Does Intravenous Lactated Ringer Solution Raise Measured Serum Lactate?
Does Intravenous Lactated Ringer Solution Raise Measured Serum Lactate?
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.
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.
Inclusion Criteria:

 -  Healthy adult volunteers

 -  18 years and older

 Exclusion Criteria:

 -  Pregnancy or currently breast-feeding

 -  Prisoner

 -  History of conditions associated with fluid overload: heart, renal or hepatic failure

 -  Baseline serum lactate level >2.2mmol

 -  Baseline creatinine > 1.5 mg/dL