Hyperchloremia: We've known it is harmful to the kidneys since 2012

It has been 7 years since this study came out, and many since. Here we are still using saline like it's benign. Part of the problem is that clinicians get set in their ways and just don't read. Sorry if that offends anyone, but it's true. Some say, "this has always worked and I haven't seen a problem with it" so they keep doing what they're doing. Our job is to cause no harm. I'm trying my best to minimize that but after all, we are all human. Being lazy is no excuse, though.

This article from 2012 shows a study that was performed on 12 healthy volunteers. It was a randomized, double blind, cross over study. I bet they were either college students or medical students; the mean age was 22. This was not disclosed in the article, of course. The participants received either 2L of 0.9% NaCl or plasma-lyte over an hour on separate occasions 7 to 10 days apart. If you still don't know what Plasma-lyte is, you must be new here. They did some bloodwork as well as MRI's. They must have had some good funding here.

Amongst the results, they found a significant difference in the serum chloride, as expected (p < 0.0001) and a much lower strong ion difference (p = 0.025) in the saline group. All the other electrolytes were unremarkable. From the MRI results, they found lower mean renal artery flow velocity (p = 0.045) and lower renal cortical tissue perfusion (p = 0.008) in the saline group. This proves that hyperchloremic metabolic acidosis is not benign.

A hat tip to the authors.

-EJ




Link to the article: 

Chowdhury AH, Cox EF, Francis ST, et al. A Randomized, controlled, double-blind crossover study on the effects of 2-L infusions of 0.9% saline and plasma-lyte 148 on renal blood flow velocity and renal cortical tissue perfusion in healthy volunteers. Ann Surg 2012; 256: 18–24.

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Diabetic Ketoacidosis: Using Balanced Salt Solutions instead of 0.9% Sodium Chloride

We all know the order sets for DKA, a bunch of 0.9% NaCl first boluses then drip, insulin drip, replace electrolytes, glucose gets to a certain number, change the fluids to 0.9% NaCl that contains dextrose, wait for the anion gap to close, give long acting insulin, wait a bit, turn off the drip, discharge planning. It's simple stuff, really. I may have oversimplified it but you know exactly what the protocol is at your facility. Truth is, though, is that the best for these sick patients? Would they do better with lactated ringers or plasma-lyte?

This study from 2011 states that there are 100,000 hospitalizations for DKA annually in the US. They knew from prior literature that using a bunch of saline solution causes a hyperchloremic metabolic acidosis. They wanted to see if it would happen in this patient population. They conducted a randomized double blind study providing these patients with either 0.9% NaCl solution or Plasma-lyte. For those of you who do not know what plasma-lyte is, go check out my YouTube videos (/shameless plug). They used their typical DKA protocol for their institution which is described in the article.

The study took 24 months and they ended up with 23 patients in the "normal saline" group and 22 patients in the plasma-lyte group. It was entertaining to see that at baseline, before a drop of fluid was even given, the serum chloride of the saline group was less than the PL group: 94 vs 98 (p=0.027). When the study was said and done, however, the chloride level was 111 in the NS group and 105 in the PL group (p < 0.001). I don't know if you've had time to look at the older things I've written/posted but there's a particular study that comes to mind where the authors found that an increase in serum chloride by 5 increases your chances of developing acute kidney injury. There was also a significant difference in the serum bicarb level where the NS group has a bicarb increase of 7 whereas the PL group had an increase of 9 (p=0.023). The authors did not follow renal function in these patients from what I am able to see. The authors admitted that they didn't know what the clinical significance of all this is. I believe we have data now with more recent studies to show us what the clinical significance actually is.

- EJ



Link to Abstract

Mahler SA, Conrad SA, Wang H, et al. Resuscitation with balanced electrolyte solution prevents hyperchloremic metabolic acidosis in patients with diabetic ketoacidosis. Am J Emerg Med 2011; 29: 670–674.

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High Flow Nasal Cannula in Acute Decompensated Heart Failure data leaves much to be desired.

Fortunately in the critical ill population, we do not necessarily have to abide by the saying that "if all you have is a hammer, everything looks like a nail". What I'm referring to is regarding utilizing high-flow nasal cannula in acute heart failure exacerbations. I already dissected how HFNC generated a "PEEP" equivalent airway pressure and the data behind that statement. The amount of PEEP varies and it drops by a statistically significant difference if the patient has their mouth open. If a patient presents to the emergency department, or someone gets overzealous with maintenance fluids, with an acute heart failure exacerbation, there is data that I will be reviewing here where HFNC is an option. But let's be honest with ourselves, though, non-invasive ventilation (colloquially known as BiPAP, although CPAP has data for working as well) is the better option because it provides positive airway pressure more reliably that HFNC. Sometimes these patients just need the ventilator as well. All three studies are FREE that I am going to be reviewing here and I recommend you read them for yourself rather than trusting my takedown of them. That's your disclaimer.

The first study published in 2011 out of Spain was a look at just 5 patients. I know, don't fall off of your seat. I can't criticize because I don't do any research outside of read other peoples research. One needs to remember that in 2011 the HFNC systems were not readily available for historical context. These 5 patients were treated in the emergency department with NIV and then I guess they were diuresed aggressively there. Why do I guess? Well the study does not report the BNP nor the achieved diuresis in these 5 patients. Big weakness in the study. They looked at a multitude of parameters that would be standard for a study of this nature, i.e. to see if HFNC is better than the other oxygen devices, but there are big problems. You see, the authors looked at the parameters before HFNC and then 24 hours AFTER HFNC. What they don't say is how much the patients were diuresed in the interim. Of course the PaO2 is going to improve. Of course the dyspnea is going to improve. Of course the respiratory rate is going to improve! Anyway, this is a study worth sticking in our back pockets to know it happened and move forward.

The second study by Roca also out of Spain in 2013 wanted to assess if HFNC helped with the hemodynamic parameters. They hypothesized that HFNC in patients with heart failure could be associated with a decrease in preload without changing the cardiac output. To look at this, patients got sequential echo's to assess cardiac function. Pretty good setup if you ask me. The 10 patients enrolled in this study were all stable. Therefore the data needs to be extrapolated to the sick patients. They did a baseline TTE on these patients, then hooked them up to the HFNC system at 20L, checked an echo, then at 40L of flow, and checked an echo. They did all sort of echocardiographic wizardry to obtain their results. They found that HFNC may be associated with a decrease in preload justified by the lack of IVC collapse on inspiration without any changes to cardiac function. IVC measurements are their own can of worms when used for resuscitation but this is very standardized and methodical. The most interesting finding that I enjoyed was the decrease in respiratory rate noted by these patients. At baseline, their RR was 23 breaths per minute. At 20L this fell to 17 bpm. At 40L this fell to 13 bpm. Cool stuff! Note that the patients were receiving just flow in this study as the FiO2 was set to 21% (room air). The authors chose to not use patients in acute decompensated heart failure for this study as there would have been too much variability in the subjects themselves along with their responses to the treatments interfering with to the measures. Obviously if they dump out a liter due to furosemide their hemodynamic parameters are going to change and it'll mask out the effect of the HFNC or provide confounders.

The third and last study I'm going to share with you all today comes from our colleagues in South Korea who performed a retrospective cohort analysis where patients were divided into a HFNC group or an intubation group after oxygenation with a facemask at a flow rate of 10L/min or more. These authors jumped on the opportunity to look at this data as they hadn't seen any published data about using HFNC in patients with acute heart failure exacerbations. They looked at approximately 5 years of data to place 73 patients in the intubation group and 76 patients in the HFNC group. Since this was a retrospective study, the decision as to what arm the patients fell in was at the discretion of the physician at bedside. The authors are just looking back in time at why they decided to do it and how the patients did. It seems as if they ignored the NIV data. I could be wrong. The baseline characteristics of the two arms were similar with nothing too eye catching. These patients were looked at for 6 hours. There were no statistically significant changes in the physiologic responses between the two groups. There was also no difference in the clinical outcomes between the two groups. This oddly, in my opinion, includes vasopressor/ionotrope use. I mention this because patients who are intubated typically have sedation. Also, the medications utilized for intubation could have an effect on hemodynamic parameters that are not noted here. It's just something that, from a personal experience standpoint, has me a bit curious. The p-value for that is 0.051. If the sample size would've been larger, I'm sure that would've been a notable difference. The authors noted all these limitations to their study and agree that what we really need is a prospective, multicentered, randomized, controlled trial. I agree

To conclude, I think the best we have right now in the absence of concrete data is clinical judgment, my favorite. One could try to place the patient on HFNC to either keep them away from the ventilator or even keep them from being annoyed by the CPAP/BiPAP mask which is typically uncomfortable, limits the ability to eat, speak, and other fun activities. If it fails, it fails. Your RT may be a little annoyed at you and may say "I told you so", but ultimately we have to do what's best for the patient. Thoughts? Please read these articles for yourself. A hat tip to all the authors. 

- EJ





Link to Abstract

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Link to Abstract

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Link to Abstract

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Ketamine for Rapid and Delayed Sequence Intubation

Alternatives to Rapid Sequence Intubation: Contemporary Airway Management with Ketamine

What are your experiences with ketamine for intubations?

I am really glad that I stumbled onto this article that was shared by @the_resuscitationist and @medicotactico.

When you're dealing with airways and medications that have can concerning adverse effects, you really shouldn't trust me on anything and should read the article yourself. Link in bio. This one is also completely free! Also, everything I typed for this post didn't fit in the space allowed by IG, so if you want to finish reading all my thoughts, you have no choice but to head over to my website. It is what it is and this article got me fired up!

For my physicians/NP/CRNA/PA colleagues who manage airways: How do you utilize ketamine for these situations?

For my ICU and ED nurses who push this medication: what have been your experiences with it?

The first thing the authors state is something those of us in the ICU or ED’s already know, establishing an airway is the riskiest commonly performed procedure in acute care. I do not proceed with pushing meds unless I have all my ducks in a row and I have plan A, B, and C easily accessible.

Here’s what happens with ketamine versus other agents that are commonly used: the patient becomes dissociated, they get that glassy look in their eyes, basically disconnected, but the brain stem reflexes stay intact... well... most of the time. You need to be prepared for it to hit the fan at any time. The patient should continue to breath spontaneously. The patients hemodynamics should also be augmented. Again, the key word is “should”. I’ve seen patients become apneic as well as hypotensive but more on that later. I’m just glad I’m not the only one who has seen these effects which are described in the literature. Nurses, don’t push ketamine like a bolus. Push it over 30-60 seconds. I know there’s a ton of adrenaline rushing in those rooms and you're used to pushing meds.

Here’s a strategy I learned from this article. Go ahead and push the ketamine when the patient is agitated and thrashing to allow for preoxygenation. The patient should chill out and when they cease thrashing, one can move forward with a preoxygenation strategy. They even explained certain cases where patients were provided with ketamine for this reason and then didn’t even need intubation.

What’s the dose? 1-2mg/kg of IDEAL body weight.

One of the things that I have noticed clinically when administering ketamine to establish and airway is the clenched jaw. Here, the authors recommend using midazolam, propofol, or even a sub-induction dose of etomidate. Just be aware that these agents bring their own baggage to the party.

Here's what the authors say about the hypotension related to ketamine. First, you need to know whether you think the patient is catecholamine depleted. In other words, they are in shock and they are running out of steam. Those patients should be resuscitated to the best of your ability and you may have to cut the dose in half. Again, read the article for yourself.

Lastly, the authors discuss using ketamine for sedation but it should be kept at dissociative doses or else your patient is going to have some no-so-good experiences. You may need to add some propofol at that point.

For respect of the authors, I will stop there. Read it for yourself. Again, it's free! Thank youuuuu!

- EJ





Link to Article

Link to FREE PDF

Merelman, A., Perlmutter, M., & Strayer, R. (2019). Alternatives to Rapid Sequence Intubation: Contemporary Airway Management with Ketamine. Western Journal of Emergency Medicine, 20(3), 466–471.

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High-flow Nasal Cannula: What is it?

High-flow nasal cannula oxygen therapy in adults

Some of you have asked what I mean every time I post something regarding high flow nasal cannula. Let's start by defining the flow in the different oxygen devices. Regular nasal cannula provides between 1-6 liters of flow. A simple face mask can get you flows between 6-10L/min. Venti masks, aka Venturi masks can get you flow rates between 4-8L/min. The best you can potentially do with a non-high flow device is the non-rebreather which can generate a flow rate of 10-15L/min. Just so we are all clear, every time I see a patient on a non-rebreather my senses step up to the next level. To me, that thing strapped on a patients face means that a decision needs to be made stat as the person who placed it on their face needs a second opinion. It's time to either place the patient on HFNC, BiPAP, intubate, or my favorite, they just panicked and didn't know what to do. It happens.

I like the image in particular because it is not signaling any machine in particular. There are a number of different companies who make these devices and I do not know the nitty gritty as to what differentiates them. I just know I love the technology. Would you all like for me to make a YouTube video where I break down the mechanisms of action of the device?

This article is a good review for the time, published in 2015, with the data that existed at the moment. The author reviews the physiologic effects, discusses the dead space washout, the PEEP effect, the benefits of heat and humidification. In addition, they discuss clinical uses such as both hypoxemic and hypercapnic respiratory failure, pre-intubation, post-extubation, sleep apnea, heart failure, and others.

It's definitely worth a quick read.

-EJ








Nishimura, M. (2015). High-flow nasal cannula oxygen therapy in adults. Journal of Intensive Care, 3(1).

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Ringers Lactate does NOT increase Potassium more than 0.9% Sodium Chloride in this study

A comparative study of impact of infusion of Ringer's Lactate solution versus normal saline on acid-base balance and serum electrolytes during live related renal transplantation

Here's yet another article discussing Ringer's Lactate versus 0.9% saline solution in renal transplant patients. They also acknowledged the consensus to provide NS rather than LR to avoid hyperkalemia in patients but they weren't happy with that, especially understanding and running into the data suggesting that NS creates the non-anion gap metabolic acidosis from hyperchloremia which can result in hyperkalemia due to the extra-cellular shift of potassium. That's the reason why they decided to proceed with a prospective double blind clinical trial on patients undergoing kidney transplants. They had 37 patients in each group. Each group of patients, the LR and the NS groups, received a little more than 5L each. Patients who received NS had a pH drop from 7.43 to 7.33. The LR group had no change in pH. The table in the article breaks down the serum electrolytes during the study as they checked it four times throughout the course of the surgery. The authors concluded that RL may not only be safe, but also superior to NS in these patients. The article cites another study where that team had to to treat more patients for hyperkalemia in the NS arm compared to the LR arm. Cool stuff, right? A 🎩 tip to the authors!

-EJ











Modi, MP. A comparative study of impact of infusion of Ringer's Lactate solution versus normal saline on acid-base balance and serum electrolytes during live related renal transplantation.Saudi J Kidney Dis Transpl. 2012 Jan;23(1):135-7.

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0.9% Saline vs. Ringer's Lactate: Which one causes an increase in potassium?

Effects of Normal Saline vs. Lactated Ringer's during Renal Transplantation

0.9% saline is 154mmol/L of sodium and 154mmol/L of chloride. That's it. There's no potassium, calcium, magnesium, nor buffering agent in there. Ringer's lactate, however, has 130mmol/L of sodium, 109mmol/L of chloride, 4mmol/L of potassium, 28mmol/L of lactate, and 3mmol/L of calcium. One would expect that the solution containing potassium would cause a greater increase in potassium than the one without potassium, right? Well, not so fast. Large volumes of sodium chloride, produce a hyperchloremic metabolic acidosis. What happens during acidosis? Well, there's a shift of potassium from the intracellular space to the extra cellular space. Much of this has to do with the strong ion difference which I will be breaking down in the near future. In this study, 52 patients patients received either LR or NS during their renal transplants.

Here are the findings: This has been copied and pasted from the article. Please download it and read it for yourself.

"Patients in the NS group had a lower mean PH level during the transplantation compared with those who received LR (p < 0. 001).

Mean serum potassium levels in the NS and LR groups were 4.88 ± 0.7 and 4.03 ± 0.8 meq/L, respectively (p < 0.001).

Mean changes of the serum potassium were +0.5 ± 0.6 meq/L in the NS group and –0.5 ± 0.9 meq/L in the LR group (p < 0.001).

Mean changes of PH were −0.06 ± 0.05 in the NS group and –0.005 ± 0.07 in the LR group (p < 0.001)"

If next time someone tells you that LR causes hyperkalemia, you can be armed with data. I have other articles with similar results that I plan on sharing in the upcoming days.

I don't know what to make of that thrombosis phenomenon they found. Must keep an eye out for more data regarding that.





Mohammad Reza Khajavi, Farhad Etezadi, Reza Shariat Moharari, Farsad Imani, Ali Pasha Meysamie, Patricia Khashayar & Atabak Najafi (2008) Effects of Normal Saline vs. Lactated Ringer's during Renal Transplantation, Renal Failure, 30:5, 535-539

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IV Fluids Types: Do you know your -ish?

Problems with solutions: drowning in the brine of an inadequate knowledge base

More than 50% of residents do not know how much sodium is in 0.9% NaCl. I know you do, though... it's 154mmol/L. Far more than our "normal" of 140mmol/L.
Why do I nag so much with intravenous fluids and what's in them? Truth be told, I did not know my fluid composition as well as I should have even as an intern. I had an ICU attending, a mentor, now someone I'm fortunate to call a colleague, who would pimp the house staff on IV fluids and make us feel ashamed if we didn't know the answer. He was right. My embarrassment was deserved. After all, these are substances that we are mindlessly pouring into our patients. The vast majority of clinicians, I'm not even talking about nurses, I AM REFERRING TO US DOCTORS, do not know what's in these bags that are so easy to click in the EMR and order. We mindlessly just do it. I was embarrassed. I do not want you to feel the same way. I have been teaching fluids now for 4 years. It's one of my passions. I have a talk that is complete and can present at any time of the day. I know it well. But I am always reading and adding to it. The talk is going to be one of the lectures I will be presenting in Hawaii in May of 2020. It will also be presented to the Department of Anesthesia at my hospital on October 20th of this year. I am currently brushing up that talk, adding and subtracting some things, and I ran into this study from 2001 which asked preregistration house officers and senior house officers (I guess that means interns and residents) about the composition of fluids amongst other things. I won't go over the methodology but the training needs to start in medical school. Overall, 11.5% said their training in the matter was poor, 22% stated it was unsatisfactory. I have to agree with this 100%. I received ZERO training in med school regarding IVF. Since it's something so ubiquitous in our daily practice of medicine, it's something we need to do better. A lot better. If you are in medical school or residency, have you been trained in the composition of IV Fluids?

-EJ



Link to the Abstract

Lobo, D.N., Dube, M.G., Neal, K.R., et al., 2001. Problems with solutions: drowning in the brine of an inadequate knowledge base. Clin. Nutr., 20(2):125-130.
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HFNC/High Flow Nasal Cannula: A beautiful image of the mechanisms of action

Not Just Oxygen? Mechanisms of Benefit from High-Flow Nasal Cannula in Hypoxemic Respiratory Failure.




Link to Abstract

Link to Image

Goligher, E. C., Slutsky, A. S. (2017). Not Just Oxygen? Mechanisms of Benefit from High-Flow Nasal Cannula in Hypoxemic Respiratory Failure. American Journal of Respiratory and Critical Care Medicine, 195(9), 1128–1131.
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HFNC/ High Flow Nasal Cannula in the Emergency Department: Can it avoid intubations?

Randomized Controlled Trial of Humidified High-Flow Nasal Oxygen for Acute Respiratory Distress in the Emergency Department: The HOT-ER Study

This study was the first randomized control trial looking at whether high-flow nasal cannula (HFNC) decreases the need for mechanical ventilation in the emergency department. In addition they looked at emergency department and hospital lengths of stays, 90 day mortality, adverse effects in the hospital, and patient experience. I sympathize for the authors of this study because their abstract shows results that my not in fact be true. I state this because, although the study took over two years to complete, they did not collect sufficient patients to demonstrate an effect on their primary outcome which was a need for mechanical ventilation. Unfortunately, they needed 900 based on post-hoc analysis and obtained 322 patients. It would have taken them approximately 6 years to get this trial done. Sigh. The other caveat to this trial is that the sickest patients were plucked out by the physicians after recruitment because they wanted to proceed with NIV/BiPAP before even trying HFNC. I can't say I blame them. I treat patients and trials be damned if my clinical judgement is telling me to do something. That's another reason why I am not in academics nor do I do research. Patients also just weren't that sick. If you're an ER doctor, could you imagine the acuity if you just intubate 7.2% of patients in respiratory failure on standard oxygen therapy? That means these patients weren't that sick. I mean, the intubation rates for all comers in patients who are on HFNC in subsequent studies flirts with 30%. Please don't quote me on that number but I believe it to be accurate based on my prior research. I can just imagine how many clinicians would irresponsibly read through the abstract and say, HFNC is not good and just throw away the technology ignoring the benefits. Then you have to fight against their cognitive dissonance to make them change their practice. That's enough for today on this study. Thanks for checking it out.
A 🎩 tip to the authors

-EJ




Jones PG, Kamona S, Doran O, Sawtell F, Wilsher M. Randomized controlled trial of humidified high-flow nasal oxygen for acute respiratory distress in the emergency department: the HOT-ER Study. Respir Care 2016;61:291–299.

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