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Table 1 Animal model studies assessing effects of volume resuscitation on the microcirculation in lipopolysaccharide-induced sepsis

From: Effects of volume resuscitation on the microcirculation in animal models of lipopolysaccharide sepsis: a systematic review

Author

Publication year

Animal species

Number per arm

Methods used for microcirculation assessment

Type and mean volumes administered

Principal findings

Motivation for study

Maciel et al. [66]

1998

Dog

7

Quantification of oxygen extraction:

Microcirculation was assessed indirectly by quantifying oxygen extraction in gas analyzers sampling to measure expired oxygen fraction and end-tidal carbon dioxide tension

a) 291 ± 62 mL (control group, isotonic saline 0.9%)

b) 123 ± 12 mL (treatment group, hypertonic saline 7.5%)

Hypertonic saline resuscitation increases oxygen extraction compared to isotonic saline by improved microvascular perfusion

Assess whether a solution of hypertonic saline hydroxyl-ethyl starch can increase tissue oxygen extraction in endotoxic shock

de Carvalho et al. [61]

1999

Hamster

6

Intravital fluorescence microscopy:

Microcirculation was assessed by intravital microscopy of cheek pouch tissue and counting extravasation sites of fluorescein isothiocyanate-labelled, FITC dextran

a) No sepsis control; 0.35 mL/100 g body weight for 4 min, 7.5% hypertonic saline

b) and c) LPS groups 1 and 2 (no volume resuscitation controls)

d) HS group; 0.35 mL/100 g body weight for 15 min prior to LPS

e) HSD group; 0.35 mL/100 g body weight for 15 min prior and 4 min after the induction of LPS

Hypertonic saline with and without dextran reduce local and systemic endotoxin-inducedplasma leakage

Assess effect of hypertonic saline with and without dextran on endotoxin-induced vascular permeability in the cheek pouch microcirculation compared to systemically

Zhang et al. [67]

1999

Dog

7

Laser Doppler perfusion monitoring:

Microcirculation was assessed by laser Doppler measurements obtained from ileum and liver microvasculature which were then used to calculate an arbitrary red blood cell flux index in 1 mm3 of tissue in each organ

a) No fluid resuscitation control group

b) 20 mL/kg/h 0.9% normal saline

Microvascular depression in endotoxaemia was more severe in the liver than in the intestinal mucosa but increased similarly after initial resuscitation

Compare alterations in hepatic and intestinal mucosal microcirculation during the acute phase of blood flow reduction in endotoxic shock and the effect of fluid resuscitation

Oi et al. [64]

2000

Pig

(7, 8 and 9)

Laser Doppler flowmetry:

Microcirculation was assessed by intestinal blood flow laser Doppler measurements expressed in arbitrary laser Doppler perfusion units, PU

a) No fluid resuscitation control group

b) 4 mL/kg over 10-min (0.9% isotonic saline in 6% dextran 70, ISD)

c) 4 mL/kg over 10-min (7.5% hypertonic saline in 6% dextran 70, HSD)

Hypertonic saline improved intestinal mucosal blood flow better than isotonic saline and no resuscitation

Compare effects of hypertonic saline, isotonic saline and no resuscitation in endotoxin shock

Hoffmann et al. [62]

2002

Hamster

(7, 6 and 8)

Intravital fluorescence microscopy:

Microscopy was assessed by intravital microscopy on dorsal skin-fold chamber and computation of;

(a) Functional capillary density, FCD (i.e. length of all erythrocyte-perfused nutritive capillaries per observation area)

(b) Vascular permeability quantified by extravasation of fluorescein isothiocyanate-labelled, FITC dextran

a) No fluid resuscitation control group

b) 16 mL/kg HES

c) 66 mL/kg 0.9% isotonic saline

Synthetic hydroxyethyl starch (HES) preserved the functional capillary density (FCD) compared to saline and no resuscitation

Assess and compare effects of different volume support administered in endotoxin-induced microcirculatory disorders

Anning et al. [63]

2004

Rat

(5, 6 and 7)

Intravital fluorescence microscopy:

Microcirculation was assessed by intravital microscopy on an exteriorised loop of intestine and its associated mesentry and computation of;

(a) Measurements of the rolling velocity of all leucocytes entering a microvessel and leucocyte flux (i.e. the number of rolling leucocytes) were defined as adherent if stationary for >30 s

(b) Vascular permeability quantified by extravasation of fluorescein isothiocyanate-labelled bovine serum albumin (FITC-BSA)

a) No fluid resuscitation control group

b) 16 mL/kg/h (0.9% saline)

c) 16 mL/kg/h (5% albumin)

Lipopolysaccharide-induced albumin flux, leucocyte rolling and adhesion in the microcirculation was reduced by both 0.9% saline and 5% human albumin solutions

Assess effect of fluid administration on lipopolysaccharide-induced changes in mesenteric microcirculation

Dubin et al. [68]

2008

Sheep

7

Sidestream dark-field imaging:

Microcirculation was assessed by the following measurements obtained from sublingual mucosa and intestinal mucosa and serosa (three different regions within each site and each image was divided into four quadrants)

(a) Microvascular flow index, MFI [i.e. based on the diameters, blood capillaries were classified as small (10–25 μm), medium (26–50 μm) or large (51–100 μm) and flow was scored as no flow (0), intermittent flow (1), sluggish flow (2), continuous flow (3) or hyperdynamic flow (4). MFI calculated as the sum of each quadrant score divided by the number of quadrants in which the vessel type is visible]

(b) Percentage of perfused villi, PV% [i.e. the number of villi in each video were counted and semi-quantitatively classified as perfused, heterogeneously perfused or unperfused; PV% was calculated as number of perfused villi divided by the total number of villi]

6% HESa

Hydroxyethyl starch fluid resuscitation restored microcirculation in the sublingual and intestinal serosa but not in the intestinal mucosa

Test hypothesis that persistent villi hypoperfusion explains intramucosal acidosis after resuscitation for endotoxaemic shock

Legrand et al. [52]

2011

Rat

(5 and 7)

Laser speckle imaging:

Microcirculation was assessed by the following measurements obtained from the renal cortex

(a) Microvascular perfusion histograms based on laser speckle imaging perfusion maps

(b) Microvascular oxygen tension histograms based on phosphorimetry

a) Early resuscitation group 40 mL/kg in 300 min (HES), administered as 20 mL/kg/h in the first hour and 5 mL/kg/h for the remaining duration of the protocol

b) Late resuscitation group 30 mL/kg in 300 min (HES), administered as 20 mL/kg/h in the first hour and 5 mL/kg/h for the remaining duration of the protocol

Despite immediate hydroxyethyl starch fluid resuscitation being better than delayed resuscitation, overall prevention of renal macrovascular hypoperfusion did not fully prevent renal microcirculatory dysfunction

Test hypothesis that prevention of endotoxaemia-induced hypotension by immediate fluid resuscitation would prevent development of renal microcirculatory dysfunction

Andersson et al. [15]

2012

Sheep

(5 and 8)

Laser Doppler flowmetry and sidestream dark-field videomicroscopy:

Microcirculation was assessed by the following measurements obtained from five sites in the ileal mucosa, with each site divided into 4 quadrants at each time-point.

(a) Microvascular flow index, MFI [i.e. average flow of all quadrants scored as no flow (0), intermittent flow (1), sluggish flow (2) or continuous flow (3)]

(b) Percentage of perfused villi, PV% [i.e. the number of villi in each video were counted and semi-quantitatively classified as perfused, heterogeneously perfused or unperfused; PV% was calculated as number of perfused villi divided by the total number of villi]

(c) Heterogeneity index, HI [i.e. highest flow velocity minus lowest flow velocity divided by the mean MFI]

a) LPS group

519 ± (SD) 342 mL (HES)

Microcirculatory dysfunction persisted in fluid resuscitated endotoxaemic shock despite increased regional blood flow

Test hypothesis that in hyperdynamic endotoxaemic shock, intestinal microcirculatory dysfunction will be present despite increased regional blood flow

Duburcq et al. [65]

2014

Pig

5

Laser Doppler flowmetry:

Microcirculation was assessed on the skin blood flow using laser Doppler measurements expressed in arbitrary perfusion units, PU [i.e. peak flow was defined as the highest flow signal obtained post-pneumatic occlusion of blood flow to the legs. Duration of the flow signal was also recorded]

a) 0.9% sodium chloride group 5 mL/kg/h

b) 8.4% hypertonic sodium bicarbonate 5 mL/kg/h

c) 11.2% hypertonic sodium lactate 5 mL/kg/h

Hypertonic sodium lactate solution improves microvascular reactivity with a negative fluid balance

Investigate effects of hypertonic sodium lactate compared to sodium chloride on the microcirculation in endotoxic shock

Lopez et al. [51]

2015

Pig

–

Sidestream dark-field videomicroscopy:

Microcirculation was assessed by the following measurements obtained from the average of 12 quadrants (i.e. three videos of sublingual mucosa, four quadrants each);

(a) Microvascular density, MVD [i.e. number of vessels per mm2 in sublingual mucosa]

(b) Microvascular flow index, MFI [i.e. average flow of individual vessels scored as no flow (0), intermittent flow (1), sluggish flow (2) or continuous flow (3)]

(c) Heterogeneity flow index, HFI [i.e. highest MFI minus lowest MFI divided by mean MFI]

(d) Proportion of perfused vessels, PPV [i.e. total number of vessels minus number of vessels with flow = 0 or 1 divided by total number of vessels]

(e) Perfused vessel density, PVD [i.e. MVD multiplied by PPV]

a) LPS group 8 mL/kg/h (saline)

b) Early resuscitation protocol, ERP 250 mL/h for 2 h (Haemacell)

c) Sham 8 mL/kg/h (saline)

Early resuscitation restored macro-haemodynamic parameters but microcirculatory alterations persisted

Assess systemic and microcirculatory correlation of early resuscitation for endotoxic shock

  1. aVolume of resuscitation fluid administered not described