sepsis

Hey CTU.

I just wanted to post some of the information we covered about sepsis in case you wanted to give it a second look.  Some good references are linked throughout the text. Here is a link for current guidelines- click here
 

Why do we care?

Mortality rate is around 1/3 with severe sepsis

SIRS (2/4):

1.     HR > 90

2.     Temp. < 36 , > 38

3.     Resp rate > 20 or pCO₂ < 32

4.     WBC > 12 000 or < 4000

Sepsis:

Inflammatory reaction (SIRS) + probable evidence of infection

Severe Sepsis:

Sepsis + plus signs of hypoperfusion. i.e hypotension, oliguria ( < .5 ml/kg/hr), elevated lactate, elevated creatinine, elevated bilirubin, hypoxia

Septic Shock:

Sepsis + signs of hypoperfusion despite adequate resuscitation

So how do we resuscitate?

Based on Rivers 2001, NEJM (Rivers paper link)

·      RCT in one centre in Detroit, sample 263 with severe sepsis or worse

·      Randomized to early goal directed therapy v. usual care

·      Mortality 46.5 v. 30.5 %

·      Attempted to meet certain benchmarks within 6 hours of admission

1.     Inserted lines

2.     CVP 8 -12 mm Hg with fluids (CVP is pressure in SVC near R. atria = JVP + ~5 cm)

3.     MAP > 65 mm Hg with vasopressors preserves perfusion (MAP = 2/3 diastole + 1/3 systole)

4.     Scv0₂ < 70 %? (N.B Superior vena cava 0₂ saturation), check hematocrit!

Scv0₂ is a measure of how much oxygen is in blood after passing through body, so it could be low to either not enough delivery or too much consumption. We need to ensure enough delivery of oxygen to tissues.

a.     < 30 %, transfuse pRBCs

b.     > 30 %, use inotropic agents (in this case dobutamine)

·      So bottom line: using a protocol with hard outcomes works!

We try to do this, also target:

1.     Urine output > .5 ml /kg/hr

2.     Normalizing lactate, can be used instead of ScvO₂ , target >20% decrease in 2 hrs

Now we are thinking about resuscitation, what else should we be doing?

Treating the underlying infection!

1.     Diagnosis à head to toe: encephalitis, meningitis, ENT, influenza, pneumonia, GI, GU, hepatobiliary, skin, deep tissue, osteomyelitis, heart

·      Hx  / Physical

·      Imaging

·      Cultures (minimum 2 sets, peripheral and central)

·      Treat (within one hour is optimal): broad spectrum, generally combination therapy because better outcomes in the sickest patients (due to resistance?)

·      N.B: each hour delay increases mortality by 8%

Some Issues:

1.     What fluid should we use?

·      Remember Interstitial ¾ + Vascular ¼

·      Normal saline is salt water, it moves from intravascular to extravascular space according to Starling Forces: hydrostatic and oncotic pressure

·      Colloids are molecules that are too big to cross semi permeable membrane from vessels to interstitial space

·      Crystalloids: normal saline (Na 154 , pH 5.5), Ringer’s lactate (Na 131, lactate, K, Ca, pH 6.5)

·      NS is acidic because the ions decrease the concentration of CO₂ in blood.

·      Colloids: Albumin, Hydroxyethyl starch (HES)

·      Albumin has been shown to be SAFE (see SAFE study, link) in comparison to crystalloids, and may be better in severe sepsis (not a primary outcome)

·      HES have been shown to not offer much benefit compared to crystalloids and may cause harm (see CHEST study, link) as it leads to more RRT (renal replacement therapy)

2.     Which pressors should we use?

·      Norepinephrine is first choice (mainly vasoconstriction) compared to dopamine in meta-analysis, 2-40 mcg/min

·      Epinephrine is a great adjunct as no evidence of worse outcomes (theoretical splanchnic vasoconstriction), 1-20 mcg/min

·      Dobutamine is the first line ionotrope for low cardiac output

3.     Should we use corticosteroids?

·      Not in the initial resuscitation phase

·      Evidence is mixed. Major trial is CORTICUS (link): no mortality benefit, but not only patients non-responsive to pressors, and probably a less sick cohort

·      If resuscitation resistant shock trial IV hydrocort 200 mg/day

·      ACTH stimulation test not useful for deciding who to treat

4.     What is our hemoglobin level?

·      Our goal is a hb of 70, based on TRICC trial (link): transfusion level of 70 v 100 with no difference in mortality.

5.     Should we have tight glucose control?

·      We should aim for blood sugars between (10 - 6) to avoid hypoglycemia

·      Initial trial (leuven protocol) found reduced mortality with tight control (4-6)

·      NICE-SUGAR trial (link)found increased mortality with tight control from hypoglycemia

·      Subsequent meta-analyses have differed, may be due to sugar level of controls in each study

6.     Should we be using bicarbonate?

·      No if pH is > 7.15, as this has been studied in two small RCTs

·      Unclear if should be used in pH < 7.15. Remember bicarb will complex with hydrogen to make CO₂ and H₂O, and CO₂ can enter cells and cause worsening acidosis