Mervyn Singer Bloomsbury Institute of Intensive Care Medicine,

Mervyn Singer Bloomsbury Institute of Intensive Care Medicine, University College London, UK Monitoring the adequacy of organ perfusion & function in shock

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
hypoxic hypoxia (low PO 2 )
circulatory hypoxia (low CO)
anaemic hypoxia (low Hb)
cytotoxic dysoxia (mitochondrial dysfunction)
VO 2 DO 2 O 2

‘ Perfusion’ vs ‘Adequacy of perfusion’
Perfusion = oxygen delivery
flow (macro- & microcirculation)
Hb
SO 2 (local PO 2 )
Adequacy of perfusion = perfusion enough to supply tissues adequately

Perfusion/Adequacy of perfusion
biochemical
lactate
base deficit
vascular and tissue respiratory gases
CO 2 - tissue tension
O 2 - venous, tissue, microvascular
- tissue tension, saturation, VO 2
microcirculation
mitochondrial redox status

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-stim’d aerobic glycolysis
high [lactate] & [epinephrine] can persist for … weeks in burn-injured patients

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

Arterial base deficit = amount of base (mmol) required to titrate 1 litre of whole blood to a normal pH, assuming normal physiological values of PaO 2 , PaCO 2 and temperature.

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’

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)

Tissue PCO 2
gut tonometry
sublingual capnometry

local metabolic acidosis (acid buffered by tissue HCO 3 - ) Tissue PCO 2 - traditional view H + HCO 3 - pCO 2 local respiratory acidosis (stagnant flow) pCO 2

Gutierrez G. Blood flow, not hypoxia, determines intramucosal PCO 2 . Crit Care 2005; 9:149-50

Henderson-Hasselbalch equation Tissue pCO 2 Tissue-arterial pCO 2 gap Tissue-end-tidal pCO 2 gap pHi = 6.1 + log HCO 3 - (0.03 x PCO 2 )

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 PCO 2
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??

Oxygen
mixed/central venous O 2 saturation
tissue oxygen tension & saturation
oxygen consumption

Mixed/central venous O 2 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 ScvO 2 -targetted study (Rivers)

SUMMARY: mixed/central SvO 2
PA catheter use decline .. ∆ reliance on ScvO 2
Rivers’ study needs repeating - recently funded
Useful in global low output states
Limited in established sepsis
(other than identification of low values)

Tissue O 2 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)

Boekstegers et al, Shock 1994;1:246-53 Muscle tissue pO 2 in septic patients control cardiogenic shock limited infection sepsis Tissue pO 2 (mmHg) 0 20 40 60

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 Haemorrhage Resuscitation Hypoxaemia 21% O 2 15% O 2 10% O 2 6% O 2 Bladder tissue pO 2 falls in other shock states time (h) Bladder epithelial PO 2 (kPa) Endotoxin Control 0 4 8 12 16 0 1 2 3

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…
Tissue O 2 tension

Acute response in tissue PO 2 to bolus of LPS (10 mg/kg) 20 30 40 50 60 70 80 20 30 40 50 60 70 80 0 10 20 30 40 0 1 2 3 0 10 20 30 40 0 1 2 3 Time post-LPS (h) Time post-LPS (h) Muscle Bladder Kidney Liver PO 2 (mmHg) PO 2 (mmHg) † † † † † † †

Can be relatively non-invasive
NIRS, spectrophotometry techniques … measures oxyHb (?Mb) in tissue/microvascul
porphyrin phosphorescence technique … measures microvascular PO 2
skeletal muscle StO 2 parallels changes in human … whole body DO 2 during trauma resuscitation
Microvascular O 2 tension/saturation

SUMMARY: tissue/microvascular O 2
tissue PO 2 (SO 2 ) = 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 PO 2 - may provide similar info but … comparative studies needed
no outcome-related PO 2 -guided studies
research tool at present until better defined in pts

Low VO 2 or poor response in VO 2 to challenge
(fluid/dobutamine) = poor prognosis
Whole body ≠ regional VO 2
How much VO 2 is coupled or uncoupled to ATP … production in shock states?
Whole body/regional O 2 consumption

Crit Care Med 2000; 28: 2837-42

mainly measured sublingually
relevance of tongue to other organ beds?
… but does correlate with gastric & s/l PCO 2
prognosticator of outcome in sepsis
Microcirculation

relevance to local tissue O 2 ??
? reactive to decreased mitochondrial utilisation c/f hyperoxia
+tive correlation between capillary O 2 extraction & degree of regional capillary stopped-flow - i.e. remaining functionally normal capillaries offload more O 2 to surrounding tissue
minimal cell death seen in sepsis
need for automated semi-quantification technique
no outcome-related microcirc’n-guided studies
Microcirculation

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

>90% of VO 2 used by mitochondria
>90% 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
Mitochondrial function

NADH fluoroscopy & NIRS NADH NAD+ oxidised reduced

Rhee P et al. Near-infrared spectroscopy: Continuous measurement of cytochrome oxidation during hemorrhagic shock. Crit Care Med 1997; 25:166-170 liver kidney muscle stomach Cyt aa 3 (%change from baseline) CO DO 2 VO 2

cannot yet be quantified in vivo
good for trend-following …
… ideally from normal baseline
limited use in patient who’s already critically ill
Mitochondrial redox state

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

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

Mervyn Singer Bloomsbury Institute of Intensive Care Medicine,

by changezkn

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