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

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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.

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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

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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

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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

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

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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

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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

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

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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

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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

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

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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

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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

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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

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

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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

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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

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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

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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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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

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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

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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

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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

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

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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.

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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

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

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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

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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

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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

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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

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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

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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

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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

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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

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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

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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

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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

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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

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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.

Fluid Resuscitation of Trauma Patients: 0.9%NaCl (saline) or Plasma-lyte?

I am not a trauma surgeon. I am not a trauma physician. I do not take care of trauma patients in my current practice. I did several rotations in the trauma intensive care unit during my fellowship training but by know means am I going to pretend to have the knowledge that my colleagues who do that every day have. The study I am going to be discussing today is a pilot study.

The authors were concerned about the metabolic acidosis that occurs from the elevated chloride concentrations in 0.9% NaCl which is 154mmol/L. Remember, reference values in the lab for chloride levels are between 98 and 109mmol/L. Also, there is data suggesting that an increase in chloride levels by just 5mmol/L could have deleterious effects on our patients. This hyperchloremic metabolic acidosis is not something new, we've known about its effects on the kidneys for decades now. I guess we've just been ignoring it.

I am a fan of whole blood to resuscitate trauma patients, but I my knowledge on the matter is weak. At the time being, patients receive a significant amount of crystalloids for resuscitation. The authors chose to use NS and plasma-lyte due to the fact that lactated ringers is contraindicated with blood products as it allows the blood to coagulate as it goes in due to the calciums effect on citrate.

Surgeons are trained, from my experience, to focus on base excess. When a patient you're taking care of them is sick, and you're giving them a call to give them the heads up of what's going on, one of the first questions you need to be prepared to answer is "what is the base deficit"? Plasma-lyte is a balanced salt solution that I have reviewed numerous times on instagram, my website, and youtube. Plenty of resources out there from me explaining this fluid. This focus on base excess is why they made this

They ended up with 46 patients enrolled in the study.

Plasma-lyte corrected the base deficit faster than 0.9% NaCl. Primary outcome achieved. Patients reached and remained in their normal acid-base physiology longer.

They also found that 0.9% NaCl leads to hyperchloremic metabolic acidosis, decreased serum bicarb levels, and worse base deficit.

Patients also had increased urine output with plasma-lyte compared to saline solution. There is some concern about whether gluconate causes some sort of increased urine production but this is not specified in this paper.

Some institutions worry about the added cost of plasma-lyte, which is approximately $1 on top of the cost of NS or LR depending on the institution and their contract. This study showed that providing plasma-lyte kept serum magnesium levels closer to normal (p=0.007). If you are a bean counter, you could potentially save some money by using plasma-lyte due to less cost of magnesium replacement. I may be stretching a bit but at least I am admitting that I'm stretching. The patients needed about 4gm of Mg in the NS group and no replacement in the PL group. I take back the part of me stretching. The authors state that the difference at their institution of cost between NS and PL is $0.76. 2gm of magnesium is $5.19. That means that PL may end up saving money and additional testing.

All in all, this is a pilot study. I have not personally seen the actual study. If you all have, feel free to correct me. This is not a full free article, unfortunately.

-EJ

Link to Abstract

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.

Diabetic Ketoacidosis: PlasmaLyte vs. 0.9% Sodium Chloride for Resuscitation

Can we start looking at our diabetic ketoacidosis protocols and changing them? This study from 2012 is admittedly small, retrospective, and leaves a lot to be desired. But their findings are significant in my opinion. Usually studies need large sample sizes to prove their endpoints. Here, the endpoints were proved (within their methodology) with this small sample size. The article is not free and I bet that more people would benefit from the knowledge one could gain from it if it wasn't hidden behind the paywall. Grrrrrrr. Here are the benefits of using plasmalyte over saline.
1. the mean arterial pressure was improved in the PL group p less than 0.05
2. there was improved urine output in the PL group in the first 4-6 hours p less than 0.05
3. the patients who received NS had higher potassium levels than the PL group between the 6-12 hour mark. Remember, PL has 5meq/L of K while NS has ZERO. Can we drop this hyperkalemia with LR and PL nonsense already?
They disclose the COST of plasma-lyte in Australia to be $1.94/L vs. $1.17/L of NS. It's not $30 a liter like I've heard in the past. This was in 2012.
Okay, this is a short one. I need to go. My wife wants us to enjoy our Saturday and for me to not be such a nerd reading articles.
BYE!
- EJ



Link to Abstract

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.

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.

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 normal saline for fluid resuscitation in critically ill patients

Link to Article

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.

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

https://journals.lww.com/annalsofsurgery/Abstract/2012/07000/A_Randomized,_Controlled,_Double_Blind_Crossover.5.aspx

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.