When resuscitating a patient in shock while working up the cause of shock, the first treatment most people turn to is IV crystalloid. It can be helpful in distributive and hypovolemic shock. But, in obstructive shock, it depends on the etiology, and in cardiogenic shock, it can actually be detrimental. What is the purpose of giving fluids in shock? It is not to increase the blood pressure, although that is a helpful result, it is to increase oxygen delivery.
Resuscitation is all based on the oxygen delivery equation (Figure 1) and fluid resuscitation on venous return and the Frank-Starling curve (Figure 2).
Figure 1:
Figure 2:
When patients are in shock they are not able to deliver the amount of oxygen needed for their organs to function. The reasons for the decrease in oxygen delivery vary depending on the cause of shock. Resuscitation increases oxygen delivery by either increasing cardiac output (CO), hemoglobin, or saturation. Cardiac output is further broken down into preload, contractility, and afterload. For a hypotensive patient, it is assumed that the patient has less preload and fallen to a lower part of the Frank-Starling curve and therefore has a lower cardiac output.
By giving the patient IV fluids, it will increase their preload and put them higher on the Frank-Starling curve.
This beneficial relationship of fluids increasing cardiac output will eventually decline as the curve plateaus. This relationship has created the dogma that IV fluids always equal better preload and better cardiac output. This has led to a trend towards over-resuscitation and complications of hypervolemia.
IV fluids do not always lead to an increase in preload. Preload is defined as the end-diastolic volume of the ventricle in question. For the right ventricle, the preload is the right ventricular end-diastolic volume (RVEDV). This is estimated by using the right ventricular end-diastolic pressure (RVEDP) as a surrogate, and the right atrial pressure (RAP) as a surrogate for RVEDP, and the central venous pressure (CVP) as a surrogate for RAP.
This line of assumptions is unreliable and problematic. But, what we can use is that venous return to the RAP dictates preload and preload dictates cardiac output. Venous return is not determined by IV fluid infusions, it is determined by a pressure gradient.
The pressure gradient that creates venous return is not the mean arterial pressure (MAP) – right atrial pressure (RAP), it is the difference between the mean systemic filling pressure (MSFP) – right atrial pressure (RAP).
The mean circulatory filling pressure (MCFP) is the pressure in the vascular system when the heart is stopped and the pressure equalizes. Guyton worked on this using dogs and found that the normal MCFP was 8mmHg. This is the assumed MCFP for humans as well (1).
Mean systemic filling pressure (MSFP) is the pressure in the venous system under normal flow conditions. The difference between MSFP and MCFP is minimal, but MCFP can be affected by left and right heart dysfunction since it includes the entire circulatory system. You may see these used interchangeably at times, but for venous return, it is the difference between MSFP and RAP (2).
Venous Return (VR) = MSFP - RAP
MSFP is the pressure at the level of the venules, which are directly after the capillaries, making venous return entirely dependent on the venous system.
As MSFP and RAP get closer in value the amount of venous return will drop. When MSFP and RAP equal each other the venous return will be zero.
Below are the results of Guyton’s experiments where he held MCFP constant, returned blood to the dogs, and monitored their venous return. There was a linear relationship found. (Figure 3). Venous return plateaued at 0mmHg due to venous collapse and not due to the gradient.
Figure 3:
Redrawn from Guyton (1)
A common practice is placing the Frank-Starling curve on the Guyton venous return curve. It is technically not the Frank-Starling curve since it uses RAP and not LVEDV. But, it can be used to understand hemodynamics better. It is often referred to as the Guyton Diagram when the X-axis is RAP (Figure 4).
Figure 4:
The Guyton diagram above shows that when fluid is added it increases MSFP which increases venous return and increases the patient’s cardiac output. So, when resuscitating a patient, it is important to understand this concept and optimize the gradient between MSFP and RAP to increase venous return and improve oxygen delivery.
The venule pressure is the MSFP and the value is due to the venule's capacitance. Capacitance is defined as the volume of blood at a certain transmural pressure. It is similar to compliance, but compliance looks at the change in volume over the change in pressure. When the capacitance is decreased there will be a higher pressure for a given volume.
The capacitance of the venules varies depending on different conditions. Sympathetic stimulation reduces capacitance and sepsis/distributive shock increases capacitance (Figure 5).
Figure 5:
The change in capacitance of the venules is different from the change in the capacitance of the right atria. This means that the venules will respond to fluid increases differently from the right atria and the gradient change as more fluid is added (Figure 6).
Figure 6:
The other concept to remark on is the stressed and unstressed volume on the venous side. 85% of the venous volume is unstressed and does not contribute to the pressure on the venous side. It is the last 15% that exerts all the pressure and creates the mean systemic filling pressure. Adding volume or increasing venous tone with sympathomimetics will both increase the amount of stressed volume but in different ways (Figure 7).
Figure 7:
This representation of stressed and unstressed volume can also show how the stressed volume creates the MSFP and its gradient to the RAP creates venous return (Figure 8).
Figure 8:
Another way to look at venous return is by graphing the change in MSFP compared to the change in RAP. It creates a venous return curve similar to the Frank-Starling curve (Figure 9).
Figure 9:
Optimizing venous return
This is where the practice of medicine starts and these are my thoughts on how to optimize venous return.
Septic Shock:
When a patient is in septic shock, the MSFP and RAP will have an increase in capacitance and drop their pressures (Figure 10). The △MSFP and △RAP with fluid resuscitation are different from their baseline and when fluid is given the MSFP will increase its pressure less compared to the increase in RAP. The drop in MSFP will decrease the gradient and decrease venous return. (Figure 11). It is the increase in HR that makes septic shock high output, the venous return is actually decreased (4).
Figure 10:
Figure 11:
When fluid is given it increases RAP at a higher rate than MSFP and actually worsens venous return after initially seeing a benefit at physiologic blood volumes (Figure 12). Vasopressors, however, will cause venoconstriction and increase MSFP and increase venous return even with hypervolemia (Figure 12). This is another example of too much fluid worsening outcomes and the importance of early vasopressors instead of more fluids.
Figure 12:
When you give vasopressors instead of fluid, it increases MSFP better than fluid. Fluids increase the stressed volume with more volume, but vasopressors shrink the dilated reservoir and change unstressed volume to stressed volume.
Cardiogenic Shock:
When a patient has cardiogenic shock there is an increase in RAP in a higher proportion to the increase in MSFP (Figure 13). This means the pressure gradient drops with fluid administration and worsens venous return (Figure 14).
Figure 13:
Figure 14:
Treating patients with inotropes will increase contractility and forward flow which will increase MSFP and decrease RAP and improve venous return (Figure 15).
Figure 15:
When the normal, septic, and cardiogenic curves are combined, the way that venous return is reduced in both types of shock is appreciated (Figure 16).
Figure 16:
Using this as a foundation, I hope it shows why hypervolemia leads to such poor outcomes no matter the underlying disease. As the volume increases to supratherapeutic levels, the RAP will increase at a higher rate than MSFP. This will give a curve similar to the myocardial dysfunction curve (Figure 17).
Figure 17:
MSFP and venous return was also described in a medical blog by @WhistlingDixie4 and a great image worth sharing.
I hope this either introduces you to mean systemic filling pressure and helps understand its importance for venous return and cardiac output, or that it helps you better understand how too much fluid can be harmful. I also hope to show that vasopressors are not a failure and should be started early.
1. Guyton AC. Determination of cardiac output by equating venous return curves with cardiac response curves. Physiol Rev. 1955;35(1):123-129. doi:10.1152/physrev.1955.35.1.123
2. Sunagawa K. Guyton's venous return curves should be taught at medical schools (complete English translation of Japanese version). J Physiol Sci. 2017;67(4):447-458. doi:10.1007/s12576-017-0533-0
3. Spiegel R. Stressed vs. unstressed volume and its relevance to critical care practitioners. Clin Exp Emerg Med. 2016;3(1):52-4.
4. Zanotti Cavazzoni SL, Dellinger RP. Hemodynamic optimization of sepsis-induced tissue hypoperfusion. Crit Care. 2006;10 Suppl 3:S2. doi: 10.1186/cc4829.
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