Balance fluid therapy.pptx

BALANCE FLUID THERAPY
Concept, Relevance, Benefits
DR ANKIT GAJJAR
MD,IDCCM,IFCCM,EDIC
Consultant Intensivist

Introduction
• Definition
• Different types of fluids
• Advantage and disadvantage of each fluid
• Concept of SID
• Evidence
• Conclusion

Balance Salt Solution
• Balance salt solution is a solution made to a
physiological pH and Isotonic salt
concentration
The ideal balanced solution
Mimic the electrolytes as in
plasma
Isotonic:280-300 mOsmol /kg H2O
Contain metabolizable anions
Physiological acid-base balance

Evolution of Infusion solutions
• 1832-Robert Lewins described the effect of the intravenous
administration of an alkalinized salt solution in treating patients
during cholera pandemic
• 1885-Physiologic salt solution was developed by Sidney Ringer for
rehydration of children with gastroenteritis's known as Ringers
solution
• 1950- Alexis Hartmann modified the Ringers solution which is
known as Hartmann solution or Ringers Lactate
• 2005 onwards- Modern balanced solutions such as Sterofundin ISO,
Plasmalyte A entered the market

Fluid Prescription
• It should be like a prescribing drug….
• Type
• Dose
• Indication
• Contraindication
• Toxicity
• Cost

Fluid Prescription
• Identify a fluid that most likely to be benefit
• Consider sodium, chloride, acid base status
and osmolarity

Fluid management boils down to…
• How to use fluids?
• How much fluid to be used?
• Which fluid to use?

Different types of
crystalloid fluids

Electrolytes Plasma Isotonic
Saline
Ringer’s
lactate
Plasmalyt
e
Sterofundin Kabilyte
Sodium 140 154 130 140 140 140
Potassium 5 0 5 5 4 5
Chloride 100 154 111 98 127 98
Calcium 2.2 0 2 0 2.5 0
Magnesium 1 0 0 1.5 1 1.5
Bicarbonate 24 0 0 0 0 0
Lactate 1 0 29 0 0 0
Acetate 0 0 0 27 24 27
Gluconate 0 0 0 23 0 23
Maleate 0 0 0 0 5 0
Osmolarity 280-300 308 273 294 297 294
SID in vivo 24-28 0 29 50 29 32

Limitations of unbalanced solutions
1. Do not contain all electrolytes essential for proper
body functioning.
2. Concentration of electrolytes is not plasma like.
3. Tonicity of fluids is not isotonic (i.e. Plasma like)
4. Do not contain buffered base.

Strong ion difference
• Strong ions are those ion that dissociate totally at the pH of
interest in a particular solution. In blood at pH 7.4:
– Strong cations are: Na+, K+, Ca2+, Mg2+
– Strong anions are: Cl- and SO42-
• Strong Ion Difference (SID) is the difference between the
concentrations of strong cations and strong anions.
• SID = (Na+ + K+ + Ca2+ + Mg2+) – (Cl- – other strong anions)
• Abbreviated SID = (Na + K+) – (Cl-)

• Increased SID leads to alkalosis (increase in unmeasured
anions)
• Decreased SID acidosis
• The SID can be changed by two methods:
Strong Ion changes
- Decreased Na+ : decreased SID and acidosis
- Increased Na+ : increased SID and alkalosis
- Increased Cl- : decreased SID and acidosis (NAGMA)
- Increased in organic acids (lactate, formate, ketoacids):
decreased SID and acidosis (HAGMA))

• Normal SID : 24 TO 28
• If fluid SID / iv fluid causes SID < 24 – causes
acidosis
• If fluid SID / iv fluid causes SID > 28 – causes
alkalosis
• So, ideal fluid SID should be between 24 – 28
• 0.9% NS SID – 0
• BSS contains buffered anions which will convert
to HCO3
- , so difficult to calculate in vitro SID but
in vivo SID is > 28 by experiments

0.9% Normal Saline
• 0.9% NS is most commonly used IV fluids
• Chloride is 1.5 times higher that of Plasma and
hyperchloremic acidosis as explained by Stewart
hypothesis, plasma chloride concentration
decreases SID and lead to acidosis.
• SID is 0
• Canine experiments on resuscitation from septic
shock have shown that 0.9% Saline accounted for
more than one third of the acidosis observed.

0.9% Normal Saline
• Increase in Cl- will replace by HCO3
- and causes
Hyperchloremic acidosis or dilutional acidosis
• Hyperchloremic acidosis is maximum level in few
hours and its effect is temporary for 1-2 days.
• Balanced crystalloids may therefore be safer than
0.9% Saline in patients with existing renal disease
and those at risk of developing renal dysfunction.

Rehm and Finsterer et al
• Effect of isotonic saline in intraabdominal
surgery
• Infusion of 0.9% NS, 40 ml/kg/hr, 6 litres in 2
hours
• Decrease in SID from 40 to 31 and increase in
chloride from 105 to 115 and decrease in base
excess to 7.

Problem: Chloride has multiple renal effects

Adverse effects
• Hyperchloremia itself can cause worsening of
renal function and metabolic acidosis
• Hyperchloremic Acidosis can further
- Coagulopathy
- Cardiac depression
- Reduce Nor-adrenaline release
- Reduce GI motility

Advantage
• Cheapest fluid
• Suitable neurological condition
• Choice of fluid in metabolic alkalosis

Balance salt solution
• Ringer’s Lactate
• Plasmalyte
• Sterofundin
• Kabilyte

Ringer’s lactate
• Cheaper than other BSS
• Contain lactate as a buffer
• In vivo SID of RL is 29
• Hypotonic than plasma

Ringer’s lactate
Disadvantage
• Can’t be use in liver failure
• False positive result of hyperlactatemia in shock
• Excessive fluid administration can cause
metabolic alkalosis
• Can’t be use in Neuro patients due to
hypotonicity
• Altered glucose metabolism
• Can not be given with blood products
• Chances of extravascular accumulation is high
due to hypotonicity

Plasmalyte /Sterofundin
• SID is much higher
• Can be used in Neuro patients
• Contains magnesium
• SID??
• Sterofundin cannot be used with blood
products

Plasmalyte /Sterofundin
• Advantage of Acetate as a buffer
• Glucose metabolism Is maintain
• Acetate metabolise in extrahepatic tissue like
muscles so safe in shock or liver failure
• Body can metabolize 300 mmol / hr of Acetate
(while lactate only 100 mmo/hr)

Plasmalyte/Sterofundin
• Costly
• Costly
• Costly
• Costly …………….
• Risk of Alkalosis
• Acetone used as a buffer can be cardiotoxic
• Drug dilutions compatibilities not clear

Methods
• Single centre prospective “before and after”
study
– 2 periods of 6 months each
• Tertiary hospital in Australia
• “Standard Care” for first period then a
“Chloride Restrictive” Strategy.
• Outcomes;
– AKI according to RIFLE
– RRT, los, mortality

Yunos JAMA 2012; 308(15): 1566-72
Impact of Chloride liberal fluids in
critically ill adults
Chloride liberal
fluids:
Sodium Chloride 0.9% /
Al
Chloride restrictive
fluids:
Hartmann’s Solution /
Plasm
An ICU chloride restrictive strategy is
associated with significantly less AKI and
use of RRT

SPLIT TRIAL
• Compared normal saline vs plasmalyte A
• No difference in risk of AKI and need of RRT
• Median amount of fluid received was only
2000 ml in first 24 hours
• Did not include the high risk patients like
trauma, shock

Does hypercholerima affects
mortality?
•
• NO EVIDENCE

Conclusion
• No fluid is ideal
• It should be used on individual basis
• In Class 1-2, young, low risk patients, doesn’t
matter whatever we give (0.9% NS better
considering it’s cost)
• Critically ill patients like AKI, high risk of AKI,
Shock, elderly, acidosis patients better to go
for BSS

Conclusion
• Among BSS, RL cannot be used in neurological
condition and in liver failure patients,
otherwise it’s a choice of BSS considering it’s
cost
• Among BSS, Plasmalyte and sterofundin is
almost similar except sterofundin contains
Calcium
• Always look for hyperkalemia and metabolic
alkalosis in excessive administration of BSS

Conclusion
• Neurological condition – 0.9 % NS is always
preferred (RL should not be used)
• DKA – BSS can directly correct acidosis
• Acute GE – 0.9% NS is better to correct fluid
and chloride loss
• Shock – 0.9% NS can be used judiciously
Monitor Cl- level and SID
Switch over to BSS

Audience
• Ringer’s lactate cannot be used in Shock or
patient’s with risk of Hyperkalemia????
• 0.45% NS cannot cause hyperchloremic
acidosis????

4
Evolution of Crystalloids
Salin
e
Ringer
‘s
Lactat
e
Ringe
r‘s
Sterofun
din ISO

Balanced crystalloid solution
Zander (2006): EJHPPractice. 12(1):1-4.
Lobo. D.N et al. Basic Concept of Fluid and Electrolyte Therapy 2013
Graphic adapted from:"1901 Composition of Blood" by OpenStax College - Anatomy & Physiology,
Connexions Web site. http://cnx.org/content/col11496/1.6/, Jun 19, 2013.. Licensed under CC BY 3.0 via
Wikimedia Commons -
The ideal balanced solution
mimic the electrolytes as in plasma
isotonic:280-300 mOsmol /kg H2O
contain metabolizable anions
physiological acid-base balance

Limitations of Unbalanced Solutions

Limitations of unbalanced solutions
1.Do not contain all electrolytes essential for proper
body functioning.
2.Concentration of electrolytes is not plasma like.
3.Tonicity of fluids is not isotonic (i.e. Plasma like)
4.Do not contain buffered base.

Consequences of unbalanced
solutions
1. Hyperchloremic Acidosis- Due to high concentration of Chloride in
the solution.
2. Hypernatremia– Due to high concentration of Sodium in the
solution.
3. Dilutional Acidosis- As the buffered base is missing.
4. Implication on Acid-base balance.
5. Influences coagulation profile.
6. Hypotonic solutions- Swelling of cells which increases the intra-
cranial pressure and brain damage can result.
7. Hypertonic solutions- Shrinking of cells.
• Note: Hypotonic & Hypertonic solutions also have there
advantages in selective clinical conditions.

Explanation by dilutional
theory:
Decreased buffer capacity of
plasma
Arterial pH value < 7.35 means
acidosis
• Administration of an
unbalanced solution reduces
the concentration of
bicarbonate [HCO3
–
] in plasma

0.9% Normal Saline
• Chloride is 1.5 times higher that of Plasma and
hyperchloremic acidosis as explained by Stewart
hypothesis, plasma chloride concentration
decreases SID and lead to acidosis.
• Canine experiments on resuscitation from septic
shock have shown that 0.9% Saline accounted for
more than one third of the acidosis observed.

0.9% Normal Saline
• Hyperchloremic acidosis associated with a 2 L
infusion of 0.9% Saline has detrimental effect on
renal artery blood flow velocity and renal cortical
tissue perfusion.
• Balanced crystalloids may therefore be safer than
0.9% Saline in patients with existing renal disease
and those at risk of developing renal dysfunction.

Na K Cl Ca++
HCO3-
Equiv
Osmolalit
y
pH
mmol/l mmol/l mmol/l mmol/l mmol/l
mmosmol
/kg
Plasma
135-
145 3.6-5.1 98-106 2.2-2.5 21-30 295-300
7.35-
7.45
0.9% Saline 154 0 154 0 0 308 4.5-7.0
Ringer
Lactate 130 4 109 2 29 273 5.0-7.0
Plasmalyte
A 140 5 98 0 27 295 6.5-8
Sterofundin 145 4 127 2.5 34 290 5.1-5.9
Chloride content of common IV
fluids
0.9% Saline has high chloride content

5
8
Composition of electrolyte solutions

Problem: Chloride has multiple renal
effects
Lobo et al. Kidney International advance online publication, 9 April 2014;
Chloride has multiple renal effects
that are independent of acidosis

0.9%
Saline
Glycoclay
x damage
More
third
spacing
GI
edema,
Ileus
Increased
intra-
operative
blood
loss
More
mortalit
y
Resourc
e
utilizatio
n
AKI &
RRT
HCMA
More post-op
complications
GIT
Hematologi
cal
Metab
olic
Body
water
Clinical
outcom
es
Renal
Adverse effects of I.V
administration of 0.9% Saline
Lobo et al. Kidney International advance
online publication, 9 April 2014;
doi:10.1038/ki.2014.105

• Retrospective cohort study
• 2003-2008
• 3 tertiary hospitals in Toronto

Impact of hyperchloremia in Peri-
operative setting
Matched Sample
McCluskey et al. Anesth Analg. Published online before print
Probability of Dying and Serum Chloride Level
Hyperchloremia After Noncardiac Surgery Is
Independently Associated with Increased
Mortality

• Chloride Loads and Mortality in
SIRS
Serum Chloride
and in-hospital
mortality
Lowest mortality:
(3.4%) if chloride
in normal range
Highest mortality:
(31.1%) if chloride
130-140mmol/L
More chloride is associated with
higher mortality in SIRS

Yunos et al. ICM 2015;41:257-269
• Study extended for 12 more months
• Control period 1 yr/ Intervention period 1 yr
• Control (n=1476)/ Intervention (n= 1518)
• AKI (stage 2 & 3 of KDIGO) 20.5% vs 15.7%
(p<0.001)
• RRT 9.8% vs 6.8% (p=0.003)
Chloride liberal fluid remained associated
with greater risk of AKI

Balanced Crystalloid Solutions

Advantages of Balanced Crystalloids-In
‘Surgery’
• Lower need of blood products
• Lower incidence of renal replacement therapy
• Lower incidence of postoperative infections

Advantages of Balanced Crystalloids-
In ‘Kidney Transplantation’
• Reduced incidences of acidosis and
Hyperkalaemia
• No difference in postoperative creatinine
values or urine output

Advantages of Balanced Crystalloids-
In ‘Critical Care Medicine’
• Reduced incidence of severe acidosis
• Better kidney because of chloride restriction
• Less renal injury, failure and fewer episodes of
renal replacement therapy

Advantages of Balanced Crystalloids-In
‘Diabetic Ketoacidosis and Choleriform
Diarrhoea
• Faster resolution of acidosis

Guidelines: Which fluid to
use?
• When crystalloid resuscitation or
replacement is indicated, balanced
salt solutions should replace
Sodium Chloride 0.9%
GIFTASUP
(Surgical
guideline)
• Specific fluids may be superior in
certain settings: e.g balanced fluids
when there is a risk of renal injury
• “Presently balanced salt solutions
may be a reasonable default
choice”
ADQI XII
Consensus
British Journal of Anaesthesia 113 (5): 772–83 (2014)
Powell-Tuck J, et al. British Consensus Guidelines on Intravenous Fluid Therapy for Adult Surgical
Patients – GIFTASUP. 2011. Available at: http://www.bapen.org.uk/pdfs/bapen_pubs/giftasup.pdf
(Accessed September 2012).

Why isotonic solutions?
Arieff A et al.: Pediatric Anaesthesia 1998; 8: 1-4
Ayus J et al.: Nerotraumatology 1996; 46: 323-328
• Hypotonic solutions: Osmolality< 280 mOsmol/kg
H2O,
• e.g. Ringer’s Lactate solution, osmolality 256
mOsmol/kg H2O
• Sodium (besides chloride) contributes most to the
osmolarity of a fluid
• Hyponatremia: sodium too low in the blood <=
hypotonic solutions

Clinical consequences of
hypotonic fluids
Hennes H-J: Neuroanästhesie (Jantzen J-P, Löffler W Hrsg), Thieme,
Stuttgart 2000

Reduced osmolarity correlates
increased intracranial pressure
(ICP)
• ICP = Intracranial pressure

Why should an IV solution be
‘lactate-free’
 Normal plasma lactate concentration: 1.5 mmol/L
 Lactate levels are used to monitor the status of critically ill
patients
• increased lactate => tissue hypoxia => increase of mortality
Zander R. 2009 Fluid Management. Second expanded edition. Bilbiomed.
Garcia-Alvarez et al. Critical Care 2014. Sepsis associated hyperlactaemia.
Wong HR 2014 Crit. Care Med. A multibiomarker-based outcome risk stratification model for
adult septic shock

Disorder of acid-base
balance
• Metabolic acidosis
•Lactic acidosis
•Ketoacidosis due to diabetes
•Dilutional /hyperchloremic acidosis
• Respiratory acidosis
•respiratory failure,insufficient ventilation => CO2
accumulate
< 6.8 < 7.37 7.40 > 7.43 > 7.7
death acidosis normal
level
alkalosis death
Blood pH
values

Why is metabolic acidosis a
problem?
Metabolic acidosis interferes with various organ functions
One Clinical Example
•the “death triad” in severe trauma
patient
Kellum. Disorders of acid-base balance. Crit. Care Med. 2007
Mitra B, Tullio F, Cameron PA, Fitzgerald M. Trauma patients with the ‘triad of death’ Emerg
Med J. 2012
"Trauma triad of death" by en:User:Cburnett – Own Work
http://commons.wikimedia.org/wiki/File:Trauma_triad_of_death.svg#/media/File:Trauma_tria

• Impaired cardiac
function
• Reduced cardiac
output
• Malperfusion of kidneys and
gut
• Inactivation of calcium channels in
cell membranes
• Inhibition of noradrenalin
release
Mythen M. Euroanesthesia Vienna 28th-31st May 2005
Possible effects of
acidosis

Is acidosis clinically relevant?
• Severe acidosis may be life-
threatening
•Slight acidosis may not be relevant
in patients undergoing smaller
elective surgery

Bicarbonate
• Normal plasma concentration: 24 mmol/L
• Function:
 Most important buffer system in blood*
• Concentration in balanced solutions:
 Bicarbonate is not stable in electrolyte solutions
 Use of metabolizable anions in adequate
concentrations
* Other buffer substances are proteins, phosphate, and haemoglobin.

1) Spahn et al. (2005)
2) Fukuda T: J Toxicol Sci 2006
By Crystal (Crystl) from Bloomington, USA (Flickr) [CC BY 2.0 (http://creativecommons.org/licenses/by/2.0)], via
Wikimedia Commons
Remarks of Calcium
 Calcium, also
called
“coagulation
factor IV”, is
essential in the
blood coagulation
cascade1
Blood coagulation cascade
 A drop in serum calcium level
will lead to a significantly
prolonged whole blood clotting
time2

Sterofundin ISO in patients with hemorragic shock
88
Stukanov et al., Anesteziol Reanimatol. 2011; (2): 27-30.
 60 patients with
hemorragic shock
 Group 1 (29 patients):
- Volume therapy
during first 24 hr:
3100 ml +/-200 ml
(normal
Saline/Gelofusine 1: 2)
 Group 2 (31 patients):
- Volume therapy
during first 24 hr:
3100 ml +/-200 ml
Serum chloride concentration [mmol/l]
Sterofunsin ISO vs Normal Saline
Sterofundin ISO doesn’t cause hyperchloremia

Sterofundin ISO in patients with traumtic shock
Clinical Studies
89
Girsh et al. Anesthesiology and critical care medicine 2011, 41-46
 105 patients with 2nd and 3rd degree traumatic shock
 Group 1 (66 paitents, 2nd degree traumatic shock) :
- Group 1.1: normal Saline/6% saline based HES 1:
2
- Group 1.2: normal Saline/Gelofusine 1: 2
- Group 1.3: Sterofundin ISO/Gelofusine 1: 2
 Group 2 (39 patients, 3rd degree traumatic shock):
- Group 1.1: normal Saline/6% saline based HES 1:
1
- Group 1.2: normal Saline/Gelofusine 1: 3
- Group 1.3: Sterofundin ISO/Gelofusine 1: 3
Sterofundin ISO doesn’t
cause hyperchloremia

Sterofundin ISO in patients with traumtic shock
Clinical Studies
90
Girsh et al. Anesthesiology and critical care medicine 2011, 41-46
Sterofundin ISO doesn’t cause
hyperchloremia

Sterofundin ISO in Major
abdominal surgery
• Effect of two different strategies of fluid administration on
inflammatory mediators, plasma electrolytes and acid-base
disorders in patients undergoing major abdominal surgery; a
randomized double blind study. Published in Journal of
inflammation 2013.
•
• Objective of this double blind randomized trial was to study the
impact of balanced vs non-balanced solutions (colloids and
Crystalloids) on inflammatory cascade triggered by surgical
procedure, the plasmatic electrolyte concentration, the acid-base
equilibrium and the renal function. 40 patients undergoing major
abdominal surgery (bowel cancer) were allocated in two groups that
is balanced solution (colloids and crystalloids) and unbalanced
solution group.
• Sterofundin ISO and Tetraspan was used in balanced solution group
whereas, venofundin and 0.9% NS was used in unbalanced solution
group.
• This study concludes that the use of balanced solution was
responsible for less alteration of plasmatic electrolytes, acid-base
equilibrium, kidney function and it might be associated with an early
anti-inflammatory mechanism triggering.
•

Sterofundin ISO in Major abdominal
surgery
• Metabolic profile in right lobe living donor
hepatectomy; comparison of lactated
Ringers solution and normal saline vs
acetate based balanced solution, a pilot
study.
•
• Published in Indian Journal of Anesthesia in
2016, aim of this prospective, observational,
randomized study was to compare the
metabolic effect of lactated vs lactate free
solution in living donor hepactectomy. The
primary outcome measure was lactate level
and secondary outcome were base excess,
bicarbonate, glucose and chloride intra and
post-operatively.
• This study concludes that acetated
fluids(Sterofundin ISO) were associated with
higher levels of bicarbonate, lesser base
deficit, glucose and chloride.

Sterofundin ISO in Neuro
surgery
• Balanced versus chloride-rich solutions for fluid
resuscitation in brain injured patients; a
randomized, double-blind pilot study. Published in
Critical Care 2013
•
• This study sought to investigate whether the use of
balanced solutions reduces the incidence of
hyperchloremic acidosis without increasing the risk
for intracranial hypertension in patient with severe
brain injury. 42 patients were divided equally in
balanced and non balanced solution groups. In
balanced group the products used were Sterofundin
ISO and Tetraspan and in unbalanced group 0.9% NS
and Venofundin were used.
• This study concludes that the use of balanced
solutions reduces the incidence of hyperchloremic
acidosis in brain injured patients compared with
saline solutions. Balanced solutions decreases
natraemia and blood osmolarity in severe brain injury.

Sterofundin ISO in Neuro surgery
• Normal saline vs balanced-salt solution as intravenous fluid therapy
during neurosurgery; effect on acid-base balance and electrolytes.
Published in journal of Neurosurgical Science 2017
• This prospective randomized controlled study was carried out to
compare the changes in acid-base balance and serum electrolytes with
the use of intravenous balanced and non-balanced solutions
intraoperatively during elective neurosurgery. Thirty patients
undergoing Craniotomy were randomly allocated in two groups of 15
patients each. The non balanced group received 0.9% normal saline
while the balanced group received Sterofundin ISO as the intraoperative
fluid for maintenance. Biochemical indices for acid-base balance and
serum electrolytes were analyzed periodically.
•
• This study concludes that a balanced solution (Sterofundin ISO) provides
significantly better control over acid-base balance, sodium and chloride
levels when used as intraoperative fluid maintenance and replacement
during elective neurosurgery.

Sterofundin ISO in
Pediatrics
• A novel balanced isotonic sodium solution versus normal saline during major surgery in
children upto 36 months: a multicenter RCT. Published in Pediatric anesthesia_2014
•
• Objective of this randomized, controlled trial was to compare the changes in chloride plasma
concentration using two intra operative solutions i.e Sterofundin ISO and Normal Saline in
children undergoing major surgery. Secondary objective were to compare changes in other
electrolytes, renal function etc. About 240 patients were included in 2 centers randomly into
2 groups i.e Sterofundin ISO and Normal saline group.
• This study concludes that Sterofundin ISO is safer then Normal Saline in protecting young
children’s undergoing major surgery against the rise in plasma chlorides and subsequent
metabolic acidosis. Also Sterofundin ISO showed a better profile in protecting against
metabolic acidosis, hyperchloremia and hypomagnesaemia.
•

Sterofundin ISO in Pediatrics
• Perioperative intravenous fluid therapy in children; guidelines from the
association of the scientific medical societies in Germany. Published in Pediatric
anesthesia 2015
• This consensus based S1 Guidelines for perioperative infusion therapy in children
is focused on safety and efficacy. The objective is to maintain or reestablish the
child’s normal physiological state that is normovolemia, normal tissue perfusion,
normal metabolic function, normal acid-base electrolyte status.
•
• Consensus-based recommendations-A balanced isotonic electrolyte solution
should be used for fluid therapy (target normal ECFV). Preoperative deficits
should whenever possible already be replaced before anesthesia is induced. In
patients with circulatory instability, balanced isotonic electrolyte solutions
without added glucose can be given as repeat-dose infusions of 10-20 ml.kg -1
until the desired effect is achieved.

Comparative studies of Sterofundin
ISO vs Ringers lactate and 0.9% NS
• Comparative study of Sterofundin ISO and
ringers lactate based infusion protocol in
Scoliosis correction surgery. Anesthesia essays
and research 2016
•
• This study was carried out to study the influence of
Sterofundin ISO and Ringers lactate on acid-base
changes, hemodynamics, and readiness for
extubating during scoliosis (abnormal lateral
curvature of spine) surgery. 30 consecutive
children’s posted for scoliosis surgery are randomly
divided into Sterofundin (n-15) and RL (n-15)
group.
•
• This study concludes that Sterofundin ISO infused
patients had non remarkable changes in acid-base
physiology in scoliosis surgery. Significantly higher
lactate levels were seen in RL group. The strong ion
difference decreased in both groups, but it
normalized earlier in Sterofundin ISO group.

Comparative studies of
Sterofundin ISO vs Ringers
lactate and 0.9% NS
• Cochrane Review on ‘Perioperative buffered vs non-buffered fluid
administration for surgery in adults’
• We included 14 publications in this Cochrane review, reporting data from 13 trials
with a total of 706 participants of whom 368 received buffered fluids and 338
received non-buffered fluids.
• The patients who received buffered fluids had an acid-base balance that was
more normal than for those who received non-buffered fluids, and the need for
transfusion of some blood products was reduced. Overall, buffered fluids are a
safe and effective alternative to non-buffered fluids when given into the veins of
patients undergoing surgery.
• Buffered fluids are appropriate to use as a fluid replacement during surgery and
should be considered for any patient who has, or is at risk of metabolic
derangement.

Role of Endothelial Glycocalyx Layer in
the use of Resuscitation Fluids

Increased capillary permeability
•SIRS (Systemic Inflammatory Response Syndrome) is the name
for a common development of the clinical picture in patients
with severe inflammatory response, irrespective of its origin
(e.g. after major trauma, in acute pancreatitis, severe burns,
sepsis, etc.).
•Consequence of SIRS are organ failures, a breakdown of the
immune response, and “capillary leak” with a potential
breakdown of the circulation.
•“Capillary leak” is a phenomenon related to the inflammatory
response, where the diameter of the pores of the capillaries
widens, leading to a reduced ability to retain macromolecules.
•The “capillary leak” reduces the COP in plasma.

Capillary “Leak”
Water,
electrolytes
*
Water,
electrolyt
es*
* depends
on the
capillary
types

Objectives of septic shock treatment
Diagnosis
– Shock due to vessel dilatation as consequence of sepsis
– Septic shock
What to do?
– Utilize central venous access
– Administer intravenous fluid as electrolyte solution or colloid
Why?
– Stabilize cardiovascular function
– Fill up the circulatory volume
– Maintain organ perfusion to prevent MOF (multiple organ failure)

Studies against the use of HES
6S
Ches
t

Developments on HES
Octobe
r 2013

Latest development on HES
HES may be withdrawn from
European market..!!!!
Octob
er
2017

Change in Package leaflet
post PRAC
recommendations

Change in Dosage and
Paediatric use

Is there a time tested
Alternative?

Alternatives of HES
 Alternative: Albumin, Gelatin, (Dextrans) and Crystalloids
- Limitations of Albumin
Too Expensive!!, Availability?, Safety?
- Limitations of Crystalloids
Efficacy, Safety
- Gelatins
Documentation of the use of Gelatin in general and
Gelofusine in
particular in ICU and Sepsis
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Gelatins are the time tested, safe,
effective alternative…
Safety profile of Gelofusine/Gelaspan
Impact on kidney function
• Schortgen et al is a randomized,
multicenter trial published in Lancet
in 2001. Aim of the study was to
study the effect of Hydroxyethyl
starch (HES) and Gelatins on renal
function in severe sepsis.
• This study found that 6% HES was
an independent risk factor for Acute
Renal Failure (ARF). The frequency
of ARF and Oliguria, as well as
peak serum creatinine were
significantly lower in Gelatin group.
Schortgen et al 2001

Safety profile of
Gelofusine/Gelaspan
Impact on blood coagulation
Niemi et al 2005, Fries et al 2002
• Neimi et al studied the impact of various colloids like HES, Gelatins
and Albumin using thromboelastometry coagulation analysis. This
study was published in Anesthesiology journal of Scandinevia in
2005. It concludes that among the artificial colloids Gelofusine shows
lowest impact on coagulation system, comparable to that of Albumin.
• Fries et al published in critical care and trauma journal in 2002
studied the effect of the combined administration of colloids and
lactated ringers solution on the coagulation system. Colloids used
were Gelatins and HES. This study concludes that the effect of
(Glatns)Gelofusine on coagulation was less then HES (Voluven)

Safety profile of Gelofusine/Gelaspan
Reduced chloride content – no hyperchloremic acidosis:
• Physiological chloride concentration of plasma is 103 mmol/l.
• Chloride concentration of normal saline or saline-based colloids is 154
mmol/l.
• The chloride concentration of Gelofusine is 120 mmol/l.
• The chloride concentration of Gelaspan is 103 mmol/l exactly matching
plasma.
• The reduced chloride content prevents hyperchloremia and thus
development of
hyperchloremic acidosis.
“A significant and sustained hyperchloraemia was noted after Voluven
but not Gelofusine, …… suggesting a tendency of Voluven to produce a
hyperchloraemic acidosis.” Award et al 2012
“Consequently, venous bicarbonate decreased after Voluven and 0.9%
saline
but increased after Gelofusine, showing that, unlike the other solutions,
Gelofusine
in the volume used produced no hyperchloremic acidosis.” Lobo et al 2012

Efficacy: Sufficient and reliable volume effect of Gelofusine
Lobo et al, published in Critical care
medicine 2010 studied the effect of
volume loading with 0.9% Saline,
4% Succinylated gelatins
(Gelofusine) and 6% HES (Voluven)
on blood volume. It was a
randomized, threeway crossover
study.
This study concluded that the effect
of Gelofusine and Voluven were
similar despite the 100 kD difference
in weight-average molecular weight.
Lobo et al 2010

Efficacy: Sufficient and reliable volume effect of Gelofusine
Awad et al is a randomized, double
blind study published in British Journal
of Anesthesia in 2012 studied the
effect of intraoperative infusion of 4%
Succinylated Gelatins (Gelofusine)
and 6% Hydroxyethyl starch (Voluven)
on blood volume.
This study concluded that the blood
volume expanding effect of two
colloids were not significantly
different, despite the increase in
urinary ACR and the 100 kD
difference in molecular weight.
Awad et al
2012

Improvement of microcirculation
The hemodynamic changes of Gelofusine were similar to 6% HES.
Improvement of gastric mucosal acidosis under infusion of Gelofusine
shows a better microcirculation, whereas gastric mucosal acidosis
deteriorated in the HES-group.
Asfar et al.
2000
Benefits of Gelofusine/Gelaspan in Sepsis and
Critically ill patients
• In patients with sepsis or at risk of
developing sepsis, it is important to
avoid disturbances of
microcirculation of the splanchnic
area. Restricted microcirculation will
cause hypoxia and can develop
acidosis.
• The influence of Gelofusine® on
macro-
circulation and microcirculation of the
splanchnic region was investigated
in septic patients:

Benefits of Gelofusine/Gelaspan in Sepsis and Critically ill
patients
• Superior transport capacity of CO2
 In extreme hemodilution, gelatin is superior to
dextrane and HES with respect
• to transport capacity of carbon-dioxide.
 This is due to the inherent buffer capacity of the NH2-
groups in modified fluid gelatin
• so that gelatin solutions contribute to reduction of
acidosis
• and thus to maintenance of systemic vascular
resistance (SVR) ,
• This is of importance especially in critically ill and
septic patients.

Gelofusine/Gelaspan-Summary
– Gelofusine/Gelaspan
 is documented to be safely used in ICU and Sepsis
 has the same efficacy as modern HES preparations
 improves microcirculation
 has the lowest impact on blood coagulation and kidney function
 provides an erythrocyte-protective effect comparable to albumin
 has a reduced chloride content preventing hyperchloremic acidosis

Gelaspan
• Gelaspan 4% (Composition)
• 1000 ml solution contains:
• Succinylated gelatine 40.00 g (= modified
fluid gelatine)
• Molecular weight, weight average: 26.500
Dalton
•
• Electrolyte concentrations
• Sodium 151 mmol/l
• Chloride 103 mmol/l
• Potassium 4 mmol/l
• Calcium 1 mmol/l
• Magnesium 1 mmol/l
• Acetate 24 mmol/l
• Theoretical osmolarity: 284 mOsm/I
• pH: 7.4+/– 0.3

Gelaspan and Sterofundin ISO…Time tested, safe
and effective

Colloid related features and
benefits
 Improved safety profile
– Fast and complete clearance
– Low incidence of anaphylaxis
– Least influence on blood
coagulation
 Rapid and reliable hemodynamic
stabilization
 Suitable for children
 No dosage limit
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Carrier solution related
features and benefits
Plasma adapted carrier solution:
 No negative influence on
coagulation
 No development of hyper-
chloremic acidosis.
 No disturbance of the acid-base
balance.
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