title: Testing a conceptual model on early opening of the microcirculation in severe sepsis and septic shock: a randomised controlled pilot study.
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.
  
  
  METHODS
  A randomised controlled pilot study.
  
  
  METHODS
  Single-centre mixed medical and surgical tertiary ICU.
  
  
  METHODS
  Ninety severe sepsis and septic shock patients randomised to early opening microcirculation resuscitation group or standard resuscitation group.
  
  
  METHODS
  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.
  
  
  METHODS
  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).
  
  
  CONCLUSIONS
  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.
  
  
  BACKGROUND
  Clinicaltrials.gov identifier NCT00484133.
authors.affiliation: From the Department of Intensive Care, Onze Lieve Vrouwe Gasthuis, Amsterdam (PHJvdV, MvZ, RJB, IvS, JPJ W, HMO-vS, DFK), the Department of Intensive Care, Tergooi Hospital, Hilversum (RvR), and the Department of Intensive Care, Free University Medical Centre, Amsterdam (HMO-vS), The Netherlands.
authors.forename: Peter H J
authors.initials: PH
authors.lastname: van der Voort
authors.forename: Mark
authors.initials: M
authors.lastname: van Zanten
authors.forename: Rob J
authors.initials: RJ
authors.lastname: Bosman
authors.forename: Ilse
authors.initials: I
authors.lastname: van Stijn
authors.forename: Jos P J
authors.initials: JP
authors.lastname: Wester
authors.forename: Rutger
authors.initials: R
authors.lastname: van Raalte
authors.forename: Heleen M
authors.initials: HM
authors.lastname: Oudemans-van Straaten
authors.forename: Durk F
authors.initials: DF
authors.lastname: Zandstra
mesh_terms: D000368:Aged; D005260:Female; D006801:Humans; D007362:Intensive Care Units; D057194:Intention to Treat Analysis; D007902:Length of Stay; D008297:Male; D008833:Microcirculation / Q000187:drug effects*; D008875:Middle Aged; D009102:Multiple Organ Failure / Q000175:diagnosis / Q000401:mortality / Q000503:physiopathology / Q000517:prevention & control*; D009426:Netherlands; D063305:Organ Dysfunction Scores; D010865:Pilot Projects; D012151:Resuscitation / Q000009:adverse effects / Q000379:methods* / Q000401:mortality; D012307:Risk Factors; D018805:Sepsis / Q000175:diagnosis / Q000401:mortality / Q000503:physiopathology / Q000628:therapy*; D012720:Severity of Illness Index; D012772:Shock, Septic / Q000175:diagnosis / Q000401:mortality / Q000503:physiopathology / Q000628:therapy*; D062606:Tertiary Care Centers; D013997:Time Factors; D016896:Treatment Outcome; D014664:Vasodilation / Q000187:drug effects*; D014665:Vasodilator Agents / Q000009:adverse effects / Q000627:therapeutic use*
chemical_list: D014665:Vasodilator Agents