In this episode I’ll:

1. Discuss an article about increased mortality from epinephrine in cardiogenic shock.

2. Answer the drug information question “Can phenytoin cause hypothermia”

3. Share two resources for students to learn the basics of pharmacology.

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Article

Current real-life use of vasopressors and inotropes in cardiogenic shock – adrenaline use is associated with excess organ injury and mortality

Lead author: Tuukka Tarvasmäki

Published in the journal Critical Care July 2016

Background

Vasopressors and inotropes are a vital part of supportive care given to patients with severely impaired hemodynamics and cardiac output in cardiogenic shock. The authors of this study sought to analyze current real-life use of these medications, and their impact on outcomes in cardiogenic shock.

Methods

The CardShock study enrolled 219 patients with cardiogenic shock in 9 hospitals across 8 European countries. The study was a prospective observational study of patients with cardiogenic shock. The use of vasopressors and inotropes was analyzed in relation to the primary outcome of 90-day mortality. Changes in cardiac and renal biomarkers over time until 96 hours from baseline were also analyzed.

Results

The mean patient age was 67 years, 26% of patients were female, and 28% had been resuscitated from cardiac arrest prior to study inclusion. On average, systolic blood pressure was 78 mmHg and mean arterial pressure 57 mmHg at detection of shock.

Overall 90-day mortality was 41%. Vasopressors and/or inotropes were administered to 94% of patients. Norepinephrine and epinephrine were given to 75 % and 21 % of patients. In multivariable logistic regression, only epinephrine was independently associated with increased 90-day mortality (OR 5.2, 95 % CI 1.88, 14.7, p = 0.002). This association was independent of prior cardiac arrest, and it remained no matter how the numbers were crunched.

Epinephrine was also associated with worsening of cardiac and renal biomarkers during the first days of study inclusion. Dobutamine and levosimendan (not available in the US) were the most commonly used inotropes (49% and 24%). There were no differences in mortality, whether norepinephrine was combined with dobutamine or levosimendan.

Conclusion

The authors concluded:

Among vasopressors and inotropes, adrenaline was independently associated with 90-day mortality in cardiogenic shock. Moreover, adrenaline use was associated with marked worsening in cardiac and renal biomarkers. The combined use of noradrenaline with either dobutamine or levosimendan appeared prognostically similar.

Discussion

Although this study was not a randomized controlled trial, it does represent another piece of evidence that suggests norepinephrine is the ideal first line vasopressor not just for septic shock but for cardiogenic shock as well. In this study epinephrine seemed to be a problem no matter what the maximum dose was.

In my practice I have found that getting norepinephrine started first is critical to maintaining the patient on the best vasopressor according to the evidence. If a patient is stabilized on phenylephrine and dopamine and appears to be “doing just fine” many clinicians are hesitant to switch vasopressors out of concern for provoking hemodynamic instability. I like to say: “You go to the code with the vasopressors you have, not the vasopressors you wish you had”.

I make every effort to have a norepinephrine infusion ready to go if I think it will be needed so that the best vasopressor therapy is available the moment it is needed for the patient.

Drug information question

Q: Can phenytoin toxicity cause severe hypothermia?

A: Yes, it has been reported twice.

An elderly male patient came in with a phenytoin level of 30 mg / dL, bradycardia, hypothyroidism, and a temperature of 32 degrees Celsius. Phenytoin toxicity could have played a role as it is known to cause bradycardia and hypothyroidism. While hypothyroidism could explain such profound hypothermia, there have also been two case reports implicating phenytoin as a cause of hypothermia.

Resource

The resources for this episode have been created by listeners of the podcast.

“Pharmacy Tony” published the book Memorizing Pharmacology: A Relaxed Approach. It is also available as an audio book.

“Pharmacy Sean” who runs the site clincalc.com has put together an online course titled The Top 250 Drugs Online Course: Learn and Review Drug Therapy Essentials.

These resources would be particularly helpful for students of pharmacy, physician assistant, or nurse practitioner programs who need additional pharmacology support.

If you like this post, check out my book – A Pharmacist’s Guide to Inpatient Medical Emergencies: How to respond to code blue, rapid response calls, and other medical emergencies.

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