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

Eur J Anaesthesiol. 2015 Mar;32(3):189-98. doi: 10.1097/EJA.0000000000000126.

Abstract

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.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Aged
  • Female
  • Humans
  • Intensive Care Units
  • Intention to Treat Analysis
  • Length of Stay
  • Male
  • Microcirculation / drug effects*
  • Middle Aged
  • Multiple Organ Failure / diagnosis
  • Multiple Organ Failure / mortality
  • Multiple Organ Failure / physiopathology
  • Multiple Organ Failure / prevention & control*
  • Netherlands
  • Organ Dysfunction Scores
  • Pilot Projects
  • Resuscitation / adverse effects
  • Resuscitation / methods*
  • Resuscitation / mortality
  • Risk Factors
  • Sepsis / diagnosis
  • Sepsis / mortality
  • Sepsis / physiopathology
  • Sepsis / therapy*
  • Severity of Illness Index
  • Shock, Septic / diagnosis
  • Shock, Septic / mortality
  • Shock, Septic / physiopathology
  • Shock, Septic / therapy*
  • Tertiary Care Centers
  • Time Factors
  • Treatment Outcome
  • Vasodilation / drug effects*
  • Vasodilator Agents / adverse effects
  • Vasodilator Agents / therapeutic use*

Substances

  • Vasodilator Agents

Associated data

  • ClinicalTrials.gov/NCT00484133