Monitoring the adequacy of
organ perfusion & function in shock
Mervyn Singer
Bloomsbury Institute of Intensive Care Medicine,
University College London, UK
Declarations of potential conflicts ..
(Deltex)
(Edwards)
Oxford Optronix - free probes
Shock
Delivery to, or utilisation of,
oxygen that is inadequate to
meet the cells’ metabolic needs
Shock - a physiological definition
o hypoxic hypoxia (low PO2)
DO2
o circulatory hypoxia (low CO)
o anaemic hypoxia (low Hb)
o cytotoxic dysoxia (mitochondrial dysfunction)
VO2
‘Perfusion’ vs ‘Adequacy of perfusion’
Perfusion = oxygen delivery
• flow (macro- & microcirculation)
• Hb
• SO2 (local PO2)
Adequacy of perfusion =
perfusion enough to supply tissues
adequately
Perfusion/Adequacy of perfusion
o biochemical
o lactate
o base deficit
o vascular and tissue respiratory gases
o CO2 - tissue tension
o O2
- venous, tissue, microvascular
- tissue tension, saturation, VO2
o microcirculation
o mitochondrial redox status
Lactate
o [lactate] predictive of poor outcome in
…sepsis, trauma, haemorrhage
o very non-specific marker of tissue hypoxia
o more due to metabolic effects of epinephrine
…than reduced tissue perfusion
o related to ∆ muscle Na+/K+-ATPase activity
…driven by epinephrine-stim’d aerobic glycolysis
o high [lactate] & [epinephrine] can persist for
…weeks in burn-injured patients
Hyperlactataemia
o .. blocked by ouabain or ß-blocker
o iatrogenic causes
o lactate-buffered haemofiltration
o epinephrine
o drugs e.g. NRTIs
o non-shock causes
o severe liver dysfunction
o ∆ muscle protein degradation
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.
Arterial base deficit
o ∆ H+ ion production in shock related to
…
..∆ hydrolysis of ATP
o arterial base deficit predictive of poor outcome
… in sepsis, trauma, haemorrhage
o many non-hypoxic causes of metabolic acidosis
o renal dysfunction
o liver dysfunction
o drug toxicity (e.g. cocaine)
o bicarbonate loss (e.g. diarrhoea)
o hyperchloraemia …
n.b. starting value of base excess may ‘camouflage’
SUMMARY: base deficit/lactate
o good early prognosticators in shock states
o good early guide to therapeutic response
o good sensitivity
o poor specificity to shock & assessment of perfusion
- many confounders (patient/iatrogenic)
Tissue PCO2
o gut tonometry
o sublingual capnometry
Tissue PCO2 - traditional view
local metabolic acidosis
(acid buffered by tissue HCO3-)
+
H
pCO2
HCO3-
local respiratory acidosis
pCO2 (stagnant flow)
Gutierrez G.
Blood flow, not hypoxia, determines intramucosal PCO2.
Crit Care 2005; 9:149-50
Henderson-Hasselbalch equation
HCO3pHi = 6.1 + log
(0.03 x PCO2)
Tissue pCO2
Tissue-arterial pCO2 gap
Tissue-end-tidal pCO2 gap
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)
Gastric pHi-guided therapy??
pHi-guided Rx improved outcome in ICU subset
•
Gutierrez (Lancet ‘92)
… or doesn’t
•
Gomersall (Crit Care Med 2000)
SUMMARY: tissue PCO2
o methodological/practical issues to be resolved
o marker of poor regional perfusion
o relevance to other regional circulations??
o reasonable prognostic tool
(as good/better than lactate/base deficit)
o ability to direct therapy & improve outcome???
o much hype in the 1990s .. why so quiet now??
Oxygen
o mixed/central venous O2 saturation
o tissue oxygen tension & saturation
o oxygen consumption
Mixed/central venous O2 saturation
o marker of global supply/demand balance
o falls in low output states e.g. heart failure
o prognosticator of outcome, failure to wean…
o elevated in resuscitated sepsis
o microvascular shunting??
o decreased cellular utilisation??
o mixed venous vs central venous differences
o one landmark ScvO2-targetted study (Rivers)
SUMMARY: mixed/central SvO2
o PA catheter use decline .. ∆ reliance on ScvO2
o Rivers’ study needs repeating - recently funded
o Useful in global low output states
o Limited in established sepsis
(other than identification of low values)
Tissue O2 tension
o marker of local supply/demand balance
o measurable with various technologies
o optode, Clark electrode, NIRS, EPR oximetry ..
o falls in low output states e.g. heart failure
o elevated in resuscitated sepsis
o studied separately in multiple tissue beds
o gut mucosa, skeletal muscle, bladder, brain, kidney (animal)
o brain, skeletal muscle, conjuctiva, subcutaneously (man)
Muscle tissue pO2 in septic patients
sepsis
limited infection
cardiogenic shock
control
0
60
20
40
Tissue pO2 (mmHg)
Boekstegers et al, Shock 1994;1:246-53
Bladder tissue pO2 falls in other shock states
16
Resuscitation
12
Endotoxin
8
Control
4
Haemorrhage
0
0
1
2
time (h)
3
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
Tissue O2 tension
o no organ-organ comparisons published
o influence of inspired oxygen in shock states?
o impact of volume of tissue being sampled
o probe size/surface area
o multi-array electrodes…
PO2 (mmHg)
Acute response in tissue PO2 to bolus of LPS (10 mg/kg)
80
80
70
70
60
60
50
50
40
40
Muscle
PO2 (mmHg)
30
Bladder
30
20
20
40
40
Kidney
Liver
30
30
20
20
†
†
†
†
†
†
10
10
†
0
0
0
1
2
3
Time post-LPS (h)
0
1
2
3
Time post-LPS (h)
Microvascular O2 tension/saturation
o Can be relatively non-invasive
o NIRS, spectrophotometry techniques
… measures oxyHb (?Mb) in tissue/microvascul
o porphyrin phosphorescence technique
… measures microvascular PO2
o skeletal muscle StO2 parallels changes in human
…whole body DO2 during trauma resuscitation
SUMMARY: tissue/microvascular O2
o tissue PO2 (SO2) = useful marker of local supplydemand balance in non-septic shock or in early
…unresuscitated sepsis
o raised in resuscitated sepsis
- marker of mitochondrial dysfunction
o microvascular PO2 - may provide similar info but
…comparative studies needed
o no outcome-related PO2-guided studies
o research tool at present until better defined in pts
Whole body/regional O2 consumption
o Low VO2 or poor response in VO2 to challenge
(fluid/dobutamine) = poor prognosis
o Whole body ≠ regional VO2
o How much VO2 is coupled or uncoupled to ATP
…production in shock states?
Crit Care Med 2000; 28: 2837-42
Microcirculation
o mainly measured sublingually
o relevance of tongue to other organ beds?
… but does correlate with gastric & s/l PCO2
o prognosticator of outcome in sepsis
Microcirculation
o relevance to local tissue O2??
o ? reactive to decreased mitochondrial utilisation c/f hyperoxia
o +tive correlation between capillary O2 extraction & degree of
regional capillary stopped-flow - i.e. remaining functionally
normal capillaries offload more O2 to surrounding tissue
o minimal cell death seen in sepsis
o need for automated semi-quantification technique
o no outcome-related microcirc’n-guided studies
SUMMARY: microcirculation
o interesting research tool for assessing perfusion
o applicability of tongue to other tissue beds?
o pathophysiological questions - causative or 2°??
o relative infancy - not a routine clinical tool yet
Mitochondrial function
o >90% of VO2 used by mitochondria
o >90% of ATP in most cells generated by ETC
o ..thus mitos play a fundamental role in shock
o degree of dysfunction in established septic shock
relates to poor outcome
o ATP not yet measurable at bedside
o redox status can be used for trend-following
NADH fluoroscopy & NIRS
oxidised
reduced
NADH
NAD+
Rhee P et al. Near-infrared spectroscopy: Continuous measurement of
cytochrome oxidation during hemorrhagic shock.
Crit Care Med 1997; 25:166-170
Cyt aa3 (%change from baseline)
CO
stomach
liver
DO2
kidney
VO2
muscle
Mitochondrial redox state
o cannot yet be quantified in vivo
o good for trend-following …
… ideally from normal baseline
o limited use in patient who’s already critically ill
SUMMARY: mitochondrion
o .. the ideal organelle to monitor the adequacy of
organ perfusion
o .. but, at present, no bedside mitochondrial monitor
that offers more than trend following
SUMMARY: overall
o shock is not an homogenous condition
o we still lack the perfect bedside tool to assess
adequacy of organ perfusion
o will there ever be one?
o is measuring site representative of other organ beds?
o should we use an amalgam of technologies?
o tool-directed outcome studies are needed