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Normal Saline: The Coke of Crystalloid Fluids

January 6, 2013

The nurse looked up from my orders with a quizzical expression on her face.

“Why do you always order Ringer’s Lactate?” She asked.

I immediately launched into an intense discussion… errr… one sided conversation… about the merits of various IV solutions and their respective electrolyte values and pH. As her eyes quickly glazed over and she glanced at the clock her expression shifted to one of regret. I sensed that I was losing her and decided to change tactics.

“So basically, Normal Saline is the Coke of crystalloid fluids!” I concluded with a flourish. Then I got the skeptical look. Residents, you know the one – it’s kind of a blank stare with some annoyance mingled in that screams “this guy has no idea what he is talking about!”

And really, can I blame her for that look? For years and years every smart and respected EM physician that has been through the department has been ordering NS for their patients. The nurses didn’t even ask anymore, they just hung it. Why on earth would she believe me, a lowly resident, when I tell her that this fluid was the equivalent of a carbonated beverage acidic enough to corrode metal? Normal saline is the standard – it even says it’s normal in the name!!

And so, I continued to be the loser in my longstanding battle against hypertonic acid that began following my months in the ICU and OR. It was there that some very smart intensivists and anesthesiologists convinced me to consider the error of my NS-loving ways. Upon examination of the literature and the FOAM contributions of legends Dr. Scott Weingart (see his EMCrit podcasts on Chloride Poisoning and Acid-Base) and Dr. Cliff Reid  from, [6/1/12 addendum: Casey Parker of BroomeDocs also weighed in here] I came to the conclusion Normal Saline is as tried, tested and true as a Chevy Vega.

I have no desire to rehash the exceptionally well thought out positions of Drs. Weingart and Reid. If Weingart’s talking about it then it’s too sexy for me anyways!

Therefore, this post has three goals:

-To direct doctors, nurses and residents that I discuss this with to the exceptional FOAM resources on this topic
-To examine just how off-base I was with my desperately provocative statement that NS is the Coke of Crystalloids
-To try to comprehend why it is that we started using NS in the first place and examine why we haven’t changed

With the links to EMCrit and my first goal was accomplished. Please feel free to provide me with any additional reviews of this topic that you think would be helpful.

How Coke-like is Normal Saline? What other options do we have?

The new PV card from ALiEM outlines some of the Crystalloid options quite concisely. As summarized in Dr. Weingart’s post, the composition of each fluid is below. Additional data has been gathered from this article on the pH and SOsm of pop. I calculated the mEq measurement Coke myself using the nutritional information found here. I’d appreciate the help of anyone that is better at chemistry than me to recheck this calculation (I haven’t used molar masses since pre-med!).

mEq pH SOsm Na Cl K Ca Mg Buffer Price (CAN$)
Plasma 7.4 289 142 103 4 5 2 HCO3 – 22-32 N/A
Normal Saline 5.5* 308 154 154 $1.26/L
Ringer’s Lactate 6.5 273 130 109 4 3 Lactate – 28 $1.44/L
Plasmalyte A 6.5 295 140 98 5 3 Gluconate 23/Acetate 27 $7/L
Coca-cola 2.4 493  2.1 #  $1.50/L

*Different references gave me a range of pH values (4.5-7) for NS with the most commonly cited value being 5.5. I have attempted to look into the reason for this without success.
#Chloride content wasn’t provided in the nutritional information. I assume that there would be the same number of moles of Cl as there were of Na, but I’m sure if this is valid so I’ll leave that box blank for now.
$ Cost information is approximate and was provided to my by a pharmacist at my institution several months ago. It may have changed and your institution may get a better/worse deal than us. For my American readers, $1 CAN dollar equates to $1.01 USD 😉

So how NS-like is Coke? From the chart it doesn’t appear to be very similar. It’s much more acidic and its high SOsm is derived from sugar, not sodium chloride. However, after looking at the information about other soft drinks I don’t think it was an unreasonable comparison! NS and Coke are similar in that they are both the most acidic and hypertonic solutions in their respective classes (excluding weird soft drinks like Schweppes Bitter Lemon that I don’t even think exist in North America).

Where did Normal Saline come from, anyways?

Put another way, how is it that Hypertonic Acid became our most prolific IV fluid? I was delighted to find a paper that answered this question. See here for a 2008 review by Awad, Allison and Lobo of the history of Normal Saline.

To paraphrase, NS basically came out of nowhere. The first time hypovolemia was recognized as a contributor to morbidity and mortality came with the cholera epidemics of the 1800’s and a few bright physicians began experimenting with fluid resuscitation with various hypotonic solutions described in the language of the apothecary’s of the time. One of the earliest solutions was created by a Dr. Latta:

Latta T. (1832). Saline venous injections in cases of malignant cholera performed while in the vapour-bath. Part i. Lancet, 19, 173-176.

Unfortunately, I’d need a museum to find the original reference. Apparently, it included Na 134, Cl 118 and HCO3- 16, making it a substantially more physiologic solution than “Normal” Saline! Unfortunately, Dr. Latta died of tuberculosis the next year and fluid resuscitation was crushed by its critics.

The story after that gets involved and speculative. Widespread use of NS seems to have started sometime in the early 20th century with multiple physicians issuing warnings about the dangers of such a concentrated salt solution that were quickly forgotten. Regardless, how this solution came into widespread use seems to defy common sense as it has been demonstrated to be detrimental and would certainly not be our “ideal solution” if we were to come up with one today.

What would be the ideal resuscitation fluid?

Check out what Dr. Weingart thinks.

Why don’t we change?

At the end of the day, I think there are a few reasons why we haven’t embraced a more physiologic IV fluid in emergency medicine. Based on the options listed above, Plasmalyte A and Ringer’s Lactate may be viable alternatives.

However, Plasmalyte gets a huge knock for being expensive. While $5 extra might not seem like a lot, with the volume of fluid that gets used in the ED it is likely prohibitive (interestingly, that hasn’t stopped the OR at my institution from using quite a bit of it intra-operatively). As for RL, I’d gladly chip in an extra $0.18 for the good stuff if I ever end up in your ED.

What are some barriers to the widespread use of Ringer’s Lactate in the ED?

Concerns with Transfusion
As it contains Calcium, there are worries that it could cause blood to clot if they are given together.  Transfusing RBC’s with it is considered contraindicated where I work, but as this study and this study and this study attest, that is likely a myth, especially when the blood is being transfused quickly. However, I’m not well-versed or experienced enough to comment on this research and Canadian Blood Services states bluntly that you should never put them in the same line together. A quick google search led me to a California Blood Bank Society who gave the practice a big thumbs down after acknowledging that people do it anyway.

Based on this, I wouldn’t run blood with it or recommend that anyone do so. However, I don’t think this is a good reason not to use it in all of the patients that are not being transfused. Changing a line doesn’t take that long.

Concerns with Drug Compatibility
When I have asked nursing staff about their concerns with RL they have noted that many commonly used ED medications are considered incompatible with it. In particular, midazolam, dilantin and tazocin are commonly used ED drugs that are apparently incompatible.

While a few incompatibilities certainly shouldn’t relegate RL to the dustbin of ED history, I’d love to hear a pharmacist’s perspective on the reasons for the contraindications and the potential complications that would result if they were not observed.

Concerns that it will cause a Lactic Acidosis
Some believe that it will cause a lactic acidosis in their patient. I went reading far and wide trying to understand the biochemistry behind this. If I am incorrect or this can be better clarified, please make a comment or send a message.

If this description is hard to follow, consider heading over to one of my presentations on Prezi and checking out a presentation I did on this topic there. The part specifically dealing with the lactic acidosis issue is on Slide #32

So far as I can tell, this is a myth that makes no sense. Yes, lactate is in RL (it has a much more honest name than NS!). However, this lactate is not being transported out of a cell with an associated H+ molecule. Therefore, it would not cause an acidosis. [6/1/12 addendum – this is explained much more elegantly in this article].

Could it falsely elevate your lactate reading on your labs? How about in a liver failure patient? Perhaps, but there is such a very small amount of Lactate in RL relative to the body’s fluid volume that I feel it would be unlikely [6/1/12 – but alas, I am wrong. 28mEq Lactate = 28mmol/3.5L plasma volume = 8mmol/L change if no lactate is cleared. It would still not be associated with an acidosis though!]. More important than lab readings, your patient would likely do better with this fluid as it is more physiologic, does not cause a NAGMA, and kidneys like it more (see previous references to and EMCrit).


In conclusion, next time you’re ordering fluids for a patient in the ED consider: should they get IV Coca-cola? Or something healthier??

Once again, thanks so much to everyone for reading. If you liked what you saw, I’d be honored if you commented (I’ve learned a ton from my comments so far!), followed my blog (RSS feed and e-mails are available), followed me on twitter @boringem and/or tweeted/forwarded it on to others. Thanks!

Brent Thoma @boringem

From → Medical

  1. Great summary.
    My take on it was here:
    Love the Cola analogy. Sweet (or not so sweet) stuff.

  2. Excellent job! In patients getting volume resuscitation with shock liver or chrinic hepatic failure, the alctate can definitely accumulate from LR. Problem in this case is not just a false reading of elevated lactate, but LR essentially becomes NS until that lactate is metabolized.

    • Thanks so much! I should have examined that a bit further.

      A bit of math shows me how that makes sense: 1L of RL = 28mEq or 28mmol of Lactate. 28mmol/~3.5L of plasma = 8mmol/L. If it isn’t cleared effectively that would certainly affect lab values.

      Also, this reference explains the difference between lactate in RL and lactate resulting from hypoperfusion. I will amend my post.

  3. Justin permalink

    HI Brent,

    Great post. I agree that ideally greater degrees of thought need to be put into resuscitation fluids of choice. The lactic acidosis arguement is a funny one and reminds me of the common practice of stopping metformin for the same reason (albeit mostly unsubstantiated and based mostly on tradition than medical fact). As for compatability issues there are valid arguements both ways.

    Phenytoin, tazocin and midazolam are all generally compatible with LR just as they are with NS. That said – things quickly become messy when you start running phenytoin + ceftriaxone + gravol + morphine etc. etc. Suddenly you’re in a “one of these things is not like the other” situation. All are good to go except the ceftriaxone and the decision becomes secondary line vs. keep with ol’Faithful NS. Couple this with the inherent interactions that may be present between the drugs themselves and we’ve got a sticky situation on our hands 🙂

    In some cases the overall well-being of the patient might dictate that instead of a catch all fluid being used – separate infusion sites with different fluids running may be most prudent. But like all good things this also increases the risk of errors in ER by confusion lines at the point of infusion.

    One of our biggest concerns is obviously solubility issues and formation of precipitate. Microprecipitate formation particularily since it may only occur at the vascular level as solubility is also affected by temperature (going from room temp to body temp) and given the small lumen size and mixing flow that may or may not happen within the vascular space. Secondly, precipitation can also be delayed whereby drugs may be listed as LR compatable but only for specified intervals – something which doesn’t typically occur with …. you guessed it. NS…

    Sooooo in the end. Yeah, in typical pharmacy fashion I’d say ” it depends” 🙂


    • Justin,

      Thanks for the post! Let me know if you’d ever be up for a guest post/rant.

      A few more questions – where might I acquire an up-to-date compatibilities chart? The information I posted regarding those drugs came from a nursing friend that looked it up for me on an SHR chart. I’m happy to hear that it’s not true, but unhappy to learn that we’ve got outdated charts somewhere. Are there any common ED drugs besides Ceftriaxone that are incompatible?

      Once again, I’m glad we have you guys around. I’m trying to learn the boring stuff, but I have negative interest in the solubility changes of drugs at various temperatures/lumen sizes/flow rates.

  4. Hartmanns ans ceftriaxone incompatible?


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