Episode 151: Ketorolac ceiling dose, paralytics for shivering, and a resource for interpreting laboratory data

In this episode I’ll:

1. Discuss an article about the ceiling dose of ketorolac.

2. Answer the drug information question “Should bolus or continuous paralytics be used to prevent shivering in therapeutic hypothermia?”

3. Share a resource for interpreting laboratory data.

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The article from this episode was one of many recently featured in a literature digest within my critical care pharmacy academy. In the Academy you will learn critical care skills, keep up with critical care literature, and connect with other pharmacists. To learn more click here.

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Article

Comparison of Intravenous Ketorolac at Three Single-Dose Regimens for Treating Acute Pain in the Emergency Department: A Randomized Controlled Trial

Lead author: Sergey Motov (@painfreeED)

Published online in the Annals of Emergency Medicine December 2016

Background

NSAIDs, especially ketorolac, are effective for a broad range of acute pain conditions. But all NSAIDs have a ceiling dose beyond which, no additional analgesic effect is seen. For ketorolac, the ceiling dose appears to be 10 mg, based on several studies from the 1990s. While analgesic benefits stop at 10 mg, side effects such as bleeding are dose-related. The authors of this study sought to evaluate the analgesic efficacy of 10, 15, and 30 mg doses of intravenous ketorolac in ED patients with acute pain.

Methods

The study was a randomized, double-blind trial in patients aged 18 to 65 years who presented to the ED with moderate to severe acute pain. The primary outcome was pain reduction at 30 minutes. IV morphine 0.1 mg/kg was used as rescue analgesia if the patient still desired additional pain relief after 30 minutes from when ketorolac was given.

Results

80 patients were in enrolled in each dosing arm of the study. Each group experienced significant pain reduction at 30 minutes, and there was no difference whether the ketorolac dose was 10, 15, or 30 mg. Rates of rescue analgesia and adverse effects were also similar between groups.

Conclusion

The authors concluded:

Ketorolac has similar analgesic efficacy at intravenous doses of 10, 15, and 30 mg, showing that intravenous ketorolac administered at the analgesic ceiling dose (10 mg) provided effective pain relief to ED patients with moderate to severe pain without increased adverse effects.

 

Discussion

I must have missed the lecture in school that discussed the ceiling dose of NSAIDs. I came across the concept years ago listening to a random lecture on freeemergencytalks.net (the resource discussed on episode 149), and ordered the full text of some of the original ketorolac studies from the 1990s. Sure enough, 10 mg of ketorolac was no better than 30 mg. I’m stunned as to how the FDA would have approved doses of 15, 30, and even 60 mg of ketorolac when the ceiling dose of 10 mg was clear as day. Since learning this, I’ve never used the 30 or 60 mg dose of ketorolac.

While there was no difference in adverse effects in this study between groups, it was a single dose study. When used repeatedly, there is a clear dose-related risk of GI bleeding from ketorolac documented in the prescribing information. I’m especially grateful to the authors of this study for highlighting this important issue in a modern trial.

Drug information question

Q: Should bolus or continuous paralytics be used to prevent shivering in therapeutic hypothermia?

A: Bolus dosing should be tried first.

Shivering in response to therapeutic hypothermia should only occur as the patient is cooling or warming, but not when they are at their target temperature. Therefore the need for paralytics is transient in most patients who shiver during therapeutic hypothermia. Following the general principle of using the lowest paralytic dose for the shortest possible time, I prefer to use bolus doses rather than continuous infusions for patients who shiver.

Resource

One of the most helpful references I used when making the transition from community to hospital-based pharmacist was Basic Skills in Interpreting Laboratory Data by Mary Lee. The book is written for pharmacists by a pharmacist. The book enhances the skills pharmacists need by providing essential information on common laboratory tests used to screen for or diagnose diseases and monitor the effectiveness and safety of treatment and disease severity.

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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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