You have a patient who is hypotensive. You want to make them not hypotensive. The first thing the vast majority of clinicians reach for is some sort of IV fluid. We give it and cross our fingers that they won't be hypotensive after the fluids were provided. This is what is done in every single hospital throughout the world. I've already posted before that even in a healthy person, if they get a liter of fluid, 68% of it will be extravasated within 1 hour. Much more and far quicker will that volume be lost in someone who is critically ill; approximately 80% in 30 minutes. No wonder the "response" to that liter of fluid was so short lived. Fluid overload has many complications which many of you know of already. Perhaps I'll do a post solely on that. This is just one post of many, so feel free to ask questions below and I will address all of them in full posts in the near future. The whole purpose of providing a fluid challenge is to increase either the cardiac output or stroke volume, not increase MAP. This excellent paper was written by some resuscitation geniuses who I often fanboy over their work. It's completely free and I suggest you download it and read it for yourself. Monnet X, Marik PE, Teboul JL. Prediction of fluid responsiveness: an update. Ann Intensive Care. 2016;6(1):111. doi:10.1186/s13613-016-0216-7 Link to Article Link to FULL FREE PDF
Whether you're a med student, intern, resident, or nurse, you've wondered why in the world we give patients who are in septic shock stress dose steroids. This article breaks down in a not-so-easy to understand fashion of the nitty details that are too complex for my post-night shift brain to digest.
The powers that be in Critical Care, SCCM and ESICM, got together for this review with some big guns in the field to write this review discussing Critical Illness-related corticosteroid insufficiency.
Annane D, Pastores SM, Arlt W, Balk RA, Beishuizen A, Briegel J, Carcillo J, Christ-Crain M, Cooper MS, Marik PE, et al.: Critical illness-related corticosteroid insufficiency (CIRCI): a narrative review from a Multispecialty Task Force of the Society of Critical Care Medicine (SCCM) and the European Society of Intensive Care Medicine (ESICM). Intensive Care Med 43(12):1781–1792, 2017.
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When one looks at the dates where the publications disproved "renal dose dopamine", you see three articles published in 2000, 2003, and 2004. It's 2020 and this has not yet been put to bed. Now, I’m all worked up about this because I’ve had clinicians tell me that it absolutely works. I saw it in residency, fellowship, and now in private practice. I’m sure some of you see it at your institutions, too. There’s data that it improves urine output transiently but no data that it improves renal outcomes in critically ill patients. No changes in creatinine. No changes in renal replacement therapy rates. In fact, that whole discussion has been put to bed so much that there haven’t been any comments made on it over the last 15 years. No further trials attempting to prove it works. Is that why we’re still seeing it? Well, it’s time to bring the arguments against renal dose dopamine, or even using dopamine altogether back into the fray. The data about it being beneficial was from the 60’s in animal and healthy human studies. The latest studies, however, say it doesn’t work and in fact may be harmful. I have attached some of my preliminary slides from my Vasopressors in 2020 lecture. These are some of my preliminary slides. More info will come from me directly as I present these but it should provide you with an idea of why we should rarely see dopamine in our ICU's anymore. Do you still all use dopamine? If so, what for? I used to use it during codes as it was already packaged in the code carts. We have since gotten rid of these and my badass pharmacy colleagues prep me levophed drips within seconds. Debaveye, Y., and Van den Berghe, G.: “Is There Still a Place for Dopamine in the Modern Intensive Care Unit?” Anesthesia and Analgesia. 98(2):461–468, February 2004. Link to FREE PDF Holmes, C., and Walley, K.: “Bad Medicine: Low-Dose Dopamine in the ICU,” Chest. 123(4):1266–1275, April 2003. Link to CHEST Article Bellomo R, Chapman M, Finfer S, et al. Low-dose dopamine in patients with early renal dysfunction: a placebo-controlled randomised trial: Australian and New Zealand Intensive Care Society (ANZICS) Clinical Trials Group. Lancet 2000; 356: 2139–2143 Link to NOT FREE Lancet Article Although great care has been taken to ensure that the information in this post is accurate, eddyjoemd, LLC shall not be held responsible or in any way liable for the continued accuracy of the information, or for any errors, omissions or inaccuracies, or for any consequences arising therefrom.
This is a post for all my Critical Care Nurses out there! Please tag and share with your friends and colleagues. When you have a patient in shock on norepinephrine and vasopressin and has turned the corner, which vasopressor do you turn off first: norepinephrine or vasopressin? From my hard digging through the internets I have only found three studies which touch on this topic. Also, this seems like a pretty simple RCT that I could actually do at my shop. Anyone interested in joining in on the fun to make it multi-centered? These slides to some extent will be featured in my Hawaii and Portland lectures later this year. Seems like I'll be heading to Brooklyn and Indian Wells, CA in 2021.
Here's what the data says. Spoiler alert: there's no 100% correct answer.
2010: Bauer, et al. did a retrospective study where the team found that patients did better if the NE was weaned first and the vasopressin was weaned second.
2017: Hammond, et al. also performed a retrospective study which found similar results: patients did better if they weaned off the NE first. So far so good for weaning off NE first.
2018: Jeon, et al. just had to throw a wrench into everything. This was a prospective randomized trial where the results were the exact opposite of the other two. Ugh. Those of you who have been hanging out with me long enough may recognize that I covered this study in March of 2019 when the page was just getting ramped up.
Well what's the right answer? I guess we just don't know. Dealers choice. The randomized trial should hold more of an answer due to it being higher on the scale of evidence. The studies are small, hence me considering on doing a trial on this since ultimately it's not going to cause any harm and I really don't have a bias. What do you think?
Bauer S, Aloi J, Ahrens C, Yeh J, Culver D, Reddy A. Discontinuation of vasopressin before norepinephrine increases the incidence of hypotension in patients recovering from septic shock: a retrospective cohort study. J Crit Care. 2010;25(2):362.e7-362. e11.
Hammond DA, McCain K, Painter JT, Clem OA, Cullen J, Brotherton AL, Chopra D, Meena N. Discontinuation of vasopressin before norepinephrine in the recovery phase of septic shock. J Intensive Care Med. 2017:885066617714209
Jeon K, Song JU, Chung CR, Yang JH, Suh GY (2018) Incidence of hypotension according to the discontinuation order of vasopressors in the management of septic shock: a prospective randomized trial (DOVSS). Crit Care 22(1):131
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Your patient is in septic shock. They've gotten the correct source control, antibiotics, fluids, vasopressors. They remain hypotensive. Getting worse, actually. Could they have relative adrenal insufficiency or one of these fancy-termed conditions such as "critical illness-related corticosteroid insufficiency" (CIRCI)?
Should you check a cortisol level to find out or just start stress dose steroids?
In my practice, I do not check cortisol levels. No need to stick the patient for more blood. No need to waste any additional money for lab tests. No need to delay care in waiting for a lab result. Once the norepinephrine dose starts creeping up, I order stress dose steroids (as well as vitamin c and thiamine at the time of this writing). This is all my medical opinion and not advice, in case you didn't know.
The most recent trials on stress dose steroids do not check cortisol levels, so why should you? I tried to dig deeper into this point as I cannot get others to stop checking random cortisol levels on their critically ill patients. But why? There's no diagnostic consensus about the appropriate cortisol level for patients in septic shock. In addition to that, there's data that states that "both cortisol and synthetic ACTH challenge assays are unreliable in critically ill patients". So then why do we keep doing it?
Is there something out there that I don't know and you all can provide me with insight on? I'm looking for help on this.
A hat tip to the author. Reddy, Pramod. Diagnosis and Management of Adrenal Insufficiency in Hospitalized Patients. American Journal of Therapeutics, 2019. E-pub ahead of print.
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Several days ago I posted a comment on @iculaughingrn's page when the cited meme was posted. I guess I need to be extremely careful with my wording because I wrote "Looks like $30 of not much evidence to support its routine use in resuscitation".
We live in a world now where every word counts and some people in the comments section let me have it. I am under a microscope and therefore this post clarifies my thought process with guidelines to support. It's also important to recognize why we do what we do or don't do. I'm not going to dissect the different albumin studies at this juncture. Maybe later.
Healthcare as a whole in the US at this time is not sustainable. This is why I am hopeful that the HAT cocktail which is extremely cheap is successful versus one of these -NIB or -MAB drugs that costs tens of thousands of dollars. Albumin, relative to crystalloids, is extremely expensive. We need to be cognizant of these things.
I should have written "routine use in sepsis resuscitation". The CVICU population is a completely different beast although I would LOVE to see data for albumin being beneficial in that population. I have not seen it. The burn population is one that terrifies me so kudos to all of you practicing there. I do not know your literature.
Many of you know I am not a big fan of guidelines but this is something I can agree with. Earlier in my career I routinely used albumin. Now, I rarely use it. During my entire fellowship, albumin was not a word that was uttered in the MICU unless you were referencing the lab value. Ultimately, the guidelines state: "The absence of any clear benefit following the administration of colloid compared with crystalloid solutions in the combined subgroups of sepsis, in conjunction with the expense of albumin, supports a strong recommendation for the use of crystalloid solutions in the initial resuscitation of patients with sepsis and septic shock."
After the initial resuscitation, the clinician needs to be the clinician. Giving fluids arbitrarily to make the BP look pretty is not something I am a fan of. Some patients may need albumin, some may not. I rarely use it in my practice, though. Use your best clinical judgement. A hat tip to the authors.
Levy, M. M., Evans, L. E.; Rhodes, A. The surviving sepsis campaign bundle: 2018 update. Crit. Care Med. 46, 997–1000 (2018).
Levy, M. M., Evans, L. E.; Rhodes, A. The surviving sepsis campaign bundle: 2018 update. Crit. Care Med. 46, 997–1000 (2018).
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The VITAMINS trial didn’t pan out was not a positive study as it was conducted. I’ve already provided my take on that with my main argument being that they took too long to initiate the study drug (median time >25 hours, not including the time to arrive in the ICU). Sepsis management is expedient, you and I see it every day. Waiting over a day is not being expedient.
I’m seeing a benefit in my clinical practice, as admittedly worthless as my opinion is on the grand scheme of evidence. But when something doesn’t make sense from a results standpoint, you need to go back to the basics and wonder what happened.
Here are some things we absolutely know: 88% of patients in septic shock have hypovitaminosis C and 38% of septic shock patients have severe vitamin C deficiency. What many of you may not know, and I’m here to help you understand why I’m so surprised by the findings of the VITAMINS trial, is that vitamin c is a co-factor to the creation of endogenous catecholamines. That means that without vitamin c, your body isn’t going to produce the appropriate amounts of dopamine, norepinephrine, and epinephrine. It also is necessary for the production of vasopressin. It’s as simple as that. 38% of people will not produce appropriate endogenous catecholamines. The fact that administering exogenous vitamin c did not decrease time that the patients were receiving vasopressors in the study makes me wonder why. I am aware that there was a delay of >24 hours to start the therapies in the study but is there more I'm missing. Hopefully you can take some basic biochem away from this post as to why it should work (although it didn't in the study).
Carr, A.C.; Shaw, G.M.; Fowler, A.A.; Natarajan, R. Ascorbate-dependent vasopressor synthesis: A rationale for vitamin C administration in severe sepsis and septic shock? Crit. Care 2015, 19, e418.
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You’re following along on my page bc you know I’m trying to find the most cutting-edge treatments and therapies for my critically ill patients. I hope to keep on pumping out eye catching content such as this article on melatonin. Please share with you’re nerdy friends who would also find this nerdy content I put out interesting.
Yes, melatonin. I finished my lecture today on metabolic resuscitation and this article was published just a few days ago. It’s actually free and you can download it from my website, eddyjoemd.com. I have learned a ton of fascinating facts regarding melatonin as to why is SHOULD work. I can see the eyes rolling already. No, there aren’t any double blind, randomized controlled trials on this but one is in the works.
It definitely makes me curious as this is yet another therapy that many of us take during the day to sleep while on night shifts and is benign (based on years and years of studies listed in this article).
Fascinating stuff, right? Did you know that melatonin did all these cool things? I surely didn’t. Now I do... and that’s why I read as much as I do. A 🎩 tip to the authors!
Colunga Biancatelli, R., Berrill, M., Mohammed, Y., & Marik, P. (2020). Melatonin for the treatment of sepsis: the scientific rationale. Journal Of Thoracic Disease, 12(S1), S54-S65.
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This data was published on January 18th, 2020. Hot and fresh stuff! This represents the most recent estimate of sepsis-related deaths globally. We're doing better from a mortality perspective in the developed world with the mortality, but 11 million people is the, per census data, the entire population of New York City and Chicago combined per year. That's a lot of people. 20% of worldwide deaths. Many of these occur in our own ICU's. We could and need to do better. I understand we are all going to die of something one day, but this is mostly treatable with quick identification, source control, and appropriate and timely antibiotics.
People ask me all the time why I spend so much time and energy on social media educating about the critically ill when I could instead be doing other things. At the time of this writing there are 26,122 people following along in my insanity on Instagram (thank you all, btw). As the number grows, and I may be an idealist on this, we may be able to put a dent into those 11 million deaths by keeping our practices in line with the best evidence available.
Rudd, Kristina E et al. Global, regional, and national sepsis incidence and mortality, 1990–2017: analysis for the Global Burden of Disease Study. The Lancet, Volume 395, Issue 10219, 200 - 211.
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You all know my bias. It shouldn't be a surprise given my body of work: I wanted this 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!
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. But 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. I am not a trialist. I do the best I can every day with what I have.
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. Early source control makes a difference. Early fluids are better than late fluids. Early vasopressor administration is showing to be better than late (data for that coming soon).
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. 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.
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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When the CITRIS-ALI study was published just a few months ago they used plasma biomarkers as a method to prove that ascorbic acid in this patient population worked. You know, the study where they gave Vitamin C to patients with acute lung injury and it failed to show its primary endpoint which was SOFA/biomarker changes but..... had a statistically significant decrease in mortality and people scoffed that that since it wasn't the primary endpoint. The study that I am posting today provided methylene blue to patients with severe sepsis and measured TNF-α, IL-1, IL-2 receptor, IL-6, IL-8. As I typed this I realized that I am such a nerd. It's a Sunday and I'm typing about interleukins. I digress. Those endpoints weren't changed by giving these patients methylene blue. You know what did change? The mean arterial pressure on these patients. You know what makes patients survive? Requiring small vasopressor doses and having an improved blood pressure. By no means does this small study mean I'm changing my practice, but I am at least going to think outside the box a little more often in my refractory shock patients who absolutely cannot die on me. -EJ
Memis D, Karamanlioglu B, Yuksel M et al (2002) The influence of methylene blue infusion on cytokine levels during severe sepsis. Anaesth Intensive Care 30(6):755–762.
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I don’t know about you all but I’m constantly working on finding new ways to treat my septic shock patients who, based on the numbers from larger studies, have a mortality rate between 25-35%. I have used methylene blue on various occasions for post-CPB vasoplegia but would it possibly work in sepsis? Well, there’s 💩 data for now. I can’t cover every nuisance regarding methylene blue on this post, team, but I chose to share this pilot study from 2001 as it was the first study on the matter (to my knowledge). The third slide in a sneak peek to the lecture I’m creating on metabolic resuscitation.
Has your shop ever used methylene blue for this indication?
I’ll be presenting this data in Hawaii and Portland in 2020.
If you like the content I’m taking apart and posting, please share it with your friends and colleagues. Who knows, maybe it will inspire someone to conduct the larger RCT we need to decide whether this actually works or not.
Kirov MY, Evgenov OV, Evgenov NV, et al. Infusion of methylene blue in human septic shock: a pilot, randomized, controlled study. Crit Care Med. 2001;29(10):1860–1867. doi:10.1097/00003246-200110000-00002
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I am constantly reading and educating myself in an attempt to gain whatever edge I possibly can for my patients. Their survival and quality of life is what I have personally dedicated my life to. Being someone who is following along on my journey, I can safely assume you're doing the same. I have become quite fond of metabolic resuscitation, using Vitamin C, thiamine, and stress dose steroids, with the Paul Marik data and have been utilizing it in my practice for several years. No harm, cheap drugs, let's do it! I've seen some great results from it but I also would like to see some better data (hopefully next month!).
That being said, this is a brand new article published in the NEJM on December 11th of this year. I can't say I was excited about the prospects of this article, but all in all I was hoping it would help. Unfortunately, it does not. Sigh.
This was a well done study with a high aspiration of enrolling 3000 patients. Unfortunately, they did not get there. They stopped the study early because of futility. I don't know if the researchers let out a sigh of relief at that point that their study was complete, or if they were defeated because they wanted to see a positive outcome. Who knows. Overall I am glad that we have an answer for this question and would like to give a hat tip to everyone who participated in this study.
-EJ
Link to Abstract National Heart, Lung, and Blood Institute PETAL Clinical Trials Network, Ginde AA, Brower RG, et al. Early High-Dose Vitamin D3for Critically Ill, Vitamin D-Deficient Patients. N Engl J Med. 2019;381(26):2529–2540. doi:10.1056/NEJMoa1911124
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There's a pendulum in medicine. Some things are over recognized and aggressively treated, some things are under appreciated (like subtle decreases in serum bicarb showing that the patient is becoming more acidotic and no one notices because the patient has obesity hypoventilation syndrome and their baseline bicarb is 34 and now has a bicarb of 22 and they look like poop).
At this time, all the rage is serum lactate and lactic acidosis. Every time someone says those words, with my biochemistry knowledge lagging far behind, everyone thinks "SEPSIS!! 30cc/kg IVF STAT!!!!" If you all knew how much this upsets me whenever I see it, you'd wonder how I'm still alive because I see it all the time. I bet you see it at your shop, too. It's very common because the pendulum has swung too far.
In order to correct this, I have embarked on discussing this topic ad nauseum in one of my lectures for Hawaii/Portland in 2020. The article linked below from the New England Journal of Medicine has a table that has been reproduced in many different forms. I will not break down the pathophysiology of each one of the etiologies, but I have been called for an ICU transfer for MANY of these.
Here are some examples where I have been called over the years where patients have received 30cc/kg of saline w/stable vital signs: 1. COPD patient receiving albuterol nebs. Lactic acid elevated because they're A. huffing and puffing, and B. receiving beta-2 agonists. 2. s/p seizure patients who are post-ictal 3. hypoglycemic diabetics 4. leukemia patients just watching TV 5. cocaine/chest pain patients in the ED 6. cardiogenic shock patients on an epinephrine gtt 7. HIV pt on Stauvidine (I should have written this one up)
I'm obviously not getting into the different subgroups of lactic acidosis at this time. Let's walk together before we run. Our job is to fix the underlying cause of the lactic acidosis, not dilute the number down with fluids.
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I need to eat my words on this one, because now there's data to show that there's a benefit to rechecking lactate levels in septic patients, but not for the reasons why one would think.
During my rounds over the course of the weekend, I recall telling several nurses that there's no data to suggest that trending lactates changes outcomes. This study, which came out last night, tells me I was wrong in saying that. A close examination of the data will show that it has nothing to do with the lactate itself, but rather the fact that the clinicians are prompted to "do something" in response to a number that makes us uncomfortable.
Okay, so the lactic acid is elevated. You're going to do one or two or all three of the following: a. start vasopressors b. start antibiotics c. give more fluids
That's the kicker, we don't know which of those interventions, or combination of which, are what decreased mortality. Maybe it just means that someone gave these patients more attention. It certainly just wasn't the "checking the lactate" part. Lactate is just an alarm of sorts, we still need to be clinicians. I will suggest, though, that earlier initiation of antibiotics plays the most important role in decreasing mortality as there's already data suggesting that earlier antibiotics leads to improved outcomes. I personally start vasopressors pretty early and will share data in the upcoming weeks as to why I do that in my practice. Giving more fluids is only useful if the patients is fluid responsive, you know, if you can prove that giving that fluid will increase the cardiac index/output or increase the stroke volume. Giving fluids just to make the blood pressure go up arbitrarily is just plain dumb. It's 2019. We're better than that.
Ultimately, early lactate measurement did not improve outcomes, nurses relaying the information to the doctors, ARNP's, or PA's did.
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This study published just this month, November 2019, suggests that providing bolus dosing of hydrocortisone, 50mg IV every 6 hours shortens the time a patient needs to be on vasopressors compared to 200mg IV through a continuous infusion every day.
Stress dose steroids are clearly in my armamentarium in the treatment of septic shock. I tend to reach for them when I’m starting my second vasopressors, usually Vasopressin when the norepinephrine hits around 10-15mcg. I also ready for the vitamin C and thiamine at that point, too. Actually, I have a quick little bundle in the EMR where I just check off all these goodies. Sometimes I stray in different directions, of course. Every patient is different and this is not a recommendation on how you should practice. I haven’t gotten on the fludrocortisone train yet, have you?
Either way, the shock reversal is faster with the bolus dosing. This should make all my nurse followers happy as they won’t have a channel and lumen bogged down with this medication and all the compatibility questions that arise with it. Whether bolus or continuous dosing you won’t see a difference in mortality, ventilator days, adverse effects, length of stay, etc.
Also not yet another study where they don’t check cortisol levels before initiating this treatment. I’m not a fan of checking cortisol levels myself. I see it done and I ask, why?
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Every possible option to decreased morbidity, mortality, and costs are worth looking at in my book. The study that I am reviewing at this moment was published in 2017. I am ashamed that I had not run into it until today. It's challenging to stay up to date in everything. I digress.
Some would quickly bash this study for it being small (n=70) and a post-hoc secondary analysis of a pilot study. I am not going to do that. Why not? Well first of all, I do not participate in research myself. Just reading and enjoying these studies. Also, thiamine has no side effects described in the literature. Third, it is an inexpensive medication. Fourth, if it does turn out to decrease the incidence of acute kidney injury and the need for renal replacement therapy, aren't you going to feel guilty for not adopting these strategies for your patients? I hate resorting to that but my responsibility is for patients. What happens if this data is wrong? Nothing. What happens if this data is right and no one does anything for several years? Many patients may suffer.
This article is completely free and I encourage you to download it and read it for yourself. Amongst the points illustrated by the authors, they mention that it's not only perfusion that injures the kidneys during sepsis. There are other factors listed in the article. The way that it is postulated that thiamine works for these patients is by assisting in the mitochondrial dysfunction. Data that I have found not listed in this article shows that thiamine deficiency could have an incidence between 20-70% of critically ill patients.
What they found was 21% of the patients in the placebo arm of the trial went on to need dialysis. Just one patient, or 3% in the thiamine group went on to require this. The authors note that acidosis was the primary indication for dialysis in 66% of the patients who required it. I personally would like to dig deeper into these numbers as there is some data that thiamine administration helps decrease lactic acidosis.
This data should make you wonder if the strategy that many clinicians take of providing more IV fluids to patients whose renal function deteriorates is the correct strategy. Are we going to look in the mirror in a decade and want to punch our past selves in the face?
Link to Full Article ADDENDUM: The prospective RCT is going to be completed in July 2022. Here is the link to clinicaltrials.gov's study details here: LINK
Moskowitz A, Andersen LW, Cocchi MN, Karlsson M, Patel PV, Donnino MW. Thiamine as a renal protective agent in septic shock. A secondary analysis of a randomized, double-blind, placebo-controlled trial. Anns Am Thorac Soc. 2017;14(5):737–41.
Although great care has been taken to ensure that the information in this post is accurate, eddyjoemd, LLC shall not be held responsible or in any way liable for the continued accuracy of the information, or for any errors, omissions or inaccuracies, or for any consequences arising therefrom.
Want some nerdy stuff? Well this is some nerdy stuff! I'm taking a nice deep look at this figure. I am not going to lie to you at this moment, October 19th, and tell you I know what all this means, because I don't. But people who are more intelligent that I am have suggested that these are the mechanisms by which thiamine, ascorbic acid, and corticosteroids should help in the treatment of septic patients. I have a lot to learn. I hope I don't get dinged for copyright stuff but honestly if this offends you, let me know. I will take it down. I will likely go deeper into this article at a later time. Wanted to share this image with you right now, though. Link to Abstract
Link to FREE FULL Article Moskowitz, A.; Andersen, L.W.; Huang, D.T.; Berg, K.M.; Grossestreuer, A.V.; Marik, P.E.; Sherwin, R.L.; Hou, P.C.; Becker, L.B.; Cocchi, M.N.; et al. Ascorbic acid, corticosteroids, and thiamine in sepsis: A review of the biologic rationale and the present state of clinical evaluation. Crit. Care 2018, 22, 283. Although great care has been taken to ensure that the information in this post is accurate, eddyjoemd, LLC shall not be held responsible or in any way liable for the continued accuracy of the information, or for any errors, omissions or inaccuracies, or for any consequences arising therefrom.
I've had very similar patients with very similar infections where one was out of the ICU in a short amount of time and the other died in flames. Many variables in play, of course, but you get my point. Could the gut microbiome hold a key regarding which patients do well and which patients don't? My ignorance on the matter is through the roof and my research made me stumble on this gem of a study. I am usually not a fan of mice studies but they have their place in medicine. Here, they showed how mice with almost genetically identical backgrounds who underwent cecal ligation and puncture to make them septic, and had completely different rates of death. One group obtained from a certain location had a mortality rate of 90% whereas the other group had a mortality rate of 53%. Then they had another group subset where they mixed females of the two groups (bc the males rip each other to shreds) for 3 weeks and then performed the same process. The group with the 90% mortality, after being cohoused, had the same mortality rate as that which had the 53% mortality. That’s absolutely fascinating! Now, the authors admit that there are other factors at play, but they did a ton of fancy genetic and bacterial testing to help explain the differences. I leave it up to them to better explain it. A definite 🎩 tip to them.
-EJ
Although great care has been taken to ensure that the information in this post is accurate, eddyjoemd, LLC shall not be held responsible or in any way liable for the continued accuracy of the information, or for any errors, omissions or inaccuracies, or for any consequences arising therefrom.
If your way of determining whether a patient is fluid responsive or not is to see if the blood pressure went up after giving a bolus, you are doing it WRONG! You need to stop, take a deep breath, and reassess your way of thinking about fluid responsiveness. This (FREE!) article dives into why fluids should not be provided arbitrarily go make us feel good inside and make us feel like we at least "did something" in response to that low mean arterial pressure. No, I do not use SBP and DBP off of the BP cuff in my practice. More on that at another time. This article also goes briefly into why we should not be checking CVP (duh). Bottom line is that we can't accurately predict fluid responsiveness without an arterial line and some sort of device to predict stroke volume, stroke volume variation, cardiac index/output. You could have some really good echo nunchuck skills as well. This study also emphasizes why looking at IVC variations is not the best test. Ultimately, we all need to get better at this, myself included. I feel that this article is particularly important for nurses as you all are the ones who relay the BP concerns to the clinicians essentially ordering the fluids. These three authors are legends of critical care. A real treat that Annals of Intensive Care published this for free.
This article is going to be part of the bibliography for the talk I will be giving in Portland, OR in August of 2020.
-EJ
Monnet, X., Marik, P.E. & Teboul, J. Prediction of fluid responsiveness: an update. Ann. Intensive Care 6, 111 (2016). https://doi.org/10.1186/s13613-016-0216-7
Although great care has been taken to ensure that the information in this post is accurate, eddyjoemd, LLC shall not be held responsible or in any way liable for the continued accuracy of the information, or for any errors, omissions or inaccuracies, or for any consequences arising therefrom.
