Brad Nichol M.D.
Valley View Hospital
Would the FDA approve Normal Saline Today?
Objecitve:
1. How has normal saline become the IVF
of choice?
2. What are it’s drawbacks?
3. What is normal saline’s composition?
4. Human and animal studies showing it’s
drawbacks.
Would the FDA approve Normal Saline Today?
History of Normal Saline
 Developed by Hamberger in 1886
 For in vitro study of RBC’s
 Found 0.9% NaCl solution prevented
chloride shift and felt to be isotonic with
human blood.
○ Unknown how this in vitro study became a
standard IV solution.
Would the FDA approve Normal Saline Today?
History of Normal Saline
 O’Shaughnessey 1831
 Indian Blue Cholera Pandemic in England
 Proposed a “new method of infusing highly
oxygenated salts into the venous system…to
restore the arterial qualities”

Latta after this article started making and
using saline preparations.
 His solutions improved survival but not adopted
by contemporaries.
 Early ones were hypotonic but evolved to
Na=134, Cl=118, Hco3=16
Would the FDA approve Normal Saline Today?
History of Normal Saline
Ringer 1883
 Experiments with muscle and heart
contractility
 Found 0.75% NaCl to be ideal
 Used water from faucet which showed to be
superior to distilled water.
○ “Some inorganic constituents in the pipe
water…”
 Calcium, magnesium, alkaline
 Later modified by Hartmann by adding
lactate in 1930’s.
Would the FDA approve Normal Saline Today?
Comparison of IVF’s and Human Plasma
pH
mOsm
Na
Cl
K
Ca
Mg
Buffer
Plasma
7.4
289
142
103
4
5
2
HCO3 22-32
0.9 NS
5.0
308
154
154
LR
6.5
273
130
109
4
3
3
Lactate 28
Would the FDA approve Normal Saline Today?
Why is 0.9% Saline Preferred?
 Higher osmolarity to expand ECF/vascular
volume
 Potential benefit for cerebral edema
Problems with 0.9 % Saline
 Hyperchloremic acidosis
○ Think lethal triad…..
Would the FDA approve Normal Saline Today?
Human Studies
 Waters 2001 randomized 66 pts
undergoing AAA repair, LR vs NS
 Goal: keep CVP and PAWP within 10% of
baseline
 NS group required more platelets and bicarb.
Still had lower pH on arrival to ICU.

O’malley randomized kidney transplant
patients to LR vs NS.
 NS patients had lower bicarb and pH after
surgery.
 Terminated because of more life threatening
episodes of hypekalemia in NS group.
Would the FDA approve Normal Saline Today?
Swine Hemorrhage Model
 Animals received Grade V liver injury
and allowed to hemorrhage for 30 min.
○ Resuscitated with NS or LR to normal
baseline level for 2 hours.
○ Followed TEG protocol to fix coagulopathy
 NS group had twice the amount of blood
loss, also required more platelets
 required more fluid to maintain BP
 Lower pH levels
Would the FDA approve Normal Saline Today?
Why are we not using Lactated Ringer’s
 “Incompatibility” with some medications
 Blood banks feel calcium may interfere with
transfusions by interacting with citrate.
 Concern for causing lactic acidosis
Would the FDA approve Normal Saline Today?
Lorenzo 1998
 Mixed blood with NS, LR, and Moidifed LR
with increasing conc. of CaCl2
 Studied infusion time and filter weight and
appearance of gross clot.
 No difference between NS and LR groups.
○ Increased clot formation when LR was mixed
5gm of CaCl2
Would the FDA approve Normal Saline Today?
Conclusions:
Normal saline
 Mysteriously anointed IVF of choice
 Hyperchloremic acidosis
 Higher IVF requirements
 Higher transfusion requirements