Those PALS folks are probably having seizures now.

[Veneficus]

Current pediatric fluid bolus guidlines increases mortality in a multinational study with thousands of patients enrolled and a control group.


http://www.medscape.com/viewarticle...6&src=wnl_edit_medp_ccmd&uac=103904SN&spon=32

http://www.nejm.org/doi/full/10.1056/NEJMoa1101549#t=articleTop

 

[Clipper1]

The PALS folks are the AAP (American Academy of Pediatrics).

The AAP already discussed this since it is not a new article. It was first publised in 2011 with data collection finishing in 2009.

http://aapgrandrounds.aappublications.org/content/26/4/41.extract


The FEAST article stated there were many factors to consider with specific disease processes for this to be conclusive. The study was also done with admissions to a hospital in Uganda, Kenya, or Tanzania.

Just like the organizations associated with the AHA and ECC, research is ongoing and new approaches are developed and observed. This is why ACLS, BCLS and PALS get updated every 5 years. This is also why it is made clear that these are guidelines especially in pediatric situations for experienced providers who specialize in critical care.

 

[WTEngel]

The study was incredibly well put together in my opinion. The only issue I have with applying this study's results broadly is that the demographic is so different than what we typically see in Western countries. Initially it looks like the results could be readily applied to most septic peds we treat, however 57% of the patients enrolled in this study were positive for malaria. I think if you conducted the study in America or Europe with similar sample sizes, your rate of malaria infection would be very nearly 0%.

I would like to see a study done in a sample without such a high rate of malarial infection before I completely convert my thinking. I agree with the general gist though, that fluids are not always used responsibly, especially in areas without ready access to peds critical care specialists.

 

[Veneficus]

The study was incredibly well put together in my opinion. The only issue I have with applying this study's results broadly is that the demographic is so different than what we typically see in Western countries. Initially it looks like the results could be readily applied to most septic peds we treat, however 57% of the patients enrolled in this study were positive for malaria. I think if you conducted the study in America or Europe with similar sample sizes, your rate of malaria infection would be very nearly 0%.

I would like to see a study done in a sample without such a high rate of malarial infection before I completely convert my thinking. I agree with the general gist though, that fluids are not always used responsibly, especially in areas without ready access to peds critical care specialists.

I think the instance of malaria actually promotes the conclusion.

Considering that malaria reduces the amount of RBCs, it can be extrapolated that in a hemorrhage patient, who also has a decrease in RBC that the rapid introduction of fluid can not only cause osmotic problems, but that increased vascular volume does not translate into increased survival.

Recently I met a doctor working there and we were actually discussing the difference in both appearance, treatment success, and prognosis in subsaharin p. falciprum compared to SE Asian P. Vivax.

It was relayed to me, that the treatment of falciprum is so efficent that it rarely presents complications, and the doctors there are very adept at treating it.

Clearly sepsis as well as other potential infective process is more challenging, but even in the best medical centers, sepsis mortality is considerable.

 

[Clipper1]

I think we can agree blood is the preferred with a low H&H. The study did point out in the appendix that 20% of the no-bolus group received blood. Only 4% in the saline group and 2% in the albumin group received blood. I agree with the AAP that is may have turned the study to a positive for blood rather than just being a negative about saline boluses. Of course just a saline bolus to someone with a hb of 5 gm/dl would not be beneficial. But, that does not mean it might not be of some benefit to someone with more normal Hb.

 

[Summit]

Added to the commute reading list for today (Text to Speech)

 

[WTEngel]

Is it fair to compare the reduction in RBCs secondary to hemorrhage vs. reduction secondary to erythrocytic infection?

 

[Veneficus]

Is it fair to compare the reduction in RBCs secondary to hemorrhage vs. reduction secondary to erythrocytic infection?

Why not? Does the manner of death somehow alter the net effects of the loss?

Perhaps the speed of death from a parasite infection is lower, but it is still loss. The measurable loss in a controlled sickness may even yield more information.

 

[Veneficus]

From the medscape update, I was particularly preoccupied with this phrase:

"The researchers conclude that the FEAST trial and their further analyses "suggest that rapid administration of fluid boluses increase the risk of subsequent cardiovascular collapse in children with shock, rather than increasing the risk of fatal fluid overload. The results suggest the need for further research to better understand the pathophysiology of shock and its treatment, and the mechanisms whereby rapid fluid resuscitation increased mortality in African children."

It's almost as if they were asking for me personally. That whole pathophys of shock thing...

But, to really consider the pathophys, I think it would help to see the hematocrit decline over time. That would determine if the nature of the most significant mechanism was oxygen delivery or end tissue damage.

Just brainstorming, things that I see causing problems are:

1. irreversible damage to RBCs by an osmotic or cyto C apoptosis cascade secondary to swelling.

The idea that small amounts of fluid do not cause damage is based soley on the concept of 3rd spacing, which suggests that there must be fluid overload to be damage.

But it does not account that some of that water may enter RBCs.

Which leads to point

2. The intracellular lipid bilayer has proteins which when exposed, like during swelling, or extrinsic damage will permit the attatchment of c3b or iGg. Which will mark those for macrophage destruction in the spleen.

3. In any event, change in structure of the RBC will affect both heme binding and oxygen disassociation.

4. Anaerobic metabolism, which leads to acidosis as a consequence, is a physiologic compensatory mechanism in end tissue. Rapid change in ph has the ability to denature proteins as well as right shift O2 diss. curve.

5. Cl- a free radical will damage anything it touches, which can set off or prolong an inflammatory response. All inflammation is destruction before construction.

6. Inflammation, clotting, and kinin, are all linked. Dilution of clotting factors also means dilution of anticlotting, the same with inflammation, kinin plays a small role for the purpose of this discussion.

7. Pressure, the basics of hemorrhage control is extravascular pressure must be greater than intravascular pressure. Even in sepsis, opposed to gross hemorrhage, capilary permiability, increases intravascular pressure and results in leakage.

8. Local mediation of hypoxic tissue causes physiologic reduction in capilary blood flow. Neither saline nor albumin transfer oxygen, so while central pressures may increase, local mediation is still in effect.

9. chatecholamine response causes an increase in circulating neutrophils, pulmonary and renal circulation is a well known location for pathologic degranulation.

10. repair vs. regeneration, is damaged tissue replaced by scar tissue prior to revascularization and regeneration when possible?

11. Electrolyte imbalance. does the addition of water or the water transfer from albumin have a local effect greater than systemic measurement? A study on free radical formation of excess cl- would support that, but it is just one study.

12. all of the above to some extent.

But I cannot reconcile off the top of my head why albumin fares worse. The only answer jumping out at me is cellular dehydration. In a cell already in anaerobic metabolism, dehydration would increase intracellular PH. But nothing in medicine is univariate.

I must ponder this more and it is bugging me.

 

[Veneficus]

and while I am thinking of it...

Does shunting to central circulation cause massive inflammatory changes resulting in nutritiona imbalance and dysregulation of the function ofassessory GI organs with other purposes such as protein synthesis in the liver or glycemic control of the pancrease...

This is really haunting me today...

Or osmotically active protein generated in central nervous cells cause tissue swelling and sequele specifc to the CNS?