Episode 350: Effect of propofol and dexmedetomidine on norepinephrine requirements in patients with septic shock, amantadine in TBI, and a tip for responding to inpatient medical emergencies

In this episode I’ll:
1. Discuss an article about the effect of propofol and dexmedetomidine on norepinephrine requirements in patients with septic shock.
2. Answer the drug information question “What is amantadine’s role in traumatic brain injury?”
3. Share a tip for responding to inpatient medical emergencies.

 

The intro for this episode is brought to you by Pharmacy Joe’s kids 🙂

Article

The Effect of Propofol and Dexmedetomidine Sedation on Norepinephrine Requirements in Septic Shock Patients

Lead author: Andrea Morelli

Published in Critical Care Medicine October 2018

Background

Both propofol and dexmedetomidine are known to have hemodynamic instability as a possible side effect. This effect can be overcome in patients with septic shock by increasing the dose of a vasopressor, such as norepinephrine. However, in animal models of septic shock, α-2 adrenergic agonists like dexmedetomidine have been reported to decrease norepinephrine requirements. The authors of this study sought to test the hypothesis that switching from sedation with propofol to the α-2 agonist dexmedetomidine may decrease norepinephrine doses in patients with septic shock.

Methods

The study was a small prospective open-label crossover study in a university hospital ICU. Thirty-eight patients with septic shock requiring norepinephrine to maintain adequate mean arterial pressure and needing deep sedation with propofol and remifentanil to maintain a Richmond Agitation-Sedation Scale score between –3 and –4 were included.

An initial set of measurements including hemodynamics, norepinephrine doses, and depth of sedation were obtained during sedation with propofol. Propofol was then replaced by dexmedetomidine and a second set of data was obtained after 4 hours of dexmedetomidine infusion. Sedation was switched back to propofol, and a final set of measurements was obtained after 8 hours. A Richmond Agitation-Sedation Scale score between –3 and –4 was maintained during the study period.

Results

Norepinephrine requirements decreased from a mean of 0.69 μg/kg/min before dexmedetomidine to 0.30 μg/kg/min 4 hours after dexmedetomidine infusion. Norepinephrine requirements increased to a mean of 0.42 μg/kg/min 8 hours after dexmedetomidine was discontinued and propofol resumed. The mean dexmedetomidine dosage was 0.7 μg/kg/hr. Propofol and remifentanil requirements were identical before and after dexmedetomidine was used.

Conclusion

The authors concluded:

For a comparable level of sedation, switching from propofol to dexmedetomidine resulted in a reduction of catecholamine requirements in septic shock patients.

 

Discussion

I think that the most important part of this study is that dexmedetomidine brought the mean norepinephrine dose down below the threshold of 0.5 mcg/kg/min. Previous studies have suggested that using norepinephrine doses above 0.5 mcg/kg/min is associated with increased mortality.  Although mortality was not evaluated in this study, it is possible that if the results were replicated in a study with a larger sample size, a mortality benefit might be found.

Drug information question

Q: What is amantadine’s role in traumatic brain injury? (Shout out to “NP Deb” for this question)
A: Amantadine has been shown to assist in the improvement of cognitive function in patients with traumatic brain injury.

In a single institution-based observational study of 50 patients with documented static or declining cognitive function at 2 months of severe TBI, cognitive function improved progressively during a 4-week treatment interval. This was shown by significant improvement on the Full Outline of Unresponsiveness (FOUR) score, Disability Rating Scale (DRS), and Glasgow Outcome Scale (GOS).

After discontinuation of the drug, the speed of recovery slowed down significantly, but the achieved recovery was not lost. Out of fifty patients, eight had convulsions as an adverse effect of amantadine, of which five patients required discontinuation of the drug with treatment for convulsions. The dose of amantadine in the study was 100 mg twice a day given orally or through enteral feeding tube.

Tip for responding to inpatient medical emergencies

When responding to emergencies, just being a pharmacist is enough to be a valuable member of the team.

The simple things like labeling medications, calculating doses, and checking IV compatibility allow the nurses and physicians on the team to focus on the patient while you handle the pharmacotherapy needs.

As you gain experience with emergency response, you will naturally start to increase your value to the team by doing things such as helping to identify and reverse the cause of the patient’s deterioration and predict pharmacotherapy needs in advance of them being requested.

No matter what skill level of code blue and rapid response you are at, the Hospital Pharmacy Academy has specific trainings to help you bring your emergency response skills to the next level. To learn more, go to pharmacyjoe.com/academy.

PS – Looking for the link from the kid’s announcement about their books in this episode? Go to evansplatform.com.

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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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