Dexamethasone in ARDS

This is a big impactful study. I'm happy it came out, really happy. To start off a big hat tip to my colleagues in España who put this together. ARDS sucks. It's a b-word to treat and patients spend a frustratingly long time to come off of the vent. Mortality rates are high. Morbidity rates are through the roof. Cost burden to the healthcare system is insane. The repercussions are unquantifiable. Many of these people never even return to work.

In my practice, when I have a patient with ARDS, I make sure to treat the underlying cause, protect their lungs with the vent, keep them as dry as humanly possible, and provide them with 4 days of vitamin C, hydrocortisone, and thiamine. The CITRIS-ALI study providing vitamin C showed a decrease in mortality in this population, less time in the ICU, and less time in the hospital (albeit with many caveats to that study). There's bench research that shows how vitamin C and corticosteroids are synergistic in preventing and repairing lipopolysaccharide-induced pulmonary endothelial barrier dysfunction. But we never had good data regarding giving these patients steroids to begin with. In theory it made sense, but we needed more help. We were simply doing our best and shrugging our shoulders in many of these cases.

Enter the DEXA-ARDS trial. They randomized patients with moderate to severe ARDS to either get dexamethasone or placebo. Note that they give the first dose immediately after randomization, something that they waited 12+ hours to do in the VITAMINS trial. I digress. Not bitter. Okay I'm bitter. Nonetheless, the pts who got steroids did better. They came off the vent quicker and had fewer deaths. Both statistically significant. One of the key takeaways regarding the vent free days is that we start thinking to trach pts around day 10-14. The dexamethasone group got off the vent around day 14. The control group around day 20. How many trachs were spared and the morbidity that comes with that? It's not specified in the article but I'm curious. Another key piece is the fact that there was no increase in side effects of the steroids.

Ultimately this trial is changing my practice. I was perhaps stopping steroids too early in the past.

-EJ



Villar J, Ferrando C, Martínez D et al. Dexamethasone treatment for acute respiratory distress syndrome: a mutlicentre, randomised controlled trial. Lancet Respir Med. 2020; (published online Feb 7.)

Link to Article (NOT FREE boooooo!)

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Non-Invasive Ventilation Algorithm

Not every patient reads the textbook, but you and I have to know where to start when managing our patients who have hypercapnic respiratory failure that we want to treat with non-invasive ventilation (or what you and I frequently call BiPAP). This algorithm is taken from the British Thoracic Society/Intensive Care Society Acute Hypercapnic Respiratory Failure Guidelines that were published in 2017. Fortunately, they are free for you to download your own copy and put it up on your wall. 

This guideline recommends starting with an EPAP of 3. If I'm honest, everywhere I've been and the way I've been trained is to start at 5. Also, they recommend uptitrating the IPAP up to 20-30. In my practice, once I start kissing 20, I start thinking very seriously about intubating the patient. 

For those who are unfamiliar with the kilopascal units (as I certainly was), the equivalent PCO2 is 48.75mmHg. Note that you need to have acidosis and hypercapnia in COPD exacerbations to have any benefit from NIV. 

A hat tip to the authors. 

Davidson AC, Banham S, Elliott M et al. BTS/ICS guideline for the ventilatory management of acute hypercapnic respiratory failure in adults. Thorax 2016;71 (Suppl 2):ii1–35.

-EJ






Link to Article with FULL FREE Algorithm

Ghosh D, Elliott MW. Acute non-invasive ventilation - getting it right on the acute medical take. Clin Med (Lond). 2019;19(3):237–242.



Link to the FREE FULL Guidelines

Davidson AC, Banham S, Elliott M et al. BTS/ICS guideline for the ventilatory management of acute hypercapnic respiratory failure in adults. Thorax 2016;71 (Suppl 2):ii1–35.

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.

Cortisol Levels: Check prior to SDS in Septic Shock?

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.

Link to 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.

Probiotics in ICU: UPDATED

It certainly got me thinking when several people messaged and commented to me regarding their hospitals not allowing probiotics on their ICU patients. I decided to take a little bit of time to see if this was an old habit that just doesn't die, you know, a resistance to change, or if it's something substantiated by data. 

At first I didn't find anything to substantiate the claims. Key words were "at first". Now I understand what they're talking about and I even more appreciate the fund of knowledge that this page brings to the medical community. 

The exact mechanism, whether translocation from the gut, contamination with a central line, or something else is unknown. What is known is that 1.1% (6 of 522) of the patients at this facility who received probiotics developed a bacteremia related to the probiotic agent. That's not a large number but at the same time a large number in my opinion. I'll stress again, my opinion, not medical advice. I do not want to cause harm to my ICU patients. For those wondering, these patients were not severely immunocompromised nor did they have bowel disintegrity. 

I will wait until more data comes out before I start implementing this in my practice. As always, I appreciate the insight that you all provide. 

A hat tip to the authors. 

-EJ

Yelin, I.; Flett, K.B.; Merakou, C.; Mehrotra, P.; Stam, J.; Snesrud, E.; Hinkle, M.; Lesho, E.; McGann, P.; McAdam, A.J.; et al. Genomic and epidemiological evidence of bacterial transmission from probiotic capsule to blood in ICU patients. Nat. Med. 2019, 25, 1728–1732.

Link to the Article

Yelin, I.; Flett, K.B.; Merakou, C.; Mehrotra, P.; Stam, J.; Snesrud, E.; Hinkle, M.; Lesho, E.; McGann, P.; McAdam, A.J.; et al. Genomic and epidemiological evidence of bacterial transmission from probiotic capsule to blood in ICU patients. Nat. Med. 2019, 25, 1728–1732.

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.

Probiotics in the ICU

ADDENDUM: I have found new data regarding probiotics leading to bacteremia that was published HERE. This changes my take on prior research. 

Here's something I'm fairly certain we (meaning your team and mine) do not do in our practice that perhaps we should give some more consideration to: providing probiotics for our patients.

There's much we don't know regarding the microbiome. It completely fascinates me. Immediately upon arrival to the ICU, damage is done to the microbiome in our intestines via stress, shock, antibiotics, etc. Bad bugs take over where the good bugs used to live. How do we get those good bugs to come back? Could providing good bugs (probiotics) help get our patients better faster?

The following slides are some of my preliminary slides for my "ICU Nutrition and Gut Health" lecture. I was a bit too excited to share to wait until they were complete.

The 2016 ASPEN guidelines state that they cannot make a recommendation regarding using them routinely. I'm curious as to whether the 2020 guidelines (coming out next month) will state the same. I have cited articles where probiotics improve antibiotic associated diarrhea, two meta-analyses where they show benefit for ventilator associated pneumonias, a meta-analysis where the show decreased overall infections, and how they help to reduce the development of C.diff.

Now, if one were to think that probiotics were a cure to everything, that person would be wrong. There will likely never be a one-treatment to cure all the ailments in critical care. But if we can keep adding tools to our tool belts as more data comes out, then we will better be able to care for our patients and improve outcomes.

A hat tip to all the authors.

-EJ

Link to Article

McClave SA, Taylor BE, Martindale RG, et al; Society of Critical Care Medicine; American Society for Parenteral and Enteral Nutrition: Guidelines for the provision and assessment of nutrition support therapy in the adult critically Ill patient: Society of Critical Care Medicine (SCCM) and American Society for Parenteral and Enteral Nutrition (A.S.P.E.N.). JPEN J Parenter Enteral Nutr 2016; 40:159–211

Link to Article

Hempel, S. et al. Probiotics for the prevention and treatment of antibiotic-associated diarrhea: a systematic review and meta-analysis. JAMA 307, 1959–1969 (2012).

Link to Article

Weng, H.; Li, J.G.; Mao, Z.; Feng, Y.; Wang, C.Y.; Ren, X.Q.; Zeng, X.T. Probiotics for preventing ventilator-associated pneumonia in mechanically ventilated patients: A meta-analysis with trial sequential analysis. Front. Pharmacol. 2017, 8, 717.

Link to Article

Manzanares, W., Lemieux, M., Langlois, P.L. et al. Probiotic and synbiotic therapy in critical illness: a systematic review and meta-analysis. Crit Care 20, 262 (2016).

Link to Article

Goldenberg JZ, Yap C, Lytvyn L, Lo CKF, Beardsley J, Mertz D, Johnston BC. Probiotics for the prevention of Clostridium difficile‐associated diarrhea in adults and children. Cochrane Database of Systematic Reviews 2017, Issue 12. Art. No.: CD006095.

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.

Nutrition in Critical Illness

I’m writing a lecture on Nutrition for the ICU patient population. It’s been quite tough to find substantial data because of the many nuances and the vast heterogeneity of the patient population. That being said, this review article came out a few days ago and it provides a guide of sorts to provide our patients with nutrition during their different phases in the ICU. My understanding is that the ASPEN group shall be meeting towards the end of March. I am looking forward to whatever guidance they can provide so I can better care for my patients.

Fortunately this article is free! A hat tip for the authors.

Lambell, K.J., Tatucu-Babet, O.A., Chapple, L. et al. Nutrition therapy in critical illness: a review of the literature for clinicians. Crit Care 24, 35 (2020).

Link to article

Link to FREE PDF

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.

Lactate Levels cannot be corrected by Giving More Oxygen

I have covered lactate quite thoroughly over the last couple weeks but I still receive comments and questions from followers talking about oxygen deficiency to the cell causing elevated lactate and lactic acidosis. They ask "why don't you just increase the O2 that you're providing to the patient to help the cells out"? This question is not out of line with traditional thinking behind lactic acidosis being the byproduct of "tissue hypoxia" which I hope at this point you understand is NOT the cause of elevated lactate levels in septic shock patients (see many other posts for further details).

This study published in JAMA in 1993. The three key findings of their work include:

1. Critical O2 delivery was identified and is considerably lower than previously estimated. Increasing O2 delivery to supra-normal levels in critically ill patients in the hope of increasing O2 consumption may be inappropriate.

2. Sepsis was not associated with an increased critical O2 delivery

3. The increased concentration of arterial lactate at baseline was not associated with global tissue hypoxia, suggesting that lactate may not be a specific marker of tissue hypoxia in critically ill patients.

Hope this helps! A hat tip to the authors!

- EJ



Link to Article

Ronco JJ, Fenwick JC, Tweeddale MG, et al. Identification of the Critical Oxygen Delivery for Anaerobic Metabolism in Critically III Septic and Nonseptic Humans. JAMA. 1993;270(14):1724–1730.

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Can We Use Something Other Than Lactate To Guide Resuscitation?

Nurses: you see those orders. q1, q2, q4h lactates to help guide resuscitation in septic shock. You have to drop what you're doing and draw labs. Hopefully, if the patient is sick enough to need the labs, they have a central line. Hold off of titrating drips, hold off on the ever important charting you are required to do, let's trend lactates which I have previously discussed the utility of (or lack of utility). Along the way we contribute to iatrogenic anemia, spend a bunch of lab money, etc.

What if there was another option? Well, the ANDROMEDA-SHOCK trial proves that you can intelligently resuscitate patients without checking lactate levels. What they did was randomize >400pts to either have their resuscitation guided by lactate or this nifty little trick called Capillary Refill Time.

One of my favorite parts of the trial wasn't even the CRT vs. lactate component but their algorithm to determine fluid responsiveness which is a major interest of mine. I am not a fan of arbitrarily giving a pt liter after liter of fluid to "clear lactate" or improve the blood pressure. That just does not work and my body of work has data to prove that. I digress. Sometimes you need to read the supplementary materials in these articles as their algorithm was hidden in there.

Standard of care by CMS (the body that pays the hospitals and therefore us in the US) has mandated checking lactates despite no good evidence that trending it does much. This study shows that checking CRT is AT LEAST as good as checking lactate levels. The mortality was not statistically significant (p=0.06) but I wonder what would've happened if they would've had an additional 200pts in the trial. The CRT group had 34.9% mortality vs 43.4% in the lactate group. The CRT group also had fewer organ failures (p=0.045). Other fun facts include the fact that the lactate group received more fluids in the first 8h (p=0.01) but not overall. I don't know what to make of this.

All in all, even with its limitations, I feel this is a solid study. I really like it. I do not use CRT in my practice but I may be asking for a microscope slide to keep in my pocket in the upcoming weeks.

A hat tip to the authors

Hernandez G, Ospina‐Tascon GA, Damiani LP, Estenssoro E, Dubin A, Hurtado J, et al. Effect of a resuscitation strategy targeting peripheral perfusion status vs serum lactate levels on 28‐day mortality among patients with septic shock: the ANDROMEDA‐SHOCK randomized clinical trial. JAMA. 2019;321(7):654–64.

- EJ




Link to FULL FREE ARTICLE

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How Does Lacate Turn Into Lactic Acid?

You have NO IDEA how much I banged my head against my desk looking for the answer to the question: how does lactate turn into lactic acid? Well, after many hours of searching for an answer, and you can think I'm a dummy for not find the answer sooner or knowing it like a useless fact off of the top of my head, I FOUND IT! It's honestly some information that's not readily available. Many articles play it off and don't mention specifics assuming that "it just happens". I am by no means a biochemist. I'm simply trying to understand all this. In my explanation, I purposefully will be oversimplifying things.

Here's how it works:
In the cytosol, pyruvate turns into lactate (rather than move towards acetyl-CoA) for a number of reasons, again that I'm not going to get into, via lactate dehydrogenase. That lactate (via shuttles) gets to the cytosol of the liver and kidneys where it eventually makes its way into the Cori/Lactic Acid Cycle. The Cori cycle eventually spits out glucose. So far so good, right? Glucose via glycolysis seems to be metabolized into lactate, ATP, and water. Said ATP gets hydrolyzed into ADP and inorganic phosphate which releases that very necessary proton (H+). When conditions get revved up, i.e. septic shock, and an excess of lactate is being produced, then the cell cannot handle the metabolism of lactate and guess what's also being overproduced? Said H+ which tags onto the lactate creating lactic acid.

The articles I've read tend to say that you start running into lactic acidosis territory when you have a lactate 5 with a concurrent acidosis (pH less than 7.35). 

Mad props to Amanda, my pharmacist teammate, for listening to me and helping me work through this while not making too much fun of me. 
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Link to article (NOT FREE)

Fall P, Szerlip H. Lactic acidosis: from sour milk to septic shock. J Intensive Care Med 2005; 20: 255-71.

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Lactate in IVF Leads to Lactic Acidosis?

"Lactate in fluids, such as Ringer's lactate, causes a lactic acidosis". Ugh. How I cringe every time I hear or read that. You should take into account your patients organ failures since lactate is metabolized approximately 60% in the liver, 30% in the kidneys, and 10% elsewhere (including the heart, muscles, etc depending on your source).

There's no perfect trial to go ahead and prove this concept, but I have linked this study which FREE where they provided patients with a sodium lactate solution versus Hartmann's solution, aka Ringers Lactate. To provide some context, LR provides the patient with Sodium Lactate, 28mmol/L to be exact. The half-molar Sodium Lactate solution described in this article has 504mmol/L of Sodium Lactate. I struggled quite a bit to find that concentration but thankfully I found it in a Spanish (Spain) article.

I have attached the table to illustrate several points. First, if you notice the Sodium Lactate did not create an acidosis in any of the patient groups, on the contrary, they trended more so towards an alkalosis, even a statistically significant alkalosis in the case of the "lactate" group. Overall, there was no increase in lactate whatsoever in the LR group which means that there's no "lactic acidosis" created by LR. It does not make patients acidotic. If you have a functioning liver and kidneys, that lactate is metabolized into bicarbonate. Hope that all makes sense.

A hat tip to the authors.

-EJ

Link to Article

Link to FULL FREE PDF

Nalos, M., Leverve, X.M., Huang, S.J. et al. Half-molar sodium lactate infusion improves cardiac performance in acute heart failure: a pilot randomised controlled clinical trial. Crit Care 18, R48 (2014)

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.