1. Hypertonic Saline – A Review of the Advantages and Disadvantages
Emily Rogers Delmas MD

2. Disclosures - None

3. Outline What is hypertonic saline? Origins Physiologic Response
Advantages
Disadvantages
Evidence

4. Saline Origins 1831 – Blue Cholera Epidemic in Europe
William Brooke O’Shaughnessy published in The Lancet use of salted fluid in dogs with no harm
Eventually adapted by physician Thomas Latta and used in patients with cholera with beneficial results

5. Hypertonic Saline Basics
Multiple forms 2% 3%
7.5%
23.4%

6. Hypertonic Saline Basics
Composition of Hypertonic Saline
0.9% = 154 mEq/L of Na and Cl
2% = 342 mEq/L of Na and Cl
3% = 513 mEq/L of Na and Cl
7% = 1200 mEq/L of Na and Cl
23.4% (bullet) = 4000 mEq/L of Na and Cl
Many hypertonic saline formulations include a colloid – dextran or hydroxyethyl starch

7. Physiologic Response to Hypertonic Saline
Increases serum osmolarity
Causes redistribution of fluid from interstitial and intracellular space to the INTRAVASCULAR SPACE!
And VIOLA! Repletion of intravascular volume

8. Suggested Benefit of Adding Hyperoncotic Colloid to Hypertonic Saline
Transient hemodynamic improvement found with use of hypertonic saline alone
Theory – addition of colloid would selectively retain more water intravascularly

9. A Comparison of Several Hypertonic Solutions of Resuscitation of Bled Sheep
Hypertonic 7.5% Saline/6% Dextran 70 resulted in sustained higher cardiac output and MAPs
Also resulted in lower total peripheral resistance compared to dextran or hypertonic saline alone
Study completed with hetastarch as well and showed similar CV results, but less sustained volume expansion
Smith GJ, Kramer GC, Perron PR, Nakayama S, Gunther RA, Holcroft JW. A comparison of several hypertonic solutions for resuscitation of bled sheep. J Surg Res. 1985;39:517–528.

11. Advantages of Hypertonic Saline
Hemodynamic
Immunologic
Infectious

12. Hemodynamic Advantages
Increase intravascular volume -> Restores MAPs
Increase preload
Increase cardiac output
Decrease systemic vascular resistance
Decrease afterload

13. Small volume resuscitation with hypertonic saline dextran solution
Study looking at systolic and diastolic pressures in conscious hemorrhaged sheep
Given 2 minute infusion of 200ml HSD
MAPs increased after half of dose infused
MAP normalized at end of infusion
CO increased to 30% above baseline at end of infusion

14. Immune Modulation with Hypertonic Saline
Blunts neutrophil activation
Decreases neutrophil-endothelium binding
Reduces TNF alpha production
Enhances function of normal T cells
Restores function of suppressed T cells by stimulating IL-2

15. Hypertonic Saline Resuscitation: A Tool to Modulate Immune Function in Trauma Patients?
In vitro study – added hypertonic saline in increasing concentrations to human peripheral blood mononuclear cells
Measured the following:
T cell proliferation -> increased
IL-2 production -> increased
Restored T cells
Junger W et al. Hypertonic Saline Resuscitation: A Tool to Modulate Immune Function in Trauma Patients? Shock 1997:Vol 8 (4)

16. Results

17. Infectious Advantages
Enhances intracellular killing of bacteria by attenuating receptor-mediated activation of pro-inflammatory cascades
Limits inflammatory response

18. Perioperative Hypertonic Saline May Reduce Postoperative Infections and Lower Mortality Rates
Retrospective study over 2 years, pair matched, case control study
Looked at adult patients post-op back surgery admitted to SICU after major spinal procedure
Matched for age, sex, operative site and magnitude, yr of operation
Each pair – one pt received hypertonic saline and one received isotonic fluid
57 pairs matched out of 364 patients
Charalambous MP, Swoboda SM, Lipsett PA. Perioperative Hypertonic Saline May Reduce Postoperative Infections and Lower Mortality Rates. Surgical Infections ; 9:67-74.

19. Results Infections Patients receiving HS in OR slightly longer Death
HS group – 3
Isotonic group - 11
Patients receiving HS in OR slightly longer
Death
HS group – 2 (p = 0.19)
Isotonic group – 7 (p = 0.08)
ICU LOS same (median time – 22hrs)
Hospital LOS
HS – 7.7 +/- 6.1 days
Isotonic – 7.3 +/- 3.5 days

20. Results

21. Disadvantages Hypernatremia Hyperchloremic acidosis
Potential for central pontine myelinosis
Association with renal failure in burn patients
Potential for extravasation injuries (tissue injury)
3% and higher must be infused via central access

22. Hypertonic Sodium Resuscitation is Associated with Renal Failure and Death
UAB
Compared burn patients resuscitated with either HS or LR
Conclusions –
Pt resuscitated with HS had fourfold increase in renal failure
Pt resuscitated with HS had 2x mortality of LR pts
After 48 hours, cumulative fluid loads similar
Huang PP et al. Hypertonic Sodium Resuscitation is Associated with Renal Failure and Death. Annals of Surgery. 1995; 221(5):

23. Hypertonic Saline and TBI/ICP Reduction
HS does not benefit neurologic function or mortality when compared with conventional fluids
Effective at reducing ICP (3 RCT)

24. Mechanism of Action for Hypertonic Saline and Lowered ICPs

25. The evidence for the widespread use of hypertonic saline in surgical/critically ill patients is controversial and inconclusive

26. The evidence is missing
Trauma
Randomized control trials
Bulger, E et al (n=209), 7.5%/dextran vs. LR
Primary outcome = ARDS-free survival at 28 days
Stopped early for futility
Subset analysis in patients requiring > 10 units PRBCs did have decreased ARDS
Vassar M et al 1993 (n=233)
4 arms= 7.5%, 7.5%/6%dextran, 7.5%/12%dextran, LR
Higher increase in systolic BP with hypertonic saline
All arms equal survival
Archive Surg. 2008; 143 (2):
Archive Surg. 1993; 128:

27. The evidence is missing
Critically-ill patients
Meta-analysis: Burns, F et al. Cochrane Review 2008
14 trials with 956 patients
Relative risk (RR) for death
Trauma: 0.84 (95% confidence interval [CI] to1.04) -> trend toward benefit
Burns: 1.49 (95% CI 0.56 to 3.95) -> harm
Surgery: 0.51 (95% CI 0.09 to 2.73) -> benefit

28. The evidence is missing
Peri-operative: favorable but not definitive
Meta-analysis: McAlister V et al Cochrane 2010
15 studies, 614 patients
Hypertonic saline benefits
Less volume received with equal diuresis -> less positive fluid balance
Increased maximum intra-operative cardiac index
The truth awaits => not enough evidence on increased survival or organ function
(small trials, not powered enough to detect outcome measures)

29. Questions?