Early Goal Directed Therapy
/Early goal directed therapy is a key concept for all of us to understand. Sepsis is something that we encounter on our service, and even more so when you rotate in the ICU. In this blog I will briefly review sepsis and early goal directed therapy, but both of these concepts are reviewed in much greater detail already (Sepsis Review Article, Early Goal Directed Therapy). Instead, I would like to go into detail on an update to early goal directed therapy, utilizing lactic acid clearance as opposed to central venous O2 sat as method to guide treatment (Lactate Clearance vs Central Venous Oxygen Saturation as Goals of Early Sepsis Therapy: A Randomized Clinical Trial).
Brief Review of Sepsis
Sepsis is the combination of systemic inflammatory response syndrome (SIRS) and an infection. I’ve always complained that SIRS is defined rather liberally.
The criteria are 2 of the following:
1. Temperatur >38C or <36C
2. HR > 90bpm
3. RR>20 or PaCO2 <32
4. WBC >12,000 or <4,000 or >10% bands.
Severe sepsis is defined as Sepsis with organ dysfunction. Again, I feel this is a bit vague (see below for a better definition). Septic shock is all of the above with hypotension despite fluids resuscitation. It is easy to spot severe sepsis and septic shock. The real key is spotting those patients that are doing ok, but are about to go down hill. In theEarly Goal Directed Therapy (EGDT) article from 2001, pts that were assigned to standard therapy seemed to die more frequently from circulatory collapse. It seems this transition from the body hanging on, but barely, to severe sepsis can be very dramatic and lead to complete collapse. By preventing the transition or decreasing it, the patients seem to do much better. Of course, patients need to be identified early for this to happen!
Brief Mechanism for Crumping (It is all about cytokines of course...)
One of the key features of the patient who is maintaining their bp, but about to go down hill, is tissue hypo-perfusion and hypoxemia. Sepsis is a proinflammatory and procoagulant process. Hypoxemia only leads to worsening inflammation and procoagulation (darn cytokines), but unfortunately the bodies protective measures to maintain the BP leads to further hypoxia.
The main job of the cardiovascular system is to perfuse the brain. The body will sacrifice everything to keep the brain perfused. When a patient gets septic and begins to have a drop in the blood pressure, the body will divert blood flow from the peripheral tissues to maintain blood pressure and blood flow to the brain. Skeletal muscle has an enormous reserve for pulling out O2 from blood (makes sense: want to have the reserve so that you can run or exercise), so the diversion may not initially cause problems. The peripheral tissues will simply initially extract more O2. This leads to a decrease O2 sat from the periphery (measured by checking O2 sat in the vena cava), but no problems.
As the problem worsens, the body has to clamp down further. This leads to tissue hypoxia, where the tissues reserves have been used up and now they must go to an anaerobic mechanism for energy production. The anaerobic mechanism of course leads to lactic acid production. With this basic concept, it becomes easier to understand how to spot those patients who will crash on you along with understanding the mechanisms to prevent the crash. The key is to stop the snow balling: stop the hypoxia of the peripheral tissues! Ok, so lets go through the steps (algorithm).
Brief Steps for Approach for Sepsis
1. First, and most important, identify sepsis! Every patient admitted for an infection should be checked for Sespis (SIRS + an infection). To be honest, it is hard to be admitted unless you meet this criteria!
2. R/o Severe Sepsis or Septic Shock: The true definition for severe sepsis is too vague for me, so I like the definition used by many of the studies: SIRS + Infection + either SBP <90 or Lactic Acid >4. These patients are to immediately be started on the sepsis pathway and EGDT started. They should be admitted to the ICU.
3. Evaluate for high risk for crashing: Lactic Acid >2 (but less than 4), or tachycardia (but bp ok), or increasing RR or UOP <0.5ml/kg/hr. The goal of treatment here is to stop the hypoperfusion of the peripheral tissue. While the SBP is ok, unless the peripheral tissues get better perfusion then the patient will worsen. To improve perfusion, the patient needs aggressive fluid resuscitation (Liters). On the floor, we are unable to do CVP monitoring, so these patients need to be monitored clinically: HR, Watch JVP, Check Orthostatics, monitor hr, and watch uop. Additionally, we need to monitor the success of the resuscitation. Here is where a change from our prior practice needs to happen: q2 hr Lactic acid checks! While we can’t do CVP monitoring or central O2 Sat monitoring, we can monitor LA to see if improving.
Lactate Clearance: Easy method for monitoring success of treatment!
In a recent study, patients with severe sepsis defined by SIRS + Infection + SBP <90 or L.A. over 4, were assigned to either standard EGDT or to a modified EGDT. All patients would have a central line placed, and given IV fluids until CVP was 8-12. Following this the patients were placed on pressers if MAP <65 (check out this interesting article andeditorial on which pressers to use). At this point, the two groups differed.
One group had central venous O2 sats monitored, and if at or under 70%, would be transfused to keep their Hct over 30%. The other group had L.A. checked at initiation of everything, then checked again at 2 hours. If less than a 10% drop occurred in L.A., then they would be transfused to keep Hct over 30%. If L.A. had not dropped by 10% after the Hct was over 30%, then dobutamine was started with L.A. checked every hour until it had dropped (with dobutamine titrated up if not acheived). The results are not surprising, the two groups did the same.
So how does this study relate to what we do?
Well, I think it shows the value of L.A. This is truly an outstanding method for evaluating your resuscitation. Lactic acid really is a key player for detecting peripheral tissue hypoxia. I believe this can be extrapolated (to a certain point) to our patients that are on the floor. This can assist us in identifying those patients who are failing floor management vs those that are stabilizing. Frequent monitoring of L.A. maybe a powerful way of improving our care.
Please review the excellent articles linked in this blog! They are truly outstanding.