Does Intravenous Lactated Ringer Solution Raise Measured Serum Lactate?
Condition: Hyperlactatemia
MeSH terms: Hyperlactatemia
Study type: Interventional
Phase: Early Phase 1

Summary: 
      Lactated Ringer's (LR) solution bolus is commonly administered in the emergency department
      setting to seriously ill patients. It is also common to obtain blood samples to determine
      serum lactate levels to aid in the assessment of the patient's degree of illness. This study
      endeavors to determine if serum lactate levels are affected by LR fluid administration in
      healthy adult individuals as compared to those who receive Normal Saline (NS). Healthy adult
      volunteers will be used as subjects so that the illness of hospital patients does not
      confound the results.
    

Detailed description: 
      Methods:

      Approximately 30 subjects will be randomized to either the Lactated Ringer's group or the
      Placebo group. The study is powered to detect a difference of 0.3mmol/L between pre- and
      post-treatment lactate levels. All subjects are healthy volunteers over 18 years old. Healthy
      volunteers are defined as subjects with no acute symptoms who do not meet any of the
      exclusionary criteria below:

        -  Pregnancy or currently breast-feeding

        -  Prisoner status

        -  Those with any history of clinical conditions associated with fluid overload: congestive
           heart failure, renal, or hepatic failure

        -  Baseline serum lactate level >2.2mmol

        -  Baseline creatinine > 1.5 mg/dL

      All volunteers will sign a written consent, approved by the Institutional Review Board (IRB).
      The consent form will discuss the risks and benefits of our study. The benefit of our study
      is to identify a possible confounder to our current interpretation of serum lactates. By
      clarifying whether Lactated Ringer's fluid can contribute to measured serum lactate level we
      hope to improve our care to septic patients and those patients with abnormal vital signs and
      elevated serum lactate levels in whom the diagnosis of sepsis is being considered. The risks
      of this study include the possible development of fluid overload state and pulmonary edema.
      We believe these sequelae would be very unlikely to occur since we are excluding anyone with
      a history of any clinical conditions associated with fluid overload.

      The intended pool of our volunteer subjects will be from residents, attendings, hospital
      staff, and medical students in the hospital. Only healthy volunteers (as described
      previously) will be allowed to participate. Volunteer subjects from the hospital will be
      instructed to only participate after their work shifts or on their days off from work so as
      not to interfere with their job duties. The consent form will clearly specify that their
      participation in the study will not impact their academic status or employment. The subjects
      will also fill out a short data collection form that will have age, gender, known medical
      problems, medications, and allergies. The subjects will designate their weight in this
      consent form.

      All subjects will receive an 18-gauge IV in one antecubital fossa. A second IV will be placed
      on the contralateral arm from which to draw serum studies.

      The subjects randomized to the Lactated Ringer's arm will receive 30ml/kg Lactated Ringer's
      solution run wide open. Those randomized to the Placebo group will receive 30ml/kg of normal
      saline wide open. The precise fluid bolus quantity will be determined using a measure of the
      patient's weight in kilograms multiplied by 30, rounding the final figure to the nearest
      100ml for simplicity. (E.g. 2077 ml would be rounded to 2100ml.) The pharmacist for the study
      will randomly assign each subject to a treatment group ensuring that there are an equal
      number of subjects in the Lactated Ringer's arm and in the Placebo arm. The pharmacist will
      obscure the fluid bag contents from the investigators to maintain the blinding. Only the
      pharmacist will know which treatment each subject received. The person administering the
      medications and those doing the analysis of the data will only know the study number of each
      patient, and will be blind to the pharmacist's randomization.

      We have chosen a bolus of 30ml/kg Lactated Ringer's solution over one hour as the regimen for
      two reasons primarily. The first is that in a clinical scenario of sepsis or septic shock a
      30ml/kg bolus is typical.[2] Therefore this protocol simulates what actually happens during
      the care of a septic patient. A second reason for the selection of a substantial quantity of
      LR given over a short time interval is to ensure detection of any change in serum lactate
      concentration secondary to this fluid bolus, if there is one to be found. A smaller quantity
      of LR over a shorter time span may result in a false negative result.

      A serum lactate level will be drawn just prior to initiating treatment. Any subject found to
      have an abnormally high baseline serum lactate level (>2.2 mmol/L) before treatment will be
      excluded from the study.

      The lactate will then be measured five minutes after the conclusion of the intravenous fluid
      treatment. 5ml of blood will be wasted to clear the line prior to this blood draw. Lactate
      will be measured with a point-of-care meter (the iSTAT-1 analyzer). The before-treatment and
      after-treatment lactate levels will be compared to see if the Lactated Ringer's caused a
      significant rise (>0.3 mmol/L) in the lactate level at any point during the data collection
      period.

      The study design described previously lends itself to a brief investigation into an important
      clinical phenomenon during fluid resuscitation that will be investigated as a secondary
      outcome to this study. One consideration for the use of the Lactated Ringer's solution
      clinically is the incidence of hyperchloremic metabolic acidosis with the use of normal
      saline during fluid resuscitation.[8] Using our point-of-care meter (the iSTAT 1 analyzer) we
      will measure not only serum lactate but also a complete metabolic panel prior to and
      subsequent to the delivery of the 30 ml/kg fluid administration. We will subsequently analyze
      changes in serum sodium, chloride, potassium, and bicarbonate in each of the treatment
      groups, assessing for the degree of derangement that occurs in those electrolytes, and
      specifically evaluating for any trend toward hyperchloremic metabolic acidosis in the normal
      saline group.

      While patients are in the process of receiving IV fluids, they will be kept on continuous
      cardiac and oxygenation monitoring. We believe it is highly unlikely that any subject will
      need any medical care during this study. However, let it be noted that there will be an
      attending and/or resident physician present at all times while patients are receiving
      treatment. Should any subject develop adverse effects as a result of our study, the physician
      will assess the patient and offer to register them in the emergency department. Any Serious
      Adverse Event (SAE) will be reported to the IRB within 5 days.

      In order to protect the privacy of the research subjects and to maintain the confidentiality
      of the data, all data will be handled only by research assistants or investigators and will
      be stored in secure cabinets and on password protected computer files in the locked research
      offices. All research assistants and investigators are HIPAA-trained and credentialed by UMC
      IRB.

      We have chosen a goal sample size of 30 based on the following calculation. A sample size of
      25 achieves 80% power to detect a mean of paired differences of 0.3 with a known standard
      deviation of differences of 0.5 and with a significance level (alpha) or 0.05 using a
      one-sided paired t-test. To allow for patient drop out or equipment failure, we will aim to
      enroll 30 patients.
    

Intervention name(s): Lactated Ringer Solution; Normal Saline
Intervention type(s): Drug; Drug
Intervention description(s): Fluid bolus of Lactated Ringer solution (30ml/kg).; Fluid bolus or Normal Saline (30ml/kg).
Other intervention name(s): LR; NS
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Diagnostic
Keywords: Elevated Serum Lactate; Serum lactate; Ringer's Lactate; Lactated Ringer's; Hyperlactatemia