Testing a conceptual model on early opening of the microcirculation in severe sepsis and septic shock: a randomised controlled pilot study.

BACKGROUND: Organ failure in severe sepsis and septic shock may be caused by microcirculatory failure.

OBJECTIVE: The objective of this study is to test a conceptual model of microcirculatory failure by using a resuscitation strategy targeting early opening of the constricted microcirculation with active vasodilatation.

DESIGN: A randomised controlled pilot study.

SETTING: Single-centre mixed medical and surgical tertiary ICU.

PATIENTS: Ninety severe sepsis and septic shock patients randomised to early opening microcirculation resuscitation group or standard resuscitation group.

INTERVENTIONS: Standard resuscitation group: fluids, noradrenaline, dobutamine and hydrocortisone were given to achieve a mean arterial pressure (MAP) of more than 60 mmHg, cardiac index more than 2.5 l min m and ScvO2 more than 70%. Microcirculation resuscitation group: nitroglycerin, enoximone, dopamine and dexamethasone targeting a microvascular flow index (MFI), measured by sublingual side-stream dark field imaging, more than 2.5.

MAIN OUTCOME MEASURE: A decrease in organ failure score (SOFA) on day four of ICU treatment.

RESULTS: Data from 37 microcirculation resuscitation and 28 standard resuscitation patients were analysed. In the microcirculation resuscitation group, MFI of more than 2.5 was achieved after a mean ± SD of 7.0 ± 4.6 h. The microcirculation resuscitation group received more fluids, and noradrenaline was equally prescribed in both groups. Per protocol, the decrease in SOFA score at day 4 was not different between groups (P = 0.64). There was a significant reduction in SOFA score in both groups compared with admission (1.2 and 1.6 in microcirculation resuscitation and standard resuscitation groups, respectively; P = 0.028 and P = 0.045).

CONCLUSION: Early opening of the microcirculation in patients with severe sepsis and septic shock using nitroglycerin, enoximone, dopamine and corticosteroids did not result in a faster reduction in organ failure than standard resuscitation.

TRIAL REGISTRATION: Clinicaltrials.gov identifier NCT00484133.