CENSER Trail AJRCCM.2019 was a single centre, randomised, double blinded, placebo controlled trial was done to evaluate if early low dose norepinephrine in adults with sepsis with shock improves shock control by 6 hours compared with standard care. Median time from emergency room arrival to norepinephrine administration was significantly shorter in the early norepinephrine group (93 vs. 192 min; P , 0.001). Shock control rate by 6 hours was significantly higher in the early norepinephrine group (118/155 [76.1%] vs. 75/155 [48.4%]; P , 0.001). The 28-day mortality was not different between groups: 24/155 (15.5%) in the early norepinephrine group versus 34/155 (21.9%) in the standard treatment group (P =0.15). The early norepinephrine group was associated with lower incidences of cardiogenic pulmonary edema (22/155 [14.4%] vs. 43/155 [27.7%]; P = 0.004) and new-onset arrhythmia (17/155 [11%] vs. 31/155 [20%]; P = 0.03).Early norepinephrine was significantly associated with increased shock control by 6 hours.
CLOVERS Trail NEJM.2023 was done to asses whether a early restrictive fluid strategy ( Prioritizing vasopressors and lower IV fluid volumes) or a liberal fluid management was beneficial for sepsis induced hypotension.
Study found that the restrictive fluid group administrated -2134ml of IV Fluids less than liberal fluid group and vasopressor use was more longer in restrictive use. Death from any cause before discharge home by day 90 occurred in 109 patients (14.0%) in the restrictive fluid group and in 116 patients (14.9%) in the liberal fluid group (estimated difference −0.9 percentage points; 95% CI, −4.4 to 2.6; P=0.61).
Among patients with sepsis-induced hypotension, the restrictive fluid strategy that was used in this trial did not result in significantly lower (or higher) mortality before discharge home by day 90 than the liberal fluid strategy.
ARISE Fluids Trail NEJM. 2026 randomly assigned adult patients who presented to the emergency department with septic shock to receive either fluids at restricted volumes and early vasopressor therapy (vasopressor group) or higher volumes of fluids and later vasopressor therapy (fluids group) for at least 6 hours and up to 24 hours.
In the first 24 hours after randomization, patients in the vasopressor group received less intravenous fluid than those in the fluids group (median difference, −1108 ml; 95% confidence interval [CI], −1395 to −850). The percentage of patients who received vasopressors was higher by 18.9 percentage points (95% CI, 13.3 to 24.5) in the vasopressor group. The median number of days alive and out of the hospital at day 90 was 76 (interquartile range, 55 to 83) in the vasopressor group and 76 (interquartile range, 55 to 82) in the fluids group (difference, 0.0 days; 95% CI, −2.7 to 2.7; P=1.00). Adverse events occurred in similar percentages of patients in the two groups, except
for pulmonary edema (0.6% in the vasopressor group vs. 5.0% in the fluids group; P<0.001).
The study concluded that Among adult patients who presented to the emergency department with septic shock, an approach that involved restricted fluid volume and early vasopressors didnot result in a greater number of days alive and out of the hospital at day 90 than an approach involving greater fluid volume and later administration of vasopressors.
Conclusion
Evidences from these studies shows that early vasopressors may help to achieve shock stabilisation early but studies have failed to show mortality benefit . At the same time liberal use of fluids have shown to be associated with adverse effects like pulmonary edema.
But we need to understand that sepsis induced hypotension can be due to decrease in vascular resistance, capillary leak, cardiac dysfunction, decreased circulatory volume or combination of all. So what suits to one patient may not be suitable for another. So now the world is moving towards personalised hemodynamic resuscitation.
