COMPARATIVE STUDY OF NORMAL SALINE AND RINGERS LACTATE

1. INTRAVENOUS FLUID THERAPY:
THE CASE OF NORMAL SALINE
VS RINGERS LACTATE
DR ANTHONY KWAW, RESIDENT PHARMACIST
ACCIDENT AND EMERGENCY
TAMALE TEACHING HOSPITAL
TAMALE, GHANA
Email: kwawanthony7@gmail.com
1

2. OUTLINE
• Introduction
• Comparative studies
• Myths on Ringers lactate use
• Specific indications for Ringers lactate
• Considerations for alternative IVF to Ringers lactate
• Practice Points
• Conclusion
• References
2

3. Patient Case Scenario
 A 70-year-old-female is brought to the ED for altered mental status. The
patient has had decreased PO intake over the last 3-4 days and fever and
confusion that worsened in the last 24 hours. Her past medical history is
significant for hypertension and coronary artery disease.
Vitals are notable for a blood pressure of 82/44mmHg, HR of 118bpm,
temperature of 39.10C, RR of 14cpm, and SPO2 96% on RA. The patient
appears confused and dehydrated. Evaluation reveals a WBC of
24,000mm3, lactate of 6.0mEq/L, K of 5.8mEq/L, and UTI on urinalysis.
You have identified that the patient is in septic shock and requires fluid
resuscitation.
What fluid will you use to resuscitate your patient? What evidence will
support that decision? Does the patients’ elevated lactic acid and potassium
play a role in your choice of fluid? 3

4. Intravenous Fluids
A 70kg adult requires 2-2.5L of fluids over 24 hours
Losses are through urine (1.5L), stool (0.2L), and insensible losses
(0.8L)
This requirement is normally met through food (1000mL) and drink
(1500mL).
IVF are given if sufficient fluids cannot be given orally.
Fluids are a standard treatment for various disease processes that
present to the ED. 4

5. Intravenous Fluids
Thought to increase intravascular and intracellular volume, fluids are
critical in treatment of multiple disease processes that cause
dehydration and loss of circulating fluid, leading to hypoperfusion and
hypotension
Historically, NS has been the fluid of choice for resuscitation
Recent debate about preferred fluids based on composition in the
treatment of various illnesses
5

6. The Composition of the Human Body
6

7. Water Content of the Body

8. Normal distribution of water (Adults)
8
• For a 70kg man, total bodily fluid is ~42L
(60% body weight); 36L in a 60kg adult
• ⅔ is intracellular (25-30L) and
• ⅓ is extracellular (13-16L).
• Of the extracellular compartment, ⅓ is
intravascular, i.e. blood (5L)
• Lymph and transcellular fluid are 1.5L each

9. Normal distribution of water (Infants)
9
• Water constitutes about 75-80% of the body weight.
• Solids constitute about 20 to 25% of the body weight.
• The total volume of water in an infant is about 3L
• The water in the intracellular compartment is ≈
30% of the body weight.
• Water in the extracellular compartment constitutes
45% of the body weight.
• Plasma constitutes about 4% of the body weight of
an infant

10. Types of Intravenous Fluids
• Dextrose 5%:
• Isotonic
• Small amount of glucose ~50g/L
• small energy (~10% daily energy per liter)
• liver rapidly metabolizes all the glucose leaving only water, which rapidly
equilibrates throughout all fluid compartments.
• Not suitable for fluid resuscitation (only 1/9 will remain in the intravascular
space), but suitable for maintaining hydration.
• Excess 5% glucose IV may lead to water overload and hyponatremia
• Dextrose 10% and 50%
• Hypertonic
• Used to correct hypoglycemia 10

11. Types of Intravenous Fluids
• Dextrose in Sodium chloride
• Required for fluid maintenance
• 1/5 Dextrose in 0.18% Sodium chloride used in pediatric setting
• 5 % Dextrose in 0.9% Sodium chloride used in adult patients
• Colloids (e.g. Gelofusine)
• Have a high osmotic content similar to that of plasma and therefore remain in
the intravascular space for longer than other fluids, making them appropriate
for fluid resuscitation, but not for general hydration.
• Colloids are expensive, and may cause anaphylactic reactions.
• In reality, effective fluid resuscitation will use a combination of colloid and
0.9% saline
11

12. Types of Intravenous Fluids
Sodium chloride 0.9%
• About the same Na+ content as plasma
(150mmol/L) and is isotonic with plasma.
• Equilibrate rapidly throughout the
extracellular compartment only, but takes
longer to reach the intracellular
compartment than 5% glucose.
• Appropriate for fluid resuscitation, as it
remains predominantly in the extracellular
space
• Also for maintaining hydration
Ringers lactate
• Considered more physiological due to
the similarity in its composition
compared to human plasma
• Less risk of causing acidosis compared
to NS
12

13. IVF COMPOSITION
Contents Human plasma NS RL Plasma-lyte A
Sodium (mEq/L) 135-145 150 130 140
Potassium (mEq/L) 4.5-5.0 0 4 5
Chloride (mEq/L) 94-111 154 109 98
Calcium (mEq/L) 2.2-2,6 0 2.7 0
Magnesium (mEq/L) 0.8-1.0 0 0 3
Bicarbonate (mEq/L) 23-27 0 0 0
Lactate (mEq/L) 1-2 0 28 0
Acetate (mEq/L) 0 0 0 27
Gluconate (mEq/L) 0 0 0 23
pH 7.4 5.5 6.5 7.4
13
• NS has relatively more chloride than human plasma; risk of hyperchloremic metabolic acidosis
• This may delay recovery in some disease process and may contribute to worsening renal function during treatment
• Elevated chloride causes renal vasoconstriction and may decrease renal perfusion via this mechanism

14. COMPARATIVE STUDIES
14

15. Saline Against Lactated ringers or Plasma-Lyte in
the Emergency Department (SALT-ED) Trial
(Wesley et al., 2018)
• An RCT conducted in 2016 (over 16 months) to compare NS and
balanced crystalloids in non-critically ill patients (n= 13,347)
• A single-center, pragmatic, multiple-crossover trial
• Trial evaluated hospital-free days (days alive after discharge before
day 28) as well as major adverse kidney events within 30 days
• composite of death from any cause
• new renal replacement therapy
• persistent renal dysfunction with creatinine >200% from baseline
15

16. SALT-ED TRIAL- Outcome
16
• Primary outcome of hospital-free days did not have a significant difference
between NS and balanced crystalloid groups
• Significantly lower rate of adverse major kidney events in 30 days between
balanced crystalloid and NS groups (4.7% vs. 5.6%)
• Patients in the balanced crystalloid arm showed lower chloride and higher
bicarbonate concentrations persisting for several days into hospitalization.
• Patients with underlying renal dysfunction or hypochloremia at presentation
appeared to have the largest benefit from the balanced crystalloid therapy by
having reduced incidents of major adverse kidney events in 30 days

17. Isotonic Solutions and Major Adverse Renal
Events Trial (SMART) (Semler et al., 2018)
• An RCT conducted in 2016 (over 16 months) to compare NS and balanced
crystalloids in critically ill patients (n= 15,802)
• A pragmatic, cluster-randomized, multiple-crossover trial
• The primary outcome was a major adverse kidney event within 30 days
• composite of death from any cause
• new renal replacement therapy
• persistent renal dysfunction with creatinine >200% from baseline
17

18. SMART TRIAL- Outcome
• Significant decrease in major adverse kidney events within 30 days for
balanced crystalloids vs NS (14.3%% vs 15.4%, p=0.04)
• Insignificant decrease in in-hospital mortality at 30 days for the
balanced crystalloid vs. NS group (10.3% vs 11.1%, p=0.06).
• Similarly, the balanced crystalloid group showed lower incidence of
hyperchloremia defined as Cl > 110 mmol/L (24.5% VS 35.6%) and
lower incidence of plasma bicarbonate concentration < 20 mmol/L
(35.2% vs. 42.1%) when compared to NS.
18

19. SMART TRIAL- Outcome
• The incidence of new renal-replacement therapy for the balanced
crystalloid vs. NS group was 2.5% and 2.9%, respectively (P=0.08)
• The incidence of persistent renal dysfunction for the balanced
crystalloid vs. NS group was 6.4% and 6.6%, respectively (P=0.60).
19

20. SMART TRIAL- Outcome
• Importantly, patients with a diagnosis of sepsis had lower incidence of 30-
day mortality in the balanced crystalloid vs. NS groups (25.2% vs 29.4%,
p=0.02).
• This is also important because fluids are a key treatment in sepsis and
volume of fluid resuscitation is often higher..
• Based on these results, 1 in every 94 patients admitted to the ICU and
treated with balanced crystalloid instead of NS may prevent the need for
new renal replacement therapy, persistent renal dysfunction, or death when
compared to NS
20

21. SALT-ED + SMART
21
• These two RCTs are groundbreaking and practice changing, leading
many emergency departments and intensive care units to transition to
more regularly using balanced crystalloids over NS.
• While conclusions of the trials often point to RL being superior to NS,
it can also be reassuring that NS was given to so many patients
without substantial harm.

22. What if……..?
22
• The volume of IVF administered in this studies may be more
important than the specific type of fluid
• i.e. worse outcomes with excess IVF

23. Balanced Solution versus Saline in Intensive
Care Study (BaSICS Trial) (Zampieri et al.,
2021)
23
• A robust RCT that compares plasma-lyte with normal saline for fluid
resuscitation in the ICU and two rates of fluid administration, 999
ml/hr and 333 ml/hr (n=11,000)
• A multicenter, double blind RCT from 75 ICUs across Brazil
• Primary outcome was a 90-day mortality rate between fluid type and
rate of IVF infusion

24. BaSICS Trial-Outcome
24
• 90-day mortality rate was;
• 26.4% in the plasma-lyte group and 27.2% in the NS group (aHR 0.97, CI
0.90-1.05, P=0.47)
• 26.6% in the slower infusion rate vs 27.0% in the faster infusion rate group
(aHR, 1.03; 95% CI, 0.96-1.11; P=0.46).
• A secondary outcome from the BaSICS trial showed no significant
difference in need for renal replacement therapy or doubled creatinine
in balanced crystalloid group (27.8%) versus NS group (28.9%) (95%
CI, 0.86-1.04, p=0.37)

25. Crystalloid Liberal or Vasopressors Early
Resuscitation in Sepsis Trial (CLOVERS TRIAL)
25
• The idea of “you have to swell to get well” is no longer the standard of
care, and permissive hypotension is preferred in several disease states.
• CLOVERS seeks to compare early transition from fluids to vasopressors
in patients with septic shock and also answer important question about
fluid volume and rate or volume given to patients during resuscitation
• A multicenter, randomized, un-blinded, two-arm clinical trial to
determine the impact of a restrictive fluids (“Medicine to Raise Blood
Pressure First”) strategy as compared with a liberal fluids (“Fluids
First”) strategy on 90-day in-hospital mortality (n=2,320)

26. Update on CLOVERS Trial
• Phase 3 stopped in February, 2022
• No significant difference observed between the two arms in the first 24 hours
of treatment (n=1,566)
• No significant difference in 90-day mortality rates nor safety concerns
• They will continue patient follow-up according to the study protocol
for those already enrolled in the trial
• Conducted by the PETAL Network and sponsored by NHLBI
26

27. RL or NS?
27
• BaSICS trial makes it clear that there is not one fluid that is ideal, and
certain populations and diseases will benefit from selected fluid choice
• SALT-ED and SMART trials showed that both non-critically ill and
critically ill patients who received balanced crystalloids were less
likely to have renal injury leading to need for renal replacement
therapy or to have persistent renal dysfunction, but an additional large
ICU based RCT (BaSICS Trial) did not show statistical difference in
balanced crystalloid versus NS.
• Fluid therapy should be targeted to specific patient populations and
presenting disease.

28. Myths surrounding Ringers lactate!!!
• Despite these studies, there are still several concerns regarding the use
of RL in the ED
28

29. 1. Hyperkalemia
• Myth – “Ringers lactate should not be used in hyperkalemia because it
contains potassium and may make the problem worse.”
• Hyperkalemia is the electrolyte abnormality most likely to quickly kill a
patient
• Causes;
• Drugs (Co-trimixazole, ACEIs, ARBs, Potassium-sparing diuretics etc.)
• Rhabdomyolysis
• Cell death
• Though Ringers lactate contain a higher concentration of potassium (4mEq/L)
when compared to NS (0 mEq/L), its potassium composition is physiologically
closest to human serum (4.5-5.0mEq/L) and is typically slightly lower 29

30. Hyperkalemia
• There is negligible effect on overall serum potassium level as a result of RL
infusion since potassium’s volume of distribution is greater in extracellular fluid
causing little to no change on the overall serum potassium level.
• It would take a significant amount of fluid to have any effect on raising overall
serum potassium level since the potassium equilibrates between intracellular and
extracellular fluid spaces.
• Hyperchloremic metabolic acidosis which can result from NS infusion will
increase cellular shifting and worsen extracellular potassium levels when
compared to RL which has no effect on the K+/H+ gradient.
• Alkalinization that occurs as a result of RL infusion due to the 28 mEq/L of
lacatate may even further drive potassium into the cell, lowering the overall
serum potassium level. 30

31. Hyperkalemia
• One subgroup analysis from the SMART trial evaluated critically ill adults
with hyperkalemia who received balanced crystalloids RL or plasma-lyte
vs. NS.
• Overall, 8 (8.5%) of the patients in the balanced crystalloid group vs. 13
(14.0%) patients in the NS group developed severe hyperkalemia (p=0.24).
• While this is not statistically significant, it does show that the higher level
of potassium that is administered from RL or plasma-lyte (4-5) vs. NS (0) is
closer to physiologic plasma and does not lead to worsening hyperkalemia.
31

32. Hyperkalemia
• Pearl:
RL is a safe fluid to use in resuscitation of patients with elevated
potassium levels. The potassium/hydrogen shifts that occur as result
of the acidic environment from normal saline infusion may worsen
serum potassium levels.
32

33. 2. Lactic acidosis
• Myth – “Ringers lactate causes lactic acidosis, and therefore should be avoided.”
• Lactic acidosis is a result of failed oxidative metabolism, leading to an anion-gap
metabolic acidosis.
• This can be secondary to decreased metabolism of naturally generated lactate in the
body (such as in liver disease) or increased production of lactate when there is
decreased oxygen available for aerobic metabolism.
• Causes;
• sepsis,
• trauma
• dehydration.
• iatrogenic causes of type B lactic acidosis secondary to beta agonist administration, such as
epinephrine or albuterol (less common)
33

34. Lactic acidosis
34
• The lactate in RL is in the form of sodium lactate which our bodies
metabolize to products that prevent cellular death.
• It is not the same lactate that is generated during anaerobic metabolism,
which causes metabolic acidosis (Robergs et al., 2017)
• One double-blind RCT evaluated the change in lactate between RL and NS
groups while also looking at the overall change in pH, bicarbonate, sodium,
and chloride levels.
• This study found that after an infusion of 30mL/kg IV RL, lactate increased
by 0.93 mmol/L compared to 0.37 mmol/L in the NS group (p=0.2), but the
NS group saw a larger decline in overall pH (0.06 vs. 0.03) and bicarbonate
level (2.35 vs. 0.36) (Zitek et al., 2018)

35. Lactic acidosis
35
• In an additional RCT published by Didwania et al. (1997), 24 healthy
adults received 1L infusions of RL, NS, dextrose, or D5W and showed
no difference in lactate levels post-infusion
• It is theorized that the lactate infused in the RL group may be
metabolized under ischemic conditions and decrease overall cell death
and is less likely to worsen an acidosis when compared to the
hyperchloremic acidosis that results from NS.
• Pearl:
Though RL contains sodium lactate, this is generally metabolized by the
body and does not contribute to worsening lactic acidosis. In fact, the
acidosis associated with NS likely has more clinically harmful effects.

36. 3. Medication Reactions
36
• Some Truth – “Because ringers lactate can have calcium precipitation with so
many medications, it is easier and safer to use normal saline.”
• It is postulated that the sodium concentration within ceftriaxone contributes to
the formation of calcium precipitates and therefore the mixture of these
solutions in the same line should be avoided.
• An additional study evaluated compatibility of RL with 94 medications by in
vitro visual observation, particle counting testing, and light obscuration particle
count testing.
• Eight drugs were considered incompatible with RL including ciprofloxacin,
cyclosporine, diazepam, ketamine, lorazepam, nitroglycerin, phenytoin, and
propofol and are recommended against administering through the same IV line
as RL (Vallee et al., 2021)

37. Medication Reactions
37
• Two separate studies were performed to evaluate the incidence of clot
formation when RL was transfused with packed RBCs and Whole Blood.
• In both studies, there was no statistically significant difference in clot
formation when NS or RL was infused or used as a diluent in emergent
transfusions.
• There is however, a theoretical risk of coagulation when RL is administered
together with preserved blood (with citrate anticoagulant) via the same
infusion set (Singh et al, 2021; Lorenzo et al., 1998; Cull et al., 1991)

38. Medication Reactions
38
• Pearl:
Though theoretical risk of clotting exists, RL can be administered
simultaneously in patients >28 days with ceftriaxone, blood products
and other calcium-containing medications. If possible, a separate line
should be used to avoid potential precipitation.

39. SPECIFIC INDICATIONS FOR
RINGERS LACTATE
39

40. 1. Diabetic Ketoacidosis (DKA)
• In DKA, the body responds to low insulin levels by burning fatty acids
and producing ketone bodies, leading to an anion-gap metabolic
acidosis.
• Often overall body potassium is low; however, it may appear to be
falsely elevated due to hydrogen ions shifting intracellularly and
potassium moving extracellularly.
• Fluids, in addition to insulin and potassium, are the main treatment for
this disease process
40

41. Diabetic Ketoacidosis (DKA)
• One subgroup analysis from the SALT-ED and SMART trial compared
patients with a clinical diagnosis of DKA to look at;
• time to resolution (glucose <200 mg/dL)
• 2 of the following: bicarb > 15, venous pH >7.3, anion gap ≤ 12)
• time to discontinuation of insulin infusion.
• Given the sheer volume of fluid required to treat this disease process,
(on average, 4.5 liters) differences in fluid composition can be a key
factor in recovery.
41

42. Diabetic Ketoacidosis (DKA)
42
Outcome
• significant decrease in both time to resolution of DKA (13 hours vs 16.9 hours)
in the balanced crystalloid group as well as time to insulin discontinuation (9.8
hours vs 13.4 hours).
• This equates to an absolute reduction of 4 hours and relative reduction of 20-
30% in time to DKA resolution and discontinuation of insulin infusion,
possibly decreasing overall hospital stay and associated morbidity.
• This is hypothesized to be due to the concentrations of sodium lactate in RL
and acetate in plasma-lyte which metabolize into bicarbonate helping to close
the anion gap metabolic acidosis.

43. Diabetic Ketoacidosis (DKA)
• Additionally, fewer patients in the balanced crystalloid group
exhibited hypokalemia (K+ < 3mmol/L) compared with the NS group.
• However, this study was in contrast to prior work on the subject which
failed to show any significant difference (Self et al., 2017; Mahler et
al., 2011; Van Zyl et al., 2012; Jayashree et al., 2019; Yung et al.,
2017)
43

44. 2. Dehydration
• In patients with dehydration (defined as dry mucous membranes, SBP <90
mmHg, HR >100 bpm or PO intolerance), a RCT comparing NS and
balanced crystalloids showed significantly lower pH levels in patients who
received NS (7.40 7.37 7.36) as well as a drop in bicarbonate levels (23.1,
22.2, 21.5) compared to an increase in the plasma-lyte group (7.40 7.42
7.45) and (23.4, 23.9, 24.4) (Hasman et al., 2012)
• A similar study conducted in pediatric patients with acute diarrhea and
severe dehydration showed no significant difference in pH between NS and
RL, but the RL group required less fluids (310 vs 530mL) and had a shorter
median hospital stay (38 vs 51 days) (Mahajan et al., 2012)
44

45. 3. Pancreatitis
• One RCT compared RL with NS in patients with acute pancreatitis and found a
significant reduction in SIRS after 24 hours in the RL group (84% vs 0%, p=0.035).
• There was also a reduction in CRP in the RL group (51.5 vs 104, p=0.02), a marker of
systemic inflammation (Wu et al., 2011)
• An additional study by Lee et al. (2021) showed that there was a significantly shorter
hospital length of stay and fewer ICU admissions in patients diagnosed with acute
pancreatitis who were treated with aggressive fluid resuscitation via RL compared to NS
• Though the exact mechanism is unknown, there are animal studies showing decrease in
enzymes involved in pancreatitis such as zymogen (Khatua et al., 2020)
Pearl:
Several studies shows balanced crystalloids are associated with improved outcomes in
patients with DKA, dehydration, and pancreatitis.
45

46. INTERLUDE
1 Corinthians 10:23
ALL THINGS ARE LAWFUL FOR ME, BUT ALL THINGS ARE
NOT EXPEDIENT…
(KJV)
46

47. CONSIDERATIONS FOR
ALTERNATIVE FLUID TO RINGERS
LACTATE
47

48. 1. Traumatic brain injury
• It is theorized that due to hyperosmolarity of the solution and ability to decrease
cerebral edema, NS is the preferred resuscitation fluid in patients with Traumatic
Brain Injuries (TBI) when compared with RL
• Additionally, RL is thought to increase neutrophil and inflammatory responses.
• One study comparing outcomes of patients with TBI who were treated with RL vs NS
prior to hospital arrival found RL was associated with higher 30-day mortality than
NS (HR = 1.78, CI 1.04 – 3.04, p=0.03) (Rowell et al., 2016)
• Subgroup analysis on this topic with the best RCT to date, BaSICS Trial, showed that
a balanced crystalloid (plasma-lyte) had higher 90-day mortality rate (31.3%) versus
NS (21.1%) (HR 1.48, 95% CI 1.03-2.12, p=0.02) (Zampieri et al., 2021)
48

49. 2. Hyponatremia
• RL contains 130 mEq/L Na compared to 135-145mEq/L Na in plasma. Because of
this, there is concern that resuscitation with RL may worsen or lead to
hyponatremia.
• There is limited data around RL causing hyponatremia or the use of RL in treating
acute hypovolemic hyponatremia in the Emergency Department setting.
• One study evaluated post-operative hyponatremia and cited quantity of fluid
resuscitation as the cause of hyponatremia versus use of RL itself.
• The theory is that increased extracellular volume leads to ADH release and worsens
hyponatremia. (Steele et al., 1997)
49

50. 3. Burns
50
• In acute burns, there is concern for both dehydration and electrolyte
imbalances such as hyponatremia and hypoglycemia secondary to
evaporative losses and changes in cellular permeability.
• One RCT evaluated the use of RL alone in burn resuscitation when
compared to use of RL and Dextrose in NS in an attempt to correct
electrolyte abnormalities.
• This study showed that due to low sodium (130mEq/L) and potassium
(4mEq/L) levels in RL when compared to human plasma, dextrose
containing NS should be used as an adjunct to assist in replenishing
electrolytes.

51. 3. Burns
• Burn patients treated with RL and DNS had statistically significant
less evidence of hyponatremia and hypoglycemia (Bedi et al., 2019)
Pearl:
In patients presenting with hyponatremia and acute burns, RL is not
necessarily the sole fluid choice for resuscitation, and NS is preferred
in patients with concern for TBI.
51

52. Practice Points
• Ringers lactate composition is more similar to human plasma than
Normal saline
• Ringers lactate is preferred to Normal saline in select ED presentations,
such as DKA, dehydration and pancreatitis
• Ringers lactate will not worsen hyperkalemia and the acidosis but
Normal saline may in fact be more detrimental
52

53. Practice Points
• Ringers lactate does contain sodium lactate but will not contribute to
clinically significant worsening lactic acidosis
• Normal saline is preferred in patients with TBI.
• Consider Normal saline when mixed with certain medications such as
ceftriaxone or blood transfusions to avoid precipitation when only a
single IV access site it available
53

54. Patient Case Scenario
• The 70-year-old female is febrile with signs of dehydration and hypotension
in the setting of sepsis due to a urinary tract infection.
• She also has lactic acidosis and hyperkalemia on her initial workup.
• Based on the data above, RL is a safe and appropriate approach to fluid
resuscitation in combination with antibiotics.
• Broad spectrum antibiotics should be started and the patient admitted to the
medical ICU for further workup and care.
54

55. CONCLUSION
• No single IVF is superior to the other and the choice should be based
on the clinical condition
• Use of Ringers lactate in most cases has better outcomes compared to
the use of NS
• RL should be the first line IVF for resuscitation in some selected
indications
55

56. REFERENCES
Wilkinson, I.B. et al. (2017). Oxford Handbook of Clinical Medicine. 10th
Edition. Oxford University Press. Page: 666-667
Self, W.H., et al. (2020). Pragmatic Critical Care Research Group. Clinical
Effects of Balanced Crystalloids vs Saline in Adults With Diabetic Ketoacidosis:
A Subgroup Analysis of Cluster Randomized Clinical Trials. JAMA Netw Open.
2020 Nov 2;3(11):e2024596
Self, W.H., et al. (2018). SALT-ED Investigators. Balanced Crystalloids versus
Saline in Non-critically Ill Adults. N Engl J Med.1;378(9):819-828.
Self, W.H., et al. (2017). Saline versus balanced crystalloids for intravenous
fluid therapy in the emergency department: study protocol for a cluster-
randomized, multiple-crossover trial. Trials. 2017;18(1):178. 56

57. REFERENCES
Semler, M.W., et al. (2018). SMART Investigators and the Pragmatic Critical Care
Research Group. Balanced Crystalloids versus Saline in Critically Ill Adults. N Engl J
Med.1;378(9):829-839.
Zampieri, F.G., et al. (2021). Effect of Intravenous Fluid Treatment With a Balanced
Solution vs 0.9% Saline Solution on Mortality in Critically Ill Patients: The BaSICS
Randomized Clinical Trial. JAMA. Published online August 10, 2021
Zampieri, F.G., et al. (2021). Effect of Slower vs Faster Intravenous Fluid Bolus
Rates on Mortality in Critically Ill Patients: The BaSICS Randomized Clinical
Trial. JAMA. Published online August 10, 2021
Frazee, E., and Kashani, K. (2016). Fluid Management for Critically Ill Patients: A
Review of the Current State of Fluid Therapy in the Intensive Care Unit. Kidney Dis
2016;2:64-71. 57

58. REFERENCES
National Library of Medicine (U.S). (2018, February – present). Crystalloid Liberal
or Vasopressors Early Resuscitation in Sepsis (CLOVERS). Identifier NCT03434028.
https://clinicaltrials.gov/ct2/show/NCT03434028
Simon LV, Hashmi MF, Farrell MW. Hyperkalemia. [Updated 2021 Feb 11]. In:
StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2021 Jan-
Farkas, J. Myth-busting. Lactated ringers is safe in hyperkalemia, and superior to
normal saline. Online Publication. www.EMcrit.org
Toporek AH, Semler MW, Self WH, Bernard GR, Wang L, Siew ED, Stollings JL,
Wanderer JP, Rice TW, Casey JD; SMART Investigators and the Pragmatic Critical
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59. REFERENCES
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Sharif Z, Al-Alawi M. Beware of beta! A case of salbutamol-induced lactic
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Didwania A et al. Effect of Intravenous Lactated Ringer’s Solution Infusion on
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64

65. ACKNOWLEDGEMENT
Dr Amos Adapalala Bugri
(Senior Specialist Pharmacist)
65

66. THANK YOU
66