- Under steady state, glycolysis is converted to pyruvate which is used in the Citric Acid Cycle (CAC) and the subsequent electron carriers produced are used in the electron transport chain (ETC) to generate ATP.
- During increased physiological stress, the rate of glycolysis ramps up 10 to 100 times. The ETC and the CAC is unable to use the amount of pyruvate generated fast enough at the rate that its being produced.
- Hence, the pyruvate is metabolized into lactate.
- It has been proposed that lactate is generated via adrenergic stimulation to fuel tissues under physiological stress and not necessarily secondary to lack of tissue oxygenation.
- So, what’s the evidence to support that lactate is associated with tissue hypoxia? Studies have concluded that in the setting of tissue hypoxia there is hyperlactemia, hence we’ve inferred that lactate is a direct indication of tissue hypoxia, but this may be erroneous.
- Hyperlactemia is strongly associated with increased morbidity and mortality.
- There are alternate mechanisms of lactate production that do not involve oxygen debt.
- Beware of over-resuscitation when aiming for normalization of lactate and using it in isolation as an end-point of resuscitation.
- SCC guidelines suggest targeting normalization of lactate.
Mean Arterial Pressure (MAP)
- The "magic number" of a MAP of 65 comes from multiple studies, (some clinical and other animal studies) that demonstrated a MAP < 60 mm Hg is generally associated with worse outcomes.
- The Rivers trial based its MAP recommendation on two small retrospective studies that showed no improvement in lactate clearance with targeting a higher MAP.
- The SEPSISSPAM study is the biggest RCT to date that targeted a high (75-85 mm Hg) versus low (65-75 mm Hg) MAP in patients with septic shock - and found that there was no difference in all-cause mortality at 28 days.
- However, this RCT did show that targeting a higher MAP in those with a history of HTN decreases the incidence of AKI. We already know from existing evidence that renal replacement therapy is associated with higher mortality.
- No difference in high versus low MAP targets in patients with septic shock.
- Knowing your patient’s baseline BP may be helpful in knowing what MAP to target – ie: low baseline BP, then targeting even a MAP of 65 mm Hg may be too high, conversely, for a patient with hypertension, consider targeting a higher MAP.
- Individualized therapy should be considered instead of a protocol-based approach.
- SSC Guidelines suggest targeting a MAP of ≥ 65 mm Hg.
Central Venous Pressure (CVP)
- Variability in CVP measurement.
- Lack of evidence to support its use, particularly in the acute setting.
Inferior Vena Cava (IVC) Ultrasound
- At extremes, IVC collapsibility – either very large or very small – may have some value in predicting volume status, however, IVC collapsibility has a wide range where it is clinically indeterminate in the spontaneously breathing patient.
- While measuring the respiratory variations in IVC seems simple, it should not be used as our sole basis for determining a patient’s fluid status
Take Home Points
- River's trial end-points are not gospel.
- Lactate = Stress
- Utilize lactate as a screen in patients with suspected sepsis, but...
- Do not interpret it as a biomarker of hypoxia, but as a major protective component of the stress response that is also a strong predictor of mortality.
- MAP = one size may not fit all:
- Individualize your MAP targets: probably not doing any good by targeting a higher MAP unless they have chronic hypertension.
- CVP = Not worth it in isolation.
- Very unreliable, and does not reflect volume status.
- IVC U/S = no evidence in spontaneously breathing patients.
- Not the magical, easy, non-invasive end-point that we originally hoped, so you can't use it as the ultimate end-point.
- If you're seeing a collapse of anywhere from 30-50%, you could interpret that the patient may be fluid responsive, but more or less than that it is difficult to draw any conclusions.
7. Asfar, Pierre, Ferhat Meziani, Jean-François Hamel, Fabien Grelon, Bruno Megarbane, Nadia Anguel, Jean-Paul Mira, et al. 2014. High versus low blood-pressure target in patients with septic shock. , no. 17 (March 18). doi:10.1056/NEJMoa1312173..