1. Brad Nichol M.D. Valley View Hospital

2. 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.

3. 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.

4. 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

5. 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.

6. Would the FDA approve Normal Saline Today? pHmOsmNaClKCaMgBuffer Plasma7.4289142103452HCO3 22-32 0.9 NS5.0308154 LR6.5273130109433Lactate 28 Comparison of IVF’s and Human Plasma

7. 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…..

8. 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.

9. 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

10. 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

11. Would the FDA approve Normal Saline Today? Lorenzo 1998 Mixed blood with NS, LR, and Moidifed LR with increasing conc. of CaCl 2 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 CaCl 2

12. Would the FDA approve Normal Saline Today? Conclusions: Normal saline  Mysteriously anointed IVF of choice  Hyperchloremic acidosis  Higher IVF requirements  Higher transfusion requirements