Podcast 85 – A Confirmation of Prejudices: Chloride and Pressure Poisoning

In this Hurricane Sandy episode of the EMCrit podcast, I talk about the confirmation of two of my clinical prejudices.

Chloride Poisoning

So I’ve always preached that grabbing normal saline for every ED patient is poor thinking and poor practice. We discussed this topic in the 4th Acid-Base Podcast on Fluids. Up until now, I did not have great evidence for my prejudice; now at least, I have reasonably good evidence:

Major complications, mortality, and resource utilization after open abdominal surgery: 0.9% saline compared to Plasma-Lyte (Ann Surg. 2012 May;255(5):821-9)

Association Between a Chloride-Liberal vs Chloride-Restrictive Intravenous Fluid Administration Strategy and Kidney Injury in Critically Ill Adults (JAMA. 2012 Oct 17;308(15):1566-72)

Definitive? Nope, but it just seems like good medicine to treat fluids like any other drug and actually choose the ideal one for the clinical situation.

Resus.me Post: What’s with all the chloride? An assault on salt | Resus M.E!


Association Between the Choice of IV Crystalloid  and In-Hospital Mortality Among Critically Ill Adults With Sepsis
Karthik Raghunathan (Crit Care Med 2014 citation pending)

A Diversion on Osmolality

Peter Sherren made a great comment in the podcast on the Brain Code regarding my statement that lactated ringers is an inappropriate fluid in high ICP. So I had a bit of a think on the topic and then was baffled as to why LR has a Na of 130 and yet a Osm of 272-5.

Brian Hayes responded to a tweet on the topic with what is probably self-evident to everyone but me: the Osm calculation we use is actually a crappy short cut; all components of a fluid need to be calculated to get the real Osm. Yet, when I thought about this still further, I realized that what is written on the bag is not actually the in-vivo Osm effects. Instead, the Na is probably the key.

Want proof of this concept? D5W has an Osm of 252 on the bag, but the effective Osm is 0 as soon as your cells take up the glucose.

So can you use LR in high ICP, yes probably not too big a deal, but the net Osm effects will probably be to lower the serum Na and Osm. If you buy choosing the ideal fluid for acid-base, it probably makes sense to choose the ideal fluid for Osm as well. Maybe this prejudice will be verified 5 years from now with a real article.

Here is the article I mentioned on the Osm effects of LR on healthy volunteers: (Anesth Analg 1999;88:999 –1003)

Here is an Osm calculator from GlobalRPH.

A Diversion on the need for Conversion of the Buffer Bases

Want what I think is the ideal resus fluid? Mix this on the fly:

Ultimate Resus Fluid? 1 amp of 44.6 bicarb in 500 ml of NS makes 550 of total volume= Na 121.6 Cl 77 Bicarb 44.6   to extended out to 1 liter= Na 217 Cl 138.6 BiCarb 80   1.3% Balanced Saline solution

There is ABSOLUTELY no evidence for this. If someone wants to do the study, please just put in me in the authorship somewhere.

Pressure Poisoning

Now I can say it: 8 ml/kg Vt by IBW for ALL ED PATIENTS should be your starting dose.

Association Between Use of Lung-Protective Ventilation With Lower Tidal Volumes and Clinical Outcomes Among Patients Without Acute Respiratory Distress Syndrome – A Meta-analysis JAMA. 2012;308(16):1651-1659

Resus.me Post: Not just in ARDS | Resus M.E!

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  1. Mike jasumback says:

    Aaaaack! I was going to stroke out until you wrote “Definitive? Nope”. My blood pressure is bakc down and i probably only had a small bleed. Certainly not definitive, but the evidence is a mounting. Might be time to author that “Plea for Normalcy” essay. You know, normal pco2, normal pao2 in head injury, normal ventilation strategy, normalish bp in ich, normal volume in sepsis, now a more normal fluid in fluid resusc. Hmmm, making things normal seems like what we ought to be doing in most cases of critical anything?

  2. What are your thoughts about a solution of 1 lt of 1/2NS+ 2 amps of bicarb with regards to using a hypochloremic fluid/ high Osmolar fluid?

    • 1/2 NS + 1 1/2 amps bicarb is an isotonic slightly alkalotic balanced solution. 2 amps would be fine as well. 2 Bags Isolyte/Plasmalyte for every bag of saline is not a bad way to go either.

  3. Mathias Tschopp says:

    I just noticed that there’s 2 flavors of Voluven.
    Voluven (with Na 154, Cl 154)
    Voluven balanced (Na 137, Cl 110, K 4, Acetate 34)

    Never paid attention to this, my unit has the balanced one. I wonder if the CHEST study was done with one or the other, since the amount of Cl seems relevant to kidney injury…

    • Check in here after you look it up.

      • Mathias Tschopp says:

        From the methods: “Patients were assigned to receive either 6% HES (130/0.4) in 0.9% saline (Voluven, Fresenius Kabi) or 0.9% saline”. I’m afraid we don’t have that level of detail, but it’s probably the unbalanced one… So is the difference in AKI due to Chloride poisoning or starch?

      • Mathias Tschopp says:

        From the methods: “Patients were assigned to receive either 6% HES (130/0.4) in 0.9% saline (Voluven, Fresenius Kabi) or 0.9% saline”. I’m afraid we don’t have that level of detail, but it’s probably the unbalanced one since they mention it’s diluter in 0.9% saline… So is the difference in AKI due to Chloride poisoning or starch?

        • agree it was prob. the unbalanced. I’m not sure if it was the starch or not though there have been balanced starch studies that have also shown unimpressive results. I would love to see a balanced albumin study for septic shock.

  4. Adam Drenzla says:

    Hi Scott. As always, great privilege listening to you. A few points of discussion on the topic of intravenous fluids.

    1.The anions. Although lots of chloride may not be great for our patients the physiological effects of the other anions used in more “balanced” fluids also merits a little circumspection. Gluconate (that other plasmalyte buffer) it seems has not been rigorously studied. A little more is known about acetate – evidence of adverse immunological, metabolic and cardio-toxic effects led to its abandonment in renal replacement fluids in Australia and elsewhere not too long ago. Also interesting in this respect is an experimental study in pigs comparing crystalloid resus fluids in haemorrhagic shock which showed worst survival with plasmalyte (as opposed to lactated ringers and NaCl) – an effect the authors speculated might be due to the added acetate and magnesium. Infusing substances either not known to be safe or indeed proven in other situations to be harmful does not seem precautionary.

    (Ishizaka S, Kikuchi E, Tsujii T. Effects of acetate on the human immune
    system. Immunopharmacol Immunotoxicol 1993;15(2-3):151-162.

    Traverso WL, Lee WP, Langford MJ. Fluid resuscitation after an
    otherwise fatal hemorrhage: I. Crystalloid solution. J Trauma. 1986;26:

    For a more thorough set of references regarding the physiological effects of acetate see,
    Davies, Venkatesh, Morgan et al. Plasma acetate, gluconate and interleukin-6 profiles during and after cardiopulmonary bypass: a comparison of plasma-lyte 148 with a bicarbonate –balanced solution. Critical Care 2011, 15, R21)

    2. Lactate deserves its own special mention. Although lactate elevations and lactic acidosis portend a poor prognosis in critically ill patients it is the cause of these metabolic alterations that lead to poor outcomes not the metabolic alterations themselves. Indeed, leaving the issue of acidosis aside for the moment, there is increasing evidence that lactate elevations in shock states may be an important adaptive response to the energetic crisis. Far from being a metabolic waste product lactate appears to provide cells, particularly in the myocardium, with an important source of high efficiency fuel (for the metabolic mechanisms see the references below). High lactate levels preserve haemodynamic function in haemorrhaged animals and exogenous lactate improves cardiac performance and reduces fluid requirements in post cardiac surgery patients.

    (Matejovic, Radermacher, Fontaine. Lactate in shock: a high-octane fuel for the heart? Intensive Care Med (2007) 33:406–408

    Wagner, Radermacher, Morimatsu. Hypertonic lactate solutions: a new horizon for fluid resuscitation? Intensive Care Med (2008) 34:1749–1751)

    Lactate does come in two isomers. There is some evidence that ringer’s lactate solutions containing racemic mixtures of l- and d- lactate elicit immunological responses which are ameliorated if only l-lactate is present. I am not aware if anyone has studied possible clinical consequences.

    (Koustova E, Stanton K, Gushchin V, Alam HB, Stegalkina S, Rhee PM. Effects of lactated Ringer’s solutions on human leucocytes. J Trauma 2002; 52:872-878

    Khan, Garner. Hartmann’s solution in haemorrhagic shock – now and the future. JR Army Med Corps 2007 153(2): 81-85)

    3. Acidosis. As suggested above, although acidosis is linked to adverse patient outcomes the contribution of the pH change to these adverse effects is not so clear. Indeed it is possible that mild to moderate acidosis in and of itself may actually be physiologically beneficial. Also, different types of metabolic acidosis have differing mortality rates associated with them – hyperchloremic acidosis of itself conferring no additional risk of mortality in most trials.

    Handy, Soni. Physiological effects of hyperchloremia and acidosis. BJA, 2008, 101(2), 141-150

    Guidet et al. A balanced view of balanced solutions. Critical Care 2010, 14, 325-337

    4. Evidence biased medicine. The title of your podcast “confirmation of prejudice” I found excellent. The most common way most of us look to the literature is exactly in that way – how wonderful it is to discover a trial or piece of data that aligns with our faith!! It reminds me of something hilarious I heard in one of Mervyn Singer’s talks (the original source he mentions but I forget) in which the levels of evidence are re-graded to align more closely with this reality. It’s entitled evidence-biased medicine. Class 0, What I believe. The best level of evidence. Class 0a. Things I believe despite the available data. Class 1, RCT’s that agree with what I believe. Class 2, Prospectively collected data that agree with me. Class 3, Expert opinion that agree’s with me. Class 4, RCT’s that don’t agree with what I believe. Class 5, What you believe but I don’t.

    Thanks again. Look forward to seeing you at SMACC down under.

    • Adam, Fantastic comments; I agree with you on all of your points. The surrogate buffer bases are all an unk quantity. That is why these two studies are important. We don’t know if LR or plasmalyte are “good”; we merely can now suspect (not confirmed yet) that they seem better than NS in the populations studied. This is why pt-important outcomes are so key.

      Brilliant acid-base folks like Kellum have believed for a while that hyperchloremia may actually be problematic, but as you mention, up until now there hasn’t been evidence. Now there is a bit, unless saline is causing harm in another way. The latter seems unlikely given that it is simply sodium and chloride.

      I too am interested in seeing some L-lactate studies. Now that both starches and gelatins seem to be crap, perhaps the pharm companies will go back to producing some decent new balanced crystalloids.

      Can’t wait for SMACC!

  5. Great podcast as always. The podcast was a bit unclear as to what would you use (assuming like in my dept only NS or LR no plasmalyte) for a DKA patient or a septic shock pt with lactic acidocis

    • If they are severe acidosis, LR would be a better choice than NS.

      • Steve Young a and e doctor in South Wales, UK says:

        Hi EMCrit
        In the pt in severe DKA with severe acidosis and high potassium should we stick to normal saline not Hartmanns as Hartmanns has potassium in it?
        Steve young

  6. Hey Scott,
    Having a great intellectual week following this post. Looking at your “ideal balanced” solution I see some potential side reactions. Ion pairing may become an issue. As you know all protanation states of the bicarb are gonna exist in solution. The pair of Na2CO3 may tie up some of your sodium thus effecting the overall deliverable sodium. While aqueous chemistry usually disreagrds side reactions and ion pairing this -2 charge carbonate ion WILL exist in solution and WILL bond up some sodium. Given the pH of the solution the concentration can be determined. It is likely to be negligible but if the pH window is small and the dominate species table lies slightly more to the basic side you will have a larger amount of the CO3 (-2) species present sucking up any cations it can. I can get you some quantitative chemistry formulas to calculate the exact concentration at a given pH if you ever want to know for sure

    • Fascinating! The fluid has a larger buffer to still be balanced, so even if there was some sodium binding, the Na/Cl difference would still be >40 from my back-of-envelope calcs, correct?

      • Overall yes I expect to see a Na/Cl difference above the 40 limit. However Two considerations.
        1. If you are doing a calculation you would want to account for Ion pairing, afterall you are doing a modified systematic treatment of equilibria so you do want to account for some. Assuming negligibility, assume <5% ,of your sodium loss due to pairing and you are still ok.
        2. Le Chatliers principle, the more basic this solution the greater the concentration of Carbonate in solution therefore the more of the carbonate that is gonna look to get back to a neutral state, taking sodium or hydrogen ions. You are looking at about a 200 millimolar Na content (back of the envelope havent actually calc'ed it out) This is gonna be much higher than the H ion content in a basic solution (<10^-7) so sodium will get taken up first.
        Again assuming less than a 5% contribution overall it should be fine however if you were to have a resident calculate it out you do wanna account for it!!!

  7. Great Podcast Scott. I quite like the mash up. I have to agree with Adam Drenzla’s comments, and he’s also written a small post on his topic having been inspired by you and Cliff here:
    After SAFE, and now CHEST, the logical next step for ANZICS CTG would be N/saline vrs a”balanced” solution…. But what that should be is still up for debate I guess. I do think a big, pragmatic MC RCT is the only way to settle this one.

  8. Scott, you’re killing me. I’ve spent the last several weeks going over all of the acid base podcasts you’ve posted plus this one.

    It’s all good though, well worth the time!

    Thanks for expanding my all too often cookbook ways.

  9. DocXology says:

    Is there such thing as an ‘ideal’ resus fluid to fit all situations? Wouldn’t it depend on the aetiology of both the water deficit and the associated acid/base electrolyte disturbances. And why bicarb? What if you have a severely volume-depleted bulimic with metabolic alkalosis. Furthermore, for shock associated with Type A lactic acidosis or DKA, the answer is to improve perfusion or halt ketogenesis – not give bicarb. In situations of iatrogenic hyperchloraemic metabolic acidosis, my understanding the issue is more with excessive chloride administration once adequate perfusion is established.

    Regarding the JAMA articles, was it just the chloride restriction that contributed to the benefit? Were there other confounders introduced during the intervention period that also afforded renal protection? Total volumes given? Earlier use of pressors? The fact that routine decisions such as fluid administration partly required senior input first may have biased the results. The abstract doesn’t comment on this (I will need to pull the paper).


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