Critical Care: Research Letters

The Relationship Between Norepinephrine Equivalent Dose of Vasopressors Within 24 Hours From the Onset of Septic Shock and In-Hospital Mortality Rate

Our understanding of hemodynamics in cirrhotic patients with sepsis remains limited. Our study aims to investigate differences in hemodynamic profiles using echocardiography between septic patients with and without cirrhosis.

This is a single-center, retrospective study of septic patients with echocardiogram within 3 days of ICU admission. We compared baseline characteristics, echocardiographic markers of LV systolic function arterial load between patients with and without cirrhosis. A propensity score-matched case-control model was developed to describe the differences in those echocardiography derived parameters between the groups.

3151 patients with sepsis were included of which 422 (13%) had cirrhosis. In the propensity score matched group with 828 patients, cirrhotic patients had significantly higher left ventricular ejection fraction (64 vs.56%, p < 0.001) and stroke volume (72 vs.48 ml, p < 0.001) along with lower arterial elastance (Ea) (1.35 1vs.20.3, p < 0.001) and systemic vascular resistance (SVR) (851 vs.1209 dynes/s/m⁻⁵, p = 0.001). The left ventricular elastance (Ees) (2.83 vs 2.45, p = 0.002) was higher and ventricular-arterial coupling (Ea/Ees) (0.48 vs. 0.86, p < 0.001) lower in cirrhotic compared to non-cirrhotic.

Septic patients with cirrhosis had higher LVEF with lower Ea and SVR with higher Ees and significantly lower Ea/Ees suggesting vasodilation as the principal driver of the hyperdynamic profile in cirrhosis.

This review discusses the rationale for vasopressin use, summarizes the results of clinical trials evaluating vasopressin, and focuses on the timing of vasopressin initiation to provide clinicians guidance for optimal adjunctive vasopressin initiation in patients with septic shock.

Patients with septic shock require vasoactive agents to restore adequate tissue perfusion. After norepinephrine, vasopressin is the suggested second-line adjunctive agent in patients with persistent inadequate mean arterial pressure. Vasopressin use in practice is heterogeneous likely because of inconsistent clinical trial findings, the lack of specific recommendations for when it should be used, and the high drug acquisition cost. Despite these limitations, vasopressin has demonstrated price inelastic demand, and its use in the United States has continued to increase. However, questions remain regarding optimal vasopressin use in patients with septic shock, particularly regarding patient selection and the timing of vasopressin initiation.

Experimental studies evaluating the initiation timing of vasopressin in patients with septic shock are limited, and recent observational studies have revealed an association between vasopressin initiation at lower norepinephrine-equivalent doses or lower lactate concentrations and lower mortality.

The impact of left ventricular (LV) systolic function on outcomes in patients with sepsis and septic shock remains uncertain. The association, if any, may be nonlinear.

Is LV systolic dysfunction associated with increased mortality among patients with sepsis and septic shock?

Retrospective cohort study comprising all adult patients admitted to the medical ICU from January 1, 2011, through December 31, 2020, with sepsis and septic shock as defined by the Third International Consensus Definitions for Sepsis and Septic Shock guidelines. All adult patients with sepsis or septic shock who underwent transthoracic echocardiography within 3 days from admission to the medical ICU were included. We divided patients into five groups based on LV ejection fraction (LVEF). In addition to univariate analysis, we also performed multivariate logistic regression analysis adjusting for patients’ baseline characteristics and severity of illness. The primary outcome was the association between each classification of LVEF and in-hospital mortality.

A total of 3,151 patients were included in this study (LVEF < 25%, 133 patients; 25% ≤ LVEF < 40%, 305 patients; 40% ≤ LVEF < 55%, 568 patients; 55% ≤ LVEF < 70%, 1,792 patients; and LVEF ≥ 70%, 353 patients). In-hospital mortalities in each LVEF category were 51.1%, 34.8%, 26.6%, 26.2%, and 41.9%, respectively. In the multivariate logistic regression analysis, LVEF of < 25% (OR, 2.75; 95% CI, 1.82-4.17; P < .001) and LVEF of ≥ 70% (OR, 1.70; 95% CI, 1.09-1.88; P = .010) were associated independently with significantly higher in-hospital mortality compared with the reference LVEF category of 55% to 70%.

The association of LVEF to in-hospital mortality in sepsis and septic shock was U-shaped. Both severe LV systolic dysfunction (LVEF < 25%) and hyperdynamic LVEF (LVEF ≥ 70%) were associated independently with significantly higher in-hospital mortality.