Urine flow rate monitoring in hypovolemic multiple trauma patients
Brotfain et al. World Journal of Emergency Surgery
Urine flow rate monitoring in hypovolemic multiple trauma patients
Evgeni Brotfain 0 1 4
Yoram Klein 0 3 4
Ronen Toledano 2 4
Leonid Koyfman 1 4
Dmitry Frank 1 4
Micha Y. Shamir 4 5
Moti Klein 1 4
0 Equal contributors
1 Department of Anesthesiology and Critical Care, General Intensive Care Unit, Soroka Medical Center, Ben-Gurion University of the Negev , Beer Sheva , Israel
2 Clinical Research Center, Soroka Medical Center, Ben-Gurion University
3 Trauma unit, Sheba Medical Center, Tel Aviv University , Tel Aviv , Israel
4 of the Negev , Beer Sheva , Israel
5 Department of Anesthesiology, Hadassah- Hebrew University Medical Center , Jerusalem , Israel
Background: The urine output is an important clinical parameter of renal function and blood volume status, especially in critically ill multiple trauma patients. In the present study, the minute-to-minute urine flow rate and its variability were analyzed in hypotensive multiple trauma patients during the first 6 h of their ICU (intensive care unit) stay. These parameters have not been previously reported. Methods: The study was retrospective and observational. Demographic and clinical data were extracted from the computerized Register Information Systems. A total of 59 patients were included in the study. The patients were divided into two study groups. Group 1 consisted of 29 multiple trauma patients whose systolic blood pressure was greater than 90 mmHg on admission to the ICU and who were consequently deemed to be hemodynamically compromised. Group 2 consisted of 30 patients whose systolic blood pressure was less than 90 mmHg on admission to the ICU and who were therefore regarded as hemodynamically uncompromised. Results: The urine output and urine flow rate variability during the first 6 h of the patients' ICU stay was significantly lower in group 2 than in group 1 (p < 0.001 and 0.006 respectively). Statistical analysis by the Pearson method demonstrated a strong direct correlation between decreased urine flow rate variability and decreased urine output per hour (R = 0.17; P = 0.009), decreased mean arterial blood pressure (R = 0.24; p = 0.001), and increased heart rate (R = 0.205; p = 0.001). Conclusion: These findings suggest that minute-to-minute urine flow rate variability is a reliable incipient marker of hypovolemia and that it should therefore take its place among the parameters used to monitor the hemodynamic status of critically ill multiple trauma patients.
Minute-to-minute urine flow rate; Urine flow rate variability; Monitoring; Multiple trauma
Trauma-associated acute hemorrhage is a leading cause
of intravascular volume depletion [
] ranging from
mild hypovolemia to hemorrhagic shock [
foremost priorities in acute trauma are hemorrhage control
and hemodynamic resuscitation . The urine output is
a vital clinical parameter of renal function and blood
volume status, especially in critically ill multiple trauma
patients during their hospital admission and ICU
(intensive care unit) stay [
]. It is typically measured hourly
and expressed in milliliters per hour. However, the blood
volume status and the renal function of multiple trauma
patients change more rapidly, especially during the first
24 h of ICU admission . In previously published
animal and human studies [
], the use of a continuous
minute-to-minute urine flow rate monitoring system
(URINFO™, FlowSense Medical, Misgav, Israel) has been
shown to detect hypovolemia earlier than other standard
parameters. The minute-to-minute UFR was found to be
a dynamic variable, which significantly decreases during
acute bleeding and is restored after rehydration .
Furthermore, an animal model of the minute-to-minute
UFR demonstrated that during euvolemia there is
variation in the flow rate and that this parameter decreases
and eventually disappears during acute hemorrhage. This
variability has also been shown to decrease and eventually
disappear during acute gradual hemorrhage [
This study analyzed minute-to-minute UFR and its
variability in hypotensive multiple trauma patients
during the first 6 h of their admission to the intensive care
unit (ICU). This is the first such study of the significance
of these parameters.
Soroka Medical Center is a University Level I trauma
center with approximately 2500–3000 trauma
admissions per year. About 10% of those trauma patients have
an Injury Severity Score (ISS) of 16 or above (severe
trauma). The study was retrospective and observational.
Clinical and laboratory data were collected
retrospectively from the records of all multiple trauma patients
hospitalized in the Soroka Medical Center general
intensive care unit (GICU) between January 2013 and January
2014. All the clinical data were extracted from the
computerized Register Information Systems (MetaVision® and
iMDsoft®, Israel). The Human Research and Ethics
Committee at Soroka Medical Center in Beer Sheva, Israel,
approved this study (RN-SOR-0158-14). The patients’
concern has not been needed because of retrospective nature
of the study. Patients were not involved in the design or
recruitment of the study.
All multiple trauma patients over the age of 18 who
were admitted to the GICU for more than 24 h were
considered eligible for inclusion in the study.
Patients who stayed in the GICU for less than 24 h were
excluded from the study. Also, anuric patients on
admission to the GICU as well as patients previously known
to have chronic renal failure or kidney disease were
excluded from the study. Lastly, patients were excluded
if their medical record data were incomplete.
Variables and measurements
The following data were collected: demographic data
(age, gender, weight); minute-to-minute UFR (see below;
urine output per hour; total fluid balance per hour; heart
rate; arterial blood pressure; body temperature; central
venous pressure (CVP); arterial blood pH and lactate
and bicarbonate levels, serum urea, creatinine, sodium
and chloride levels; hemoglobin level; admission trauma
diagnosis; and the APACHE-II score on admission to
the ICU. Clinical data was collected for the first 6 h of
ICU stay. Data on significant therapeutic measures
(administration of intravenous fluids, blood products, and
vasopressors) and clinical parameters (vital signs) were
collected for the first 6 h of the patients’ ICU stay.
Severity of critical illness and multiorgan failure were
evaluated by the APACHE II (Acute Physiology and
Chronic Health Evaluation II) score within 24 h of
admission to the GICU.
URINFO2000™ (FlowSense Medical, Misgav, Israel)
All multiple trauma patients admitted to the GICU
underwent insertion of a Foley catheter which was
routinely connected to a URINFO 2000™ device. URINFO
2000™ (FlowSense Medical, Misgav, Israel) is a novel
urine collecting and urine flow measurement system that
uses an optical drop detector to measure urine flow
every 3 min through a measuring chamber. The detector
enables the reliable calculation of the UFR at varying
flow rates and urine osmolarities. The system was
connected to the computerized patients’ record system of
The minute-to-minute UFR variability was defined and
calculated as the variance of UFR changes from minute
to minute [
]. The URINFO 2000™ (Flow Sense Medical,
Misgav, Israel) is a novel urine collecting and urine flow
measurement system that uses an optical drop detector
to measure urine flow every 3 min through a measuring
chamber. The difference between two consecutive values
(total 6 min), divided by the first value, multiplied by
100. The result of the formula represents the percentage
of change from the measured value every 3 min.
The patients were divided into two study groups. Group
1 consisted of 29 multiple trauma patients and who were
consequently deemed hemodynamically stable on
admission to ICU (systolic blood pressure (SBP) was greater
than 90 mmHg, mean arterial pressure more than
65 mmHg, central venous pressure more than 8 cmH2O)
on admission to the ICU. Group 2 consisted of 30 patients
and who regarded as hemodynamically unstable (SBP was
less than 90 mmHg, mean arterial pressure less than
65 mmHg, central venous pressure less than 8 cmH2O,
elevated blood lactate level) at admission to the ICU.
The two study groups (“compromised” and
“uncompromised”) were compared for UFR variability which was
the primary parameter under study.
The patients’ characteristics and outcomes were
compared using chi-square or Fisher’s exact tests for
categorical variables. Continuous variables were analyzed with a
Student’s t test or the Mann-Whitney Test, depending
on the validity of the normality assumption.
For comparison of minute-to-minute urine rate
variability, the coefficient of variation was calculated and
analyzed with a Student’s t test. The Pearson method
was used to analyze statistical correlation between
different vital parameters.
Dynamic changes of UFR variability during the first
6 h of ICU stay were demonstrated by the LOESS curves
non-parametric regression method. A p value of less
than 0.05 represents a statistically significant finding.
Statistical analyses were performed using IBM SPSS
Statistics 20 (IBM Corp.).
Initially, the clinical and laboratory data of 120 critically
ill multiple trauma patients admitted to the ICU during
the study period were analyzed. Of these, 59 patients
were eventually included in the study (Table 1).The
remaining 61 patients were excluded on the basis of the
exclusion criteria (of them, 30 patients were oligo-anuric
on admission to ICU have chronic renal failure or
kidney disease or had previously documented chronic
renal failure or kidney disease, 9 patients had incomplete
medical record data and 22 patients were hospitalized in
our ICU less than 24 h). The patients’ epidemiological
and clinical characteristics are summarized in Table 1.
The two groups (“uncompromised” and “compromised”)
were similar in age, gender, weight, APACHE score, and
length of ICU stay.
The patients in group 2 had significantly lower
systemic and mean arterial pressures and higher heart
rates on admission to the ICU compared to the patients
in group 1 (p < 0.001, Table 2).
The UO and the UFR variability during the first 6 h of
the patients’ ICU stay were significantly lower in the
group 2 patients than in the group 1 patients (p < 0.001
and 0.006 respectively).
The CVP and arterial blood pH were also significantly
lower in the group 2 patients than in the group 1 patients
(p < 0.001; Table 3). The laboratory parameters and body
temperatures of the patients in both groups were similar
during the first 6 h of their ICU stay (Table 3).
Statistical analysis by the Pearson method
demonstrated strong direct correlation between decreased UFR
variability and the following parameters: decreased urine
output per hour (R = 0.17; p = 0.009); decreased mean
arterial blood pressure (MAP) (R = 0.24, p = 0.001); and
increased heart rate (R = 0.205, p = 0.001). No
correlation with systolic blood pressure (R = 0.11, p = 0.073).
The dynamic changes in UFR variability are graphically
presented in Fig. 1. In contrast to the wide UFR
variability found in the group 1 (uncompromised) patients, we
demonstrated a significant trend towards decreased UFR
variability in the group 2 (compromised) patients during
the first 6 h of their ICU stay (Fig. 1).
The American College of Surgeons Committee on
Trauma guidelines define hypotension as a systolic blood
pressure (SBP) of less than 90 mmHg [
]. This threshold
is often used as a marker of hemodynamic instability in
adult patients with multiple trauma [
cornerstone of appropriate management of multiple trauma
patients is the early evaluation of their hemodynamic
status to detect potential hemorrhage or subacute
(“occult”) hypoperfusion [
]. The initial
assessment of these patients and decisions regarding further
administration of resuscitatory fluid or blood products
are accomplished by monitoring the patients’ vital
signs, especially blood pressure, heart rate, and urine
output. However, there are cases in which the clinical
picture is difficult to interpret because of the presence of
pain, hyper/hypothermia, neurogenic or cardiogenic shock,
or other factors [
]. An ideal monitoring device for such
patients would be noninvasive, small in size, transportable,
and easy to use and understand. It should be able to
provide early assessment of even a very minor degree of
hypoperfusion and as well as information on the adequacy of
blood volume resuscitation [
Optimal and adequate treatment of hypoperfusion is
crucial in preventing the development of reperfusion
injury, the systemic inflammatory response syndrome
(SIRS) and further progression to irreversible multiple
organ failure [
]. Despite “normalization of vital signs”,
including maintenance of a urine output of 0.5–1 cm3/kg/h,
occult hypoperfusion can still be present in multiple
trauma patients [
]. In the last two decades, a large
variety of noninvasive continuous hemodynamic
monitoring devices have been introduced into trauma centers
*P values less than 0.05 considered to be statistically significant
*P values less than 0.05 considered to be statistically significant
aVital signs at admission to ICU (mean ± SD)
bMean of urine output and urine flow rate variability per hour during first 6 h of ICU stay
worldwide. However, UO is the single important clinical
parameter that is not monitored electronically in most
centers. Early recognition of renal dysfunction in multiple
trauma patients is extremely important in the prevention
of further kidney injury, a complication which often
adversely affects the clinical outcome [
]. In recent years,
Urinfo, a new digital continuous minute-to-minute UFR
monitoring device (URINFO™, FlowSense Medical, Misgav,
Israel) has been shown to be significantly superior to
manual nurse-handled urinometers in terms of accuracy of
measurement, ease of handling, and staff satisfaction [
In a previous study, Shamir et al. [
] described the
successful use of continuous minute-to-minute UFR
monitoring in 11 patients who underwent elective spine surgery.
They demonstrated that the kidneys show rhythmic
variation in the minute-to-minute UFR, a phenomenon which
is probably mediated by pacemaker activity located in the
proximal portion of the upper urinary tract and influenced
by prostaglandins and sensory nerves [
]. A decrease in
the variability of the minute-to-minute UFR was an early
sign of bleeding or hypovolemia in these previously
healthy patients during their elective spinal surgical
]. Moreover, these authors [
] showed that the
UFR variability not only decreased during the bleeding
process but also returned to baseline after rehydration. In
animal models, Klein et al. [
] demonstrated a strong
correlation between the decrease in URF variability and the
onset of hypovolemia induced by controlled bleeding.
In the present study, we analyzed clinical data
describing minute-to-minute UFR and urine flow variability in
multiple trauma patients. We found a significant
decrease in minute-to-minute UFR and urine flow
variability in multiple trauma patients who presented to the
ICU with hemodynamic compromise (SBP less than
90 mmHg) compared to trauma patients who were
hemodynamically normal. In both study groups,
minuteto-minute UFR and urine flow variability decreased
during the first 6 h of ICU admission in parallel with
decreases in SBP and MAP and increases in heart
rate and arterial blood lactate levels. Importantly,
trauma patients in both study groups had an
“adequate” (about 1 cm3/kg/h) urine output. We found a
strong clinical correlation between decreased UFR
variability and decreased urine output per hour, decreased
mean arterial pressure and increased heart rate in the
group 2 (unstable) trauma patients. Thus, the
minute-tominute UFR/urine flow variability as a continuous,
sensitive measurement has a significant clinical advantage and
superior to other vital parameters as an early diagnosis of
hypovolemia in multiple trauma patients.
Our study has a number of limitations. The main
limitations are its retrospective design and the small number
of patients included in the study. Also, there is no
sample size calculation. Furthermore, because our study is
retrospective, the influence of directed, active control of
SBP on the minute-to-minute UFR, and urine flow
variability could not be estimated or taken into account.
Finally, it seems that low minute-to-minute UFR
variability correlate with hypovolemia and that means it occur
in opposite. Future investigations in a new prospective
p value (95%CI)*
*P values less than 0.05 considered to be statistically significant
design setup with control of all resuscitative parameters
need to be provided to clarify that.
We suggest that UFR variability can serve as a reliable
incipient marker of occult hypovolemia and also as an
indicator of the end-point of blood volume resuscitation.
We therefore propose that it should be one of the
parameters used to monitor the hemodynamic status of
critically ill multiple trauma patients. Furthermore, in
view of our findings, we suggest that more
comprehensive randomized and prospective studies should be
undertaken to evaluate the potential clinical role of UFR
variability and its influence on the ICU outcome of
multiple trauma patients.
UFR: Urine flow rate
There are no acknowledgements.
This research did not receive any specific grant from any funding agency in
the public, commercial or not-for-profit sectors.
Availability of data and materials
The datasets used and/or analyzed during the current study are available
from the corresponding author on reasonable request.
Dr. EB participated in study design, data collection, data analysis, data
interpretation, writing. Dr. YK participated in literature search, study design,
data collection, data analysis, data interpretation. Dr. RT participated in data
collection, performed the statistical analysis, data interpretation. Dr. LK
participated in the design of the study, performed the statistical analysis
and helped to revise the manuscript. Dr. DF participated in the design
of the study, performed the statistical analysis and helped to revise the
manuscript. Dr. MYS participated in the sequence alignment and drafted
the manuscript. Dr. MK participated in the design of the study, coordination
and helped to draft the manuscript. All authors read and approved the
manuscript. The manuscript has not been submitted to more than one journal
for simultaneous consideration.
Ethics approval and consent participate
The Human Research and Ethics Committee at Soroka Medical Center, Beer
Sheva, Israel, approved this study (RN- SOR-0158-14). The patients’ concern
has not been needed because of retrospective nature of the study.
Consent for publication
Consent to submit has been received explicitly from all co-authors.
The authors declare that they have no competing interests.
Springer Nature remains neutral with regard to jurisdictional claims in
published maps and institutional affiliations.
1. Committee on Trauma, American College of Surgeons. ATLS: advanced trauma life support program for doctors . 8th ed. Chicago: American College of Surgeons; 2008 .
2. Søreide E , Deakin CD . Pre-hospital fluid therapy in the critically injured patient-a clinical update . Injury. Int J Care Injured . 2005 ; 36 : 1001 - 10 .
3. Shackelford SA , Colton K , Stansbury LG , Galvagno SM , Anazodo AN , DuBose JJ , et al. Early identification of uncontrolled hemorrhage after trauma: current status and future direction . J Trauma Acute Care Surg . 2014 ; 77 : 222 - 7 .
4. Hersch M , Einav S , Izbicki G . Accuracy and ease of use of a novel electronic urine output-monitoring device compared with standard manual urinometer in the intensive care unit . J Crit Care . 2009 ; 24 ( 629 ): 13 - 7 .
5. Gutierrez G , Reines HD , Wulf-Gutierrez ME . Clinical review: hemorrhagic shock . Crit Care . 2004 ; 8 : 373 - 81 .
6. Shamir MY . MD, Kaplan L. , Marans R.S. , Willner D. , Klein Y. Urine flow is a novel hemodynamic monitoring tool for the detection of Hypovolemia . Anesth Analg . 2011 ; 112 : 593 - 6 .
7. Klein Y , Grinstein M , Cohn SM , Silverman J , Klein M , Kashtan H , et al. Minute-to-minute urine flow rate variability: a new renal physiology variable . Anesth Analg . 2012 ; 115 : 843 - 7 .
8. Parks JK , Elliott AC , Gentilello LM , Shafi S. Systemic hypotension is a late marker of shock after trauma: a validation study of advanced trauma life support principles in a large national sample . Am J Surg . 2006 ; 192 : 727 - 31 .
9. American College of Surgeons Committee on Trauma. FAQ for resources for optimal Care of the Injured Patient: 2006 . Chicago, IL: American College of Surgeons; 2006 . Available at: www.facs.org/trauma/faq_answers.html. Accessed May 20 , 2008
10. Wiencek RG , Wilson RF , Demaeo P . Outcome of trauma patients who present to the operating room with hypotension . Am Surg . 1989 ; 55 : 338 - 42 .
11. Schulman AM , Claridge JA , Carr G , Diesen DL , Young JS . Predictors of patients who will develop prolonged occult Hypoperfusion following blunt trauma . J Trauma . 2004 ; 57 : 795 - 800 .
12. Drucker W , Pearce F , Glass-Heidenreich L , et al. Subcutaneous tissue oxygen pressure: a reliable index of peripheral perfusion in humans after injury . J Trauma . 1996 ; 40 : 116 - 22 .
13. Moore FA , Haenel JB , Moore EE , Whitehill TA . Incommensurate oxygen consumption in response to maximal oxygen availability predicts postinjury multiple organ failure . J Trauma . 1992 ; 33 : 58 - 65 .
14. Kuster M , Exadaktylos A , Schnürige B . Non-invasive hemodynamic monitoring in trauma patients . World J Emerg Surg . 2015 ; 10 : 11 .
15. Moore FA , McKinley BA , Moore EE . The next generation in shock resuscitation . Lancet . 2004 ; 363 : 1988 - 96 .
16. Costantini TW , Fraga G , Fortlage D , Wynn S , Fraga A , Lee J , et al. Redefining renal dysfunction in trauma: implementation of the acute kidney injury network staging system . J Trauma . 2009 ; 67 : 283 - 8 .
17. Weiss RM , Tamarkin FJ , Wheeler MA , M. A. Pacemaker activity in the upper urinary tract . J Smooth Muscle Res . 2006 ; 42 ( 4 ): 103 - 15 .