Episode 48 – Urine Drug Screen, Cocaine, and PCP


The Free Open Access Medical Education (FOAM)

We review a post by Dr. Seth Trueger (@MDaware) on false positives of common medications in the urine drug screen.  We delve into posts by Dr. Bryan Hayes (@PharmERToxGuy) on false negatives for benzodiazepines and opioids in the urine drug screen.

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Core Content

We delve into core content on cocaine and phencyclidine (PCP) using Rosen’s (8th edition), Chapter 154 and Tintinalli (8th edition)




Note: Beta-blockers are contra-indicated in cocaine induced hypertension and chest pain.  Much of the ischemia induced by cocaine is thought to be due to vasospasm, predominantly from alpha-1 receptor effects.  Beta-blockers block the relaxation provided by beta-2 stimulus on muscles, leaving alpha-1 constricting vessels, “unopposed.”  This is largely theoretical/based on canine literature as there are only two human studies on this, (a) 10 humans given propranolol + cocaine with vasospasm and (b) 9 humans given labetalol + cocaine without vasospasm [4,5]. However, recent papers attempting to dispel this teaching don’t quite prove the point. One retrospective chart review looked at cocaine positive urine screens in patients with chest pain and found no worsened troponins. Cocaine stays positive in the urine for 3 days so it is not clear that these were patients presenting with cocaine associated chest pain [6].

Phencyclidine (PCP)

Generously Donated Rosh Review Questions

  1.  An 18-year-old man is brought to the ED by the police after being found running around a parking lot, screaming at bystanders. He reportedly smoked phencyclidine (PCP) earlier that day. His vital signs are notable for a heart rate of 130 beats per minute and a blood pressure of 150/86 mm Hg. On physical exam, he is diaphoretic, with vertical nystagmus and equal pupils and appears acutely agitated. 

2. A 39-year-old woman presents with chest pain and difficulty breathing that began shortly after smoking crack cocaine. Vital signs are BP 190/85 mm Hg, HR 105, RR 18, T 99.1℉. The ECG demonstrates ST segment depression and T wave inversions in the lateral leads. 


  1. B. The most common cause of morbidity and mortality in patients with phencyclidine (PCP) intoxication is rhabdomyolysis. Fluid hydration with normal saline is the initial therapy for rhabdomyolysis. Creatinine kinase (CK) should be obtained in patients with PCP intoxication. If abnormal, serial levels should be obtained until a downward trend is noted. Serum creatinine should also be monitored for evidence of renal insufficiency. PCP is a dissociative anesthetic drug that works on the NMDA glutamate receptor. People who abuse PCP can have sensations of euphoria initially, but this can be followed by an emergence reaction that is characterized by dysphoria and psychosis. If initial calming measures such as placing the patient in a calm environment fail and chemical restraints are needed, benzodiazepines are the treatment of choice. Benzodiazepines are also the preferred medication for acute agitation. Haloperidol (A) may cause dysrhythmias and hypotension. It also lowers the seizure threshold and may precipitate PCP-induced movement disorders. PCP is a weak base and its excretion is increased in acidic urine. Physical restraints (C) may be required for patients with PCP intoxication, but they should be used in conjunction with chemical restraints (preferably benzodiazepines). An agitated patient fighting against physical restraints is at risk for worsening rhabdomyolysis, which, if unrecognized, can precipitate cardiac arrest. Traumatic injuries (D)frequently occur in PCP-intoxicated patients; however, rhabdomyolysis with subsequent renal insufficiency is the most common cause of associated morbidity and mortality. Patients with PCP intoxication should be evaluated for suspected trauma, and any injuries should be stabilized and treated. Acidification of the urine (E) can cause a metabolic acidosis, which is potentially harmful and has not demonstrated improved outcomes. For these reasons, urinary acidification is not routinely recommended.
  2. A. D  Diazepam, a benzodiazepine, should be administered to this patient who is hyperadrenergic from cocaine intoxication. Signs and symptoms of cocaine intoxication include, dilated pupils, diaphoresis, tachycardia, hypertension and hyperthermia. Many patients experience euphoria, though some will develop acute psychosis. Benzodiazepines decrease the cocaine-induced hyperadrenergic state. Reduction of sympathetic tone induces coronary and peripheral vasodilation. Coronary artery dilation directly improves myocardial blood flow. Peripheral vasodilation reduces preload and afterload. Reductions in preload and afterload decrease blood pressure and improve myocardial oxygen demand. Several factors, including, excess sympathetic stimulation, dehydration, hyperthermia, and cocaine-induced cardiac sodium channel blockade, may cause patients with cocaine intoxication to develop dysrhythmias. These contributing factors should be treated with benzodiazepines, IV fluid resuscitation and temperature management. In some patients, cocaine-induced cardiac sodium channel blockade may cause wide complex tachycardia that should be treated with sodium bicarbonate. Hyperthermia should be managed aggressively with a target temperature of less than or equal to 102.0℉. Severe agitation, aggression or psychosis should be initially managed with benzodiazepines. Most antipsychotic agents have pronounced anticholinergic side effects. This may worsen dysrhythmias.and decrease sweating, further complicating temperature management.
  1. Rao R, Hoffman RS.  Cocaine and other Sympathomimetics. Rosen’s Emergency Medicine (8e). Chapter 154, 1999-2006.e2
  2. “Cocaine and Amphetamines.” Tintinalli’s Emergency Medicine: A Comprehensive Study Guide (8e). Chapter 187
  3. “Prison Medicine.” Tintinalli’s Emergency Medicine: A Comprehensive Study Guide (8e). Chapter 301
  4. Lange RA, Cigarroa RG, Flores ED, et al. Potentiation of cocaine, induced coronary vasoconstriction by beta adrenergic blockade. Ann Intern Med. 1990;112:897–90
  5. Boehrer JD, Moliterno DJ, Willard JE, Hillis LD, Lange RA. Influence of labetalol on cocaine-induced coronary vasoconstriction in humans. Am J Med. 1993;94(6):608–610
  6. Ibrahim M, Maselli DJ, Hasan R, Hamilton A. Safety of β-blockers in the acute management of cocaine-associated chest pain. The American Journal of Emergency Medicine. 31(3):613-616.


Episode 43 – Alcohols


The Free Open Access Medical Education (FOAM)

The Skeptic’s Guide to Emergency Medicine Episode 144, “That Smell of Isopropyl Alcohol for Nausea in the Emergency Department.” This podcast reviews an article by Beadle et al, an RCT on the use of inhalational isopropyl alcohol for nausea.

Population – Adults in the Emergency Department

Intervention – Nasal inhalation of an isopropyl alcohol pad for ~ 60 seconds (time 0 and, if still nauseated, at 2 minutes and 4 minutes)

Comparison – Nasal inhalation of an identical pad soaked in saline.

Outcome -Nausea score at 10 minutes post treatment using an 11-point verbal numeric response scale (0:“no nausea”; 10:“worst nausea imaginable”)

  • Lower in the isopropyl group (Median score of 3 vs. 6 on an 11 point scale, p<0.001). This gave an effect size of 3 (95% CI 2 to 4).

Limitations – single center, convenience sample, unclear blinding as isopropyl likely has a particular smell to it, outcome nausea score, not vomiting

Eagerton-Warburton et al conducted an RCT of intravenous ondansetron 4mg, metoclopramide 20mg, or saline (placebo) of adult patients with nausea and found  no significant difference in nausea scores on a visual analog scale between groups (n=270).

Core Content

We delve into core content on vertigo using Rosen’s Medicine (8e),  Chapter 155 “Toxic Alcohols”  and Tintinalli’s Emergency Medicine: A Comprehensive Study Guide  (7e) Chapter 179“Alcohols.”

Any alcohol can be “toxic,” the ramifications depend on the dose. Toxic alcohols typically refer to ethylene glycol (EG) and methanol.  In these cases, the parent compound (EG or methanol) is inebriating but not particularly toxic. These compounds are metabolized, like any alcohol, but unfortunately the metabolites (oxalic acid – EG, formic acid – methanol) have unique toxic properties. For example, the oxalic acid produced from EG metabolism combines with calcium.  These deposit into tissues causing renal failure and neurologic sympotms. The formic acid has a predilection for the retina, causing visual symptoms.

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Toxic Alcohols

Osmolal Gap (calculator) – One of the touted features of toxic alcohols is the elevated anion gap, that is, the difference between the measured serum osmolality and the calculated osmolarity.

Calculated Osmolarity: 2[Sodium] + [Glucose]/18 + [BUN]/2.8 + [ETOH]/4.6    (Note: Some references use ETOH/3.7)

  • Problems:  A normal osm gap does not exclude the presence of toxic alcohols as the osm gap decreases as the alcohol is metabolized.  Also, other disease processes can increase the osm gap, including shock, diabetic ketoacidosis, etc [2,3].
Osm Gap vs Anion Gap As Toxic Alcohols Metabolize

Osm Gap vs Anion Gap As Toxic Alcohols Metabolize

A common pearl exists that urine can be placed under a Wood’s lamp for fluorescence due to the fluorescein in ethylene glycol antifreeze (to detect leaks). Unfortunately this is neither sensitive nor specific [4,5].


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Rosh Review Questions

Question 1. 

Question 2. 


1. A. Hypocalcemia. Most laboratories do not have the capability to measure serum levels of toxic alcohols in a timely fashion. As a result, physicians must use other clinical markers to determine the presence of these unmeasured toxins. The classic laboratory abnormality is an elevated serum osmolality with an osmolar gap since the actual toxic alcohol is not measured in its own quantity but contributes to the osmolality of the blood. When calculating the osmolar gap, it is important to have a measured serum ethanol level as this is a large contributor to the final osmolality.Ethylene glycol ingestion leads to the formation of calcium oxalate crystals. As a result, serum calcium levels will decrease and hypocalcemia is a surrogate marker for ethylene glycol toxicity.Hypoglycemia (B) is not characteristic of a toxic alcohol ingestion. Hypoglycemia is often seen in chronic alcoholics due to poor nutritional intake. In children, ethanol may induce hypoglycemia. Other toxic ingestions which may lead to hypoglycemia include beta-blockers, sulfonylureas and insulin. Hypokalemia (C) is not associated with any toxic alcohol ingestions. As patients become more acidemic from alcohol ingestions, hyperkalemia may develop. Hyponatremia (D) is not associated with toxic alcohol ingestions. Evidence of hyponatremia on laboratory analysis should prompt further investigation for other underlying causes.

2.C.  Glycolic acid level greater than 8 mmol/L. A glycolic acid level greater than 8 mmol/L is an indication for emergent hemodialysis following an acute ethylene glycol overdose. Ethylene glycol is found in automobile coolants, antifreeze, hydraulic brake fluid, de-icing agents and industrial solvents. Symptoms progress through 4 stages: inebriation and intoxication, cardiopulmonary symptoms (tachycardia, hypertension, pulmonary edema), renal symptoms (acute renal failure), and delayed neurologic symptoms (cranial neuropathy). Treatment includes 1.) Alcohol dehydrogenase (ADH) enzyme blockade with fomepizole or ethanol to prevent toxic and acidic metabolite production, 2.) Correction of the metabolic acidosis with sodium bicarbonate, and 3.) Hemodialysis for removal of the parent compound and toxic metabolites. Although somewhat controversial with the advent of fomepizole other indications for hemodialysis following ethylene glycol ingestion include severe metabolic acidosis, renal failure, deterioration despite intensive care, and electrolyte disturbances.Other indications for emergent hemodialysis following an acute ethylene glycol overdose include: ethylene glycol level greater than 50 mg/dL (B), anion gap greater than 20 mmol/L (A)and initial pH less than 7.3 (D).


  1.  Beadle KL, Helbling AR, Love SL, April MD, Hunter CJ. Isopropyl Alcohol Nasal Inhalation for Nausea in the Emergency Department: A Randomized Controlled Trial. Annals of emergency medicine. 2015. [pubmed]
  2. Chapter 155.  “Toxic Alcohols. ” In: Marx JA, Hockberger RS, Walls RM eds.  Rosen’s Emergency Medicine, 8th e.
  3. Chapter 179. Alcohols. In: Tintinalli JE, Stapczynski J, Ma O, Cline DM, Cydulka RK, Meckler GD, T. eds. Tintinalli’s Emergency Medicine: A Comprehensive Study Guide, 7e.New York, NY: McGraw-Hill; 2011.
  4. Tobe TJM, Braam GB, Meulenbelt J, et al: Ethylene glycol poisoning mimicking Snow White. Lancet 2002; 359: pp. 444
  5. Wallace KL, Suchard JR, Curry SC, et al: Diagnostic use of physicians’ detection of urine fluorescence in a simulated ingestion of sodium fluorescein–containing antifreeze. Ann Emerg Med 2001; 38: pp. 49

Episode 28 – Neuroleptic Malignant Syndrome, Serotonin Syndrome, & Malignant Hyperthermia

(ITUNES OR Listen Here)

The Free Open Access Medical Education (FOAM)

We review a post from Dr. Charles Bruen from ResusReview on  Malignant Hyperthermia and dantrolene.

Malignant hyperthermia – a rare condition typically associated with volatile anesthetics, so more often an OR/inpatient issue; however, has been associated with succinylcholine use.

Cause: most often a mutation of the ryanodine receptor which, in the presence of certain anesthetics or succinylcholine causes too much intracellular calcium.  This leads to increased ATP production.

Signs/Symptoms: tachycardia, hypercarbia, muscle rigidity, hyperthermia

Treatment – Dantrolene.

  • Administer though a large vein
  • Caution with calcium channel blockers – may lead to hyperkalemia or myocardial depression
  • Dantrolene has also been used in severe dinitrophenol (industrial chemical and weight loss supplement) toxicity – see this Poison Review post.

The Bread and Butter

We cover syndromes associated with psychiatric medications and polypharmacy including neuroleptic malignant syndrome (NMS), serotonin syndrome, and some extrapyramidal side effects.  We do this based on  Rosen’s Emergency and Tintinalli. But, don’t just take our word for it.  Go enrich your fundamental understanding yourself.

Ref: Boyer EW, Shannon M. The serotonin syndrome. N Engl J Med. 2005;352:(11)1112-20.


Neuroleptic Malignant Syndrome

Caused by atypical antipsychotics, rare, idiosyncratic and may persist for 2+ weeks after discontinuation of the offending medication

Symptoms – Varied diagnostic criteria but requires temp >100.4F + muscle rigidity + at least two of the following (in rough order of frequency):

  • Diaphoresis
  • Leukocytosis
  • AMS
  • Elevated creatine kinase
  • Labile blood pressure
  • Tachycardia
  • Tremor
  • Incontinence
  • Dysphagia
  • Mutism

Treatment – remove offending agents, supportive care (intravenous fluids, cooling), benzodiazepines. Dantrolene, amantadine, and bromocriptine are not recommended.

Serotonin Syndrome

(PV card from Academic Life in Emergency Medicine).  Caution with the elderly as these symptoms may be attributed to infection or delirium (and vice versa).

Symptoms – Classical clinical triad of AMS + Autonomic instability (Hyperthermia, Tachycardia, diaphoresis) + Neuromuscular Abnormalities: Myoclonus, ocular clonus, rigidity, hyperreflexia, tremor.  Yet like most clinical triads, this performs poorly. The Hunter Criteria are often used (Sensitivity ~84%):

  • Serotonergic agent plus 1 of the following:
    • Spontaneous clonus
    • Inducible clonus + agitation or diaphoresis
    • Ocular Clonus + agitation or diaphoresis
    • Tremor + hyperreflexia
    • Hypertonia + temp >38F AND ocular clonus or inducible clonus

Serotonin syndrome often begins with akathisia (restlessness) and body systems become increasingly “ramped up” with tremors, followed by altered mental status, and then incereasing amounts of rigidity (inducible clonus -> Sustained clonus (+/- ocular clonus) -> Muscular rigidity -> Hyperthermia -> Death)

Causes – While often associated with antidepressants, polypharmacy seems to be the culprit here. Serotonin syndrome is commonly associated with some of these medications

  • Antidepressants –
    • SSRIs/SNRIs – sertraline, fluoxetine, paroxetine, citalopram, venlafaxine, etc
    • Trazodone, Buspirone
    • TCAs
    • MAOIs
  • Analgesics – fentanyl and tramadol
  • Antibiotics – Linezolid (Poison Review post)
  • Antiemetics – ondansetron, metoclopramide
  • Anti-epileptics – depakote
  • Anti-tussive – dextromethorphan
  • Herbs – St. John’s wort, ginseng

Extrapyramidal Symptoms

Acute Dystonia – involuntary motor tics or muscle spasms classically including torticollis, tongue or lip protrusion, or oculogyric crisis

Akathisia – a feeling of restlessness often accompanied by tapping, pacing, rocking. Reversible.

  • ~40% of patients given 10 mg of intravenous prochlorperazine developed akathisia within 1 hour.

Treatment: Benzodiazepines, Benadryl (diphenydramine), Benztropine

Generously Donated Rosh Review Questions 

Question 1. A 35-year-old man presents with fever, hypertension and altered mental status. He was recently started on haloperidol for schizophrenia. Physical examination reveals a confused patient with muscle rigidity. 


1. C.  FOAMcast editorial: This is an exercise in selecting the *best* answer, not the one that is most correct. You’ve probably noted that a benzodiazepine is not an option, the next best option is dantrolene.

This patient presents with signs and symptoms concerning for neuroleptic malignant syndrome (NMS) and should be treated with dantrolene. NMS is a life-threatening complication of neuroleptic drug treatment. It is rare and only effects 0.5 – 1% of patients receiving these drugs. Although it is more common with use of the typical neuroleptic medications, it can also be seen with the atypical agents. It usually occurs within the first few weeks of starting neuroleptic medications but can also be seen after an increase in dosage. NMS is characterized bymuscle rigidity, fever, altered mental status and autonomic instability. Muscle contraction leads to an elevated serum creatinine kinase. Due to similarities, the disease may be confused with serotonin syndrome. NMS can become complicated by respiratory, hepatic or renal failure, cardiovascular collapse, coagulopathy or gastrointestinal hemorrhage. Dantrolene is a direct acting muscle relaxant that can be beneficial in severe cases.

Episode 20 – Anticoagulation


The Free Open Access Medical Education (FOAM)

We review Dr. Rory Spiegel’s, A Case of Identity Part Two, post on EMNerd which is essentially a take down of dual antiplatelet therapy (DAT) in acute coronary syndrome (ACS).  The bottom line?  There’s no demonstrable and clinically significant benefit from DAT as demonstrated in the trials below.

CURE trial – composite endpoints of questionable clinical significance and an enormous sample size.

  • 2.1% absolute decrease in cardiovascular death and myocardial infarction (MI), completely powered by the 1.5% absolute difference in MIs. Almost all of these MIs were Type IV and peri-procedural. Mortality between groups was identical at 30 days and end of follow up (1.0% vs 1.1% and 2.3% vs 2.4%, respectively).

ACCOAST – RCT of prasugrel or placebo prior to angiography

  • No difference in cardiovascular death, myocardial infarct, stroke, urgent revascularization or glycoprotein IIb/IIIa rescue therapy (10.8% vs 10.8%)
  • Approximately 1% increase in major bleeding

CREDO – RCT with placebo or clopidogrel 3-24 hours prior to urgent cardiac catheterization

  • No statistical difference  in the rates of death, stroke or MI at 28 days
  • Statistical significance of a secondary endpoint of the 1-year outcomes with a 2% absolute reduction in the rate of death, MI, and stroke, largely the result of a 1.9% reduction of MIs.
  • 1% increase in major bleeding events

Thienopyridine Meta-Analysis

  • In patients with non-ST elevation ACS, pretreatment with thienopyridines is not associated with reduced mortality but comes at a cost of a significant excess of major bleeding.

Composite endpoints are problematic (see this post, “Would You Rather“) and statistical significance claimed in these trials is largely a product of composite outcomes rather than patient oriented measures.

The Bread and Butter

We summarize some key topics from the following readings, Goldfrank (10th ed) Chapter 60, EMPractice October 2013 (there’s almost nothing in Rosenalli on this topic) but, the point isn’t to just take our word for it.  Go enrich your fundamental understanding yourself!


  • Irreversibly inhibits platelets (for the duration of platelet’s life)


  • Reversibly inhibits platelets

Novel Oral Anticoagulants (NOACs)

NOACs have gained increased popularity and are slowly supplanting warfarin for common anticoagulation indications such as non-valvular atrial fibrillation (NVAF) as well as treatment of venous thromboembolisms such as pulmonary embolism (PE) and deep venous thrombosis (DVT).

Direct thrombin inhibitor – dabigatran (Pradaxa).  This drug was the first to supplant warfarin for NVAF in the United States, billed as more patient friendly given the lack of purported need for routine monitoring.  Recent investigations by Cohen et al, however, demonstrate that monitoring may, in fact, be safer.  Further, in a real world, retrospective cohort of Medicare beneficiaries given either dabigatran or warfarin for atrial fibrillation, major bleeding of the dabigatran cohort was higher than in the warfarin cohort 9.0% (95% CI 7.8 – 10.2) versus 5.9% (95% CI 5.1 – 6.6) after propensity matching [Hernandez].  For more on the problems with dabigatran, check out Emergency Medicine Literature of Note.

  • Predominantly renal excretion
    • Caution with impaired renal function (can cause dabigatran to stick around longer)
    • Hemodialysis an option in acute overdose; however, most people would probably not want to put a dialysis catheter in a coagulopathic patient.
  • Half-life ~ 15 hours
  • Can elevate the PTT. If the PTT is normal, likely not coagulopathic secondary to dabigatran [Dager et al].
  • No reversal agent

Factor XA inhibitors – these have XA in the name….rivaroXAban, apiXAban, edoXAban.

Rivaroxaban – approved for NVAF and treatment of DVT/PE.  Half life approximately 6-9 hours.

Apixaban – approved for NVAF and treatment of DVT/PE. Half life about 12 hours.

Edoxaban – approved for NVAF. Half life about 10-14 hours.

Bleeding Duration from ACCP

Bleeding Duration from ACCP

  • Cleared by liver and kidneys.
  • Can elevate the prothrombin time (PT), but not reliably. Specific assays exist but are not widely available and are expensive.
  • No specific reversal agent although andexanet alfa is in the pipeline.  It’s a Factor Xa decoy (Andexanet Alfa) that binds up the F10A inhibitors like a sponge. Read more here.
  • In the setting of major bleeding, guidelines recommend 4 factor PCCs.  A recent study demonstrates reduction in bleeding using 4 factor PCCs on healthy patients given edoxaban [Zahir et al, EMLitofNote].  The benefit of 4 factor PCCs is predominantly based on improvement in numbers, not patient oriented benefit and is discussed in these posts by Dr. Spiegel The Sign of Four, The Sign of Four Part 2.

More FOAM on Anticoagulation Reversal

Generously Donated Rosh Review Questions 

Question 1. A 65-year-old man with a metal aortic valve presents with hematemesis. His vitals are BP 95/50 and HR 118. The patient is on warfarin and has an INR of 7.3. 

Question 2. A 66-year-old woman with atrial fibrillation on warfarin presents with dark stools for 2 days. Her vitals are T 37.7°C, HR 136, BP 81/43, RR 24, and oxygen saturation 94%. Her labs reveal a hematocrit of 19.4% (baseline 33.1%) and an INR of 6.1. 



1. D.  The patient presents with life-threatening bleeding and an elevated INR from warfarin use requiring immediate anticoagulant reversal regardless of the indication for anticoagulation. Warfarin acts by inhibiting vitamin K recycling thus limiting the effectiveness of vitamin K dependant clotting factors (factors II, VII, IX and X). The effect of warfarin can be measured using the prothrombin time or the INR. Warfarin is indicated for anticoagulation for a number of disorders including the presence of a metal valve. Patients with metal valves are at a higher 1-year risk of clot formation around the valve and subsequent embolic stroke. The therapeutic goal of warfarin in a patient with a metallic valve is usually between 2.5 –  3.5 or 3.0 – 4.0. Despite the increased stroke risk, patients with life-threatening bleeding should always have their warfarin reversed by administration of vitamin K and fresh frozen plasma (FFP). Alternatively, prothrombin complex concentrates can be given instead of FFP.

Warfarin is not amenable to hemodialysis (A) for removal or reversal. Although patients with a mechanical valve are at an increased stroke risk (increased 1 year risk) reversal should not be delayed (B), as the patient is more likely to die in the immediate situation from their gastrointestinal bleed. Platelet transfusion (C) will not help, as warfarin does not inhibit platelet function.

2. C.  The patient has a life-threatening gastrointestinal bleed in the setting of anticoagulation with warfarin, a vitamin K antagonist. Warfarin acts by inhibiting the synthesis of vitamin K-dependant factors in the coagulation cascade (II, VII, IX, X, protein C, and protein S). The anticoagulant effect of warfarin should be reversed as part of the patient’s emergent treatment. Fresh frozen plasma (FFP) contains all factors in the coagulation cascade and should be given in patients with major bleeding and elevated INR. Vitamin K should be given IV in critically ill patients with elevated INR because it shortens the time to effect.

Vitamin K should not be given intramuscularly (B) because absorption via this route is highly variable. Vitamin K should also not be given orally (D) in critically ill patients because the onset of action will be delayed. Additionally, absorption in patients with gastrointestinal bleeding may be variable. Vitamin K should be given along with FFP (A) because the factors inhibited rely on vitamin K for function.

Episode 19 – Environment: Mushrooms and Hypothermia


The Free Open Access Medical Education (FOAM)

We review the Tox Talk podcast, Episode 23 – Mushrooms.  Our favorite pearls:

Clitocybe, Inocybe – contain muscarine which stimulates muscarinic receptors (acetylcholine/parasympathetic), causing a cholinergic toxidrome. Think SLUDGE (salivation, lacrimation, urination, defecation, gastric emptying/emesis) and the Killer B’s (bradycardia, bronchorrhea, bronchospasm) or DUMBELLS (diarrhea/diaphoresis, urination, miosis, bradycardia, emesis, lacrimation, lethargy, salivation). Basically, cholinergic toxidrome: SMALL, WET, SLOW.

  • Memory aid: these mushrooms end in -yBE, akin to the “killer B’s” that make cholinergic toxicity deadly.

Gyromitra – (false morel) contains gyromitrin which can cause seizures, in addition to gastrointestinal upset and liver failure.  Treatment: pyridoxine (B6).

  • Memory aid: gyromitra named because they look like the gyri of the brain and, conveniently, make the brain seize through depletion of GABA.

Amanita phalloides – contains amatoxins which cause delayed gastrointestinal symptoms and liver failure., echoing acetaminophen toxicity.

  • Caution: this is different than the amanita muscaria ‘mushroom, which is tricky because that amanita muscaria has neither muscarinic properties nor the toxicity of amanita phalloides.

Bonus pearl: Coprinus species can cause a disulfiram like reaction.

FOAM article on mushrooms by Jo et al

The Bread and Butter

We summarize some key topics from the following readings, Tintinalli (7e) Chapter  ; Rosen’s 8(e) Chapter  – but, the point isn’t to just take our word for it.  Go enrich your fundamental understanding yourself!

Hypothermia starts at 35°C and then is categorized based on severity.


  • Ethanol + hypothermia = bad news.  Ethanol is the most common cause of excessive heat loss in urban areas as people tend to not take warming measures, may be homeless or without heat, and have impaired thermoregulation.  Hypothermia also slows alcohol metabolism, making people drunker for longer.
  • Elderly patients are more susceptible to hypothermia, particularly as they may not sense the cooler temperatures.  Some may also have impaired thermoregulation.
  • Have a low threshold


  • Get a temperature, on all patients.  This applies to patient’s “found down” as well as the chronic alcoholic who just seems really drunk.
  • If patients aren’t rewarming 1°C/hr and they’re above 32°C, consider: sepsis, cortisol deficiency, myxedema, ethanol.
  • The J wave or “Osborn” wave is found in many cases of hypothermia, often quoted at ~80%.  However, it is not pathognomonic for hypothermia.

From the Rosh Review

Treatment: Warm the patient.  Don’t call the patient dead until they’re warm and dead, which means their temp is above 30-32°C.

Screen Shot 2014-11-22 at 9.30.13 PM

Passive Rewarming – effective when the patient can still shiver (33-35°C).

  • Generates ~1.5°C of heat/hr

Active Rewarming – direct transfer of heat to the patient.

  • Indications: Cardiovascular instability, temp ≤30-32° C, inadequate rate of rewarming or failure to rewarm, endocrine problem, trauma, tox, secondary hypothermia impairing thermoregulation
  • Can be external or internal (which can be minimally invasive like IV fluids or quite invasive with things like bypass or pleural lavage).


  • Unlikely survival with a potassium > 12 mmol/L and recommendations are to terminate resuscitation for potassium >12 mmol/L and consider cessation for potassium between 10-12 mmol/L

FOAM Resources:

EBM Gone Wild on Prognostication

ScanCrit on ECMO in Accidental Hypothermia

EMCrit on Severe Accidental Hypothermia

Generously Donated Rosh Review Questions (Scroll for Answers)

Question 1.  A 40-year-old man with a history of substance abuse is brought in by EMS after being found unconscious outside of a nightclub in the middle of winter. It is unclear how long he was outside. He is unresponsive with a GCS of 3.

Question 2.  What is the most common cause of death in hypothermic patients after successful resuscitation?

Question 3.

Question 4. What abnormal rhythm is common with temperatures below 32°C?


Danzl DF, Zafren K. Accidental Hypothermia, in Marx JA, Hockberger RS, Walls RM, et al (eds): Rosen’s Emergency Medicine: Concepts and Clinical Practice, ed 7. St. Louis, Mosby, Inc., 2013, (Ch) 140: pp 1883-1885.

Brown D JA, Brugger H, et al. Accidental Hypothermia. N Engl J Med 2012;367:1930-1938.

Mair P, Kornberger E, et al. Prognostic markers in patients with severe accidental hypothermia and cardiocirculatory arrest. Resuscitation 1994;27:47-54.


1. D. When the serum potassium is greater than 12 mmol/L resuscitative efforts should be halted as the patient is unlikely to survive and further efforts constitute futile care. Accidental hypothermia is not an uncommon occurrence particularly in colder climates. It may occur in conjunction with substance abuse when an individual becomes impaired and is subsequently exposed to the outdoors. It can also occur as a result of drowning, avalanche and other trauma. Bio-makers other than potassium have been studied including serum lactate (B), pH (C) and clotting time. None have been proven prognostically reliable and therefore should not be used as a guide to determine if resuscitation should be continued. Hypothermic patients that present in cardiac arrest should be warmed to a minimum of 32°C (A) preferably via ECMO or cardiopulmonary bypass. However, if a hypothermic patient is warmed to 32°C and remains in asystole, recovery is unlikely and resuscitative efforts should be terminated. Other indications to cease resuscitative efforts include: obvious signs of irreversible death (e.g. major trauma), valid DNR order, conditions that are unsafe for the rescuer or provider, and an avalanche burial > 35 minutes in which the airway is packed with snow and the patient is asystolic.

2. Pulmonary edema.

2. C. Hypothermia. The ECG demonstrates the presence of J waves or Osborn waves which are seen in hypothermia. One of the first cardiac effects of hypothermia is bradycardia secondary to decreased firing of the cardiac pacemaker cells in cold temperatures. Osborn waves may appear at any temperature below 32°C. The waves are an upward deflection at the terminal portion of the QRS complex. They may represent abnormal ion flux in cold temperatures along with delayed depolarization and early repolarization of the left ventricular wall. As temperatures continue to drop, the ECG will demonstrate prolonged intervals: PR, followed by QRS and then QTc. Both diabetic ketoacidosis (A) and digoxin toxicity (B) may lead to hyperkalemia. In diabetic ketoacidosis, hyperkalemia develops as a result of the acidic pH in the blood and the transport of hydrogen ions intracellularly in exchange for a potassium ion. Digoxin toxicity poisons the cellular Na+/K+ ATPase resulting in elevated extracellular levels of potassium. The ECG manifestations of hyperkalemia begin with peaked T waves. Multiple other findings eventually develop including a shortened QT interval, ST depression, bundle branch blocks, widened QRS, prolonged PR interval, flattened T wave and ultimately a sine wave. Hyperparathyroidism (D) may lead to hypercalcemia. In hypercalcemia, the ECG shows a shortened QT interval, flattened T waves and QRS widening at very high levels.

4.  Atrial fibrillation.

Episode #1: EMCrit Episode #122 – Cyanide and Carbon Monoxide Toxicity


Welcome to FOAMcast, a podcast created by residents who love Free Open Access Medical education (FOAM).  We are looking at cutting edge FOAM and distilling it down to the basics.  We’re not doing this to replace reading and hard work but increase interest and direct listeners to linking sexy FOAM with core content.  So listen, and go read it yourself.

What Did Weingart and Dr. Nelson say?

  • Patient in extremis or arrest after a fire and burn size doesn’t correlate to severity of illness?  Treat for cyanide toxicity.
  • Treatment: hydroxocobalamin 5g IV in ~250mL normal saline in adults or 70 mg/kg in pediatric patients.
  • Get labs, including lactate, carboxyhemoglobin level, and transaminases prior to giving hydroxocobalamin if possible because the drug turns everything red and interferes with these tests.

And the Basics of Chemical Asphyxiants?

If a patient presents after smoke exposure, consider cyanide and carbon monoxide toxicity (Case Quiz).  These toxicities have many similarities such as: impaired oxygen delivery and utilization, metabolic acidosis with elevated lactate, and presence in patients with smoke inhalation.

Cyanide Toxicity – Tintinalli (7e) Ch 198; Rosen’s (8e) Ch 179

Mechanism – Binds to the iron of the cytochrome a3 of complex IV in the mitochondria, the last step of oxidative phosphorylation, effectively shutting down the mitochondria and ATP production leading to tissue hypoperfusion.


  • Cyanide level is worthless in the acute setting.  If suspicious, treat without waiting for labs.
  • Labs often demonstrate a metabolic acidosis and, in a fire victim, a lactate >10 mmol/L is suspicious for cyanide toxicity.


  • ABCs – 100% oxygen, crystalloids and vasopressors for hypotension
  • Hydroxocobalamin 5 g IV for adults or 70 mg/kg IV for pediatrics
    • Cyanide binds to hydroxocobalamin, forming cyanocobalamin (vitamin B12) which is renally excreted.  It also turns everything red, which can interfere with labs and dialysis.
    • Note: Tintinalli cautions that there’s no good evidence on hydroxocobalamin over the traditional sodium nitrite kits.
  • There’s also the traditional cyanide antidotes which include: inhaled amyl nitrite, Sodium nitrite 3% – 300 mg IV (10 mL), and sodium thiosulfate.
    •  Sodium nitrite forms methemoglobin from hemoglobin, for which cyanide has enormous affinity.  Cyanide leaves the cytochrome, setting the mitochondria free, forming cyanmethemoglobin. This is transformed to thiocyanate by an enzyme (rhodanese) and renally excreted. 
    • If using this approach in a patient with carbon monoxide poisoning, use only sodium thiosulfate given these patient already have impaired tissue oxygenation and methemoglobinemia only further exacerbates this.

Carbon Monoxide (CO) – Tintinalli (7e) Ch 217; Rosen’s (8e) Ch 159

Carbon monoxide poisoning is non-specific and may manifest as headache, flu like illness, or coma and death and occurs throughout the year, not just during heat/generator seasons.

Mechanism –

  • Most well recognized – CO has a far greater affinity for hemoglobin than oxygen, leading to impaired delivery of oxygen to tissues.
  • Causes a left shift of the hemoglobin-oxygen dissociation curve (Right shift = Removal of oxygen from hemoglobin.  Left shift = loaded hemoglobin).
  • Inhibits the cytochrome system in aerobic metabolism, akin to cyanide toxicity, leading to a shift toward anaerobic metabolism.

Diagnostics –

  • Clinical suspicion is key.
  • Labs may show a metabolic acidosis with elevated lactate.
  • Carboxyhemoglobin level is often available and for boards, remember that levels >15% in pregnant patients or >25% in other patients may be a trigger to think about hyperbaric oxygen therapy.  These levels do not correlate with symptoms.

Treatment –

  • ABCs, including high inspired oxygen which reduces the half-life of CO from ~4 hrs to 90 minutes.
  • Hyperbaric oxygen (HBO) or “diving” patients in controversial but if a patient is near-dead, pregnant with significant toxicity (level >15), consider HBO, at least on the boards.

Questions generously donated by the Rosh Review

Question 1.  


Question 2.


Episode 1: Cyanide and Carbon Monoxide Toxicity



Gresham C, LoVecchio F.  Chapter 198.  Inhaled Toxins. Tintinalli’s Emergency Medicine: A Comprehensive Study Guide, 7e. New York, NY: McGraw-Hill; 2011. p 1317-1320.

Nelson RS, Hoffman RS.  Chapter 159.  Inhaled Toxins.  Rosen’s Emergency Medicine, 8e.  2014.  p 2036-2043.

Maloney G. Chapter 217. Carbon Monoxide.  Tintinalli’s Emergency Medicine: A Comprehensive Study Guide, 7e. New York, NY: McGraw-Hill; 2011. p 1410-1413.


Answers.  1) A  2)A