UMEM Educational Pearls - By Ashley Martinelli

Category: Pharmacology & Therapeutics

Title: TXA Quick Review (submitted by Kortney Morrell, PharmD)

Keywords: bleeding, epistaxis, tranexamic acid (PubMed Search)

Posted: 3/2/2019 by Ashley Martinelli (Updated: 4/18/2024)
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Mechanism of Action 

Tranexamic Acid (TXA) is an antifibrinolytic agent that is a competitive inhibitor of plasminogen activation, and a non-competitive inhibitor of plasmin 

Inhibits the breakdown of fibrin mesh allowing clot formation

  • Vial Concentration: 1000mg/10 mL 

When is it Indicated? 

Epistaxis/Oral Bleeds/Fistula Bleeds

  • Local application of injectable form of TXA 
  • Dose: Gauze soaked with 500 mg (5 mL) applied topically to the site of bleeding 

Trauma

  • Criteria for use: Significant hemorrhage or significant risk of hemorrhage in adult trauma patients (SBP <90 mmHg and/or HR >110 bpm) 
  • Dose: 1g in 100 mL 0.9% NaCl infused over 10 minutes followed by 1g in 100 mL 0.9% NaCl over 8 hours 

Adverse Reactions 

  • Generally well tolerated
  • GI Disturbances: nausea, vomiting, diarrhea 
  • Thrombotic Events 
  • Hypersensitivity reactions: anaphylaxis and anaphylactoid reactions 
  • Hypotension following rapid injection (maximum rate is 100 mg/minute) 

 



Category: Pharmacology & Therapeutics

Title: Prevent Hypoglycemia when Treating Hyperkalemia

Keywords: hypoglycemia, hyperkalemia (PubMed Search)

Posted: 2/2/2019 by Ashley Martinelli (Updated: 4/18/2024)
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Question

A recent retrospective study examined the incidence of hypoglycemia for 1307 adult patient encounters with hyperkalemia (>5.3 mmol/L) over a five-year timeframe.
 
409 (31%) of patients were treated with IV insulin.
Within 3 hours of insulin administration:
-344/409 (84%) had a glucose test
-68/409 (17%) experienced hypoglycemia (glucose <70 mg/dL)
-31/409 (8%) experienced severe hypoglycemia (glucose < 50 mg/dL)
 
Patients with serum glucose <100mg/dL prior to insulin administration experienced even higher rates of hypoglycemia, 38/112 (34%).
 
Patients who did not receive IV insulin had a hypoglycemia rate of 4%.
 
In patients with critical illness, a single episode of hypoglycemia has been independently associated with increased mortality.  Ensure patients receive adequate dextrose loading doses based on their pre-insulin blood glucose and monitor point of care glucose every 30-60 minutes for the first 3 hours of care. Use automated order sets when available.

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Category: Pharmacology & Therapeutics

Title: Barriers to Care: Naloxone

Keywords: naloxone, overdose (PubMed Search)

Posted: 12/3/2018 by Ashley Martinelli (Updated: 4/18/2024)
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Providing naloxone to patients at risk for opioid overdose is now standard of care. A retrospective study evaluated the rate of naloxone obtainment after standardizing the process for prescribing naloxone in the emergency department and dispensing from the hospital outpatient pharmacy. 

55 patients were prescribed naloxone.  Demographics: mean age 48 years old, 75% male, 40% primary diagnosis of heroin diagnosis, 45.5% were prescribed other prescriptions.

Outcomes:

  • 25.5% brought the prescription to the pharmacy
  • 18.2% completed education and obtained naloxone
  • 10% higher rate of success if patient had multiple prescriptions to fill

Barriers identified included lack of ED dispensing program, cost of medication, even though cost is minimal and can be waived, and likely multifactorial reasons why patients did not present to pharmacy as instructed.

Take Home Points:

  • In this complex and challenging patient population, naloxone should be provided
  • Utilize UMMC ED Meds to Beds technicians 1130-1900 M-F to prevent patients from having to travel to pharmacy post-ED visit as this can be a barrier.  The pharmacy technician
  • Prescribe AED To-Go naloxone after hours to improve access to naloxone

 

 

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Clonidine is an alpha-2 agonist commonly used to treat hypertension. Clonidine can also be used to mitigate symptoms of opioid withdrawal as it easily crosses the blood brain barrier and reduces sympathetic effects.

When using clonidine for acute withdrawal or blood pressure control, oral tablets are the preferred route.  Clonidine transdermal patches have slow absorption and take 2-3 days for the effect to be seen.  Once removed, clonidine patches can provide therapeutic levels for up to 20 hours.

Bottom Line: If clonidine is needed acutely for your patient, select oral tablets and titrate to effect.

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Category: Infectious Disease

Title: Update to C. Difficile Treatment

Keywords: clostridium difficile, antibiotics, vancomycin (PubMed Search)

Posted: 8/4/2018 by Ashley Martinelli (Updated: 4/18/2024)
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  • IDSA/SHEA recently released a guideline update for the management of Clostridium difficle infections
  • Discontinue inciting antibiotic therapy as soon as possible
  • Metronidazole is no longer considered first line therapy for C. difficle infection
  • Treatment course for 10 days unless initial fulminant or recurrence requiring vancomycin taper
  • Remember: Vancomycin IV does not cross into the GI tract and cannot be used to treat C. difficile

Clinical Definition

Treatment

Initial episode, non-severe

WBC ≤ 15,000 AND  SCr <1.5

  • Vancomycin PO 125mg 4x daily, OR
  • Fidaxomicin PO 200mg 2x daily

If above agents unavailable, metronidazole PO 500mg 3x daily

 

Initial episode, severe

WBC ≥ 15,000 OR  SCr >1.5

  • Vancomycin PO 125mg 4x daily, OR
  • Fidaxomicin PO 200mg 2x daily

 

Initial episode, fulminant

Hypotension, shock, ileus, megacolon

  • Vancomycin PO 500mg 4x daily
  • Ileus? Give vancomycin enema 500mg q8h

 

First Recurrence

 

  • Prolonged vancomycin PO taper 125mg 4x daily, OR
  • Vancomycin PO 125mg 4x daily x 10 days if metronidazole was used initially
  • Consider fidaxomicin PO 200mg 2x daily if vancomycin used for initial treatment


 

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Category: Pharmacology & Therapeutics

Title: Steroid Induced Leukocytosis

Keywords: steroids, infection, leukocytosis (PubMed Search)

Posted: 6/2/2018 by Ashley Martinelli (Updated: 4/18/2024)
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Steroids induce leukocytosis through the release of cells from bone marrow and the inhibition of neutrophil apoptosis.   This effect typically occurs within the first two weeks of steroid treatment. 

Leukocyte elevation is commonly used in the diagnosis of septic patients; however, this can be hard to discern in patients on concomitant steroid therapy.

A retrospective cohort study of adult patients presenting with fevers and a diagnosis of pneumonia, urinary tract infection, bacteremia, cellulitis, or COPD exacerbation was conducted to determine the maximal level of WBC within the first 24h of admission between patients on acute, chronic, or no steroid treatment.

Results: maximal WBC levels (p< 0.001)

·        Acute steroid therapy: 15.4 ± 8.3 x 10 9/L

·        Chronic steroid therapy: 14.9 ± 7.4 x 10 9/L

·        No steroid therapy: 12.9 ± 6.4 x 10 9/L

An increase in WBC of 5 x 10 9/L can be found in acute and chronic steroid use when presenting with an acute infection and fever.

 

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  • The current Surviving Sepsis Campaign Guidelines recommend treating septic patients with bundled care to improve outcomes. 
  • The first bundle should be completed within 3 hours of suspicion of sepsis and includes:
    • Obtain blood cultures before antibiotics
    • Obtain lactate level
    • Administer broad-spectrum antibiotics
    • Administer 30mL/kg crystalloid fluid for hypotension  (MAP <65, lactate >4)
  • A recent study in Critical Care Medicine examined the time frame when the delay of specific 3-hour bundle guideline recommendations applied to severe sepsis or septic shock becomes harmful and impacts mortality.
  • Retrospective cohort study of all adult patients hospitalized with severe sepsis or septic shock from January 2011 to July 31, 2015. Of the 5,072 patients enrolled, 95.8% received the 3-hour bundle.
  • Results:
    • Overall in-hospital mortality = 27.8%
    • If patient did not receive any of the 3-hr bundle items, in-house mortality = 41.1%
    • Statistically significant delays were linked to increased mortality for all bundle items
    • Delays beyond 3 hours were associated with minimal additional harm already caused by the 3-hour delay

Bottom Line: Implement sepsis protocols as soon as sepsis is suspected prior to the end of the 3 hour treatment window.

 

 

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Question

Debating between cefepime or piperacillin/tazobactam for your septic patient? Use this table to help you decide.

 

 

Cefepime

Piperacillin/Tazobactam

Gram Negative Spectrum

Pseudomonas aeruginosa 

Yes

Yes

Aerobic gram negative organisms 

E. coli 

Klebsiella sp. 

Proteus mirabilis 

M catarrhalis  

H. influenza 

E. coli 

Klebsiella sp. 

Proteus mirabilis 

M. catarrhalis 

H. influenza 

Anerobic gram negative organisms 

No

B. fragilis 

 

Gram Positive Spectrum

MRSA 

No

No

Aerobic gram positive organisms 

MSSA 

CoNS 

Group A Strep 

S. pneumoniae 

 

MSSA 

CoNS 

Group A Strep 

S. pneumoniae 

E. faecalis 

Anaerobic gram positive organisms 

P. acnes 

Peptostreptococci 

P. acnes 

Peptostreptococci 

Clostridium sp. 

Infection Site Concerns

CNS Penetration 

Yes

No1

Urine Penetration 

Yes

Yes

Lung Penetration 

Yes

Low2

Dosing Frequency (Normal Renal Function)

Q8h 

Q6h 

1Tazobactam CNS penetration is limited, thus limiting antipseudomonal activity in the CNS 

2. Low pulmonary penetration, may not achieve therapeutic levels in patients with critical illness 

 

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Category: Infectious Disease

Title: Risk Factors for Community Associated C. difficile Infection

Keywords: c. difficile, antibiotic (PubMed Search)

Posted: 12/2/2017 by Ashley Martinelli (Emailed: 12/6/2017) (Updated: 12/6/2017)
Click here to contact Ashley Martinelli

Community-associated Clostridium difficile infection (CA-CDI) represents 41% of all CDI cases annually.  The association of specific outpatient exposures was assessed in a case control study by Guh, et al. They reviewed the CDC’s active surveillance reporting from 10 states through the Emerging Infections Program (Maryland participates).

Cases: ≥18, + C. difficile stool specimen collected as an outpatient or within 3 days of hospitalization, with no overnight stay in a health care facility in the prior 12 weeks, and no prior CDI diagnosis

Controls: matched 1:1 for age and sex within the same surveillance catchment area as the case patient on the date of the collection specimen. Exclusion criteria: prior diagnosis of CDI, diarrheal illness, overnight stay in health care facility in the prior 12 weeks

Data Collection: telephone interview, standardized questionnaire or comorbidities, medication use, outpatient health care visits, household and dietary exposures in the prior 12 weeks

Results: 452 participants (226 pairs), over 50% were ≥ 60 years of age, 70.4% female, and 29% were hospitalized within 7 days of diagnosis, no patients developed toxic megacolon or required colectomy.

Cases had more health care exposures, including the emergency department (11.2% vs 1.4% p <0.0001), urgent care (9.9% vs 1.8%, p=0.0003). In addition, cases also reported higher antibiotic exposures (62.2% vs 10.3%, p<0.0001) with statistically significant higher exposure to cephalosporins, clindamycin, fluoroquinolones, metronidazole, and beta-lactam and/or beta-lactamase inhibitor combination. The most common antibiotic indications were ear or sinus infections, URI, SSTI, dental procedure, and UTI. No differences were found in household or dietary exposures.

Take-home point: This study highlighted the risk for CA-CDI infection for patients presenting to an ED and reiterates that exposures to fluoroquinolones, cephalosporins, beta-lactam and/or beta-lactamase inhibitor combinations, and clindamycin significantly increases the risk of CA-CDI infection. Reducing unnecessary outpatient antibiotic prescribing may prevent further CA-CDI. 36% of case patients did not have any antibiotic or outpatient health care exposure; therefore, additional risk factors may exist.

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Category: Pharmacology & Therapeutics

Title: Fever Treatment in Sepsis

Keywords: antipyretic, sepsis, fever (PubMed Search)

Posted: 10/7/2017 by Ashley Martinelli (Emailed: 10/10/2017) (Updated: 4/18/2024)
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Fever occurs in 40% of patients with sepsis.  Historically, there has been conflicting evidence of whether patient outcomes improve with antipyretic therapy.

A recent large meta-analysis assessed the effect of antipyretic therapy on mortality of critically ill septic patients.  The analysis included 8 randomized studies (1,531 patients) and 8 observational studies (17,432 patients) that assessed mortality of septic patients with and without antipyretic therapy.

The authors found no difference in mortality at 28 days or during hospital admission.  There was also no difference in shock reversal, heart rate, or minute ventilation.

As expected, they found a statistically significant reduction in posttreatment body temperature (-0.38°C, 95% IC -0.63 to -0.13) in patients who received antipyretic therapy.  NSAIDs and cooling therapies were more effective than acetaminophen, however no agent or dosing information was provided and only one study included physical cooling therapies.

Bottom Line: Antipyretic therapies do not reduce mortality in patients with sepsis, but they may improve patient comfort by reducing body temperature.

 

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Question

Take Home Point: In patients with diabetic gastroparesis, haloperidol may be an effective adjunctive treatment to prevent hospitalizations and reduce opioid requirements. 

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