Ringer's Lactate

Mechanism of Action

Understanding the metabolism of lactate and briefly reviewing its biochemistry and physiology is important to recognize the specific benefits of Ringer’s lactate utilization. Lactate is the compensatory base of lactic acid. Under aerobic physiologic conditions, the metabolism of glucose leads to the production of pyruvate into cellular respiration. However, there is always a small state of anaerobic metabolism taking place at any given time, causing pyruvate to undergo an oxidation-reduction reaction with NADH which leads to oxidation of NADH to NAD+ and the formation of lactate via the enzyme lactate dehydrogenase (LDH). This reaction maintains NAD+ levels, even in anaerobic metabolism, to allow further glycolysis to occur in the absence of oxygen. Normally, through cellular respiration, there is always a balanced ratio of NADH/NAD+ with the transfer of protons and electrons to finally make ATP, water (H2O), and carbon dioxide (CO2) as the final products. If this aerobic system shuts down, the protons have nowhere to go. Lactate is formed and shuttled out of the cells to keep the NADH/NAD+ ratio constant. The increased production of lactate, in turn, acts as a buffer system as it takes up the H+ forming lactic acid. Furthermore, lactate can be metabolized back into pyruvate via LDH and cellular respiration, forming CO2 and H2O. This CO2 and H2O form carbonic acid (H2CO3) via carbonic anhydrase, rapidly dissociating to form HCO3. Lactate can be metabolized to form bicarbonate.[2]

Administering a liter of Ringer’s lactate does two important things:

1. Volume resuscitation: In that intravascular volume expands, increasing preload and thus, perfusion 
2. Provides the body with sodium lactate: Sodium lactate is a bioenergetic fuel that the human body is designed to metabolize under ischemic conditions, thus decreasing cellular death from ischemia.[3]

Volume kinetics is a complex topic but can be simplified with the following fluid characteristics: osmolarity and tonicity. By way of review, the intracellular fluid compartment is about 67% of total body water, while the extracellular fluid compartment is about 33%. The extracellular fluid compartment can further be broken down into the interstitial fluid, approximately 75% to 80% of the extracellular compartment, and intravascular, approximately 20% to 25% of the extracellular compartment. Osmolarity among all fluid compartments at any given time will remain equal or actively equalizing, as water-free flows between all compartments. Tonicity is a measure of the osmotic (water) gradient between 2 fluids across a semipermeable membrane and is a relative concept between these two fluids. When describing a fluid in terms of tonicity, in other words, hypotonic, isotonic, or hypertonic, tonicity refers to the osmotic gradient between the intracellular and extracellular compartments. Thus, isotonic fluid is given intravenously (IV) does not move across into the intracellular compartment but does distribute across the entire extracellular compartment (interstitial and intravascular), usually proportionally to the compartment volumes (interstitial 75% to 80%, intravascular 20% to 25%).

Administration

Ringer’s lactate is administered most commonly via IV route but may also be safely administered intraosseously. The goal of administering Ringer's lactate is to replenish the intravascular volume to permit adequate organ perfusion.[4]

Adverse Effects

There is a fear of Ringer’s lactate causing hyperkalemia and worsening lactic acidosis.  To put it in perspective, Ringer’s lactate does include a concentration of potassium 4 mEq/L. Logically, giving a hyperkalemic patient additional potassium would worsen hyperkalemia; however, this is not the case. A patient's potassium volume of distribution is larger than the extracellular compartment and equilibrates between the intracellular and extracellular compartments. Therefore, giving a patient, even a patient with renal failure, 4 mEq/L of potassium is not an additive effect.[5] In fact, giving Ringer’s lactate to a patient with hyperkalemia will trend the patient’s potassium level to 4 mEq/L.[6][7] Furthermore, patients' hyperkalemia may worsen with metabolic acidosis. Consequently, large-volume IV administration of normal saline may give patients a hyperchloremic non-anion gap metabolic acidosis. Ringer’s lactate does not have this effect.

Ringer’s lactate is often avoided in septic patients secondary to the fear of worsening lactic acidosis. This is also untrue, as the content of Ringer’s lactate is sodium lactate, not lactic acid. Administration of Ringer’s lactate will cause an excess of lactate, which will be utilized by the body for energy. However, in today’s practicing culture, there tends to be an emphasis on blood lactate levels.[3] This emphasis can lead to confusion in the interpretation of lactic acid levels. The adverse effect of worsening lactic acid is not seen with Ringer’s lactate.

Ringer’s lactate also has a calcium concentration which prohibits its use as a diluent for blood transfusions. Some blood products use citrate as an anticoagulant and, when mixed with calcium, leads to the precipitation of calcium citrate, which may cause clotting and obstruction of the IV line. Patients can receive blood products and Ringer’s lactate simultaneously; however, not within the same line.

As with any IV fluid administration, there is a possibility of swelling and edema. At-risk patients are those with congestive heart failure, chronic kidney disease, liver cirrhosis, and hypoalbuminemia. These patients must be monitored during IV administration with serial physical exams to determine if they are becoming clinically hypervolemic.

Further adverse effects may include allergic reactions ranging from mild local redness and itching to generalized symptoms, local infection, redness, and even regional cellulitis, which can progress to systemic infection if not intervened. Many of these symptoms may be secondary to the actual intravenous site access rather than the contents of Ringer’s lactate itself. Allergic reactions are more common with adhesive dressings to secure IV access rather than the contents of Ringer’s lactate itself. IV infiltration is also a possibility, which can cause localized swelling, redness, and pain and ultimately is treated with conservative management and replacement of the IV access. Infection therapy can include local to systemic antibiotic therapy, depending on the severity.

Contraindications

Not an absolute contraindication, but more of a consideration, is the administration of Ringer’s lactate in patients with liver dysfunction. Most of the lactate is metabolized in the liver, and any hepatic dysfunction will result in an accumulation of lactate. This can confuse the interpretation of lactate levels.

In the acute setting, patients with cerebral edema requiring osmotic therapy should avoid all hypotonic or isotonic fluid, including Ringer’s lactate.  The goal of therapy is to draw out free water from brain parenchyma using hypertonic fluid administration. Although studies have compared the 2, a single study compared conventional fluid resuscitation versus hypertonic saline in hypotensive patients with traumatic brain injury in the prehospital setting. Findings were nearly identical neurological function 6 months after the injury between the 2 groups; however, conventional therapy is to avoid isotonic saline in the acute setting.[8]

Monitoring

Patients on any intravenous fluid replacement need to be monitored for fluid overload. As stated above, any crystalloid fluid distributes across the extracellular fluid compartment equally in an approximately 3 to 1 ratio (interstitial: intravascular) under normal physiologic conditions. That is to say, giving 1 L of Ringer’s lactate causes only 250 mL to remain in the intravascular fluid compartment. Giving too much crystalloid fluid causes fluid overload that can progressively worsen peripheral and pulmonary edema. High-risk patients at high risk for fluid overload include those with congestive heart failure, renal disease, and liver cirrhosis. In these cases, IV fluid administration should proceed cautiously.[9]

Additionally, monitoring of electrolytes may be warranted with Ringer’s lactate administration. Given that Ringer’s lactate contains sodium and potassium, it may be warranted to check these levels frequently in some cases. The sodium concentration in Ringer’s lactate is less than the physiologic range in plasma, and large amounts of administration can drive sodium levels to hyponatremic ranges. With a concentration of 130 mEq/L, administration of this fluid brings the plasma sodium concentration closer to 130 mEq and, depending on the clinical situation, and hyponatremia should be avoided.[10][11]

Monitoring of the site of infusion and IV access is necessary to make sure that the fluid is, in fact, being delivered into the vein. IV sites should be monitored for any signs of infiltration, redness, pain, swelling, or discomfort. If present, the infusion should be stopped, and other IV access should be established. Infusion-site monitoring holds across all IV access sites with any drug administration, not just to Ringer’s lactate.

Toxicity

The toxicity of Ringer’s lactate is more associated with volume overload due to IV fluid administration rather than the contents of Ringer’s lactate itself. As previously stated, excessive IV fluid administration can cause fluid overload. Patients may present anywhere on the spectrum from mild peripheral edema to respiratory distress secondary pulmonary edema. Symptomatic patients should be given diuretic therapy and have serum electrolytes monitored closely. In the most severe cases of respiratory distress, patients may require noninvasive positive pressure ventilation or even intubation. Asymptomatic fluid overload can be managed conservatively with fluid restriction and continued monitoring.

Enhancing Healthcare Team Outcomes

All interprofessional healthcare team members should be familiar with Ringer's lactate and its indications. Ringer’s lactate is a versatile IV-fluid choice for resuscitation. Ringer’s lactate is superior to normal saline in many ways; however, at times avoided by clinicians due to the stigma of containing lactate. Again, the lactate in Ringer’s lactate is only a problem in patients who have liver dysfunction. In many clinical scenarios, lactate is a beneficial molecule, given its metabolism. Ringer’s lactate is surprisingly cost-effective, better understood, and much more studied than the newer buffered solution and has a role in many illnesses as a strong choice for physiologic fluid replacement. The solution is safe; the only drawback results not from electrolyte changes but the fluid overload that may occur. Hence attention should be paid to the amount of volume infused.