UMEM Educational Pearls - Pharmacology & Therapeutics

Category: Pharmacology & Therapeutics

Title: Calcium for Out-of-Hospital Cardiac Arrest

Keywords: Calcium, cardiac arrest (PubMed Search)

Posted: 12/4/2021 by Ashley Martinelli (Updated: 1/21/2022)
Click here to contact Ashley Martinelli

Calcium is commonly administered during cardiac arrest, but there is little data to support or refute its use.  The Calcium for Out-of-Hospital Cardiac Arrest trial was a randomized, double-blind, placebo-controlled parallel group study conducted in Denmark.  Their EMS system responds to all cardiac arrests with an ambulance and a physician-manned mobile emergency care unit.

Adult patients were included if they had out of-of-hospital (OOH) cardiac arrest and received at least 1 dose of epinephrine. Exclusion criteria were traumatic arrest, known or suspected pregnancy, prior enrollment in the trial, receipt of epinephrine from an EMS unit not in the trial, or a clinical indication for calcium during the arrest (i.e. hyperkalemia or hypocalcemia).

Patients received 735mg calcium chloride dihydrate (5 mmol CaCl –US standard product is 1000mg) or saline control immediately after the first dose of epinephrine.  A second dose was administered after the second dose of epinephrine if cardiac arrest ongoing. Teams were blinded to the treatments. The primary outcome was ROSC for at least 20 minutes.

397 patients were randomized (197 calcium, 200 saline). The average age was 68 years old, 70% were male, and over 80% of the cardiac arrests occurred at home, 60% witnessed arrests, and 82% received bystander CPR. Only 25% were in a shockable rhythm. The time to first epinephrine and study drug was approximately 17 minutes and over 70% received two doses.

ROSC rates were low and not statistically different between groups, 19% in the calcium group vs 27% in the saline group.  There was no difference in survival to 30d or neurologic function. In the patients who did achieve ROSC in the calcium arm, 74% had hypercalcemia.

Bottom Line: The routine use of calcium in out-of-hospital cardiac arrest is not recommended.

 

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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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 Vancomycin infusion reactions can manifest as pruritus and an erythematous rash of the neck, face, and torso during or after a vancomycin infusion.  This is a histamine reaction caused by degranulation of mast cells and basophils, and can be caused short infusion times <60 min.  It is commonly treated with antihistamines and/or a slowing of the infusion rate. 

Historically, this has been called “Red Man Syndrome.”  As we move towards more inclusive language in medicine, it is increasingly necessary to remove language that is insensitive and/or offensive.  Not only is “Red Man Syndrome” offensive towards Native Americans, it also is an inaccurate term that implies a clinical presentation in white male patients when this reaction can occur in any race or gender. 
The preferred terminology is now “vancomycin infusion reaction” or “vancomycin flushing reaction” and is supported by physician, pharmacist, and pediatric professional publications.    
Allergy documentation matters.  Always include descriptors of the reaction to avoid labeling patients “vancomycin allergic” if it truly was an infusion reaction as this can lead to suboptimal second line therapy being unnecessarily selected.  
 
What you can do:
1.       Replace “Red Man Syndrome” with vancomycin infusion reaction in your teaching and vernacular
2.       Remove “Red Man Syndrome” from patient allergies and replace with Vancomycin Infusion Reaction with a short description of what the patient experienced
3.       Avoid using “Red Man Syndrome” in your future scholarly works and publications

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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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Tranexamic acid (TXA) is an antifibrinolytic medication that has been trialed in previous small studies to treat epistaxis. The data to this point has not reliably shown a reduction in bleeding at 30 minutes, but has demonstrated an increased rate of discharge at 2 hours and a reduction in re-bleeding events.

The NoPAC study was the largest study to date on TXA for epistaxis. It was a double-blind, placebo-controlled, randomized study of TXA in adult patients with persistent atraumatic epistaxis to determine if TXA use decreased the rate of anterior nasal packing. Patients were excluded if they had trauma, out of hospital nasal packing, allergy to TXA, nasopharyngeal malignancy, hemophilia, pregnancy, or if they were referred to ENT.

Eligible patients completed 10 minutes of first aid measures followed by 10 minutes of topical vasoconstrictor application prior to randomization to either placebo of 200mg TXA soaked dental rolls inserted in the nare.

496 patients were enrolled. The average patient was 70 years old with stable vitals 150/80mmHg, HR 80 bpm with >60% on oral anticoagulants.

TXA did not reduce the need for anterior nasal packing: 100 (41.3% placebo) vs 111 (43.7% TXA) OR 1.11 (0.77-1.59). There were no differences in the rates of adverse events.

Bottom Line: TXA does not improve rates of anterior nasal packing for patients with persistent epistaxis.

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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
Click here to contact Wesley Oliver

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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Opioid Conversion Updates

Updated in 2018, some clinicians are unaware of the changes to the opioid conversion tables.

 

2010 Recommendations

 

2018 Updates

Opioid

IV (mg)

PO (mg)

 

IV (mg)

PO (mg)

Morphine

10

30

 

10

25

Fentanyl

0.1

NA

 

0.15

NA

Hydromorphone

1.5

7.5

 

2

5

Oxycodone

NA

20

 

NA

20

 

When converting between opioids, it is important to remember the following steps:

  1. Determine the patient’s level of pain and current response to therapy.
  2. Calculate current opioid requirement.
  3. Convert the opioid using table above.
  4. ASSESS! Combine Steps 1-3 to determine what is most appropriate clinically.  If the patient is suffering from severe pain, using the calculated dose may be appropriate.  If the patient is requesting a switch but is otherwise pain controlled, consider a general dose reduction of 25-50% in the new opioid.
  5. Monitor the patient for efficacy and side effects.

 

While online calculators can be helpful, opioid conversions should be done thoughtfully with a full patient assessment to determine the correct conversion for the individual patient.

 

 

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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: Nitroglycerin Drug-Drug Interactions

Keywords: nitroglycerin, hypotension, PDE5 inhibitors (PubMed Search)

Posted: 10/3/2020 by Ashley Martinelli
Click here to contact Ashley Martinelli

Nitroglycerin is a potent vasodilator used most commonly for the treatment of angina and ACS.  It can also be administered as a continuous infusion for acute management of a hypertensive emergency or sympathetic crashing acute pulmonary edema.  

 

Most are aware of asking men for history of medications for erectile dysfunction (PDE5 inhibitors: sildenafil, tadalafil, vardenafil) but many overlook the fact that men and women may be on these medications chronically for pulmonary hypertension. Men can also be on these medications for the treatment of BPH. Be broad in your history taking and do not limit the discussion to erectile dysfunction or a specific gender.

 

Drug interaction:

-PDE5 inhibitors prevent the breakdown of cGMP

-Nitrates are nitric oxide donors that increase the production of cGMP

-The combination can lead to excessive vasodilation

 

If accidentally co-administered:

There is no antidote for this medication error.  Support the patient with Trendelenburg positioning, fluid administration, and if needed, vasopressors such as norepinephrine until blood pressure stabilizes.

 

How long should you wait to administer nitrates after a patient takes a PDE5 Inhibitor?

Sildenafil and vardenafil: 24 h after last dose*

Tadalafil > 48 h after last dose*

*Even if acute ACS event

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Category: Pharmacology & Therapeutics

Title: Esmolol for Refractory Ventricular Fibrillation (VF) or Pulseless Ventricular Tachycardia (VT)

Keywords: esmolol, cardiac arrest, ventricular tachycardia, ventricular fibrillation (PubMed Search)

Posted: 9/5/2020 by Ashley Martinelli (Updated: 1/21/2022)
Click here to contact Ashley Martinelli

Patients with cardiac arrest due to VF/VT have a higher likelihood of survival compared to those with unshockable rhythms.  Unfortunately some will still not survive even with following the AHA/ACLS algorithms leading to “refractory VF/VT.”  The survival rate of refractory VF/VT is 3-15%, with poor neurologic outcomes. 
 
Esmolol has been proposed as a treatment for the electrical storm of VF/VT to counteract the deleterious effect of beta receptor stimulation by epinephrine.
 
A recent meta-analysis of 3 trials of beta-blockade vs control patients for refractory VF/VT found:
 
Beta-blockade
N=22
Control
N= 44
OR/CI
Temporary ROSC, n (%)
19 (86.4)
14 (31.8)
OR 14.46, 95% CI 3.63-57.57
Sustained ROSC, n (%)
13 (59.1)
10 (22.7)
OR 5.76, 95% CI 1.79-18.52
Survival with neurological function, n (%)
6 (27.3)
4 (9.1)
OR 4.42; 95% CI 1.05-18.56
 
Takeaway: Esmolol needs to be studied further in prospective trials, but may be reasonable to attempt in refractory VF/VT.
 
Esmolol products:
§  Esmolol vial: 10 mg/mL (10mL)
o   Vial strength listed in mg, not mcg
o   Can cause complications with calculations, especially in high risk code scenario
§  Conversion of mg à mcg weight à based calculation 500mcg/kg
§  Do not ask anyone to do this calculation during a code!
§  Esmolol pre-made infusion: 2500 mg/250mL
o   Pump is set up to deliver weight based doses in mcg/kg
o   No mental math required!
 
How to do it at UMMC to limit mistakes in calculation:
1.       Obtain an esmolol pre-made infusion bag
2.       Program the pump for 50 mcg/kg/min continuous infusion (this is a required step in pump programming)
3.       Program the pump to give a 500 mcg/kg bolus x 1
4.       Permit the background infusion to run
5.       Can give an additional bolus of 500 mcg/kg x 1 and increase rate to 100 mcg/kg/min depending on clinical response

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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: 1/21/2022)
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.

 

Show References


Category: Pharmacology & Therapeutics

Title: Safe Opioid Use in Renal Failure

Keywords: opioid, renal failure, dialysis (PubMed Search)

Posted: 7/6/2020 by Ashley Martinelli (Updated: 1/21/2022)
Click here to contact Ashley Martinelli

Pain management can be challenging in patients with acute or chronic renal failure.  Opioid medications should always be used with caution, but some are safer than others.  Morphine and codeine specifically should be avoided in these patients due to accumulation of active metabolites that can prolong the duration of effect and adverse events. 

Opioid

Renal Failure Impacts

Renal Failure Recommendation

Dialysis Recommendation

Morphine

Active metabolites accumulate

no

no

Codeine

Active metabolites accumulate

no

no

Hydromorphone

Minimal active metabolites

yes

yes

Oxycodone

Minimal active metabolites

yes

yes

Fentanyl

No active metabolites

yes

yes

Methadone

Active metabolites are inactive

yes

yes

 

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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
Click here to contact Wesley Oliver

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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Short periods of AKI have been linked to prolonged hospitalizations, development of CKD/ESRD and in-hospital mortality.  Historically, AKI in the ED has been studied with respect to the receipt of contrast media with little data available on nephrotoxic medications.

A recent 5-year retrospective cohort study sought to determine the impact of prescribing nephrotoxic medications in the ED and the development of AKI within 7 days defined as an increase in SCr of ≥ 0.3 mg/dL or 1.5 x baseline.  The categories of potentially nephrotoxic medications included ACE-i/ARB, antibiotics, diuretics, NSAIDs, and other (antifungal, antineoplastic, and antivirals).

Inclusion: Adult patients ≥ 18 years, with an initial and repeat SCr measured 24-168h after the initial test, under admitted or observation status (discharged patients were included if they had a repeat SCr in the time window).

Exclusion: previous hospital or ED visit within 7 days, initial SCr < 0.4 mg/dL, initial SCr > 4.0 mg/dL, missing data, dialysis, or transplant history.

The authors assessed 46,965 hospitalized encounters and found that 13.8% of patients developed AKI.  Risk factors included older age, African American patients, history of CHF or CKD, higher initial SCr, and higher complexity and mortality.  AKI developed within 48 hours in half of the patients and the reminder did so by 120 hours.  Approximately 22% had ≥ 1 potentially nephrotoxic medication administered and 6% had ≥ 2 classes.

Diuretics were associated with the highest risk of AKI (64% increased risk), followed by ACE-i/ARBs (39%), and antibiotics (13%).  NSAIDs were not associated with an increased risk. The antibiotics associated with the highest risk of AKI were piperacillin-tazobactam, sulfamethoxazole-trimethoprim, and quinolones.

Bottom Line: Medications prescribed in the ED have an impact on the development of AKI during hospitalization.  While these cannot always be avoided, use caution when combining multiple nephrotoxic medications and discontinue therapy early when feasible.

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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: Adenosine Administration

Keywords: adenosine, SVT (PubMed Search)

Posted: 12/8/2019 by Ashley Martinelli (Updated: 1/21/2022)
Click here to contact Ashley Martinelli

Adenosine is an atrioventricular nodal blocking agent that is commonly used in the treatment of supraventricular tachycardia.  It is dosed as 6 mg IV Push x 1, followed by dose escalation to 12 mg IV Push if the initial dose was unsuccessful.  In patients with central access or prior orthotopic heart transplantation, the initial recommended dose is 3 mg.

Due to its short half-life (< 10 seconds) it is imperative to administer in the most proximal access and follow with a 20 mL bolus of saline.  Traditionally this is done using a two-way stopcock. 

A new study compared single syringe (adenosine 6mg + 18 mL saline) vs two syringes (adenosine 6mg in one, 20 mL saline in the other) in 53 patients with SVT.  The single syringe arm converted to NSR 73.1% after one dose compared to 40.7% in the two-syringe arm (p=0.0176).  After up to three doses, the single syringe arm had 100% conversion compared to 70.4% in the two-syringe arm (p=0.0043).

Single syringe adenosine has been recommended in FOAM for several years.  Although small, this study is the first to compare the two methods.  This method simplifies administration and may improve cardioversion rates.

 

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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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