All the previous parts of this series looked at the physiology of fluids and how they interact in the different compartments. The original question I asked was why do we give fluid in resuscitation? There are 4 different types of shock and I have previously discussed that there should be a 5th.
1. Distributive Shock
2. Hypovolemic Shock
3. Cardiogenic Shock
4. Obstructive Shock
Resuscitating patients in shock is based on reversing organ failure. This means that all resuscitation comes down to the oxygen delivery equation.
The Answer:
We give fluids in resuscitation because of the oxygen delivery equation.
Figure 1: Oxygen Delivery Equation
Basically, in order to get oxygen to your organs you need hemoglobin, you need oxygen attached to the hemoglobin, and you need to pump it around to deliver it. It helps to remember these big three.
Oxygen Delivery = Cardiac Output x Hemoglobin x Saturation
The oxygen delivery equation is essential to almost every intervention we do in the ICU. The triad of organ failure, resuscitation, and oxygen delivery, encompasses all of critical care.
Figure 2: Critical Care Triad
How does fluid fit into the oxygen delivery equation? It is used to increase cardiac output. When patients fall on the Starling curve they drop their cardiac output. Decreased cardiac output leads to a decrease in oxygen delivery and organ failure. Giving fluids puts them higher up on the Starling curve and improves their cardiac output.
Figure 3: Starling Curve
Fluids will not help in resuscitation if there is not an issue of decreased preload causing decreased cardiac output. This means that cardiogenic shock, obstructive shock, and cirrhotic shock do not benefit from fluids.
Keeping fluid in the intravascular space
With hypovolemic shock, it is easier to identify the finite level of fluid needed to resuscitate the patient. If it is dehydration, then isotonic fluid is given until the patient is euvolemia. If it is hemorrhagic shock, blood products are given, typically 1:1:1 with red blood cells, fresh frozen plasma, and platelets, until the lost blood is replaced. There can be uncontrolled bleeds that need intervention but otherwise, the vasculature itself is relatively intact and it is just about returning the lost volume.
With distributive shock and fluids, everything is completely different. We will discuss septic shock since it is the most common distributive shock. You could spend a career discussing the place for fluids in septic shock. In septic shock, the patient has a relative and absolute hypovolemia within the vasculature system. This is due to vasodilation and a loss of intercellular bridges in the endothelium leading to leakage. Both of these issues are due to the cytokine release caused by the infection. This vasodilation and increased venous reservoir were discussed in a previous post about mean systemic filling pressure.
Figure 4: Mean Systemic Filling Pressure and Septic Shock
In septic shock, the amount of venous dilatation and the amount of fluid leaking into the interstitium is unknown and continues until the cause is reversed. Additionally, since the fluid is not outside the body but just shifted into the interstitial space, the problem is not lack of fluid, but that the vasculature is dilated and the fluid is now in the interstitium.
Let’s look at the intravascular space as a bucket of syrup. This bucket holds 4 liters of syrup and it is important to keep this bucket full.
Figure 5: Normal intravascular space bucket
Throughout the day the bucket will lose some volume due to evaporation, so some water will be needed to replace the evaporation. The thickness of the syrup helps keep it in the bucket and is typically kept at 4L very easily.
Now, when the person becomes sick the bucket expands to a 6L bucket and it springs multiple leaks.
Figure 6: Septic shock intravascular space bucket
It is easy to see why this leads to organ failure. There is a significant drop in preload and a subsequent drop in cardiac output. And this is why fluid resuscitation has become a mainstay in septic shock resuscitation.
But fluid resuscitation is about getting fluid into the intravascular space to move up the Starling curve and keeping it in there. It is important to consider the factors that put the patient in this position. In other words, what is making the 4L originally in the bucket not be enough.
Cytokine Vasodilation: 4L -> 6L – now it is already 2/3 full instead of completely full
Cytokine endothelial leak: holes in the bucket - now the 4L is down to 2-3L with the holes
Drop in oncotic pressure: Syrup is thinned out – now it is easier to flow out of the holes
Tying this into the previous parts, the patient will also lose oncotic pressure due to crystalloid resuscitation and critical illness. The albumin levels drop, and since it makes up most of the oncotic pressure, the oncotic pressure drops, and fluid is more likely to leak out according to the Starling equation.
How a lot of people currently treat septic shock:
Figure 7: Pour water in faster
Looking at the physiology, it is easy to see why this method does not work well and leads to complications. This does not fix the problem, all it does is overload the patient and lead to organ edema and worse outcomes. The answer cannot be to just pour fluid in faster than the bucket leaks.
A better way to treat septic shock:
Figure 8: Physiological approach
The answer:
1. Shrink the bucket: add vasopressors and decrease the reservoir and increase MSFP
2. Patch the holes: add stress dose steroids, decrease cytokines and fix the leakiness
3. Ensure thickness: add 25% albumin if the oncotic pressure is low (albumin <2.5g/dL) or hypertonic fluid
4. Ensure volume: some crystalloids may be needed while the antibiotics, steroids, vasopressors, albumin are being ordered.
If the physiology is correct then the research should show that adding stress dose steroids, vasopressors, and 25% albumin should help reduce the amount of fluid needed to give, improve time to shock resolution, and may even help with mortality.
Stress dose steroids in septic shock:
APROCCHSS Trial- Hydrocortisone 50mg every 6 hours + Fludrocortisone 0.05mg daily
- Improved mortality at 90 days
- Less time on vasopressors, less time in organ failure
Early vasopressors in Septic Shock
CENSER Trial – Norepinephrine
- Less time in shock
- Less pulmonary edema, less arrhythmias
Hyperoncotic albumin in septic shock
SWIPE Trial – 20% albumin
- Less fluid resuscitation needed
- Lower cumulative fluid balance
Hypertonic fluids in septic shock
BICAR-ICU Trial – 4.2% Sodium Bicarbonate
- Decreased organ failure and mortality in patients with acute kidney injury
Putting it all together:
Fluid resuscitation should only be done when there is organ failure due to low preload. If there is no problem with the preload, then fluid resuscitation leads to volume overload and worse outcomes. Every time fluid is given for low preload a reevaluation should be done to monitor if more fluid is needed or if the preload is repleted.
We need to move on from the world of overly aggressive fluid resuscitation in shock. We need to move on from the idea that the answer is just pouring fluid in faster. It is time to treat fluid resuscitation correctly and work on ensuring intravascular volume from a physiological basis.
References:
1. Starling forces and fluid exchange in the microcirculation: Deranged Physiology. https://derangedphysiology.com/main/cicm-primary-exam/required-reading/cardiovascular-system/Chapter%20471/starling-forces-and-fluid-exchange-microcirculation. Accessed 7/12/21.
2. Tobias A, Ballard BD, Mohiuddin SS. Physiology, Water Balance. [Updated 2020 Oct 7]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2021 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK541059/
3. Annane D, Renault A, Brun-Buisson C, et al. Hydrocortisone plus Fludrocortisone for Adults with Septic Shock. N Engl J Med. 2018;378(9):809-818. doi:10.1056/NEJMoa1705716
4. Permpikul C, Tongyoo S, Viarasilpa T, Trainarongsakul T, Chakorn T, Udompanturak S. Early Use of Norepinephrine in Septic Shock Resuscitation (CENSER). A Randomized Trial. Am J Respir Crit Care Med. 2019;199(9):1097-1105. doi:10.1164/rccm.201806-1034OC
5. MÃ¥rtensson J, Bihari S, Bannard-Smith J, et al. Small volume resuscitation with 20% albumin in intensive care: physiological effects : The SWIPE randomised clinical trial. Intensive Care Med. 2018;44(11):1797-1806. doi:10.1007/s00134-018-5253-2
6. Jaber S, Paugam C, Futier E, et al. Sodium bicarbonate therapy for patients with severe metabolic acidaemia in the intensive care unit (BICAR-ICU): a multicentre, open-label, randomised controlled, phase 3 trial [published correction appears in Lancet. 2018 Dec 8;392(10163):2440]. Lancet. 2018;392(10141):31-40. doi:10.1016/S0140-6736(18)31080-8