The document discusses fluid strategy in the perioperative setting and whether more or less fluid is better. It summarizes that while goal-directed therapy aimed at optimizing hemodynamics has been shown to reduce mortality and morbidity in some studies, the evidence is still being questioned. Excessive fluid administration can also lead to detrimental fluid overload, and a restrictive fluid strategy may be advantageous in reducing postoperative complications and shortening hospital stay.

1. 2nd
IFAD, Antwerpen 2012
Azriel PerelAzriel Perel
Professor and ChairmanProfessor and Chairman
Department of Anesthesiology and Intensive CareDepartment of Anesthesiology and Intensive Care
Sheba Medical Center, Tel Aviv UniversitySheba Medical Center, Tel Aviv University
IsraelIsrael
Fluid strategy in the perioperative settingFluid strategy in the perioperative setting
IS MORE, OR LESS, BETTER?IS MORE, OR LESS, BETTER?

2. Disclosure
The speaker cooperates with the following companies
BMEYE
FlowSense
iMDsoft
Pulsion
perelao@shani.net

3.  The mortality rate for patientsThe mortality rate for patients
undergoing non-cardiac surgery isundergoing non-cardiac surgery is
higher than anticipated.higher than anticipated.
 There is a need for strategies toThere is a need for strategies to
improve care for this group of patients.improve care for this group of patients.

4. PerioperativePerioperative
goal-directed therapy (GDT)goal-directed therapy (GDT)
improves outcomeimproves outcome

5. The use of a preemptive strategy ofThe use of a preemptive strategy of
hemodynamic monitoring and coupledhemodynamic monitoring and coupled
therapy reduces surgical mortality andtherapy reduces surgical mortality and
morbidity.morbidity.

6. Short-term peri-Short-term peri-
operative GDT mayoperative GDT may
improve long-termimprove long-term
outcomes, in partoutcomes, in part
due to its ability todue to its ability to
reduce the numberreduce the number
of perioperativeof perioperative
complications.complications.

7. Gurgel ST et al. Anesthesia Analgesia 2011

8.  A bolus of 200 ml colloid is administeredA bolus of 200 ml colloid is administered
over 2 min, and 5 min later the stroke volumeover 2 min, and 5 min later the stroke volume
(SV) is assessed.(SV) is assessed.
 The procedure is repeated if there was anThe procedure is repeated if there was an
increase in SV of >10%.increase in SV of >10%.
 When the fluid bolus does not result in a SVWhen the fluid bolus does not result in a SV
increment >10%, optimization is regarded asincrement >10%, optimization is regarded as
achieved.achieved.
GDT – the ‘basic’ techniqueGDT – the ‘basic’ technique

9. Fluids should be given to increase CO,Fluids should be given to increase CO,
and inodilators added once the patientand inodilators added once the patient
is no longer fluid (preload) responsiveis no longer fluid (preload) responsive
or not achieving the following goals:or not achieving the following goals:
 CICI >> 4.5 L/min/m4.5 L/min/m22
 DODO22I ≥ 600 ml/min/mI ≥ 600 ml/min/m22

10. ““It may be considered unethicalIt may be considered unethical
not to use goal-directednot to use goal-directed
perioperative therapyperioperative therapy””

11. ““We believe that a minimally invasiveWe believe that a minimally invasive
cardiac output monitor should becardiac output monitor should be
considered in all major surgery toconsidered in all major surgery to
optimize preload.”optimize preload.”

12. The oesophageal Doppler monitorThe oesophageal Doppler monitor ‘‘should be‘‘should be
considered for use in patients undergoingconsidered for use in patients undergoing
major or high-risk surgery…(major or high-risk surgery…(since its use issince its use is
associated with)associated with) a reduction in post-operativea reduction in post-operative
complications, use of central venous catheterscomplications, use of central venous catheters
and in-hospital stay…The cost saving perand in-hospital stay…The cost saving per
patient…is about £1100 based on a 7.5-daypatient…is about £1100 based on a 7.5-day
hospital stay.’’hospital stay.’’

13. What hemodynamic monitoring do youWhat hemodynamic monitoring do you
routinely use for the management ofroutinely use for the management of
high-risk surgery patients?high-risk surgery patients?

14.  Cannesson and colleagues show us thatCannesson and colleagues show us that
practice remains out of sync with the currentpractice remains out of sync with the current
evidence base with regards to GDT.evidence base with regards to GDT.
 Whether this is because physicians still doubtWhether this is because physicians still doubt
the evidence base, worry about inaccuracies inthe evidence base, worry about inaccuracies in
monitoring techniques or simply lack the energymonitoring techniques or simply lack the energy
and motivation needed to change practice isand motivation needed to change practice is
unclear.unclear.

15. The mechanisms underlyingThe mechanisms underlying
the reported benefit of GDTthe reported benefit of GDT
remain uncertainremain uncertain

16.  Major surgery generates a strong systemicMajor surgery generates a strong systemic
inflammatory response and an overallinflammatory response and an overall
substantial increase in oxygen demand, whichsubstantial increase in oxygen demand, which
is normally met by an increase in cardiacis normally met by an increase in cardiac
output (CO) and in oxygen extraction.output (CO) and in oxygen extraction.
 Patients that do not have the physiologicalPatients that do not have the physiological
reserve to increase the CO to the required levelreserve to increase the CO to the required level
may have inadequate tissue perfusion andmay have inadequate tissue perfusion and
therefore be at higher risk for postoperativetherefore be at higher risk for postoperative
complications.complications.
The rationale of perioperative GDTThe rationale of perioperative GDT

18.  Postoperative fluid therapy, guided by SV +Postoperative fluid therapy, guided by SV +
low-dose dopexamine, was associated withlow-dose dopexamine, was associated with
improved sublingual and cutaneousimproved sublingual and cutaneous
microvascular flow.microvascular flow.
 However, this improvement was notHowever, this improvement was not
associated with differences in inflammatoryassociated with differences in inflammatory
markers or in overall complication rate.markers or in overall complication rate.

19. There is an urgent need to evaluateThere is an urgent need to evaluate
the pathophysiological mechanismsthe pathophysiological mechanisms
that are responsible for the positivethat are responsible for the positive
results reported by most clinical GDTresults reported by most clinical GDT
studies.studies.

20.  In most studies GDT was performed inIn most studies GDT was performed in
the intraoperative period and in somethe intraoperative period and in some
within the very early postoperative period.within the very early postoperative period.
 WhenWhen to institute GDT needs to beto institute GDT needs to be
clarified.clarified.

22. British consensus guidelines on intravenous fluidBritish consensus guidelines on intravenous fluid
therapy for adult surgical patients. 2011.therapy for adult surgical patients. 2011.
Powell-Tuck J, et al.Powell-Tuck J, et al.
www.bapen.org.uk/pdfs/bapen_pubs/giftasup.pdf.www.bapen.org.uk/pdfs/bapen_pubs/giftasup.pdf.
““Concern arose from a high incidence of post-Concern arose from a high incidence of post-
operative sodium and water overload, and evidenceoperative sodium and water overload, and evidence
to suggest that preventing or treating this, by moreto suggest that preventing or treating this, by more
accurate fluid therapy, would improve outcome.accurate fluid therapy, would improve outcome.

23. British consensus guidelines on intravenous fluidBritish consensus guidelines on intravenous fluid
therapy for adult surgical patients. 2011.therapy for adult surgical patients. 2011.
Powell-Tuck J, et al.Powell-Tuck J, et al.
www.bapen.org.uk/pdfs/bapen_pubs/giftasup.pdf.www.bapen.org.uk/pdfs/bapen_pubs/giftasup.pdf.

24. The evidence behind GDTThe evidence behind GDT
is still being questionedis still being questioned

25. Despite the apparent improvements inDespite the apparent improvements in
postoperative outcome by the GDTpostoperative outcome by the GDT
concept all studies have problems inconcept all studies have problems in
their design.their design.

26.  The evidence underpinning ODM-guidedThe evidence underpinning ODM-guided
fluid administration has not been criticallyfluid administration has not been critically
appraised despite quantitative meta-analyses.appraised despite quantitative meta-analyses.
 The observed initial clinical benefits mayThe observed initial clinical benefits may
be largely offset by recent advances inbe largely offset by recent advances in
surgical techniques and peri-operative care.surgical techniques and peri-operative care.

27.  There are distinct challenges associated with theThere are distinct challenges associated with the
design and conduct of GDT trials which are not easilydesign and conduct of GDT trials which are not easily
solved. The findings of all previous GDT trials must besolved. The findings of all previous GDT trials must be
interpreted in the context of the design choices that theinterpreted in the context of the design choices that the
investigators have made.investigators have made.
 Blinding is an important potential source of bias inBlinding is an important potential source of bias in
GDT trials and small GDT trials in particular areGDT trials and small GDT trials in particular are
vulnerable to bias.vulnerable to bias.
 The lack of confirmation in large trials is a significantThe lack of confirmation in large trials is a significant
limitation of the evidence base for GDT.limitation of the evidence base for GDT.

28.  A double-blinded, prospective, randomized study inA double-blinded, prospective, randomized study in
patients undergoing laparoscopic colectomy, whopatients undergoing laparoscopic colectomy, who
received standard care, GDT with hetastarch, or GDTreceived standard care, GDT with hetastarch, or GDT
with lactated Ringer's.with lactated Ringer's.
 The hetastarch group had the longest hospital stay.The hetastarch group had the longest hospital stay.
 Goal-directed fluid management with a colloidGoal-directed fluid management with a colloid
solution offers no advantage and is more costly.solution offers no advantage and is more costly.
Fluid management for laparoscopic colectomy: a prospective,
randomized assessment of goal-directed administration of balanced
salt solution or hetastarch coupled with an enhanced recovery
program.
Senagore AJ, et al. Dis Colon Rectum. 2009 ;52:1935

29.  Intraoperative SV optimization conferred noIntraoperative SV optimization conferred no
additional benefit over standard fluid therapy.additional benefit over standard fluid therapy.
 In an aerobically fit subgroup of patients, GDT wasIn an aerobically fit subgroup of patients, GDT was
associated with detrimental effects on the primaryassociated with detrimental effects on the primary
outcome.outcome.
 GDT focusing on SV maximization may haveGDT focusing on SV maximization may have
important limitations including a risk of iatrogenicimportant limitations including a risk of iatrogenic
fluid overload which may be associated withfluid overload which may be associated with
prolonged hospital stay.prolonged hospital stay.

30. Anesth Analg 2011;112:130–8
The routine use of dopexamineThe routine use of dopexamine
does not confer an additionaldoes not confer an additional
clinical benefit.clinical benefit.

31. Ghosh S, Arthur B, Klein AA
 When reading the clinical trials relating to use of theWhen reading the clinical trials relating to use of the
esophageal Doppler, it is striking that the primeesophageal Doppler, it is striking that the prime
intervention differentiating controls from study groupintervention differentiating controls from study group
patients is the infusion of about 500 ml colloidpatients is the infusion of about 500 ml colloid
intraoperatively.intraoperatively.
 Can it really be that a monitoring device used for up toCan it really be that a monitoring device used for up to
four hours out of an eight-day hospital stay, and thefour hours out of an eight-day hospital stay, and the
infusion of a small bag of fluid, can save the NHS £1100infusion of a small bag of fluid, can save the NHS £1100
per patient?per patient?
 If so, why not just adopt a less conservative approachIf so, why not just adopt a less conservative approach
to intra-operative fluid balance and dispense with theto intra-operative fluid balance and dispense with the
monitoring device as well?monitoring device as well?

32. Can GDT lead toCan GDT lead to
detrimental fluid overload?detrimental fluid overload?

35. Cecconi M et alCecconi M et al

36.  Patients undergoing major abdominal surgeryPatients undergoing major abdominal surgery
underwent pre-operative fluid loading with 25 ml/kgunderwent pre-operative fluid loading with 25 ml/kg
of Ringer’s solution in the six hours before surgery.of Ringer’s solution in the six hours before surgery.
 Pre-operative intravenous fluid loading leads to aPre-operative intravenous fluid loading leads to a
non-significant reduction in hospital length of staynon-significant reduction in hospital length of stay
after high-risk major surgery and is likely to be cost-after high-risk major surgery and is likely to be cost-
effective.effective.

37. ““We have to re-examine whether we have indeedWe have to re-examine whether we have indeed
started to underestimate the effects of fluidstarted to underestimate the effects of fluid
overload even in patients undergoing medium-overload even in patients undergoing medium-
risk surgery…risk surgery…
…….IV fluids, the most commonly used drug in the.IV fluids, the most commonly used drug in the
hospital, are a double-edged sword.”hospital, are a double-edged sword.”
Kudsk KA, Ann Surg 2003; 238:649 (editorial)

38.  Blood volume after fasting is normal, and a fluid-Blood volume after fasting is normal, and a fluid-
consuming third space has never been reliablyconsuming third space has never been reliably
shown.shown.
 The endothelial glycocalyx plays a key role and isThe endothelial glycocalyx plays a key role and is
destroyed not only by ischemia and surgery, butdestroyed not only by ischemia and surgery, but
also by acute hypervolemia.also by acute hypervolemia.
 Undifferentiated fluid handling may increase theUndifferentiated fluid handling may increase the
shift toward the interstitial space.shift toward the interstitial space.

39. Avoiding hypervolemia plays a pivotalAvoiding hypervolemia plays a pivotal
role when treating patients bothrole when treating patients both
perioperatively and in the ICU.perioperatively and in the ICU.

40. In patients undergoing elective intra-abdominalIn patients undergoing elective intra-abdominal
surgery, intraoperative use of restrictive fluidsurgery, intraoperative use of restrictive fluid
management may be advantageous because itmanagement may be advantageous because it
reduces postoperative morbidity and shortensreduces postoperative morbidity and shortens
hospital stay.hospital stay.

41. Crit Care Med 1990; 18:728
 Patients who had >20% weight gain hadPatients who had >20% weight gain had
more vasopressor dependence and highermore vasopressor dependence and higher
mortality.mortality.
 The morbidity of fluid overload can beThe morbidity of fluid overload can be
significant and warrants a fresh look at thesignificant and warrants a fresh look at the
methods of intraoperative fluid resuscitation.methods of intraoperative fluid resuscitation.

42.  Both fluid overload and changes in serumBoth fluid overload and changes in serum
creatinine are independent prognosticcreatinine are independent prognostic
markers after cardiac surgery.markers after cardiac surgery.
 Fluid overload was the variable mostFluid overload was the variable most
related length of stay in the ICU.related length of stay in the ICU.

43. National Confidential Enquiry intoNational Confidential Enquiry into
Patient Outcome and Death.Patient Outcome and Death.
1999 Report: Extremes of Age.1999 Report: Extremes of Age.
http://www.ncepod.org.ukhttp://www.ncepod.org.uk
 National Confidential Enquiry into PerioperativeNational Confidential Enquiry into Perioperative
Death have highlightedDeath have highlighted over-hydrationover-hydration as aas a
contributory cause in the genesis of postoperativecontributory cause in the genesis of postoperative
problems leading to death.problems leading to death.
 Carefully considered case histories have led toCarefully considered case histories have led to
specific recommendations regarding careful fluidspecific recommendations regarding careful fluid
management (the implication beingmanagement (the implication being restrictionrestriction) in) in
vulnerable patients and those most at risk, such asvulnerable patients and those most at risk, such as
the elderly.the elderly.

45. A reductions in SV of >10% as measuredA reductions in SV of >10% as measured
by the E-Doppler has a sensitivity of onlyby the E-Doppler has a sensitivity of only
37%37% in identifying fluid responsiveness,in identifying fluid responsiveness,
and therefore may be related to otherand therefore may be related to other
factors aside from preload.factors aside from preload.

46. The 24 studies included 803 patients.The 24 studies included 803 patients.
Overall,Overall, 5656 ± 16% of the patients± 16% of the patients
responded to a fluid challenge.responded to a fluid challenge.

49. Should optimization toShould optimization to
supra-normal values be donesupra-normal values be done
in all patients?in all patients?

50. Prospective trial of supra-normal values of survivors as
therapeutic goals in high-risk surgical patients
Shoemaker WC, et al. Chest 1988; 94: 1176
A randomized clinical trial of the effect of deliberate
perioperative increase of oxygen delivery on mortality
in high-risk surgical patients
Boyd O, Grounds RM, Bennett ED. JAMA 1993;270:2699

52.  Boluses of 250 ml of HES were administered until theBoluses of 250 ml of HES were administered until the
stroke volume failed to further increase by 10%.stroke volume failed to further increase by 10%.
 If at this stage the DOIf at this stage the DO22I was < 600 ml/mI was < 600 ml/m22
then 3then 3
mcg/kg/min dobutamine was started and then increasedmcg/kg/min dobutamine was started and then increased
every 20 minutes in order to reach the described target.every 20 minutes in order to reach the described target.
 The protocol was based on the postoperative GDTThe protocol was based on the postoperative GDT
protocol of St George’s Hospital.protocol of St George’s Hospital.
Cecconi M et alCecconi M et al

53. Cecconi M et alCecconi M et alCecconi M et al
There were an increased number of minorThere were an increased number of minor
complications in the CTRL group.complications in the CTRL group.

54. Cecconi M et alCecconi M et alCecconi M et al

55.  Patients who received catecholamines hadPatients who received catecholamines had
a higher incidence of both major cardiaca higher incidence of both major cardiac
morbidity and all-cause intra-hospitalmorbidity and all-cause intra-hospital
mortality as compared with the control group.mortality as compared with the control group.
 Dobutamine should only be administeredDobutamine should only be administered
when the benefit is judged to outweigh thewhen the benefit is judged to outweigh the
risks.risks.

56. In patients undergoing cardiac surgery inotropeIn patients undergoing cardiac surgery inotrope
exposure appeared to be independentlyexposure appeared to be independently
associated with increased hospital mortalityassociated with increased hospital mortality
and renal dysfunction.and renal dysfunction.

57.  It seems clear that the continued pursuit ofIt seems clear that the continued pursuit of
hemodynamic goals in patients who do nothemodynamic goals in patients who do not
respond is harmful.respond is harmful.
 The adverse effects of fluid and inotropicThe adverse effects of fluid and inotropic
therapy will be most serious for patients withtherapy will be most serious for patients with
significant heart disease.significant heart disease.

58.  It is essential that the presentIt is essential that the present individualizedindividualized
GDT approach includes optimization within theGDT approach includes optimization within the
limit of the individual patient’s cardiac capacity.limit of the individual patient’s cardiac capacity.
 The concept is therefore different from theThe concept is therefore different from the
original Shoemaker concept for optimization,original Shoemaker concept for optimization,
which used predetermined supra-physiologicwhich used predetermined supra-physiologic
values of CI and DOvalues of CI and DO22 as therapeutic goals.as therapeutic goals.

59. Conclusions:Conclusions:
 The reported benefits of perioperative GDT areThe reported benefits of perioperative GDT are
too important to be disregarded although sometoo important to be disregarded although some
conceptual and practical issues still need to beconceptual and practical issues still need to be
resolved.resolved.
 An individualized GDT approach that includesAn individualized GDT approach that includes
optimization of CO seems safer than the quest foroptimization of CO seems safer than the quest for
pre-defined “supra-normal” values.pre-defined “supra-normal” values.
 GDT should not lead to a forgiving attitudeGDT should not lead to a forgiving attitude
towards aggressive and potentially detrimentaltowards aggressive and potentially detrimental
fluid administration.fluid administration.
Thank you for your attention! perelao@shani.netThank you for your attention! perelao@shani.net