Resuscitation in Sepsis using Fluid/Volume Responsiveness

This post is a work in progress blog post for my lecture titled “Resuscitation and Fluid Responsiveness”. In the lecture, I discuss fluid resuscitation in sepsis in volume responsiveness. After all, only 50% of critically ill patients are fluid responsive and 66% of patients in septic shock are volume overloaded on hospital day 1 (Douglas, et al.). Those are crazy numbers, right? This means that although we think we’re good at providing our patients with appropriate IV fluid resuscitation when they are critically ill, say with septic shock, we aren’t as good as we think we are. We can’t keep on drowning our patients. Preload responsiveness is another term used for this. Last updated 05/29/22 and is a work in progress. It is definitely not all inclusive and complete at the moment (and I doubt it ever will be).

This is extremely important because the last data I’ve found from 2017 shows that there are 11 million sepsis-related deaths (or 19.7% of all global deaths per year). We need to resuscitate these people well to decrease the death rate from sepsis.

If you use contents from this post on your own work, please cite this post as:
Eddy J. Gutierrez, “Fluid Resuscitation in Sepsis and Volume Responsiveness”, eddyjoemd blog, May 29, 2022. Available at: https://eddyjoemd.com/fluid-resuscitation/

Table of Contents (In the works)

  • How Quickly are IV Fluids Extravasated?
  • What is Fluid Responsiveness?
    • Tying Fluid Responsiveness to the MAP
    • How much Fluids Should we use to determine volume responsiveness?
    • Can 100cc be used to determine fluid responsiveness?
  • The Adverse Effects of Giving Too Much Fluid
  • Static Markers
    • Central Venous Pressure
    • SvO2 and ScVO2
  • Dynamic Markers
    • Passive Leg Raising
    • Delta Stroke-Volume
    • Using Stroke Volume and Cardiac Output
    • Pulse Pressure Variation
    • Stroke Volume Variation
    • Echocardiography Principles: Velocity Time Integral
    • Dynamic arterial elastance
    • End-expiratory occlusion (EEXPO/EOP/EEO)
  • Citations

A Quick One-Stop for Fluid Responsiveness in Fluid Resuscitation

This is a one-minute journal club-ish.
This is not medical advice. Do not trust me.
Read the article for yourself by clicking the link. 
Hat tip to the authors: Xavier Monnet and Jean-Louis Teboul are legends in this space.
This paper was published on May 25th, 2022.
We don’t want to drown our patients.
Assessing for fluid responsiveness is just good medicine.
How do we go about it, though?
Here are some strategies.
I will create videos like this on each of these as time permits.
#1 Passive leg raising.
#2 End-expiratory occlusion testing
#3 Pulse pressure variation and stroke volume variation testing
#4 Tidal volume challenge
#5 IVC measurements
#6 Mini-fluid challengwe with 100cc
Although the most important part of the article is where the authors admit limitations to all this
There’s no perfect way to manage fluid status in patients.
We are still figuring this out.

Citation:
Monnet X, Shi R, Teboul JL. Prediction of fluid responsiveness. What’s new? Ann Intensive Care. 2022 May 28;12(1):46. doi: 10.1186/s13613-022-01022-8. PMID: 35633423.
Link to Article
Link to FULL FREE PDF

Tools for Fluid Responsiveness: One...
Tools for Fluid Responsiveness: One-Minute Journal Club-ish

How quickly are the IVF we bolus our patients extravasted into the interstitium?

First of all, just because you give a patient a liter of fluids does not mean that those 1000cc of your fluid of choice, plasma-lyte, lactated ringers, or 0.9% NaCl are going to stay in the intravascular space. I will defer to more expert physiologists to explain the integrity of the endothelium and how the glycocalyx gets angry during sepsis at this time. What we do know, if that if you or I, healthy people (in theory) receive a liter of fluid. I clarify, healthy people, because if these are the data for healthy people, then you KNOW it’s going to be worse for the critically ill who we take care of.

Lobo et al. found that “68% of the saline infused had escaped into the extravascular fluid compartment at 1 hr” when their team provided 1L of 0.9% NaCl over 1 hour to health volunteers. Take a second to think about this as it is important. This means that what stated in the blood vessels was ONLY 32%. ONLY 32%. The rest would be doing absolutely nothing to benefit our patients.

Now that we know what it is like in healthy volunteers, let’s take it a step further and look for data in patients who are deemed critically ill. Here, Ragaller et al. cited a paper from 1998 that I cannot get my hands on and stated “Isotonic crystalloid solutions… their effect on plasma volume expansion of approximately 200 ml for every 1000 ml administered, with an intravascular half-life of 20 to 30 min, is very limited”. My interpretation of these data is that if a critically ill patient is provided with 1L of IV fluids, 80% of this fluid is extravasated. 50% of the fluid infused is lost within 20 to 30 minutes and does into the interstitial space. These data justify the rationale as to why nurses should not place a liter bag of fluids on the pump and hit 999ml/hr. These patients will need at least a pressure bag to provide an amount of fluids that would actually determine fluid responsiveness.

Now that we have an idea of how much fluid stays in the intravascular space at around one hour, do we have any data to teach us how much hangs around in the intravascular space?

What is Fluid Responsiveness?

Fluid responsiveness is defined as an increase in stroke volume or cardiac output/cardiac index after being provided with a bolus of IV fluids.
The whole purpose of providing a fluid challenge is to increase either the cardiac output or stroke volume, not increase MAP. Here are some examples in the literature of dynamic parameters that could be used to determine fluid responsiveness:

  • PLR or fluid challenge: Stroke Volume increase >10%
  • Stroke volume variation (SVV) >10-15%
  • Pulse Pressure Variation (PPV) >10-13%
  • Cardiac Output/Index increase by 7-15%

You have a patient who is hypotensive. You want to make them not hypotensive. That part is simple. The first thing the vast majority of clinicians reach for is some sort of IV fluid. We give it and cross our fingers that they won’t be hypotensive after the fluids were provided. This is what is done in every single hospital throughout the world every day.

I’ve already posted before that even in a healthy person, if they get a liter of fluid, 68% of it will be extravasated within 1 hour. Much more and far quicker will that volume be lost in someone who is critically ill; approximately 80% in 30 minutes. No wonder the “response” to that liter of fluid was so short lived. Doing this over and over without guidance causes fluid overload which has many complications. Marik has a great paper on the matter.

Why we don’t tie Fluid Responsiveness to the Mean Arterial Pressure (MAP)

We take care of sick patients. In doing so, we have various tools in our disposal including the physical exam, history, and hemodynamic parameters. We check the blood pressure on our patients and depending on that number, we do things for them (hopefully not to them). 
The blood pressure cuff goes on their extremity, hopefully the right size, and cycle it. We have learned about the limitations of the oscillometric devices as I have covered that extensively and we have learned to trust the mean arterial pressure (MAP). Check out my YouTube video explaining oscillometric devices for blood pressure.

We all learned that the equation for MAP is:
MAP= [(2 x diastolic)+systolic]/3
We also learned that we should target a MAP of 65 based on the surviving sepsis guidelines and I generally agree with this. Sometimes I target a higher MAP, sometimes a lower MAP. Every patient is needs personalized care in my book. 

Here’s the other equation that we should know but don’t. 
MAP= (CO x SVR) + CVP
– CO= cardiac output, also HR x SV (and don’t forget that the stroke volume is affected by preload, contractility, and afterload)  
– SVR= systemic vascular resistance
– CVP= central venous pressure (tends to be zero in a spontaneously breathing patient). This value tends to be ignored for the sake of simplicity. 

We all give IV fluids to increase the MAP, because that is what we see on the monitor, but that’s the missing the point. As above, fluid responsiveness is defined as an increase in stroke volume or cardiac output/cardiac index after being provided with a bolus. 

Studies have shown us that only 50% of patients who are septic actually respond to fluid resuscitation. The other 50% who we blast with fluids, well, they just get overloaded and have complications secondary to that. 

The point of this post is for us to think a bit more outside the box when we have a patient who is hypotensive. We can’t just look at the blood pressure after being given a liter of fluid and call the patient fluid responsive. 

The FENICE study looked at 2213 patients and 42.7% of the time, the clinicians gave IV fluids without looking at any hemodynamic parameters. Even when the patient had a “negative response” to the fluid bolus, 49.4% of the time, the clinician gave an additional bolus after that! I think you can call that insanity per the Einstein definition of it. 

The clinicians were looking at primarily an increase of BP followed by urine output, decrease in HR, decrease in lactate rather than changes in CO or SV. Let’s just say that we have all been guilty of this in the past but need to get better on the matter. 

Here are some examples on where that thinking can lead us astray:
If the MAP is low but their CO or SV is looking great but their SVR is on the floor, they may need earlier vasopressors and nuanced fluid challenges. In the case of cardiogenic shock, you may find that the CO is on the floor and their SVR is sky high, those patients may benefit from some careful peripheral vasodilators with some inotropes. That undefined patient who is hypotensive and we give a liter of fluids to indiscriminately is quite dangerous at the end of the day. People come to the hospital to be helped, in those cases, we may actually be causing harm. 

What does fluid responsiveness NOT tell us?

Manecke G. Volume Responsiveness: What It Does Not Tell Us. J Cardiothorac Vasc Anesth. 2021 May;35(5):1307-1309. doi: 10.1053/j.jvca.2020.12.038. Epub 2021 Jan 2. PMID: 33455888.
Link to Article
Link to FULL FREE PDF

Adverse Effects of Volume Overload

I created an entire post on this HERE. Paul Marik provided the list below in THIS PAPER in 2014.

Pulmonary edema and increased extra-vascular lung water

– Impaired oxygenation
– Altered pulmonary and chest wall mechanics
– Increased work of breathing

Myocardial edema
– Decreased contractility
– Diastolic dysfunction
– Conduction defects

Increased intraabdominal pressure
– Acute kidney injury
– Hepatic dysfunction
– Decreased lung volumes
– Ileus

Gastrointestinal
– Ileus
– Malabsorption
– Bacterial translocation
– Hepatic congestion

Sure, a list is nice to read and all that, but what happens in clinical practice when a patient has a positive fluid balance and is on mechanical ventilation? In February of 2022, Wang et al. published a paper where they found that the high cumulative fluid balance on patients on mechanical ventilation led to more ventilator-associated events. We need to be judicious with our fluid resuscitation and test fluid/volume responsiveness rather than potentially harming our patients.

Malbrain MLNG, Van Regenmortel N, Saugel B, De Tavernier B, Van Gaal PJ, Joannes-Boyau O, Teboul JL, Rice TW, Mythen M, Monnet X. Principles of fluid management and stewardship in septic shock: it is time to consider the four D’s and the four phases of fluid therapy. Ann Intensive Care. 2018 May 22;8(1):66. doi: 10.1186/s13613-018-0402-x. PMID: 29789983; PMCID: PMC5964054.
Link to Article
Link to FULL FREE PDF

Chaudhuri D, Herritt B, Lewis K, Diaz-Gomez JL, Fox-Robichaud A, Ball I, Granton J, Rochwerg B. Dosing Fluids in Early Septic Shock. Chest. 2020 Oct 13:S0012-3692(20)34890-X. doi: 10.1016/j.chest.2020.09.269. Epub ahead of print. PMID: 33058814.
Link to Article
Link to FULL FREE PDF

The Fluid Challenge per Dr. Louis Vincent

The legend, Dr. Louis Vincent wrote an editorial on the fluid challenge in December 2020 that’s free for you to download. Amongst the takeaways of this short and to the point paper is a focus on the duration of the fluid challenge that we administer. Too often I walk into a room, whether it be the ER, a ward, or even an ICU for that matter and see that the fluids are running at 999cc/hr on the pump or just hanging to gravity. Then I hear the clinician tell me, based on the blood pressure, that the patient either “responded” or “did not respond to fluids”. Hate to burst your bubble but this does not work this way. After all, fluid responsiveness, as mentioned above, has little to do with change in the blood pressure but rather change in the cardiac output/index.

Regardless, the main takeaway point stated in this article that I found it necessary to share was the duration of the fluid bolus. To quote the great Dr. Vincent, “a fluid challenge over a 20 or 30 min time period would not make sense and a shorter period of 5–10 min during which all other factors can be kept unchanged is recommended”. Boom, straight from someone who knows what they’re talking about and not some random ICU doctor on the internet.

Is JUST 100cc of IV Fluids Enough to Define Fluid Responsiveness?

I am going to reference by buddy @memenurseofficial with whom I have maintained a relationship over the last several years. He makes memes that are intentional to create controversy for the sake of entertainment and many battles ensue in the comments section. In several hilarious memes, he jokes about doctors only providing patients with 250cc or 500cc of fluids. In the comments section, many proudly emphasize about how they disregard the orders of physicians and provide “nurse-dose” IV fluids to resuscitate their patients. I am here to tell you what is being done is dangerous and potentially harmful to the patient.

Defining fluid responsiveness does not include the blood pressure going up with fluids. The table listed is from the Japanese Guidelines of Sepsis and Septic Shock published yesterday (8/25/21). Note the low-dose fluid challenge. Note that it states that “cardiac output needs to be measured directly and accurately”. Yes, this may be challenging to perform, and I cannot admit to ever having done this before, but there are technologies that we have in our respective EDs and ICUs that allow us to do this. One can grab two 50cc syringes and let it rip over the course of 1 minute as noted by Muller et al. Note that they used echocardiography as their tool although Vincent states that other techniques can be used as well. His exact words were “thermodilution, transesophageal Doppler, or other techniques could also be considered”.

The whole purpose of this exercise is to reiterate that we ALL have a lot to learn with regards to managing critically ill patients. It is asinine to think we know everything and do everything perfectly. That being said, our mission is to not cause harm in the efforts of saving peoples lives. Providing arbitrary fluids because it’s going to make the blood pressure go up or “because I think the patient is dry” needs to stop.

Egi M, Ogura H, Yatabe T, Atagi K, Inoue S, Iba T, Kakihana Y, Kawasaki T, Kushimoto S, Kuroda Y, Kotani J, Shime N, Taniguchi T, Tsuruta R, Doi K, Doi M, Nakada TA, Nakane M, Fujishima S, Hosokawa N, Masuda Y, Matsushima A, Matsuda N, Yamakawa K, Hara Y, Sakuraya M, Ohshimo S, Aoki Y, Inada M, Umemura Y, Kawai Y, Kondo Y, Saito H, Taito S, Takeda C, Terayama T, Tohira H, Hashimoto H, Hayashida K, Hifumi T, Hirose T, Fukuda T, Fujii T, Miura S, Yasuda H, Abe T, Andoh K, Iida Y, Ishihara T, Ide K, Ito K, Ito Y, Inata Y, Utsunomiya A, Unoki T, Endo K, Ouchi A, Ozaki M, Ono S, Katsura M, Kawaguchi A, Kawamura Y, Kudo D, Kubo K, Kurahashi K, Sakuramoto H, Shimoyama A, Suzuki T, Sekine S, Sekino M, Takahashi N, Takahashi S, Takahashi H, Tagami T, Tajima G, Tatsumi H, Tani M, Tsuchiya A, Tsutsumi Y, Naito T, Nagae M, Nagasawa I, Nakamura K, Nishimura T, Nunomiya S, Norisue Y, Hashimoto S, Hasegawa D, Hatakeyama J, Hara N, Higashibeppu N, Furushima N, Furusono H, Matsuishi Y, Matsuyama T, Minematsu Y, Miyashita R, Miyatake Y, Moriyasu M, Yamada T, Yamada H, Yamamoto R, Yoshida T, Yoshida Y, Yoshimura J, Yotsumoto R, Yonekura H, Wada T, Watanabe E, Aoki M, Asai H, Abe T, Igarashi Y, Iguchi N, Ishikawa M, Ishimaru G, Isokawa S, Itakura R, Imahase H, Imura H, Irinoda T, Uehara K, Ushio N, Umegaki T, Egawa Y, Enomoto Y, Ota K, Ohchi Y, Ohno T, Ohbe H, Oka K, Okada N, Okada Y, Okano H, Okamoto J, Okuda H, Ogura T, Onodera Y, Oyama Y, Kainuma M, Kako E, Kashiura M, Kato H, Kanaya A, Kaneko T, Kanehata K, Kano KI, Kawano H, Kikutani K, Kikuchi H, Kido T, Kimura S, Koami H, Kobashi D, Saiki I, Sakai M, Sakamoto A, Sato T, Shiga Y, Shimoto M, Shimoyama S, Shoko T, Sugawara Y, Sugita A, Suzuki S, Suzuki Y, Suhara T, Sonota K, Takauji S, Takashima K, Takahashi S, Takahashi Y, Takeshita J, Tanaka Y, Tampo A, Tsunoyama T, Tetsuhara K, Tokunaga K, Tomioka Y, Tomita K, Tominaga N, Toyosaki M, Toyoda Y, Naito H, Nagata I, Nagato T, Nakamura Y, Nakamori Y, Nahara I, Naraba H, Narita C, Nishioka N, Nishimura T, Nishiyama K, Nomura T, Haga T, Hagiwara Y, Hashimoto K, Hatachi T, Hamasaki T, Hayashi T, Hayashi M, Hayamizu A, Haraguchi G, Hirano Y, Fujii R, Fujita M, Fujimura N, Funakoshi H, Horiguchi M, Maki J, Masunaga N, Matsumura Y, Mayumi T, Minami K, Miyazaki Y, Miyamoto K, Murata T, Yanai M, Yano T, Yamada K, Yamada N, Yamamoto T, Yoshihiro S, Tanaka H, Nishida O. The Japanese Clinical Practice Guidelines for Management of Sepsis and Septic Shock 2020 (J-SSCG 2020). J Intensive Care. 2021 Aug 25;9(1):53. doi: 10.1186/s40560-021-00555-7. PMID: 34433491; PMCID: PMC8384927.
Link to Article
Link to FULL FREE PDF

Muller L, Toumi M, Bousquet PJ, Riu-Poulenc B, Louart G, Candela D, Zoric L, Suehs C, de La Coussaye JE, Molinari N, Lefrant JY; AzuRéa Group. An increase in aortic blood flow after an infusion of 100 ml colloid over 1 minute can predict fluid responsiveness: the mini-fluid challenge study. Anesthesiology. 2011 Sep;115(3):541-7. doi: 10.1097/ALN.0b013e318229a500. PMID: 21792056.
Link to Article
Link to FULL FREE PDF

Vincent JL. “Let’s give some fluid and see what happens” versus the “mini-fluid challenge”. Anesthesiology. 2011 Sep;115(3):455-6. doi: 10.1097/ALN.0b013e318229a521. PMID: 21792055.
Link to Article
Link to FULL FREE PDF

Central Venous Pressure (CVP)

The follow links will eventually be incorporated into this post but for the time being….
Read about the origin of CVP HERE.
Read about the limitations of CVP that we’ve known about since 1962 HERE.
More data regarding CVP not being able to predict fluid responsiveness HERE.

Does an increase or change in Central Venous Pressure (CVP) indicated fluid unresponsiveness?

Some clinicians have proposed trending CVP and the change in CVP to indicate fluid responsiveness and unresponsiveness. This, however, does not have much data to support it. Hamzaoui, et al looked at this in a recently published a prospective observational study in Critical Care Medicine in June 2020. They analyzed 50 patients and took 57 sets of measurements. As the “gold standard” of sorts to compare CVP, they used Velocity Time Integral (VTI). VTI is an echocardiogram measurement. Going down the path of explaining it is beyond this section of the post, see below in the echocardiogram section. Just be aware that it is very good for assessing stroke volume which helps calculate cardiac output (CO) and therefore fluid responsiveness, hence the authors using it as the baseline.

Rather than providing the patients with IV fluids and potentially cause harm by overloading patients, the authors perform passive leg raising (PLR) on the patients. They defined an increase in CVP ≥ 5mmH2O or 4mmHg as a stopping point for more fluids. This means that the patient would not be fluid responsive moving forward. A positive PLR was defined as an increase in VTI ≥ 10%.

The authors found the neither baseline CVP nor ΔCVP were any good for predicting lack of fluid responsiveness. This means DON’T USE IT. The area under the curve was 0.54 (p=0.6) and 0.59 (p=0.25) respectively. An acceptable AUC is at least 0.7 as a point of reference. Yet another example of why you should not use CVP to guide fluid resuscitation. Consider other alternatives. The authors concluded that “a marked increase in CVP during PLR does not indicate that the PLR test is negative and hence that preload responsiveness is unlikely.”

Citation: Hamzaoui, et al, CCM 2020.

SvO2 and ScVO2

Stroke Volume Guided Resuscitation

This is a one-minute journal club-ish.
This is not medical advice. Do not trust me.
Read the article for yourself by clicking the link although it is not free.
Hat tip to the authors.
How do you decide whether your sepsis or septic shock patient needs IV Fluids?
We are going to look at stroke volume guided resuscitation.
This study was a retrospective look at almost 200 patients.
Half had stroke volume guided resuscitation.
The other half had usual care.
They defined fluid responsiveness as an increase in the SVI by 10% or more.
Overall, they found that only 53% of patients were fluid responsive.
The SV-based resuscitation group had some key differences in outcomes.
At 24, 48, and at the end of their ICU stay, there was a significant difference in the amount of fluid received.
1.77-ish liters vs. 5.36-ish liters.
There was no difference in mortality.
The SV group spent 2 fewer days in the ICU. This saves money.
Fewer patients ended up on the vent, 29% vs. 57%. Morbidity matters.
We were not drowning our patients anymore.
Fluids may be good for the kidneys, but too much fluid is harmful.
6.25% of the patients in the SV group needed dialysis vs. 19.5% in the usual care group.
Are you doing anything like this at your institution? Well, you should.

Latham HE, Bengtson CD, Satterwhite L, Stites M, Subramaniam DP, Chen GJ, Simpson SQ. Stroke volume guided resuscitation in severe sepsis and septic shock improves outcomes. J Crit Care. 2017 Dec;42:42-46. doi: 10.1016/j.jcrc.2017.06.028. Epub 2017 Jun 28. PMID: 28672146.
Link to Article (NOT FREE)

Stroke Volume Assessments with Passive Leg Raising

Passive Leg Raising and Looking at the Blood Pressure to Determine Fluid Responsiveness

When I was a younger whipper snapper in training, I thought I could perform the passive leg raise assessments by picking up some legs, looking at the BP increase and call it a day. Boy, was I wrong. I learned some further principles behind why I was wrong but today (8/28/20) I found the data as to how wrong I was. Needless to say, I was very wrong. Did I mention I was wrong? Glad we’re clear. I wasn’t born knowing everything and still have a ton to learn.

In a paper by Monnet, et al. they placed a swan in their patients and did some other stuff . As some background and to define certain principles, a person who is fluid responsive is one who receives an amount of fluid, in this case PLR is approximately 300cc, is one who has an increase in their stroke volume or cardiac index/output. It is NOT someone who’s blood pressure goes up just because they got fluids. Looking at the sensitivity and specificity of looking at the arterial blood pressure versus the measures generated via thermodilution, you can see how looking at the BP is absolute poop and should not be used. 

The authors found that the area under the curve of PLR-induced changes in arterial pulse pressure was 0.65. That is not good at all. As a point of reference, when they looked at changes in cardiac index and changes in end-tidal CO2 (EtCO2) the area under the curve was 0.98 and 0.93 respectively. Both of those are considered to be outstanding. Looking at the pulse pressure, not so much.

Further analysis on this paper here.

Pulse Pressure Variation (PPV)

What is pulse pressure variation?

Pulse pressure variation is a dynamic parameter for fluid responsiveness that incorporates the heart-lung interaction in patients on mechanical ventilation with an arterial line to predict if a patient needs additional volume.

When did we learn that pulse pressure variation appropriately predicts fluid responsiveness?

The first analysis on pulse pressure variation that I could find was by Michard et al. in the Blue Journal circa 2000. This was the publication where it was determined that “the threshold ΔPp value of 13% allowed discrimination between responder and non-responder patients with a sensitivity of 94% and a specificity of 96%”. The areas under the ROC curves (±SE) were 0.98±0.03 for ΔPp in that study.

What is a normal pulse pressure variation?

As mentioned, Michard et al. determined that using a PPV of 13% “allowed discrimination between responders and nonresponders with a sensitivity of 94% and a specificity of 96%”. So if the variation is ≤ 13%, then the patient likely does not need additional fluids.

Limitations of Pulse Pressure Variation

Patient needs to be on mechanical ventilation to enact the heart-lung interaction. They cannot be taking spontaneous breaths which means they need to be deeply sedated or paralyzed. Then, the tidal volume needs to be set at ≥ 8cc/kg of ideal body weight. Typically, we try to keep the the tidal volume at 6cc/kg IBW but one may quickly adjust this to obtain a better result. If the patient has an arrhythmia, this test is a no-go. In addition, the patient will need to have an arterial line to obtain the proper waveforms to analyze (Monnet et al.). The data has described using a radial or femoral line but the others should get the job done as well.

Can Pulse Pressure Variation be used on patients on Pressure Support or breathing over the vent?

Going back to the limitations mentioned before, there is some data from Grassi et al. that it could be used in patients on pressure support as well as those who are on mechanical ventilation and breathing at rates 20% above the set respiratory rate on the ventilator. In my career, I have no attempted PPV in this patient population because I do not have patients who I am actively resuscitating on pressure support, and generally speaking, I attempt to match their respiratory drive to avoid fatigue and other issues. They did find that the “receiver operator characteristic curve for pulse pressure variation was 0.87 (95% CI 0.74-0.99; p<0.0001) and the grey zone limits were 10% and 15%”. To me knowledge this has not been replicated.

How do we know it does not work in spontaneously breathing extubated patients?

Heenan et al. performed a trial where they attempted to use PPV on patients who were spontaneously breathing on a face mask. Here, they found that “the ROC curve area of ΔPP… was 0.29 ± 0.17 in patients breathing through a face mask”. This AUC is not reliable. We should not use it.

Does using Pulse Pressure Variation actually work to predict fluid/volume responsiveness?

A meta-analysis by Yang et al. took a deep dive into 22 studies and 807 patients and they found that the AUC of using PPV to determine fluid responsiveness was 0.94 which is considered to be outstanding.

How to set up the Pulse Pressure Variation calculator on your monitor.

The term “multi parametric monitor” is thrown around here so that we don’t have to whip out the rulers and start measuring things by hand like in the old days. The best image I have found of what the waveform tracings would look like when we slow down the monitor from 25mm/s to 6.25mm/s was published by Bronzwaer AS et al. I cannot show it here for copyright reasons. For the sake of simplicity, thankfully, multiple monitors now possess the software to be able to calculate the pulse pressure variation for us. Although one cannot forget the limitations that make it inaccurate.

Stroke Volume Variation (SVV)

I have a full post on stroke volume variation HERE.

What is Stroke Volume Variation (SVV) definition?

Stroke volume variation is another dynamic form of assessing for volume responsiveness in patients who may be in need resuscitation with IV fluids. The major downside to this methodology is that you need some sort of device that uses pulse contour analysis or bioreactance to sort this out. You’ll need an arterial line in the case of pulse contour analysis (except for one particular device to my knowledge). I am quite familiar with one of these devices although I am not going to divulge any further information for sake of possible bias.

What is the Stroke Volume Variation Equation?

SVV= (SVmax – SVmin) / SVmean

Fortunately, we don’t have to do it by hand. The machine/device does it for us and we get a pretty number.

What Stroke Volume Variation (SVV) is considered “normal”?

Depending on the literature, a patient who is predicted to be volume responsive will have an SVV>13% in most literature, but some will say >10%. In my practice, I use the former. The normal range of stroke volume variation is <13%. One could interpret the number that if it’s over 13%, they potentially need a 500cc fluid bolus.

Does the data reflect that it works for predicting fluid responsiveness?

There was a meta-analysis that looked at 568 patient in 23 different studies using a variety of different devices. The correlation coefficient to fluid responsiveness was 0.718 which means a “highly positive correlation”. The AUC of using SVV for fluid responsiveness is 0.84. 0.8-0.9 is considered “excellent”. It’s not all sunshine and roses, though. I know we’re rusty on our stats.

Limitations of Stroke Volume Variation:

– needs to be on mechanical ventilation
– no cardiac arrhythmias
– tidal volume needs to be >8cc/kg of ideal body weight
– you need a fancy machine
– most devices need an arterial line
Part of the issue is that clinicians are quick to forget these limitations.

Does SVV work on patients who are spontaneous breathing?

Stroke Volume Variation doesn’t work in patients who are spontaneously breathing. I have seen clinicians who are well respected where they’ve said that it works “to trend” but I am not a fan of shortcuts. The AUC in those patients is 0.53 per the linked Zhang paper.

What devices can help you assess the SVV?

Devices such as the Vigileo or Flotrac from Edwards Lifesciences can obtain these numbers for you. I do not have any disclosures at the time of this writing.

Putting it all together for Stroke Volume Variation in Fluid Resuscitation

All in all, it’s another tool in the tool belt. We need as many as we can. I personally would prefer to have this value showing up on a screen over numerous other parameters that require me to be at the bedside on x minute intervals.

Dynamic Arterial Elastance

Dynamic arterial elastance is a completely new-to-me way to determine fluid responsiveness. It takes into account both the PPV and SVV. Zhou et al. defines it as “Eadyn is defined as the ratio of pulse pressure variation (PPV) to stroke volume variation (SVV)” in the systematic review and meta-analysis that I am using as a reference to this section. My main question is that if you are using PPV which has an AUC of >0.9 and SVV which has an AUC >0.8 based on above studies, how much more value can you get from this particular assessment?

Upon a closer inspection as this peaked my curiosity, Monge Garcia et al. conducted a validation study and they better described that Eadyn is useful “as a predictor of the arterial pressure response to fluid administration…”

What values predict the utility of Dynamic Arterial Elastance?

In the meta-analysis by Zhou et al., they noted that “if the measured baseline Eadyn is above 0.8, fluid expansion would increase arterial pressure in hypotensive patients with preload dependency.” If the “measured baseline Eadyn is below 0.7, fluid administration might not increase arterial pressure despite the increase in CO”. There was a gray zone between 0.7 and 0.8 where they didn’t know what to do with those values. I am creating a specific eadyn post HERE.

Echocardiography Principles for Fluid Responsiveness

Velocity Time Integral (VTI)

VTI can be recorded using a five-chamber apical view and a parasternal long-axis view. One needs to record the flow in the left ventricular outflow tract. The contours will need to be hand-drawn using the echo/ultrasound machine. Some studies use the average of three consecutive end-expiratory measurements for patients in sinus rhythm, and five measurements for patients with atrial fibrillation. Using the VTI and the cross-sectional area of the left ventricular outflow tract, you can obtain the stroke volume. Cardiac output is equal to stroke volume times heart rate.

A caveat to calculating VTI is poor echogenicity. That is when one has the inability to correctly align the Doppler beam to obtain reliable Doppler measurements.

In various studies, fluid responsiveness has been defined as an increase in VTI ≥ 10%.

Citation: Hamzaoui, et al, CCM 2020.

End-expiratory occlusion testing (EEXPO)

What is end-expiratory occlusion testing?

It is a method we can use at the bedside to determine whether a patient is fluid responsive. We have actually known about this since 2009 when Monnet et al. explored this concept in a not-free article. The full description of the heart-lung interaction that allows this to work is beyond the scope of this post. Since then, at least 12 additional studies have been published on the matter.

What patient characteristics are we interested in to perform end-expiratory occlusion testing?

Patients need to be mechanically ventilated and in need of an evaluation for fluid responsiveness. If they are tachypneic with the inability to sustain a 15 second expiratory hold, then we just can’t do it. Some studies have even pushed the expiratory hold to 30 seconds but Gavelli’s 2020 meta-analysis showed that there was really no difference between the 15 second hold and the 30 second hold.

What should the tidal volume be?
It is unclear at this time whether having patients on 6cc/kg/IBW or 8cc/kg/IBW will provide a difference per Gavelli et al. The same group published a meta-analysis in 2020 which showed that tidal volumes less than or equal to 7 were better with an AUC of 0.96 (which is outstanding) but tidal volumes over 7cc/kg IBW was 0.89 which is still excellent.

Is there a PEEP level we should worry about?
The same 2019 Gavelli et al. paper states that if patients have a PEEP between the range of 5-14, they should be fine. The meta-analysis written by Gavelli and his colleagues showed that PEEP settings greater than or equal to 7 perform better but this is marginal in my opinion. I won’t be changing PEEP settings on my patients to assess the EEXPO.

Would this work on proned patients?
Don’t try this on proned patients. It does not seem to work there.

What do we need to do at the bedside to perform an end-expiratory occlusion (EEXPO)?

While the patient is on the ventilator, you are going to perform an expiratory hold on the ventilator for 15 seconds. The patient needs to be in a clinical state where they can tolerate this 15 second expiratory hold, of course. Simultaneously, there needs to be some sort of way to capture your favorite way of determining the change in stroke volume, cardiac output, or cardiac index. I have yet to find a study that looks at VTI in this setting. The original study by Monnet et al. used pulse-contour analysis. If your shop uses bioreactance, Gavelli has you covered with a 2021 paper that explains how to set up your device to make the EEXPO accurate.

Diagnostic Thresholds
The thresholds for a positive EEOP test are lower than the standard definitions of fluid responsiveness listed above. Gavelli’s meta-analysis states that an increase in cardiac output by approximately 5.0% (5.1 ± 0.2%) to be the best diagnostic threshold to determine volume responsiveness.

Also, make sure to discuss when you’re doing with your respiratory therapist. Many of them don’t like us messing with their vents.

What have the studies found when looking at end-expiratory occlusion to predict fluid/volume responsiveness?

Monnet et al. actually found it to be better than using passive leg raising although the AUC of both was excellent at over 0.95. As a bonus, compared to other methods of assessing fluid responsiveness, they found that watching the MAP increase while performing this assessment also predicted volume responsiveness!

Okay, the end-expiratory occlusion is positive. What next?

The next step would be to go ahead and administer a bolus of IV fluids. The 2009 Monnet study provided patients with a 500cc bolus.

Conclusions….

There is no perfect way to determine fluid responsiveness. The answer eludes us at the current time. We are left with these tools to do the best we can for our critically ill patients who are counting on us to provide the best possible care. There is absolutely NO TEST that is perfect. Anyone who states that their way of assessing patients is perfect is either lying or lacks humility.

The Citations to my Fluid Resuscitation lecture:

Rudd KE, Johnson SC, Agesa KM, Shackelford KA, Tsoi D, Kievlan DR, Colombara DV, Ikuta KS, Kissoon N, Finfer S, Fleischmann-Struzek C, Machado FR, Reinhart KK, Rowan K, Seymour CW, Watson RS, West TE, Marinho F, Hay SI, Lozano R, Lopez AD, Angus DC, Murray CJL, Naghavi M. Global, regional, and national sepsis incidence and mortality, 1990-2017: analysis for the Global Burden of Disease Study. Lancet. 2020 Jan 18;395(10219):200-211. doi: 10.1016/S0140-6736(19)32989-7. PMID: 31954465; PMCID: PMC6970225.
Link to Article
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Douglas IS, Alapat PM, Corl KA, Exline MC, Forni LG, Holder AL, Kaufman DA, Khan A, Levy MM, Martin GS, Sahatjian JA, Seeley E, Self WH, Weingarten JA, Williams M, Hansell DM. Fluid Response Evaluation in Sepsis Hypotension and Shock: A Randomized Clinical Trial. Chest. 2020 Oct;158(4):1431-1445. doi: 10.1016/j.chest.2020.04.025. Epub 2020 Apr 27. PMID: 32353418.
Link to Article
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Lobo DN, Stanga Z, Aloysius MM, Wicks C, Nunes QM, Ingram KL, Risch L, Allison SP. Effect of volume loading with 1 liter intravenous infusions of 0.9% saline, 4% succinylated gelatine (Gelofusine) and 6% hydroxyethyl starch (Voluven) on blood volume and endocrine responses: a randomized, three-way crossover study in healthy volunteers. Crit Care Med. 2010 Feb;38(2):464-70. doi: 10.1097/CCM.0b013e3181bc80f1. PMID: 19789444.
Link to Article (NOT FREE)
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Ragaller MJ, Theilen H, Koch T. Volume replacement in critically ill patients with acute renal failure. J Am Soc Nephrol. 2001 Feb;12 Suppl 17:S33-9. PMID: 11251029.
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Bark BP, Persson J, Grände PO. Importance of the infusion rate for the plasma expanding effect of 5% albumin, 6% HES 130/0.4, 4% gelatin, and 0.9% NaCl in the septic rat. Crit Care Med. 2013 Mar;41(3):857-66. doi: 10.1097/CCM.0b013e318274157e. PMID: 23318490.
Link to Article (NOT FREE)

Guerin L, Monnet X, Teboul JL. Monitoring volume and fluid responsiveness: from static to dynamic indicators. Best Pract Res Clin Anaesthesiol. 2013 Jun;27(2):177-85. doi: 10.1016/j.bpa.2013.06.002. PMID: 24012230.
Link to Article (NOT FREE)

Marik PE. Iatrogenic salt water drowning and the hazards of a high central venous pressure. Ann Intensive Care. 2014 Jun 21;4:21. doi: 10.1186/s13613-014-0021-0. PMID: 25110606; PMCID: PMC4122823.
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Kelm DJ, Perrin JT, Cartin-Ceba R, Gajic O, Schenck L, Kennedy CC. Fluid overload in patients with severe sepsis and septic shock treated with early goal-directed therapy is associated with increased acute need for fluid-related medical interventions and hospital death. Shock. 2015 Jan;43(1):68-73. doi: 10.1097/SHK.0000000000000268. PMID: 25247784; PMCID: PMC4269557.
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Wang W, Zhu S, He Q, Wang M, Kang Y, Zhang R, Ji P, Zou K, Klompas M, Zong Z, Sun X. Fluid Balance and Ventilator-Associated Events Among Patients Admitted to ICUs in China: A Nested Case-Control Study. Crit Care Med. 2022 Feb 1;50(2):307-316. doi: 10.1097/CCM.0000000000005227. PMID: 34473657; PMCID: PMC8797004.
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Cecconi M, Hofer C, Teboul JL, Pettila V, Wilkman E, Molnar Z, Della Rocca G, Aldecoa C, Artigas A, Jog S, Sander M, Spies C, Lefrant JY, De Backer D; FENICE Investigators; ESICM Trial Group. Fluid challenges in intensive care: the FENICE study: A global inception cohort study. Intensive Care Med. 2015 Sep;41(9):1529-37. doi: 10.1007/s00134-015-3850-x. Epub 2015 Jul 11. Erratum in: Intensive Care Med. 2015 Sep;41(9):1737-8. multiple investigator names added. PMID: 26162676; PMCID: PMC4550653.
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Shippy CR, Appel PL, Shoemaker WC. Reliability of clinical monitoring to assess blood volume in critically ill patients. Crit Care Med. 1984 Feb;12(2):107-12. doi: 10.1097/00003246-198402000-00005. PMID: 6697726.
Link to Abstract

HUGHES RE, MAGOVERN GJ. The relationship between right atrial pressure and blood volume. AMA Arch Surg. 1959 Aug;79(2):238-43. doi: 10.1001/archsurg.1959.04320080074009. PMID: 13669851.
I took apart this article to some degree on my website HERE.
Link to Abstract

WILSON JN, GROW JB, DEMONG CV, PREVEDEL AE, OWENS JC. Central venous pressure in optimal blood volume maintenance. Arch Surg. 1962 Oct;85:563-78. doi: 10.1001/archsurg.1962.01310040035005. PMID: 14001047.
I took apart this article to some degree on this post.
Link to Abstract

Rivers E, Nguyen B, Havstad S, Ressler J, Muzzin A, Knoblich B, Peterson E, Tomlanovich M; Early Goal-Directed Therapy Collaborative Group. Early goal-directed therapy in the treatment of severe sepsis and septic shock. N Engl J Med. 2001 Nov 8;345(19):1368-77. doi: 10.1056/NEJMoa010307. PMID: 11794169.
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Dellinger RP, Levy MM, Rhodes A, Annane D, Gerlach H, Opal SM, Sevransky JE, Sprung CL, Douglas IS, Jaeschke R, Osborn TM, Nunnally ME, Townsend SR, Reinhart K, Kleinpell RM, Angus DC, Deutschman CS, Machado FR, Rubenfeld GD, Webb SA, Beale RJ, Vincent JL, Moreno R; Surviving Sepsis Campaign Guidelines Committee including the Pediatric Subgroup. Surviving sepsis campaign: international guidelines for management of severe sepsis and septic shock: 2012. Crit Care Med. 2013 Feb;41(2):580-637. doi: 10.1097/CCM.0b013e31827e83af. PMID: 23353941.
Link to Article

ARISE Investigators; ANZICS Clinical Trials Group, Peake SL, Delaney A, Bailey M, Bellomo R, Cameron PA, Cooper DJ, Higgins AM, Holdgate A, Howe BD, Webb SA, Williams P. Goal-directed resuscitation for patients with early septic shock. N Engl J Med. 2014 Oct 16;371(16):1496-506. doi: 10.1056/NEJMoa1404380. Epub 2014 Oct 1. PMID: 25272316.
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ProCESS Investigators, Yealy DM, Kellum JA, Huang DT, Barnato AE, Weissfeld LA, Pike F, Terndrup T, Wang HE, Hou PC, LoVecchio F, Filbin MR, Shapiro NI, Angus DC. A randomized trial of protocol-based care for early septic shock. N Engl J Med. 2014 May 1;370(18):1683-93. doi: 10.1056/NEJMoa1401602. Epub 2014 Mar 18. PMID: 24635773; PMCID: PMC4101700.
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Mouncey PR, Osborn TM, Power GS, Harrison DA, Sadique MZ, Grieve RD, Jahan R, Harvey SE, Bell D, Bion JF, Coats TJ, Singer M, Young JD, Rowan KM; ProMISe Trial Investigators. Trial of early, goal-directed resuscitation for septic shock. N Engl J Med. 2015 Apr 2;372(14):1301-11. doi: 10.1056/NEJMoa1500896. Epub 2015 Mar 17. PMID: 25776532.
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Gupta RG, Hartigan SM, Kashiouris MG, Sessler CN, Bearman GM. Early goal-directed resuscitation of patients with septic shock: current evidence and future directions. Crit Care. 2015 Aug 28;19(1):286. doi: 10.1186/s13054-015-1011-9. PMID: 26316210; PMCID: PMC4552276.
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Nguyen HB, Jaehne AK, Jayaprakash N, Semler MW, Hegab S, Yataco AC, Tatem G, Salem D, Moore S, Boka K, Gill JK, Gardner-Gray J, Pflaum J, Domecq JP, Hurst G, Belsky JB, Fowkes R, Elkin RB, Simpson SQ, Falk JL, Singer DJ, Rivers EP. Early goal-directed therapy in severe sepsis and septic shock: insights and comparisons to ProCESS, ProMISe, and ARISE. Crit Care. 2016 Jul 1;20(1):160. doi: 10.1186/s13054-016-1288-3. PMID: 27364620; PMCID: PMC4929762.
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Central Venous Pressure (CVP) Citations

Marik PE. Iatrogenic salt water drowning and the hazards of a high central venous pressure. Ann Intensive Care. 2014 Jun 21;4:21. doi: 10.1186/s13613-014-0021-0. PMID: 25110606; PMCID: PMC4122823.
Link to Article
Link to FULL FREE Article

Vincent JL, Cecconi M, De Backer D. The fluid challenge. Crit Care. 2020 Dec 28;24(1):703. doi: 10.1186/s13054-020-03443-y. PMID: 33371895; PMCID: PMC7771055.
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Rhodes A, Evans LE, Alhazzani W, Levy MM, Antonelli M, Ferrer R, Kumar A, Sevransky JE, Sprung CL, Nunnally ME, Rochwerg B, Rubenfeld GD, Angus DC, Annane D, Beale RJ, Bellinghan GJ, Bernard GR, Chiche JD, Coopersmith C, De Backer DP, French CJ, Fujishima S, Gerlach H, Hidalgo JL, Hollenberg SM, Jones AE, Karnad DR, Kleinpell RM, Koh Y, Lisboa TC, Machado FR, Marini JJ, Marshall JC, Mazuski JE, McIntyre LA, McLean AS, Mehta S, Moreno RP, Myburgh J, Navalesi P, Nishida O, Osborn TM, Perner A, Plunkett CM, Ranieri M, Schorr CA, Seckel MA, Seymour CW, Shieh L, Shukri KA, Simpson SQ, Singer M, Thompson BT, Townsend SR, Van der Poll T, Vincent JL, Wiersinga WJ, Zimmerman JL, Dellinger RP. Surviving Sepsis Campaign: International Guidelines for Management of Sepsis and Septic Shock: 2016. Crit Care Med. 2017 Mar;45(3):486-552. doi: 10.1097/CCM.0000000000002255. PMID: 28098591.
Link to Article and FULL FREE PDF

Marik PE, Cavallazzi R. Does the central venous pressure predict fluid responsiveness? An updated meta-analysis and a plea for some common sense. Crit Care Med. 2013 Jul;41(7):1774-81. doi: 10.1097/CCM.0b013e31828a25fd. PMID: 23774337.
Link to Article

Mandrekar JN. Receiver operating characteristic curve in diagnostic test assessment. J Thorac Oncol. 2010 Sep;5(9):1315-6. doi: 10.1097/JTO.0b013e3181ec173d. PMID: 20736804.
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Mukaka MM. Statistics corner: A guide to appropriate use of correlation coefficient in medical research. Malawi Med J. 2012 Sep;24(3):69-71. PMID: 23638278; PMCID: PMC3576830.
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Eskesen TG, Wetterslev M, Perner A. Systematic review including re-analyses of 1148 individual data sets of central venous pressure as a predictor of fluid responsiveness. Intensive Care Med. 2016 Mar;42(3):324-332. doi: 10.1007/s00134-015-4168-4. Epub 2015 Dec 9. PMID: 26650057.
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Hamzaoui O, Gouëzel C, Jozwiak M, Millereux M, Sztrymf B, Prat D, Jacobs F, Monnet X, Trouiller P, Teboul JL. Increase in Central Venous Pressure During Passive Leg Raising Cannot Detect Preload Unresponsiveness. Crit Care Med. 2020 Aug;48(8):e684-e689. doi: 10.1097/CCM.0000000000004414. PMID: 32697509.
Link to Article NOT FREE

De Backer D, Vincent JL. Should we measure the central venous pressure to guide fluid management? Ten answers to 10 questions. Crit Care. 2018 Feb 23;22(1):43. doi: 10.1186/s13054-018-1959-3. PMID: 29471884; PMCID: PMC5824587.
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Rivers EP, McIntyre L, Morro DC, Rivers KK. Early and innovative interventions for severe sepsis and septic shock: taking advantage of a window of opportunity. CMAJ. 2005 Oct 25;173(9):1054-65. doi: 10.1503/cmaj.050632. PMID: 16247103; PMCID: PMC1266331.
I have taken a deep dive into this article HERE.
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SvO2 and ScvO2 Citations

Walley KR. Use of central venous oxygen saturation to guide therapy. Am J Respir Crit Care Med. 2011 Sep 1;184(5):514-20. doi: 10.1164/rccm.201010-1584CI. PMID: 21177882.
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Khalil MH, Sekma A, Zhani W, Zorgati A, Ben Soltane H, Nouira S; GREAT Network. Variation in central venous oxygen saturation to assess volume responsiveness in hemodynamically unstable patients under mechanical ventilation: a prospective cohort study. Crit Care. 2021 Jul 13;25(1):245. doi: 10.1186/s13054-021-03683-6. PMID: 34256822.
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Inferior vena cava measurement Citations

Long E, Oakley E, Duke T, Babl FE; Paediatric Research in Emergency Departments International Collaborative (PREDICT). Does Respiratory Variation in Inferior Vena Cava Diameter Predict Fluid Responsiveness: A Systematic Review and Meta-Analysis. Shock. 2017 May;47(5):550-559. doi: 10.1097/SHK.0000000000000801. PMID: 28410544.
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Millington SJ. Ultrasound assessment of the inferior vena cava for fluid responsiveness: easy, fun, but unlikely to be helpful. Can J Anaesth. 2019 Jun;66(6):633-638. doi: 10.1007/s12630-019-01357-0. Epub 2019 Mar 27. PMID: 30919234.
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Muller L, Bobbia X, Toumi M, Louart G, Molinari N, Ragonnet B, Quintard H, Leone M, Zoric L, Lefrant JY; AzuRea group. Respiratory variations of inferior vena cava diameter to predict fluid responsiveness in spontaneously breathing patients with acute circulatory failure: need for a cautious use. Crit Care. 2012 Oct 8;16(5):R188. doi: 10.1186/cc11672. PMID: 23043910; PMCID: PMC3682290.
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Long E, Oakley E, Duke T, Babl FE; Paediatric Research in Emergency Departments International Collaborative (PREDICT). Does Respiratory Variation in Inferior Vena Cava Diameter Predict Fluid Responsiveness: A Systematic Review and Meta-Analysis. Shock. 2017 May;47(5):550-559. doi: 10.1097/SHK.0000000000000801. PMID: 28410544.
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Vieillard-Baron A, Evrard B, Repessé X, Maizel J, Jacob C, Goudelin M, Charron C, Prat G, Slama M, Geri G, Vignon P. Limited value of end-expiratory inferior vena cava diameter to predict fluid responsiveness impact of intra-abdominal pressure. Intensive Care Med. 2018 Feb;44(2):197-203. doi: 10.1007/s00134-018-5067-2. Epub 2018 Jan 22. PMID: 29356854.
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Vignon P, Repessé X, Bégot E, Léger J, Jacob C, Bouferrache K, Slama M, Prat G, Vieillard-Baron A. Comparison of Echocardiographic Indices Used to Predict Fluid Responsiveness in Ventilated Patients. Am J Respir Crit Care Med. 2017 Apr 15;195(8):1022-1032. doi: 10.1164/rccm.201604-0844OC. PMID: 27653798.
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Stroke Volume Citations

Latham HE, Bengtson CD, Satterwhite L, Stites M, Subramaniam DP, Chen GJ, Simpson SQ. Stroke volume guided resuscitation in severe sepsis and septic shock improves outcomes. J Crit Care. 2017 Dec;42:42-46. doi: 10.1016/j.jcrc.2017.06.028. Epub 2017 Jun 28. PMID: 28672146.
Link to Article

Bednarczyk JM, Fridfinnson JA, Kumar A, Blanchard L, Rabbani R, Bell D, Funk D, Turgeon AF, Abou-Setta AM, Zarychanski R. Incorporating Dynamic Assessment of Fluid Responsiveness Into Goal-Directed Therapy: A Systematic Review and Meta-Analysis. Crit Care Med. 2017 Sep;45(9):1538-1545. doi: 10.1097/CCM.0000000000002554. PMID: 28817481; PMCID: PMC5555977.
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Douglas IS, Alapat PM, Corl KA, Exline MC, Forni LG, Holder AL, Kaufman DA, Khan A, Levy MM, Martin GS, Sahatjian JA, Seeley E, Self WH, Weingarten JA, Williams M, Hansell DM. Fluid Response Evaluation in Sepsis Hypotension and Shock: A Randomized Clinical Trial. Chest. 2020 Oct;158(4):1431-1445. doi: 10.1016/j.chest.2020.04.025. Epub 2020 Apr 27. PMID: 32353418.
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Passive Leg Raise Citations

Monnet X, Teboul JL. Passive leg raising: five rules, not a drop of fluid! Crit Care. 2015 Jan 14;19(1):18. doi: 10.1186/s13054-014-0708-5. PMID: 25658678; PMCID: PMC4293822.
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Monnet X, Marik P, Teboul JL. Passive leg raising for predicting fluid responsiveness: a systematic review and meta-analysis. Intensive Care Med. 2016 Dec;42(12):1935-1947. doi: 10.1007/s00134-015-4134-1. Epub 2016 Jan 29. PMID: 26825952.
Link to Article NOT FREE

End-Tidal CO2 Citations

Monnet X, Bataille A, Magalhaes E, Barrois J, Le Corre M, Gosset C, Guerin L, Richard C, Teboul JL. End-tidal carbon dioxide is better than arterial pressure for predicting volume responsiveness by the passive leg raising test. Intensive Care Med. 2013 Jan;39(1):93-100. doi: 10.1007/s00134-012-2693-y. Epub 2012 Sep 19. PMID: 22990869.
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Monnet X, Marik PE, Teboul JL. Prediction of fluid responsiveness: an update. Ann Intensive Care. 2016 Dec;6(1):111. doi: 10.1186/s13613-016-0216-7. Epub 2016 Nov 17. PMID: 27858374; PMCID: PMC5114218.
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Hofer CK, Cannesson M. Monitoring fluid responsiveness. Acta Anaesthesiol Taiwan. 2011 Jun;49(2):59-65. doi: 10.1016/j.aat.2011.05.001. Epub 2011 Jun 24. PMID: 21729812.
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Pulse Pressure Variation Citations

Michard F, Boussat S, Chemla D, Anguel N, Mercat A, Lecarpentier Y, Richard C, Pinsky MR, Teboul JL. Relation between respiratory changes in arterial pulse pressure and fluid responsiveness in septic patients with acute circulatory failure. Am J Respir Crit Care Med. 2000 Jul;162(1):134-8. doi: 10.1164/ajrccm.162.1.9903035. PMID: 10903232.
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Grassi P, Lo Nigro L, Battaglia K, Barone M, Testa F, Berlot G. Pulse pressure variation as a predictor of fluid responsiveness in mechanically ventilated patients with spontaneous breathing activity: a pragmatic observational study. HSR Proc Intensive Care Cardiovasc Anesth. 2013;5(2):98-109. PMID: 23888232; PMCID: PMC3722341.
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Heenen S, De Backer D, Vincent JL. How can the response to volume expansion in patients with spontaneous respiratory movements be predicted? Crit Care. 2006;10(4):R102. doi: 10.1186/cc4970. PMID: 16846530; PMCID: PMC1750965.
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Michard F, Lopes MR, Auler JO Jr. Pulse pressure variation: beyond the fluid management of patients with shock. Crit Care. 2007;11(3):131. doi: 10.1186/cc5905. PMID: 17521454; PMCID: PMC2206397.
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Yang X, Du B. Does pulse pressure variation predict fluid responsiveness in critically ill patients? A systematic review and meta-analysis. Crit Care. 2014 Nov 27;18(6):650. doi: 10.1186/s13054-014-0650-6. PMID: 25427970; PMCID: PMC4258282.
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Umbrello M, Formenti P, Galimberti A, Curti M, Zaniboni M, Iapichino G. On-line measurement of systolic pressure variation and pulse pressure variation on a multiparametric monitor. Intensive Care Med. 2008 Feb;34(2):386-7. doi: 10.1007/s00134-007-0913-7. Epub 2007 Oct 25. PMID: 17960363.
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Bronzwaer AS, Stok WJ, Westerhof BE, van Lieshout JJ. Arterial pressure variations as parameters of brain perfusion in response to central blood volume depletion and repletion. Front Physiol. 2014 Apr 23;5:157. doi: 10.3389/fphys.2014.00157. PMID: 24795652; PMCID: PMC4006039.
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Michard F, Chemla D, Teboul JL. Applicability of pulse pressure variation: how many shades of grey? Crit Care. 2015 Mar 25;19(1):144. doi: 10.1186/s13054-015-0869-x. PMID: 25887325; PMCID: PMC4372274.
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Teboul JL, Monnet X, Chemla D, Michard F. Arterial Pulse Pressure Variation with Mechanical Ventilation. Am J Respir Crit Care Med. 2019 Jan 1;199(1):22-31. doi: 10.1164/rccm.201801-0088CI. PMID: 30138573.
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Stroke Volume Variation Citations

Zhang Z, Lu B, Sheng X, Jin N. Accuracy of stroke volume variation in predicting fluid responsiveness: a systematic review and meta-analysis. J Anesth. 2011 Dec;25(6):904-16. doi: 10.1007/s00540-011-1217-1. Epub 2011 Sep 4. PMID: 21892779.
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Perner A, Faber T. Stroke volume variation does not predict fluid responsiveness in patients with septic shock on pressure support ventilation. Acta Anaesthesiol Scand. 2006 Oct;50(9):1068-73. doi: 10.1111/j.1399-6576.2006.01120.x. Epub 2006 Aug 25. PMID: 16939480.
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Vignon P, Repessé X, Bégot E, Léger J, Jacob C, Bouferrache K, Slama M, Prat G, Vieillard-Baron A. Comparison of Echocardiographic Indices Used to Predict Fluid Responsiveness in Ventilated Patients. Am J Respir Crit Care Med. 2017 Apr 15;195(8):1022-1032. doi: 10.1164/rccm.201604-0844OC. PMID: 27653798.
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Hofer CK, Cannesson M. Monitoring fluid responsiveness. Acta Anaesthesiol Taiwan. 2011 Jun;49(2):59-65. doi: 10.1016/j.aat.2011.05.001. Epub 2011 Jun 24. PMID: 21729812.
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Dynamic Arterial Elastance Citations

Zhou X, Pan W, Chen B, Xu Z, Pan J. Predictive performance of dynamic arterial elastance for arterial pressure response to fluid expansion in mechanically ventilated hypotensive adults: a systematic review and meta-analysis of observational studies. Ann Intensive Care. 2021 Jul 31;11(1):119. doi: 10.1186/s13613-021-00909-2. PMID: 34331607; PMCID: PMC8325731.
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García MI, Romero MG, Cano AG, Aya HD, Rhodes A, Grounds RM, Cecconi M. Dynamic arterial elastance as a predictor of arterial pressure response to fluid administration: a validation study. Crit Care. 2014 Nov 19;18(6):626. doi: 10.1186/s13054-014-0626-6. PMID: 25407570; PMCID: PMC4271484.
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End Expiratory Occlusion Testing Citations

Monnet X, Osman D, Ridel C, Lamia B, Richard C, Teboul JL. Predicting volume responsiveness by using the end-expiratory occlusion in mechanically ventilated intensive care unit patients. Crit Care Med. 2009 Mar;37(3):951-6. doi: 10.1097/CCM.0b013e3181968fe1. PMID: 19237902.
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Gavelli F, Teboul JL, Monnet X. The end-expiratory occlusion test: please, let me hold your breath! Crit Care. 2019 Aug 7;23(1):274. doi: 10.1186/s13054-019-2554-y. PMID: 31391083; PMCID: PMC6686261.
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Gavelli F, Shi R, Teboul JL, Azzolina D, Monnet X. The end-expiratory occlusion test for detecting preload responsiveness: a systematic review and meta-analysis. Ann Intensive Care. 2020 May 24;10(1):65. doi: 10.1186/s13613-020-00682-8. PMID: 32449104; PMCID: PMC7246264.
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Si X, Song X, Lin Q, Nie Y, Zhang G, Xu H, Chen M, Wu J, Guan X. Does End-Expiratory Occlusion Test Predict Fluid Responsiveness in Mechanically Ventilated Patients? A Systematic Review and Meta-Analysis. Shock. 2020 Dec;54(6):751-760. doi: 10.1097/SHK.0000000000001545. PMID: 32433213.
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Gavelli F, Beurton A, Teboul JL, De Vita N, Azzolina D, Shi R, Pavot A, Monnet X. Bioreactance reliably detects preload responsiveness by the end-expiratory occlusion test when averaging and refresh times are shortened. Ann Intensive Care. 2021 Aug 28;11(1):133. doi: 10.1186/s13613-021-00920-7. PMID: 34453633; PMCID: PMC8401368.
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Continued…

Chaudhuri D, Herritt B, Lewis K, Diaz-Gomez JL, Fox-Robichaud A, Ball I, Granton J, Rochwerg B. Dosing Fluids in Early Septic Shock. Chest. 2020 Oct 13:S0012-3692(20)34890-X. doi: 10.1016/j.chest.2020.09.269. Epub ahead of print. PMID: 33058814.
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Bentzer P, Griesdale DE, Boyd J, MacLean K, Sirounis D, Ayas NT. Will This Hemodynamically Unstable Patient Respond to a Bolus of Intravenous Fluids? JAMA. 2016 Sep 27;316(12):1298-309. doi: 10.1001/jama.2016.12310. PMID: 27673307.
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Egi, M., Ogura, H., Yatabe, T. et al. The Japanese Clinical Practice Guidelines for Management of Sepsis and Septic Shock 2020 (J-SSCG 2020). j intensive care 9, 53 (2021). https://doi.org/10.1186/s40560-021-00555-7
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Muller L, Toumi M, Bousquet PJ, Riu-Poulenc B, Louart G, Candela D, Zoric L, Suehs C, de La Coussaye JE, Molinari N, Lefrant JY; AzuRéa Group. An increase in aortic blood flow after an infusion of 100 ml colloid over 1 minute can predict fluid responsiveness: the mini-fluid challenge study. Anesthesiology. 2011 Sep;115(3):541-7. doi: 10.1097/ALN.0b013e318229a500. PMID: 21792056.
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Horejsek J, Kunstyr J, Michalek P, Porizka M. Novel Methods for Predicting Fluid Responsiveness in Critically Ill Patients-A Narrative Review. Diagnostics (Basel). 2022 Feb 16;12(2):513. doi: 10.3390/diagnostics12020513. PMID: 35204603; PMCID: PMC8871108.
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A thank you.

A hat tip to all these authors for their great work in looking into fluid resuscitation and volume responsiveness. Although great care has been taken to ensure that the information in this post is accurate, eddyjoe, LLC shall not be held responsible or in any way liable for the continued accuracy of the information, or for any errors, omissions or inaccuracies, or for any consequences arising therefrom.

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