title: Elevated central venous pressure is associated with impairment of microcirculatory blood flow in sepsis: a hypothesis generating post hoc analysis.
abstract: BACKGROUND
  Microcirculatory driving pressure is defined as the difference between post-arteriolar and venular pressure. In previous research, an absence of correlation between mean arterial blood pressure (MAP) and microcirculatory perfusion has been observed. However, the microcirculation may be considered as a low pressure compartment with capillary pressure closer to venous than to arterial pressure. From this perspective, it is conceivable that central venous pressure (CVP) plays a more important role in determination of capillary perfusion. We aimed to explore associations between CVP and microcirculatory perfusion.
  
  
  METHODS
  We performed a post-hoc analysis of a prospective study in septic patients who were resuscitated according a strict non-CVP guided treatment protocol. Simultaneous measurements of hemodynamics and sublingual Sidestream Dark Field imaging were obtained 0 and 30 minutes after fulfillment of resuscitation goals. Data were examined for differences in microcirculatory variables for CVP ≤ or > 12 mmHg and its evolution over time, as well as for predictors of a microvascular flow index (MFI) < 2.6.
  
  
  RESULTS
  In 70 patients with a mean APACHE II score of 21, 140 simultaneous measurements of CVP and sublingual microcirculation (vessels < 20 µmeter) were obtained. (MFI) and the percentage of perfused small vessels (PPV) were significantly lower in the 'high' CVP (> 12 mmHg) group as compared to patients in the 'low' CVP (≤12 mmHg) group (1.4 ± 0.9 vs. 1.9 ± 0.9, P = 0.006; and 88 ± 21% vs. 95 ± 8%, P = 0.006 respectively). Perfusion pressure (MAP-CVP) and cardiac output did not differ significantly between both CVP groups. From time point 0 to 30 minutes, a significant increase in MFI (from 1.6 ± 0.6 to 1.8 ± 0.9, P = 0.027) but not in PPV, was observed, while CVP and perfusion pressure significantly decreased in the same period. In a multivariate model CVP > 12 mmHg was the only significant predictor for a capillary MFI < 2.6 (Odds ratio 2.5 (95% confidence interval 1.1-5.8), P = 0.026).
  
  
  CONCLUSIONS
  We observed a significant association between a higher CVP and impairment of microcirculatory blood flow. Further research is needed to elaborate on our hypothesis generating findings that an elevated CVP may act as an outflow obstruction of organ perfusion.
authors.affiliation: Department of Intensive Care Adults, Erasmus MC University Medical Center, Room H625, P.O. Box 2040, Rotterdam 3000 CA, Netherlands ; Department of Intensive Care, Medical Center Leeuwarden, P.O. Box 888, Leeuwarden 8901 BR, Netherlands.
authors.forename: Namkje Ar
authors.initials: NA
authors.lastname: Vellinga
authors.affiliation: Department of Intensive Care Adults, Erasmus MC University Medical Center, Room H625, P.O. Box 2040, Rotterdam 3000 CA, Netherlands.
authors.forename: Can
authors.initials: C
authors.lastname: Ince
authors.affiliation: Department of Intensive Care, Medical Center Leeuwarden, P.O. Box 888, Leeuwarden 8901 BR, Netherlands ; Department of Translational Physiology, Academic Medical Center, P.O. Box 22660, Amsterdam 1100 DD, Netherlands.
authors.forename: E Christiaan
authors.initials: EC
authors.lastname: Boerma
keywords: Central venous pressure; Microcirculation; Sepsis; Sidestream dark field imaging
references.citation: Crit Care. 2011;15(5):R222
references.pmid: 21936903
references.citation: Surgery. 2010 Jul;148(1):71-7
references.pmid: 20149401
references.citation: Crit Care. 2007;11(5):R101
references.pmid: 17845716
references.citation: Crit Care Med. 2009 Jun;37(6):1961-6
references.pmid: 19384212
references.citation: Med Biol Eng Comput. 2008 Jul;46(7):659-70
references.pmid: 18427850
references.citation: Intensive Care Med. 2013 Feb;39(2):165-228
references.pmid: 23361625
references.citation: Chest. 2008 Jul;134(1):172-8
references.pmid: 18628220
references.citation: Crit Care. 2005;9(6):R601-6
references.pmid: 16280059
references.citation: Crit Care Med. 2010 Jan;38(1):93-100
references.pmid: 19730258
references.citation: Crit Care Med. 2012 May;40(5):1443-8
references.pmid: 22430243
references.citation: Intensive Care Med. 2010 Dec;36(12):2004-18
references.pmid: 20811874
references.citation: Microcirculation. 2005 Jan-Feb;12(1):33-45
references.pmid: 15804972
references.citation: Curr Opin Crit Care. 2010 Jun;16(3):250-4
references.pmid: 20179590
references.citation: Circ Res. 1986 Nov;59(5):483-95
references.pmid: 3542277
references.citation: Am J Physiol. 1999 Dec;277(6 Pt 2):S203-10
references.pmid: 10644247
references.citation: Crit Care Med. 2004 Sep;32(9):1825-31
references.pmid: 15343008
references.citation: Crit Care Med. 2011 Feb;39(2):259-65
references.pmid: 20975548
references.citation: Anesth Analg. 2005 Apr;100(4):1107-1111
references.pmid: 15781529
references.citation: Am J Physiol. 1999 Dec;277(6):H2145-57
references.pmid: 10600832
references.citation: J Trauma. 2009 Mar;66(3):713-9
references.pmid: 19276743
references.citation: Opt Express. 2007 Nov 12;15(23):15101-14
references.pmid: 19550794
references.citation: Intensive Care Med. 2013 Apr;39(4):612-9
references.pmid: 23263029
references.citation: Crit Care. 2009;13(3):R92
references.pmid: 19534818
references.citation: Microcirculation. 1997 Mar;4(1):75-81
references.pmid: 9110285
references.citation: J Physiol. 1997 Sep 1;503 ( Pt 2):463-7
references.pmid: 9306287