Colchicine tablets and injectable solution is frequently used for the treatment of gout and familial Mediterranean fever.  An overdose is extremely serious, with considerable mortality that is often delayed.  It is considered a cellular poison due to its inhibition of cellular mitosis of dividing cells. 

After an acute overdose, symptoms typically are delayed for 2-12 hours and include nausea, vomiting, abdominal pain, and severe bloody diarrhea.

Chronic poisoning presens with a more insidious onset.

Late complications include bone marrow suppression, particularly leukopenia and thrombocytopenia (4-5 days) and alopecia (2-3 weeks).

Treatment includes aggressive supportive care, monitoring and treatment of fluid and electrolyte disturbances.

The usual cause of death from acute poisoning is due to hemodynamic collapse and cardiac arrhythmias (typically 24-36 hours after ingestion or could be sudden) or from infectious or hemorrhagic complications.

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General Information: Tetanus is caused by the toxin of Clostridium tetani--a gram-positive bacillus found in soil and animal excrement. It is a life-threatening but preventable disease. Cases have declined by > 95% in the past 65 years, but dozens of cases still occur annually in the US and it is still frequently seen in developing countries.

Clinical Presentation:

• Generalized increased rigidity
• Convulsive spasms of skeletal muscles
• Risus sardonicus (severe facial spasms with a “sardonic” smile)
• autonomic instability (fever, sweating, tachycardia, salivation, hyper- or hypo prefusion)
• Lucid mental state

Diagnosis:

Clinical Case Definition: In the absence of a more likely diagnosis, an acute illness with muscle spasms or hypertonia.  There is no diagnostic laboratory test for tetanus.

Treatment:

• Supportive care (including ventilator support as needed)
•  Control symptoms with muscle relaxants and anticonvulsants as needed
• Wound debridement and antibiotics (metronidazole, e.g. 0.5 gm every 6 hours) to decrease C tetani
• Passive immunization with human tetanus immune globulin (TIG) (may shorten course and decrease severity--Dose: TIG 3,000-6,000 units IM)
• Tetanus toxoid vaccine (clinical disease does not produce immunity!)

Bottom Line:

Tetanus is not as rare as we would like to think.  Acute diagnostic acumen and assertive clinical management can help save the life of someone with this potentially deadly disease

University of Maryland Section for Global Emergency Health

Author:  Jon Mark Hirshon, MD, MPH, PhD

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Prophylactic FFP for Procedures?

• FFP is commonly transfused to correct abnormal coagulation studies prior to performing procedures in nonbleeding critically ill patients.
• Despite common practice, there is little to no supportive evidence to demonstrate a clinical benefit to transfusing FFP in this patient population.
• Muller, et al recently evaluated the use of FFP before invasive procedures in critically ill patients.  Brief highlights include:
  • Prospective, randomized, open-label study at 4 sites in the Netherlands
  • 76 adult ICU patients with INRs between 1.5 and 3.0
  • Procedures: central line placement, thoracentesis, percutaneous tracheostomy
  • Result: no difference in major bleeding events between those who received FFP and those randomized to no FFP
• Take Home Point: In the nonbleeding critically ill patient, routine transfusion of FFP to correct lab abnormalities prior to procedures is not indicated.

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Question

35 year-old female presents with nausea and vomiting 1 week post-op for an abdominal surgery. Abdominal ultrasound is below; what's the diagnosis? 

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Some quick facts about Knee Injuries:

• The most common cause of acute traumatic hemarthrosis of the knee is an anterior cruciate ligament tear.
  • Most patients with an ACL injury will give a history of immediate pain, disability, knee swelling and audible pop.
• The most common ligament injuried in the knee is the medial collateral ligament.
• Patella dislocations
  • Usually lateral dislocations and often spontaneous reduce.
  • Hyperextend the knee to make the reduction easier.
• Dislocation of the knee:
  • Anterior is the most common and usually secondary to hyperextension
  • Popliteal artery injury is commonly seen and must be looked for.  Easy bedside test is Ankle Brachial Index.
  • Normal pulses do NOT exclude a vascular injury.
  • Patients should be monitored for vascular complications and compartment syndrome.
  • Vascular injuries due to knee dislocation are associated with a high rate of amputation, which markedly increases if not repaired within 6-8 hours.

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NAC is an effective antidote against acetaminophen (APAP) toxicity in preventing acute hepatotoxicity. It provides cysteine that is essential for glutathione synthesis and its availability is rate limiting.

Currently, PO and IV formulation is available in the U.S. Regardless of the route, NAC is equally effective in preventing APAP induced acute hepatotoxicity when administered within 8 hours after single acute ingestion. ¹

Adverse effects of NAC

1.     Anaphylactoid reaction

a.     More frequently reported with IV administration and during the first regimen of NAC (150 mg/kg over 60 min) administration. (dose and rate dependent)

b.     Higher risk of anaphylactoid reaction in patients with negative APAP vs. patients with elevated APAP level.²

c.      Management: Benadryl as needed and slow infusion rate.

2.     Hyponatremia in children if inappropriate volume of diluent (D5W) used. Dose calculator: http://acetadote.com/dosecalc.php

3.     Laboratory: increase Prothrombin time (PT).3

4.     Fatality from iatrogenic NAC overdose has been reported.

Advantage of IV NAC

1.     Convenience

2.     100% bioavailability

3.     Shorter hospital length of stay

4.     Minimum GI symptoms (nausea & vomiting) compared to PO route

Indication of IV NAC

1.     Severe hepatotoxicity or fulminant liver failure

2.     APAP poisoning during pregnancy

3.     Unable to tolerate PO intake (nausea, vomiting, altered mental status)

However many clinicians administer IV NAC for their advantages over PO NAC.

 Take home message:

1.     PO and IV NAC are equally effective when administered within 8 hours after single acute ingestion.

2.     Anaphylactoid reaction is frequently encountered AE during the infusion of 1^st NAC regimen and patients with negative/low APAP level may be at higher risk.

3.     No emergent need to start NAC in presumed acetaminophen overdose patients prior to obtaining APAP level.

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Clinical Presentation:

A 35-year-old female presents to your emergency department complaining of fever, malaise, myalgias, headache and an urticarial rash.  Her physical exam reveals a papular rash and hepatosplenomegaly. You also find out that she traveled to Sudan 6 weeks earlier. She stayed mostly in Kharotum, but while there, she swam in the Nile. You send a smear for malaria, which is negative.  What other major parasite should you consider?

Diagnosis:

• Schistosomiasis, also know as bilharzia, is a disease caused by parasitic worms.
• While not found in the US, it impacts more than 200 million people globally, and is second only to malaria as a major parasitic infection.

Discussion:

While the acute presentation is generally non-specific, chronic complications may be more serious. Many organ systems can be impacted and symptoms of chronic infection can include liver dysfunction, including portal hypertension and esophageal varacies or hematuria and renal failure.

Treatment:

• Treatment is a one-day course of Praziquantel but must be initiated 6-8 weeks after infection. (It's most effective against the adult worm so timing is key!)

Bottom Line:

Consider a broader differential in travelers. There are many infectious killers that can be easily treated.

University of Maryland Section of Global Emergency Health

Author: Jon Mark Hirshon, MD, MPH, PhD

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Thrombelastography for Management of Non-Traumatic Hemorrhagic Shock

The use of thrombelastography (TEG, ROTEM) has traditionally been utilized and studied in the management of acute coagulopathy of trauma (ACoT) developed by patients in hemorrhagic shock secondary to trauma.

Functional coagulation tests such as the TEG may provide valuable information when resuscitating the hemorrhaging patient, especially if there is any concern for an underlying coagulopathy.  

The following is a TEG recently returned during the resuscitation of a 60 y/o male with a history of HCV cirrhosis presenting with hemorrhagic shock secondary to a massive upper GIB.  The University's Massive Transfusion Protocol was promptly activated and at this point, the patient had received approximately 4 units of PRBCs & FFP along with 1 liter of crystalloid.  His Hgb was 5, PT/PTT/INR were undetectable, and his fibrinogen was 80.

Below is a table that simplifies the treatment, based on the test's abnormalities:

• Prolonged R:  Fresh frozen plasma
• Prolonged K or reduced α angle: Cryoprecipitate
• Low MA: Platelets, desmopressin (DDAVP)
• Elevated LY 30%: Consider antifibrinolytics (aminocaproic acid, TXA)

After reviewing the initial TEG, all perameters were abnormal in addition to the presence of significant fibrinolysis.  The patient was given an additional 4 units of FFP, DDAVP, cryoprecipitate, a unit of platelets, and aminocaproic acid.  The patient still required significant resuscitation, however bleeding had significantly decreased as well has his pressor requirement.  Below is the patient's follow-up TEG 2 hours later.

There is growing enthusiasm for the use of functional coagulopathy testing in the patient with hemorrhagic shock.  Early resuscitation with blood products as your fluid of choice with limited fluid administration while arranging for definitive source control are critical, but also consider early thrombelastography to detect additional causes for uncontrolled hemorrhage.

References

1. Walsh M, Thomas SG, Howard JC, et al. Blood component therapy in trauma guided with the utilization of the perfusionist and thromboelastography. Journal of Extra-Corporeal Technology. 2011 Sep; 43(3):162-7.
2. The Use of TEG & Goal Directed Blood Component Therapy.  MarylandCCProject.org

Follow Me On Twitter: @JohnGreenwoodMD
email: johncgreenwood@gmail.com

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Question

41year-old male without past medical history presents with the image below. What's the diagnosis and what's the most likely causative organism?

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Methadone prolongs the QTc interval. Is the degree of QTC widening correlated to worse outcomes after overdose?

The authors of a new study concluded the triage QTc can predict death, intubation, and respiratory arrest. QTc thresholds of 470, 447.5, and 450 msec had sensitivity (95 % CI) and specificity (95 % CI) of 87.5 (47.3-99.7), 86.8 (74.7-94.5), and 77.3 (62.2-88.5), respectively.

My Thoughts

Respiratory depression is the predominant cause of death in methadone overdoses. QTc interval prolongation may have the potential to help predict outcomes, but the QTc thresholds in this study were really not that prolonged. Patients on chronic methadone without overdose have baseline QTc intervals longer than those in this study after overdose.

Application to Clinical Practice

Many factors contribute to the ultimate disposition of methadone overdose cases. Even if QTc widening is correlated to outcomes, it really won't change our management.

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Case Presentation:

A 64 yo male with a history of IDDM presents with generalized fatigue. He felt so weak last night that he missed his pm dose of Lantus and vomited this morning. He arrived with a critically elevated BG of 590. He flew to the US from Sierra Leone 3 days ago.

Labs include:

Wbc 3.5 Plt 34 Hb 12 Hct 36

Na 125 CL 93 Co2 14 K 4.5 BUN 25 Cr 1.9 Glu 590 AG 18

VBG pH 7.23

Clinical Question:

Other than treating his diabetic ketoacidosis and renal failure, would you send any further tests?

Answer:

Thick smear for Malaria.

Bottom Line:

• DKA is often a symptom of an underlying metabolic or infectious insult
• Have a high suspicion for malaria in those travelers coming from endemic regions and don't forget malaria symptoms are often insidious presenting with myalgia and fatigue, as well as the traditional undulating fevers and chills
• In addition to anemia, thrombocytopenia has been seen in  P. vivax and P. falciparum. (In the at-risk traveler, this finding should raise your suspicion for malaria.)

University of Maryland Section of Global Emergency Health

Author: Bradford Schwartz, MD

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Question

28 year-old female with history of chronic back pain presents with right-foot numbness and inability to move her foot at the ankle joint. What’s the diagnosis and what neurologic finding would you expect to find?

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In a prospective cohort of 598 ED patients, 5 risk factors were independently associated with uncomplicated cellulitis patients who fail initial antibiotic therapy as outpatients and require a change of antibiotics or admission to hospital: 

1. Fever (temperature > 38°C) at triage (OR = 4.3, 95% CI = 1.6 to 11.7)
2. Chronic leg ulcers (OR = 2.5, 95% CI = 1.1 to 5.2)
3. Chronic edema or lymphedema (OR = 2.5, 95% CI = 1.5 to 4.2)
4. Prior cellulitis in the same area (OR = 2.1, 95% CI = 1.3 to 3.5)
5. Cellulitis at a wound site (OR = 1.9, 95% CI = 1.2 to 3.0)

Patients presenting with uncomplicated cellulitis and any of these risk factors may need to be considered for observation +/- IV antibiotics.

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This is a must memorize simple table of the toxic doses of local anesthetics. Toxicity of local anesthetics starts with slurred speech, lethargy to seizures and lethal cardiac dysrhythmias. There should be zero tolerance to actual cause toxicity when repairing a laceration or performing a fascia iliaca block.

Remember that a Bupivcaine solution 0.5% = 0.5 g/dL (%=g/dL) so a 70kg person, you can use a  maximum of 2mg/kg x 70kg person. You can inject 140 mg in a 70kg person. This is a maximum volume injection of 28 mL if you were doing a fascia iliaca block. You can double the volume if you use a more dilute solution of 0.25%.

Treatment for cardiac dysrhythmias due to local anesthetics is 20% lipid emulsion therapy - don't follow ACLS protocol as epinephrine or other antidysrhythmics (especially lidocaine) will be lethal.

General Information:

This year there have been over 280 cases of measles in the US, spanning 18 states; early recognition is key to preventing transmission.

Remember the 3 c's for recognition:

Cough, Coryza (runny nose), Conjunctivitis + febrile rash

-Incubation period is 10-12 days

-Symptoms usually start with fever, followed by rash 2-3 days later starting from the hairline and spreading to the trunk and extremities

-Completion of the first series of vaccines provides 90-95% immunity from measles

Relevance to the EM Physician:

-Immediately place any patient suspected of having measles on airborne precautions

-Look for koplik spots on the oral mucosa (commonly described as appearing like small grains of salt)

-Complications include diarrhea, otitis media, “measles croup,” pneumonia, encephalitis (1/1000 cases), and death (2-3/1000 cases)

-Post exposure prophylaxis (PEP) is recommended for unvaccinated exposed individuals and is effective up to 72 hours after exposure; however, vaccination is contraindicated in pregnant women

Bottom Line:

-The incidence of measles is rising sharply in the US. Vaccination, early detection, and post exposure prophylaxis for exposed individuals is key to reversing this trend.

University of Maryland Section of Global Emergency Health

Author: Bradford Schwartz, MD

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Emergent reversal of Dabigatran

What is it:

Direct thrombin inhibitor used for stroke prevention in non-valvular atrial fibrillation

When do I worry about reversal:

Patients can have clinically important bleeding (GI hemorrhage, or Intracranial bleeding) or need reversal for emergent surgery

Patients with renal failure can have a prolonged medication effect

What can I do:

1.     Activated charcoal: good for recent overdose or recent ingestion (within 2 hours)

2.     Hemodialysis:  around 60-65% can be removed within 2-4 hrs; putting in a dialysis line can be…bloody

3.     FFP: in rat studies, has been shown to reduce the volume of intracranial hemorrhage. Unknown in humans. No good evidence of use based on coagulation mechanisms. Still worth a try though. 

4.     Recombinant activated factor VII: Has been shown to correct the bleeding time in animal studies. Probably the best bet in severe bleeding

5.     Pro-thrombin complex concentrate: has been shown to decrease the bleeding time in animal studies

How do I monitor effect?

No great way here. Check aPTT and thrombin time (TT). At supra-therapeutic doses there is no good test. 

Coming attractions: Dabigatran-fab for emergent reversal (see previous pearl: https://umem.org/educational_pearls/2415/) 

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Question

30 year-old female with elbow pain following a fall. What's the diagnosis? (bonus points if you name the fracture with an associated radio-ulnar joint dislocation)

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