Dr. Paul S. Anderson
Scientific papers published in 2013 [1] and then a scientific review article {2] reporting on a 2018 paper [3] all discussed and highlighted the differences between the use of 0.9% Normal Saline (NS) and Lactated Ringers Solution (LR) and health outcomes associated with the use of one versus another. The headlines make the difference look fairly shocking and imply that there is danger in the use of NS verses the use of LR.
The first paper from 2013 [1] was done in pigs in an attempt to imitate battlefield shock conditions. They created hemorrhage in the pigs and then fluid replaced with either NS or LR and looked at their physiological response. The conclusions drawn were that “total peripheral resistance was decreased with NS and LR, with a larger drop shown in NS. Serum potassium was increased with NS, but not affected with LR. Coagulation changes were similar between LR and NS.”
Then the 2018 paper looking at a large sample of critically ill hospitalized patients [3] and subsequent review article [2] created a public (or at least medical professional) surge in interest around the topic and as is usual some confusion. So, what should we do with this information? Ignore it, change all our IV’s to LR or something else? It has been proposed that the focus on critical care and shock trauma may cause us to ignore these data in regard to outpatient infusion medicine. In one sense this idea is reasonable as very little of the data truly relate to outpatient hydration or micronutrient therapies provided by intravenous means. The patient health, administration times and volumes are not analogous. That said, it does illustrate a concept elucidated through intravenous therapy research which does apply to outpatient hydration or micronutrient intravenous therapies.
What research then does relate and how does it connect this “NS and LR” data to outpatient intravenous therapy? The data which does connect the topics came from the oncology research funded by the US National Institutes of Health (NIH). In this research there was a subset of patient care utilizing intravenous therapies and a human intervention regarding biochemical changes before and after intravenous therapies undertaken as part of the research. The data which came from this research showed that some intravenous therapies (especially high dose ascorbic acid) do shift electrolytes and can be formulated either to aggravate or minimize electrolyte shifts. [4]
So what did this NIH research show us that relates to outpatient intravenous therapy and patient safety? The bottom line (that relates to the other studies mentioned above and LR versus NS) is that in the majority of outpatient intravenous micronutrient therapies shift sodium levels in the patient (due to sodium based buffers, typically low chloride additives and other factors) which then put a transient strain on the renal tubular system. One core genesis of this is the fact that these higher sodium and lower chloride infusions inadvertently trigger increased chloride decrease based on renal sodium tubular transporters mainly being yoked with chloride (so extra sodium being pumped out “drags” extra chloride out into the urine. This creates transient kidney stress and an increased sodium to chloride ratio. What does this do? It creates higher excitable tissue reactivity and while the transient kidney stress progresses the heart and other muscles, smooth muscle sites and brain / nervous system are hyperexcitable.
All of this has the net effect of requiring a more balanced intravenous solution to minimize these and other electrolyte shifts to lower the transient kidney stress and the excitable tissue activation. How then is this accomplished? A few basic, but critical, factors can be considered and implemented to achieve this goal of “balance”. The critical factors (some of which are mirrored in the NS versus LR data mentioned) include osmolarity, sodium load, chloride levels and various other effectors of electrolytes such as calcium, magnesium and potassium. Before describing how this affects outpatient intravenous micronutrient therapy it should be noted that the above critical factors are addressed best by the use of LR as opposed to NS. This however does not mean that in intravenous micronutrient therapy either NS or LR are neither better than one another nor desired for use as base solutions. In the three sections below I will use the most common data and clinical outcomes derived from the NIH and later work to illustrate this balance.
A. High Dose Intravenous Vitamin C (HDIVC) and Electrolyte Shifts
In the previously mentioned research [4] it was shown that the infusion of HDIVC shifted the chemistry of the blood, and created transient stress on the kidneys, by altering the primary factors of balance. Those factors altered included osmolarity, sodium load and chloride shifts. In the specific case of HDIVC calcium, magnesium and potassium were also affected. Using blood draws before and after multiple iterations of intravenous HDIVC we proved that by shifting the intravenous HDIVC formula we could create an almost completely stable electrolyte chemistry before and after the HDIVC even with the high osmolarity and all the potential for electrolyte shifts. While the data can be viewed at the reference below the basic successful intervention involved adding potassium, magnesium and calcium in their chloride salt forms in particular doses and ratios. This allowed for the electrolyte stability and decreased the sodium to chloride ratio.
B. Atrial Fibrillation (A Fib) and Intravenous Formulas
I have had many A Fib patients “convert” to normal sinus rhythm during and after IV with balanced (and most importantly chloride salt forms) of magnesium, calcium and potassium in a base solution with Taurine. They usually never “convert” permanently however unless you catch them early in their A Fib. But the IV if balanced properly can help a great deal, even eliminating A Fib for a time. Obviously for A Fib all underlying issues (including hormonal, toxic, allergic etc.) must be tracked down and eliminated. From all the A Fib patients I’ve given IV to I’d never use just magnesium as some advocate as the need to calm the excitable membrane activity involves all the above mentioned factors. How does this relate to intravenous fluid or formula “balance”? In the case of A Fib or any other excitable membrane issue as a trial you can take the 25 gram HDIVC formula from the research [4], DROP the ascorbate to 10 grams, add 500 mg Taurine and 1-2 mL B-100 complex. If they tolerate that and then raise the mineral levels each IV (use the 50 and 75 gram HDIVC formulas as basis for mineral dose and balance but drop the ascorbate to 10 grams as above and increase the taurine to 1 gram minimum). I have used this format in cases of A Fib, anxiety, muscle spasm and many other excitable membrane issues with success. What does this formula have to do with the NS versus LR data? Basically this formula takes the benefits of LR over NS to the next and more therapeutic level.
C. Magnesium “Sensitivity”
Sensitivity to oral or intravenous magnesium (Mg) is actually not totally uncommon in chronic fatigue, fibromyalgia, dysrhythmia and other depleted or chronically ill patients. It seems (based on patient responses to treatment) to generate from many places. Aggravation of heart rhythm is well documented in IV magnesium therapy for MI for example (an extreme example) and that aggravation has multiple separate causes. I have found those causes give insight into ‘magnesium sensitivity’ in cases I have seen.
These causes most commonly include:
- Taurine deficiency / insufficiency or aberrant taurine metabolism
- Potassium (K) and or Calcium (Ca) imbalance (including GLUT receptor issues which affect potassium movement) or metabolic “Ca or K” derangement
- Vitamin B6 insufficiency or metabolic derangement
- And occasionally GI dysbiosis / infection / biofilms and other factors
Of course looking at levels of Na / Ca / K / Cl in the serum is first priority. Any of these minerals at either the high or low end of normal, or frankly high or low, will cause abnormal response to magnesium, and when the cause of the imbalance is found and treated (if possible) the sensitivity goes away.
Next is looking at red blood cell magnesium (RBC Mg) and GGTP as they can show the relationship of magnesium to cell uptake and glutathione activity. Glutathione (GSH) cellular levels and magnesium are directly related to one another and an aggravation in one aggravates the other. People with low or high levels often are intolerant of Mg until the GSH and Mg levels normalize. In those cases (common in the chronically ill) a broader GSH improvement protocol including all the GSH uptake support except Mg is required. This includes precursors for GSH (unless glutathione synthetase (GSS) SNPs are present in which case glutathione is required) and or IV and Liposomal GSH with the main cofactors for uptake and cycling of GSH (B2, 3, 5, ASC, Zn, Se) [5]. As GSH cellular levels and activity rise so does acceptance of Mg and the sensitivity decreases or stops.
SNP aggravations can work their way in but in my experience are secondary and aggravations rather than causes. These can be multiple methyl cycle SNPs affecting the GI turnover rate and GI immunity and hence Mg absorption. They also seem to be those associated with poor use of vitamin B6 of which there are many SNPs.
In some a trial of IV Mg can show if it is a GI absorption or dysbiotic response. If IV is no problem then it is almost certainly a GI cause.
In a lot of cases using an IV intervention we saw those with dysrhythmia or other reactions to magnesium have absolutely no reaction when we would infuse taurine and or B6 prior to the Mg (depending on the cause). In my experience taurine and B6 issues are far more common than the others. Taurine is the master cell membrane osmolyte and even minor insufficiency causes slower uptake of Mg / K and appropriate movement of Na and Ca as well. Adding to this osmolyte activity B6 and taurine have reciprocal deficiency and loss of one can diminish the other. Additionally magnesium in non-excitable cell activity (i.e. as an enzymatic cofactor) almost always uses B6 as its organic cofactor portion.
In most people if the Ca/K/Na isn’t the problem, and there is no severe RBC Mg/GGT issue then it is Taurine / B6. In those cases I have given Taurine PO 2-6 grams a day then after a few weeks added mixed trace elements without Mg with the P5P. In IV formulas we will use 200 – 500 mg taurine per bag. Then in 2-3 months try Mg again. Most times it works and the sensitivity goes away.
The above are based on a lot of patient responses matched with our understanding of biology of magnesium (as opposed to theory). Those noted above are most likely causes in my clinical interactions and experience.
Summary:
While the very “exciting” news of a study showing less renal trouble and all cause death in critically ill hospitalized patients makes us believe the issue is “NS versus LR” the real gem in this information (controversy) is that it underscores what my research and teaching has been increasingly focusing on since 2010. Balance of intravenous formulations in regard to mineral / electrolyte content is by far the most critical factor we can consider in making intravenous nutrient therapies safe and effective in outpatient practice. And these factors affecting electrolyte physiology and balance post infusion are actually much more important than osmolarity or any other factor (except solution pH potentially). Yes, in cases where hospital policy dictate NS or LR in the critical care setting, this data is extremely helpful. But beyond that (and I am sure without intending to do so) the concepts of controlling sodium load, balancing chloride salts and attending to specific patient reactions to minerals are confirmed by this data as well.
References
- Martini WZ, Cortez DS, Dubick MA. Comparisons of normal saline and lactated Ringer’s resuscitation on hemodynamics, metabolic responses, and coagulation in pigs after severe hemorrhagic shock. Scandinavian Journal of Trauma, Resuscitation and Emergency Medicine. 2013;21:86. doi:10.1186/1757-7241-21-86.
- Salynn Boyles, Contributing Writer: Balanced IV Fluids Seem to be Safer than Saline in ICU Giving balanced crystalloids led to a lower rate of composite outcome of death from any cause. Meeting Coverage > SCCM February 27, 2018 https://www.medpagetoday.com/meetingcoverage/sccm/71414
- Self WH, Semler MW et al. Balanced Crystalloids versus Saline in Noncritically Ill Adults. March 1, 2018. N Engl J Med 2018; 378:819-828. DOI: 10.1056/NEJMoa1711586
- Anderson PS. IV ASCORBATE FORMULAS AND ELECTROLYTE RESEARCH. https://www.academia.edu/13255726/IV_Ascorbate_and_Electrolytes [Original reference: Anderson P., Naydis E., Standish L. (2011, November). High Dose IV Ascorbic Acid Therapy: the Bastyr Experience. Poster session presented at the Society for Integrative Oncology, Cleveland, OH.]
- Anderson PS. GLUTATHIONE AUGMENTATION https://www.academia.edu/21925456/Glutathione_Augmentation_in_a_nerve_injury_model