UMEM Educational Pearls - By Wesley Oliver

Category: Pharmacology & Therapeutics

Title: Alteplase for Pulmonary Embolism

Keywords: alteplase, pulmonary embolism (PubMed Search)

Posted: 7/6/2019 by Wesley Oliver
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Alteplase may be considered in some patients with a presumed or confirmed pulmonary embolism.  Below is a list of the different patient populations and the associated alteplase dosing.

-Hemodynamically Stable/Submassive: Alteplase usually not indicated.

-Hemodynamically Unstable/Massive: Alteplase IV 100 mg as an infusion over 2 hours.

-Cardiac Arrest: Alteplase IV/IO 50 mg bolus over 2 minutes.  Can repeat a second 50 mg bolus 15 minutes later if unable to achieve return of spontaneous circulation.

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Identifying serotonin syndrome in the emergency department can be difficult without an accurate patient history. Furthermore, the physical symptoms may look similar to many other disorders such as neuroleptic malignant syndrome and anticholinergic toxicity. If you remember the acronym SHIVERS, you can easily recognize the signs and symptoms of serotonin syndrome.

Shivering: Neuromuscular symptom that is unique to serotonin syndrome

Hyperreflexia and Myoclonus: Seen in mild to moderate cases. Most prominent in the lower extremities. This can help differentiate from neuroleptic malignant syndrome which would present with lead-pipe rigidity.

Increased Temperature: Not always present, but usually observed in more severe cases

Vital Sign Abnormalities: Tachycardia, tachypnea, and labile blood pressure

Encephalopathy: Mental status changes such as agitation, delirium, and confusion

Restlessness: Common due to excess serotonin activity

Sweating: Autonomic response to excess serotonin. This symptom can help differentiate from anticholinergic toxicity in which the patients would present with increased temperature but dry to the touch

Once serotonin syndrome is identified, it is important to discontinue all serotonergic agents, provide supportive care with fluids, and sedate with benzodiazepines. Sedation with benzodiazepines helps to decrease myoclonic jerks which also helps with temperature control. If patients are hyperthermic, they will require intensive cooling. Cyproheptadine, a potent antihistamine and serotonin antagonist, should also be administered. The initial dose of cyproheptadine in serotonin syndrome is 12mg which can be followed by 2 mg every 2 hours as needed for symptom control.

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Category: Pharmacology & Therapeutics

Title: Flu Season is Upon Us: Treatment with Oseltamivir

Keywords: Flu, Treatment, Oseltamivir (PubMed Search)

Posted: 1/8/2019 by Wesley Oliver (Updated: 6/19/2024)
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Question

---Early antiviral treatment can shorten the duration of fever and illness symptoms, and may reduce the risk of some complications from influenza.

---Early treatment of hospitalized adult influenza patients with oseltamivir has been reported to reduce death in some observational studies.

---Clinical benefit is greatest when antiviral treatment is administered within 48 hours of influenza illness onset.

 

Antiviral treatment is recommended for patients with confirmed or suspected influenza who:

---are hospitalized;

---have severe, complicated, or progressive illness; or

---are at higher risk for influenza complications. (See below for in-depth information)

Oral oseltamivir is the recommended antiviral for patients with severe, complicated, or progressive illness who are not hospitalized, and for hospitalized influenza patients.

 

Treatment:

Doses: Oseltamivir 75 mg twice daily

Renal Impairment Dosing

CrCl >60 mL/minute: No dosage adjustment necessary

CrCl >30 to 60 mL/minute: 30 mg twice daily

CrCl >10 to 30 mL/minute: 30 mg once daily

ESRD undergoing dialysis: 30 mg immediately and then 30 mg after every hemodialysis session

 

Duration of Treatment:

Recommended duration for antiviral treatment is 5 days for oral oseltamivir. Longer daily dosing can be considered for patients who remain severely ill after 5 days of treatment.

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Category: Pharmacology & Therapeutics

Title: Intranasal Administration of Common Emergency Department Medications

Keywords: Intranasal Administration, Alternative Administration (PubMed Search)

Posted: 11/2/2018 by Wesley Oliver (Emailed: 11/3/2018) (Updated: 11/8/2018)
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The most common methods of medication administration in the emergency department are oral, intravenous (IV), and intramuscular (IM).  If the oral route is not available, if IV/IM are not necessary, or if obtaining IV access is challenging, intranasal (IN) medication delivery is a reasonable alternative.  More concentrated products are preferred and a volume of 1 mL or less per nostril should be utilized.  Below is a table of the commonly used medications used via the IN route. 

Drug Concentration Indication IN Dose

Time to Peak Effect

Adverse Events
Fentanyl 50 mcg/mL Analgesia 0.5-2 mcg/kg 5 min

Nasal irritation, rhinitis, headache

Ketamine 100 mg/mL

Analgesia, Agitation, Sedation

3-6 mg/kg 5-10 min

Poor taste, HTN, hypersalivation, agitation, emergence reaction

Lorazepam 2 mg/mL

Agitation, Seizures

0.1 mg/kg

Max: 4 mg

30 min

Poor taste, lacrimation, nasal/throat irritation

Midazolam 5 mg/mL

Agitation, Sedation, Seizures

0.1-0.4 mg/kg

Max: 10 mg

5-10 min Same as lorazepam
Naloxone 1 mg/mL

Opioid Reversal

0.1 mg/kg

Usual dose:

0.4-2 mg

1-5 min

N/V, headache, withdrawal symptoms

 

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Question

The Centers for Medicare and Medicaid Services (CMS) require broad spectrum antibiotics to be administered within 3 hours of presentation of sepsis to be in compliance with the sepsis measure. 

 

Not only do the antibiotics that are chosen determine compliance with this measure, but the order in which antibiotics are given can also significantly affect compliance. 

 

According to CMS, for combination antibiotic therapy, both antibiotics must be started within the three hours following presentation; however, they do not need to be completely infused within this time frame. 

 

Combination therapy typically includes a monotherapy antibiotic (see list in detailed information below) plus vancomycin (daptomycin or linezolid could also be used). 

 

So which antibiotic should be given first? 

 

If a monotherapy antibiotic is given first within the 3 hours of presentation, then compliance for the sepsis measure is met.  These antibiotics cover a broader range of bacteria and are typically infused over ~30 minutes, which allows plenty of time for your second antibiotic to be initiated.  

 

If vancomycin is given first, compliance with this measure can become difficult. First, vancomycin has a narrower spectrum of activity and is not a monotherapy antibiotic. Second, vancomycin infusion rates range from 1 to 2 hours.  Given that antibiotics are usually given after sepsis is flagged, this infusion rate only gives a short period of time for the second antibiotic to be initiated. Thus, vancomycin should almost always be the second antibiotic infused. 

 

In addition, patients may also have limited intravenous access or antibiotics may not be compatible with resuscitation fluids.  All of these factors together must be considered when trying to gain compliance with this measure. 

 

Take-Home Point: 

Administer monotherapy antibiotics (e.g. piperacillin/tazobactam and cefepimeprior to administering vancomycin in your septic patients to improve compliance with the sepsis measure. 

 
 

 

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Category: Pharmacology & Therapeutics

Title: New-Onset Diabetes with DKA in Adults

Keywords: Diabetes, DKA (PubMed Search)

Posted: 7/7/2018 by Wesley Oliver (Updated: 6/19/2024)
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Question

Pearl submitted by James Leonard, PharmD, Clinical Toxicology Fellow
 
A 54-year-old male 1-year post-renal transplant arrives to the emergency department in diabetic ketoacidosis (DKA). He has no history of diabetes and is not currently taking steroids for immunosuppression. Home medications include tacrolimus, mycophenolate, and hydrochlorothiazide. Is this latent auto-immune diabetes or something else?
 

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Category: Pharmacology & Therapeutics

Title: Fosfomycin for UTIs

Keywords: Fosfomycin, urinary tract infection, cystitis (PubMed Search)

Posted: 3/3/2018 by Wesley Oliver
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Fosfomycin is an antibiotic infrequently used for the treatment of urinary tract infections (UTIs). It has a broad spectrum of activity that covers both gram-positive (MRSA, VRE) and gram-negative bacteria (Pseudomonas, ESBL, and carbapenem-resistant Enterobacteriaceae), which is useful in the treatment of multidrug-resistant bacteria. 

Fosfomycin is FDA approved for the treatment of uncomplicated UTIs in women due to susceptible strains of Escherichia coli and Enterococcus faecalis (3g oral as a single dose). Data has also demonstrated that it can be used for complicated UTIs; however, dosing is different in this population (3 g oral every 2-3 days for 3 doses).  Fosfomycin is not recommended for pyelonephritis.

The broad spectrum of activity, in addition to only needing a single dose in most cases, makes fosfomycin an attractive option; however, it should be reserved for use in certain circumstances.  Fosfomycin should not be considered as a first-line option.  It is also more expensive than other medications (~$100/dose) and in countries with high rates of utilization bacteria are developing resistance to fosfomycin.  In addition, most outpatient pharmacies do not keep this medication in stock.

Take-Home Point:

Fosfomycin should be reserved for multidrug-resistant UTIs in which other first-line options have been exhausted.

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Question

Patients with severe asthma exacerbations that are unresponsive to inhaled beta-agonists may require the use of epinephrine to control their symptoms.  When patients get to this point what route of administration should be used for the administration of epinephrine?

The most recent asthma guidelines (published in 2007) recommend the use of SubQ epinephrine 0.3-0.5 mg every 20 minutes for 3 doses.  Drug references typically list SubQ or IM epinephrine 0.01 mg/kg (~0.3-0.5 mg) every 20 minutes as appropriate routes of administration.  There is currently no data demonstrating that one route of administration is better than the other in patients with asthma; however, in other disease states, such as anaphylaxis, IM epinephrine is preferred due to the more rapid and reliable absorption over SubQ administration.

Auto-injectors that administer IM epinephrine 0.3 mg are available.  These auto-injectors may decrease the risk of medications error; however, they can be expensive.  SubQ administration requires the use of a syringe and a vial/ampule of 1 mg/mL epinephrine.

Bottom Line: Either SubQ or IM epinephrine administration is appropriate for patients with severe asthma exacerbations.  The preferred method at a given institution will be dictated by historical practice, risk of medication dosing errors, and drug cost.

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Category: Pharmacology & Therapeutics

Title: Insulin for Hyperkalemia

Keywords: Insulin, Hyperkalemia, Dextrose (PubMed Search)

Posted: 11/6/2017 by Wesley Oliver (Updated: 6/19/2024)
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Strategies for Hyperkalemia Management

Stabilize cardiac membrane

Calcium gluconate

Intracellular movement in skeletal muscles

Albuterol

Sodium Bicarbonate

Insulin

Potassium excretion

Loop Diuretics

Kayexalate

Patiromer (chronic use only)

Potassium removal

Dialysis

 

Insulin mechanism of action for hyperkalemia:

· Binds to skeletal muscle receptors

· Increased activity of the sodium-potassium adenosine triphosphatase and glucose transporter GLUT4

· Glycemic response occurs at lower levels of insulin

· Potassium transport activity increases as insulin levels increase

Patients with insulin resistance due to type-2 diabetes do not become resistant to the kalemic effects of insulin.

 

Hypoglycemia following insulin administration for hyperkalemia:

· Occurs 1-3 hours post dose, even with initial bolus of dextrose

· The amount of glucose is insufficient to replace the glucose utilized in response to the administered dose of insulin

· Insulin’s half-life is increased in ESRD leading to longer duration of action

 

A systematic review of 11 studies regarding insulin dosing for hyperkalemia:

· 22 patients (18%) experienced hypoglycemia

· Studies that only gave 25 grams (1 amp) of dextrose had the highest incidence of hypoglycemia (30%)

 

Tips:

· Consider insulin dose reduction in patients with renal failure

· Use an order set to ensure patients receive appropriate POC glucose monitoring to detect delayed onset of hypoglycemia

· Dextrose 50% (25 grams) should be given to all patients with pre-insulin BG <350 mg/dL

Subsequent PRN dextrose 50% (25 grams) should be used to maintain BG >100 mg/dL after insulin administration

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Category: Pharmacology & Therapeutics

Title: Alpha-Blockers for the Management of Ureteral Stones

Keywords: Ureteral stones, Alpha-blockers (PubMed Search)

Posted: 9/2/2017 by Wesley Oliver (Updated: 6/19/2024)
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Question

Alpha-blockers (tamsulosin, alfuzosin, doxazosin, and terazosin) are antagonists of alpha1A-adrenoreceptors, which results in the relaxation of ureteral smooth muscle.    Current evidence suggests alpha-blockers may be useful when ureteral stones are 5-10 mm; however, there is no evidence to support the use of alpha-blockers with stones <5 mm.  Patients with ureteral stones >10 mm were excluded from studies utilizing these medications.

The size of most ureteral stones will be unknown due to the lack of need for imaging able to measure stone size. Given that the median ureteral stone size is <5 mm, most patients will not benefit from the use of an alpha-blocker.

Also, keep in mind that the data for adverse events with alpha-blockers used for ureteral stones is limited and that these medications have a risk of hypotension.

 

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