In this episode I’ll:

1. Review an article about using melatonin to decrease the need for sedation in the ICU

2. Answer the drug information question “How long can I take NSAIDs before I need to take GI prophylaxis?

3. Share a resource I use when taking care of a patient with myasthenia gravis

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Article

Melatonin reduces the need for sedation in ICU patients: a randomized controlled trial

Lead Author: Giovanni Mistraletti

Published in the journal Minerva Anestesiologica December 2015

Background

Critically ill patients suffer from physiological sleep deprivation and have reduced blood melatonin

levels.

Purpose

The purpose of this study was to determine whether nocturnal melatonin supplementation would reduce the need

for sedation in critically ill patients.

Methods

This double-blind randomized placebo-controlled trial was carried out in a mixed medical-surgical Intensive Care Unit in Milan, Italy. Of 1158 patients admitted to ICU, 82 critically-ill patients with mechanical ventilation >48 hours and Simplified Acute Physiology Score II > 32 points were randomized 1:1 to receive melatonin 3 mg at eight p.m. and midnight, or placebo from the third ICU day until ICU discharge. The primary outcome was the total amount of enteral hydroxyzine administered (more about this interesting outcome later).

Results

Melatonin treated patients received a lower amount of enteral hydroxyzine. Other neurological indicators

(the amount of neuroactive drugs, pain, agitation, anxiety, sleep observed by nurses, need for restraints, need for

extra sedation, and nurse evaluation of sedation adequacy) seemed improved, with reduced cost for neuroactive drugs.

Post-traumatic stress disorder prevalence did not differ between groups, nor did ICU or hospital mortality. Study

limitations include the differences between groups before intervention, the small sample size, and the single-center

observation.

Conclusion

The authors concluded that long-term enteral melatonin supplementation may result in a decreased need for sedation, with improved

neurological indicators and cost reduction. Further multi-center evaluations are required to confirm these

results with different sedation protocols.

Enteral sedation protocol

One of the more fascinating details with this article is the unique sedation protocol. The sedation protocol starts off with giving propofol or midazolam IV infusions as is standard in most ICUs. Within 48 hours, ICU patients are weaned off the propofol or midazolam and converted to an enteral sedation regimen using lorazepam (up to 16 mg per day) and hydroxyzine (up to 600 mg per day). The sedation target for this protocol is a RASS of 0 to -1.

The idea that inexpensive enteral sedation could be effective for ICU sedation, possibly with fewer side effects, is extremely interesting. There is a multicenter trial underway comparing this enteral sedation protocol to IV sedation with midazolam or propofol according to clinicaltrials.gov. There is not enough information to adopt this protocol now but it is certainly something I look forward to seeing more research on!

Personal connection

I contacted the lead author for this article regarding one of his prior studies many years ago. He was very helpful to me and gave me detailed answers to my questions. He asked me to review the English language version of this manuscript since his primary language is Italian. It was a great experience and my name appears in the acknowledgement section! Thank you Giovanni!

I’ve mentioned this before on the podcast and it is worth repeating – don’t hesitate to use the correspondence email provided in every published journal article. You’re nearly guaranteed to get a response from the author and you never know where it might lead!

Drug information question

Q: How long can I take NSAIDs before I need to take GI prophylaxis?

A: Start right away (but only if you really need to).

In the process of answering this question for a physician colleague of mine I came across something I had never heard before. My colleague was taking ibuprofen chronically for stiffness in his hands. In my research I determined that he was low risk for bleeding and didn’t need GI prophylaxis while taking ibuprofen. To answer his question I used the 2009 ACG practice Guidelines for Prevention of NSAID-Related Ulcer Complications. On page 2 the guidelines state:

In a large series based on autopsy findings on patients with a history of NSAID use, gastric and duodenal ulcers were found to be more common among patients who had consumed NSAIDs for less than 3 months.

Then there is this curiously unreferenced statement:

Although the risk of ulcer complications decreases after the first few months of NSAID use, it does not vanish with longterm therapy.

Previous to reading this I had no idea that the chance of a GI bleed from chronic NSAID use was higher in the first few months of therapy. If the patient is high risk for GI bleeding from NSAID therapy, start the GI prophylaxis right away.

Resource

I recently took care of a patient with myasthenia gravis who had post-op respiratory failure. Whenever I am involved in the care of a patient with myasthenia gravis, I review their meds against the list of meds at myasthenia.org that are known to exacerbate myasthenia gravis. After I make sure the patient is not inadvertently taking a medication that could worsen their myasthenia, I’ll print out the list and place it in the chart so that clinicians can review it prior to ordering new medications for the patient.

I’d like 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 120 other Pharmacy Nation members there! You can sign up at pharmacynation.org.

Listeners can support the show by shopping through my amazon link at the bottom of this page, or by purchasing something they find useful from my resource page at pharmacyjoe.com/resources.

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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