Balanced crystalloids are solutions designed to closely mimic human plasma, offering predictable increases in intravascular volume without altering electrolyte concentrations, unlike normal saline, which can lead to hyperchloremic metabolic acidosis. Clinical evidence suggests that balanced crystalloids reduce mortality, acute kidney injury, and complications in critically ill patients, sepsis, diabetic ketoacidosis, and postoperative recovery compared to normal saline. Guidelines recommend the use of balanced crystalloids for fluid resuscitation over normal saline due to these beneficial outcomes.

1. BALANCED CRYSTALLOIDS IN CLINICAL
SETTINGS

2. POINTS TO BE DISCUSSED
1) What is Balanced Crystalloid?
2) A brief history
3) Balanced Crystalloids Vs NS?
4) Global Clinical Evidence: Balanced Crystalloid
5) Clinical Guidelines
6) Balanced Crystalloid: Unmet needs of Indian patients- A clinician’s opinion
7) Clinician’s perspective (case studies)
8) Closing remarks 2

3. BALANCED CRYSTALLOIDS
 A crystalloid solution with chemical composition as close as possible to that of plasma
 Produces a predictable and sustainable increase in intravascular volume without changing
electrolytes concentration in plasma
 This is important for maintaining fluid and electrolyte balance during IV infusion in
hospitalized patients
 So called “Normal” saline is neither “Normal” or “Balanced”!
 50% higher chloride Vs Plasma
 No electrolytes except Na+ and Cl-
 Leads to hyperchloremic metabolic acidosis in some patients
3

4. HISTORY: BALANCED CRYSTALLOIDS
4

5. HISTORY OF IV FLUID INFUSION
1831: “Saline (salt solution)” was initially used in UK during Cholera Pandemic
1883: Hamburger, a Dutch scientist “discovered” that human blood has 0.9%
salt. This led to development of “Normal” Saline
1883: Sydney Ringer developed a multi-salt saline including KCl and CaCl2,
AKA Ringer’s solution
1932: Alex Hartmann added “lactate to Ringer’s solution to avoid acidosis, and it
became “Ringer”s Lactate!
1982: PL-148 (PlasmaLyte-A) launched, Later on various other formulations
were developed

6. HUMAN PLASMA VS IV INFUSION SOLUTIONS
Osmolality
mOsm/kg
Tonicity Na+ Cl- K+ Mg+ Ca2+ Buffer
Plasma 288 Reference 140 103 4.5 2 2.5 42
0.9% NaCl 308 So Called
Isotonic
154 154 0 0 0 0
Balanced
Crystalloids
294 Isotonic 140 98 5.0 3 0 50
Balanced Crystalloids have more similar electrolytes and osmolarity with human plasma than so called
“Normal Saline”.

7. SID (STRONG ION DIFFERENCE) & BUFFERING CAPACITY OF IV
FLUIDS
• Weak anions are responsible for buffering capacity of IV fluids. Plasma proteins are major
buffers in blood
• A buffer pair is a week acid, which enters equilibrium with its corresponding week base at
the given pH
• Strong cations predominate in the plasma at physiologic pH leading to a net positive
plasma charge of approximately +40 to 45. SID can be estimated as follows:
• SID = [strong cations] – [strong anions] = [Na+ + K+ + Ca2+ + Mg2+] – [Cl- + lactate-]

8. STRONG ION DIFFERENCE
• Lower SID: Acidosis- As Normal Saline has SID of 0, its infusion to plasma will reduce SID of
plasma (which is around 40) and will lead to acidosis
• Balanced Crystalloids have SID of 50, similar to plasma. Infusion of Balanced Crystalloids will
not lead to any major change in pH, No acidosis

9. BALANCED CRYSTALLOIDS VS NS?
9

10. 52 serving packets
ONE LITER NS SALT = SALT IN 53 SERVING OF LAYS CHIPS

11. LIMITATIONS OF SO CALLED “NORMAL” SALINE
Electrolytes
Imbalance
• Hyperchloremic Metabolic Acidosis: Acidic pH and 50% higher CL- (Vs plasma) in NS
Electrolytes
Imbalance
• Hyperkalemia: Any acidosis will shift H+ into ICF and consequent movement of K+ into ECF
(Blood)
Clinical
Outcomes
• AKI : More risk of renal vasoconstriction, (renal blood flow)
• GIT: paralytic Ileus, oedema

12. GLOBAL CLINICAL EVIDENCE: BALANCED
CRYSTALLOIDS
12

13. CONDITIONS WHERE BALANCED CRYSTALLOIDS ARE PREFERRED
1. Critically ill patients
2. Sepsis/septic shock
3. Diabetic Ketoacidosis (DKA)
4. Surgical patients
NS: Normal Saline, RL: Ringer Lactate

14. 1. BALANCED CRYSTALLOIDS IN CRITICALLY ILL ADULTS:
A SYSTEMATIC REVIEW AND META-ANALYSIS
• 13 studies (n = 30 950) were included.
• Balanced crystalloids demonstrated lower hospital or 28-/30-day mortality (risk ratio [RR] = 0.86; 95% CI = 0.75-
0.99; I2 = 82%) in observational studies (RR = 0.64; 95% CI = 0.41-0.99; I2 = 63%)
• New acute kidney injury occurred less frequently with balanced crystalloids (RR = 0.91; 95% CI = 0.85-0.98; I2 = 0%),
though progression to renal replacement therapy was similar (RR = 0.91; 95% CI = 0.79-1.04; I2 = 38%).
Annals of Pharmacotherapy 2020, Vol. 54(1) 5–13
Conclusion and Relevance:
• Resuscitation with balanced crystalloids demonstrated lower hospital or 28-/30-day mortality compared with saline in
critically ill adults.
• Balanced crystalloids should be provided preferentially to saline in most critically ill adult patients.

15. I. CHLORIDE RICH VS CHLORIDE RESTRICTED IV FLUID INFUSION AND
KIDNEY INJURY IN CRITICALLY ILL PATIENTS
• To assess the association of a chloride-restrictive (vs chloride-liberal) intravenous fluid strategy with AKI in critically ill
patients.
Objective:
• Prospective, open-label, study
Design:
• During the control period, patients received standard intravenous fluids.
• After a 6-month phase-out period, in intervention period balanced solution was used*
• 760 patients were enrolled during the control period compared with 773 patients during the intervention period.
Methods:
* a lactated solution (Hartmann solution), a balanced solution (Plasma-Lyte 148), and chloride-poor 20% albumin was used during intervention period
JAMA. 2012;308(15):1566–1572. doi:10.1001/jama.2012.13356

16. I. CHLORIDE RICH VS CHLORIDE RESTRICTED IV FLUID INFUSION AND
KIDNEY INJURY IN CRITICALLY ILL PATIENTS
Comparing the control period with the intervention period:
 The mean serum creatinine level was increased in control period [22.6 µmol/L (95% CI,
17.5-27.7 µmol/L) vs 14.8 µmol/L (95% CI, 9.8- 19.9 µmol/L) (P=.03)]
 The incidence of AKI* was 14% (95% CI, 11%-16%; n=105) vs 8.4% (95% CI, 6.4%-10%;
n=65) (P.001)
 The use of RRT was 10% (95% CI, 8.1%-12%; n=78) vs 6.3% (95% CI, 4.6%- 8.1%; n=49)
(P=.005).
*Incidence of AKI according to the risk, injury, failure, loss, end-stage (RIFLE) system definitions.
Results:
JAMA. 2012;308(15):1566–1572. doi:10.1001/jama.2012.13356

17. Incidence of Acute Kidney Injury Stratified by Risk, Injury, Failure, Loss, and End-Stage (RIFLE) Serum Creatinine Criteria
The implementation of a chloride-restrictive strategy in a tertiary ICU was associated
with a significant decrease in the incidence of AKI and use of RRT.
I. CHLORIDE RICH VS CHLORIDE RESTRICTED IV FLUID INFUSION AND
KIDNEY INJURY IN CRITICALLY ILL PATIENTS

18. 2. BALANCED CRYSTALLOIDS IN SEPSIS:
SMART STUDY SUB-ANALYSIS
 Total 1641 patients with sepsis admitted in Medical ICU
were treated with either balanced crystalloids (n=824)
or normal saline (n=817)
 Benefits observed with Balanced crystalloids Vs NS
o Lower 30 days in-hospital mortality
o Lower incidence of MAKE30 (major adverse kidney
events) within 30 days
aOR: adjusted odds ratio, CI: Confidence Interval, Am J Respir Crit Care Med 2019; 200(12): 1487–1495
MAKE30: Death, new receipt of renal replacement therapy, or persistent renal dysfunction at the first of hospital discharge at 30 days
31.2
40.1
26.3
35.4
0
5
10
15
20
25
30
35
40
45
30 days hospital mortality MAKE30
NS Balanced Crystalloids
Conclusions
In ICU patients with sepsis, use of balanced crystalloids was associated with a lower 30-day
in-hospital mortality and better renal outcomes Vs use of saline

19. 3. BALANCED CRYSTALLOIDS IN DKA
A recent (2022) meta-analysis compared use of Balanced crystalloids* and NS for
DKA management
Total 482 patients were included from 8 randomized controlled trials in the
analysis.
Use of Balanced crystalloids had following advantages over NS
1. Faster resolution of DKA by 3.51 hours (p=0.008)
2. Reduced hospital stay by 0.89 days (p=0.001)
No difference in mortality between two groups,
A trend toward lower serum chloride and higher serum bicarbonate in Balanced crystalloids
group
Diabetic Ketoacidosis (DKA) NS: Normal Saline, DKA: Diabetic Ketoacidosis, * including PlasmaLyte, Ringer’s lactate, Ringerfundin, and Hartmann’s solution
Crit Care Explor 2022 Jan 6;4(1):e0613).

20. 4. BALANCED CRYSTALLOIDS IN POSTOPERATIVE PATIENTS A.
LIVER SURGERY
• A clinical study compared use of Balanced Crystalloids vs RL in 104 donors undergoing liver
surgery (right hepatectomy)
• Benefits of Balanced Crystalloids Vs RL group.
• Lower lactate concentration (3.3 Vs 4.2 mmol/L, p=0.005)
• Lower Prothrombin time and total bilirubin (Liver function)
• Higher albumin levels
4.2
3.3
0
1
2
3
4
5
Ringer's Lactate Balanced Crystalloids
Serum Lactate Levels
P=0.005
Conclusion:
Non-lactated balanced crystalloids may have important advantages Vs RL, concerning lactate and
liver function profiles, in living donors undergoing right hepatectomy.
Acta Anaesthesiol Scand 2011 May;55(5):558-64

21. 4. BALANCED CRYSTALLOIDS IN POSTOPERATIVE PATIENTS B.
OPEN LAPAROTOMY
In a retrospective observational study, use of Balanced Crystalloids in postoperative (open abdominal surgery)
patients had following benefits over NS
1. Lower rates of in-hospital mortality (2.9% Vs 5.6% P < 0.001)
2. Lower risk of major complications (23% Vs 33.7% P < 0.001),
3. Post-operative infection (P < 0.006),
4. Blood transfusions (P < 0.001),
5. Electrolyte disturbance (P < 0.046) and
6. Acidosis investigation (P < 0.001) and intervention (P = 0.02)
Ann Surg 2012; 255: 821-829)

22. 2019 ERAS/ESTS GUIDELINES: LUNG SURGERY
Recommendation statement Evidence Level Recommendation
grade
For Perioperative fluid management,
Balanced crystalloids are the intravenous
fluid of choice and are preferred to 0.9%
saline
High Strong
European Journal of Cardio-Thoracic Surgery 55 (2019) 91–115
ERAS: Enhanced Recovery After Surgery ESTS: European Society of Thoracic Surgeons
2019 guidelines for lung surgery by ESTS strongly recommend balanced crystalloids over
normal saline for perioperative fluid management

23. 2021 SURVIVING SEPSIS CAMPAIGN: GUIDELINES FOR
MANAGEMENT OF SEPSIS AND SEPTIC SHOCK
Recommendation statement Evidence Level Recommendation
For adults with sepsis or septic shock, we suggest
using balanced crystalloids instead of normal
saline for resuscitation.
low quality of
evidence
Weak
Evans L et al. Critical Care Medicine 2021;49(11):e1063-e1143
This recommendation is based on the pre-specified subgroup analysis of SMART trial with patients
admitted with sepsis in all participating ICUs, 30-day mortality was lower in those receiving balanced
solutions,
compared to normal saline (OR, 0.80; 95% CI, 0.67−0.94)

24. BALANCED CRYSTALLOID: UNMET NEEDS OF INDIAN PATIENTS- A
CLINICIAN’S OPINION
 there is no major emphasis on the chloride as electrolyte in day to day clinical practice.
 Hyperchloremic acidosis is not seen as iotrogenic
 Since the childhood NORMAL SALINE is considered as the synonimaus of the crystaloids no major
challenge has posted against the supremacy of the title
 No trial’s so far has given outright advantages
 Always acidosis/alkalosis refered in reference to the hydrogen ions and bicarbonates
 Cost of the newer balanced saline were more than five times higher.
24

25. CASE STUDIES
 Case no 1
a case of the acute appendicitis, perforation and septicaemia got operated for same
Required fluid resuscitation , had acute renal failure recovered
25
Day 1
Fluid resuscitation {2
litre ns with in 10 hr}
Serum sodium 134 Serum chloride 98 PH 7.23 Creat 1.4
Day 2
Fluid resuscitation
{3.4 litre ns plus 1
litre in ot}
Sodium 144 Chloride 107 PH 7.3 Creat 1.8
Day 3
Fluid resuscitation{ 2
litre in 24 hrs}
Sodium 151 Chloride 117 PH 7.2 Creat 2.2

26.  SID SID
 40 30
26
K,
MG
CA
NA
140
lactat
e
Cl
104
K,
MG
CA
NA
144
lac
tat
e
Cl 114
Chloride rich
resuscitation
(0.9%)

27. CASE STUDY CASE NO. 2
 A case 50 yrs old female with diabetes ketosis,HBA1c 13 ,acetone 75 with severe respiratory distress
admiited to hospital
27
On
admissi
on
NA
136
K
5.5
CL
99
Creat
0.93
PH
6.9
Fluid
3lit/6hr
s
Crystalo
ids
0.9%
After 12
hrs
146 3.4[repl
acemen
t]
110 1.3 7.08 200ml/
hrs
0.9%
After 24
hrs
153 3.6 118 1.7 7.2 150ml/
hr
0.45%
After 48
hrs
153 3.7 118 2.0 7.18 100ml/
hr
Alternat
e 0.45%
and
dextros

28. TAKE HOME MESSAGE
• Electrolyte profile is more (physiologically) similar with human
plasma than NS or RL
• Achieving volume resuscitation is important thing in initial
resuscitation but important but ignored hyperchloremic acidosis
may nullify achieved goal.
• Normal Saline is not “Normal. Its use have limitations in specific
patient populations
• There is a strong evidence demonstrating clinical benefits with
Balanced Crystalloids in various patient populations (Laparotomy,
critical, DKA, Septic shock, etc)
• Multiple International guidelines recommend use of balanced
crystalloids over NS
Balanced
Crystalloids