Association of Catecholamine Dose, Lactate, and Shock Duration at Vasopressin Initiation With Mortality in Patients With Septic Shock*

Abstract

OBJECTIVES: To determine the association of catecholamine dose, lactate concentration, and timing from shock onset at vasopressin initiation with in-hospital mortality. DESIGN: Retrospective, observational study using segmented and multivariable logistic regression to evaluate the associations of catecholamine dose, lactate concentration, and timing from shock onset at vasopressin initiation with in-hospital mortality. SETTING: Multiple hospitals within the Cleveland Clinic Health System. PATIENTS: Adult patients who met criteria for septic shock based on the U.S. Centers for Disease Control and Prevention Adult Sepsis Event definition. INTERVENTIONS: All patients received continuous infusion vasopressin as an adjunct to catecholamine vasopressors. MEASUREMENTS AND MAIN RESULTS: In total, 1,610 patients were included with a mean Acute Physiology and Chronic Health Evaluation III 109.0 ± 35.1 and Sequential Organ Failure Assessment 14.0 ± 3.5; 41% of patients survived the hospital admission. At the time of vasopressin initiation, patients had median (interquartile range) lactate concentration 3.9 mmol/L (2.3–7.2 mmol/L), norepinephrine-equivalent dose 25 µg/min (18–40 µg/min), and 5.3 hours (2.1–12.2 hr) elapsed since shock onset. The odds of in-hospital mortality increased 20.7% for every 10 µg/min increase in norepinephrine-equivalent dose up to 60 µg/min at the time of vasopressin initiation (adjusted odds ratio, 1.21 [95% CI, 1.09–1.34]), but no association was detected when the norepinephrine-equivalent dose exceeded 60 µg/min (adjusted odds ratio, 0.96 [95% CI, 0.84–1.10]). There was a significant interaction between timing of vasopressin initiation and lactate concentration (p = 0.02) for the association with in-hospital mortality. A linear association between increasing in-hospital mortality was detected for increasing lactate concentration at the time of vasopressin initiation, but no association was detected for time elapsed from shock onset. CONCLUSIONS: Higher norepinephrine-equivalent dose at vasopressin initiation and higher lactate concentration at vasopressin initiation were each associated higher in-hospital mortality in patients with septic shock who received vasopressin.

When to start vasopressin in septic shock: the strategy we propose

“…This questions the interest of a weight-based threshold. Interestingly, several recent publications from experts report NE dose in µg/min, independently of weight [ 4 ]. The weight-based strategy could lead to a delay of AVP initiation in some patients, particularly in the growing proportion of obese critically ill patients.…”

“…The weight-based strategy could lead to a delay of AVP initiation in some patients, particularly in the growing proportion of obese critically ill patients. High doses of NE at AVP initiation may be associated with an increased risk of mortality [ 4 ]. Also, AVP doses are not adjusted for weight but rather used at a fixed dosage (up to 0.04 units/min).…”

Timing of vasoactive agents and corticosteroid initiation in septic shock

“…One evaluation found that norepinephrine-equivalent dose at vasopressin initiation was independently associated with increased odds of ICU mortality (OR, 3.14; 95% CI 1.36–7.28) [ 41 ]. Additionally, a recent evaluation found that after adjustment for severity of illness covariates, including SOFA score and APACHE III score, odds of in-hospital mortality increased 20.7% for every 10 mcg/min increase in norepinephrine-equivalent dose under 60 mcg/min at the time vasopressin initiation (OR, 1.21; 95% CI 1.09–1.34) [ 42 ]. No association was detected when norepinephrine-equivalent dose exceeded 60 mcg/min at vasopressin initiation.…”

Early Multimodal Vasopressors—Are We Ready for It?*

“…This calls into question whether the death sparing effects found by Sacha et al (3) are true vasopressin drug effect or artifact of a more rapidly tempered shock state. Not surprisingly, their patients (who all received vasopressin) were more likely to survive if they: 1) spent less time in shock, 2) had lower lactate concentrations, and 3) lower norepinephrine requirements (3), all characteristics consistent with a better resuscitated, better perfused, and less progressed shock. Accordingly, delays in restoring perfusion increase the risk of death, even in the early phases of septic shock (11).…”

“…Further, changes in plasma concentrations have not been associated with predicting a response to vasopressin in septic shock (5). Putting all of this into perspective, Sacha et al (3) do provide a very good argument for adding vasopressin early during the resuscitation of septic shock. However, we are also left with a very open-ended question, in that is it the delay in “decatecholaminization” that is the true problem or is it a specific vasopressin mechanism that helps improve outcomes?…”