronic Myeloid Leukemia for Primary Care Physicians. Korean J Fam Med 2015 Sep;36(5):197-202.
  12. Sahu KK, Malhotra P, Uthamalingam P, Prakash G, Bal A, Varma N, Varma SC. Chronic Myeloid Leukemia with Extramedullary Blast Crisis: Two Usual Sites with Review of Literature. Indian J Hematol Blood Transfus 2016 Jun;32:89-95.
  13. Said MR, Yap E, Jamaluddin WF, Wahid FS, Shuib S. A case of chronic myeloid leukaemia in blast transformation with leukemic ascities. Med J Malayasia 2016 Apr;71(2):85-7.
  14. Ai DI, Liu W, Lu G, Patel KP, Chen Zl. Extramedullary blast crisis as initial presentation in chronic myeloid leukemia with the e1a2 BCR-ABL1 transcript: A case report. Mol Clin Oncol 2015 Nov;3(6):1319-1322.
  15. Zeng DF, Chang C, Li JP, Kong PY, Zhang X, Gao L. Extramedullary T-lymphoblastic blast crisis in chronic myelogenous leukemia: A case report of successful diagnosis and treatment. Exp Ther Med 2015 Mar;9(3):850-852.
  16. Tsukamoto S, Ota S, Ohwada C, Takeda Y, Takeuchi M, Sakaida E, et al. Extramedullary blast crisis of chronic myelogenous leukemia as an initial presentation. Leuk Res Rep 2013 Aug 13;2(2):67-69.
  17. Yu HH, Lu MY, Lin DT, Lin KH, Tang JL, Jou ST. Pathological fracture as a manifestation of extramedullary blast crisis in chronic myelogenous leukemia: a report of one case. Acta Paediatr Taiwan 2006 May-Jun;47(3):150-4.
  18. Kantarjian HM, Larson RA, Cortes JE, Deering KL, Mauro MJ. Current Practices in the Management of Chronic Myeloid Leukemia. Clin Lymphoma Myeloma Leuk 2013 Feb; 13(1):48-54.
  19. Saglio G, Kim DW, Issaragrisil S, le Coutre P, Etienne G, Labo C, et al. Nilotinib versus imatinib for newly diagnosed chronic myeloid leukemia. N Engl J Med 2010 Jun 17;362(24):2251.
  20. Axdorph U, Stenke L, Grimfors G, Carneskog J, Hansen J, Linder O et al. Intensive chemotherapy in patients with chronic myelogenous leukaemia (CML) in accelerated or blastic phase-a report from the Swedish CML Group. Br J Haematol 2002 Sep;118(4):1048-54.



Immune Thrombocytopenic Purpura: Pearls and Pitfalls

Authors: Patrick C Ng, MD (EM Chief Resident, SAUSHEC Emergency Medicine Department) and Brit Long, MD (@long_brit, EM Attending Physician, SAUSHEC Emergency Medicine Department) // Edited by: Jennifer Robertson, MD, MSEd and Alex Koyfman, MD (@EMHighAK, EM Attending Physician, UTSW / Parkland Memorial Hospital)


A 7-year-old male, previously healthy and born at term, presents to the emergency department (ED) accompanied with his parents with a chief complaint of knee pain and subsequent difficultly walking. The child woke up with the knee pain, and it progressed throughout the day to the point where the child could not bear weight.  Oral acetaminophen and ibuprofen provided minimal pain relief at home. To add to the history, the patient was seen recently in the ED for a fever, nonproductive cough, and runny nose approximately 14 days prior. He was diagnosed with a viral syndrome, and his symptoms resolved with supportive care. A review of systems (ROS) is negative for numbness, weakness, fever, nausea, vomiting, or pedal edema. Surgical history is significant for a circumcision shortly after birth. There are no significant medical problems in the family.

On examination in the ED, vital signs are all within normal limits. The child holds his left knee in approximately 120 degrees of flexion. He displays significant pain with extension and flexion of the knee. There is no obvious deformity, nor is there any significant swelling or joint line tenderness. He has no tenderness on the tibial tuberosity or with manipulation of the patella. The rest of the child’s exam is unremarkable.

His workup consists of x-rays of the left lower extremity, revealing a knee effusion and mild soft tissue swelling, and a normal basic metabolic panel (BMP). His complete blood count (CBC) reveals a platelet count of 6,000/ uL. A diagnosis of hemarthrosis is made and it is likely secondary to immune thrombocytopenic purpura (ITP). Thus, the child is admitted for further management.

Immune Thrombocytopenic Purpura (ITP)

Immune thrombocytopenic purpura was once known as idiopathic thrombocytopenic purpura until it was discovered that the pathophysiology of the thrombocytopenia involved the host immune system [1]. In ITP, thrombocytopenia occurs secondary to antiplatelet antibodies that are produced in the spleen. These antibodies first bind to platelets, followed by phagocytosis of the platelet/antibody complex by the reticuloendothelial system [1,8,9]. ITP is the leading cause of thrombocytopenia in children [2]. It is defined as a platelet count of <100,000/uL. Other common characteristics of ITP include petechiae and/or purpura, normal hemoglobin and white blood cell (WBC) count, and the absence of other signs of identifiable causes of thrombocytopenia. Acute ITP typically resolves within 6-12 months and often occurs shortly after an infection or a vaccination [2,3]. The disease is considered chronic if the thrombocytopenia lasts longer than 6-12 months without another identified etiology. ITP can occur in both children and adults. Approximately 80% of ITP seen in children is acute. Adults are typically affected with the chronic form [3].  Regardless of the patient’s age and his or her form of ITP, the most feared complication of the disease is major bleeding. This includes, but is not limited to, life threatening gastrointestinal bleeding and intracranial hemorrhage. According to Farhangi et al, the overall risk of serious bleeding in children with ITP is 3%, while the risk of intracranial hemorrhage (ICH) is 0.5% [2]. Most cases present with less significant bleeding, however. In a retrospective analysis of infants with ITP from 1987 to 2002, the majority were found to present with purpura and active mucosal bleeding [4]. Other studies have found serious bleeding rates ranging from 2.9% to 17%. The definitions of serious bleeding were defined differently in each study, however ICH, bleeding with a drop in hemoglobin, bleeding that required hospitalization or blood transfusion, epistaxis requiring cautery or nasal packing, and/or gross hematuria were all included as definitions of severe bleeding [5, 6,7]. In a more in 2008, Neunert et al reported on 1106 ITP patients enrolled into the Intercontinental Childhood ITP Study group (ICIS). In this report, the authors conclude that severe bleeding is uncommon at diagnosis of ITP in children [7].  Finally, there a few reports, in form of case studies, that focus on other complications of ITP such as spontaneous hemarthrosis, as in the case above. The rates of such presentations are not well characterized in the literature but are important for the emergency physician to recognize as a potential presentation [8].

Some studies describe ITP as a more serious disease in adults due to higher ICH rates (5%) as compared to children [9]. Typically, adult cases have a more insidious onset, often without any preceding infection on history and physical [10].

The clinical presentation of ITP, particularly in children, is variable. There is no consensus on how to predict the chances of serious bleeding on initial presentation. Recognizing this is important as the emergency medicine provider must maintain a high degree of suspicion for a major bleed, particularly in patients with platelet counts <50,000/ uL and in those with wet purpura (mucosal sites with purpura).

What are the key ED laboratory studies?

The laboratory tests that are essential include CBC and peripheral smear, as the hemoglobin, WBC, and WBC morphology may suggest other diagnoses such as malignancy. Thrombocytopenia is essential to making the diagnosis of ITP.

So you have a patient with plt count 20,000/uL. Is this ITP?

History and physical, CBC, and peripheral smear can suggest a more sinister condition. Evaluate closely for a history of joint/bone pain or a family history of easy bruising. These are signs of malignancy or familial coagulopathy, respectively. Examination findings that are not consistent with ITP include soft tissue or bony abnormalities, a non-petechial rash, hepatosplenomegaly, and lymphadenopathy. Laboratory findings such as an abnormal hemoglobin, an abnormal WBC morphology, and abnormal WBC count suggest another etiology.

Is there a scoring system available?

The spectrum of ITP presentations can range from asymptomatic to life threatening bleeds. An objective measurement of bleeding in patients with ITP can be accomplished using the ITP Bleeding Scale (IBLS) and/or ITP-specific bleeding assessment tool (ITP-BAT) [11,12]. The ITP-BAT scoring system is more prevalent in the literature. In essence, the scoring system takes into account the bleeding manifestations by organ system: Skin(S), visible Mucosae (M) and Organs (O) with Gradation of severity (SMOG). The emergency provider (EP) may not be specifically calculating this score upon initial evaluation, as it is primarily used to evaluate the patient’s response to treatment. However, the EP should be aware of this score, paying particular attention to the specific organ systems to evaluate for major bleeding when considering the diagnosis of ITP.


The initial treatment is targeted at blunting the activity of the reticuloendothelial system and is primarily based on expert opinion. Treatment and admission is indicated in patients that have a major bleeding episode and/or platelet counts < 10,000/ uL [10]. Corticosteroids are the initial treatment for non-life threatening bleeds. Examples of corticosteroid regimens include prednisolone/prednisone at 1-2mg/kg per day or dexamethasone at 40mg/day for 4 days [10]. For ITP patients with major bleeds, treatment includes IVIG at 1g/kg, IV methylprednisolone 1g/d x 3 days, and platelet transfusions [9,10,13].

Patients may present with wet or dry purpura and management of both is similar. However, it is important to make this clinical distinction. Wet purpura indicates active bleeding which puts patients at increased risk for anemia. These patients may need to be monitored more closely, with serial laboratory studies and more frequent physical examinations to assess for the extent of bleeding. These patients may also require more aggressive transfusions cases of severe bleeding.

Newer therapeutic approaches with medications such as rituximab, cyclophosphamide, vinca alkaloids, and mycophenolate mofetil have been explored in cases of refractory ITP [10]. Splenectomy serves as an effective second line therapy in cases refractory to initial treatments [15]. These approaches are more often needed in adults.


  • ITP can present with severe, life threatening bleeding including, but not limited to, intracranial hemorrhage.
  • Physical examination should focus on signs of bleeding intracranially, intra-abdominally, in the skin, and from the mucosa.
  • Initial workup includes CBC, WBC morphology, and peripheral smear.
  • Initial management of steroids and admission should be considered depending on the clinical presentation.
  • There are atypical presentations of ITP such as hemarthrosis that the EP should consider.
  • Emergency physicians should maintain a broad differential, as subtle abnormalities in the workup other than low platelets can suggest alternative diagnoses such as malignancy.

References/Further Reading

  1. Lusher JM, Zuelzer WW. Idiopathic thrombocytopenic purpura in childhood. J Pediatr 1966;68:971-9.
  2. Fargangi H, Ghasemi A, Banihashem A, Badiei Z, Jarahi L, Esami G, Langaee T. Clinical Features and Treatment Outcomes of Primary Immune Thrombocytopenic Purpura in Hospitalized Children Under 2-Years Old. Iran J Ped Hematol Oncol. 2016; 6(1): 24-31.
  3. Kuhne T. Idiopathic thrombocytopenic purpura of childhood: a problem-oriented review of the management. Transfus Apher Sci 2003 Jun;28(2):243-8.
  4. Sandoval C, Visintainer P, Ozkaynak MF, Tugal O, Jayabose S. Clinical features and treatment outcomes of 79 infants with immune thrombocytopenic purpura. Pediatr Blood Cancer 2004 Jan;42(1):109-12.
  5. Watts RG. Idiopathic thrombocytopenia purpura: a 10-year natural history study at the Children’s hospital of Alabama. Clin Pediatr (Phila). 2004 Oct;43(8):691-702.
  6. Medeiros D, Buchanan GR. Major hemorrhage in children with idiopathic thrombocytopenic purpura: immediate response to therapy and long-term outcome. J Pediatr 1998 Sep;133(3):334-9.
  7. Neunert CE, Buchanan GR, Imbach P, Bolton-Maggs PH, Bennett CM, Neufeld EJ. Severe hemorrhage in children with newly diagnosed immune thrombocytopenic purpura. Blood 2008 Nov 15;112(10):4003-8.
  8. Moller DE, Goldstein K. Hemarthrosis and idiopathic thrombocytopenic purpura. J Rheumatol 1987 Apr;14(2):382-3.
  9. George JN, Woolf SH, Raskob GE, Wasser JS, Aledort LM, Ballem PJ, et al. Idiopathic Thrombocytopenic Purpura: A Practice Guideline Developed by Explicit Methods for The American Society of Hematology. Blood 1996;88:3-40.
  10. Stasi R. Pathophysiology and therapeutic options in primary immune thrombocytopenia. Blood Transfus 2011 Jul; 9(3): 262-273.
  11. Page LK, Psaila B, Provan D, Hamilton JM, Jenkins JM, Elish AS, et al. The immune thrombocytopenic purpura (ITP) bleeding score: assessment of bleeding in patients with ITP. British Journal of Haematology 138, 245-248.
  12. Rodeghiero F, Michel M, Gernsheimer T, Stasi R. Standardization of bleeding assessment in immune thrombocytopenia: report from the International Working Group. Blood 2013;121(14).
  13. Stasi R, Provan D. Management of immune thrombocytopenic purpura in adults. Mayo Clin Proc 2004 Apr;79(4):504-22.
  14. Supe A, Parikh M, Prabhu R, Kantharia C, Farah J. Post-splenectomy response in adult patients with immune thrombocytopenic purpura. Asian J Transfus Sci 2009 Jan; 3(1):6-9.
  15. Kojouri K, Vesely SK, Terrell DR, George JN. Splenectomy for adult patients with idiopathic thrombocytopenic purpura: a systematic review to assess long-term platelet count responses, prediction of response and surgical complications. Blood 2004;10:2623-34.