The Elective Rotation: A Critical Care Hospital Pharmacy Podcast

In this episode I'll:

1. Review an article on propofol related infusion syndrome

2. Answer a drug information question about surgical antibiotic prophylaxis

3. Share a great resource I use for investigating drug induced thrombocytopenia

Article

Propofol infusion syndrome: a structured review of experimental studies and 153 published case reports

Lead Author: Adéla Krajčová

Published in Critical Care November 12, 2015

Background

Propofol is one of the more popular medications for continuous sedation in the intensive care setting. Propofol, along with dexmedetomidine are preferred over benzodiazepines in mechanically ventilated ICU patients according to the SCCM Pain, Agitation, and Delirium guidelines (class 2B recommendation).

Propofol infusion syndrome (PRIS) is an uncommon but potentially deadly side effect of propofol. There is not wide agreement on a definition of PRIS but most cases include several of the following:

-unexplained metabolic acidosis

-rhabdomyolysis

-hyperkalemia

-hepatomegaly

-renal failure

-hyperlipidemia

-arrhythmia

-Brugada-type ECG (elevated ST-segment and coved T-wave)

-rapidly progressive cardiac failure.

The first cases were described in pediatric patients in the early 1990s, followed shortly by adult case reports.

Methods

The paper analyzed data from 153 patients from case reports and case series published between 1990 and 2014.

The authors used multiple regression analysis to analyze factors associated with fatal outcome of PRIS.

Purpose

The primary purpose of the study was to determine the relationship of propofol exposure in patients identified with PRIS. Secondary outcomes were to find a link between the clinical presentations of PRIS with proposed cellular mechanisms and to describe trends in the reporting of PRIS over time.

Results

The fatality rate among the 153 published cases was 51%. This rate decreased over time from 74% before 2001 to 64% between 2001 and 2006, to 32% between 2006 and 2014.

Show notes at pharmacyjoe.com/episode34. In this episode I ll: 1. Review how to recognize severe hyperkalemia 2. Review the 3 categories of hyperkalemia treatments and the order which they should be used 3. Discuss the nuances of each treatment

In this episode I’ll:

1. Review how to recognize severe hyperkalemia

2. Review the 3 categories of hyperkalemia treatments and the order which they should be used

3. Discuss the nuances of each treatment

Recognizing hyperkalemia

Severe hyperkalemia can be recognized by cardiac conduction abnormalities on ECG, muscle weakness / paralysis, or a serum potassium value greater than 7. In a patient without chronically high potassium, a value lower than 7 may still have severe consequences.

While a patient with severe hyperkalemia can progress from any level of ECG change to ventricular tachycardia / ventricular fibrillation / asystole, in general a peaked T wave with shortened QT interval is the earliest change , followed by progressive lengthening of the PR interval and QRS duration. The P wave may disappear, and ultimately the QRS widens further to a sine wave until asystole occurs. Don't bother trying to learn at which level of potassium the ECG changes occur - the changes do not correlate well with the serum potassium concentration.

Show notes at pharmacyjoe.com/episode33. In this episode I’ll: 1. Review the FDA briefing documents for sugammadex 2. Answer a drug information question about dabigatran 3. Share a great resource I use for evaluating drug interactions

In this episode I'll:

1. Review the FDA briefing documents for sugammadex

2. Answer a drug information question about dabigatran

3. Share a great resource I use for evaluating drug interactions

Before we get to the topic for today’s show I want to invite you to join the Pharmacy Nation Slack group. This is a free group with other pharmacists from around the world collaborating with each other using real-time messaging to help better care for patients. I hope you join me and the over 85 other Pharmacy Nation members there! You can sign up at pharmacynation.org.

Article

Even though they are not published in a peer-reviewed journal, FDA briefing documents are a treasure trove of information. In these documents you can read FDA expert opinions as they analyze published and unpublished data about new medications seeking FDA approval. Reviewing these briefing materials can give you an in-depth understanding of the risks and benefits of new medications that you won’t be able to find in the prescribing information or even published articles in medical journals.

I know I’m dating myself here, but do you remember when rofecoxib was recalled in 2004? The events surrounding the recall of rofecoxib involved the purposeful non-reporting by the manufacturer of adverse cardiac events with the medication. The medication was on the market for 5 years before the “discovery” of the cardiac risk led to its withdrawal. But the concern for cardiac adverse events was well documented in the 2001 FDA briefing materials for rofecoxib. Anyone who read these documents would have been able to see it, but these documents are seldom reviewed by prescribers or other health care practitioners.

Also made routinely available on the FDA website are transcripts of the FDA advisory committee meetings - these can also provide fascinating insights into new medications by the questions & answers experts provide at the advisory committee meetings.

The documents are sometimes hundreds of pages long, so don’t go to the FDA website if you are looking for leisure reading material!

So when I heard that the Anesthesia FDA advisory committee recommended the approval of sugammadex, one of the first things I checked out was the FDA briefing material. Here is what I learned:

I’ve got to thank a critical care doc I work with - Pulmonology Tony - for taking the time to teach me about hyponatremia from SIADH several years ago.

In this episode I’ll share with you what he taught me and I'll:

1. Review the pathophysiology of hyponatremia from SIADH

2. Explain how normal saline makes it worse

3. Discuss basic treatment of severe, symptomatic hyponatremia from SIADH and what to do if you correct the sodium too fast

Before we get to the topic for today’s show I want to update you on 2 projects I’m working on. The first is the Pharmacy Nation Slack group. This is a free group with other pharmacists from around the world collaborating with each other using real-time messaging to help better care for patients. I hope you join me and the over 80 other Pharmacy Nation members there - request an invite at pharmacynation.org!

Since I’ve started this podcast, I’ve noticed there are a lot of pharmacists and other medical professionals sharing their expertise with the world using blogs and facebook pages and twitter accounts. But there are only a handful of high quality medical podcasts that are being published regularly. I’m hoping to change that. That’s why I’m putting together a step-by-step course on how to start a medical podcast - so that other medical professionals can bring their knowledge, expertise, and voice to the world of podcasting. To learn more about the course, and to sign up to be notified when it is available, head over to howtostartamedicalpodcast.com.

Learning about SIADH

The approach to the diagnosis and treatment of hyponatremia is complex. I recommend you read a review article such as this one or read the monograph in a tertiary reference such as UpToDate to get a more in-depth understanding of hyponatremia.

One of the best ways that I have found to learn concepts about treating diseases is to focus on the basic underlying pathophysiology of the disease. Back in pharmacy school I didn’t focus much on anatomy & physiology - but in practice I’ve learned that was one of the most important classes in my training. Each time I study about the best way to treat a disease (with or without medications) I focus on learning the pathophysiology.

That’s how Pulmonology Tony helped me understand hyponatremia in SIADH. SIADH stands for Syndrome of Inappropriate Anti-Diuretic Hormone. In this syndrome, there is too much antidiuretic hormone in circulation. Anti-diuretic hormone promotes water retention and solute loss in the collecting duct of the nephron. Too much ADH, and you end up with too much water retention & solute loss. The solute that is lost is primarily sodium, and this combined with excess water retention is what leads to hyponatremia in SIADH. SIADH can be caused by CNS damage or CNS disorders, cancer, lung disease, and medications. The list of medications that have been associated with causing SIADH is long! The most common classes that I see cause SIADH in patients are antiepileptics, antipsychotics, and antidepressants. You can find a detailed list here.

Show notes at pharmacyjoe.com/episode32. In this episode I ll share with you what he taught me and I’ll: 1. Review the pathophysiology of hyponatremia from SIADH 2. Explain how normal saline makes it worse 3. Discuss basic treatment of severe, symptomatic hyponatremia from SIADH and what to do if you correct the sodium too fast

Show notes at pharmacyjoe.com/episode31. In this episode, I will: Review an article about monitoring vancomycin by trough levels Answer a drug information question: Why do some of my trauma patients get heparin and some enoxaparin for DVT prophylaxis? Share sleep hygiene resources that I personally use.

In this episode, I will:

Review an article about monitoring vancomycin by trough levels

Answer a drug information question: Why do some of my trauma patients get heparin and some enoxaparin for DVT prophylaxis?

Share sleep hygiene resources that I personally use.

Article

Vancomycin Trough Concentration as a Predictor of Clinical Outcomes in Patients with Staphylococcus aureus Bacteremia: A Meta-analysis of Observational Studies

Author: John P. Prybylski

Published in Pharmacotherapy October 24, 2015

Background

Can you believe vancomycin is over 50 years old and we still don’t know the best way to dose it?

Joint guidelines on dosing vancomycin were published by the Infectious Disease Society of America and the Association of Health Systems Pharmacists in 2009.

In these guidelines the authors recommend attaining a trough of 15-20 mg/L when treating serious infection due to Staphylococcus aureus.

This trough goal of 15-20 mg/L in serious infection was controversial when it came out in 2009 and remains so today.

This goal was proposed as a way to ensure that patients achieve the ideal 24-hour area under the concentration-time curve to minimum inhibitory concentration ratio (AUC:MIC) of at least 400 hours. However, analyses have demonstrated that patients with adequate renal function can typically achieve the AUC:MIC goal with a more conservative trough concentration.

If you haven’t already joined the Pharmacy Nation slack group where pharmacists collaborate about patient care in real-time, sign up at pharmacynation.org. I hope you join me and the over 70 other Pharmacy Nation members there already!

In this episode I'll

1. Discuss some cases of using IV lipid emulsion for drug toxicity

2. List which patient care areas in my institution are stocked with IV lipid emulsion

3. Review the dosing of IV lipid emulsion

I first heard of the idea of using IV lipid emulsion as an antidote to drug overdose in 2008. An emergency physician showed me an article discussing a case that was reported in Annals of Emergency Medicine. A 17 year old female ingested nearly 8 grams buproprion and 4 grams lamotrigine in a suicide attempt. She developed seizure and cardiovascular collapse. She was coded for 70 minutes, until an anesthesiologist suggested giving IV lipid emulsion. Within 1 minute of receiving lipid emulsion, the patient had return of spontaneous circulation (ROSC). She recovered with near-normal neurologic function.

The case presented a compelling temporal relationship between the administration of IV lipids and ROSC. Previous to this case, lipid emulsion had only been used as an antidote for local anesthetic systemic toxicity (LAST). The first research using lipids to treat LAST was published in 1998 with a rat model of bupivicaine toxicity, and the first published human case report of lipid emulsion to treat LAST was in 2006. A 58 year old male had a cardiac arrest after placement of an interscalene block with bupivacaine and mepivacaine. After 20 minutes of advanced cardiac life support his rhythm had progressed to vtach, vfib, and asystole. He was given IV lipid emulsion and within 15 seconds had ROSC.

After reading the above cases, I took steps at my hospital to make sure that IV lipid emulsion was available in all critical care and peri-operative PYXIS machines. Several uneventful years went by, and wouldn’t you know it, on my day off a patient coded in our pre-op area 40 minutes after a ropivicaine block was placed. He had a very long code with many shocks and amiodarone administrations. Utimately, IV lipid emulsion was administered. Within 1 minute the patient had ROSC. He was eventually discharged home neurologically intact. The only adverse event from the lipid emulsion that was noted was his blood draws looked like strawberry milkshakes for 24 hours.