Sepsis and Septic Shock

See Surviving Sepsis guidelines for official guidelines. However, the literature is nuanced.

Fluid management

SSC guidelines recommend blanket 30 mL/kg bolus to anyone in sepsis/septic shock but this recommendation is NOT based on strong evidence. Recent/prior RCTs examine fluids in septic shock:

  1. FEAST (2011) showed that fluid boluses were associated with increased mortality in children in Africa with sepsis and severe febrile illness.
  2. CLASSIC (NEJM 2022) showed that in 1554 ICU patients with septic shock, a restrictive-fluid strategy did not result in a different 90-day mortality rate (42.3 vs 42.1%) as compared to a standard-fluid resuscitation strategy.
  3. CLOVERS (NEJM 2023) RCT randomized 1563 patients with sepsis-induced hypotension (refractory to initial treatment with 1-3 L IV fluids) to a restrictive fluid strategy vs a liberal fluid strategy for a 24h period.
    1. About 2.1 litres less IV fluids were given in the 24h period in the restrictive arm;
    2. There was earlier, more prevalent, and longer duration of vasopressor use in the restrictive arm
    3. There was no significant difference (14.0 vs 14.9%) in the primary outcome of death before discharge by 90 days between the two arms

Restrictive Vs Liberal Fluids in Septic Shock?

Based on the large and well-powered CLASSIC and the CLOVERS trials, it is reasonable to pursue a restrictive fluids approach for septic shock. While this may lead to longer/high vasopressor requirements, there is no difference seen in key clinical outcomes.

Hemodynamic Support

Septic shock leads to organ hypoperfusion through a combination of vasodilatory shock, cardiac depression, microcirculatory dysfunction, mitochondrial dysfunction.

Vasopressors in Septic Shock

Indicated for fluid-unresponsive septic shock. Consider adjunctive steroids as well if refractory to low-medium dose single vasopressor therapy.

  1. Norepinephrine (8 mg in 250 mL, 0.03-2 mcg/kg/min)
  2. Vasopressin (2 units/h)
  3. Epinephrine (8 mg in 250 mL, 0.05 to 0.5 mcg/kg/min)

BP Targets in Septic Shock

Overall the data suggest a minimum MAP of 65 mmHg in septic shock. A MAP target that is too low may be associated with organ hypoperfusion, whereas one that is too high may be associated with ischemic injury due to excessive vasoconstriction.

The SEPSISPAM (NEJM 2014) trial compared BP targets in septic shock (MAP 80-85 vs 65-70 mmHg). There was no difference in 28-d mortality, 90-d mortality, serious adverse events. There was slightly increased atrial fibrillation with a higher target. There was slightly less RRT in patients with chronic HTN with the higher target, but this was not associated with improved mortality.

Steroids

Sepsis

The HYPRESS (2016) trial examined hydrocortisone in 380 patients with severe sepsis without shock. In summary, there was no difference at 14 days for the outcome of septic shock, and no differences in 28d and 90d mortality. Possible 13% reduction in delirium. No excess infections. Slight risk of hyperglycemia.

Septic Shock

See Steroids for Septic Shock.

References

  1. Asfar P, Meziani F, Hamel JF, et al. High versus Low Blood-Pressure Target in Patients with Septic Shock. New England Journal of Medicine. 2014;370(17):1583-1593. doi:10.1056/NEJMoa1312173
  2. Kato R, Pinsky MR. Personalizing blood pressure management in septic shock. Annals of Intensive Care. 2015;5(1):41. doi:10.1186/s13613-015-0085-5
  3. Hylands M, Moller MH, Asfar P, et al. A systematic review of vasopressor blood pressure targets in critically ill adults with hypotension. Can J Anesth/J Can Anesth. 2017;64(7):703-715. doi:10.1007/s12630-017-0877-1