mervyn singer bloomsbury institute of intensive care medicine,
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Mervyn SingerBloomsbury Institute of Intensive Care Medicine,University College London, UK
Monitoring the adequacy of organ perfusion & function in shock
Monitoring the adequacy of organ perfusion & function in shock
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Declarations of potential conflicts ..Declarations of potential conflicts ..
(Deltex)(Edwards)Oxford Optronix - free probes
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ShockShock
Delivery to, or utilisation of, oxygen that is inadequate to meet the cells’ metabolic needs
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Shock - a physiological definitionShock - a physiological definition
o hypoxic hypoxia (low PO2)
o circulatory hypoxia (low CO)
o anaemic hypoxia (low Hb)
o cytotoxic dysoxia (mitochondrial
dysfunction) VO2VO2
DO2DO2O2O2
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‘Perfusion’ vs ‘Adequacy of perfusion’‘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 perfusionPerfusion/Adequacy of perfusion
o biochemicalo lactateo base deficit
o vascular and tissue respiratory gaseso CO2 - tissue tensiono O2 - venous, tissue, microvascular - tissue tension, saturation, VO2
o microcirculationo mitochondrial redox status
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LactateLactate
o [lactate] predictive of poor outcome in …sepsis, trauma, haemorrhageo 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 glycolysiso high [lactate] & [epinephrine] can persist for …weeks in burn-injured patients
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HyperlactataemiaHyperlactataemia
o .. blocked by ouabain or ß-blockero iatrogenic causes
o lactate-buffered haemofiltrationo epinephrineo drugs e.g. NRTIs
o non-shock causeso severe liver dysfunctiono ∆ muscle protein degradation
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Arterial base deficitArterial 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 deficitArterial base deficit
o ∆ H+ ion production in shock related to … ..∆ hydrolysis of ATPo arterial base deficit predictive of poor outcome … in sepsis, trauma, haemorrhageo many non-hypoxic causes of metabolic acidosis
o renal dysfunctiono 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’
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SUMMARY: base deficit/lactateSUMMARY: 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)
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Tissue PCO2Tissue PCO2
o gut tonometry
o sublingual capnometry
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H+
local metabolic acidosis(acid buffered by tissue HCO3
-)
HCO3-
pCO2
local respiratory acidosis (stagnant flow)pCO2
Tissue PCO2 - traditional viewTissue PCO2 - traditional view
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Gutierrez G. Blood flow, not hypoxia, determines intramucosal PCO2. Crit Care 2005; 9:149-50
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pHi = 6.1 + log HCO3-
(0.03 x PCO2)
Henderson-Hasselbalch equationHenderson-Hasselbalch equation
Tissue pCO2 Tissue-arterial pCO2 gapTissue-end-tidal pCO2 gap
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Gastric pHi - prognosticatorGastric 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??Gastric pHi-guided therapy??
pHi-guided Rx improved outcome in ICU
subset• Gutierrez (Lancet ‘92)
… or doesn’t• Gomersall (Crit Care Med 2000)
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SUMMARY: tissue PCO2SUMMARY: tissue PCO2
o methodological/practical issues to be resolvedo marker of poor regional perfusiono 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??
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OxygenOxygen
o mixed/central venous O2 saturation
o tissue oxygen tension & saturation
o oxygen consumption
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Mixed/central venous O2 saturationMixed/central venous O2 saturation
o marker of global supply/demand balanceo falls in low output states e.g. heart failureo prognosticator of outcome, failure to wean…o elevated in resuscitated sepsis
o microvascular shunting??o decreased cellular utilisation??
o mixed venous vs central venous differenceso one landmark ScvO2-targetted study
(Rivers)
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SUMMARY: mixed/central SvO2SUMMARY: mixed/central SvO2
o PA catheter use decline .. ∆ reliance on ScvO2
o Rivers’ study needs repeating - recently fundedo Useful in global low output stateso Limited in established sepsis (other than identification of low values)
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Tissue O2 tensionTissue O2 tension
o marker of local supply/demand balanceo measurable with various technologies
o optode, Clark electrode, NIRS, EPR oximetry ..
o falls in low output states e.g. heart failureo elevated in resuscitated sepsiso studied separately in multiple tissue beds
o gut mucosa, skeletal muscle, bladder, brain, kidney (animal)o brain, skeletal muscle, conjuctiva, subcutaneously (man)
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Boekstegers et al, Shock 1994;1:246-53
Muscle tissue pO2 in septic patientsMuscle tissue pO2 in septic patients
controlcontrol
cardiogenic shockcardiogenic shock
limited infectionlimited infection
sepsissepsis
00 2020 4040 6060
Tissue pO2 (mmHg)Tissue pO2 (mmHg)
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Rosser et al. J Appl Physiol 1995; 79: 1878Singer et al. Intensive Care Med 1996; 22: 324Stidwill et al. Intensive Care Med 1998; 24: 1209
Rosser et al. J Appl Physiol 1995; 79: 1878Singer et al. Intensive Care Med 1996; 22: 324Stidwill et al. Intensive Care Med 1998; 24: 1209
HaemorrhageHaemorrhage
ResuscitationResuscitation HypoxaemiaHypoxaemia21% O221% O2
15% O215% O2 10% O210% O2
6% O26% O2
Bladder tissue pO2 falls in other shock statesBladder tissue pO2 falls in other shock states
00
44
88
1212
1616
00 11 22 33time (h)time (h)
Bladder epithelial PO2 (kPa)Bladder epithelial PO2 (kPa)
Endotoxin
Control
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o no organ-organ comparisons publishedo influence of inspired oxygen in shock states?o impact of volume of tissue being sampled
o probe size/surface area
o multi-array electrodes…
Tissue O2 tensionTissue O2 tension
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Acute response in tissue PO2 to bolus of LPS (10 mg/kg)Acute response in tissue PO2 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 30
10
20
30
40
0 1 2 3
Time post-LPS (h)Time post-LPS (h)
Muscle Bladder
KidneyLiver
PO
2 (
mm
Hg)
PO
2 (
mm
Hg)
†
†
†
† †
†
†
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o Can be relatively non-invasiveo NIRS, spectrophotometry techniques … measures oxyHb (?Mb) in tissue/microvasculo porphyrin phosphorescence technique
… measures microvascular PO2
o skeletal muscle StO2 parallels changes in
human …whole body DO2 during trauma
resuscitation
Microvascular O2 tension/saturationMicrovascular O2 tension/saturation
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SUMMARY: tissue/microvascular O2SUMMARY: tissue/microvascular O2
o tissue PO2 (SO2) = useful marker of local
supply- demand balance in non-septic shock or in early …unresuscitated sepsiso raised in resuscitated sepsis - marker of mitochondrial dysfunction o microvascular PO2 - may provide similar info
but …comparative studies neededo no outcome-related PO2-guided studieso research tool at present until better defined in pts
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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?
Whole body/regional O2 consumptionWhole body/regional O2 consumption
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Crit Care Med 2000; 28: 2837-42
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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
MicrocirculationMicrocirculation
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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
MicrocirculationMicrocirculation
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SUMMARY: microcirculationSUMMARY: 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
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o >90% of VO2 used by mitochondria
o >90% of ATP in most cells generated by ETCo ..thus mitos play a fundamental role in shocko degree of dysfunction in established septic shock relates to poor outcomeo ATP not yet measurable at bedsideo redox status can be used for trend-following
Mitochondrial functionMitochondrial function
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NADH fluoroscopy & NIRSNADH fluoroscopy & NIRS
NADH NAD+
oxidisedreduced
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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 aa3 (%change from baseline)
CO
DO2
VO2
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o cannot yet be quantified in vivoo good for trend-following … … ideally from normal baseline o limited use in patient who’s already critically ill
Mitochondrial redox stateMitochondrial redox state
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SUMMARY: mitochondrionSUMMARY: mitochondrion
o .. the ideal organelle to monitor the adequacy of organ perfusiono .. but, at present, no bedside mitochondrial monitor that offers more than trend following
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SUMMARY: overallSUMMARY: 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
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