Turning of the Tides: An Evidence-Based Approach to IV Fluid Selection in the ED
September 2024
Author: Dr. Justine Sweeney, MD PGY2
Peer Reviewer: Dr. Reena Sheth, MD PGY4
Faculty Editor: Dr. Trudi Cloyd, MD, MS, Assistant Professor of Emergency Medicine at Columbia University Irving Medical Center
The authors of this article have no financial or industry relationships to disclose.
There are a number of reasons to administer fluids in the ED: dehydration, electrolyte derangements, hypotension, metabolic abnormalities, and the list goes on.
Like all other topics in medicine, there are trends and phases. It can be challenging to keep up with all the new changes and literature, but hopefully this post will help simplify your approach. Think about IV fluid administration as an opportunity to have an overall positive influence on physiology by both correcting and preventing metabolic derangements.
Normal Saline vs Lactated Ringers
The two most common IV fluids used in most EDs for resuscitation are normal saline (NS) and Lactated Ringer’s (LR). Both NS and LR are considered isotonic fluids, but they do differ from plasma itself in several important ways.
NS is a hyperchloremic fluid that is slightly hypertonic and hypernatremic to plasma, but contains no potassium. The excess chloride depletes bicarbonate, causing a hyperchloremic metabolic acidosis in large volumes. LR, on the other hand, is slightly hypotonic to plasma. It has slightly less sodium and chloride than plasma and contains a small amount of potassium that resembles the potassium concentration of most normokalemic patients.[1,2]
Figure 1. Composition of intravenous fluid types [3].
So how do we choose the optimal IV fluid for each patient? Let’s take a look at what the data says…
The Saline Against Lactated Ringer’s or Plasma-Lyte in the ED (SALT-ED) Trial found that use of balanced crystalloids (95% of them being LR), in contrast to NS, reduced renal-related morbidity in non-critically ill patients, without any significant increase in adverse effects. Patients with pre-existing renal disease, significant AKI, or hyperchloremia benefitted the most from balanced crystalloids.[4] The Isotonic Solutions and Major Adverse Renal Events Trial (SMART) Trial aimed to investigate similar outcomes, but in critically ill ICU-level patients. It found that use of balanced crystalloids like LR, when compared to NS, was associated with lower rates of renal-related morbidity, new need for hemodialysis, and death. Septic patients benefited the most from LR when compared to the NS group.[5] Additionally, there is a plethora of studies demonstrating an association between NS administration and various adverse effects including metabolic acidosis, electrolyte derangements, higher rates of AKI and other renal complications, poorer clinical outcomes in sepsis, and prolonged hypotension.[6-14]
This is not to say that there is never a role for NS. Realistically, the majority of relatively healthy ED patients likely will not experience any significant physiologic difference whether they receive LR or NS, especially in smaller quantities. NS has also been shown to be non-inferior in some studies [15-16]. But if we look at the totality of existing literature, there appear to be few pathologies in which NS definitively confers a more favorable metabolic shift than LR. Rather than thinking about “when should I use LR?”, it may be simpler to remember when NOT to use LR:
Head Trauma:
NS is safer if there is any concern for neurotrauma and/or possibly impending herniation. Because NS is slightly hypertonic compared to plasma, it draws fluid and pressure out of the brain, lowering ICP.[1]Metformin-associated metabolic acidosis (MALA):
Fluid choice is difficult in MALA, as both NS and LR can be suboptimal. LR typically acts as a natural buffer by metabolizing to bicarbonate. Because this process is impaired in the setting of MALA, you are unable to take advantage of the main benefit of LR. Administration of LR may also slightly increase the actual quantitative lactate value itself, but because the lactate in LR is sodium lactate (NOT lactic acid), it won’t actually contribute to acidemia.[17] Still, LR may not be the best choice in these patients as you lose out on one of the main benefits of LR, and it makes trending lactate levels more difficult. Alternatively, NS in high quantities can exacerbate the acidosis, as we discussed earlier. In this case, we suggest tThe optimal fluid in this scenario may be 5% dextrose in 0.45% or 0.9% NS.[1]Severe hypercalcemia:
LR contains a small amount of calcium, while Plasma-Lyte contains none. Because the calcium concentration in LR is lower than the calcium concentration of human blood, LR will not necessarily worsen hypercalcemia. Still, Plasma-Lyte is the better choice in severe hypercalcemia as it will help lower calcium levels faster than LR.[1]Liver Failure:
We need adequate liver function in order to metabolize the sodium lactate found in LR, so hypovolemic liver patients who need IV fluids would benefit more from a colloid solution like albumin than LR.[1]
Now let’s go over some common scenarios you’ll encounter in the ED to guide your selection of IV fluids:
Diabetic Ketoacidosis (DKA) is a high anion gap metabolic acidosis. LR is preferred in DKA because its metabolism converts hydrogen ions to bicarbonate, which acts as a buffer to improve acidemia. On the contrary, NS causes an iatrogenic metabolic acidosis, which would be detrimental in an already acidemic patient.[18-19] Not only does this make logical sense, but LR was shown to close the anion gap in DKA patients significantly faster in a large subgroup analysis of DKA patients.[20]
Hyperkalemic patients experience faster improvement with LR administration.[21] Alkalinization promotes movement of potassium intracellularly, which brings down the serum potassium concentration. Avoid NS as it will promote acidemia and prolong the hyperkalemic state. You can also consider adding bicarbonate for the severely acidemic (pH <7.2) and hyperkalemic patients, which was demonstrated in the BICAR-ICU trial (more on that later).
A common misunderstanding is that we should avoid giving LR to hyperkalemic patients because LR contains 4 mmol of potassium, while NS contains none. While this is a good thought, it doesn’t translate to meaningful physiologic changes. Those 4 mmol of potassium is still a much lower potassium concentration than that of plasma. Instead, we SHOULD give LR to hyperkalemic patients because they will benefit from its acid-base effects of driving potassium into cells and out of serum.[21] This idea was summed up well in the SMART trial: “...the acid-base effects of isotonic crystalloids are more important for potassium homeostasis than the relatively small amount of potassium…”[5].
In Chronic Kidney Disease (CKD), you’ll want to avoid NS because the high chloride concentration can lead to renal vasoconstriction. This can cause a pre-renal AKI and metabolic acidosis.[2,4-5] Many CKD patients also struggle with hyperkalemia, for which LR is also the preferred fluid as discussed above.
Our understanding and management of Sickle Cell Disease has changed significantly over the last decade. Newer data shows that gentle resuscitation, as opposed to aggressive administration of fluids, leads to better patient-centered outcomes and to decreased complications such as acute chest syndrome, AKI, and hypoxia. A recent meta-analysis showed poorer outcomes with NS (versus LR); it’s suspected that the slight hypertonicity and potential to cause metabolic acidosis worsen sickling and vaso-occlusive crises. Emerging data suggests hypotonic fluids, such as maintenance rate 5% dextrose in 0.45% NS may be even better than LR, but larger scale studies are needed.[22]
pH-Guided Resuscitation
This is the idea of killing two birds with one stone: volume resuscitating while we correct metabolic derangements. There is a finite amount of time to manipulate acid/base status with fluids before the patient is adequately volume-resuscitated, at which point more fluids would risk overload. Before this happens, consider intentionally acidifying or alkalizing a patient to improve their overall clinical status.
The BICAR-ICU trial included very sick patients who were either severely acidotic or had a high SOFA (total Sequential Organ Failure Assessment) score. Sodium bicarbonate therapy (versus no infusion) improved survival in patients with severe metabolic acidemia and AKI. It also reduced their need or urgency for dialysis. Finally, the bicarb group had significant improvement in hyperkalemia.[23]
Figure 2. pH-Guided Resuscitation. [1]
Indications for Isotonic Bicarbonate Administration:
Uremic metabolic acidosis is probably the most common example of how pH-guided resuscitation can be helpful in the ED. Patients with uremic acidosis had the greatest reduction in mortality and dialysis avoidance in the BICAR-ICU trial. These patients often have oliguria and may not be able to tolerate large volumes of IV fluid. Consequently, if you are treating a patient with uremic metabolic acidosis, remember to give bicarbonate early before risking fluid overload.[23]
Note that uremic acidosis is the only instance in which you purposely alkalinize for high anion gap metabolic acidosis (HAGMA). Avoid using sodium bicarbonate in most cases of HAGMA, like lactic acidosis and ketoacidosis. In these cases, it is more important to treat their underlying pathology.[1]
Other patients that would benefit from deliberate alkalinization include those with non-anion gap metabolic acidosis (NAGMA). Patients often develop NAGMA by losing bicarbonate into the urine or stool (e.g. diarrhea, renal tubular acidosis, and certain diuretics). Patients with normal kidneys will eventually re-generate bicarbonate, but critically ill patients with severe acidosis or patients with renal insufficiency cannot compensate quickly enough. In these cases, administration of bicarbonate helps replace their deficit and improve their acidemia.[1,4-5]
Indications for Normal Saline Administration Using pH-Guided Resuscitation:
Patients with acute metabolic alkalosis can also benefit from pH-guided resuscitation. This is a state usually caused by toxic ingestion, large volume diuresis (e.g. contraction alkalosis), or gastric losses (e.g. vomiting, continuous NG suction). In these cases, the goal is to acidify the patient with normal saline. Remember: Do not correct chronic metabolic alkalosis as this would interfere with the patients’ compensatory mechanisms.[1]
Conclusions
Hopefully this discussion encourages you to be intentional and smart about fluid choice, just as you would be when choosing antibiotics or any other medication.
Summary:
Consider using LR as your go-to IV fluid choice in most patients, unless you have a good reason to use an alternative like Normal Saline or Plasma-Lyte.
Keep in mind the relative contraindications to LR: head trauma, MALA, severe hypercalcemia, and acute liver failure.
Bicarbonate can be an excellent adjunct for severely hyperkalemic patients with poor renal function and/or severely acidotic patients (pH <7.2 in the setting of HAGMA secondary to uremia or NAGMA secondary to bicarbonate losses).
References
1. Farkas A. Fluid selection & pH-guided fluid resuscitation. EMCrit Project. EMCrit Project. https://emcrit.org/ibcc/fluid/. Published June 27, 2019.
2. Myburgh JA, Mythen MG. Resuscitation fluids. N Engl J Med. 2013;369(13):1243-1251.
3. Avigan Z, Farouk S, Sparks M, William J, Trivedi SP. What’s in a fluid? Fluids: 5 Pearls Segment. Core IM Podcast. Published April 27, 2022. Accessed June 10, 2024. https://www.coreimpodcast.com/2022/04/27/fluids-colloids-5-pearls-segment/.
4. 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.
5. 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.
6. de-Madaria E, Herrera-Marante I, González-Camacho V, et al. Fluid resuscitation with lactated Ringer's solution vs normal saline in acute pancreatitis: A triple-blind, randomized, controlled trial. United European Gastroenterol J. 2018;6(1):63-72.
7. 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.
8. Modi MP, Vora KS, Parikh GP, Shah VR. 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;23(1):135-137.
9. Ocskay K, Mátrai P, Hegyi P, Párniczky A. Lactated Ringer's Solution Reduces Severity, Mortality, Systemic and Local Complications in Acute Pancreatitis: A Systematic Review and Meta-Analysis. Biomedicines. 2023;11(2):321.
10. Pfortmueller CA, Funk GC, Reiterer C, et al. Normal saline versus a balanced crystalloid for goal-directed perioperative fluid therapy in major abdominal surgery: a double-blind randomised controlled study. Br J Anaesth. 2018;120(2):274-283.
11. Weinberg L, Harris L, Bellomo R, et al. Effects of intraoperative and early postoperative normal saline or Plasma-Lyte 148® on hyperkalaemia in deceased donor renal transplantation: a double-blind randomized trial. Br J Anaesth. 2017;119(4):606-615.
12. Wu BU, Hwang JQ, Gardner TH, et al. Lactated Ringer's solution reduces systemic inflammation compared with saline in patients with acute pancreatitis. Clin Gastroenterol Hepatol. 2011;9(8):710-717.e1.
13. Hammond NE, Zampieri FG, Di Tanna GL, et al. Balanced crystalloids versus saline in critically ill adults — a systematic review with meta-analysis. NEJM. 2018;1(2).
14. 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.
15. Dong WH, Yan WQ, Song X, Zhou WQ, Chen Z. Fluid resuscitation with balanced crystalloids versus normal saline in critically ill patients: a systematic review and meta-analysis. Scand J Trauma Resusc Emerg Med. 2022;30(1):28.
16. 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. JAMA. 2015;314(16):1701–1710.
17. Zitek T, Skaggs ZD, Rahbar A, Patel J, Khan M. Does Intravenous Lactated Ringer's Solution Raise Serum Lactate? J Emerg Med. 2018 Sep;55(3):313-318.
18. Chua HR, Venkatesh B, Stachowski E, et al. Plasma-Lyte 148 vs 0.9% saline for fluid resuscitation in diabetic ketoacidosis. J Crit Care. 2012;27(2):138-145.
19. 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.
20. Self WH, Evans CS, Jenkins CA, et al. Clinical Effects of Balanced Crystalloids vs Saline in Adults With Diabetic Ketoacidosis: A Subgroup Analysis of Cluster Randomized Clinical Trials. JAMA Netw Open. 2020;3(11):e2024596.
21. O'Malley CM, Frumento RJ, Hardy MA, Benvenisty AI, Brentjens TE, Mercer JS, Bennett-Guerrero E. A randomized, double-blind comparison of lactated Ringer's solution and 0.9% NaCl during renal transplantation. Anesth. Analg. 2005 May;100(5):1518-24.
22. Ojo AS, Ojukwu S, Asmare W, Odipe O, Larbi D. Intravenous Fluid Administration and the Risk of Adverse Outcomes in Sickle Cell Disease Patients Hospitalized for Vaso-Occlusive Crisis. J Hematol. 2022;11(5):159-166.
23. Jaber S, et al. Sodium bicarbonate therapy for patients with severe metabolic acidaemia in the intensive care unit (BICAR-ICU): a multicentre, open-label, randomised controlled, phase 3 trial. The Lancet 392, 31 - 40 (2018).
