Importance, Pros & Cons of Balanced Fluid therapy in various specialties of healthcare

1. Balanced Fluid Therapy- Strike the Right
Balance
Dr BODHISATWA CHOUDHURI
MBBS, MD(Med), MRCEM(UK), MRCP Acute Medicine,
Dip Rheumatology (UK), FCCS, CCEBDM
Consultant, Emergency & Critical Care, ILS Hospital, Howrah

2. Pharmacological Principles
 Fluids are drugs
 Must be prescribed for a specific purpose
 Treatment objective is critical
 Choice of fluid must be related to physiological principles

3. Definition
Fluid replacement
 Replacement of fluid (intravascular, interstitial)
 Use of a Chloride-reduced, Acetate-buffered crystalloidal
solution
Volume replacement
 Replacement of intravascular volume
 Use of an oncotically effective substance
 As colloidal component use of a modern 3rd generation starch

4. ERA of Balanced Fluid Therapy

5. Saline-based resuscitation strategies were first proposed in 1831 during the Cholera
Epidemic by Dr. O’Shaughnessy which he published in the Lancet
The theories of Dr. O’Shaughnessy were put into practice by Dr. Thomas Latta.
https://emcrit.org/emnerd/case-balanced-solution/. Accessed on 24/08/2017

6. Discovery of 0.9% Saline
• Hartog Jacob Hamburger through a
series of in-vitro experiments
concluded that the blood of majority
of warm-blooded animals including
man was isotonic with a NaCl solution
of 0.9%
• Scientific evidence supporting the
use of 0.9% saline in clinical
practice seems to be based solely
on this in vitro study.
• It is a mystery how it came into
general use as an intravenous fluid in-
vivo
Awad et al, Clinical Nutrition 2008 ;27 : 179-188
https://en.wikipedia.org/wiki/Hartog_Jacob_H
amburger#/media/File:Hartog_Jacob_Hambur
ger_(1908).jpg. Accessed on 15/05/2018

7. Fluid Resuscitation of Shock
Which fluid to Use??
http://www.nejm.org/doi/story/10.1056/feature.2013.09.11.14. Accessed on 24/08/2017

8. 0.9% Normal Saline
Is
Abnormal

9. Adapted from Correa et al. Rev Bras Ter Intensiva. 2016;28(4):463-471
What’s Wrong with
0.9% Saline?
• Potentially Hypertonic
• Other electrolytes absent
• Supra-physiological
chloride levels which can
lead to hyperchloraemic
metabolic acidosis
Human Plasma 0.9% Saline
pH 7.35-7.45 5.5
Osmolarity
(mOsm/L)
291 308
Sodium
(mmol/L)
135-145 154
Potassium
(mmol/L)
4.5-5.5
Calcium
(mmol/L)
2.2-2.6
Magnesium
(mmol/L)
0.8-1.0
Chloride
(mmol/L)
94-111 154
Bicarbonate
(mmol/L)
23-27
Lactate
(mmol/L)
1.0-2.0

10. Hyperchloremic Acidosis
• First described by Hartmann 1935
• Increased Cl- load increases dissociation of
water into H+ and OH-
• Acidosis is the result of an increase in [H+]
• Does this matter?

11. Stewart approach of acid-base balance

13. BSS
John A. Kellum Nature Reviews Nephrology, 2018, Volume 14, Number 6, Page 358

14. Lobo D.N., Awad S. (2014) Kidney International, 86 (6) , pp. 1096-1105

15. Li H et al. Journal of Zhejiang University Science B. 2016;17(3):181-187. doi:10.1631/jzus.B1500201.
Effect of Large Volume Saline on Kidney
• Decrease GFR
• Decrease RBF
• Decrease Urine and
Sodium Output

16. Ideal Crystalloid Solution?
Electrolytes
Mmol/l Plasma 0.9% NS
Ringer
Acetate
Ringer
Lactate
Calcium Free
Balanced
Crystalloid
Na 135-145 154 131 130 140
Cl 94-111 154 110 109 98
K 4.5-5.5 4 4 5
Acetate - 30 0 27
Lactate 0.5-2 - 29 0
Gluconate - - 0 23
Malate - - 0 0
Calcium 2.2-2.6 2 1.5 0
Magnesium 0.8-1.0 1 0 1.5
pH 7.35-7.45 5.5 6.7 6.5 7.4
Osmolarity
(mOsm/l) 275-295 308 270 273 294
Corrêa et al. Rev Bras Ter Intensiva. 2016;28(4):463-471

17. Pfortmueller, C.A. et al Wien Klin Wochenschr. 2018 Mar 2. doi: 10.1007/s00508-018-1327-y.

18. Advantages of Lactate Free Balanced Crystalloid
• Isotonic
• Acetate as a source of bicarbonate – metabolized extra-
hepatically
• Allows use of Lactate as hypoxia marker in critically ill patients
• Unlike lactate , no effect on glucose metabolism
• Compatible with blood and blood products

19. Disadvantages of RL
• Neither isotonic nor balanced
• With an osmolarity of 273 mOsmol/L and measured
osmolality of 254 mOsm/kg, infused RL solution leads to
decrease in plasma osmolality
• Potential increase in brain water and effects on diuresis.
• In liver disease, severe hypoxia and shock RL infusion can
lead to lactate acidosis

20. Lactate and Liver Function Tests after Living Donor
Right Hepatectomy: A Comparison of Solutions
With and Without Lactate
A total of 104 donors undergoing right hepatectomy for liver
transplantation were randomly allocated to receive lactated
Ringer’s (LR) solution (n = 52) or Lactate free BSS (n = 52).
The lactate concentrations were significantly
higher in the LR group than in the Plasmalyte
group 1 h after hepatectomy [4.2 (3.2–5.7)
vs. 3.3 (2.6–4.6)mmol/l; P0.005)
Results:
Conclusion:
Crystalloid solution may have important advantages over LR
solution, concerning lactate and liver profiles, in living donors
undergoing right hepatectomy
Shin et al Acta Anaesthesiol Scand 2011; 55: 558–564

21. Lactate vs Acetate
• Multicentre double blind randomized study during major
liver resection
• 30 patients received hartmann’s solution and another 30
received acetate buffered solution
• Patients receiving hartmann’s solution had a
significantly higher blood loss, were more
hyperchloremic, hyperlactemic, had more number of
complications and a longer length of hospital stay
Weinberg et al Minerva Anestesiol. 2015 Dec;81(12):1288-97

22. Clinical Studies

23. Effects of 2-L Infusions of 0.9% Saline and BSS
on Renal Blood Flow Velocity and Renal Cortical Tissue
Perfusion in Healthy Volunteers
• Chowdhury et al. studied the effects of iv infusion of 0.9% NS
vs a BSS on renal hemodynamics in healthy humans.
• Changes in Renal Artery Blood Flow Velocity, Renal Volume,
and Renal Cortical Tissue Perfusion Determined by MRI
• Following the initial infusion of 2 l of NS, there was a
progressive decrease in renal blood flow, which was
significantly lower with balanced solution.
Kidney perfusion - significantly lower with 0.9% NS
Chowdhury AH et al. Ann Surg 2012;256:18–24

24. Association Between Choice of
Crystalloid and Mortality in Critically ILL
Adult Patients with Sepsis
• Retrospective cohort study of patients admitted with sepsis
not undergoing any surgical procedures and treated in an
ICU by hospital day 2
• Setting: 360 U.S. hospitals between Nov 2005 and Dec 2010
• Primary outcome was in-hospital mortality occuring after
hospital day 2
Raghunathan et al. Crit Care Med 2014; 42:1585–1591

26. Raghunathan et al. Crit Care Med 2014; 42:1585–1591

27. Conclusion:
Among critically ill adults with sepsis, resuscitation with
balanced fluids was associated with a lower risk of in-
hospital mortality.
Raghunathan et al. Crit Care Med 2014; 42:1585–1591

28. SMART Study
• The Isotonic Solutions and Major Adverse Renal Events Trial
(SMART) was a pragmatic, cluster-level allocation, cluster-level
crossover trial conducted in the US.
• Compared saline (7860 patients) with balanced crystalloids (7940
patients)
• The primary outcome was Major Adverse Kidney Events within 30
days (MAKE30), the composite of death, new renal replacement
therapy, or persistent renal dysfunction (creatinine elevation ≥
200% of baseline).Major Adverse Kidney Events within 30 days
(MAKE30), the composite of death, new renal
• replacement therapy, or persistent creatinine elevation ≥200% of
baseline
Semler MW, et al. N Engl J Med 2018;378:829-839

29. Patients Receiving Balanced
Crystalloids had Higher Bicarbonate
Levels and Lower Chloride Levels
Semler MW, et al. N Engl J Med 2018;378:829-839

30. • Patients using balanced crystalloids had a 1.1% absolute
significant decrease in MAKE 30
• Replacing saline with balanced crystalloids might prevent 1
patient among every 94 patients admitted to an ICU from the
need for new renal-replacement therapy, from persistent
renal dysfunction, or from death.
Semler MW et al. N Engl J Med 2018;378:829-839
Conclusion:
Use of balanced crystalloids compared to saline for
intravenous fluid administration among critically ill adults
can reduce the incidence of death, new renal replacement
therapy, or persistent renal dysfunction

31. • Subgroup analysis of the Isotonic Solutions
and Major Adverse Renal Events Trial (SMART)
• 1,641 patients admitted to the medical ICU
with a diagnosis of sepsis
• Compared the balanced crystalloids
and saline groups with regard to mean arterial
pressure and dose of vasopressors (in
norepinephrine equivalents) over the five days
following ICU admission
• Patients in the balanced crystalloids group
received lower doses of vasopressors than
patients in the saline group

32. SALT-ED Study
Objective Compare clinical effects of Saline and Balanced Crystalloids
in non-critically ill patients outside the ICU
Study Method Single centre, pragmatic multiple cross-over trial
6708 patients received 0.9% saline while 6639 patients
received balanced crystalloids (RL or Plasma-Lyte)
Self, W. H. et al . N. Engl. J. Med. 378, 819–828 (2018).
Primary Endpoints Hospital-free days (number of days alive and out of the
hospital to day 28)
Secondary Endpoints Major Adverse Kidney Events within 30 days (MAKE30),
defined as the composite of death, new renal replacement
therapy, and persistent renal dysfunction (defined as
creatinine elevation ≥200% of baseline

33. • Absolute decrease in MAKE 30 with balanced crystalloids was
0.9%
• Replacing saline with balanced crystalloids might prevent 1
patient among every 111 non-critically ill patients admitted to
the emergency from the need for new renal-replacement
therapy, from persistent renal dysfunction, or from death
Self, W. H. et al . N. Engl. J. Med. 378, 819–828 (2018).
Conclusion:
• No difference in hospital free days between patients
treated with saline or balanced crystalloids in the
emergency department.
• Significantly lower Major Adverse Kidney Events within 30
days in patients receiving balanced crystalloids

34. Conclusion:
• Although in both trials the effect size was rather small
(about a 1% absolute risk reduction in MAKE30), the fact
that virtually every hospitalized patient receives
intravenous fluids means that switching to balanced
crystalloid solutions will have an enormous impact on
society, potentially reducing the annual number of
worldwide annual MAKE events by about 2 million.

36. Clinical Studies in Surgery

37. Advantages of balanced salt solution in
surgery
Advantages of balanced salt solutions might include:
• Lower incidence of acidosis
• Lower incidence of renal failure and RRT
• Decrease in postoperative complications

38. Saline vs Balanced Crystalloids in Non
Renal Surgeries: A Meta-Analysis
• 871 patients from 9 randomized clinical trials in adult
patients undergoing non-renal surgery.
• 2 groups: 0.9 Saline vs Balanced Crystalloids
• Significantly lower base excess, pH in patients in
saline group
• Significantly higher chloride levels in saline group
Conclusion:
• Use of balanced crystalloids during non renal surgeries results in
a better post operative metabolic profile compared to saline
• More research focussing on clinical outcomes when comparing
both these crystalloids
Huang L, Zhou X, Yu H, International Journal of Surgery (2018), doi:10.1016/j.ijsu.2018.01.003.

39. Saline vs Balanced Crystalloids in
Abdominal Surgery
• 60 patients randomized into 2 groups of 30 patients
each
• Group 1 received saline (median: 3427 mL) and
Group 2 received Balanced Crystalloids (median:
3144 mL)
• Primary outcome was need for vasopressors
Pfortmueller, C.A. et al. British Journal of Anaesthesia , 2018; Volume 120 , Issue 2 , 274 - 283

40. Significantly lower no of patients in Balanced Group (67%) required
vasopressors compared to saline group (97%)
Pfortmueller, C.A. et al. British Journal of Anaesthesia , 2018 ; Volume 120 , Issue 2 , 274 - 283

41. Significantly lower serum chloride levels, higher pH and less negative base excess in
Balanced Crystalloid Group.
Conclusion:
Use of a calcium-free balanced crystalloid for replacement of fluid
losses during abdominal surgery was associated with lower need for
vasopressors to achieve hemodynamic stability compared to 0.9%
saline
Pfortmueller, C.A. et al. British Journal of Anaesthesia , 2018; Volume 120 , Issue 2 , 274 - 283

42. Objective To assess the association of 0.9% saline use versus a calcium-free
physiologically balanced crystalloid solution with major morbidity and
clinical resource use after abdominal surgery.
Study Method An observational study to evaluate adult patients undergoing major open
abdominal surgery who received either 0.9% saline (2778 patients) or a
balanced crystalloid solution (926 patients) on the day of surgery
Primary Endpoint Major morbidity
Results:
• In-hospital mortality was 5.6% in the saline group and 2.9% in the balanced group
(P < 0.001)
• One or more major complications occurred in 33.7% of the saline group and 23% of
the balanced group (P < 0.001)
• Postoperative infection (P = 0.006), renal failure requiring dialysis (P < 0.001), blood
transfusion (P < 0.001), electrolyte disturbance (P = 0.046), acidosis investigation (P
< 0.001), and intervention (P = 0.02) were all more frequent in patients receiving
0.9% saline.
Major complications, mortality after
open abdominal surgery: 0.9% NS vs BSS
Shaw AD. Ann Surg 2012; 255: 821–829
Conclusion:
Use of a calcium-free balanced crystalloid for replacement of fluid
losses on the day of major surgery was associated with less
postoperative morbidity than 0.9% saline

43. Objective To evaluate intraoperative use of a calcium free Balanced Crystalloid and
0.9% Saline in terms of mean change in arterial pH, standard bicarbonate,
base deficit and
serum electrolytes immediate postoperatively and 24 hours after
surgery.
Primary Endpoint Mean change in arterial pH, base deficit and serum electrolytes immediate
postoperatively and 24 hours after surgery.
A Comparison of Calcium Free Balanced Crystalloid
Solution vs 0.9% Saline for Intraoperative
Fluid Replacement in Abdominal Surgeries in an
Indian Setting (1)
Chatrath et al . International Journal of Contemporary Medical Research 2016;3(12):3579-3583
Study Method • Prospective randomized double blind study
• 60 patients of ASA grade 1 or 2 were randomized into two groups to
received either intravenous Balanced Crystalloid or 0.9% Saline during
surgery at the rate of 15 ml/kg/hr

44. Balanced Crystalloid group (Group A) had
significantly higher mean pH levels in the
immediate postoperative period
Balanced Crystalloid group (Group A) had
significantly less negative base excess in the
immediate postoperative period
(1) first reading taken before starting of surgery;
(2) second reading taken immediately postoperatively;
(3) third reading taken 24 hr after surgery
A Comparison of Calcium Free Balanced Crystalloid Solution vs 0.9%
Saline for Intraoperative
Fluid Replacement in Abdominal Surgeries in an Indian Setting (2)
Chatrath et al. International Journal of Contemporary Medical Research 2016;3(12):3579-3583

45. Balanced Crystalloid group (Group A)
had significantly less serum chloride
levels in the immediate post-operative
period
Conclusions:
• Both calcium free balanced crystalloid solution and 0.9%
saline may be used safely intraoperatively in elective abdominal
surgeries because of lack of impact on long term metabolic
profile in healthy patients.
• Calcium free balanced crystalloid solution maintained a
more physiological picture of acid base balance and electrolytes
in the immediate postoperative period.
A Comparison of Calcium Free Balanced Crystalloid
Solution vs 0.9% Saline for Intraoperative
Fluid Replacement in Abdominal Surgeries in an
Indian Setting (3)
Chatrath et al International Journal of Contemporary Medical Research 2016;3(12):3579-3583

46. Clinical Studies in Trauma/Emergency
Department

47. Saline versus Calcium Free Balanced
Crystalloid Solution in initial resuscitation of
trauma patients: a randomized trial
Objective Compare resuscitation with 0.9% NaCl versus a calcium-free
balanced crystalloid solution (BCS), hypothesizing that the balanced
crystalloid solution would better correct the base deficit 24 hours
after injury.
Study Method • Randomized, double-blind, parallel-group trial (of adult trauma
patients requiring blood transfusion, intubation, or operation
within 60 minutes of arrival at the University of California Davis
Medical Centre (65 patients in all)
• Subjects received either 0.9% NaCl or calcium free BSS for
resuscitation during the first 24 hours after injury.
Primary Endpoint Change in base excess from 0 to 24 hours
Results:
• Improvement in base excess from 0-24 hours was significantly greater with calcium
free BCS compared with saline
• Arterial pH was higher and serum chloride levels were lower in the calcium-free BCS
group
Young JB et al. Annals of Surgery. 259(2):255-262, February 2014
Conclusion:
Compared with 0.9% NaCl, resuscitation of trauma patients with
calcium-free BCS resulted in improved acid-base status and less
hyperchloremia at 24 hours post-injury

48. Renal effects of an emergency department
chloride restrictive intravenous fluid strategy in
patients admitted to hospital for more than 48
hours
Objective Assess the effects of restricting i.v. chloride administration in the
ED on the incidence of acute kidney injury (AKI).
Study Method • Prospective, open label, before-and-after study in the ED of
the Austin Hospital, Melbourne
• 6 month chloride liberal control period and 6 month chloride
restrictive intervention period
Primary
Endpoint
Incidence of AKI according to KDIGO definitions
Yunos N. M et al. Emergency Medicine Australasia, 2017

49. Conclusions:
Chloride-restrictive strategy in an ED was associated with a
significant decrease in the incidence of stage 3 of KDIGO-
defined AKI
Yunos N. M et al. Emergency Medicine Australasia, 2017

50. Saline vs Acetate Buffered Balanced
Crystalloids in Deceased Donor Renal
Transplantation
• Randomized double blind study
• Patients received either saline (n=25) or acetate buffered
balanced crystalloids (n=24)
• Patients receiving saline had a higher incidence of
hyperkalaemia, hypochloraemia and were more
acidaemic
Weimberg et al. British Journal of Anaesthesia, 0 (0): 1–10 (2017)

51. Acetate-buffered crystalloid infusate versus infusion of 0.9% saline
and hemodynamic stability in patients undergoing renal
transplantation : Prospective, randomized, controlled trial (1)
Objective Investigate whether use of acetate-based balanced
crystalloids leads to better hemodynamic stability compared
to 0.9% saline
Study Method Sub-analysis of a prospective, randomized, controlled trial
comparing effects of 0.9% saline or an acetate-buffered,
balanced crystalloid during the perioperative period in
patients with end-stage renal disease undergoing cadaveric
renal transplantation
Primary Endpoint Need for catecholamine therapy and blood pressure were
the primary measures.
Pfortmueller C et al. Wien Klin Wochenschr (2017) 129:598

52. Acetate-buffered crystalloid infusate versus infusion of 0.9%
saline and hemodynamic stability in patients undergoing renal
transplantation : Prospective, randomized, controlled trial (2)
Mean minimum arterial blood pressure was significantly lower in
patients randomized to 0.9% saline than in patients receiving the
balanced infusion solution (57.2 [SD 8.7] versus 60.3 [SD 10.2]
mm Hg, p = 0.024)
Conclusion:
• The use of an acetate-buffered, balanced infusion solution results
in reduced need for use of catecholamines and cumulative
catecholamine dose for hemodynamic support and in less
occurrence of arterial hypotension in the perioperative period.
• Further research in the field is strongly encouraged.
Pfortmueller C et al. Wien Klin Wochenschr (2017) 129:598

53. What do the Guidelines Say?

54. Recommendations for Fluid Resuscitation in
Acutely ILL Patients
J Myburgh and M Mythen. N Engl J Med 2013;369:1243-51.

55. Intravascular volume therapy in adults-
Guidelines from the Association of the Scientific Medical Societies in
Germany
Published online 1 April 2016 Eur J Anaesthesiol 2016; 33:488–521

56. Recommendations
Recommendation 5b-1 GoR
Hypo-osmolar solutions must not be used for volume therapy in ICU
patients with severe traumatic brain injury
Recommendation 6a-3 GoR
As they do not influence diagnostic criteria, balanced infusions containing
acetate or malate instead of lactate may be integrated into the treatment
algorithm for volume substitution in
Recommendation 6b-3 GoR
Balanced electrolyte solutions containing acetate or malate instead of lactate
may be used as a volume substitute for critically ill ICU patients
Recommendation 6b-1 GoR
An isotonic saline solution must not be used as a volume substitute in
intensive care medicine
Eur J Anaesthesiol 2016; 33:488–521

57. • Because of the risk of inducing hyperchloremic acidosis in routine
practice, when crystalloid resuscitation or replacement is indicated,
balanced salt solutions should be used
• Hypovolemia due to severe inflammation such as infection,
peritonitis, pancreatitis or burns should be treated with either a
balanced crystalloid or a suitable colloid.

58. Final Conclusions
• Use of large volumes of saline is associated with development of
hyperchloremic metabolic acidosis
• Balanced fluids cut down the risk of hyperchloremic metabolic acidosis
• Acetate buffered balanced crystalloids can have some added advantages in
diabetic patients and patients undergoing hepatectomy compared to
lactate buffered solutions
• Recent results from the SMART and SALT-ED study has provided very
strong evidence about the clinical advantages of balanced crystalloids in
critically ill as well as not-critically ill patients compared to 0.9% NS
• Fluids are drugs and should be prescribed as such

59. ERA of Balanced Fluid Therapy
Large Volumes of 0.9% NS =
Hyperchloremic Metabolic
Acidosis
Balanced Crystalloids cut down
the risk of developing
hyperchloremic metabolic
acidosis
Acetate Buffered Balanced Crystalloids:
Advantageous in:
• Sepsis Patients
• Patients Undergoing Liver Procedures
• Diabetes Patients
SMART study and SALT-ED study
• Largest clinical trial till date
• Provided strong evidence clinical
benefits of balanced crystalloids vs
0.9% NS in critically ill and non-
critically ill patients.

60. Thank You