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The effect of increasing doses of norepinephrine on tissue oxygenation and microvascular flow in patients with septic shock*

Jhanji, Shaman MRCP, FRCA; Stirling, Sarah MRCP, FRCA; Patel, Nakul MBBS; Hinds, Charles J. FRCP, FRCA; Pearse, Rupert M. FRCA, MD

doi: 10.1097/CCM.0b013e3181a00a1c
Clinical Investigations

Objective: To investigate the effect of escalating doses of norepinephrine, aimed at achieving incremental increases in mean arterial pressure (MAP), on microvascular flow and tissue oxygenation in patients with septic shock.

Design: Single-center interventional study.

Setting: University hospital intensive care unit.

Patients: Sixteen patients with established septic shock.

Interventions: The norepinephrine dose was escalated to achieve incremental increases in the MAP from 60 to 70, 80, and 90 mm Hg.

Measurements and Main Results: In addition to routine clinical measurements, cardiac output was determined using lithium dilution and arterial waveform analysis, cutaneous tissue Pto2 was measured using a Clark electrode, cutaneous red blood cell flux was assessed using laser Doppler flowmetry, and sublingual microvascular flow was evaluated using sidestream darkfield imaging. The mean (sd) norepinephrine dose increased from 0.18 (0.18) μg·kg−1·min−1 at 60 mm Hg to 0.41 (0.26) μg·kg−1·min−1 at 90 mm Hg (p < 0.0001). During this period, global oxygen delivery increased from 487 (418–642) to 662 (498–829) mL·min−1·m−2 (p < 0.01), cutaneous Pto2 increased from 44 (11) to 54 (13) mm Hg (p < 0.0001) and cutaneous microvascular red blood cell flux increased from 26.1 (16.2–41.9) to 33.3 (20.3–46.7) perfusion units (p < 0.05). No changes in sublingual microvascular flow index, vessel density, the proportion of perfused vessels, perfused vessel density, or heterogeneity index were identified by sidestream darkfield imaging.

Conclusions: In patients with septic shock, targeting higher MAP by increasing the dose of norepinephrine resulted in an increase in global oxygen delivery, cutaneous microvascular flow, and tissue oxygenation. There were no changes in preexisting abnormalities of sublingual microvascular flow. Further research is required to clarify the optimal end points for vasopressor therapy in patients with septic shock.

From the Barts and The London School of Medicine and Dentistry, Queen Mary’s University of London, London, United Kingdom.

Supported, in part, by a research grant from the Barts and The London Charity.

Dr. Pearse has received an unrestricted research grant from LiDCO Ltd. The remaining authors have not disclosed any potential conflicts of interest.

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© 2009 by the Society of Critical Care Medicine and Lippincott Williams & Wilkins