Does Intravenous Lactated Ringer Solution Raise Measured Serum Lactate?
Phase: EARLY_PHASE1
Conditions: Hyperlactatemia
Sponsor: University Medical Center of Southern Nevada

 
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Official Title:  “Does Intravenous Lactated Ringer’s Solution Raise 
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Serum Lactate?” 
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NCT number:  NCT02950753 
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Date approved by IRB:  Nov 17, 2016 
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Introduction 
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Since “early goal-directed therapy,” early recognition of septic shock using the serum 
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lactate has become standard of care [1-4].  Indeed, the central place of lactate in sepsis 
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care has been promoted by the Surviving Sepsis campaign, and it is now backed by 
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financial incentives for hospitals with its adoption as a CMS Core Measure [5]. 
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In this context, it is important to elucidate all possible causes of hyperlactatemia. 
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Previous studies have shown that serum lactate increases in all shock states, not just 
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septic shock [6].  Furthermore, lactate has also been shown to increase from albuterol [7], 
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anti-retroviral medications, metformin, propofol, and alcohols [8]. 
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According to Surviving Sepsis Guidelines, patients diagnosed with septic shock should 
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receive 30 mL/kg of crystalloid solution within three hours [9].  One commonly used 
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crystalloid, Lactated Ringer’s solution (LR), contains 28 mmol/L of racemic lactate in the 
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form of sodium lactate. While lactate is rapidly metabolized by the liver and kidney, 
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aggressive fluid resuscitation with LR may transiently raise serum lactate, potentially 
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confounding the interpretation of this test. 
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There has only been one trial looking at the question of whether administration of LR 
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raises serum lactate. That study did not show a difference in lactate levels in those 
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receiving LR versus those receiving alternative crystalloid solutions. However, that study 
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used only 1 liter of LR delivered over one hour [10].  As mentioned above, patients in 
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septic shock are mandated to receive 30 mL/kg of crystalloid solution, and the fluids are 
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typically given at a rate faster than 1 liter per hour.  Therefore, when LR is given at a 
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volume and rate more similar to what is done for septic shock patients, LR may have an 
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effect on serum lactate level that was not identified in the previous study.  
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Thus, we propose a double-blind, randomized controlled trial to investigate whether the 
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administration of intravenous LR at 30 mL/kg increases levels of serum lactate. As our 
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study compares the effect of NS and LR, it lends itself easily to secondarily investigating 
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changes in sodium (Na), chloride (Cl), and pH in the NS group compared to the LR 
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group. 
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Materials and Methods 
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Study Design and Setting 
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This will be a double-blind, randomized controlled trial performed on a group of healthy 
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volunteers, made up primarily of family, friends, and colleagues of the investigators.   
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All subjects will be healthy volunteers aged 18 years or older. Healthy volunteers are 
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defined as subjects with no acute symptoms who meet none of the following exclusion 
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criteria: pregnant, breast-feeding, prisoners, history of conditions associated with fluid 
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overload (congestive heart, renal, or hepatic failure), baseline serum lactate level >2.2 
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mmol, and baseline creatinine >1.5 mg/dL. 
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All volunteers will fill out a short data collection form assessing their age, weight, 
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gender, and medical history. All volunteers will signed a written consent, approved by the 
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IRB. 
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A random-number generator will be used to assign each subject to either LR or NS. After 
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assignment, a pharmacist with no role in data collection prepared the fluids in a locked 
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room.  The pharmacist will use an opaque black bag to obscure the fluids. The subjects 
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will then receive 30 mL/kg rounded to the nearest 100 mL of the solution to which they 
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were randomized.  
 
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An investigator will place an 18 gauge IV in one upper extremity, and an initial serum 
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lactate and electrolyte panel will be drawn, measured using the i-STAT 1 analyzer 
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(Abbott Point of Care, Princeton, NJ). Fluids will be administered as a rapid bolus via 
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pressure bag. Post-treatment blood will be drawn from the contralateral upper extremity 
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five minutes after the conclusion of the IV fluid administration.      
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Outcomes 
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The primary outcome will be the difference in change in serum lactate levels between the 
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LR and NS groups. Secondarily, we will compare the change in lactate within each group 
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(before and after treatment), and we will compare the change in pH, creatinine, 
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bicarbonate, Na, and Cl levels between NS and LR groups.    
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Data Analysis 
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We powered the study as follows. A sample size of 30 achieves 80% power to detect a 
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difference of 0.5 mmol/L in the mean change in lactate between the NS and LR groups 
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assuming a standard deviation of differences of 0.5 and an alpha of 0.05.  We chose the 
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value of 0.5 mmol/L by clinical gestalt based on what we consider a clinically significant 
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difference in lactate levels. Before and after treatment lactate levels will be compared 
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within each group using paired t-tests. We will compare the change in mean lactate and 
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the change in other variables (pH, creatinine, bicarbonate, Na, and Cl) between the LR 
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and NS groups using two-tailed t-tests.   
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References 
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1. Rivers E, Nguyen B, Havstad S, et al. Early goal-directed therapy in the treatment of 
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severe sepsis and septic shock. N Engl J Med. 2001; 345 (19): 1368–77. 
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2. Process Investigators, Yealy DM, Kellum JA, et al, A randomized trial of protocol-
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based care for early septic shock. N Engl J Med. 2014;370:1683–1693. 
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3. Mouncey PR, Osborn TM, Power GS, et al. Trial of early, goal-directed resuscitation 
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for septic shock. N Engl J Med. 2015;372:1301–1311. 
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4. ARISE Investigators, Anzics Clinical Trials Group, Peake SL, et al. Goal-directed 
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resuscitation for patients with early septic shock. N Engl J Med. 2014;371:1496–1506. 
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5. Centers for Medicare & Medicaid Services. CMS specifications manual version 5.2a. 
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Available at:  
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 https://www.qualitynet.org/dcs/ContentServer?c=Page&pagename=QnetPublic%2FPage
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%2FQnetTier3&cid=1228775749207.  Accessed August 22, 2017 
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6. Cecconi M., De Backer D., Antonelli M, et al. Consensus on circulatory shock and 
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hemodynamic monitoring. Task force of the European Society of Intensive Care 
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Medicine. Intensive Care Med. 2014; 40:1795–815. 
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7. Zitek T, Cleveland N, Rahbar A, et al. Effect of Nebulized Albuterol on Serum Lactate 
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and Potassium in Healthy Subjects. Acad Emerg Med. 2016; 23(6):718-21. 
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8. Kraut, JA. Madias NE.  Lactic Acidosis.  N Engl J Med.  2014;371:2309-19.   
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9. Dellinger R, Levy M, Rhodes A, et al. Surviving Sepsis Campaign: international 
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guidelines for the management of severe sepsis and septic shock 2012. Crit Care Med. 
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2013; 41: 580–637.  
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10. Didwania A, Miller J, Kassel D, et al. Effect of intravenous lactated Ringer's solution 
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infusion on the circulating lactate concentration: Part 3. Results of a prospective, 
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randomized, double-blind, placebo-controlled trial. Crit Care Med. 1997; 25(11):1851-4. 
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