So recently published was the Andromeda SHOCK trial (jama_hernndez_2019_oi_190001) in JAMA this month.
Definitely interesting stuff, and have to commend the authors on a complex resuscitation strategy that had some real-world flexibility built in in terms of later generalizability and applicability for real-world cases. However there are some fundamentals I have concerns about. Let’s see what Rory thinks:
Yeah. I think the bottom line of opening resuscitationists’ eyes to NOT apply monosynaptic reflexes of giving fluids to elevated lactate is good. In that sense, definitely a step forward.
However, the insistence on maximizing CO under the illusion of optimizing perfusion remains problematic and leads to a congested state unless only a small or perhaps moderate amount of fluid is required to achieve non-volume responsiveness. I think it’s important to realize that the most rapid correction of hemodynamics is a surrogate marker and has not been definitively associated with survival across the board (eg the FEAST study and others), and it’s only proven clinical impact may be on health care workers’ level of anxiety.
Tune in soon for some other smart docs’ take on this!
cheers
Philippe
oh yes and don’t forget The Hospitalist & The Resuscitationist 2019:
thinking critical care 
Very nice comments and assessment gentlemen!
Since the topic of this study was essentially on the value of lactate guided resuscitation (although it’s presented the other way around as if the physical exam is the new monitoring tool), I’ll start with some of my thoughts and opinions on lactate. I think lactate does have important value. It makes me pay attention when its elevated, and it also makes me pay attention when my resuscitation doesn’t make it clear to normal levels.
The problem with using lactate as recommended by SSC and mandated by CMS isn’t measuring it. The problem lies with how it is understood and acted upon (or rather expected to be acted upon). Lactate can be elevated for a LOT of reasons. I hear the majority of people citing poor tissue perfusion and anaerobic metabolism as the major cause of hyperlactatemia in sepsis. I have a really hard time buying this.
The CO is almost always augmented in sepsis syndromes and thus the DO2 to the tissues is most likely at least normal if not hyper normal . Moreover, DO2 is almost always 4-5 times the VO2 rate except in moderate to severe cardiogenic shock or immediate pre-cardiac arrest states. Can regional splanchnic beds be clamped down and hypo perfused? I guess maybe, but I still don’t believe this argument. I think the weight of the evidence points to an AEROBIC mechanism of lactate generation in sepsis driven by beta-2 adrenergic agonism. I would be more inclined to believe a hypoxic model later on in the sepsis progression, but still not due to tissue perfusion issues but rather by metabolic dysfunction in very sick mitochondria.
So if lactate isn’t related to tissue perfusion, CO, and DO2, it doesn’t make sense to try to fix it (if it even needs to be fixed or should be fixed, by the way) with an augmentation of CO and DO2. This is where this quests to stamp out volume responsiveness comes from. This is also exactly what my problem is in trying to use lactate as a resuscitation guide: because of the likely fallacy that lactate is elevated because of tissue hypo perfusion, the “logical” assumption would lead to the second fallacy that the CO and DO2 must then be increased to meet the tissue O2 demands. Furthermore, the less logical approach to this supposed lack of CO, is to fix it with crystalloid if the patient is volume responsive, and volume loading with IVF is by far the first, if not only strategy people take to address an elevated lactate.
We must recall that if the hemodynamic derangement is distributive, the drop in ventricular preload is NOT due to a hypovolemic state, but rather a lack of vascular tone where the stressed volume is converted to unstressed volume. A more logical approach to fix the CO would therefore be to give a vasopressor to convert the unstressed volume back to stressed volume rather than IVF to augment the cardiac performance.
I think by this time, anyone who has been nice enough to listen to me knows that I feel that the what the MAP level is as important as where it comes from (i.e. a more normal/physiologic balance of CO, SVR, and preload to generate the BP). Giving a vasopressor instead of IVF to resuscitate the patient has the effect of decreasing the CO (which is abnormally elevated), and increasing the SVR and stressed volume, which are low. Thus the hypotensive patient not only gets a better perfusing BP, but it is generated in a more physiologic way. Also, I’d like to point out that this approach is different than the hemodynamic approach to sepsis in the FEAST trial and others. In those trials the when hemodynamics are mentioned, what is meant is largely blood pressure, not normalization of what generates the blood pressure.
In my opinion (and I’m sure Rory and Phil agree with me here), before any fluids are given, the presence of LV and RV fluid tolerance should be considered. If there is signs of congestion, there needs to be a very compelling reason to start checking for fluid responsiveness. Furthermore if fluid responsiveness is there, there also should be a good reason to try to make it go away (sorry, hyperlactatemia isn’t a good enough reason). Finally, if you decide to treat the fluid responsiveness, you need to decide if you will fix it with IVF or a shifting for unstressed volumes with a vasopressor.
If I sound like I hate fluids, I don’t. I’m not against giving fluids, and surely they have a very valuable place in resuscitation. I only want to point out that fluids are probably given far too frequently without adequate consideration if they are indicated or not and without thought as to what downstream consequences the administration of fluids will have in your patient in the future. Rory mentioned sepsis being a leaky state. IVF will make things more leaky through a variety of mechanisms most notably endovascular damage/glycocalyx shedding.
There’s a whole bunch more to discuss about the implications of this study, but I’ve probably rambled on to long. I’d really like to hear what others think about this as well!
[…] For more discussion on this trial check out Rory Spiegel’s breakdown at https://emcrit.org/emnerd/em-nerd-the-case-of-the-deceitful-lantern/ and our discussion at https://thinkingcriticalcare.com/2019/02/19/the-andromeda-shock-study-a-physiological-breakdown-with… […]