#143 NephMadness: Fluid Wars

March 15, 2019 | By Justin Berk

The ultimate showdown between Normal Saline and Lactated Ringers. (Oh hey albumin, didn’t see you over there.)

The battle over the superiority of resuscitation fluids is coming to a boil. Enter the Fluid Wars. Are Lactated Ringers superior to normal saline? Will LR increase a patient’s lactate? What about albumin? The Curbsiders quench the thirst for knowledge by turning to masters Dr. Pascale Khairallah (@Khairallah_P), Dr. Charlie Wray (@WrayCharles) and Dr. Joel Topf (@kidney_boy) for guidance in this special @NephMadness episode that will get your feet wet with the complicated world of fluid resuscitation.

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Credits

Written and produced by: Justin Berk, MD, Pascale Khairallah MD

NephMadness Pun Contest produced by: Hannah R Abrams MS3

Hosts: Matthew Watto MD, Paul Williams MD, Stuart Brigham MD

Edited by: Matthew Watto, MD

Guest:  Pascale Khairallah MD, Charlie Wray DO, Joel Topf MD

Time Stamps

• 00:00 Nephmadness pun contest
• 02:18 Disclaimer
• 02:52 Intro to the show and NephMadness, guest bios
• 08:04 Guest one-liners,
• 10:58 Joel explains NephMadness
• 12:58  Guest book recommendations and career advice
• 17:30 Clinical case; goals of fluid resuscitation; choice of initial IV fluid
• Corporate (TV series) Comedy Central
• 19:41 Complications of normal saline
• 21:29 Colloids versus crystalloids
• LR versus normal saline is not an innocuous decision
• 26:32 Saline versus balance fluids. What’s the makeup?
• 28:19 Does lactated ringers elevate lactate?
• 31:03 Is hyperkalemia a contraindication for LR?
• 32:39 Lactated ringers versus plasma-lyte and cost of fluid
• 34:49 In vitro risks of normal saline
• 40:31 SMART and SALT-ED trial
• 46:08 Stuart finds the IV fluid price list
• 44:37 Each panelist weighs in on saline versus balanced fluids
• 46:45 Why do patients with metabolic alkalosis thrive on saline?
• 49:04 Outro

Fluid Wars Pearls

Colloids and crystalloids are probably equally efficacious for fluid resuscitation.

Colloids are more expensive and may cause more brain injury in trauma patients.

Recent data shows Lactated Ringers (LR) may be superior to Normal Saline (NS) for fluid resuscitation based on SALT-ED and SMART trial data (less MAKE30 aka major adverse kidney events in 30 days).

High chloride content in Normal Saline can cause hyperchloremia. Consequently, the macula densa senses elevated chloride leading to vasoconstriction, which in turn can cause acute kidney injury.

The lactate in lactated ringers is benign (sodium lactate, NOT lactic acid). Checking a lactate for tissue perfusion is a proxy for lactic acidosis. The acidosis is the concern, not the lactate itself.

Patients with cirrhosis cannot metabolize lactate quickly. Thus, LR may cause a benign increase in lactate even if there is good tissue perfusion.

Normal Saline may be indicated in specific situations such as metabolic alkalosis.

LR may be more beneficial than NS in patients with hyperkalemia (even though it has added potassium). [see this post by PulmCrit for evidence review]

Fluid Wars – In-depth Show Notes

Definitions

Crystalloid: “Electrolytes mixed with water.” This can include Normal Saline or “Balanced Fluids.”

Normal Saline: Salt and Water: 0.9% Saline = 9g Sodium and Chloride in 1L of water.

Balanced Fluids: Solutions that contain more electrolytes to better simulate plasma; they contain potassium, calcium, magnesium, and buffer (e.g. lactate, acetate). Examples include Lactated Ringers, PlasmaLyte, Hartmann’s solution.

Colloid: Colloid fluids contain a greater osmolar load including albumin, Hetastarch (synthetic albumin), or blood products.

Fluid Resuscitation: LR vs. NS

Goal of Fluid Resuscitation

• The goal of resuscitation is to replenish bodily fluid that has been lost and restore tissue perfusion.
• Tissue perfusion can be measured through several ways
• The decision seems to be benign as any complication is relatively rare. (@kidney_boy expert opinion)

The Evidence behind Colloids

In 1998, a Cochrane Systematic Review showed increased mortality with albumin compared to normal saline.

The SAFE Trial

A large (7,000 patients) follow-up study (SAFE trial) in 2004, showed NO change in mortality between albumin and crystalloid. However, in sub-group analysis:

Trauma patients

Trauma patients (and traumatic brain injuries) had increased risk of death and associated brain injury with albumin use in the SAFE trial.

Septic patients

Septic patients showed possible benefit with albumin in the SAFE trial. BUT, a follow-up study for albumin in sepsis (ALBIOS Trial) showed albumin was confirmed to NOT be associated with improved mortality in septic patients

Cochrane Review of colloids

A Cochrane review states: “using colloids…for fluid replacement probably makes little or no difference to the number of critically ill people who die.”

• Colloid remains more expensive despite lack of advantage

Hetastarch

Hetastarch (hydroxylethyl starch; synthetic albumin) was an attempt to have colloid fluids without the extra cost. Unfortunately, it’s been associated with increased bleeding and acute kidney injury

Comparing Normal Saline to Balanced Solutions

• There has been prospective data suggestive of damage from NS
• Though the SPLIT Trial did not show increase in AKI from NS, new trial data suggests balanced solutions may have improved outcomes

Fluid Wars: the SMART and SALT-ED trials

These trials used a composite outcome not used before: MAKE-30 aka Major Adverse Kidney Events in 30 days (death, RRT, persistent renal dysfunction at discharge).

• SALT-ED (in ED): 4.7% (LR) vs 5.6% (NS)
• SMART (in ICU): 14.3% (LR) vs. 15.4% (NS)
• Calculated NNT is 100 in the composite end-point of major adverse kidney events
• New trials to come including:  The Plasma-Lyte 148 Versus Saline (PLUS) study, The Balanced Solution versus Saline in Intensive Care Study (BaSICS) study, the Plasmalyte Versus Saline in Trauma Patients (ASTRAU)

Why Normal Saline May Cause Harm

Normal saline can lead to:

• A non-anion gap hyperchloremic metabolic acidosis which may cause worsening inflammation and coagulopathy
• Hyperchloremia: The macula densa (in distal tubule) senses chloride (elevated chloride concentration in NS solution) → stimulates  release of vasoconstrictors → constriction of afferent arteriole → decrease glomerular filtration rate → acute kidney injury. Check out this Image from PulmCrit article.
• Thromboxane and angiontension released in response which also worsens vasoconstriction.
• Macula densa: If it detects increased chloride it suggests a failure of electrolyte reabsorption and the solution to this issue: it will shut down the glomeruli.

Addressing Concerns with Lactated Ringers

Will Lactate Ringers elevated the lactate level in critically ill patients?

In patients with sepsis, anaerobic glycolysis will cause an increase of lactic acid.

Lactic acid = Lactate plus a Hydrogen Ion.

The hydrogen ion causes all the complications (ie the acidosis). The lactate is just the accompanying ion and is benign. Lactated ringers is Sodium Lactate and does not not contain the H+.

Kashlak Pearl: Patients with cirrhosis cannot convert lactate quickly (60% of lactate metabolism is in the liver). Thus, Lactate may go up in patients with liver disease receiving LR. BUT, this is not a sign of poor tissue perfusion. It simply reflects the slow metabolism of the benign lactate in LR. In summary, patients with a sick liver receiving LR might have a benign lactate elevation. This is not the same as lactic acidosis.

Specific Indications of Normal Saline

Metabolic alkalosis (e.g. after significant vomiting or overdiuresis):

These patients need chloride.

• Chloride depletion is driving the metabolic alkalosis.
• Give Normal Saline (or potassium chloride) to correct metabolic alkalosis.

Is Hyperkalemia a contraindication to LR?

Why give more K to a patient with elevated potassium?

• A couple of studies suggest that the metabolic acidosis from NS causes an transcellular shift. Thus, More hyperkalemia with NS than balanced solutions. Though beware: these studies only performed in kidney transplant patients.
• See discussion at NephMadness. (And learn more about Hyperkalemia from a previous episode).
• Also check out discussion over at PulmCrit.

Goals and Learning Objectives

Goal

Listeners will recognize the key differences among fluid resuscitation options and be familiar with recent data that guides these decisions.

Learning objectives

After listening to this episode listeners will…

1. Identify common fluid resuscitation terms: crystalloid, colloid, lactated ringers, normal saline, PlasmaLyte, Hartmann’s solution, albumin
2. Recognize the potential harms of hyperchloremic non-anion gap metabolic acidosis from saline resuscitation
3. Identify the possible mechanisms of injury from normal saline resuscitation
4. Describe the recent literature and trial data comparing LR vs. NS in the ED and ICU setting.
5. Address the fears of LR complications, particularly hyperkalemia and lactic acidosis.
6. Identify specific clinical situations where NS may be more beneficial.

Disclosures

The authors report no relevant financial disclosures. The Curbsiders report no relevant financial disclosures.

Links from the show

1. NephMadness
2. Twitter
3. AJKD Editorial Internship
4. Book recommendation: Ending Medical Reversal
5. TV Series: Corporate
6. The Expanse
7. Initial 1998 Cochrane Systematic Review on colloids vs. crystalloid (suggesting a mortality difference)
8. SAFE trial (NEJM 2004) showing no difference in mortality
9. Post-Hoc SAFE Trial analysis (NEJM 2007) showing increased mortality with albumin in traumatic brain injuries
10. ALBIOS Trial showing albumin not associated with decreased mortality in septic patients
11. Updated 2018 Cochrane review on colloids vs crystalloids
12. Hetastarch associated with increased bleeding and acute kidney injury (JAMA 2013)
13. Yunus et al. JAMA 2012 – Initial data of possible harm from chloride from NS
14. SPLIT Trial – No AKI in NS vs. LR
15. SALT-ED Trial (Emergency Department: LR vs NS)
16. SMART Trial (Intensive Care Unit: LR vs NS)
17. NS increasing inflammation reference (Kellum et al. Chest 2006)
18. Editor Rec: PulmCrit discussion on hyperchloremic acidosis and hyperkalemia