UMEM Educational Pearls - By Ashley Martinelli

For patients with bleeding due to warfarin, prothrombin complex concentrate (PCC) is the recommended antidote. Historically, PCC has been dosed on weight and INR:

·         INR 2 - 4: 25 units/kg, max 2500 units

·         INR 4 - 6: 35 units/kg, max 3500 units

·         INR > 6: 50 units/kg, max 5000 units

New data demonstrates that fixed dosing offers several advantages with similar efficacy outcomes:

·         Standardized dosing

·         Improved time to administration

·         Decreased cost

The University of Maryland Health System has adopted a fixed dose strategy for all patients with warfarin-associated critical bleeding:

·         Bleeding site other than intracranial hemorrhage AND INR 1.4 - 6 AND weight ≤ 100 kg = 1500 units

·         Intracranial hemorrhage OR > 100 kg OR INR >6 = 2000 units

**Note: PCC is also the antidote of choice for reversing critical bleeding due to factor Xa inhibitors (rivaroxaban, apixaban, edoxaban).  All critical bleeds due to these agents should receive 50 units/kg, max 5000 units.

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Continuous home infusion therapies of medications such as insulin, milrinone, dobutamine, and pulmonary hypertension medication such as treprostinil are becoming more common.  As a result, you may see these patients present to the emergency room and need to know the basics for checking the pump.

• Is the pump working correctly?
  • Check the infusion lines for leaks or holes
  • Is the screen on, and does it show the correct dose information
• How long will the current battery last?
• How long will the current infusion bag last or expire?
  • Also consider the half-life of the medication. Infusions for pulmonary hypertension have a very short half-life and cannot be stopped abruptly.
• Is the medication carried by the hospital or will the patient need to provide their own medication for pump refills?
• What is the current dose?
  • Look for doses in weight based increments (i.e. mcg/kg/min, or ng/kg/min)
  • Insulin may have a basal rate and a bolus dose.
• What is the patient's "dosing weight"?
  • Ensure that the weight used to program the pump is the same weight used to enter a continuation order in the electronic medical record. This may be different from their current weight and can lead to dose changes if not done properly.
• What is the current bag concentration?

These questions are very important to determine if you will need to order a replacement infusion bag and run it on a hospital infusion pump, or if the patient can safely remain on their pump during the initial medical evaluation. 

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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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• 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

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

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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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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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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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