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GOAL DIRECTED FLUID THERAPY
E THANIGAI ARASU
Introduction
• Intravenous fluid therapy - core part of
perioperative practice - potential to influence
patient outcomes.
• One of the most frequently discussed issues of
peri-opearative medicine.
• UK confidential Enquiry into peri-operative death
reveals
Errors in the fluid management (usually
In Excess): Most common cause of peri-operative
morbidity & mortality.
2LOBO DN. Best Pract Clin Anaesth 2006;20(3):439
Why do we give so much fluid??
 Pre op fasting
 Surgical blood loss many litres of
 Evaporation fluid during a
 Vasodilatation caused by anaesthesia a standard
 Transfer to third space
 Transcapillary leak of albumin caused by operation
inflammatory mediators
 Urinary excretion
Hahn RG. Anesth Analg 2007;105:304.
"Standard" management grossly
overestimates IV fluid requirements
Maintanace: 4:2:1 rule
Deficit: Maintanace Hr fasting
3rd space loss: 5-7ml/Kg
Blood loss: 3:1 replacement with crystalloid
Goal directed fluid therapy
Goal directed fluid therapy
• So another concept has been raised is RFT.
• Also referred as zero balance approach.
• No clear definition of RFT in the medical
literature.
• Generally the approach - smaller peri-
operative fluid infusion volumes than the
'traditional' approach.
Goal directed fluid therapy
Goal directed fluid therapy
Goal directed fluid therapy
Goal directed fluid therapy
Goal directed fluid therapy
‘Efforts in the past to restrict fluids - oliguria, anuria and
occasionally acute renal shutdown. Many (if not most)
instances of postsurgical shock were unquestionably
related to this same practice of forced hypovolaemia.
though some RCT address this issue (Brandstrup
2012; Phan 2014; Srinivasa 2013; Zhang 2012);
however, no systematic review has so far evaluated this
new evidence.
Restrictive versus liberal fluid therapy in major abdominal surgery
(RELIEF): rationale and design for a multicentre randomised trial
Myles P, Bellomo R, Corcoran T on behalf of the Australian and New Zealand College of Anaesthetists Clinical Trials
Network, and the Australian and New Zealand Intensive Care Society Clinical Trials Group, et al
Restrictive versus liberal fluid therapy in major abdominal surgery (RELIEF): rationale and design for a multicentre
randomised trial
BMJ Open 2017;7:e015358. doi:10.1136/bmjopen-2016-015358
Perioperative restrictive versus GDFT for adults
undergoing major non cardiac surgery
Primary outcome:
1. Major complications during longest
follow up period.
2. All cause mortality during longest
follow up period.
Wrzosek A et al. cochrane Database of systematic Reviews 2017, issue 8 Art. No.: CD012767
RIFTS trial
No Intervention: Usual
Care Participants will
receive an initial 30
ml/kg bolus and then IV
fluids as needed and
without limit as well as
IV vasopressors to
maintain a MAP>65,
determined by the
primary care team for
the duration of the
study.
Restrictive Care:
Participants will be
LIMITED to 60 ml/kg (up
to 6000 ml) of IV fluids
as initial resuscitation
followed by
administration of IV
vasopressors to maintain
a MAP>65 mm Hg for
the first 72 hours of care.
Discharge Mortality and Persistent Organ
Dysfunction (POD) a composite outcome
Goal directed fluid therapy
So the answer is GDFT
• GDT is a term used to describe the use of
cardiac output(CO) or similar parameters to
guide the IV fluids and inotropic therapy.
• It involves goal directed manipulation of
Tissue
oxygenation
preload
contractility
afterload
Ideal is Do2 index
Integration of arterial pressure and flow
• This is misleading
• Fundamentally MAP = CO * Resistance
• Local resistance are controlled in a organ specific
manner.
• Under normal circumstances it will be matching.
• However the flow regulatory capacity of different
organs in the face of changing BP are not equivalent &
varies among organs.
• The limits of pressure auto regulation are not specific
numbers but a range of distribution- that can vary
widely depending upon the physical status,
physiological stress, drugs.
• Furthermore at microcirculatory level, tissue perfusion
is also influenced by the outflow venous pressure.
• Therefore without considering total and regional
arterial resistance, organ specific autoregulation, and
the potential for tissue edema & venous congestion
assuming a good flow based on good pressure can be
misleading.
From: Perioperative goal-directed haemodynamic therapy based on flow parameters: a concept in evolution
Br J Anaesth. 2016;117(suppl_3):iii3-iii17. doi:10.1093/bja/aew363
Br J Anaesth | © The Author 2016. Published by Oxford University Press on behalf of the British Journal of Anaesthesia. All rights reserved.
For Permissions, please email: journals.permissions@oup.com
Invasive(PAC)
• Intermittent
• continuous
Minimally
invasive
• LidCO
• PCA(PiCCO &
Flo Trac)
• ED
• TEE
• PRAM
Non-invasive
• Partial gas
rebreathing
• ECOM
• Thoracic bio-
impedance &
bioractance
• Doppler
• Photo electric
plethysmography(
PEP)
• Non invasive PCA
Static parameters-Pulmonary Artery
Catheter
• Though it has been associated with various
complications it is still considered gold standard
monitor to measure CO since 1970s.
• Apart from CO it measures the central filling pressures
& Svo2.
• Literature review of PAC revealed both benefits and
risks.
• Gore et al,(CHEST 1987) – showed mortality after MI.
• SUPPORT trial(JAMA 1996)- mortality at 30 days
• PAC-MAN trial(Lancet 2005) –failed to show any
harm or benefit.
• Its use in OPCAB also showed no difference in
mortaity and final outcome.
• ESCAPE trial(JAMA 2005) – functional improvement
with PAC guided therapy in pts with CHF.
• However due to inherent risk associate with its use
investigators are moved to minimally or non invasive
monitors.
Contd,,
Static parameters
Goal directed fluid therapy
Goal directed fluid therapy
Fluid responsiveness
Regulation of
Venous return
Frank-starling
relationship
Incidence of
Non-responders
Venous return
• IV infusion- Increases VR. However, in that much of
the circulating blood volume resides in highly
distensible venous capacitance vessels
• There is not necessarily a linear relationship.
• In fact, at any point a portion of the venous
capacitance volume is “unstressed”.
• In contrast, the “stressed” venous volume does
create transmural pressure, and it is the gradient,
that drives venous return [Venous return = (mean
systemic filling pressure – right atrial
pressure)/venous resistance].
• This relationship is dynamic - factors affected by
respiration, autonomic tone, IAP, and body position.
Cherpanath TGGeerts BFLagrand WKSchultz MJGroeneveld AB. Basic concepts of fluid
responsiveness. Neth Heart J 2013; 21: 530–6
Frank-starling curve
Goal directed fluid therapy
Goal directed fluid therapy
• Many investigations of this matter in the presence of
a complete circulation have been either inadequate
or misleading largely because… stroke volume or
cardiac output and not stroke work has been used as
the measure of the "energy of contraction"… and
• perhaps most important, a single Starling curve
cannot always satisfactorily explain the observed
phenomena; for any given heart there is a series of
curves.“
Sarnoff SJBerglund E. Ventricular function. I. Starling's law of the heart studied by means of simultaneous
right and left ventricular function curves in the dog. Circulation 1954; 9: 706–18
Contd,
• They also challenged the notion that a descending
limb - could be achieved in normal hearts, and
emphasized- "juxta-cardiac" pressure when
interpreting pressure indices of preload (i.e.
transmural vs absolute pressure),
• a factor later emphasized by Braunwald in clinical
studies
Braunwald ERoss J.Jr. Applicability of starling's law of the heart to man. Circ Res 1964; 15 (Suppl
2):169–81
High incidence of Non-Responders
• Central blood volume augmentation done by either
endogenous(PLR) or exogenous(fluid bolus)
• And response measured by SV, CO, flow velocity.
• Somewhat surprisingly, studies across a range of
patient populations and monitoring methodologies
have consistently indicated that roughly half of the
subjects evaluated are non-responders.
Biais MVidil LSarrabay PCottenceau VRevel PSztark F. Changes in stroke volume induced by passive leg raising
in spontaneously breathing patients: comparison between echocardiography and Vigileo/FloTrac device. Crit
Care 2009; 13: R195
Contd,
• For PLR in particular, two meta-analyses incorporating ill
patients in whom SV and CO were measured by a range
of technologies -reported responder rates of 53 and 54%
• Overall, the physiological basis for non-responsiveness
remains unclear, and might vary among patients.
• Techniques measures SV- no direct verification that left
ventricular preload (end-diastolic volume) actually
increased significantly.
Monnet XMarik PTeboul JL. Passive leg raising for predicting fluid responsiveness: a systematic review and meta-
analysis. Intensive Care Med 2016; 42: 1935–47
Contd,
• Furthermore, both SV and EDV are affected by heart
rate (HR) and afterload.
• In this context, consideration of Sarnoff and
Berglund’s comments that, "a single Starling curve
cannot always satisfactorily explain the observed
phenomena", or that stroke work not SV is the more
appropriate dependent variable may be warranted. ‘
• Finally, a fixed cut-off for differentiating responders
from non-responders can contribute to a significant
"grey zone"
Is it number or we want scalar
variable???
• Cooke R et al, reviewed volume responsiveness-
focused on Pmsa.
• 11 studies – 572 pts – 52% responders analyzed.
• CO ↑by 12% & 22% following PLR & volume challenge
respectively.
• No statistical difference found between responders &
Non-responders in terms of CO/MAP/CVP
• In contrast the calculated mean systemic filling
pressure analougue ↓ in responders(P=0.007)
• Non responders also demonstrated deteriorating Heart
efficiency of -15% & CP of -7% .
• The results demonstrated Pmsa, heart efficiency,
cardiac power can identify response
and provides scalar results rather than merely
a dichotomous outcome of responder or non-
responder.
cooke R et al, volume responsiveness assessed by passive leg raising and a fluid challenge: a critical review
focused on mean systemic filling pressure. Anesth 2018;73:313-22.
Minimally invasive monitors
• LiDCO – combines PPA with lithium indicator dilution –
SV & SVV.
• Principle- change of BP about the mean ~ SV.
• Root mean square method applied to arterial signal –
Nominal SV & using calibration factor scaled to actual
SV.
• Requires calibration every 8th hr & major hemodynamic
changes.
• And affected by NMBD.(Electrode drift)
• Contraindication – Li therapy.
• Accuracy – IABP, Damped line, post aortic surgery,
arrhythmias, intra/extra cardiac shunts.
• Found good correlation with PAC.(Linton et al)
• Pearse et al studied it for GDT revealed fewer
complication & shorter LOH.
Pearse R et al, Early goal directed therapy after major surgery reduces complications and
duration of hospital stay. A randomised , controlled trial. Crit Care 2005;9:687-93.
Pulse Contour Analysis(PCA)
• Principle- area under the systolic part of the arterial
waveform ~ SV
• Area is measured post diastole to end of ejection phase
divided by aortic impedance measures SV.
• Also measures SVV, PPV.
• In addition to shape of dP/dt, arterial compliance, SVR,
pt specific calibration factors are also required for
calibration.
Hofer Ck et al, Minimally invasive hemodynamic monitoring. Eur J Anaesthesiol 2009;26:996-1002.
• PICCO- was the first PCA device introduced & replaced
with PiCCO 2 in 2007.
• Requires both central & arterial line.
• Combines PCA & transpulmonary thermodilution CO –
hemodynamic variables.
• ITBV, GEDV, EVLW, SVV,PPV.
• 8th hr calibration & major hemodynamic changes
Sakka SG et al, Measurement of cardiac output: a comparison between transpulmonary
thermodilution and uncalibrated pulse contour analysis. Br J Anaesth 2007;99:337-42.
• Accuracy – vascular compliance, aortic impedance,
PAR, air bubbles, clots, inadequate indicator,
regurgitant lesions, arrythmia, rapid changing
temperature.
FloTRAC : - introduced in 2005, requires only arterial line
• Latest is 3rd gen device with dynamo tone technology –
automatic adjustment for change in vascular tone.
Goal directed fluid therapy
Goal directed fluid therapy
EV1000/volume view
• Based on pulse pressure analysis which is calibrated by
transpulmpnary thermodilution
• In comparison with PiCCO2 system in critically ill
patients found comparable results.
• However very few studies are available for its
validation,
• Recently Kapoor PM et al, successfully used this
monitor as one of the GDT monitoring in High risk
patients OPCAB.
Kapoor PM et al. Goal directed therapy improves the outcome of High risk cardiac patients undergoing off-
pump coronary artery bypass. Ann Card Anaesth 2017;20:83-9.
Goal directed fluid therapy
Goal directed fluid therapy
• SV= CSA * VTi
• Limiting factor – flow in descending thoracic aorta –
70% of total flow.
• coA, aneurysm, crossclamp, IABP.
• Accurate velocity can only be determined by proper
positioning of the probe- 20° of the axial flow.
• Various studies have compared ED vs PAC –found good
agreement with low bias.
Sharma J etal. Hemodynamic measurements after cardiac surgery: transesophageal
Doppler versus pulmonary artery caheter. J Cardiothorac Vasc Anesth 2005;19:746-50.
Goal directed fluid therapy
Goal directed fluid therapy
Funk DJ et al. Minimally Invasive Cardiac Output Monitoring in the Perioperative Setting. Anesth Analg
2009;108(3):887-97.
TEE
• Important tool for assess – structures, filling status,
contractility.
• LVEDV By disc summation, modified simpson method.
• LVEDA Tg SAX.
• SVC collapsibility.
• Assessment of ventricular function.
• limitations – skilled operator, limited
availability.
• Hemodynamic TEE – thinner disposable probe
– in situ for several days.
Dynamic parameters
• More recently, focus has shifted toward beat-to-beat
dynamic parameters -adequacy of preload.
• As a consequence, many monitoring technologies now
include approaches to continuously assessing SVV, PPV
SPV, PVI.
• During the inspiratory phase of MV, pressure
increases in the proximal (airway > alveolar > pleural)-
compress structures within the thorax, with low-
pressure/high-compliance structures.
• As a result- VR ↓ and cardiac filling ↓leading to a
↓preload and SV, and a downstream decrease in extra-
thoracic arterial pressure.
• As ITP ↓ with passive exhalation, absolute intra-
cardiac pressures initially ↓ and VR -↑, with left
ventricular preload then stabilizing during the nadir in
airway pressure achieved between breaths.
• The cyclic variation in preload and SV by respiration is
the foundation of GDT using dynamic parameters.
Goal directed fluid therapy
• Importance of these considerations is highlighted -
recently terminated RCT - 88% of high-risk surgical
patients were excluded from an SVV-based goal-
directed fluid therapy - laparoscopic surgery and/or
atrial fibrillation.
• positive fluid response is indicative of improved
cardiac performance,
a negative response cannot rule out that the
left ventricle remains relatively under-filled as a result
of RVD.
1.Jammer ITuovila MUlvik A. Stroke volume variation to guide fluid therapy: is it suitable for high-risk surgical
patients? A terminated randomized controlled trial. Perioper Med (Lond) 2015; 4: 6,
2.Hofer CKCannesson M. Monitoring fluid responsiveness. Acta anesthesiol taiwan 2011; 49:59-65.
• A recent review identified 31 goals, 22 monitoring
methods, and 118 different goal/method combinations in
81 papers - included all studies that assessed the clinical
utility of a specific goal, or set of goals, for fluid therapy
based on any monitoring method,
• highlights the difficulty in defining a consensus optimal
goal/method combination.
• Overall, the superiority of different monitoring methods
remains to be determined, and some cannot be
universally applied (i.e. ODM in awake patients or PPV
with an open chest).
Wilms HMittal AHaydock MDvan den Heever MDevaud MWindsor JAA. Systematic review of goal directed fluid
therapy: rating of evidence for goals and monitoring methods. J Crit Care 2014; 29: 204–9
Goal directed fluid therapy
Outcomes based on SV
• A wide range of RCTs of GDT based on SV optimization have
been published . To date, the largest is the OPTIMISE trial,
• a pragmatic, multicentre, randomized, observer-blinded
study that recruited 734 high-risk patients aged ≥ 50 yr
undergoing major gastrointestinal surgery.
• Importantly, the study standardized monitoring and
haemodynamic management and continued GDT for 6 h
after surgery.
Pearse RMHarrison DAMacDonald N, et al. . Effect of a perioperative, cardiac output–guided hemodynamic therapy
algorithm on outcomes following major gastrointestinal surgery: a randomized clinical trial and systematic review.
JAMA 2014; 311: 2181–90
Contd..
• This trial failed to find an outcome difference
(composite complications and 30-day mortality).
• However, other RCTs have shown that GDT targeting SV
optimization can lead to faster return of GI function,
fewer peri-operative complications, and shorter LOH.
• Reasons for the disparity in results are complex,
approaches to optimisation, including whether the
protocol was extended into the postoperative
period.
Contd..
• GDFT Vs GDHT.
• Different surgical populations.
• ERAS protocol.
• Ultimately, given the heterogeneity in study design and
methodology (type of surgery, monitoring method,
goal(s), intervention(s), control groups, outcome
measures),
it currently remains difficult to determine specific
morbidity or length of hospital stay benefits of SV-
guided GDT as a broad entity.
Phan TAn VD'souza BRattray MJohnston MCowie B. A randomised controlled trial of fluid restriction
compared to oesophageal Doppler-guided goal-directed fluid therapy in elective major colorectal
surgery within an enhanced recovery after surgery program. Anesth Intensive care 2014;42:752.
Goal directed fluid therapy
Goal directed fluid therapy
Outcomes based on dynamic parameters
• A meta-analysis - 14 studies with 961 patients
compared GDT based on SPV, PPV, SVV (one study
with PVI) on various outcomes relative to standard
care, and
• concluded that fluid administration guided by target
changes in ventilation-related dynamic parameters can
lead to a significant reduction in postoperative
morbidity.
Benes JGiglio MBrienza NMichard F. The effects of goal-directed fluid therapy based on dynamic
parameters on post-surgical outcome: a meta-analysis of randomized controlled trials. Crit Care 2014;
18: 584
Contd..
• In light of the potential for SVV and PPV,
MacDonald and colleagues - analysed data from 100
patients included in the OPTIMISE trial, to test that
SVV and PPV could accurately predict an increase in
SV of ≥ 10% in response to a fluid bolus .
• Thry concluded that both during and after surgery,
the predictive value was poor, and only slightly
improved by analytic techniques that compensated
for outlying values.
MacDonald NAhmad TMohr O, et al. . Dynamic preload markers to predict fluid responsiveness during and after
major gastrointestinal surgery: an observational substudy of the OPTIMISE trial. Br J Anaesth 2015; 114: 598–
604
Goal directed fluid therapy
Bio-impedance/bioreactance
• High frequency/low voltage current is applied to the chest-
impedance oscillates with cardiac filling and ejection.
• amplitude of this oscillation is œ to SV, and technologies
are available to estimate the proportionality constant and
provide clinically useful information.
• Poor SNR
• alternative, a modified tracheal tube has been developed
that provides internal bioimpedance measurements,
eliminating technical limitations associated with external
sensors.
• Bio-reactance -- a current of constant frequency is
applied to chest.
• bioreactance analyses the phase difference between
the applied current and the resultant voltage:
• oscillation of this phase difference is œ to SV.
• Better SNR making it more amenable to the
perioperative environment, and allows for flexibility in
sensor placement.
• Waldron and colleagues compared GDT protocol
guided by ODM and NICOM®, a bioreactance-based
technology.
• They concluded that the two methods were similar in
regard to assessing fluid responsiveness, and that there
were no clinically significant differences in outcomes.
• A randomized, multicentre trial of a GDT protocol
based upon NICOM® monitoring in 142 patients
undergoing open abdominal surgery was conducted
(the POEMAS trial).
• Overall, the study failed to show outcome benefit in
terms of complications or length of hospital stay.
Pestaña DEspinosa EEden A, et al. . Perioperative goal-directed hemodynamic optimization using noninvasive
cardiac output monitoring in major abdominal surgery: a prospective, randomized, multicenter, pragmatic trial:
POEMAS Study. Anesth Analg 2014;119:579-87.
Non invasive PCA
• Refinement of the “volume clamp” technique for
continuous, NIBP measurement by finger
probe,(NEXFIN)
• combination of a pressure cuff and plethysmographic
infrared light in the probe, and ultrafast processing,
beat to beat waveforms can be used to estimate SV
without cross calibration.
• Broch and colleagues randomized 79 patients to
receive standard treatment (n = 40) or early GDT (n =
39) based upon Nexfin®
• measurements of PPV and cardiac index were done.
• They concluded that no significant impact on
complications or mortality
Broch OCarstens AGruenewald M, et al. . Non-invasive haemodynamic optimization in major abdominal
surgery: a feasibility study. Minerva Anestesiol Advance Access published on June 28, 2016
PPG(Photo electric plethysmography)
• Early work with pulse oximetry PPG signals focused upon
respiratory variation in signal amplitude or “ΔPOP”.
• More recently, greater emphasis has been placed on PVI,
a measurement derived from respiratory variation in the
perfusion index,
• a variable derived as the ratio of pulsatile to non-pulsatile
infrared signals.
• Based upon the assumption that SV and (PWTT) are
inversely correlated, SV is derived from an algorithm.
Antonsen LPKirkeboen KA.Evaluation of fluid responsiveness: is photoplethysmography a noninvasive
alternative?Anesthesiol Res Pract 2012; 2012: 617380
Goal directed fluid therapy
GDT in cardiac surgery
Aya HD et al. Goal directed therapy in cardiac surgery: a systematic review and
meta-analysis. Br J Anaesth 2013;110:510-17.
Goal directed fluid therapy
ESA Protocols - SV
SVV
Do2I
Goal directed fluid therapy
Optimisation of Perioperative Cardiovascular Management to
Improve Surgical Outcome II (OPTIMISE II) Trial
Methodology - International, open, multi-centre, randomised
controlled trial
Primary objective - incidence of postoperative infection
within 30 days of randomisation.
Secondary objectives – mortality, other forms of
postoperative morbidity, improves quality of life and is cost-
effective.
Study design -Pragmatic multicentre open randomised trial
supported by data from National Emergency Laparotomy Audit
(NELA).
Sample size - 7646 patients – to demonstrate an absolute
reduction in mortality at 90-days post-surgery from 19% to
16% in the intervention group with 90% power.
Primary outcome – 90 days mortality .
Secondary outcomes –
1 year mortality; ICU stay & LOH,
hospital readmission within 90 days;
cost effectiveness.
The right fluid, for the right patient, at
the right time.
OPTIMISE trial
Weaknesses
• Baseline difference: higher incidence of renal
impairment in intervention group.
• Composite outcome is pragmatic and relevant to
patient care. yet, cannot ascertain if individual
components are associated with benefit, no effect or
harm.
• External generalisability:
– median surgery was 4.5 hours, 70% received epidurals and
70% attended critical care for level 3 care; incidence of
laparoscopic surgery not available. Although this appears
to describe a very high-risk surgical cohort, 30-day
mortality was only ~3%. Difficult to define which of my
patients I can apply these findings to.

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Goal directed fluid therapy

  • 1. GOAL DIRECTED FLUID THERAPY E THANIGAI ARASU
  • 2. Introduction • Intravenous fluid therapy - core part of perioperative practice - potential to influence patient outcomes. • One of the most frequently discussed issues of peri-opearative medicine. • UK confidential Enquiry into peri-operative death reveals Errors in the fluid management (usually In Excess): Most common cause of peri-operative morbidity & mortality. 2LOBO DN. Best Pract Clin Anaesth 2006;20(3):439
  • 3. Why do we give so much fluid??  Pre op fasting  Surgical blood loss many litres of  Evaporation fluid during a  Vasodilatation caused by anaesthesia a standard  Transfer to third space  Transcapillary leak of albumin caused by operation inflammatory mediators  Urinary excretion Hahn RG. Anesth Analg 2007;105:304.
  • 4. "Standard" management grossly overestimates IV fluid requirements Maintanace: 4:2:1 rule Deficit: Maintanace Hr fasting 3rd space loss: 5-7ml/Kg Blood loss: 3:1 replacement with crystalloid
  • 7. • So another concept has been raised is RFT. • Also referred as zero balance approach. • No clear definition of RFT in the medical literature. • Generally the approach - smaller peri- operative fluid infusion volumes than the 'traditional' approach.
  • 13. ‘Efforts in the past to restrict fluids - oliguria, anuria and occasionally acute renal shutdown. Many (if not most) instances of postsurgical shock were unquestionably related to this same practice of forced hypovolaemia. though some RCT address this issue (Brandstrup 2012; Phan 2014; Srinivasa 2013; Zhang 2012); however, no systematic review has so far evaluated this new evidence.
  • 14. Restrictive versus liberal fluid therapy in major abdominal surgery (RELIEF): rationale and design for a multicentre randomised trial Myles P, Bellomo R, Corcoran T on behalf of the Australian and New Zealand College of Anaesthetists Clinical Trials Network, and the Australian and New Zealand Intensive Care Society Clinical Trials Group, et al Restrictive versus liberal fluid therapy in major abdominal surgery (RELIEF): rationale and design for a multicentre randomised trial BMJ Open 2017;7:e015358. doi:10.1136/bmjopen-2016-015358
  • 15. Perioperative restrictive versus GDFT for adults undergoing major non cardiac surgery Primary outcome: 1. Major complications during longest follow up period. 2. All cause mortality during longest follow up period. Wrzosek A et al. cochrane Database of systematic Reviews 2017, issue 8 Art. No.: CD012767
  • 16. RIFTS trial No Intervention: Usual Care Participants will receive an initial 30 ml/kg bolus and then IV fluids as needed and without limit as well as IV vasopressors to maintain a MAP>65, determined by the primary care team for the duration of the study. Restrictive Care: Participants will be LIMITED to 60 ml/kg (up to 6000 ml) of IV fluids as initial resuscitation followed by administration of IV vasopressors to maintain a MAP>65 mm Hg for the first 72 hours of care. Discharge Mortality and Persistent Organ Dysfunction (POD) a composite outcome
  • 18. So the answer is GDFT
  • 19. • GDT is a term used to describe the use of cardiac output(CO) or similar parameters to guide the IV fluids and inotropic therapy. • It involves goal directed manipulation of Tissue oxygenation preload contractility afterload
  • 20. Ideal is Do2 index
  • 21. Integration of arterial pressure and flow • This is misleading • Fundamentally MAP = CO * Resistance • Local resistance are controlled in a organ specific manner. • Under normal circumstances it will be matching. • However the flow regulatory capacity of different organs in the face of changing BP are not equivalent & varies among organs.
  • 22. • The limits of pressure auto regulation are not specific numbers but a range of distribution- that can vary widely depending upon the physical status, physiological stress, drugs. • Furthermore at microcirculatory level, tissue perfusion is also influenced by the outflow venous pressure. • Therefore without considering total and regional arterial resistance, organ specific autoregulation, and the potential for tissue edema & venous congestion assuming a good flow based on good pressure can be misleading.
  • 23. From: Perioperative goal-directed haemodynamic therapy based on flow parameters: a concept in evolution Br J Anaesth. 2016;117(suppl_3):iii3-iii17. doi:10.1093/bja/aew363 Br J Anaesth | © The Author 2016. Published by Oxford University Press on behalf of the British Journal of Anaesthesia. All rights reserved. For Permissions, please email: journals.permissions@oup.com
  • 24. Invasive(PAC) • Intermittent • continuous Minimally invasive • LidCO • PCA(PiCCO & Flo Trac) • ED • TEE • PRAM Non-invasive • Partial gas rebreathing • ECOM • Thoracic bio- impedance & bioractance • Doppler • Photo electric plethysmography( PEP) • Non invasive PCA
  • 25. Static parameters-Pulmonary Artery Catheter • Though it has been associated with various complications it is still considered gold standard monitor to measure CO since 1970s. • Apart from CO it measures the central filling pressures & Svo2. • Literature review of PAC revealed both benefits and risks. • Gore et al,(CHEST 1987) – showed mortality after MI. • SUPPORT trial(JAMA 1996)- mortality at 30 days
  • 26. • PAC-MAN trial(Lancet 2005) –failed to show any harm or benefit. • Its use in OPCAB also showed no difference in mortaity and final outcome. • ESCAPE trial(JAMA 2005) – functional improvement with PAC guided therapy in pts with CHF. • However due to inherent risk associate with its use investigators are moved to minimally or non invasive monitors. Contd,,
  • 30. Fluid responsiveness Regulation of Venous return Frank-starling relationship Incidence of Non-responders
  • 31. Venous return • IV infusion- Increases VR. However, in that much of the circulating blood volume resides in highly distensible venous capacitance vessels • There is not necessarily a linear relationship. • In fact, at any point a portion of the venous capacitance volume is “unstressed”.
  • 32. • In contrast, the “stressed” venous volume does create transmural pressure, and it is the gradient, that drives venous return [Venous return = (mean systemic filling pressure – right atrial pressure)/venous resistance]. • This relationship is dynamic - factors affected by respiration, autonomic tone, IAP, and body position. Cherpanath TGGeerts BFLagrand WKSchultz MJGroeneveld AB. Basic concepts of fluid responsiveness. Neth Heart J 2013; 21: 530–6
  • 36. • Many investigations of this matter in the presence of a complete circulation have been either inadequate or misleading largely because… stroke volume or cardiac output and not stroke work has been used as the measure of the "energy of contraction"… and • perhaps most important, a single Starling curve cannot always satisfactorily explain the observed phenomena; for any given heart there is a series of curves.“ Sarnoff SJBerglund E. Ventricular function. I. Starling's law of the heart studied by means of simultaneous right and left ventricular function curves in the dog. Circulation 1954; 9: 706–18
  • 37. Contd, • They also challenged the notion that a descending limb - could be achieved in normal hearts, and emphasized- "juxta-cardiac" pressure when interpreting pressure indices of preload (i.e. transmural vs absolute pressure), • a factor later emphasized by Braunwald in clinical studies Braunwald ERoss J.Jr. Applicability of starling's law of the heart to man. Circ Res 1964; 15 (Suppl 2):169–81
  • 38. High incidence of Non-Responders • Central blood volume augmentation done by either endogenous(PLR) or exogenous(fluid bolus) • And response measured by SV, CO, flow velocity. • Somewhat surprisingly, studies across a range of patient populations and monitoring methodologies have consistently indicated that roughly half of the subjects evaluated are non-responders. Biais MVidil LSarrabay PCottenceau VRevel PSztark F. Changes in stroke volume induced by passive leg raising in spontaneously breathing patients: comparison between echocardiography and Vigileo/FloTrac device. Crit Care 2009; 13: R195
  • 39. Contd, • For PLR in particular, two meta-analyses incorporating ill patients in whom SV and CO were measured by a range of technologies -reported responder rates of 53 and 54% • Overall, the physiological basis for non-responsiveness remains unclear, and might vary among patients. • Techniques measures SV- no direct verification that left ventricular preload (end-diastolic volume) actually increased significantly. Monnet XMarik PTeboul JL. Passive leg raising for predicting fluid responsiveness: a systematic review and meta- analysis. Intensive Care Med 2016; 42: 1935–47
  • 40. Contd, • Furthermore, both SV and EDV are affected by heart rate (HR) and afterload. • In this context, consideration of Sarnoff and Berglund’s comments that, "a single Starling curve cannot always satisfactorily explain the observed phenomena", or that stroke work not SV is the more appropriate dependent variable may be warranted. ‘ • Finally, a fixed cut-off for differentiating responders from non-responders can contribute to a significant "grey zone"
  • 41. Is it number or we want scalar variable??? • Cooke R et al, reviewed volume responsiveness- focused on Pmsa. • 11 studies – 572 pts – 52% responders analyzed. • CO ↑by 12% & 22% following PLR & volume challenge respectively. • No statistical difference found between responders & Non-responders in terms of CO/MAP/CVP
  • 42. • In contrast the calculated mean systemic filling pressure analougue ↓ in responders(P=0.007) • Non responders also demonstrated deteriorating Heart efficiency of -15% & CP of -7% . • The results demonstrated Pmsa, heart efficiency, cardiac power can identify response and provides scalar results rather than merely a dichotomous outcome of responder or non- responder. cooke R et al, volume responsiveness assessed by passive leg raising and a fluid challenge: a critical review focused on mean systemic filling pressure. Anesth 2018;73:313-22.
  • 43. Minimally invasive monitors • LiDCO – combines PPA with lithium indicator dilution – SV & SVV. • Principle- change of BP about the mean ~ SV. • Root mean square method applied to arterial signal – Nominal SV & using calibration factor scaled to actual SV. • Requires calibration every 8th hr & major hemodynamic changes. • And affected by NMBD.(Electrode drift)
  • 44. • Contraindication – Li therapy. • Accuracy – IABP, Damped line, post aortic surgery, arrhythmias, intra/extra cardiac shunts. • Found good correlation with PAC.(Linton et al) • Pearse et al studied it for GDT revealed fewer complication & shorter LOH. Pearse R et al, Early goal directed therapy after major surgery reduces complications and duration of hospital stay. A randomised , controlled trial. Crit Care 2005;9:687-93.
  • 45. Pulse Contour Analysis(PCA) • Principle- area under the systolic part of the arterial waveform ~ SV • Area is measured post diastole to end of ejection phase divided by aortic impedance measures SV. • Also measures SVV, PPV. • In addition to shape of dP/dt, arterial compliance, SVR, pt specific calibration factors are also required for calibration. Hofer Ck et al, Minimally invasive hemodynamic monitoring. Eur J Anaesthesiol 2009;26:996-1002.
  • 46. • PICCO- was the first PCA device introduced & replaced with PiCCO 2 in 2007. • Requires both central & arterial line. • Combines PCA & transpulmonary thermodilution CO – hemodynamic variables. • ITBV, GEDV, EVLW, SVV,PPV. • 8th hr calibration & major hemodynamic changes Sakka SG et al, Measurement of cardiac output: a comparison between transpulmonary thermodilution and uncalibrated pulse contour analysis. Br J Anaesth 2007;99:337-42.
  • 47. • Accuracy – vascular compliance, aortic impedance, PAR, air bubbles, clots, inadequate indicator, regurgitant lesions, arrythmia, rapid changing temperature. FloTRAC : - introduced in 2005, requires only arterial line • Latest is 3rd gen device with dynamo tone technology – automatic adjustment for change in vascular tone.
  • 50. EV1000/volume view • Based on pulse pressure analysis which is calibrated by transpulmpnary thermodilution • In comparison with PiCCO2 system in critically ill patients found comparable results. • However very few studies are available for its validation, • Recently Kapoor PM et al, successfully used this monitor as one of the GDT monitoring in High risk patients OPCAB. Kapoor PM et al. Goal directed therapy improves the outcome of High risk cardiac patients undergoing off- pump coronary artery bypass. Ann Card Anaesth 2017;20:83-9.
  • 53. • SV= CSA * VTi • Limiting factor – flow in descending thoracic aorta – 70% of total flow. • coA, aneurysm, crossclamp, IABP. • Accurate velocity can only be determined by proper positioning of the probe- 20° of the axial flow. • Various studies have compared ED vs PAC –found good agreement with low bias. Sharma J etal. Hemodynamic measurements after cardiac surgery: transesophageal Doppler versus pulmonary artery caheter. J Cardiothorac Vasc Anesth 2005;19:746-50.
  • 56. Funk DJ et al. Minimally Invasive Cardiac Output Monitoring in the Perioperative Setting. Anesth Analg 2009;108(3):887-97.
  • 57. TEE • Important tool for assess – structures, filling status, contractility. • LVEDV By disc summation, modified simpson method. • LVEDA Tg SAX. • SVC collapsibility. • Assessment of ventricular function.
  • 58. • limitations – skilled operator, limited availability. • Hemodynamic TEE – thinner disposable probe – in situ for several days.
  • 59. Dynamic parameters • More recently, focus has shifted toward beat-to-beat dynamic parameters -adequacy of preload. • As a consequence, many monitoring technologies now include approaches to continuously assessing SVV, PPV SPV, PVI. • During the inspiratory phase of MV, pressure increases in the proximal (airway > alveolar > pleural)- compress structures within the thorax, with low- pressure/high-compliance structures.
  • 60. • As a result- VR ↓ and cardiac filling ↓leading to a ↓preload and SV, and a downstream decrease in extra- thoracic arterial pressure. • As ITP ↓ with passive exhalation, absolute intra- cardiac pressures initially ↓ and VR -↑, with left ventricular preload then stabilizing during the nadir in airway pressure achieved between breaths. • The cyclic variation in preload and SV by respiration is the foundation of GDT using dynamic parameters.
  • 62. • Importance of these considerations is highlighted - recently terminated RCT - 88% of high-risk surgical patients were excluded from an SVV-based goal- directed fluid therapy - laparoscopic surgery and/or atrial fibrillation. • positive fluid response is indicative of improved cardiac performance, a negative response cannot rule out that the left ventricle remains relatively under-filled as a result of RVD. 1.Jammer ITuovila MUlvik A. Stroke volume variation to guide fluid therapy: is it suitable for high-risk surgical patients? A terminated randomized controlled trial. Perioper Med (Lond) 2015; 4: 6, 2.Hofer CKCannesson M. Monitoring fluid responsiveness. Acta anesthesiol taiwan 2011; 49:59-65.
  • 63. • A recent review identified 31 goals, 22 monitoring methods, and 118 different goal/method combinations in 81 papers - included all studies that assessed the clinical utility of a specific goal, or set of goals, for fluid therapy based on any monitoring method, • highlights the difficulty in defining a consensus optimal goal/method combination. • Overall, the superiority of different monitoring methods remains to be determined, and some cannot be universally applied (i.e. ODM in awake patients or PPV with an open chest). Wilms HMittal AHaydock MDvan den Heever MDevaud MWindsor JAA. Systematic review of goal directed fluid therapy: rating of evidence for goals and monitoring methods. J Crit Care 2014; 29: 204–9
  • 65. Outcomes based on SV • A wide range of RCTs of GDT based on SV optimization have been published . To date, the largest is the OPTIMISE trial, • a pragmatic, multicentre, randomized, observer-blinded study that recruited 734 high-risk patients aged ≥ 50 yr undergoing major gastrointestinal surgery. • Importantly, the study standardized monitoring and haemodynamic management and continued GDT for 6 h after surgery. Pearse RMHarrison DAMacDonald N, et al. . Effect of a perioperative, cardiac output–guided hemodynamic therapy algorithm on outcomes following major gastrointestinal surgery: a randomized clinical trial and systematic review. JAMA 2014; 311: 2181–90
  • 66. Contd.. • This trial failed to find an outcome difference (composite complications and 30-day mortality). • However, other RCTs have shown that GDT targeting SV optimization can lead to faster return of GI function, fewer peri-operative complications, and shorter LOH. • Reasons for the disparity in results are complex, approaches to optimisation, including whether the protocol was extended into the postoperative period.
  • 67. Contd.. • GDFT Vs GDHT. • Different surgical populations. • ERAS protocol. • Ultimately, given the heterogeneity in study design and methodology (type of surgery, monitoring method, goal(s), intervention(s), control groups, outcome measures), it currently remains difficult to determine specific morbidity or length of hospital stay benefits of SV- guided GDT as a broad entity. Phan TAn VD'souza BRattray MJohnston MCowie B. A randomised controlled trial of fluid restriction compared to oesophageal Doppler-guided goal-directed fluid therapy in elective major colorectal surgery within an enhanced recovery after surgery program. Anesth Intensive care 2014;42:752.
  • 70. Outcomes based on dynamic parameters • A meta-analysis - 14 studies with 961 patients compared GDT based on SPV, PPV, SVV (one study with PVI) on various outcomes relative to standard care, and • concluded that fluid administration guided by target changes in ventilation-related dynamic parameters can lead to a significant reduction in postoperative morbidity. Benes JGiglio MBrienza NMichard F. The effects of goal-directed fluid therapy based on dynamic parameters on post-surgical outcome: a meta-analysis of randomized controlled trials. Crit Care 2014; 18: 584
  • 71. Contd.. • In light of the potential for SVV and PPV, MacDonald and colleagues - analysed data from 100 patients included in the OPTIMISE trial, to test that SVV and PPV could accurately predict an increase in SV of ≥ 10% in response to a fluid bolus . • Thry concluded that both during and after surgery, the predictive value was poor, and only slightly improved by analytic techniques that compensated for outlying values. MacDonald NAhmad TMohr O, et al. . Dynamic preload markers to predict fluid responsiveness during and after major gastrointestinal surgery: an observational substudy of the OPTIMISE trial. Br J Anaesth 2015; 114: 598– 604
  • 73. Bio-impedance/bioreactance • High frequency/low voltage current is applied to the chest- impedance oscillates with cardiac filling and ejection. • amplitude of this oscillation is œ to SV, and technologies are available to estimate the proportionality constant and provide clinically useful information. • Poor SNR • alternative, a modified tracheal tube has been developed that provides internal bioimpedance measurements, eliminating technical limitations associated with external sensors.
  • 74. • Bio-reactance -- a current of constant frequency is applied to chest. • bioreactance analyses the phase difference between the applied current and the resultant voltage: • oscillation of this phase difference is œ to SV. • Better SNR making it more amenable to the perioperative environment, and allows for flexibility in sensor placement.
  • 75. • Waldron and colleagues compared GDT protocol guided by ODM and NICOM®, a bioreactance-based technology. • They concluded that the two methods were similar in regard to assessing fluid responsiveness, and that there were no clinically significant differences in outcomes. • A randomized, multicentre trial of a GDT protocol based upon NICOM® monitoring in 142 patients undergoing open abdominal surgery was conducted (the POEMAS trial). • Overall, the study failed to show outcome benefit in terms of complications or length of hospital stay. Pestaña DEspinosa EEden A, et al. . Perioperative goal-directed hemodynamic optimization using noninvasive cardiac output monitoring in major abdominal surgery: a prospective, randomized, multicenter, pragmatic trial: POEMAS Study. Anesth Analg 2014;119:579-87.
  • 76. Non invasive PCA • Refinement of the “volume clamp” technique for continuous, NIBP measurement by finger probe,(NEXFIN) • combination of a pressure cuff and plethysmographic infrared light in the probe, and ultrafast processing, beat to beat waveforms can be used to estimate SV without cross calibration.
  • 77. • Broch and colleagues randomized 79 patients to receive standard treatment (n = 40) or early GDT (n = 39) based upon Nexfin® • measurements of PPV and cardiac index were done. • They concluded that no significant impact on complications or mortality Broch OCarstens AGruenewald M, et al. . Non-invasive haemodynamic optimization in major abdominal surgery: a feasibility study. Minerva Anestesiol Advance Access published on June 28, 2016
  • 78. PPG(Photo electric plethysmography) • Early work with pulse oximetry PPG signals focused upon respiratory variation in signal amplitude or “ΔPOP”. • More recently, greater emphasis has been placed on PVI, a measurement derived from respiratory variation in the perfusion index, • a variable derived as the ratio of pulsatile to non-pulsatile infrared signals. • Based upon the assumption that SV and (PWTT) are inversely correlated, SV is derived from an algorithm. Antonsen LPKirkeboen KA.Evaluation of fluid responsiveness: is photoplethysmography a noninvasive alternative?Anesthesiol Res Pract 2012; 2012: 617380
  • 80. GDT in cardiac surgery
  • 81. Aya HD et al. Goal directed therapy in cardiac surgery: a systematic review and meta-analysis. Br J Anaesth 2013;110:510-17.
  • 84. SVV
  • 85. Do2I
  • 87. Optimisation of Perioperative Cardiovascular Management to Improve Surgical Outcome II (OPTIMISE II) Trial Methodology - International, open, multi-centre, randomised controlled trial Primary objective - incidence of postoperative infection within 30 days of randomisation. Secondary objectives – mortality, other forms of postoperative morbidity, improves quality of life and is cost- effective.
  • 88. Study design -Pragmatic multicentre open randomised trial supported by data from National Emergency Laparotomy Audit (NELA). Sample size - 7646 patients – to demonstrate an absolute reduction in mortality at 90-days post-surgery from 19% to 16% in the intervention group with 90% power. Primary outcome – 90 days mortality . Secondary outcomes – 1 year mortality; ICU stay & LOH, hospital readmission within 90 days; cost effectiveness.
  • 89. The right fluid, for the right patient, at the right time.
  • 90. OPTIMISE trial Weaknesses • Baseline difference: higher incidence of renal impairment in intervention group. • Composite outcome is pragmatic and relevant to patient care. yet, cannot ascertain if individual components are associated with benefit, no effect or harm. • External generalisability: – median surgery was 4.5 hours, 70% received epidurals and 70% attended critical care for level 3 care; incidence of laparoscopic surgery not available. Although this appears to describe a very high-risk surgical cohort, 30-day mortality was only ~3%. Difficult to define which of my patients I can apply these findings to.

Hinweis der Redaktion

  1. Fig 1 Changes in mean arterial blood pressure (MAP), cardiac output (CO) measured using oesophageal Doppler, and cerebral tissue oxygen saturation (SctO<sub>2</sub>) measured using near-infrared spectroscopy after phenylephrine and ephedrine bolus treatments, respectively, in two propofol-anaesthetized patients. (A–C) Recordings during phenylephrine treatment. (D–F) Recordings during ephedrine treatment. Vertical arrows indicate the drug administration time. Measurements show the divergent changes in MAP and cardiac output, and that change in tissue oxygenation is in accordance with change in cardiac output, not BP. (Reproduced with permission, from: Meng L, Cannesson M, Alexander BS, Yu Z, Kain ZN, Cerussi AE, Tromberg BJ, Mantulin WW. Effect of phenylephrine and ephedrine bolus treatment on cerebral oxygenation in anaesthetized patients. Br J Anaesth. 2011 Aug;107(2):209-17).