1

Background Information
Hypovolemia is a significant decrease in the volume of circulating blood in the body that can be
attributed to blood loss resulting from external/internal hemorrhage. Oxygen (O2) delivery to critical
organs and tissues decreases as a result of the decrease in red blood cells containing hemoglobin.
Additionally, urine production decreases (indicative of low renal perfusion), heart rate increases in the
attempt to compensate for low stroke volume, and hypotension occurs as a result of low mean arterial
pressure (MAP). It is critical to monitor a hypovolemic patient’s heart rate, urine production, and
hematocrit in order to efficiently administer the appropriate treatments and prolong survival.
Hypovolemic patients immediately require an ample flow of supplemental O2 to increase the
oxygen saturation of the blood to about 95-100%, which in turn maximizes O2 delivery and compensates
for low blood perfusion due to hypotension. As blood volume decreases, fluid levels in the kidneys fall,
renal perfusion decreases, and subsequently urine output begins to decrease, potentially causing kidney
function to deteriorate. In response, fluid resuscitation is performed by supplying isotonic (0.9%) or
hypertonic (about 3%) saline (NaCl) solution intravenously (IV). Continuously administering fluids may
cause hemodilution, however, thereby decreasing hematocrit as well as the O2-transporting ability of the
blood. Epinephrine serves to increase heart rate when it is released by sympathetic innervations in blood
vessels and binds to adrenergic receptors in the sinoatrial node of the heart.
Hypothesis
The length of hypovolemic patient survival is defined as how long the urine output stays above
0.25 mL/min, hematocrit above 10%, or heart rate above 0 beats/min (bpm). I hypothesize that a
combination treatment of isotonic saline solution, 100% supplemental O2, and epinephrine at low rates
(no higher than 1000 ng/min) will extend the patient’s survival time past the control time.
Experimental Design/Methods
Using Just Physiology, a control was established by letting the simulation run with all treatment
variables fixed at default settings (without touching them). After recording the endpoint of the control, the
simulation was reset and the hypothetical treatment was initiated. For the first 60 minutes, IV NaCl
solution was supplied at a concentration of 0.1 mmol/L and a rate of 11 mL/min, and supplemental O2
was fixed at 100%. After 60 minutes passed, the epinephrine pump was turned on and set to 1000 ng/min
for 20 minutes. After the 20 minute interval, epinephrine rate was reduced by 200 ng/min every 10
minutes for a total of 20 minutes. For an additional 10 minutes, NaCl concentration was increased to 150
mmol/L, IV rate decreased to 5 mL/min, and epinephrine rate increased to 800 ng/min.
Results
The endpoint of the control was 60 minutes. Heart rate reached its first maximum after 60
minutes, with that of the treated patient lower than the control by 0.80 bpm (refer to Figures 1a and 1b).
However, at the 60-minute mark, the heart rate of the treated patient abruptly fell to about the same level
as the control heart rate in less than 4 minutes. Hematocrit level for the treated patient fell at a slightly
higher rate and with a more apparent linear trend compared to the control (see Figures 2a and 2b). The
most notable difference between the two was the control hematocrit momentarily increasing between 70
and 90 minutes. Overall, both levels stayed above 10%. Urine production was the first of the three
measured variables to fall below threshold level. However, in the control, this change occurred after only
40 minutes, while in the treated patient, it took over twice as much time (refer to Figures 3a and 3b).
Conclusion
Ultimately, the results appear to support the hypothesis. It appears that administering an isotonic
NaCl solution was enough to sustain renal perfusion by compensating for low fluid volume in the system.
Also, applying epinephrine stimulated the heart to work slightly harder and did not let the rate dip too
low. It is yet uncertain if the final change in NaCl concentration and IV rate helped to add several more
minutes of survival, raising a larger biomedical problem: the selection of medical treatments necessary to
support homeostatic functions in a body afflicted by other abnormal physiological conditions. Addressing
this problem requires examining where the physiological feedback loop is disrupted and restoring it
accordingly. In this case, a hemorrhage disrupts flow between the heart and body tissues contained in the
systemic loop, so IV fluids, epinephrine, and an O2 supply serve to temporarily sustain the loop.
 2

Figure 1a Figure 1b

Heart Rate (Treatment) Heart Rate (Control)

82 86
80 84
82

Heart Rate (bpm)

Heart Rate (bpm)

78 80
76 78
74 76
74
72 72
70 70
0 20 40 60 80 100 120 0 50 100 150
Time (min) Time (min)
Aside from the sharp and brief drop in heart rate at around 60 minutes (treatment trial), the only other
difference is that the final recorded heart rate is slightly higher in the control trial.

Figure 2a Figure 2b
Hematocrit (Treatment) Hematocrit (Control)
43 42
42
41.5
41
Hematocrit (%)
Hematocrit (%)

40 41
39 40.5
38
40
37
36 39.5
0 20 40 60 80 100 120 0 20 40 60 80 100 120
Time (min) Time (min)
At 60 minutes, epinephrine seems to have had some role in slightly offsetting the linear decrease in the
treated patient’s hematocrit level. In the untreated patient the offset happens about 10 minutes later.
Figure 3a Figure 3b
Urine Output (Treatment) Urine Output (Control)
5 0.8
0.7
Urine Output (mL/min)

Urine Output (mL/min)

4
0.6
3 0.5
0.4
2 0.3
0.2
1
0.1
0 0
0 20 40 60 80 100 120 0 20 40 60 80 100 120
Time (min) Time (min)
In the untreated patient, urine output falls below 0.25 mL/min just before 40 minutes have passed. In the
treated patient, it falls below 0.25 mL/min after approximately 110 minutes.