Emily Rogers Delmas MD






What is hypertonic saline?
Origins
Physiologic Response
Advantages
Disadvantages
Evidence

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

Multiple forms
◦
◦
◦
◦
2%
3%
7.5%
23.4%

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



Increases serum osmolarity
Causes redistribution of fluid from interstitial
and intracellular space to the
INTRAVASCULAR SPACE!
And VIOLA! Repletion of intravascular volume


Transient hemodynamic improvement found
with use of hypertonic saline alone
Theory – addition of colloid would selectively
retain more water intravascularly

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.



Hemodynamic
Immunologic
Infectious





Increase intravascular volume -> Restores
MAPs
Increase preload
Increase cardiac output
Decrease systemic vascular resistance
Decrease afterload





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





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


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.


Enhances intracellular killing of bacteria by
attenuating receptor-mediated activation of
pro-inflammatory cascades
Limits inflammatory response

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.

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





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



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.


HS does not benefit neurologic function or
mortality when compared with conventional
fluids
Effective at reducing ICP (3 RCT)

Trauma
◦ Randomized control trials
1.Bulger, E et al. 2008 (n=209), 7.5%/dextran vs.
LR
a)
b)
c)
Primary outcome = ARDS-free survival at 28 days
Stopped early for futility
Subset analysis in patients requiring > 10 units
PRBCs did have decreased ARDS
2.Vassar M et al 1993 (n=233)
a)
b)
c)
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
1. Archive Surg. 2008; 143
(2):139-148.
2. Archive Surg. 1993;

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





Peri-operative: favorable but not definitive
Meta-analysis: McAlister V et al Cochrane
2010
15 studies, 614 patients
Hypertonic saline benefits
1) Less volume received with equal diuresis ->
less positive fluid balance
2) 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)