Shock Syndromes I
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Recent studies have evaluated approaches of restricting early fluid resuscitation
in patients with septic shock.
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The Crystalloid Liberal or Vasopressors Early Resuscitation in Sepsis
(CLOVERS) trial compared clinical outcomes associated with a restrictive fluid
strategy with early vasopressors to a liberal fluid strategy (consisting of 2 L
crystalloid followed by additional boluses triggered by clinical markers). There
was no detected difference in death before discharge home by 90 days between
therapeutic strategies (absolute difference –0.9 [ 95% CI –4.4 to 2.6]) or other
clinical outcomes.
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The 2022 CLASSIC trial randomized 1554 patients with septic shock who had
received at least 1 L of intravenous fluids to either a restrictive-fluid group
or a standard-fluid group in which fluid administration was protocolized and
restricted to 250−500 mL of crystalloids. No difference in death by 90 days was
seen between intervention arms (42.3% vs 42.1%; RR 1.00; 95% CI, 0.89−1.13) or
serious adverse events (29.4% vs. 30.8%; RR 0.95; 95% CI, 0.77−1.15).
| d. | Lactate clearance |
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In one study of patients with sepsis and septic shock, failure to achieve a lactate clearance of
at least 10% was associated with a higher mortality rate than was failure to achieve an Scvo2
greater than 70%.
ii.
A large, multicenter, noninferiority study randomized patients to a quantitative resuscitation
protocol that incorporated Scvo2 as a treatment goal or to a quantitative resuscitation protocol
that incorporated a lactate clearance of 10% or greater as a treatment goal.
| (a) | The study aimed to address whether using Scvo2 as a treatment goal was necessary in a |
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quantitative resuscitation protocol.
| (b) | The lactate clearance strategy was noninferior to the Scvo2 strategy (in-hospital mortality |
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17% vs. 23%, respectively; 95% CI for mortality difference -3% to 15% [above the -10%
predefined noninferiority threshold]).
| (c) | Only 10% of the patients in each arm received a therapy specifically directed to improve |
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either lactate clearance or Scvo2, which biased the study toward finding no difference
between treatment arms (and incorrect rejection of a true null hypothesis of the existence
of a difference between groups in this noninferiority study; a type I error).
| (d) | Equally pertinent is that most patients with septic shock in this study (90%) achieved |
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adequate Do2 with only fluids and vasopressors.
iii.
Another multicenter, open-label study randomized ICU patients with a lactate concentration
of 3 mmol/L or greater to the addition of lactate clearance of 20% or more (evaluated every
2 hours for the first 8 hours of therapy) or standard therapy (in which the treatment team was
blinded for lactate concentrations).
| (a) | Both treatment arms had resuscitation targets of CVP 8–12 mm Hg, MAP 60 mm Hg or |
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greater, and urinary output above 0.5 mL/kg/hour. Scvo2 monitoring was optional in the
standard therapy group but was mandated as part of the lactate clearance group. In the
lactate clearance group, if the Scvo2 was 70% or greater but the lactate concentrations
did not decrease by 20%, vasodilators (e.g., nitroglycerin) were initiated to improve
microvascular perfusion.
| (b) | Adding lactate clearance as a treatment goal was not associated with a difference in hospital |
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mortality on bivariate analysis (33.9% vs. 43.5%, p=0.067). After adjustment for baseline
differences between groups with multivariable analysis, a significant difference favored the
lactate clearance group (HR 0.61; 95% CI, 0.43– 0.87; p=0.006).