Shock Syndromes I

ii.

A systematic review and fixed-effect meta-analysis of albumin compared with alternative fluids

for resuscitation in patients with sepsis found an association between albumin use and lower

mortality (OR 0.82; 95% CI, 0.67–1.0; p=0.047). The benefit of albumin was retained when the

analysis was restricted to crystalloids as the comparator (OR 0.78; 95% CI, 0.62–0.99; p=0.04).

These data should be interpreted with caution, however, because many of the included studies

had poor methodological quality, and when a random-effects model was used, the results for

the overall analysis were not statistically significant (OR 0.84; 95% CI, 0.69–1.02, p=0.08).

iii.

These data have renewed interest in 4%–5% albumin as a resuscitation fluid for patients with

sepsis and septic shock. As such, the 2021 SSC guidelines suggest albumin as a component

of the fluid resuscitation regimen when patients require a substantial amount of crystalloids.

Hydroxyethyl starch solutions should not be used for fluid resuscitation.

Compared with patients with sepsis allocated to lactated Ringer’s solution, those allocated to

pentastarch (a hydroxyethyl starch formulation) had a significantly higher incidence of acute

renal failure (34.9% vs. 22.8%, p=0.002) and need for renal replacement therapy (31.0% vs.

18.8%, p=0.001), with no difference in 28-day mortality (26.7% vs. 24.1%, p=0.48).

ii.

Compared with patients with sepsis randomized to receive Ringer’s acetate solution, patients

with sepsis randomized to receive hydroxyethyl starch had a significantly higher 90-day

mortality (51% vs. 43%, p=0.03) and need for renal replacement therapy (22% vs. 16%, p=0.04).

iii.

The increased need for renal replacement therapy and lack of mortality benefit in these studies

led to the strong recommendation against the use of hydroxyethyl starch for fluid resuscitation

in patients with sepsis and septic shock in the 2021 SSC guidelines.

Hyperoncotic (20%–25%) albumin replacement may be beneficial in patients with septic shock.

An open-label study compared the replacement of albumin (with 20% albumin) to a goal serum

albumin concentration of 3 g/dL plus crystalloid solution administration with the administration

of crystalloid solution alone in patients with sepsis or septic shock. The albumin and crystalloid

groups did not differ in the incidence of 28-day mortality (31.8% vs. 32.0%, p=0.94), but patients

allocated to albumin had a shorter time to cessation of vasoactive agents (median 3 vs. 4 days,

p=0.007). A post hoc subgroup analysis of patients with septic shock at enrollment showed that

those randomized to albumin had a lower 90-day mortality rate (RR 0.87; 95% CI, 0.77–0.99); 90-

day mortality did not differ in patients without septic shock (RR 1.13; 95% CI, 0.92–1.39; p=0.03

for heterogeneity). Of note, this post hoc subgroup analysis was performed on the secondary end

point of 90-day mortality, and an analysis of the primary outcome of 28-day mortality was not

reported. These data suggest that albumin replacement does not improve outcomes in patients with

sepsis but that it has hemodynamic (and potentially mortality) advantages in patients with septic

shock. Hence, the role of albumin replacement in patients with septic shock warrants further study.

Norepinephrine is the recommended first-line vasoactive medication. A meta-analysis of

randomized trials that compared norepinephrine with dopamine for the treatment of septic shock

found a higher risk of short-term mortality (RR 1.12; 95% CI, 1.01–1.20; p=0.035) and arrhythmias

(RR 2.34; 95% CI, 1.46–3.77; p=0.001) in patients allocated to dopamine.

The optimal approach to using vasoactive agents and inotropes beyond the choice of initial

vasopressor is unclear, but the choice should be based on patient-specific clinical factors.

Potential interventions could include using norepinephrine monotherapy (with appropriate

dose escalation) or initiating an additional therapy (i.e., a second catecholamine vasopressor,

arginine vasopressin (AVP), corticosteroids, an inotrope, or a combination of these therapies).

ii.

The optimal time or norepinephrine dose at which to consider additional therapies is unknown.

A dose that constitutes the failure of norepinephrine is not well defined in the literature, and

the maximal doses used by clinicians (or institutions) are variable and often subjective.