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Yerke et al
that hemodynamic benefit can be expected across a wide
spectrum of septic shock patients regardless of ACTH
response status, severity of illness, and use or omission of
fludrocortisone. However, the patient population that may
derive survival benefit from corticosteroids is much more
nuanced. As previously noted, the 2 trials that demonstrated
a survival benefit enrolled patients with more significant
hemodynamic instability than those that found no mortality
benefit. Based on these findings, we suggest that mortality
benefit is most likely to be realized in patients who cannot
maintain hemodynamic stability with fluid resuscitation and
vasopressors alone or in those patients who require moderate
doses of norepinephrine and have a SOFA score of 3 or 4 for
at least 2 individual organs. Although they were published
prior to the 2 most recent studies of corticosteroids, current
guidelines are consistent with this recommendation. The
most recent Surviving Sepsis Campaign guidelines recommend the use of corticosteroids only in patients who cannot
maintain hemodynamic stability through fluid resuscitation
and vasopressor therapy.23 Guidelines from the Society of
Critical Care Medicine and European Society of Intensive
Care Medicine further specify that corticosteroids should
only be used in patients with septic shock that is not responsive to fluids and moderate- to high-dose vasopressor therapy.24 Second, in patients who are most likely to experience
hemodynamic improvement without mortality benefit, the
potential risks of adverse events must be considered. The
most consistently observed adverse effects in septic shock
patients treated with corticosteroids are hyperglycemia and
hypernatremia.14-16,18,19 Because of this, hydrocortisone therapy should be undertaken cautiously in patients with diabetes (particularly those presenting with concomitant diabetic
ketoacidosis or hyperosmolar hyperglycemic state) and in
those with hypernatremia at baseline. Hyperglycemia associated with corticosteroid therapy may be partially mitigated
with the use of a continuous hydrocortisone infusion rather
than intermittent boluses.25 However, comparisons of a bolus
dosing strategy with a continuous infusion strategy are not
robust in regard to clinical outcomes, and neither major trial
that observed mortality benefit utilized a continuous infusion
strategy.13,16,25,26 If a continuous infusion administration
strategy is used, it should be initiated with a hydrocortisone
bolus of 50 to 100 mg. Perhaps most concerning regarding
adverse effects associated with corticosteroids is the small
increase in neuromuscular weakness observed in the metaanalysis by Rochwerg et al18 (RR = 1.21, 95% CI = 1.011.52). However, this result was considered to be of low
certainty by the authors of the meta-analysis given variability in the timing and method of assessment and variability in
the magnitude of effect in the analyzed studies.18 Notably,
there has been no consistent increase in superinfections or
death from superinfections in patients treated with low-dose,
prolonged-course corticosteroids.18,19
In conclusion, we suggest that low-dose hydrocortisone
therapy should be administered to patients with septic shock

that require moderate- to high-dose vasopressors (more than
30 μg/min of norepinephrine) to maintain hemodynamic stability and have at least one additional (noncardiovascular)
organ failure. When the decision to start corticosteroids is
made, we suggest hydrocortisone (without fludrocortisone)
at doses of 50 mg IV every 6 hours for 7 days or until vasopressors are no longer needed to maintain hemodynamic stability (whichever is shorter, with no corticosteroid taper).
The same dose of corticosteroids may be cautiously considered to shorten shock duration in the remaining population of
septic shock patients, although we do not routinely advocate
for use in this subpopulation given the lack of consistent
mortality benefit associated with shortening shock duration.
Declaration of Conflicting Interests
The author(s) declared no potential conflicts of interest with respect
to the research, authorship, and/or publication of this article.

Funding
The author(s) received no financial support for the research, authorship, and/or publication of this article.

ORCID iDs
Jason Yerke
Seth R. Bauer

https://orcid.org/0000-0002-4391-9645
https://orcid.org/0000-0002-0420-0320

References
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https://www.orcid.org/0000-0002-4391-9645 https://www.orcid.org/0000-0002-0420-0320

Hospital Pharmacy - April 2020

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