Aggressive fluid therapy in Severe Septic Shock and ARDS.

Specialties CRNA

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This isn't meant to be an official scientific document, so I apologize in advance for the sloppy work.

It's been widely known that increased fluid volume can lead to edema. My theory is based upon the intentional inducement of mild to moderate edema in order to increase capillary leakage from intravascular to extravascular spaces. Increased capillary leakage would allow increased antibiotics to diffuse from intravascular to extravascular space. The fluids I would think most appropriate would be normal saline and lactated ringers. Large macromolecules, such as hespan and blood, should not be used as their properties would prevent diffusion in the appropriate direction. Maintainance of CVP=12 would seem to induce adequate edema, although that may be somewhat excessive, especially in pts with aneurysms.

In some cases of pneumonia-induced ARDS(from whatever specific microbial agent, such as TB, streptococcus, etc), pulmonary edema may be extraordinarily beneficial. It's my theory that bacteria may reside in areas of the lungs that antibiotics may have difficulty penetrating to. Induction of pulmonary edema would allow for increased diffusion of the antibiotic and allow for deeper penetration to needed tissues where bacteria may reside.

While intentionally induced pulmonary edema may exacerbate the ARDS, several modes of ventilation exist to support the patient during these times, including bilevel. The clinician's own judgement, experience, and pt's lab values, should be used to determine the best mode of ventilation while also following conventional medication for adequate ventilation (ie, paralysis and sedation for pts on bilevel).

There are a variety of complications to be considered. The two most notable are hemorrhage from aneurysms, which may result from weakened blood vessels and increased intravascular pressures, and cerebral edema. To prevent hemorrhage, a decrease in CVP may be used, although it may also decrease the amount of extravascular leakage needed for proper antibiotic concentration. Personal judgement and experience will play a factor. To prevent cerebral edema, which will occur in a small minority of patients, I would suggest use of an intracranial pressure monitoring device.

In addition for aggressive fluid therapy, hypothermic therapy would also play an important factor in pt outcome. There are a number of trial studies using hypothermia, and you may look any number of them up (I recommend the Cool MI studies) and see for yourself the benefits of hypothermia. The cool MI studies suggest a temp between 33-34 degrees Celsius.

Thoughts, comments?

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i love the fact that you are so interested in thinking about problems and trying to think of novel ways of managing them.... however you are unfortunately confusing a lot of issues

1) creating pulmonay edema does not necessarily create capillary leak --- volume loading somebody will just lead to increased hydrostatic pressure in the lungs and thus the edema, not necessarily a breakdown of the endothelium leading to leakage.

2) CVP has nothing to do with pulmonary edema and definitely has nothing to do with capillary leak... capillary leak is an inflammatory response, not something that happens with increased intravascular pressure

3) with ARDS the last thing you want to do is create more fluid in the alveolar space.... the limitation of oxygen diffusion is what kills you (hence the needs for high PEEP and FIO2) and if you don't improve oxygen diffusion you are on your way to ECMO. So adding more fluid is not a good idea

4) hypothermia is the last thing you want to induce in a septic patient.... hypothermia is great in improving neurologic outcomes in patients with MIs or Embolic strokes.... however hypothermia really messes with the coagulation pathways which are intimately involved with the septic/inflammatory cascade....

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I was hoping you'd reply.

i love the fact that you are so interested in thinking about problems and trying to think of novel ways of managing them.... however you are unfortunately confusing a lot of issues

1) creating pulmonay edema does not necessarily create capillary leak --- volume loading somebody will just lead to increased hydrostatic pressure in the lungs and thus the edema, not necessarily a breakdown of the endothelium leading to leakage.

What I've noticed in the practice is that pts will start to develop generalized edema. It's only later on, after they've developed edema, that the pulmonary vascular endothelial cells will start to leak, so we're looking first at generalized edema of +4. I'm sure you've seen pts like these. Gross generalized edema, but it's common medical practice to start diuresing the pt. This is bad in my opinion. I will explain later. After you reach this point (generalized edema +4), you then fill them up with more fluid to induce a pulmonary edema. And I know you know that it is possible to induce a pulmonary edema. I've seen anesthesiologists say they gave X liters of fluid and then yell at nurses to stop the maintanance fluids because they didn't want to induce a pulmonary edema. Also, we're not looking at BREAKING DOWN the endothelium. We're just looking to create enough hydrostatic pressure so as to force the capillary musculature open to enable capillary leakage out into the pulmonary spaces.

2) CVP has nothing to do with pulmonary edema and definitely has nothing to do with capillary leak... capillary leak is an inflammatory response, not something that happens with increased intravascular pressure.

Not true:

Background: Pulmonary edema refers to extravasation of fluid from the pulmonary vasculature into the interstitium and alveoli of the lung. The formation of pulmonary edema may be caused by 4 major pathophysiologic mechanisms: (1) increased capillary hydrostatic pressure....

http://www.emedicine.com/med/topic1955.htm

Also, I know CVP doesn't have anything directly to do with pulmonary edema. However, CVP does measure fluid volume, and it was an objective way to measure how much fluid to give whereas the idea initially started by giving fluid according to assessment skills (assess edema, pulses, lung auscultation, strict i/o, and maintainance of blood pressure). So if we're measuring fluid volume, then we can measure the force of the fluid. If we increase that force, then we can increase the hydrostatic pressure within the vasculature of the body. If we increase the hydrostatic pressure high enough within the body, we can induce a pulmonary edema. Also, I'd argue that if we can increase the hydrostatic pressure high enough and at a fast enough rate, we can induce a pulmonary edema with minimal generalized edema because the pulmonary system is essentially one-sided: You've got the capillary on one side and then open space on the other, whereas in the rest of the body, you've got capillary and then some body organ. (I'm not sure how tenuous the musculature of the pulmonary capillary vasculature is vs. the vasculature of the rest of the body. Maybe the same?)

Also, edema in and of itself, as far as I know, doesn't pose as any real significant complication. Yes, the pt is bloated and swollen, and family members freak out on you, but so long as the cardiopulmonary system and the brain are unaffected, edema will resolve without significan complication. I've seen generalized edema +4 resolve on its own after the pt's disease process was resolved and the kidneys began removing excess fluid. If I've seen it, I know you've seen it.

3) with ARDS the last thing you want to do is create more fluid in the alveolar space.... the limitation of oxygen diffusion is what kills you (hence the needs for high PEEP and FIO2) and if you don't improve oxygen diffusion you are on your way to ECMO. So adding more fluid is not a good idea.

You can induce a pulmonary edema and support the pt's ventilation on various modes. You know the different modes--CPAP, IMV, AC, BILEVEL. Each mode has special properties and can be used in various grades of ARDS. If one level doesn't provide adequate oxygenation as evidenced by assessment, lactic acid level, abg, then modify your O2 sat or move onto the next level. Or you could do SIMV with intermittent peeps of 30. I personally prefer bilevel because of the properties associated with bilevel and the fact that I don't have to sit there and occasionally give the pt a sigh. Of course, the patient would have to be sedated and paralyzed because bilevel is uncomfortable. You're reversing the I:E ratio. I've seen patients on bilevel with an inverse ratio of I:E of 25:10, 100% FIO2, PS 15, p02 sat of 80 with an 02 sat of 84. You know what? That's still enough to support the patient while we try and correct the disease process because as long as the disease process remains the pt will never leave the hospital. You can pound the pt with as many antibiotics as you want, but as long as these antibiotics don't reach the site of infection, the pt will never leave the hospital. The antibiotics have to reach the site of infection. For hospital-acquired pneumonia, the sites can be abnormal due to a variety of reasons, especially considering all the chest tubes being placed.

4) hypothermia is the last thing you want to induce in a septic patient.... hypothermia is great in improving neurologic outcomes in patients with MIs or Embolic strokes.... however hypothermia really messes with the coagulation pathways which are intimately involved with the septic/inflammatory cascade....

I know sepsis results in inflammation, leading to microvascular hemorrhaging, leading to overloading of the anticoagulation system, leading to clots which create thrombi in distal organs, leading to organ failure, leading to multiorgan failure. It's my belief that if you control this inflammation, as evidenced by WBC count and temperature, you can slow down and maybe even prevent the development of sepsis. That's why I advocate a temperature drop of around 33-34 degrees Celsius. COOL MI studies also advocate a temperature drop of this degree because 1> WBC migrate more easily through the vasculature. 2> Body metabolism decreases with temperature drop. If we have decreased body metabolism, then we have decreased oxygen expenditure, and if the pt is in ARDS, decreased oxygen expenditure, when the pt is already starving for oxygen, is good. 3> Hypothermia creates vasoconstriction. In a pt that is bleeding microvascularly, this is good. 4> Viscious cycle of inflammatory responses are controlled.

Just as a side note: Hypothermia is painful and will cause shivering within the pt. If the pt isn't adequately sedated, with or without paralysis, then I don't encourage this use.

I'm giving this idea to anyone who wants to use it. A certain school is doing trials on it, but they modified it with CVP usage, whereas I initially proposed general assessment skills, so now it's not really my idea. All I wanted as my name included in the credits and maybe grad school. No monetary reward or anything physical. I realize I'm just an individual and can't go up against the whole school, so whatever. The intial studies are pretty good, but they haven't even used hypothermia and intracranial pressure monitoring. That's why a few of the pts come out neurologically deficit. Heh.

Please feel free to ask me anything else if you have questions. I know I came out with this idea. I know it works. I've seen it work. Patients who would have died wound up living; patients that might resolve wound up having shorter hospital stay. I'm giving you all this idea for free for you to use in those patients that you think qualify and have no other alternative until you feel confident to use this as general practice, which I'm confident it will someday become. Peace.

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Nevermind....

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....hmmmmmmmmmm..................this should be a lively discussion...

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(IMHO) Antimicrobial accessiblity in these situations is going to be circulation dependent, increasing the pulmonary edema will only increase the shunting, decreasing antimicrobial availability.

The other issue is that protiens leak along with the "fluid", these proteins are implicated in the exacerbation of injury. One example being PAI 1 which is associated with a higher incidence of fibrosis

Sometimes none of those ventilator modes are effective. All ventilator strategies can cause ALI, the goal is to minimize that risk, by placing a patient in the position of needing inverse ratio ventilation you are certainly increasing their risk of ARDS etc,.

I would say the list of potential complications is a whole lot longer than you state. In a later posting you stated that they were already performing this study. How did they ever convince an IRB much less a patient to agree to this. Must be in a county other than America because I can't imagine an IRB board approving it here.

Please provide some references to the physiology you are proposing.

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well i will start w/ this question...

those pt's who are in a +4 state of edema are wet and sloughing skin...like a burn patient - major electrolyte imbalances which in a state such as you mentioned could easily kill a pt.

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(IMHO) Antimicrobial accessiblity in these situations is going to be circulation dependent, increasing the pulmonary edema will only increase the shunting, decreasing antimicrobial availability.

I'm not sure of what you mean. Are you saying that causing a mild pulmonary edema will cause pulmonary shunting secondary to pulmonary hypertension? If so, from my understanding, the time for intentional induction of pulmonary edema isn't long enough to cause pulmonary arteries to alter their structure. Also, you wouldn't be inducing such a major increase in pulmonary pressures so as to cause the arteries to have to change their structure. This is because you're only inducing a mild pulmonary edema, enough to provide increased capillary leakage across the capillary walls. Just imagine your fingers wrapped around a tube of chicken wire so as to form a ceal. Imagine that chicken wire expanding just slightly so that there are now spaces between your fingers. This is the effect I'm talking about.

The other issue is that protiens leak along with the "fluid", these proteins are implicated in the exacerbation of injury. One example being PAI 1 which is associated with a higher incidence of fibrosis.

This is a good question. We have to look at the size of proteins vs. normal saline molecules/lactated ringers and the size of the antibiotics. Proteins are much larger than NS, LR, and antibiotics. So again, you have to find the right hydrostatic pressure so as to induce the capillaries to open up but not so much so that proteins will leak across. If proteins begin to leak across, you're causing injury to the capillaries. We don't want that. We simply want gentle opening up of the capillaries so that fluid will leak ("ooze" might be a better word) across the capillary membranes.

In the case that there is protein leakage across the extravascular space, the pt can be supported by insertion of a chest tube, with the serosanguinous fluids to be drained by low wall suction.

Sometimes none of those ventilator modes are effective. All ventilator strategies can cause ALI, the goal is to minimize that risk, by placing a patient in the position of needing inverse ratio ventilation you are certainly increasing their risk of ARDS etc,

You aren't increasing their risk for ARDS. You're might actually exacerbate their ARDS, but like I've said before, until we get use to this procedure, I would advise using it for only certain candidates, pts that don't have any hope. Also, again, I'm stressing the fact that you aren't putting a fire hose to these people turning the ON-knob all the way. In fact, I would advise against using an IV-pump at all. I would advise boluses to be given to gravity.

I would say the list of potential complications is a whole lot longer than you state. In a later posting you stated that they were already performing this study. How did they ever convince an IRB much less a patient to agree to this. Must be in a county other than America because I can't imagine an IRB board approving it here.

I know the potential complications are extent. That's why I prefaced this with the fact that this isn't an official scientific journal. However, the major complications are cerebral edema, ARDS, and bleeding.

I don't know the procedure in in IRB. I just know that doctors are doing it with consent from family members because the pts themselves are so sick that they can't consent. Family members are relatively easy to convince to give consent because the pts are already extremely sick.

Please provide some references to the physiology you are proposing.

http://www.emedicine.com/med/topic1955.htm

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well i will start w/ this question...

those pt's who are in a +4 state of edema are wet and sloughing skin...like a burn patient - major electrolyte imbalances which in a state such as you mentioned could easily kill a pt.

I have seen some pts with +4 edema with sloughing and wet skin, but not to the extent that they were like burn pts. Pts can easily obtain electrolyte imbalances, however. That's why electrolytes should be monitored on a scheduled basis. BMP, Mag, PO4 should be monitored at least qAM, or in the case you mentioned--with the sloughing of skin, etc--on a more frequent basis. Maybe q12 or q6 even. And replace lytes as needed. I'd also check urine lytes qAM, ABG at least qAM, or if the pt is in severe ARDS, then q1h. Again, you're going to have to use your clinical judgement on how frequent to measure these. I've had pts that required q1h abg's, lytes q4, lactic acid levels QD.

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Thanks for the questions. I really appreciate them. I'd like to discuss dialysis on these sorts of pts since many of them are also in acute renal failure. I think that Dopamine 2-5 mcg/kg/min would benefit most of these pts, and I've seen many of the pts recover from their acute renal failure after being on renal dose dopamine. However, to support the pts, dialysis may be ordered. Often times, the renal doctor will order 2-3 liters off the pt, and the dialysis nurse will crank up the machine to remove all this fluid and then some. This is not good. In fact, it goes against what you are trying to do. This is why I would strongly suggest good communication between the primary doctor, hopefully a pulmonologist, and the renal doctor. In most cases, the dialysis machine is able to correct serum lytes without removing fluid. Personally, I would favor removing the fluids while at the same time introducing fresh IVF. Example: For every 175 cc of fluid removed by the dialysis machine, the dialysis nurse introduces 175 cc of fresh IVF at the same time. This may require strict monitoring of lytes, but most dialysis machines I know of are able to adjust automatically. Then there's the CVVHD machines that provide constant and slow dialysis. Personally, I think these machines would benefit the entire process, and I'm in favor of them.

In the case where the pt's kidneys are still fully functional, we've modified the aggressive fluid therapy so that we'd have sustained increases in hydrostatic pressure for approximately 4 hrs, pulsed the pt with antibiotics, and then approximately 8-10 hrs after the antibiotics were given, diuresed the pt. This is simply to prevent the generalized edema that eventually ensues. Family members tend to be highly emotional when they see their family members so swollen. But this technique doesn't seem to be as effective.

Again, thanks for the questions. I welcome any insight, advice, words of wisdom, and discussion available.

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From an idiot's point of view and from someone who really knows NOTHING, but by doing what the OP stated, it seems like putting the patient at a risk. With patient's with Severe Septic Shock, the BP is already dangerously low but by overloading them rapidly wouldn't that cause flash pulmonary edema or too quick of volume shift?

I dunno, why bother when there are such great anti-septic meds like XIGRIS that work absolute wonders with Severe Septic shock.

Just a thought.

Pokey

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I have seen some pts with +4 edema with sloughing and wet skin, but not to the extent that they were like burn pts. Pts can easily obtain electrolyte imbalances, however. That's why electrolytes should be monitored on a scheduled basis. BMP, Mag, PO4 should be monitored at least qAM, or in the case you mentioned--with the sloughing of skin, etc--on a more frequent basis. Maybe q12 or q6 even. And replace lytes as needed. I'd also check urine lytes qAM, ABG at least qAM, or if the pt is in severe ARDS, then q1h. Again, you're going to have to use your clinical judgement on how frequent to measure these. I've had pts that required q1h abg's, lytes q4, lactic acid levels QD.

Ventilator injury;

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=14508153

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=12793874

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=12793866

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=12770853

Pulmonary edema;

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=14729508

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=12449188

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=11719296

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=11316656

As to HPV, whenever you decrease oxygenation to an area of the lung pulmonary vasoconstriction occurs. So if you are fluid overloading them, then you are also creating areas of HPV.

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