CASS
Trial question
What is the role of induced hypothermia among patients with septic shock and ventilator-dependent respiratory failure?
Study design
Multi-center
Open label
RCT
Population
Characteristics of study participants
40.4% female
59.6% male
N = 436
436 patients (173 female, 259 male).
Inclusion criteria: patients with at least 50 years of age admitted to the ICU for at least 24 hours with severe sepsis or septic shock who were on mechanical ventilation.
Key exclusion criteria: uncontrolled bleeding; clinically important bleeding disorder; recent open surgery; pregnancy or lactation; involuntary psychiatric admission.
Interventions
N=217 induced hypothermia (a target temperature of 32-34 degree Celsius for 24 hours and subsequent normothermia).
N=215 control (routine thermal management).
Primary outcome
Rate of all-cause mortality by day 30
44.2%
35.8%
44.2 %
33.2 %
22.1 %
11.1 %
0.0 %
Induced
hypothermia
Control
Borderline significant
increase ▲
Borderline significant increase in the rate of all-cause mortality by day 30 (44.2% vs. 35.8%; RR 1.2, 95% CI 1 to 1.6).
Secondary outcomes
No significant difference in death at day 180 (56.2% vs. 50.7%; RR 1.1, 95% CI 0.9 to 1.3).
Significant increase in alive without respiratory support to day 30 (3 days vs. 15 days).
Borderline significant increase in length of stay in the ICU (8 days vs. 9 days).
Safety outcomes
No significant differences in delirium, need for blood transfusion and surgery.
Significant differences in SOFA score at 72 hours (11 vs. 9), > 30% decrease in CRP (33.3% vs. 50.3%).
Conclusion
In patients with at least 50 years of age admitted to the ICU for at least 24 hours with severe sepsis or septic shock who were on mechanical ventilation, induced hypothermia was inferior to control with respect to the rate of all-cause mortality by day 30.
Reference
Theis Skovsgaard Itenov, Maria Egede Johansen, Morten Bestle et al. Induced hypothermia in patients with septic shock and respiratory failure (CASS): a randomised, controlled, open-label trial. Lancet Respir Med. 2018 Mar;6(3):183-192.
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