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How to assess and optimize
macro- and microcirculation
in splanchnic region
Joel Starkopf
Department of Anaesthesiology and Intensive Care
University of Tartu
Tartu University Hospital
Estonia
Disclosure
• Faculty: Joel Starkopf
• Relationships with commercial interests:
– Grants/Research Support: B. Braun Melsungen
– Consulting Fees: B. Braun Melsungen
Splanchnic region
• σπλαγχνικός splanchnikos; from
• σπλάγχνον splanchnon, pl. form
σπλάγχνα splanchna
• inward parts,organs, usually used to
describe organs in the abdominal cavity
(visceral organs)
Splanchnic circulation
Blood flow to the abdominal gastrointestinal organs
including the stomach, liver, spleen, pancreas, small
intestine, and large intestine.
Circulation in splanchnic region
Celiac axis Superior mesenteric artery Inferior mesenteric artery
• Anatomy for thrombemboli
• Tight network of collaterals
Splanchnic blood flow:
• 20…30% of cardiac output
• 20…30% of O2 consumption
• Liver blood flow
• Mesenteric blood flow
• Portal blood flow
Portal vein (SMV, IMV) Internal iliac vein (inferior, middle rectal)
Microcirculation in splanchnic region
Intestinal villi
• Counter-current exchange of solutes
• Tip of the villus highly susceptible to
damage from hypoxia and
hypotension
• Prolonged hypoperfusion - barrier
disruption - cascade of MOF?
• Impaired absorption of nutrients
Splanchnic blood flow
• Sympathetic activity: vasoconstriction of splanchnic vessels
• Parasympathetic activity: intestinal motility and secretion, metabolism –
indirect increase in local tissue perfusion
• Splanchnic blood flow  vasodilatory metabolites
• Liver
• Intestines
Poli de Figueiredo LF, et al. Acta Cir Bras 2002; 17(4): 211-219
Circulation in splanchnic region
• Arterial hypotension vs venous congestion
Verbrugge FH. J Am Coll Cardiol 2013;62:485–95
Capacitance function of the splanchnic vasculature
How to assess - macrocirculation
Splanchnic blood flow:
Hepatic vein catheterisation and Fick principle
• Invasive, risk of bleeding/thrombosis
• Hepatosplanchnic blood flow
• Continuous monitoring of hepatic venous saturation and
pressure
• Variablity, interpretation difficult
Dye-extraction methods (indocyanine green)
• Static, snapshot measurements
• Liver function and splanchnic perfusion
Ultrasound and laser Doppler flowmetry
• Operator dependent
• Patient characteristics
Jakob S, et al. Crit Care Med. 2009;37(2):483-9
Takala J. BJA 1997; 77:50-58
Hoffmann D, et al. Acta Anaesthesiol Scand 2005; 49:1280-1286
How to assess - macrocirculation
There is no easily applicable method for continuous monitoring of splanchnic
blood flow
Indirect, surrogate parameters
• General blood flow; cardiac output measurement
• Intra-abdominal pressure
‒ Case reports, animal experiments: IAP  splanchnic blood flow
‒ Abdominal perfusion pressure, APP=MAP-IAP?
Clinical signs, which may suggest insufficient splanhnic blood flow
• Pain, abdominal distention
• Bowel paralysis, feeding intolerance
• Diarrhoea, melaena
Radiology
• Anatomical lesions
How to assess - macrocirculation
Biomarkers
• Lactate, general marker of hypoperfusion, non-specific to
splanhnic region
Novel biomarkers to detect acute mesenteric ischemia:
No of
studies
Sensitivity (95% CI) Specificity (95% CI)
Intestinal fatty acid-binding protein
(I-FABP), kit Uden
4 79.0 (66.5-88.5) 91.3 (87.0-94.6)
Intestinal fatty acid-binding protein
(I-FABP), kit Osaka
6 75.0 (67.9-81.2) 79.2 (76.2-82.0)
Glutathione S-transferases (GSTs) 3 67.8 (54.2-79.5) 84.2 (75.3-90.9)
D-Lactate 3 71.7 (58.6-82.5) 74.2 (69.0-79.0)
Ischaemia modified albumin 2 94.7 (74.0-99.9) 86.4 (65.1-97.1)
Citrulline 1 39 100
Treskes N, et al. Diagnostic accuracy of novel serological biomarkers to detect acute mesenteric
ischemia: a systematic review and meta-analysis. Intern Emerg Med. 2017 May 6.
How to assess - microcirculation
• Capillary refill, mottled skin
Gastric tonometry
• PCO2 and arterial blood gases measured, luminal pH
(=intramucosal pH) calculated
• pHi reflects the splanhnic microcirculation
• Limitations: time needed to equilibrate CO2 between
the balloon and the lumen; acid secretion, enteral
feeding
Hand-held videomicroscopes HVM
• Sublingual area
• Orthogonally polarized spectral (OPS) imaging
• Sidestream dark-field (SDF) or incident dark-field (IDF) imaging
• Microcirculatory alterations
- independent from systemic haemodynamics
- associated with adverse clinical outcome
• Over 600 articles about clinical and experimental use of HVM
Ince C, et al. Intensive Care Med. 2018;44(3):281-299
How to assess - microcirculation
Sublingual videomicroscopy
• Assessment of videos (analysis of
datasets)
• Manual or automated?
• Related to splanhnic perfusion?
• Related to general perfusion?
Ileostoma videomicroscopy
• Limited group of patients
• Animal experiments
Further developments are needed prior to its integration into routine clinical practice
Ince C, et al. Second consensus on the assessment of sublingual microcirculation in critically ill patients: results from a task
force of the European Society of Intensive Care Medicine. Intensive Care Med. 2018;44(3):281-299.
How to optimise - macrocirculation
• Splanchnic blood flow is difficult to assess, therefore, seldom it can be set as
individual treatment target (vs cerebral blood flow, renal blood flow, coronary
blood flow). Rather, the total blood flow (cardiac output) is important.
• What are the changes of splanchnic blood flow
- in critical conditions?
- In response to therapies?
To optimize blood flow:
• Fluids
• Vasopressors
• Inotropes
• Treatment targets? MAP, IAP. APP? Fluid balance? Clinical signs of AGII?
Feeding intolerance, high gastric residuals. Bowel paralysis, Diarrhoea, rtc.
Their effect on:
- splanchnic blood flow?
- Splanchnic oxygen demand?
Sepsis
• Splanchnic blood flow increased
• O2 demand increased
Splanchnic blood flow, critical conditions and therapies
Takala J. BJA 1997; 77:50-58.
Other forms of distributive shock,
inflammatory states.
Splanchnic blood flow, critical conditions and therapies
Takala J. BJA 1997; 77:50-58.
After cardiac surgery
Septic shock and vasopressors
In low flow states (cardiogenic shock, hypovolemia)
• Splanchnic blood flow decreased
• O2 demand covered by increased O2 extraction ratio
Gatt M, et al. Crit Care Med. 2009;37(1):171-6.
Enteral feeding: increase of splanchnic blood flow and oxygen demand
Parenteral nutrition: no changes or decrease
Splanchnic blood flow, critical conditions and therapies
Healthy volunteers Patients
Takala J. BJA 1997; 77:50-58.
EN PN
Malbrain ML et al. Relationship between intra-abdominal pressure and indocyanine green plasma
disappearance rate: hepatic perfusion may be impaired in critically ill patients with intra-
abdominal hypertension. Ann Intensive Care. 2012 Dec 20;2 Suppl 1:S19
Splanchnic blood flow, critical conditions and therapies
Intra-abdominal hypertension
IAP Cardiac output   hepatosplanchnic blood flow 
IAP hepatosplanchnic blood flow 
40 pt, serial measurements, retrospective analysis
 non-survivors
 survivors Mean ICG dis-
appearance rate
Mean IAP
Mean APP
Correa-Martín L, et al. Tonometry as a predictor of inadequate splanchnic perfusion in an intra-
abdominal hypertension animal model. J Surg Res. 2013 Oct;184(2):1028-34
Intra-abdominal hypertension
5 hours 5 hours
Splanchnic blood flow, critical conditions and therapies
25 pigs, IAH induced by capnoperitoneum
IAP APP  pHi
Usefulness of gastric tonometry in assessment of splanchnic blood flow
IAP 30 mmHg
IAP 20 mmHg
IAP 30 mmHg
IAP 20 mmHg
Splanchnic blood flow, critical conditions and therapies
Takala J. BJA 1997; 77:50-58.
Vasopressors and inotropes
Variable effects depending on volemic status and underlying disease state
Septic shock and vasopressors Dobutamine after cardiac surgery
Ruokonen E, et al. CCM 1993; 21:1304-1311 Parviainen I, et al. BJA 1995; 74:277-282
• All solutions restored the MAP
and decreased the serum
lactatemia
• intestinal microcirculation
effectively resuscitated only
with hypertonic saline or
synthetic colloids
• Colloids: the greatest
formation of renal ROS in vivo
after reperfusion
SHAM Control
0,9% NaCl
Hypertonic saline
Gelatine HES
Fluids and splanchnic microcirculation
Wu CY, et al. Effects of different types of fluid resuscitation for hemorrhagic shock on splanchnic
organ microcirculation and renal reactive oxygen species formation. Crit Care. 2015; 19:434
male Wistar rats, haemorrhage 30 ml/kg
• Anesthetised sheeps
• Endotoxin vs sham 24 hrs
• Fluid resuscitated
endotoxin
sham
Macrocirculation
Norepinephrine
Microcirculatory blood flow
Laser Doppler probes to monitoring microcirculatory blood flow in the muscularis
layer (MCQmusc) and mucosa (MCQmuc) of the ileum.
endotoxin
sham
How to optimise – macro- vs microcirculation
Andersson A, et al. Gut
microcirculatory and mitochondrial
effects of hyperdynamic
endotoxaemic shock and
norepinephrine treatment.Br J
Anaesth. 2012;108(2):254-61.
Loss of coherence between macro- and microcirculation in several experimental and clinical studies
Endotoxin:
• Drop in MAP
• Increased splanhnic
blood flow
• decreased
microcirculatory blood
flow
How to assess How to optimise
Macrocirculation in
splanchnic region
- Hepatic vein catheterisation
and Fick principle
- ICG disappearance rate
- Cardiac output
- Arterial pressure
- Intra-abdominal pressure
- Abdominal perfusion pressure
- Lactate
- Other biomarkers
- Clinical signs (diarrhoae,
feeding intolerance, bleeding)
- Global haemodynamic
management with
individualised targets
- Vasopressors and inotropes
(pro-s and cons)
- Avoid fluid overload
- Management of IAH
- Effect of feeding
Microcirculation in
splanchnic region
- Remains experimental
- Videomicroscopy (sublingual,
stomas)
- Gastric tonometry
- CO2 a-v difference
- Limited evidence
- Poorly correlates with
macrohemodynamics
- Different type of fluids
- Vasopressors
- Inotropes
- Nitrates?
Summary
Take home message
Splanchnic blood flow
• Takes up to one third of cardiac output in normal physiology
• Is increased postprandially, and in septic shock
Splanhnic microcirculation
• Indirect assessment via clinical signs and biomarkers
• Role for sublingual videomicroscopy in the future?
Optimisation of splanhnic blood flow
• Fluid management
• Intra-abdominal pressure and abdominal perfusion pressure
• Vasopressors and inotropes
• Hypovolemia and hypotension vs venous congestion
• Little coherence between macro- and microcirculation

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Monitoring macro and microcirculation (Joel Starkopf WSACS session ESA 2018 #EA18)

  • 1. How to assess and optimize macro- and microcirculation in splanchnic region Joel Starkopf Department of Anaesthesiology and Intensive Care University of Tartu Tartu University Hospital Estonia
  • 2. Disclosure • Faculty: Joel Starkopf • Relationships with commercial interests: – Grants/Research Support: B. Braun Melsungen – Consulting Fees: B. Braun Melsungen
  • 3. Splanchnic region • σπλαγχνικός splanchnikos; from • σπλάγχνον splanchnon, pl. form σπλάγχνα splanchna • inward parts,organs, usually used to describe organs in the abdominal cavity (visceral organs) Splanchnic circulation Blood flow to the abdominal gastrointestinal organs including the stomach, liver, spleen, pancreas, small intestine, and large intestine.
  • 4. Circulation in splanchnic region Celiac axis Superior mesenteric artery Inferior mesenteric artery • Anatomy for thrombemboli • Tight network of collaterals Splanchnic blood flow: • 20…30% of cardiac output • 20…30% of O2 consumption • Liver blood flow • Mesenteric blood flow • Portal blood flow Portal vein (SMV, IMV) Internal iliac vein (inferior, middle rectal)
  • 5. Microcirculation in splanchnic region Intestinal villi • Counter-current exchange of solutes • Tip of the villus highly susceptible to damage from hypoxia and hypotension • Prolonged hypoperfusion - barrier disruption - cascade of MOF? • Impaired absorption of nutrients Splanchnic blood flow • Sympathetic activity: vasoconstriction of splanchnic vessels • Parasympathetic activity: intestinal motility and secretion, metabolism – indirect increase in local tissue perfusion • Splanchnic blood flow  vasodilatory metabolites • Liver • Intestines Poli de Figueiredo LF, et al. Acta Cir Bras 2002; 17(4): 211-219
  • 6. Circulation in splanchnic region • Arterial hypotension vs venous congestion Verbrugge FH. J Am Coll Cardiol 2013;62:485–95 Capacitance function of the splanchnic vasculature
  • 7. How to assess - macrocirculation Splanchnic blood flow: Hepatic vein catheterisation and Fick principle • Invasive, risk of bleeding/thrombosis • Hepatosplanchnic blood flow • Continuous monitoring of hepatic venous saturation and pressure • Variablity, interpretation difficult Dye-extraction methods (indocyanine green) • Static, snapshot measurements • Liver function and splanchnic perfusion Ultrasound and laser Doppler flowmetry • Operator dependent • Patient characteristics Jakob S, et al. Crit Care Med. 2009;37(2):483-9 Takala J. BJA 1997; 77:50-58 Hoffmann D, et al. Acta Anaesthesiol Scand 2005; 49:1280-1286
  • 8. How to assess - macrocirculation There is no easily applicable method for continuous monitoring of splanchnic blood flow Indirect, surrogate parameters • General blood flow; cardiac output measurement • Intra-abdominal pressure ‒ Case reports, animal experiments: IAP  splanchnic blood flow ‒ Abdominal perfusion pressure, APP=MAP-IAP? Clinical signs, which may suggest insufficient splanhnic blood flow • Pain, abdominal distention • Bowel paralysis, feeding intolerance • Diarrhoea, melaena Radiology • Anatomical lesions
  • 9. How to assess - macrocirculation Biomarkers • Lactate, general marker of hypoperfusion, non-specific to splanhnic region Novel biomarkers to detect acute mesenteric ischemia: No of studies Sensitivity (95% CI) Specificity (95% CI) Intestinal fatty acid-binding protein (I-FABP), kit Uden 4 79.0 (66.5-88.5) 91.3 (87.0-94.6) Intestinal fatty acid-binding protein (I-FABP), kit Osaka 6 75.0 (67.9-81.2) 79.2 (76.2-82.0) Glutathione S-transferases (GSTs) 3 67.8 (54.2-79.5) 84.2 (75.3-90.9) D-Lactate 3 71.7 (58.6-82.5) 74.2 (69.0-79.0) Ischaemia modified albumin 2 94.7 (74.0-99.9) 86.4 (65.1-97.1) Citrulline 1 39 100 Treskes N, et al. Diagnostic accuracy of novel serological biomarkers to detect acute mesenteric ischemia: a systematic review and meta-analysis. Intern Emerg Med. 2017 May 6.
  • 10. How to assess - microcirculation • Capillary refill, mottled skin Gastric tonometry • PCO2 and arterial blood gases measured, luminal pH (=intramucosal pH) calculated • pHi reflects the splanhnic microcirculation • Limitations: time needed to equilibrate CO2 between the balloon and the lumen; acid secretion, enteral feeding Hand-held videomicroscopes HVM • Sublingual area • Orthogonally polarized spectral (OPS) imaging • Sidestream dark-field (SDF) or incident dark-field (IDF) imaging • Microcirculatory alterations - independent from systemic haemodynamics - associated with adverse clinical outcome • Over 600 articles about clinical and experimental use of HVM Ince C, et al. Intensive Care Med. 2018;44(3):281-299
  • 11. How to assess - microcirculation Sublingual videomicroscopy • Assessment of videos (analysis of datasets) • Manual or automated? • Related to splanhnic perfusion? • Related to general perfusion? Ileostoma videomicroscopy • Limited group of patients • Animal experiments Further developments are needed prior to its integration into routine clinical practice Ince C, et al. Second consensus on the assessment of sublingual microcirculation in critically ill patients: results from a task force of the European Society of Intensive Care Medicine. Intensive Care Med. 2018;44(3):281-299.
  • 12. How to optimise - macrocirculation • Splanchnic blood flow is difficult to assess, therefore, seldom it can be set as individual treatment target (vs cerebral blood flow, renal blood flow, coronary blood flow). Rather, the total blood flow (cardiac output) is important. • What are the changes of splanchnic blood flow - in critical conditions? - In response to therapies? To optimize blood flow: • Fluids • Vasopressors • Inotropes • Treatment targets? MAP, IAP. APP? Fluid balance? Clinical signs of AGII? Feeding intolerance, high gastric residuals. Bowel paralysis, Diarrhoea, rtc. Their effect on: - splanchnic blood flow? - Splanchnic oxygen demand?
  • 13. Sepsis • Splanchnic blood flow increased • O2 demand increased Splanchnic blood flow, critical conditions and therapies Takala J. BJA 1997; 77:50-58. Other forms of distributive shock, inflammatory states.
  • 14. Splanchnic blood flow, critical conditions and therapies Takala J. BJA 1997; 77:50-58. After cardiac surgery Septic shock and vasopressors In low flow states (cardiogenic shock, hypovolemia) • Splanchnic blood flow decreased • O2 demand covered by increased O2 extraction ratio
  • 15. Gatt M, et al. Crit Care Med. 2009;37(1):171-6. Enteral feeding: increase of splanchnic blood flow and oxygen demand Parenteral nutrition: no changes or decrease Splanchnic blood flow, critical conditions and therapies Healthy volunteers Patients Takala J. BJA 1997; 77:50-58. EN PN
  • 16. Malbrain ML et al. Relationship between intra-abdominal pressure and indocyanine green plasma disappearance rate: hepatic perfusion may be impaired in critically ill patients with intra- abdominal hypertension. Ann Intensive Care. 2012 Dec 20;2 Suppl 1:S19 Splanchnic blood flow, critical conditions and therapies Intra-abdominal hypertension IAP Cardiac output   hepatosplanchnic blood flow  IAP hepatosplanchnic blood flow  40 pt, serial measurements, retrospective analysis  non-survivors  survivors Mean ICG dis- appearance rate Mean IAP Mean APP
  • 17. Correa-Martín L, et al. Tonometry as a predictor of inadequate splanchnic perfusion in an intra- abdominal hypertension animal model. J Surg Res. 2013 Oct;184(2):1028-34 Intra-abdominal hypertension 5 hours 5 hours Splanchnic blood flow, critical conditions and therapies 25 pigs, IAH induced by capnoperitoneum IAP APP  pHi Usefulness of gastric tonometry in assessment of splanchnic blood flow IAP 30 mmHg IAP 20 mmHg IAP 30 mmHg IAP 20 mmHg
  • 18. Splanchnic blood flow, critical conditions and therapies Takala J. BJA 1997; 77:50-58. Vasopressors and inotropes Variable effects depending on volemic status and underlying disease state Septic shock and vasopressors Dobutamine after cardiac surgery Ruokonen E, et al. CCM 1993; 21:1304-1311 Parviainen I, et al. BJA 1995; 74:277-282
  • 19. • All solutions restored the MAP and decreased the serum lactatemia • intestinal microcirculation effectively resuscitated only with hypertonic saline or synthetic colloids • Colloids: the greatest formation of renal ROS in vivo after reperfusion SHAM Control 0,9% NaCl Hypertonic saline Gelatine HES Fluids and splanchnic microcirculation Wu CY, et al. Effects of different types of fluid resuscitation for hemorrhagic shock on splanchnic organ microcirculation and renal reactive oxygen species formation. Crit Care. 2015; 19:434 male Wistar rats, haemorrhage 30 ml/kg
  • 20. • Anesthetised sheeps • Endotoxin vs sham 24 hrs • Fluid resuscitated endotoxin sham Macrocirculation Norepinephrine Microcirculatory blood flow Laser Doppler probes to monitoring microcirculatory blood flow in the muscularis layer (MCQmusc) and mucosa (MCQmuc) of the ileum. endotoxin sham How to optimise – macro- vs microcirculation Andersson A, et al. Gut microcirculatory and mitochondrial effects of hyperdynamic endotoxaemic shock and norepinephrine treatment.Br J Anaesth. 2012;108(2):254-61. Loss of coherence between macro- and microcirculation in several experimental and clinical studies Endotoxin: • Drop in MAP • Increased splanhnic blood flow • decreased microcirculatory blood flow
  • 21. How to assess How to optimise Macrocirculation in splanchnic region - Hepatic vein catheterisation and Fick principle - ICG disappearance rate - Cardiac output - Arterial pressure - Intra-abdominal pressure - Abdominal perfusion pressure - Lactate - Other biomarkers - Clinical signs (diarrhoae, feeding intolerance, bleeding) - Global haemodynamic management with individualised targets - Vasopressors and inotropes (pro-s and cons) - Avoid fluid overload - Management of IAH - Effect of feeding Microcirculation in splanchnic region - Remains experimental - Videomicroscopy (sublingual, stomas) - Gastric tonometry - CO2 a-v difference - Limited evidence - Poorly correlates with macrohemodynamics - Different type of fluids - Vasopressors - Inotropes - Nitrates? Summary
  • 22. Take home message Splanchnic blood flow • Takes up to one third of cardiac output in normal physiology • Is increased postprandially, and in septic shock Splanhnic microcirculation • Indirect assessment via clinical signs and biomarkers • Role for sublingual videomicroscopy in the future? Optimisation of splanhnic blood flow • Fluid management • Intra-abdominal pressure and abdominal perfusion pressure • Vasopressors and inotropes • Hypovolemia and hypotension vs venous congestion • Little coherence between macro- and microcirculation

Editor's Notes

  1. IAH has been shown to reduce hepatic perfusion [82]. ICG-PDR correlates well with global hepato-splanchnic blood flow [83] and has been demonstrated to be an early indicator of hepatocellular injury [84]. In critically ill patients, ICG-PDR appears to reflect changes in hepatic perfusion associated with IAH [85, 86] and correlates well with IAP and APP [67].
  2. IAH has been shown to reduce hepatic perfusion [82]. ICG-PDR correlates well with global hepato-splanchnic blood flow [83] and has been demonstrated to be an early indicator of hepatocellular injury [84]. In critically ill patients, ICG-PDR appears to reflect changes in hepatic perfusion associated with IAH [85, 86] and correlates well with IAP and APP [67].
  3. splanchnic perfusion. This technique requires a gastric catheter to measure the concentration of carbon dioxide within the stomach and arterial measurements of carbon dioxide and bicarbonate. Using the Henderson–Hasselbalch equation the gastric intramucosal pH (pHi) can be calculated. Alternatively the concentration difference between gastric and arterial carbon dioxide concentration (PgCO2) can be calculated. Both pHi and PgCO2 are prognostic indicators in the critically ill. Although not directly part of the splanchnic circulation assessments of the sublingual circulation have now been developed. This utilizes its greater accessibility within the gastrointestinal tract. The use of sublingual capnometry allows sublingual CO2 to be measured (PslCO2) which has been correlated with lactate concentrations and outcomes. 18 At present, this remains an area of interest for the future without any clear evidence to support its widespread use. Laser Doppler flowmetery utilizes the frequency shift (Doppler principle) in a laser beam to measure flow. This has been used in trials to establish colonic blood flow, as have ultrasound-based Doppler measurements
  4. Further developments are needed prior to its integration into routine clinical practice
  5. Changes in superior mesenteric artery blood flow after oral, enteral, and parenteral feeding in humans.