Kriess NEJM

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Monitoring the adequacy of organ perfusion
function in shock
Mervyn Singer Bloomsbury Institute of Intensive
Care Medicine, University College London, UK
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Declarations of potential conflicts ..
(Deltex) (Edwards) Oxford Optronix - free probes
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Shock
Delivery to, or utilisation of, oxygen that is
inadequate to meet the cells metabolic needs
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Shock - a physiological definition

• hypoxic hypoxia (low PO2)
• circulatory hypoxia (low CO)
• anaemic hypoxia (low Hb)
• cytotoxic dysoxia (mitochondrial dysfunction)

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Perfusion vs Adequacy of perfusion

• Perfusion oxygen delivery
• flow (macro- microcirculation)
• Hb
• SO2 (local PO2)

Adequacy of perfusion perfusion enough to
supply tissues adequately
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Perfusion/Adequacy of perfusion

• biochemical
• lactate
• base deficit
• vascular and tissue respiratory gases
• CO2 - tissue tension
• O2 - venous, tissue, microvascular
• - tissue tension, saturation, VO2
• microcirculation
• mitochondrial redox status

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Lactate

• lactate predictive of poor outcome in
  sepsis, trauma, haemorrhage
• very non-specific marker of tissue hypoxia
• more due to metabolic effects of epinephrine
  than reduced tissue perfusion
• related to ? muscle Na/K-ATPase activity
  driven by epinephrine-stimd aerobic glycolysis
• high lactate epinephrine can persist for
  weeks in burn-injured patients

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Hyperlactataemia

• .. blocked by ouabain or ß-blocker
• iatrogenic causes
• lactate-buffered haemofiltration
• epinephrine
• drugs e.g. NRTIs
• non-shock causes
• severe liver dysfunction
• ? muscle protein degradation

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Arterial base deficit
amount of base (mmol) required to titrate 1
litre of whole blood to a normal pH, assuming
normal physiological values of PaO2, PaCO2 and
temperature.
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Arterial base deficit

• ? H ion production in shock related to
  ..? hydrolysis of ATP
• arterial base deficit predictive of poor
  outcome in sepsis, trauma, haemorrhage
• many non-hypoxic causes of metabolic acidosis
• renal dysfunction
• liver dysfunction
• drug toxicity (e.g. cocaine)
• bicarbonate loss (e.g. diarrhoea)
• hyperchloraemia
• n.b. starting value of base excess may
  camouflage

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SUMMARY base deficit/lactate

• good early prognosticators in shock states
• good early guide to therapeutic response
• good sensitivity
• poor specificity to shock assessment of
  perfusion
• - many confounders (patient/iatrogenic)

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Tissue PCO2

• gut tonometry
• sublingual capnometry

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Tissue PCO2 - traditional view
local metabolic acidosis (acid buffered by tissue
HCO3-)
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Gutierrez G. Blood flow, not hypoxia, determines
intramucosal PCO2. Crit Care 2005 9149-50
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Henderson-Hasselbalch equation
Tissue pCO2 Tissue-arterial pCO2
gap Tissue-end-tidal pCO2 gap
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Gastric pHi - prognosticator

• Low pHi related to poor outcome
• Doglio (CCM 91)
• Maynard (JAMA 93)
• Mythen (ICM 94)
• Low pHi related to inability to wean
• Mohsenifar (Ann Intern Med 93)

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Gastric pHi-guided therapy??

• pHi-guided Rx improved outcome in ICU subset
• Gutierrez (Lancet 92)
• or doesnt
• Gomersall (Crit Care Med 2000)

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SUMMARY tissue PCO2

• methodological/practical issues to be resolved
• marker of poor regional perfusion
• relevance to other regional circulations??
• reasonable prognostic tool
• (as good/better than lactate/base deficit)
• ability to direct therapy improve outcome???
• much hype in the 1990s .. why so quiet now??

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Oxygen

• mixed/central venous O2 saturation
• tissue oxygen tension saturation
• oxygen consumption

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Mixed/central venous O2 saturation

• marker of global supply/demand balance
• falls in low output states e.g. heart failure
• prognosticator of outcome, failure to wean
• elevated in resuscitated sepsis
• microvascular shunting??
• decreased cellular utilisation??
• mixed venous vs central venous differences
• one landmark ScvO2-targetted study (Rivers)

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SUMMARY mixed/central SvO2

• PA catheter use decline .. ? reliance on ScvO2
• Rivers study needs repeating - recently funded
• Useful in global low output states
• Limited in established sepsis
• (other than identification of low values)

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Tissue O2 tension

• marker of local supply/demand balance
• measurable with various technologies
• optode, Clark electrode, NIRS, EPR oximetry ..
• falls in low output states e.g. heart failure
• elevated in resuscitated sepsis
• studied separately in multiple tissue beds
• gut mucosa, skeletal muscle, bladder, brain,
  kidney (animal)
• brain, skeletal muscle, conjuctiva,
  subcutaneously (man)

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Muscle tissue pO2 in septic patients

sepsis
limited infection
cardiogenic shock
control
Tissue pO2 (mmHg)
Boekstegers et al, Shock 19941246-53
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Bladder tissue pO2 falls in other shock states
Bladder epithelial PO2 (kPa)



Resuscitation
Hypoxaemia
21 O2
Endotoxin
Control
15 O2
10 O2
Haemorrhage
6 O2
time (h)
Rosser et al. J Appl Physiol 1995 79
1878 Singer et al. Intensive Care Med 1996 22
324 Stidwill et al. Intensive Care Med 1998 24
1209
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Tissue O2 tension

• no organ-organ comparisons published
• influence of inspired oxygen in shock states?
• impact of volume of tissue being sampled
• probe size/surface area
• multi-array electrodes

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Acute response in tissue PO2 to bolus of LPS (10
mg/kg)


80
80
70
70
60
60
PO2 (mmHg)
50
50
40
40
Muscle
Bladder
30
30
20
20
40
40
Kidney
Liver
30
30



PO2 (mmHg)
20
20

10
10

0
0
0
1
2
3
0
1
2
3
Time post-LPS (h)
Time post-LPS (h)
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Microvascular O2 tension/saturation

• Can be relatively non-invasive
• NIRS, spectrophotometry techniques
  measures oxyHb (?Mb) in tissue/microvascul
• porphyrin phosphorescence technique
  measures microvascular PO2
• skeletal muscle StO2 parallels changes in human
  whole body DO2 during trauma resuscitation

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SUMMARY tissue/microvascular O2

• tissue PO2 (SO2) useful marker of local
  supply-
• demand balance in non-septic shock or in early
  unresuscitated sepsis
• raised in resuscitated sepsis
• - marker of mitochondrial dysfunction
• microvascular PO2 - may provide similar info but
  comparative studies needed
• no outcome-related PO2-guided studies
• research tool at present until better defined in
  pts

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Whole body/regional O2 consumption

• Low VO2 or poor response in VO2 to challenge
• (fluid/dobutamine) poor prognosis
• Whole body ? regional VO2
• How much VO2 is coupled or uncoupled to ATP
  production in shock states?

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Crit Care Med 2000 28 2837-42
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Microcirculation

• mainly measured sublingually
• relevance of tongue to other organ beds?
• but does correlate with gastric s/l PCO2
• prognosticator of outcome in sepsis

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Microcirculation

• relevance to local tissue O2??
• ? reactive to decreased mitochondrial
  utilisation c/f hyperoxia
• tive correlation between capillary O2
  extraction degree of regional capillary
  stopped-flow - i.e. remaining functionally
  normal capillaries offload more O2 to surrounding
  tissue
• minimal cell death seen in sepsis
• need for automated semi-quantification technique
• no outcome-related microcircn-guided studies

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SUMMARY microcirculation

• interesting research tool for assessing
  perfusion
• applicability of tongue to other tissue beds?
• pathophysiological questions - causative or 2??
• relative infancy - not a routine clinical tool
  yet

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Mitochondrial function

• gt90 of VO2 used by mitochondria
• gt90 of ATP in most cells generated by ETC
• ..thus mitos play a fundamental role in shock
• degree of dysfunction in established septic
  shock
• relates to poor outcome
• ATP not yet measurable at bedside
• redox status can be used for trend-following

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NADH fluoroscopy NIRS
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Rhee P et al. Near-infrared spectroscopy
Continuous measurement of cytochrome oxidation
during hemorrhagic shock. Crit Care Med 1997
25166-170
Cyt aa3 (change from baseline)
stomach
CO
liver
DO2
kidney
VO2
muscle
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Mitochondrial redox state

• cannot yet be quantified in vivo
• good for trend-following
• ideally from normal baseline
• limited use in patient whos already critically
  ill

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SUMMARY mitochondrion

• .. the ideal organelle to monitor the adequacy
  of
• organ perfusion
• .. but, at present, no bedside mitochondrial
  monitor
• that offers more than trend following

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SUMMARY overall

• shock is not an homogenous condition
• we still lack the perfect bedside tool to assess
• adequacy of organ perfusion
• will there ever be one?
• is measuring site representative of other organ
  beds?
• should we use an amalgam of technologies?
• tool-directed outcome studies are needed

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