Vasopressor Initiation Within 1 Hour of Fluid Loading Is Associated With Increased Mortality in Septic Shock Patients: Analysis of National Registry Data*

Abstract

OBJECTIVES: To investigate whether administration of a vasopressor within 1 hour of first fluid loading affected mortality and organ dysfunction in septic shock patients. DESIGN: Prospective, multicenter, observational study. SETTING: Sixteen tertiary or university hospitals in the Republic of Korea. PATIENTS: Patients with septic shock (n = 415) were classified into early and late groups according to whether the vasopressor was initiated within 1 hour of the first resuscitative fluid load. Early (n = 149) patients were 1:1 propensity matched to late (n = 149) patients. INTERVENTIONS: None. Measurement and Main Results: The median time from the initial fluid bolus to vasopressor was shorter in the early group (0.3 vs 2.3 hr). There was no significant difference in the fluid bolus volume within 6 hours (33.2 vs 35.9 mL/kg) between the groups. The Sequential Organ Failure Assessment score and lactate level on day 3 in the ICU were significantly higher in the early group than that in the late group (Sequential Organ Failure Assessment, 9.2 vs 7.7; lactate level, 2.8 vs 1.7 mmol/L). In multivariate Cox regression analyses, early vasopressor use was associated with a significant increase in the risk of 28-day mortality (hazard ratio, 1.83; 95% CI, 1.26–2.65). CONCLUSIONS: Vasopressor initiation within 1 hour of fluid loading was associated with higher 28-day mortality in patients with septic shock.

Prediction of vasopressor requirement among hypotensive patients with suspected infection: usefulness of diastolic shock index and lactate

“…Previous studies have suggested the potential benefits of early vasopressor use [ 8 - 12 , 22 , 23 ], but there is no precise index for the timing of vasopressor administration during initial sepsis management. Moreover, we could not conclude that prompt vasopressor use would improve outcomes in all hypotensive patients with suspected sepsis [ 14 ].…”

“…Early vasopressor use might allow faster achievement of the mean arterial pressure target. However, there are also traditional concerns regarding the impact of early vasopressor use [ 14 , 28 ]. Vasopressors may have potentially harmful effects in masking inadequate fluid resuscitation, and vasoconstriction may induce tissue hypoperfusion and organ dysfunction [ 14 ].…”

“…Early initiation of NE for septic shock might be beneficial in terms of more quickly correcting hypotension, maintaining organ perfusion and limiting the amount of fluid administration [ 9 - 12 ]. However, some controversial results have been reported [ 13 , 14 ]. In addition, there is no clear consensus on the appropriate time to initiate vasopressors during initial fluid resuscitation, and it has not been determined which index can be used to select patients who require vasopressors early [ 15 ].…”

Timing of vasoactive agents and corticosteroid initiation in septic shock

“…While both groups received more than 30 mL/kg of fluid, a greater volume was administered to the late vasopressor group within 6 h of shock identification (33.4 ± 21.0 vs. 38.0 ± 15.7 mL/kg; p = 0.046). Vasopressor dosing is not reported in this study, limiting the comparison to previously mentioned publication [ 28 ]. Future studies are needed to assess the relationship between fluid and vasopressor initiation and restrictive fluid strategies in sepsis.…”

“…Importantly, all these analyses in the CHASERS study were adjusted for severity of illness factors such as APACHE III score, comorbidities, and other resuscitative interventions. In contrast, a recently published prospective, multicenter, observational study classified patients into early and late vasopressor groups based on vasopressor timing in relation to fluid resuscitation [ 28 ]. In this propensity-matched analysis, there was a greater risk of 28-day mortality when vasopressor initiation occurred within 1 h after fluid bolus administration (47.7% vs. 33.6%; p = 0.013).…”