Abstract:
A creatinine clearance monitoring and fluid level management system for use in the treatment of patients. The system establishes and adjusts the dosing of intravenous fluids based upon periodic creatinine clearance calculations based upon a system specified frequency. Warning or alert messages or signals are produced if creatinine clearance levels indicate the need for the administration of additional fluids based upon a creatinine clearance result below an established normal threshold. Furthermore, the system generates a warning to trigger a more serious intervention in the event a patient&#39;s creatinine clearance rate falls below a lower established threshold or the system determines that an inordinate amount of fluids have been administered without the anticipated response. The creatinine clearance monitoring and fluid level management system is particularly useful for patients in a hospital or in-patient environment, and particularly those post-operative patients or those in intensive care.

Description:
CROSS REFERENCE TO RELATED APPLICATIONS 
       [0001]    The present application claims the benefit of U.S. Provisional Patent Application Ser. No. 61/616,527 filed Mar. 28, 2012 which is hereby incorporated by reference in its entirety to the extent not inconsistent. 
     
    
     FIELD OF THE INVENTION 
       [0002]    The invention relates to the maintenance of fluid levels in patients, and in particular, to a system that aids in the administration of fluids to patient and monitors for an indication that immediate intervention is necessary through the use of computerized fluid calculations that are made with the use of creatinine clearance rates. 
       BACKGROUND 
       [0003]    Maintaining a proper fluid level is important for many patients, particularly post-op and critical care patients, in order to prevent further complications. Once such complication, which often occurs in light of a lack of fluids, is renal failure. Additionally, studies have suggested that a decrease in renal function is an early indicator to the failure of other vital organs, including the heart. Effective renal function depends upon glomerular filtration of serum into the renal tubules and selective tubular re-absorption and some renal tubular excretion. The glomerular filtration rate (GFR) is closely regulated by the constriction and dilation of afferent and efferent arterioles. Renal tubular function depends upon transmembrane pump mechanisms that affect the selective molecular passage against concentration gradients at a metabolic energy cost usually in the form of high energy phosphate compounds (e.g., adenosine triphosphate, or ATP). With physiologic stresses such as circulatory shock and overwhelming sepsis, energy supply and/or utilization is impaired, and consequently tubular function deteriorates. Without compensatory mechanisms, massive polyuria and uncontrollable hypovolemia may ensue, leading to further complications. However, intrinsic tubuloglomerular feedback mechanisms exist to limit volume losses in such states severely, primarily through the action of the macula densa at the juxtaglomerular apparatus. This appears to produce primarily an intrarenal release of renin producing afferent arteriolar constriction and probably some efferent arteriolar dilation, leading to a reduction in the filtration fraction, and a reduced GFR. This response occurs at the stage of tubular dysfunction and precedes the onset of acute tubular necrosis (ATN). Thus, close monitoring of the GFR provides a mechanism to detect renal compensation in a timely manner, allowing the potential for clinical interventions to reverse the physiologic stress and prevent decompensation in the form of ATN. It also appears that renal dysfunction and failure often precedes the onset of other or multiple organ failures. Thus, if renal function could be observed in near-real time, effective prevention of renal failure could potentially prevent the syndrome of multiple organ failure in many cases. 
         [0004]    Other attempts to provide for monitoring a patient&#39;s GFR have focused upon the introduction of a marker substance, such as inulin, into the patient&#39;s bloodstream which is subsequently filtered out by the patient&#39;s kidneys at a measurable rate. The marker substance must be stable in the bloodstream and freely filtered by the kidneys without being reabsorbed nor secreted by the kidneys. However, these attempts have achieved limited success due to the requirement that a marker substance be administered into the bloodstream. Furthermore, the biosensors for detecting these substances with the required level of accuracy, both in the bloodstream and in the urine, are not cost effective. As such, a need exists for a system and method which will provide for a periodic measurement of the renal function of a patient in order to provide recommendations pertaining to the amount of fluid a patient should receive, and other potential interventions if necessary. 
       SUMMARY 
       [0005]    It is therefore an object of one embodiment of the present invention to provide a system for monitoring creatinine clearance rates in a patient, calculating proper intravenous fluid administration levels, and providing relevant feedback information and messages to the patient&#39;s physician, nurse, or other caregiver. A creatinine clearance rate below an established threshold results in the indication of a need for an intravenous fluid volume bolus, provided that the patient has not reach an established ceiling, while a creatinine clearance rate below a second threshold will generate a warning that requires additional measurement or caregiver intervention to insure the correct treatment is administered. 
     
    
     
       BRIEF DESCRIPTION OF THE DRAWINGS 
         [0006]      FIG. 1  is a diagrammatic view of a creatinine clearance monitoring and fluid level management system in accordance with one embodiment of the present invention. 
           [0007]      FIG. 2  is a flowchart illustrating a process which controls the operation of a creatinine clearance monitoring and fluid level management system in accordance with one form of the present invention. 
           [0008]      FIG. 3  is a flowchart illustrating a process which controls the operation of one step for determining a proper fluid infusion in the process of the creatinine clearance monitoring and fluid level management system of  FIG. 2 . 
           [0009]      FIG. 4  is a flowchart illustrating a process which controls the operation of one step for determining in tubular function is present in the process of the creatinine clearance monitoring and fluid level management system of  FIG. 2 . 
       
    
    
     DETAILED DESCRIPTION 
       [0010]    For the purposes of promoting understanding of the principles of the invention, reference will now be made to the embodiments illustrated in the drawings and specific language will be used to describe the same. It will nevertheless be understood that no limitation of the scope of the invention is hereby intended and alterations and modifications in the devices, systems and representations illustrated in the drawings, and further applications of the principles of the present invention as illustrated herein being contemplated as would normally occur to one skilled in the art to which the invention relates. 
         [0011]    While inulin clearance is a more commonly used method for measuring the glomerular filtration rate (GFR), a suitable stand-in is the determination of creatinine clearance. Creatinine is an endogenous molecule continuously released in the process of muscle metabolism, and therefore no infusion of a foreign substance is necessary for its determination. The creatinine clearance is determined from the following equation: 
         [0000]    
       
         
           
             Ccr 
             = 
             
               
                 Ucr 
                 × 
                 V 
               
               
                 Pcr 
                 × 
                 T 
               
             
           
         
       
     
         [0012]    Where C cr  is the creatinine clearance (usually in ml/min), U cr  and P cr  are the creatinine concentrations in urine and plasma respectively (usually in mg/dl), V is the volume of urine (usually in ml) collected over a period of time, T (in minutes). The normal C cr  is age dependent, averaging 125 ml/min in the prime of life and deteriorating to lower levels with aging. 
         [0013]    There are two established uses of creatinine clearance determinations. The most common is its use as a monitor of renal function in patients with chronic renal insufficiency and failure. A 24-hour urine collection is obtained for this determination, providing a 24-hour average of the GFR estimate. Less commonly creatinine clearance is used as an assessment of renal function on an acute basis in critically ill individuals who are at risk of developing acute renal failure. Clinical studies have demonstrated a rapid renal response to physiologic stress with a sharp drop in C cr  (usually obtained over a 2-hour collection period). The drop in C cr , if sustained, precedes the onset of renal insufficiency and subsequent acute renal failure. The drop in C cr  occurs in patients with normal systemic blood pressures and urinary flow rates, which are the indicators commonly monitored by current medical procedures to track fluid levels. The drop in C cr  usually precedes the oliguria that accompanies acute renal failure by some 16 to 18 hours. On the other hand, if the acute drop in C cr  reverses, no subsequent renal dysfunction is experienced. 
         [0014]    Despite the clinical evidence of the value of C cr  monitoring in critically ill patients, clinicians rarely use it. In part, this is due to inadequate understanding of renal function and traditional medical practices. It has been standard practice for over four decades to monitor hourly urine output and serum creatinine. The concept that glomerular filtration can suffer acute changes that manifest themselves as oliguria and elevated creatinine several hours or sometimes days later is not a part of standard clinical knowledge. However, another major reason for the infrequent use of C cr  as a renal function monitor is that the timed collection of urine, transfer of the specimen to the laboratory for analysis, and calculation of the result is tedious and cumbersome. As such, it is the goal of the system described herein to provide an automated continuous read-out of the C cr  along with alarms/alerts and instructions presented as screen displays and/or electronically spoken phrases. 
         [0015]    Referring to  FIG. 1 , there is shown an creatinine clearance monitoring and fluid level management system  10  for a patient  12  who is illustratively being cared for in a hospital critical care setting, e.g., within an intensive care unit following surgery, although other patient settings are of course possible. The condition and vital signs of patient  12  on bed  14  is shown as being illustratively monitored directly by a nurse or caregiver  16 , but at least some functions that are performed by nurse  16  could be performed by automatic monitoring (pulse, blood pressure), data entry, and/or intravenous medication delivery equipment (not shown), to name only a few possible examples. For purposes of explaining an embodiment of the present invention, patient  12  is shown as receiving a continuous drip of fluid from reservoir  18  that is controlled by drip regulator  20  through an intravenous (IV) line  22 . Additionally, patient  12  has a urinary catheter  21  in place which drains into a urine collection vessel  23 , which includes a biosensor  25 . 
         [0016]    The system  10  includes various components for accurately determining and reporting the necessary elements to make an assessment of the patient&#39;s creatinine clearance. As discussed above, a proper C cr  calculation requires the input of a patient&#39;s creatinine concentrations in urine (U cr ) and creatinine concentrations in plasma respectively (P cr )(usually in mg/dl), in addition to the volume of urine (V)(usually in ml), and a time (T) over which that volume of urine was collected (in minutes). 
         [0017]    The first element, time (T), is to be determined either statically by the user or dynamically by the system  10  based upon the user&#39;s criteria and is stored by data handling device  24 . For example, the time element (T) may be defined within system  10  as any of a number of different intervals (e.g., 1 hour, 2 hours, 4 hours, 6 hours, 8 hours, 12 hours, 24 hours) and may be programmed so as to adapt automatically based upon the user&#39;s desires. This interval will set the cutoff for measurement of the volume (V) element to be used in the calculation of the C cr . In addition, the T interval will be used to average all the U cr  values obtained during the prescribed interval, as described below. 
         [0018]    In order to determine the patient&#39;s urine volume (V), the system utilizes catheter  21  and urine collection vessel  23 . In operation, urine from patient  12  is carried via catheter  21  into collection vessel  23 . In one form, catheter  21  is a Foley catheter, but it shall be appreciated that alternate catheter types may be utilized. According to another form, collection vessel  23  is a urimeter which is capable of determining and reporting urine volumes automatically. A suitable urimeter for use in this form is the CritiCore® Monitor manufactured by C.R. Bard, located at 730 Central Avenue, Murray Hill, N.J. 07974. This device is capable of accurate electronic monitoring of urine output using an embedded ultrasonic sensor. Furthermore, the urine volume can be collected and reported programmatically to data handling device  24 , and interpreted in accordance with the timing intervals desired. Alternate methods of calculating the volume of urine output may be utilized, whether or not they capture the urine for measurement or estimate its volume based upon flow in discrete time intervals or the like. 
         [0019]    According to the form illustrated, the system  10  utilizes a biosensor  25  in order to automatically collect the urinary concentration of creatinine (U cr ) of patient  12 . The biosensor  25  may be one or more chemical field-effect transistors (chemFET), which periodically/continuously monitors the urinary concentration of creatinine (U cr ) in the urine passing through catheter  21  and reports its results to data handling device  24 . A suitable type of chemFET for use as biosensor  25  is that described in “Creatinine Biosensors: Principles and Designs” by Anthony J. Killard and Malcolm R. Smyth, published in the Trends in Biotechnology Journal, Volume 18, Issue 10 (October 2000). Alternatively, other suitable biosensors known to those of skill in the art could be utilized as biosensor  25 . 
         [0020]    Finally, in order to determine the creatinine concentrations in plasma (P cr ), the nurse  16  orders a lab test based upon a blood sample drawn from patient  12 . This is a lab test which nearly all critically ill patients at risk for renal failure have as a daily routine under current medical procedures. As such, the system  10  will be able to utilize this information without any additional burden on the hospital staff. Upon receiving the results of the P cr  value, the nurse  16  enters the P cr  value determined from the blood drawn from patient  12  into data handling device  24 . Device  24  is illustratively shown as having a display  26  and an input interface  28 . Display  26  may be of any conventional or available display type, such as, for example, a CRT or LCD screen, while input interface  28  may be a computer keyboard or touchscreen, for example. When the patient&#39;s P cr  test results have been entered into device  24 , the entered information, along with the other values received (including T, V, and U cr ) are sent via communications channel  30  to computer or data processor  32  which may be located locally or at a central location, such as a nurse&#39;s station or hospital-wide patient monitor center. Communications channel  30  may be of the form of a hardwired connection, a local area network, a wireless network, or an internet-based wide area network, to cite a few non-limiting examples. A similar connection may exist between device  24  and one or more of urimeter  23 , biosensor  25 , and regulator  20 . Network access may advantageously provide access to patient data from other hospitals or in-patient facilities, and it can allow patent  12  to be moved within a networked facility or between network-linked facilities, while still maintaining active monitoring of the patient&#39;s condition and providing access to historical patient data. 
         [0021]    Data processor  32  illustratively comprises a central processing unit (CPU)  34  and memory  36 , which may be of any known or available form, such as, for example, ROM, PROM, RAM, EPROM or EEPROM. Also shown as being connected or associated with data processor  32  are display  38  (such as, for example, a CRT, plasma, LED or LCD screen) and input device  40 , such as a keyboard, for example. 
         [0022]    Data processor  32  utilizes the creatinine concentration in urine (U cr ), creatinine concentration in plasma P cr )(usually in mg/dl), volume of urine (V)(usually in ml), and time (T) associated with patient  12 , which were received from the data handling device  24 , to calculate a continuous creatinine clearance rate (CCC) for patient  12 . In the described form, this calculation is performed according to the equation described above. Additionally, the calculated CCC and other values, such as urine flow rate, may be determined and displayed on display  26  or some other in-room display or the like so as to be easily referenced by the attending medical staff. Additionally, prior to or at the outset of the CCC being monitored, the user is prompted to provide an Empiric Fluid Limit (EFL), which is the maximum amount of fluid that may be administered before an elevated evaluation is warranted for that patient in order to provide decision support. Such input may be provided by input interface  28 . 
         [0023]    Based upon the determine creatinine clearance rate (C cr ), along with additional variables, the system  10  will determine if the fluid levels of patient  12  are sufficient. If the patient&#39;s fluid levels are determined to be too low, data processor  32  will issue an alert and instruct the nurse  16  to administer a predetermined fluid intravenously to the patient  12 . The information is sent back to device  24  via communications channel  30  where it appears on display  38 . Nurse or caregiver  16  then makes any necessary adjustments to or initially sets up drip regulator  20  so that the proper amount of the selected fluid is delivered to patient  12  from reservoir  18 . The calculation used by CPU  34  of data processor  32  illustratively utilizes a process which will be described below. 
         [0024]      FIG. 2  illustrates a flowchart which, with continued reference to  FIG. 1 , shows a creatinine clearance monitoring and fluid level management process  41  in accordance with one form of the present invention, which will be used to illustrate the manner in which creatinine clearance monitoring and fluid level management system  10  of  FIG. 1  may operate. Beginning at step  42  of process  41 , a particular patient is selected for creatinine clearance monitoring and fluid level management by system  10 . For illustrative purposes, we assume that the user or system  10  selects critical care patient  12  in step  42 . Step  44  determines the current time and updates that information within the system  10 . The system  10  then requests and receives the current urine volume (V) from urimeter  23  via data handling device  24  in step  46 . Upon receiving this information, the system  10  updates the display of the current urine flow rate on display  38  in step  48 . In continuing to collect the data necessary, the system  10  requests and receives the current creatinine concentrations in urine (U cr ) of patient  12  from biosensor  25  via data handling device  24  in step  50 . In one form, this information is communicated to data collection device  24  electronically, such as via a wired or wireless connection. Additionally, in step  52  the system  10  receives the creatinine concentrations in plasma (P cr ) of patient  12 . As discussed above, the P cr  value used by system  10  according to this form is a lab value determined from a sample of the blood of patient  12 . As such, the P cr  value is entered into the system manually (such as via device  24 ) or through some other testing procedure sufficient to deliver an accurate P cr  value to system  10 . It shall be appreciated by one of skill in the art that steps  46 ,  50 , and  52  may occur simultaneously or in various order, with varying time intervals between steps also being possible. 
         [0025]    Once system  10  has collected the necessary data, data processor  32  of system  10  calculates a continuous creatinine clearance rate (CCC) for patient  12  in step  54 . This may occur once data handling device  24  has transmitted or made the received data accessibly to data processor  32 . Once the CCC is calculated, it is preferably displayed on display  38  along with other information concerning patient  12 . Moving on to step  56 , the system  10  prompts the user to input the Empiric Fluid Limit (EFL) for patient  12 . In this illustrated form, the EFL is input via device  24 , such as by nurse  16  based upon the recommendation of the physician attending to patient  12 . In alternate forms, the EFL for patient  12  may be provided earlier in process  41  or may be dynamically determined by system  10 . Step  58  serves as a block which will prevent decision support of system  10  from being functional absent a specified EFL. As such, once an EFL is provided in step  56 , the process  41  may advance to step  60 . Alternatively, if the EFL has been entered previously, then step  58  is quickly satisfied and does not hold up process  41 . 
         [0026]    According to step  60 , the data processor  32  of system  10  compares the CCC calculated in step  54  against a pre-determined threshold which represents the lower bound of a preferred range. This safe threshold may be determined based upon the sex, age, medical condition, and other characteristics of patient  12 . For exemplary purposes, the threshold may be 100 mL/min and the system  10  may interpret a CCC greater than the 100 mL/min threshold to be satisfactory. As such, upon determining that the CCC of patient  12  determined in step  54  is above the first set threshold, process  41  iteratively returns to step  44  and begins a cyclic monitoring loop which repeatedly runs so long as the patient&#39;s CCC is above the safe threshold. However, if the system  10  determines that the CCC of patient  12  is below the desired threshold at any time then the process  41  proceeds to step  62 . In step  62 , system  10  determines whether the calculated CCC for patient  12  is below an emergency threshold, such as 20 mL/min. 
         [0027]    If the CCC of patient  12  is determined to be above the emergency threshold in step  62 , then process  41  proceeds to step  64  in order to determine if additional fluids may be administered in order to attempt to raise the patient&#39;s fluid levels. As such, at step  64  a determination is made by system  10  as to whether or not the total volume of fluids given to patient  12  exceeds the EFL specified in step  56 . In the event that it does not exceed the EFL, the process  41  proceeds to step  66  in which data processor  32  determines an optimal fluid order for infusion into patient  12 . One exemplary process for use in making the determination in step  66  according to one form is described in detail below with reference to  FIG. 3 . Once the proper fluid infusion is determined, the system  10 , such as through display  38 , prompts the nurse  16  or other hospital staff to administer the determined fluid volume bolus to patient  12 . Once the order is completed, the user indicates that the fluid order was filed and the process  41  returns to step  44  and begins anew. Additionally, the determined fluid volume provided to patient  12  is automatically added to the total volume of fluids administered to patient  12  for subsequent comparison against the EFL. 
         [0028]    Returning to step  64 , if the system  10  alternatively determines that the quantity of fluids administered to patient  12  exceeds the EFL, then the process advances to step  70  as the infusion of additional fluids has likely been previously attempted without success. At step  70 , the system  10  prompts nurse  16  any other attending medical staff to effect the placement of a Continuous Right Ventricular End-Diagnostic (CEDV) catheter, or some other medically identified intervention. Additionally, in step  70 , an alert may be issued to display  38  or otherwise, such as to the mobile device of nurse  16  or over the hospital&#39;s paging network. Once the CEDV catheter is in place, the system  10  receives a determination of the End Diastolic Volume Index (EDVI) in step  72 . EDVI indicates the volume of blood in a ventricle at the end load or filling in diastole. An increase in EDVI increases the preload on the heart and, through the Frank-Starling mechanism of the heart, increases the amount of blood ejected from the ventricle during systole. Once the EDVI value is received, the system  10  compares the EDVI to an EDVI threshold, such as 100 ml/M 2 . In the event the EDVI value of patient  12  is below the EDVI threshold, then process  41  returns to step  66  where a fluid infusion order is determined and the process continues from there. Alternatively, in the event the EDVI value of patient  12  is above the EVDI threshold, the process  41  proceeds to step  76  where the system  10  receives an SvO 2  value for patient  12 . SvO 2  provides an assessment of total tissue oxygen balance (i.e., the relationship between oxygen delivery and oxygen consumption). SvO 2  varies directly with cardiac output, Hb, and SaO 2 , and inversely with VO 2  (oxygen consumption). The normal SvO 2  is 75%, which indicates that under normal conditions, tissues extract 25% of the oxygen delivered. An increase in VO 2  or a decrease in arterial oxygen content (SaO 2 ×Hb) is compensated by increasing CO or tissue oxygen extraction. When the SvO 2  is less than 30%, tissue oxygen balance is compromised, and anaerobic metabolism ensues. As such, in the step  78  the system  10  determines if the SvO 2  of patient  12  is below a SvO 2  threshold, such as 70%. If the SvO 2  is greater than 70%, then the process  41  ends at this point and, in one form, would restart by returning to step  44  as it is intended to be a continuous monitoring process. 
         [0029]    In the event that the SvO 2  value is below this threshold, the process proceeds to step  80  in which the system prompts for and receives a cardiac index associated with patient  12 . Cardiac index (CI) is a vasodynamic parameter that relates the cardiac output (CO) to body surface area (BSA), thus relating heart performance to the size of the individual. The unit of measurement is liters per minute per square meter (l/min/m 2 ). The process  41  proceeds to step  82  in which the cardiac index of patient  12  is compared to a cardiac index threshold, such as 3.5 l/min/m 2 . In the event that the cardiac index of patient  12  is below this threshold, the system  10  provides an alert, such as via display  38 , instructing that dobutamine be administered to patient  12 . Dobutamine is a sympathomimetic drug used in the treatment of heart failure and cardiogenic shock. Its primary mechanism is direct stimulation of β 1  receptors of the sympathetic nervous system. 
         [0030]    Returning to step  62 , if the CCC of patient  12  is determined to be below the emergency threshold, then process  41  proceeds to step  90  which questions the medical staff as to whether tubular function is present. In the event that tubular function is prevent, the process  41  proceeds to step  70  and proceeds accordingly. However, in the event tubular function is not determined to be present, upon being notified, the system  10  instructs the attending medical staff to consult with the nephrology department as the patient has acute tubular necrosis (ATN) which requires dialytic therapy. In such an event, the process  41  ends at this point. 
         [0031]    Turning to  FIG. 3 , with continued references to  FIGS. 1 and 2 , a flowchart is illustrated showing the detail of step  66  of  FIG. 2  in which a fluid determination is made according to one embodiment of system  10 . The process of step  66  begins at start point  100  with a fluid deficiency being identified. The process proceeds to step  102  in which a determination is made as to whether the hemoglobin level of the patient  12  is less than a hemoglobin threshold, such as 10 gm/dL. If the hemoglobin level is less that the hemoglobin threshold, then the process proceeds to step  104  in which determination is made that 1 pack of Packed Red Blood Cells (PRBCs) be transfused into patient  12 . Upon reaching step  102 , the process of step  66  returns to step  68  where an alert is issued according to the interventions determined to be needed by system  10 . Alternatively, if the hemoglobin level is greater than the hemoglobin threshold, then the process proceeds to step  106  in which system  10  seeks the patient&#39;s colloid osmotic pressure (COP). The COP is a pressure normally exerted by proteins in blood plasma that usually tends to pull water into the circulatory system. In the event the COP can be readily determined, the process moves to step  108 . Alternatively, in the event the COP is not readily determinable, the process moves to step  110  to calculate a COP for patient  12 . No matter the path, the process of step  66  arrives at step  112  where the patient  12 &#39;s COP is compared to a COP threshold. For exemplary purposes, this COP threshold is set at  12 . In the event the patient&#39;s COP is below  12 , the process proceeds to step  114  in which the system  10  recommend the infusion of hydroxyethyl starch for patient  12 . Alternatively, when the patient&#39;s COP is above  12 , the process proceeds to step  116  in which the system  10  recommend the infusion of a crystalloid solution for patient  12 . Upon reaching either step  114  or  116 , the process of step  66  returns to step  68  where an alert is issued according to the interventions determined to be needed by system  10 . 
         [0032]    Turning to  FIG. 4 , with continued references to  FIGS. 1 and 2 , a flowchart is illustrated showing the detail of step  90  of  FIG. 2  in which a determination is made as to whether or not tubular function is present within patient  12  according to one embodiment of system  10 . The process of step  90  begins at start point  120  with the need to assess the tubular function of patient  12  being identified. The process proceeds to step  122  in which it is determined whether the patient has received a diuretic in the past 12 hours. If the patient  12  has not been given a diuretic, then the process proceeds to step  124  in which the system  10  prompts the nurse  16  to obtain plasma and urine samples from patient  12  for sodium concentration testing. Subsequently, the process proceeds to step  126  where the nurse  16  is requested to input plasma and urine sodium concentrations based on the assay results from the samples taken in step  124 . The process then proceeds to step  128  where a fractional excretion of sodium (FE Na ) for patient  12  is determined using the known U cr  and P cr  for patient  12 . FE Na  is the percentage of the sodium filtered by the kidney which is excreted in the urine. If the determined FE Na  is less that a FE Na  threshold, such as 1%, the process proceeds to step  142  where the presence of tubular function for patient  12  is indicated. Alternatively, if the determined FE Na  is greater than the threshold, the process proceeds to step  132  where the process rejoins the outcome where patient  12  has been given a diuretic in the past 12 hours from step  122 . From here, in step  132 , the system  10  prompts the nurse  16  to obtain plasma and urine samples from patient  12  for urea concentration testing. Subsequently, the process proceeds to step  134  where the nurse  16  is requested to input plasma and urine urea concentrations based on the assay results from the samples taken in step  132 . The process then proceeds to step  136  where a fractional excretion of urea (FE Urea ) for patient  12  is determined using the known U cr  and P cr  for patient  12 . FE Urea  is the percentage of the urea filtered by the kidney which is excreted in the urine. If the determined FE Urea  is less that a FE Urea  threshold, such as 35%, the process proceeds to step  142  where the presence of tubular function for patient  12  is indicated. Alternatively, if the determined FE Na  is greater than the threshold, the process proceeds to step  140  where the system  10  indicates the presence of acute tubular necrosis (ATN). Upon reaching step  140  the process of step  90  returns to the process  41  of  FIG. 2  at step  92 . Alternatively, upon reaching step  142  of the process of step  90  returns to the process  41  of  FIG. 2  at step  70  for subsequent handling by stem  10 . 
         [0033]    It shall be appreciated that many of the functions of system  10  that have been described with reference to  FIGS. 2-4  may be performed by electronic circuitry and/or with computer software, including but not limited to the steps of retrieving values, calculating creatinine clearance rates, determining whether calculated amounts are above specified thresholds, issuing alert messages, and determining fluid volume bolus orders. 
         [0034]    The previous description has been made based on treatment of patients in an in-patient medical/surgical setting, such as a hospital or nursing home, as the novel features of the invention lend themselves particularly well to a critical or intensive care setting. The scope of the invention, however, is not limited to an in-patient environment. Significant advantages can also be realized by ambulatory or otherwise medically attendant individuals with a need for fluid level monitoring through the use of, for example, periodic infusions. The manner in which such as system, incorporating one or more embodiments of the present invention, could provide automatic tests and administration of proper infusion amounts while still maintaining sufficient safeguards to protect against an inadvertent application of an incorrect dose due to an equipment malfunction or some incident of human error. 
         [0035]    While the invention has been illustrated and described in detail in the drawing and foregoing description, the same is to be considered as illustrative and not restrictive in character, it being understood that only the preferred embodiment has been shown and described and that all changes, modifications and equivalents that come within the spirit of the inventions disclosed are desired to be protected. The articles “a”, “an”, “said” and “the” are not limited to a singular element, and include one or more such elements.