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Max Vasopressors? ASA STEMI Dosing? Early High Dose Statins? K-Hole Content? - #DQI v1

Updated: Mar 15

🔍 Dive into the world of pharmacotherapy with #DrugQueryInbox! 💊 From post recaps to viewer Q&A, we've got your prescription for understanding medications covered. Tune in for expert insights and answers to your burning questions! 📚

 


 

Hello there Pharmers and Friends, Mark with PHARMWYZE. I am a Board-certified Emergency Medicine pharmacist that makes clinical pharmacotherapy content for learners of all medicine backgrounds. I often get drug-related questions in the comments on the social medias, and will compile them into a weekly to biweekly video series called the Drug Query Inbox. (#DQI)


For this week's questions we've got,

Is there a max dose to vasopressors? Thoughts on ASA STEMI dosing? Use of acute statins? Am I in the K-hole making content? Let's dive into our first question that comes from my instagram page


Is there a max dose to vasopressors? - @pharmwyzepharmfax, IG poll

Technically, there is no maximum dose of vasopressors but there are limits placed by your hospital. There comes a point of diminishing return and you should be working towards a solution. Increasing rates of vasopressors for someone appropriately resuscitated in refractory shock are going to need what their body needs.


Let me emphasize that high dose vasopressors are independently associated with mortality; they're a banaid, not a solution.


Plurad and colleagues in 2010 published a retrospective single-center trial and included all ICU admissions that survived past 24 hours. They were assessing whether fluid status had an impact on mortality in patients who required vasoactive support. Mortality occurred in roughly 44% of patients needing vasopressors compared to 4% of the no vasoactive group. These findings were independent of fluid status


Vasopressors are a useful tool in order to buy time, but don't forget the general risks of extravasation, dysrrythmias, and human error amongst many other complications.


Whenever you are increasing the rate on vasopressors, always triage to ensure medication delivery. Is there a backer of fluids to keep the line patent? Did the line blow? Has the patient actually been resuscitated appropriately?


Additionally, consider if this is a case for vasopressin and/or corticostoids which have shown earlier resolution of septic shock. There is a lot going on with complex patients, just remember what is the underlying etiology causing your shock.

 

Thoughts on (STEMI; 162 - 325 mg) ASA dosing, and if patient on daily ASA and anticoagulant? @darrenfiggis, X

Guidelines recommend a range of 162 - 325 mg since there really isn't an established lowest effective dose. In a lab, 100 mg of ASA would theoritically completely block synthesis in throboxane A2, the pathway for platelet aggregation.


Berger and colleagues in 2007 retrospectively evaluated mortality and bleeding risk in 162 vs 325 mg of ASA from two landmark 2 large STEMI fibrinolytic trials, GUSTO I and III, that contained over 56,000 patients. From their results, there was an association of reduced bleeding and possible similiar efficacy with the lower dose. However, thats the issue with retrospective aggregate numbers. you remove the robustness each individual trial inclusion/exclusion criteria, leading to results without causation and only association.


Mehta and colleagues completed the CURRENT OASIS-7 trial in 2010. This was a randomized, 2-by- factorial design trial that includes over 25,000 patients with an acute coronary syndrome and arranged for percutaneous coronary intervention

Patients were to receive clopdiogrel 600 or 300 mg on day 1, followed by 150 and 75 mg daily respectively. Additionally, patients would receive higher dose aspirin determined as 300 - 325 mg daily or lower-dose, consisting of 75 to 100 mg daily. Their primary outcome was a composite of cardiovascular death, myocardial infarction, or stroke at 30 days. There was no difference in efficacy, nor safety outcomes between the larger clopidogrel and aspirin doses compared to the lower regimens.


I lean towards full dose 325 mg ASA unless rare patient-specific considerations warrant a lower 162 mg dose. Even if a patient is on daily aspirin and an anticoagulant, I would still give 325 mg. The patient could die from a heart attack , and the solution is PCI or thrombolytics. A possible increased downstream bleeding risk can be managed, but you need the patient alive to get there.

 

Hello, question. Why are statins given in an acute setting? I have always thought the take some time to take effect? - @zubie797, Instagram

The proposed benefit is potential downstream effects on modulating endothelial function, inflammation and thrombosis. There may be a reduction in stent rethrombosis, contrast-induced nephropathy, periprocedural MI, etc. Cardiology studies use compositive outcomes.


Lee and colleagues did a RCT in 2010 for more definitive evidence since meta-analysis associated early high dose statins with a reduction major cardiac adverse events at the time. From their results, there was not a reduction in the primary outcome, but did see improved coronary flow as a secondary analysis. Possible benefit and questionable clinical significance, but with low risk. Recent meta-analysis continue to support the potential benefits of early statins, but also not the increase in ADE specific to statins such as transaminitis and mylagias.


I wouldn't force a horse-sized tablet down a patient's throat or delay care to grab a cup of water. If the patient's stable enough and conditions are appropriate, I'd consider it after prioritized antithrombotics are given.


 

Is he in the K-hole while recording this? - @susaninvenicebach, TikTok

No, none of my videos are recorded while in the K-hole, including the ones on pharmaceutical ketamine. Let me explain how ketamine works.


Ketamine antagonizes the N-methyl-D-aspartic-acid or NMDA receptor, leading to a reduction in glutamate, an excitatory neurotransmitter, This results in dissociating your brain from external stimuli like sound and pain. Thats what makes ketamine such a strong anesthetic and sedative.

Another property of ketamine is the potent amnestic properties. I would be impressed with anyone who can produce logical educational content and remember exactly what they said afterwards.


Ketamine has gained huge media traction recently given use for refractory depression and ketamine clinics. Thats FDA-approved ketamine, I'm not sure what your street ketamine does.



It is often preferred since it maintains respiratory drive and considered to be cardiovascular stimulating compared to the other gabanergic sedatives that are more depressing. Ketamine is sympatomimetic since it inhibits reuptake of catecholamines. Caution in patients who are catecholamine depleted. ketamine’s minor mechanism include negative inotropic effects which would be detrimental in someone without circulating catecholamines. All of ketamine mechanisms, properties, and pharmacokinetics can be discussed entirely in a separate video, which I’ll do sometime in the future since theres so much interest in its multiple indications.


Let me know what questions you have about medications, emergency medicine, or critical care below. If you enjoyed dropping into the drug query inbox, I'd appreciate if you hit the subscribe and notification bell. Stay tuned for my #CODEBLUEDEBRIEF YOUTUBE AND PODCAST EPISODES. Follow my social medias for pharmacotherapy infographics and reels, or stop by my website at pharmwyze.com, and I hope you learned something new.


Reference

  1. Plurad et al. Early vasopressor use in critical injury is associated with mortality independent from volume status. J Trauma . 2011 Sep;71(3):565-70; discussion 570-2.

  2. Benjo et al. High dose statin loading prior to percutaneous coronary intervention decreases cardiovascular events: a meta-analysis of randomized controlled trials. Catheter Cardiovasc Interv . 2015 Jan 1;85(1):53-60.

  3. Ye et al. Do We Really Need Aspirin Loading for STEMI? Cardiovasc Drugs Ther . 2022 Dec;36(6):1221-1238.

  4. Berger et al. Initial aspirin dose and outcome among ST-elevation myocardial infarction patients treated with fibrinolytic therapy . Circulation . 2008 Jan 15;117(2):192-9.

  5. Mehta et al. Dose comparisons of clopidogrel and aspirin in acute coronary syndromes. N Engl J Med . 2010 Sep 2;363(10):930-42.

  6. Nusca et al. Statin loading before percutaneous coronary intervention: proposed mechanisms and applications. Future Cardiol . 2010 Sep;6(5):579-89.

  7. Lee et al. Efficacy of high-dose atorvastatin loading before primary percutaneous coronary intervention in ST-segment elevation myocardial infarction: the STATIN STEMI trial. JACC Cardiovasc Interv. 2010 Mar;3(3):332-9.

  8. Zanos et al. Ketamine and Ketamine Metabolite Pharmacology: Insights into Therapeutic Mechanisms. Pharmacol Rev . 2018 Jul;70(3):621-660.

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