So in this month’s issue of Critical Care Medicine, an interesting article was published, where investigators took a (necessarily) simplified version of EGDT to Zambia and applied it to septic patients. It turned out they had to stop it early due to an excessive number of cases of respiratory failure in the treatment group. The difference was – you guessed it – they got “aggressive” volume resuscitation – up to 4l in the first 6 hours – guided by JVP assessment, and blood and dopamine if needed.
Simplified_Severe_Sepsis_Protocol___A_Randomized.1
The amounts received by 6, 24 and 72h were 2.9, 3.9 and 5.6 l for the treatment group vs 1.6, 3.0 and 4.3 l.
Now lets keep in mind that the patients, for the most part, did not have access to critical care, so the limited resources for ventilatory support made stopping the trial a bit early the only reasonable thing to do. Mortality in the treatment group was 64% and control 60%. High numbers, but this is explained in part by the prevalence of HIV (80%) and TB (37% of the HIV positive patients), so this data can’t necessarily be extrapolated to all populations, but to me, this is physiological support for the concept that aggressive fluid resuscitation – as I have stated in prior posts/podcasts – is most dangerous in those patients where the septic source – presumably “leaky” is ill-equipped to handle extra-physiological fluid. In these patients, as Myburgh states in a sepsis talk, “noradrenaline is the fluid of choice,” and although perhaps a bit tongue in cheek, this certainly speaks to my beliefs of resuscitating to euvolemia rather than to the lack of volume responsiveness (http://intensivecarenetwork.com/myburgh-john-beta-blockers-and-sepsis/).
Additionally, these patients were not hypotensive, and lactate was not available – local limitations of medical system. Hence the definition of severe sepsis triggering aggressive fluid resuscitation was based on SIRS type criteria, rather than some form of volume assessment.
Bottom line?
Be cautious in aggressive fluid administration in pulmonary sepsis. What, I really dislike when people say “be careful” or “be cautious,” because let’s face it, that doesn’t really mean anything, does it? It doesn’t tell you what to actually do… We are frontline clinicians, so I’ll say to limit fluid resuscitation in pulmonary sepsis. 2 litres up front? Probably ok so long as I have a varying, mid-size IVC (maybe 10-15mm – arbitrary and chronic pulmonary disease and hypertension have to be factored in) and a decent heart, but I don’t want to get to the point of no longer being fluid-responsive. Rather, go to pressors a bit earlier, perhaps, and no need for ongoing “maintenance” fluids at 100-150 cc’s an hour – remember that 80% of this wonderful therapy ends up where we don’t want it to.
cheers!
Philippe
PS for awesome talks by amazing speakers, don’t forget to register for CCUS 2015!!! For more info: http://wp.me/p1avUV-aU and register at http://www.ccusinstitute.org!
thinking critical care 
Totally agree Philippe:
I find it interesting to look at the quantity of actual therapy given in River’s landmark trial. From what i recall, in the first 6 hours, the protocol group got a good 5-6 L of crystalloid, whereas only 25% were getting vasoactive substances. Then if you look at the ‘River’s arm’ of ProCESS, these therapies are almost inverse [about half as much crystalloid is given in the first 6 hours, and 50% are on vasoactive substances]. Further, there seemed to be an increase in the risk of renal failure in ProCESS as a function of the amount of fluid given [speaking to your previous post on renal edema].
To me, in the decade + of critical care medicine between Rivers and ProCESS, it seems like we’ve realized [through study – e.g. FACCT trial, and anecdote] that too much fluid can be a bad thing in all organ systems.
I also want to remind everyone of the FEAST trial in NEJM Jun 2011 which showed that “Fluid boluses significantly increased 48-hour mortality in critically ill children with impaired perfusion in these resource-limited settings in Africa” so these findings should not be startling!
As a very crude rule of thumb, I think the severely septic patient should get a good 30 cc/kg of crystalloid and then if still hypotensive, then yes, levophed should be the fluid of choice.
Thanks!
Thanks Jon-Emile, your comments always add great points!
Interestingly enough, Kathryn Maitland, one of the authors of the FEAST study, had contacted me in 2009-2010 as they were interested in learning how to do optic nerve sheath ultrasound to detect cerebral deem, as they had concerns about these kids worsening deem with therapy. Unfortunately we didn’t manage to get this done before their excellent trial, and it would have been very interesting data. Perhaps in the future!
cheers!
This is an excellent point and It applies particularly to diffuse pulmonary conditions such as
PCP patients with HIV which present a sepsis phenotype which is poorly tolerant of fluid loading.
It is important to add that this may not be the case for some sepsis phenotypes involving infections of the lung (for example focal pneumonia and bacteremia or a toxigenic strain producing SuperAntigens). In an example, treating sepsis associated with focal pneumonia infection with toxigenic GAS requires massive fluid loading and death is almost certain if NE is the primary support for BP.
This is why we cannot think in broad terms about sepsis and septic shock. .The categorization of “pulmonary sepsis” is a step forward but there is not unique phenotype for pulmonary sepsis.
Great to see the movement of the clinicians toward thinking of sepsis in terms of different phenotypes. This is just more evidence that the concept of an all inclusive “sepsis or septic shock” which could be treated or studied in large clinical trails by a unifying protocol is an 1980s myth.
Time to get the trialists to think think like this
Thanks Lawrence and absolutely – that type of thinking is what I like to refer to as N=1 principle, which in a sense is difficult to obtain in an RCT, and diametrically opposed to a meta-analysis. Our challenge as clinicians is to take meaningful data from these RCTs and extrapolate it to the one patient in the bed in front of us. Sometimes, that may not be the exact treatment from the study, but a variant.
Indeed, I may be committing a crime against the very N=1 principle by lumping all pulmonary sepsis together, so excellent point! In a sense Daniel’s FALLS Protocol – an appearance of B lines with fluid resuscitation – if properly tracked in time (i.e. in the hour or so following the bolus), may detect the “leakier” lungs, unless the underlying pathology is very rapidly progressing. More questions than answers!
thanks again!