Intravenous Fluid Lecture: Citations

I have been missing for a few weeks as I am putting the finishing touches on my lectures that are due on the 15th of this month. The amount of time and effort necessary to write a CME lecture is insane. I've written 7 of them in this last year. Voluntarily, of course. I'm not complaining. For my intravenous fluid lecture, I have cited 43 different articles listed below. I have attempted to cite these articles as well as I know how to but there will be some inevitable errors. If you plan on creating an IVF lecture of your own, this is my gift to you. My only request is that you credit me in some way, shape, or form. Ultimately, I did not write any of these articles. I have to tip my hat to everyone who contributed to the writing of all of these articles. They are the ones who did the leg work and I am ultimately piggybacking on their efforts. 

This lecture discusses the three fluids we use for resuscitation in critically ill patients: 0.9% NaCl, Lactated Ringers, and Plasma-Lyte. I go over the history of the three fluids, and also break down the contents of these fluids, based on the data on how they affect our patients and our organs, then present the relevant data on how these data changes outcomes in our critically ill patients. The reason why this is a controversial topic is because most clinicians use saline because they really do not understand what is in it, nor the effects of it. As I mention in one of my slides, if the FDA had to approve 0.9% NaCl today, chances are that it would not be approved. 

I am sorting out how to provide you all with this lecture, youtube or some other medium. The issue is that youtube has a thing for demonetizing my videos the moment I say the words "mortality", "death" and others. I do earn some income from you all visiting my website, eddyjoemd.com to check out the links and download the articles I share. Thank you all for your support! 

-EJ

Citations:

Lobo DN, Stanga Z, Aloysius MM, et al. Effect of volume loading with 1 liter intravenous infusions of 0.9% saline, 4% succinylated gelatine (Gelofusine) and 6% hydroxyethyl starch (Voluven) on blood volume and endocrine responses: a randomized, three-way crossover study in healthy volunteers. Crit Care Med. 2010;38(2):464–470. doi:10.1097/CCM.0b013e3181bc80f1

Link to Abstract

Ragaller MJ, Theilen H, Koch T. Volume replacement in critically ill patients with acute renal failure. J Am Soc Nephrol. 2001;12 Suppl 17:S33–S39.

Link to Abstract


Link to FULL FREE Article

Bark BP, Persson J, Grände PO. Importance of the infusion rate for the plasma expanding effect of 5% albumin, 6% HES 130/0.4, 4% gelatin, and 0.9% NaCl in the septic rat. Crit Care Med. 2013;41(3):857–866. doi:10.1097/CCM.0b013e318274157e

Link to Abstract

Lobo DN, Dube MG, Neal KR, Simpson J, Rowlands BJ, Allison SP. Problems with solutions: drowning in the brine of an inadequate knowledge base. Clin Nutr. 2001;20(2):125–130. doi:10.1054/clnu.2000.0154

Link to Abstract

Awad S, Allison SP, Lobo DN. The history of 0.9% saline. Clin Nutr. 2008;27(2):179–188. doi:10.1016/j.clnu.2008.01.008

Link to Abstract

Lewins, Robert. Injection of Saline Solutions into the Veins. (1832). The Boston Medical and Surgical Journal, 6(24), 373–375.

Link to Abstract

Link to FULL FREE Article

Hartmann AF, Senn MJ. STUDIES IN THE METABOLISM OF SODIUM r-LACTATE. II. RESPONSE OF HUMAN SUBJECTS WITH ACIDOSIS TO THE INTRAVENOUS INJECTION OF SODIUM r-LACTATE. J Clin Invest. 1932;11(2):337–344. doi:10.1172/JCI100415

Link to Abstract


Link to FULL FREE Article

Weinberg L, Collins N, Van Mourik K, Tan C, Bellomo R. Plasma-Lyte 148: A clinical review. World J Crit Care Med. 2016;5(4):235–250. Published 2016 Nov 4. doi:10.5492/wjccm.v5.i4.235

Link to Abstract


Link to FULL FREE Article

Rizoli S. PlasmaLyte. J Trauma. 2011;70(5 Suppl):S17–S18. doi:10.1097/TA.0b013e31821a4d89

Link to Abstract


Link to FULL FREE Article

Brown RM, Wang L, Coston TD, et al. Balanced Crystalloids versus Saline in Sepsis. A Secondary Analysis of the SMART Clinical Trial. Am J Respir Crit Care Med. 2019;200(12):1487–1495. doi:10.1164/rccm.201903-0557OC

Link to Abstract


Link to FULL FREE Article

Li H, Sun SR, Yap JQ, Chen JH, Qian Q. 0.9% saline is neither normal nor physiological. J Zhejiang Univ Sci B. 2016;17(3):181–187. doi:10.1631/jzus.B1500201

Link to Abstract


Link to FULL FREE Article

Wilcox CS. Regulation of renal blood flow by plasma chloride. J Clin Invest. 1983;71(3):726–735. doi:10.1172/jci110820

Link to Abstract


Link to FULL FREE Article

Quilley CP, Lin YS, McGiff JC. Chloride anion concentration as a determinant of renal vascular responsiveness to vasoconstrictor agents. Br J Pharmacol. 1993;108(1):106–110. doi:10.1111/j.1476-5381.1993.tb13447.x

Link to Abstract


Link to FULL FREE Article

Chowdhury AH, Cox EF, Francis ST, Lobo DN. 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 [published correction appears in Ann Surg. 2013 Dec;258(6):1118]. Ann Surg. 2012;256(1):18–24. doi:10.1097/SLA.0b013e318256be72

Link to Abstract


Link to FULL FREE Article

McCluskey SA, Karkouti K, Wijeysundera D, Minkovich L, Tait G, Beattie WS. Hyperchloremia after noncardiac surgery is independently associated with increased morbidity and mortality: a propensity-matched cohort study. Anesth Analg. 2013;117(2):412–421. doi:10.1213/ANE.0b013e318293d81e

Link to Abstract


Link to FULL FREE Article

Myburgh JA, Mythen MG. Resuscitation fluids. N Engl J Med. 2013;369(13):1243–1251. doi:10.1056/NEJMra1208627

Link to Abstract


Link to FULL FREE Article

Noritomi DT, Soriano FG, Kellum JA, et al. Metabolic acidosis in patients with severe sepsis and septic shock: a longitudinal quantitative study. Crit Care Med. 2009;37(10):2733–2739. doi:10.1097/ccm.0b013e3181a59165

Link to Abstract


Link to FULL FREE Article

Neyra JA, Canepa-Escaro F, Li X, et al. Association of Hyperchloremia With Hospital Mortality in Critically Ill Septic Patients. Crit Care Med. 2015;43(9):1938–1944. doi:10.1097/CCM.0000000000001161

Link to Abstract


Link to FULL FREE Article

Suetrong B, Pisitsak C, Boyd JH, Russell JA, Walley KR. Hyperchloremia and moderate increase in serum chloride are associated with acute kidney injury in severe sepsis and septic shock patients. Crit Care. 2016;20(1):315. Published 2016 Oct 6. doi:10.1186/s13054-016-1499-7

Link to Abstract


Link to FULL FREE Article

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.

Link to Abstract

Link to FULL FREE Article

Khajavi MR, Etezadi F, Moharari RS, et al. Effects of normal saline vs. lactated ringer's during renal transplantation. Ren Fail. 2008;30(5):535–539. doi:10.1080/08860220802064770

Link to Abstract


Link to FULL FREE Article

Piper GL, Kaplan LJ. Fluid and electrolyte management for the surgical patient. Surg Clin North Am. 2012;92(2):189–vii. doi:10.1016/j.suc.2012.01.004

Link to Abstract


Link to FULL FREE Article

Andersen LW, Mackenhauer J, Roberts JC, Berg KM, Cocchi MN, Donnino MW. Etiology and therapeutic approach to elevated lactate levels. Mayo Clin Proc. 2013;88(10):1127–1140. doi:10.1016/j.mayocp.2013.06.012

Link to Abstract


Link to FULL FREE Article

Ichai C, Orban JC, Fontaine E. Sodium lactate for fluid resuscitation: the preferred solution for the coming decades?. Crit Care. 2014;18(4):163. Published 2014 Jul 7. doi:10.1186/cc13973

Link to Abstract


Link to FULL FREE Article

Farkas, Josh. “Three myths about Plasmalyte, Normosol, and LR” https://emcrit.org/pulmcrit/three-myths-about-plasmalyte-normosol-and-lr/\.1/26/15

Link to Abstract

Link to FULL FREE Article

Nalos M, Leverve XM, Huang SJ, Weisbrodt L, Parkin R, Seppelt IM, Ting I, Mclean AS: Half-molar sodium lactate infusion improves cardiac performance in acute heart failure: a pilot randomized controlled clinical trial. Crit Care 2014, 18:R48.

Link to Abstract

Link to FULL FREE Article

Weinberg L, Collins N, Van Mourik K, Tan C, Bellomo R. Plasma-Lyte 148: A clinical review. World J Crit Care Med. 2016;5(4):235–250. Published 2016 Nov 4. doi:10.5492/wjccm.v5.i4.235

Link to Abstract


Link to FULL FREE Article

Yartsev, Alex. Metabolic Fate of Lactate, Acetate, Citrate and Gluconate. http://www.derangedphysiology.com/main/core-topics-intensive-care/manipulation-fluids-and-electrolytes/Chapter%204.1.4/metabolic-fate-lactate-acetate-citrate-and-gluconate. Accessed 3.13.2020

Spriet I, Lagrou K, Maertens J, Willems L, Wilmer A, Wauters J. Plasmalyte: No Longer a Culprit in Causing False-Positive Galactomannan Test Results. J Clin Microbiol. 2016;54(3):795–797. doi:10.1128/JCM.02813-15

Link to Abstract


Link to FULL FREE Article

Stocker RA. "Normal" Saline and Co: What Is Normal?. Crit Care Med. 2016;44(12):2282–2283. doi:10.1097/CCM.0000000000002030

Link to Abstract


Link to FULL FREE Article

Zampieri FG, Ranzani OT, Azevedo LC, Martins ID, Kellum JA, Libório AB. Lactated Ringer Is Associated With Reduced Mortality and Less Acute Kidney Injury in Critically Ill Patients: A Retrospective Cohort Analysis. Crit Care Med. 2016;44(12):2163–2170. doi:10.1097/CCM.0000000000001948

Link to Abstract


Link to FULL FREE Article

Shaw AD, Bagshaw SM, Goldstein SL, et al. Major complications, mortality, and resource utilization after open abdominal surgery: 0.9% saline compared to Plasma-Lyte. Ann Surg. 2012;255(5):821–829. doi:10.1097/SLA.0b013e31825074f5

Link to Abstract


Link to FULL FREE Article

Gupta RG, Hartigan SM, Kashiouris MG, Sessler CN, Bearman GM. Early goal-directed resuscitation of patients with septic shock: current evidence and future directions. Crit Care. 2015;19(1):286. Published 2015 Aug 28. doi:10.1186/s13054-015-1011-9

Link to Abstract


Link to FULL FREE Article

Ince C, Groeneveld AB. The case for 0.9% NaCl: is the undefendable, defensible?. Kidney Int. 2014;86(6):1087–1095. doi:10.1038/ki.2014.193

Link to Abstract


Link to FULL FREE Article

Hammond NE, Taylor C, Saxena M, et al. Resuscitation fluid use in Australian and New Zealand Intensive Care Units between 2007 and 2013. Intensive Care Med. 2015;41(9):1611–1619. doi:10.1007/s00134-015-3878-y

Link to Abstract


Link to FULL FREE Article

Mahler SA, Conrad SA, Wang H, Arnold TC. Resuscitation with balanced electrolyte solution prevents hyperchloremic metabolic acidosis in patients with diabetic ketoacidosis. Am J Emerg Med. 2011;29(6):670–674. doi:10.1016/j.ajem.2010.02.004

Link to Abstract


Link to FULL FREE Article

McFarlane C, Lee A. A comparison of Plasmalyte 148 and 0.9% saline for intra-operative fluid replacement. Anaesthesia. 1994;49(9):779–781. doi:10.1111/j.1365-2044.1994.tb04450.x

Link to Abstract


Link to FULL FREE Article

Young JB, Utter GH, Schermer CR, et al. Saline versus Plasma-Lyte A in initial resuscitation of trauma patients: a randomized trial. Ann Surg. 2014;259(2):255–262. doi:10.1097/SLA.0b013e318295feba

Link to Abstract


Link to FULL FREE Article

Young P, Bailey M, Beasley R, et al. Effect of a Buffered Crystalloid Solution vs Saline on Acute Kidney Injury Among Patients in the Intensive Care Unit: The SPLIT Randomized Clinical Trial [published correction appears in JAMA. 2015 Dec 15;314(23):2570]. JAMA. 2015;314(16):1701–1710. doi:10.1001/jama.2015.12334

Link to Abstract


Link to FULL FREE Article

Self WH, Semler MW, Wanderer JP, et al. Balanced Crystalloids versus Saline in Noncritically Ill Adults. N Engl J Med. 2018;378(9):819–828. doi:10.1056/NEJMoa1711586

Link to Abstract


Link to FULL FREE Article

Semler MW, Self WH, Wanderer JP, et al. Balanced Crystalloids versus Saline in Critically Ill Adults. N Engl J Med. 2018;378(9):829–839. doi:10.1056/NEJMoa1711584

Link to Abstract


Link to FULL FREE Article

Young PJ. Balanced Crystalloids or 0.9% Saline in Sepsis. Beyond Reasonable Doubt?. Am J Respir Crit Care Med. 2019;200(12):1456–1458. doi:10.1164/rccm.201908-1669ED

Link to Abstract


Link to FULL FREE 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.

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.

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.

Link to Abstract

Link to FULL 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.

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

Link to Abstract

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.

Does using Balanced Crystalloids vs. Saline improve mortality in sepsis?

Balanced Crystalloids Versus Saline in Sepsis: A Secondary Analysis of the SMART Trial

Sometimes we need to make minor adjustments in what we do in the ICU to see a difference. I have been going off for several years now on my instagram account as well as YouTube channel regarding the importance of utilizing balanced crystalloids such as lactated ringers or plasma-lyte and I keep on hearing "there's no mortality benefit". Well, now there's data showing that there is. I knew it was just a matter of time. It just makes sense. This analysis is a piggyback on the SMART trial performed by the good people over at Vanderbilt published last year in the NEJM. In that study and therefore this study, they looked at using saline solution versus either lactated ringers or plasma-lyte. You may be asking yourself "but I thought that study didn't show any mortality benefit". You are correct, it didn't, but that finding was regarding all critically ill patients.

This study looked at 30 day mortality in patients in the MICU who were septic. All in all, they looked at 1641 patients with the diagnosis of sepsis. Note: not necessarily septic shock. 34.1% of patients were on vasopressors and 40% were on the vent.

Here are the outcomes:
30 day mortality: 26.3% in the balanced crystalloids group vs. 31.2% in the saline group (p=0.01)
Patients who received balanced crystalloids had more days free of vasopressors, free of dialysis days, lower plasma lactate concentrations after ICU admission.
Debate settled? Well, no. But check out the article for yourself before taking my opinion as gospel.

-EJ




Link to Abstract

Link to FULL FREE 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.

Balanced Crystalloids Versus Saline in Critically Ill Adults: A Systematic Review and Meta-analysis

Link to Abstract

I honestly wonder how much data is enough data to change some minds. This is why I am counting on you all, people who are trying to keep up with this flurry of data to the best of your ability, to go through medical school, residency, possibly fellowship with a healthy respect for 0.9% saline solution. It may seem like it's hopeless from time to time to change decades worth of practice. Heck, my first IVF resuscitation video is almost 2.5 years old and has almost 39000 views! Hopefully the studies which will be published within the upcoming 2 years will hit the nail on the head. You can see the data from the slides, using saline versus balanced salt solutions increased mortality in the critically ill, increased acute kidney injury, and kept the patients on the ventilator for a longer period of time. To those harping about the increased costs of one fluid versus the next, consider the cost of one ventilator day. Consider the risks involved with each day on the vent. Consider the financial strain from working up every-single-case of AKI. This stuff adds up, colleagues. Anyway. A hat tip to the authors! 

- 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.