VITAMINS Trial: Timing was delayed to administer the “vitamins”

You all know my bias. It shouldn’t be a surprise given my body of work: I wanted the VITAMINS Trial to be a positive study. I wanted patients to benefit from this therapy and SURVIVE. I cannot understand the vitriol I have received in my direct messages when I shared my initial take on the study. I’m prepared to deal with more. Bring it! I have looked deep into using IV vitamin C for sepsis and have broken much of it down here.

Results of the VITAMINS Trial

Ultimately, there’s no difference in the the endpoints, whether primary or secondary. No need to go through them in depth. That’s what the data says, that’s what the study concluded. Hat tip to the authors. It is what it is. I can agree with their conclusions based on the study conducted.

Clinicians should not take the study as the end of HAT therapy. It would be scientifically irresponsible to do so. The study had a fatal flaw that doomed it from the beginning. Let me explain why. I practice real world medicine and am not a trialist. I do the best I can every day with what I have.

How I manage my septic shock patients

Here’s a take on how I care for septic shock patients for some perspective. There are plenty of nurses and physicians who work with me currently and have worked with me in the past following along on IG who can vouch for my style of practicing medicine.

This is NOT MEDICAL ADVICE. Do not do what I do because I say so. This post is not all 100% all inclusive for every nuisance. Every pt is different. That is your disclaimer.

1. I get a call from a colleague: ED physician, hospitalist, or surgeon regarding a patient who is in septic shock. At this point they have already gotten antibiotics and fluids bc everyone is excellent at this.

2. I go see the patient IMMEDIATELY

3. I assess, as quickly as possible with my limited tools a guesstimate on their fluid status

4. I start vasopressors EARLY while fluid resuscitating

5. pt arrives in the ICU, central line placed, arterial line placed, EV1000 hooked up.

6. I camp out at the nurses station next to the patient with them in my line of sight.

7. I watch how the patient behaves to my interventions, how the vasopressors go up, if they go up

8. As the vasopressor requirement increases, says NE around 10mcg, I start feeling uneasy. Especially how quickly their requirement increases.

9. I pull the trigger after 10-15mcg of NE to start vasopressin, hydrocortisone 50mg IV q6h, vitamin C 1500mg IV q6h and thiamine 200mg IV q12hours. I hit click, click, click, click, on an order set I created for myself on my EMR.

10. I keep on monitoring the patient closely to assess their response and provide additional fluids and learn more about their physiology.

Thing I do on the side: airway, bedside echo, talk to family and patient, management of other sick patients happen in this time period as needed. This post is not all-inclusive. Needless to say, all of this happens WITHIN 6 HOURS. One has a general idea, within 6 hours of the patient being in septic shock, a pathology that has a 25-40% mortality rate depending on the study, what is the likelihood of the patient turning the corner.

What can we all agree on regarding management for sepsis: early antibiotics make a difference. Source control makes a difference, the earlier the better. Early fluids are better than late fluids. Early vasopressor administration is showing to be better than late (data for that coming soon).

Taking issue with parts of the study

Here’s my main problem with the study:
– Time for patients to get randomized: I CAN’T FIND THIS DATA
– Time from ICU admission to randomization: 13.7 hours (IQR 7.1-19.3 hrs).
– Median time for patients to receive study study from randomization: 12.1 hours (IQR, 5.7-19 hours).
13.7 + 12.1 = 25.8 hours PLUS time for patients to get randomized!
For those who don’t know what IQR means: click here. Why in the world did they take so long to start the study drugs? That’s my problem with the study.

Final opinions

My larger problem with the study is the fact that, since it was published in JAMA, a very high impact factor journal, clinicians are going to take it as gospel and dismiss the therapy entirely.
If they would have provided the study drugs appropriately, there may have been a difference in outcomes. Since they didn’t, patients who could have potentially benefitted will not.
Or maybe I’m just wrong. All in all I hope the upcoming trials provide better results that the VITAMINS trial. Our patients need it.



Fujii T, Luethi N, Young PJ, et al. Effect of Vitamin C, Hydrocortisone, and Thiamine vs Hydrocortisone Alone on Time Alive and Free of Vasopressor Support Among Patients With Septic Shock: The VITAMINS Randomized Clinical Trial. JAMA. Published online January 17, 2020.

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