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Hypertonic Saline – A Review of the Advantages and Disadvantages

Hypertonic Saline – A Review of the Advantages and Disadvantages. Emily Rogers Delmas MD. Disclosures - None . Outline. What is hypertonic saline? Origins Physiologic Response Advantages Disadvantages Evidence. Saline Origins. 1831 – Blue Cholera Epidemic in Europe

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Hypertonic Saline – A Review of the Advantages and Disadvantages

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  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.

  10. Advantages of Hypertonic Saline • Hemodynamic • Immunologic • Infectious

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

  12. 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

  13. 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

  14. 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) 235-241.

  15. Results

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

  17. 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. 2008; 9:67-74.

  18. Results • Infections • 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

  19. Results

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

  21. 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):543-554.

  22. 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)

  23. Mechanism of Action for Hypertonic Saline and Lowered ICPs

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

  25. The evidence is missing • Trauma • Randomized control trials • Bulger, E et al. 2008 (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):139-148. Archive Surg. 1993; 128:1003-1013.

  26. 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] 0.69 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

  27. 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)

  28. Questions?

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