Norepinephrine increases preload

Noradrenaline (norepinephrine) may improve blood pressure in part through its venoconstriction effects, providing more venous return to the heart which increases cardiac output. A study of septic shock patients supports this.

An accompanying editorial by Drs Milzman and Napoli comments: “This study tells us something we probably already knew, that norepinephrine (NE) has the ability to provide venoconstriction, increase central venous pressure, provide a marginal increase in cardiac output, and improve the MAP in patients with septic shock. Importantly, it also demonstrates that Passive Leg Raise (PLR) continues to be a good predictor of preload responsiveness even in the presence of low doses of NE.”

OBJECTIVE: To assess the effects of norepinephrine on cardiac preload, cardiac index, and preload dependency during septic shock.

DESIGN: Prospective interventional study.

SETTING: Medical Intensive Care Unit.

PATIENTS: We included 25 septic shock patients (62 ± 13 yrs old, Simplified Acute Physiology Score II 53 ± 12, lactate 3.5 ± 2.1 mmol/L, all receiving norepinephrine at baseline at 0.24 [25%-75% interquartile range: 0.12-0.48] μg/kg/min) with a positive passive leg raising test (defined by an increase in cardiac index ≥10%) and a diastolic arterial pressure ≤40 mm Hg.

INTERVENTIONS: We performed a passive leg raising test (during 1 min) at baseline. Immediately after, we increased the dose of norepinephrine (to 0.48 [0.36-0.71] μg/kg/min) and, when the hemodynamic status was stabilized, we performed a second passive leg raising test (during 1 min). We finally infused 500 mL saline.

MEASUREMENTS AND MAIN RESULTS: Increasing the dose of norepinephrine significantly increased central venous pressure (+23% ± 12%), left ventricular end-diastolic area (+9% ± 6%), E mitral wave (+19% ± 23%), and global end-diastolic volume (+9% ± 6%). Simultaneously, cardiac index significantly increased by 11% ± 7%, suggesting that norepinephrine had recruited some cardiac preload reserve. The second passive leg raising test increased cardiac index to a lesser extent than the baseline test (13% ± 8% vs. + 19% ± 6%, p < .05), suggesting that norepinephrine had decreased the degree of preload dependency. Volume infusion significantly increased cardiac index by 26% ± 15%. However, cardiac index increased by <15% in four patients (fluid unresponsive patients) while the baseline passive leg raising test was positive in these patients. In three of these four patients, the second passive leg raising test was also negative, i.e., the second passive leg raising test (after norepinephrine increase) predicted fluid responsiveness with a sensitivity of 95 [76-99]% and a specificity of 100 [30-100]%.

CONCLUSIONS: In septic patients with a positive passive leg raising test at baseline suggesting the presence of preload dependency, norepinephrine increased cardiac preload and cardiac index and reduced the degree of preload dependency.

Norepinephrine increases cardiac preload and reduces preload dependency assessed by passive leg raising in septic shock patients
Crit Care Med 2011;39(4):689-94