The Elective Rotation: A Critical Care Hospital Pharmacy Podcast

In this episode I’ll focus on 2 examples of medication overdose that require more than supportive care to treat effectively:

1. Acetaminophen poisoning

2. Methanol & ethylene glycol poisoning

A special shout out to my kids for the artwork & audio bumper for this episode!

Many poisons, few antidotes

Expert Consensus Guidelines for Stocking of Antidotes in Hospitals That Provide Emergency Care list just 21 antidotes to medications for stocking. Compare that to the over 1500 medications that have been approved by the FDA and it is readily apparent that most medications do not have antidotes.

Supportive care is the mainstay of treatment for overdose patients. Most medications, even when taken in overdose, will be safely cleared if a patient’s vital organ systems can be supported long enough.

But some overdose situations require an antidote in addition to supportive care for the the patient to survive.

Two common examples are acetaminophen poisoning and methanol or ethylene glycol poisoning.

Acetaminophen poisoning

At therapeutic doses, most acetaminophen is metabolized via sulfation and glucuronidation into safe metabolites and eliminated in the urine. About 8 % is metabolized via the hepatic cytochrome P450 pathway into the hepatotoxic metabolite N-acetyl-p-benzoquinoneimine (NAPQI). This toxic metabolite is readily and safely neutralized by hepatic glutathione before any damage to hepatocytes can occur.

After the administration of a toxic dose of acetaminophen (generally considered to be 7.5 g or more in adults), the safe metabolic pathways of sulfation and glucuronidation are saturated, and more of the toxic NAPQI is produced. Hepatic glutathione stores eventually deplete and NAPQI begins to damage hepatocytes.

If only supportive care is given, NAPQI will continue to be formed and fulminant hepatic failure and death will ensue.

Antidote for acetaminophen

The antidote for acetaminophen toxicity - N-acetylcysteine (NAC) - restores hepatic glutathione stores, allowing NAPQI to be safely neutralized and preventing hepatic damage.

If N-acetylcysteine is given within 10 hours of ingestion of toxic doses of acetaminophen, prognosis is excellent.

N-acetylcysteine can be given IV or orally using either a 20 hour or 72 hour protocol.

Show notes at pharmacyjoe.com/episode50. In this episode I ll focus on 2 examples of medication overdose that require more than supportive care to treat effectively: 1. Acetaminophen poisoning 2. Methanol & ethylene glycol poisoning

Show notes at pharmacyjoe.com/episode49. In this episode I’ll: 1. Review an article about fixed dosing of 4-factor prothrombin complex concentrate for emergent warfarin reversal 2. Answer the drug information question: What is the dose of subcutaneous heparin to provide full therapeutic anticoagulation? 3. Share a resource for information about drug-induced & iatrogenic respiratory disease

Show notes at pharmacyjoe.com/episode49

In this episode I'll:

1. Review an article about fixed dosing of 4-factor prothrombin complex concentrate for emergent warfarin reversal

2. Answer the drug information question: What is the dose of subcutaneous heparin to provide full therapeutic anticoagulation?

3. Share a resource for information about drug-induced & iatrogenic respiratory disease

Thank you to Emergency Medicine Alex for sharing this article!

Article

Evaluation of fixed dose 4-factor prothrombin complex concentrate for emergent warfarin reversal

Lead author: Lauren Klein

Published in: The American Journal of Emergency Medicine, May 2015

Background

Four-factor prothrombin complex concentrates (4FPCC) for warfarin reversal are faster to prepare and administer than fresh frozen plasma. The optimal dose of 4FPCC is not known. Current dose recommendations in the US involve calculations based on pretreatment INR. Waiting for the pretreatment INR value to be resulted by the hospital laboratory may delay administration of 4FPCC by 30 minutes or more.

Purpose

The authors sought to characterize the safety and efficacy of 4FPCC in patients who received a fixed dose of 1500 units regardless of pretreatment INR for emergent warfarin reversal.

Methods

The study was a retrospective, single-center review of patients who received 1500 IU of 4FPCC for emergent warfarin reversal between March 2014 and January 2015.

Results

A total of 39 patients were reviewed. The most common indication for treatment was intracranial hemorrhage ( 71.8%). The median INR at presentation was 3.3, and the median INR after a single dose of 1500 IU was 1.4. A total of 36 patients (92.3%) achieved successful reversal with a target INR of less than 2. 28 patients (71.8%) achieved successful reversal with a target INR of 1.5 or less. There were no thrombotic adverse events within 7 days.

Conclusion

The authors concluded that administration of a fixed dose of 1500 units of 4FPCC leads to high rates of successful INR reversal and no related thrombotic adverse events within 7 days.

Discussion

Administering 4FPCC quicker by eliminating the need for a pretreatment INR is great in theory. The advantage 4FPCC has over fresh frozen plasma is speed of administration and this fixed dosing strategy enhances that advantage. The hope is that this will translate into improved clinical outcomes.

It is important to examine the treatment failures in the study which were 3 patients who did not have a post treatment INR below 2:

Show notes at pharmacyjoe.com/episode48. In this episode I ll review the medications used to support the treatment of shock from 12 different etiologies.

Show notes at pharmacyjoe.com/episode48

In this episode I’ll review the medications used to support the treatment of shock from 12 different etiologies.

During the treatment of shock, the patient’s life hangs in the balance while the care team quickly delivers interventions to identify and treat the underlying cause. Many of these interventions require medications to facilitate treatment.

I see the pharmacist’s role in the treatment of shock as “setting the table” by having the necessary medications immediately available so the rest of the team can deliver supportive care or other interventions to the patient.

Recognizing shock

Typical features for shock include:

- Altered mental status

- Tachycardia

- Hypotension

- Oliguria

- Cool, clammy skin

- Metabolic acidosis

Supportive care

Airway, breathing, and circulation need to be addressed immediately. Obtain medications to facilitate endotracheal intubation, IV fluids, and vasopressors to maintain circulation. You might not have a central line at first but this is not a reason to delay the administration of vasopressors.

Any (IV) port in a storm.

Show notes at pharmacyjoe.com/episode47. In this episode I’ll: 1. Review an article about augmented renal clearance of antibiotics in critically ill patients 2. Answer the drug information question “For a patient with rash to penicillin that is 5 months s/p TAVR and has 4/4 bottles positive for gram positive cocci resembling staph, what antibiotic regimen [...]

Show notes at pharmacyjoe.com/episode47

In this episode I'll:

1. Review an article about augmented renal clearance of antibiotics in critically ill patients

2. Answer the drug information question "For a patient with rash to penicillin that is 5 months s/p TAVR and has 4/4 bottles positive for gram positive cocci resembling staph, what antibiotic regimen should be used?"

3. Share a resource I use to visually show the risks and benefits of tPA use in acute ischemic stroke

Thank you to Pharmacy Monique for sharing this article!

Article

Implications of Augmented Renal Clearance on Drug Dosing in Critically Ill Patients: A Focus on Antibiotics

Authors: Athena L V Hobbs, Katherine M Shea, Kirtsen M Roberts, and Mitchell J Daley

Published in: Pharmacotherapy November 2015

Background

Augmented renal clearance (ARC) of medications has been reported in 30–85% of patients in the intensive care unit, depending on patient specific factors.

Purpose

This review article characterizes ARC in the critically ill, describes risk factors, reviews screening methods and assessment strategies, and illustrates its effect on in vivo drug concentrations and clinical outcomes.

Methods

The authors conducted a PubMed search that included all pertinent articles from January 1990 through April 2015.

Discussion

The authors state:

There is a clear association between ARC and subtherapeutic antibiotic concentrations as well as literature suggesting worse clinical outcomes; thus, the risk of underdosing antibiotics in a patient with ARC could increase the risk of treatment failure.

Discussed in the article is a weighted scoring system previously published for ARC. Patients get 6 points if they are 50 years or younger, 3 points if they are admitted for trauma, and 1 point if their SOFA score is 4 or less upon ICU admission.

Show notes at pharmacyjoe.com/episode46. In this episode I’ll review the pharmacologic treatments for anaphylaxis.

Show notes at pharmacyjoe.com/episode46

In this episode I'll review the pharmacologic treatments for anaphylaxis.

Definition

Anaphylaxis is a potentially fatal allergic reaction with a rapid onset.

Immunoglobulin E (IgE)-mediated allergic reactions to food, insect stings and medications are the most common triggers for anaphylaxis.

As a result of the IgE reaction, mast cells release histamine and other mediators of anaphylaxis. If not properly treated, it will progress to respiratory arrest and cardiovascular collapse.

Diagnostic criteria

According to World Allergy Organization guidelines, anaphylaxis is highly likely when any one of the following three criteria is fulfilled:

1. Acute onset of an illness (within minutes to several hours) with involvement of the skin, mucosal tissue, or both (eg, generalized urticaria, itching or flushing, swollen lips-tongue-uvula)

AND AT LEAST ONE OF THE FOLLOWING:

A) Respiratory compromise (eg, dyspnea, wheeze-bronchospasm, stridor, reduced PEF, hypoxemia)

B) Reduced blood pressure or associated symptoms of end-organ dysfunction (eg. hypotonia [collapse], syncope, incontinence)

2. Two or more of the following that occur rapidly after exposure to a likely allergen for that patient (within minutes to several hours)

A) Involvement of the skin-mucosal tissue (eg, generalized urticaria, itch-flush, swollen lips-tongue-uvula)

B) Respiratory compromise (eg, dyspnea, wheeze-bronchospasm, stridor, reduced PEF, hypoxemia)

C) Reduced blood pressure or associated symptoms (eg, hypotonia [collapse], syncope, incontinence)

D) Persistent gastrointestinal symptoms (eg, crampy abdominal pain, vomiting)

3. Reduced blood pressure after exposure to known allergen for that patient (within minutes to several hours)

A) Infants and children: low systolic blood pressure (age-specific) or greater than 30% decrease in systolic blood pressure

B) Adults: systolic blood pressure of less than 90 mm Hg or greater than 30% decrease from that person's baseline

Treatment of anaphylaxis

Epinephrine, IV fluids, and airway management are the main treatments for anaphylaxis.

Epinephrine

Epinephrine is the drug of choice for anaphylaxis. Epinephrine has no absolute contraindications to use in the treatment of anaphylaxis.

Epinephrine stabilizes mast cells, prevents or reverses obstruction to airflow in the upper and lower respiratory tracts and prevents or reverses cardiovascular collapse.

Intramuscular (IM) injection is the preferred route of administration for the treatment of anaphylaxis. Several different preparations of epinephrine are available - take care to select the correct one! The epinephrine preparation for intramuscular injection contains 1 mg per mL and will also be labeled as epinephrine 1:1000.

The recommended adult dose of epinephrine (1 mg per mL) is 0.3 to 0.5 mg per single dose, injected IM into the mid-outer thigh. If needed, this dose may be repeated every 5 to 15 minutes.