UMEM Educational Pearls - By Wesley Oliver

A recent prospective cohort study investigated the effect of low-dose droperidol on QTc in an emergency department:

  • 68 patients
  • Droperidol dose: median 1.875 mg (range: 0.625-2.5 mg)
  • Given as a 2-minute bolus
  • 94.1% received for headache management
  • Mean change in QTc: +29.9 ms (SD 15)
  • 17.6% (n=12) experienced QTc interval >=500 ms
  • 4.4% (n=3) had a change >=+60 ms
  • No serious arrhythmias or deaths
  • 13.2% (n=9) had at least one non-serious event (restlessness and/or anxiety)


Low-dose droperidol has a small effect on QTc and most patients remained below 500 ms.

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Background:

Multisystem inflammatory syndrome in children (MIS-C) as defined by CDC Health Advisory in May 2020 is:

1) An individual aged <21 years presenting with fever*, laboratory evidence of inflammation**, and evidence of clinically severe illness requiring hospitalization, with multisystem (>2) organ involvement (cardiac, renal, respiratory, hematologic, gastrointestinal, dermatologic or neurological); AND

2) No alternative plausible diagnoses; AND

3) Positive for current or recent SARS-CoV-2 infection by RT-PCR, serology, or antigen test; or exposure to a suspected or confirmed COVID-19 case within the 4 weeks prior to the onset of symptoms.

*Fever >38.0°C for ≥24 hours, or report of subjective fever lasting ≥24 hours

**Including, but not limited to, one or more of the following: an elevated C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), fibrinogen, procalcitonin, d-dimer, ferritin, lactic acid dehydrogenase (LDH), or interleukin 6 (IL-6), elevated neutrophils, reduced lymphocytes and low albumin

As of January 31st, 2022 the CDC reports the following statistics related to MIS-C in the United States:

·         Total MIS-C patients meeting case definition= 6,851

·         Total MIS-C deaths meeting case definition = 59

·         The median age of patients with MIS-C was 9 years. Half of children with MIS-C were between the ages of 5 and 13 years.

·         59% of the reported patients with race/ethnicity information available occurred in children who are Hispanic/Latino (1,746 patients) or Black, Non-Hispanic (2,050 patients).

·         98% of patients had a positive test result for SARS CoV-2, the virus that causes COVID-19. The remaining 2% of patients had contact with someone with COVID-19.

·         60% of reported patients were male.

 

Management:

First-Line Treatment:

·         IVIG 2 g/kg dosed based on ideal body weight with a maximum of 100 grams (1000 mL)  

o   For patients with significant myocardial dysfunction and concern for fluid overload, the infusion can be given in divided doses over 2 days (1g/kg q12 x 2 doses)

PLUS

·         Methylprednisolone 1 mg/kg (max of 30 mg/dose) IV twice daily and switch to PO and taper when clinically appropriate

Upon Consultation with Pediatric Hematology/Cardiology will consider adding the following therapies to IVIG and steroids:

·         Enoxaparin treatment versus prophylactic dosing depending on D-dimer elevation and whether or not being admitted to PICU

·         Aspirin 3-5 mg/kg (max 81 mg/dose) daily unless platelet count < 80 K/mcl

Second-Line Treatment (refractory to IVIG defined by symptoms and fever persisting >36 hours)*:

·         Methylprednisolone pulse dosing- 30 mg/kg (max of 1000 mg/dose) x 3-5 days

OR

·         High dose anakinra

OR

·         Infliximab 5-10 mg/kg IV x1  

*All second-line treatment options require peds infectious diseases and PICU attending approval

UMMS COVID/MIS-C Pathway: https://intra.umms.org/-/media/intranets/umms/pdfs/dept/pharmacy-and-therapeutics/guidelines/umms-pediatric-covid-pathway.pdf?upd=20220125144550

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Category: Pharmacology & Therapeutics

Title: Kcentra for Anticoagulant Reversal

Keywords: Kcentra, AC Reversal, Anticoagulant (PubMed Search)

Posted: 11/6/2021 by Wesley Oliver
Click here to contact Wesley Oliver

Kcentra (four-factor prothrombin complex concentrate, 4f-PCC) is approved for the reversal of warfarin using a weight-based dosing strategy based on INR. However, since the approval of Kcentra, data has shown a fixed-dose strategy and use for direct-acting oral anticoagulants (DOAC) is appropriate. There are even recommendations to use a fixed-dose for DOACs in some situations. Utilizing a fixed-dose strategy can help with decreasing drug preparation/delivery times and costs.

 

Our institution now only uses a weight-based Kcentra dose of 50 units/kg for patients on DOACs with ICH or trauma-induced coagulopathy. All other patients receive a fixed-dose of Kcentra 1,500 units or 2,000 units based on anticoagulant and other criteria.

 

Below is a diagram summarizing our current dosing strategy for Kcentra at our institution.

 

ICH=intracerebral hemorrhage

DOAC=direct-acting oral anticoagulant (rivaroxaban, apixaban, and edoxaban)

 

Other points of interest at our institution:

  • Based on recommended monitoring parameters, patients may receive additional doses of Kcentra.
  • Idarucizumab (Praxbind) is the preferred agent for dabigatran reversal.

 

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Take-Home Point:
Based on antibiotic resistance and PK/PD data, CDC recommends a single dose of intramuscular ceftriaxone 500 mg for uncomplicated gonococcal infections. Treatment for coinfection with Chlamydia trachomatis is now only recommended if coinfection cannot be excluded. Doxycycline 100 mg BID x 7 days is recommended as treatment for chlamydial coinfection, but adherence should be heavily considered and may preclude the use of doxycycline instead of previously recommended single dose of oral azithromycin 1 g.
 
Background:
• Neisseria gonorrhoeae is the second most commonly reported notifiable sexually transmitted
infection (STI) in the United States
• Treatment of gonococcal infections prevents complications and transmission, but resistance has
developed against several treatment options (i.e., penicillin, fluoroquinolones, cefixime, and
most recently, azithromycin) leading to changes in treatment recommendations over the years
 

Uncomplicated Gonococcal

Infections

2015 Recommendations [1]

2020 Recommendations [2]

Cervical, urethral, rectal, and

pharyngeal infection

Ceftriaxone 250 mg IM x 1 dose, plus azithromycin 1 g PO x 1 dose

Ceftriaxone 500 mg IM x 1 dose

>=150 kg

No recommendation

Ceftriaxone 1 g IM x 1 dose

If coinfection with chlamydia

cannot be excluded

Coverage provided by gonococcal treatment regimen

Add doxycycline 100 mg PO BID x 7 days

 
Clinical Data:
• Efficacy of ceftriaxone is best predicted by the fraction of time the unbound drug concentration
exceeds the minimum inhibitory concentration (fT>MIC)
• Monte Carlo simulations estimated fT>MIC of 20-24 hours is required for effective urogenital
gonococcal treatment – a 250 mg-dose did not achieve reliable levels for an extended duration,
while a 500 mg-dose did [3]
• In a gonorrhea mouse model, 5 mg/kg (which correlates to 500 mg for an 80-100 kg human) was
the lowest dose 100% effective at eradicating ceftriaxone-susceptible N. gonorrhoeae 48 hours
after treatment, with fT>MIC of 23.6 hours [4]
 
Conclusion:
• Higher intramuscular doses of ceftriaxone are required in order to optimize urogenital
gonococcal eradication
• Practical considerations pose challenges in implementing a protocol for delayed treatment of
chlamydial coinfection pending laboratory confirmation
• If treating for chlamydial coinfection:
o Heavily consider patient adherence to a 7-day course of doxycycline
o If adherence is a concern, treat with 1 gm oral azithromycin
o There are instances (i.e., rectal chlamydia) where doxycycline has demonstrated higher rates of treatment success compared to azithromycin and may be considered as first-line therapy [5,6]
 
Lauren Groft, PharmD; Infectious Disease Pharmacist

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Category: Pharmacology & Therapeutics

Title: Outpatient Treatment of Pyelonephritis

Keywords: Pyelonephritis, Outpatient, Fluoroquinolones, TMP-SMX, Beta-lactams (PubMed Search)

Posted: 4/3/2021 by Wesley Oliver
Click here to contact Wesley Oliver

While fluoroquinolones have fallen out of favor for many indications due to the ever growing list of adverse effects, they still play an important role in the outpatient treatment of pyelonephritis. Fluoroquinolones and TMP-SMX are the preferred agents due to higher failure rates with beta-lactams.

 

Preferred Therapies:
Ciprofloxacin 500 mg PO BID*
Levofloxacin 750 mg PO daily*
TMP-SMX 1 DS tab PO BID**

 

*Consider a single dose of long-acting parenteral agent, such as ceftriaxone, if community prevalence of fluoroquinolone resistance >10%.
**Consider a single dose of long-acting parenteral agent, such as ceftriaxone, if using TMP-SMX.

 

Alternative Therapies#:
Cefpodoxime 200 mg PO BID
Cefdinir 300 mg PO BID

 

#Beta-lactams are not preferred agents due to higher failure rates when compared to fluoroquinolones. Consider a single dose of long-acting parenteral agent, such as ceftriaxone, if using beta-lactams.

 

Duration of Therapy: 10-14 days

 

Take Home Point:
Utilize ciprofloxacin, levofloxacin, or TMP-SMX over beta-lactams when discharging patients with oral antibiotics for pyelonephritis.

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Buprenorphine is a partial opioid receptor agonist that has a higher binding affinity than pure opioid agonists. There can be unease in managing acute pain in patients sustained on buprenorphine for opioid use disorder due to many factors.

The main barriers to effective pain management in these patients are:

  1. Opioid-Induced Hyperalgesia
    1. Patients maintained on buprenorphine can have an increased sensitivity to pain.
    2. Consider using a multimodal approach that optimizes non-opioid analgesics, such as acetaminophen and nonsteroidal anti-inflammatory drugs.
  2. Opioid Tolerance
    1. Patients maintained on buprenorphine require higher doses of opioids to treat acute pain due to the decreased effectiveness of opioids over time.
    2. As in hyperalgesia, a multimodal approach can be beneficial.
    3. Higher doses of supplemental opioids will be required in these patients compared with opioid-naïve patients.
    4. Titrate supplemental opioids to effect and monitor for toxicity.
  3. Opioid Withdrawal
    1. Opioid withdrawal symptoms can contribute to stress and anxiety, increasing pain sensitivity.
    2. To prevent withdrawal symptoms it is appropriate to continue buprenorphine throughout the episode of acute pain.
    3. The patient's typical home dose of buprenorphine can be utilized.

 

Take Home Points
In general, the treatment strategy for acute pain in patients on buprenorphine should be:

  • Optimize non-opioid analgesia.
  • Use supplemental opioids when needed.
    • Will likely require higher doses.
    • Titrate to effect.
    • Monitor for toxicity.
  • Continue buprenorphine therapy at home dose throughout the acute pain episode.

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Category: Pharmacology & Therapeutics

Title: Octreotide Shortage: Vasopressin for Variceal Bleeding

Keywords: Octreotide, Vasopressin, Variceal Bleeding (PubMed Search)

Posted: 1/2/2021 by Wesley Oliver
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With a national shortage of octreotide an alternative treatment plan had to be implemented at our institution for patients presenting with variceal bleeding.

 

Drug references recommend a continuous infusion of vasopressin at 0.2 to 0.4 units/minute. Dose may be titrated as needed to a maximum dose of 0.8 units/minute with maximum duration of 24 hours to reduce incidence of adverse effects. Administer IV nitroglycerin concurrently to prevent ischemic complications and monitor closely for signs/symptoms of myocardial, peripheral, and bowel ischemia.

 

Protocol at our institution:

Vasopressin

  • Initiate vasopressin at 0.2 units/min.

  • Increase by 0.2 units/min if bleeding is not controlled after one hour (max dose: 0.8 units/min).

  • If bleeding controlled for 2 hours, can decrease by 0.2 units/min and reassess.

  • Limit use to 24 hours.

Nitroglycerin

  • Use nitroglycerin infusion to prevent adverse effects from vasopressin.

  • Initiate nitroglycerin at 40 mcg/min, titrate by 40 mcg/min to a max dose of 400 mcg/min.

  • Goal systolic blood press pressure of 90-100 mmHg.  Do not start nitroglycerin if SBP <90 mmHg.

***Please note the vasopressin dose for this indication is significantly higher than the typical dose of 0.03 units/min we use for shock.***

 

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Allergy documentation in the medical record is not always clear, nor does it provide clarifying details to understand timing and severity of beta-lactam allergies.  Approximately 8-10% of the population report beta-lactam allergies and 90% of those are not IgE-mediated reactions that would preclude the use of this class.  
 
A recent retrospective, single-center study of 438 patients was performed to assess the impact of these allergies on mortality and time to effective antibiotics in sepsis or septic shock.
 
-26% of the patients reported a beta-lactam allergy
-No significant differences with respect to primary source of infection (bacteremia and UTI most common)
-No difference in incidence of prior resistant organisms
 
Results:
-Overall, there was no difference in the combined endpoint of in-hospital mortality or transfer to hospice, time to antibiotics, ICU length of stay, hospital length of stay, and total hospital cost
-There was a significant difference in the susceptibility of the cultured organism to the initial antibiotic therapy in patients without a beta-lactam allergy (78% vs 57% p=0.009)
 
Bottom line:
Clarify all beta-lactam allergies in the medical record when they are encountered as they may impact care during the hospitalization or in subsequent encounters.  Do not delete the allergy, instead note the reaction or false report in the event that it is reported by the patient again in the future.

 

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Category: Pharmacology & Therapeutics

Title: Pain Management in Cirrhosis

Keywords: Cirrhosis, Pain, Acetaminophen, NSAID, Opioid (PubMed Search)

Posted: 8/1/2020 by Wesley Oliver (Updated: 8/15/2022)
Click here to contact Wesley Oliver

The liver performs an essential role in the metabolism and clearance of many drugs. Liver damage due to cirrhosis can decrease first-pass metabolism of oral medications and increase free-drug concentrations of protein-bound medications due to decreased albumin production. In the absence of cirrhosis, patients with chronic hepatitis or hepatic cancer may only have a small decrease in drug clearance. Hepatic dose adjustments are not as prevalent or readily available as renal dose adjustments, which can create difficulty in finding the balance between pain relief and adverse effects.

The most common medications used for pain control in the emergency department are acetaminophen, NSAIDs, and opioids.

Acetaminophen

It is sometimes misconceived that acetaminophen should never be used in patients with cirrhosis due to the common knowledge that acetaminophen overdoses can cause hepatotoxicity. Alcoholics may have an increased risk of hepatotoxicity due to induction of CYP2E1 and decreased glutathione stores. However, acetaminophen is safe in patients with cirrhosis when used at appropriate doses. Limit the total daily dose of acetaminophen to 2 g daily in patients with cirrhosis and avoid acetaminophen in patients that are actively drinking.  Also, educate patients that over-the-counter (OTC) and prescription medications may contain acetaminophen.

NSAIDs

In patients with cirrhosis, NSAIDs have increased bioavailability due to decreased CYP metabolism and decreased protein binding. In addition, prostaglandin inhibition can precipitate renal failure and sodium retention, worsening ascites and increasing the risk of hepatorenal syndrome, and increase the risk of gastrointestinal bleeding. Thrombocytopenia from NSAID use can further increase the risk of bleeding. Thus, avoid NSAID use in patients with cirrhosis. Topical NSAIDs can be considered.

Opioids

Opioid metabolism is altered in patients with cirrhosis and can contribute to complications with cirrhosis, such as precipitating encephalopathy. Generally, the bioavailability is increased and half-life is extended; thus, lower doses of immediate-release (IR) formulations at extended dosing intervals should be utilized. Common opioids for acute pain control in the emergency department are fentanyl, hydrocodone/oxycodone, hydromorphone, and morphine.

  • Fentanyl: Largely unaffected by cirrhosis. High potency so utilize only in appropriate clinical situations.
  • Hydrocodone/Oxycodone: Metabolized by CYP to active metabolites (hydromorphone/oxymorphone). Due to decreased CYP metabolism, analgesia may be less potent and clearance decreased. Also, be aware that some formulations are combined with acetaminophen.
  • Hydromorphone: Metabolized by glucuronidation to inactive metabolite. Metabolism and clearance less affected by cirrhosis.
  • Morphine: Increased bioavailability and concentration due to decreased first-pass metabolism. Decreased clearance and longer half-life. Avoid use in renal impairment and hepatorenal syndrome due to risk of neurotoxic metabolite accumulation.
  • Tramadol, codeine, meperidine, methadone, and buprenorphine not recommended for acute pain control in the emergency department.

 

 

Take Home Points

Drug/Class

Preferred Agent

Considerations

Acetaminophen

Max daily dose 2 g/day

Avoid if actively drinking. Be cautious if patient also taking OTC or combination products.

NSAIDs

None; Avoid

Topical NSAIDs may be considered.

Opioids

Hydromorphone, Fentanyl

Start with IR products at lower doses and extended intervals.

 

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Category: Pharmacology & Therapeutics

Title: Disulfiram-like Reaction with Metronidazole

Keywords: Metronidazole, Disulfiram-like Reaction (PubMed Search)

Posted: 6/6/2020 by Wesley Oliver
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While taking metronidazole it is advised that patients avoid ethanol use for at least 3 days after therapy due to the possibility of a disulfiram-like reaction.  The disulfiram-like reaction presents as abdominal cramps, nausea, vomiting, headaches, and/or flushing and can cause extreme discomfort for patients.  A recent case report describes a case of a disulfiram-like reaction in a patient receiving metronidazole and an oral prednisone solution that contained 30% alcohol.  This case highlights an important point.  Not only should we counsel patients about avoiding alcoholic beverages for at least 3 days after metronidazole therapy, but they should also avoid all alcohol-containing products, such as oral solutions and mouthwash.

 

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Empirical Anti-MRSA vs Standard Antibiotic Therapy and Risk of 30-Day Mortality
A recent article published in JAMA Internal Medicine questioned the utility of empiric anti-MRSA pneumonia therapy.  It was a retrospective multicenter cohort study conducted in the Veteran’s Health Administration healthcare system that looked at 88,605 patients with community-onset pneumonia. They compared 30-day mortality of patients hospitalized for pneumonia receiving empirical anti-MRSA therapy plus standard therapy against standard therapy alone. Secondary outcomes analyzed development of kidney injury and secondary infections with C. difficile, VRE, or gram-negative rods. They also analyzed subgroups: ICU admission, MRSA risk factors, positive MRSA surveillance test, and positive MRSA culture on admission.

 

Anti-MRSA Therapy: Vancomycin (98%), Linezolid (2%)

Standard Therapy: Beta-lactam + macrolide/tetracycline, or respiratory fluoroquinolone

 

Outcomes
Mortality: aRR=1.4 [95% CI, 1.3-1.5]
Kidney Injury: aRR=1.4 [95% CI, 1.3-1.5]
Secondary C. difficile: aRR=1.6 [95% CI, 1.3-1.9]
Secondary VRE: aRR=1.6 [95% CI, 1.0-2.3]
Secondary gram-negative rods: aRR=1.5 [95% CI, 1.2-1.8]

 

Mortality in Subgroups

ICU: aRR=1.3 [95% CI, 1.2-1.5]

MRSA Risk Factors*: aRR=1.2 [95% CI, 1.1-1.4]

Positive MRSA Surveillance: aRR=1.6 [95% CI, 1.3-1.9]

MRSA Detected on Culture: aRR=1.1 [95% CI, 0.8-1.4]

 

*MRSA Risk Factors
-History of MRSA infection/colonization within the past year
-Or 2 of the following: previous hospitalization, nursing home residence, and previous intravenous antibiotic therapy

 

Take-Home Point

Empirical anti-MRSA therapy did not decrease mortality for any groups of patients hospitalized for pneumonia. Given that healthcare-associated pneumonia is no longer a definition supported by the IDSA/ATS, be judicious in your use of anti-MRSA therapy in community-onset pneumonia and reserve for those patients at higher risk for MRSA, such as those with post-influenza pneumonia.

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Influenza is a common cause of community-acquired pneumonia and invasive bacterial coinfection may occur.  In addition, secondary bacterial pneumonia due to MRSA is becoming more prevalent.  Due to the higher incidence of MRSA, it is recommended that antibiotics with activity against MRSA (vancomycin or linezolid) be included in the empiric treatment regimen, especially if the patient is critically ill.

Take Home Point: Don’t forget to add MRSA coverage to your empiric treatment regimen in those influenza patients with severe disease or secondary bacterial pneumonia.

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Category: Pharmacology & Therapeutics

Title: Simplifying Phenytoin in the ED

Keywords: Phenytoin, Fosphenytoin (PubMed Search)

Posted: 11/2/2019 by Wesley Oliver (Updated: 11/3/2019)
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Takeaways

Phenytoin can be a complex medication.  There are different levels than can be ordered, adjustments based on albumin, various pharmacokinetic equations, and multiple formulations.  Below are the simplified answers to some of the most common questions (see in-depth section for explanations):

Which phenytoin level (free or total) do I order?

Total Phenytoin Level.

 

What do I do after the level results?

Undetectable Level: Load patient with 20 mg/kg of total body weight (max dose 1,500 mg).

Subtherapeutic Level (<10 mcg/mL): Calculate an approximate loading dose using this equation….Phenytoin Dose (mg)=(15-measured total level)*(0.7*patient weight).

Therapeutic Level (10-20 mcg/mL): Add an additional agent.

Supratherapetutic/Toxic Level (>20 mcg/mL): Contact Poison Center (1-800-222-1222).

 

What formulation do I order for loading?

IV: Use fosphenytoin.

PO: Any formulation will work.  Give as a single loading dose or, if concerned for GI upset, give in 2-3 divided doses separated by 2 hours.

 

 

***Disclaimer: These answers are simplified for the initial management of most patients in the ED. More complex answers may be required in some situations.***

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The American Diabetes Association requires a plasma glucose concentration greater than 250 mg/dL to diagnose diabetic ketoacidosis (DKA).  However, with the new diabetic agents this is not always the case. With the introduction of SGLT2 inhibitors (canagliflozin [Invokana], dapagliflozin [Farxiga], empagliflozin [Jardiance]) there have been reported cases of DKA and patients being euglycemic. 

 

Take Home Point

Patients with a low/normal blood glucose can still have DKA.  Especially if they are taking newer medications, such as the SGLT2 inhibitors.

 
 

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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: 8/15/2022)
Click here to contact Wesley Oliver

Takeaways

---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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Takeaways

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: 8/15/2022)
Click here to contact Wesley Oliver

Takeaways

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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