Question 5

With respect to the use of hypertonic saline (HTS} in the critically ill, list the indications, mechanisms of action and outline the supporting evidence as well as the potential adverse effects.

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College answer

The main indications for the use of hypertonic saline in the critically ill are: 
Osmotherapy to manage intracranial hypertension  
Correction of (symptomatic) hyponatraemia. 
Fluid resuscitation in hypovolaemic shock (uncommon) 
Burns resuscitation 
Has been used in tricyclic poisoning 
Mucolytic in nebulized form – e.g. for cystic fibrosis, induced sputum sample, used in bronchiolitis with positive trial evidence 
The range of concentrations of HTS used clinically varies from 1.8 – 30%.  Needs to be given via central venous access 
Mechanisms of action 
•    Marked osmotic shift of fluid from the intracellular to the interstitial and intravascular space.  
•    Reverses the increase in endothelial cell volume in shock and ischaemia, limiting capillary leak.  
•    Plasma viscosity is reduced by increased water content improving blood flow.  
•    Hypertonicity has a direct relaxant effect on vascular smooth muscle. End result is increased capillary blood flow. This may help counteract vasospasm in SAH.  
•    HTS induced increase in intravascular volume leads to an autoregulatory reduction in intracerebral blood volume. 
•    Increased cardiac output – increased preload, reduced PVR and SVR and reduced myocyte oedema. 
•    Immuno-modulatory effects and reduction of intestinal apoptosis in haemorrhagic shock 
Potential adverse effects 
Acute hyperosmolar state 
•    Osmotic demyelination syndrome 
•    Acute heart failure 
•    Pulmonary oedema 
•    Hyperchloraemic acidosis 
•    Hyperosmolar renal failure 
•    Dilutional coagulopathy 
Theoretical risks 
•    Increased rate of blood loss secondary to rapid volume expansion  
•    Reverse osmosis phenomenon in disrupted blood brain barrier with worsening cerebral oedema 
•    Severely dehydrated risk of worsening cellular dehydration 
•    Acute cerebral dehydration potentially result in shearing on bridging vessels and SAH 
Most of these risks are theoretical or can be avoided by careful use in patients with hyponatraemia and monitoring  
Evidence supporting use of HTS 
Fluid resuscitation 
Studies evaluating HTS in resuscitation in various shock states have shown benefit in outcomes including blood pressure, fluid balance and mortality. Comparison is difficult as different concentrations of HTS used, different case mix and other methodological issues. 
Concerns about potential of HTS to increase bleeding have not been proven. 
Overall HTS seems effective in increasing blood pressure in haemorrhagic shock. Its use in other forms of shock is not so well supported. 
Osmotherapy to control ICH 
Studies have evaluated HTS in traumatic brain injury and subarachnoid haemorrhage and used as either 7.5% boluses or 3% continuous infusions and HTS appears to be effective in reducing ICP. No evidence to suggest a better neurological outcome or survival benefit. 
Summary of clinical use 
Note: This template was long and complex and candidates were not expected to cover all the points in order to pass. 


The potential adverse effects of hypertonic saline are common to all (or, most) of its various uses. These are listed in a nice review of 3% saline among neuroICU patients where a nice table (Table 1) lists the potential adverse effects of hypertonic saline administration. I will reproduce the relevant parts of this table below.

  • Hyperosmolarity
  • Overshoot hypernatremia
  • Congestive heart failure and pulmonary oedema
  • Hypokalemia
  • Normal anion gap metabolic acidosis
  • Coagulopathy
  • Phlebitis (hypertonic saline is a sclerosant)
  • Renal failure (due to vasoconstriction)
  • Decreased level of consciousness
  • Rebound intracranial hypertension
  • Seizures
  • Central pontine myelinolysis
  • Subdural and intraparenchymal hemorrhage

As for the indications mechanisms and evidence, this answer would certainly work well as a table, if only there were fewer columns. Fortunately, with the right monitor DerangedPhysiology is 1200 pixels wide. 

The Various Uses of Hypertonic Saline
Mechanism Evidence Advantages and disadvantages
As sodium replacement, for hyponatremia:

Replacement of the missing ion

The recent overview of published guidelines by Verbalis et al (2014) covers the recommendations for the use of hypertonic saline in symptomatic hyponatremia.

Ideal when fluid restriction is needed, eg. in SIADH.

Not ideal in situations where hypovolemia accompanies hyponatremia, i.e. when volume as well as sodium need to be replaced. 

As osmotherapy, for raised ICP:
Osmotic dehydration of brain tissue

The (2016)  publication of the BTF Guidelines was  unable to make a firm recommendation in favour of hypertonic saline.

A reasonably recent review (Lazarides et al, 2013) found a small statistically significant benefit for its use, as compared to mannitol.

Cheap, stable in storage, very rapid effect.

At least as potent as mannitol when it comes to reducing ICP

Less potential for hypovolemia than with mannitol

Safe endpoint (serum sodium around 145-155) is easily monitored with serial ABGs.

Needs central venous access, and should not be used if the patient is chronically hyponatremic

As a resuscitation fluid for shock:
Increased preload, some vasoactive properties 

Poor quality data in support (Oliveira et al , 2002)

No benefit in sepsis
(Ashfar et al, 2017)

Poor quality data and no benefit in trauma (de Crescenzo et al, 2017)

Smaller volume means less haemodilution (in trauma for example)

Small volume also means a more neutral fluid balance

All the haemodynamic and immunomodulatory benefits should also be helpful

For management of tissue oedema:
Improved diuresis

Paterna et al (2011) found some benefit in CCF patients.

Evidence is inconsistent and based on small scale studies.

Improved fluid balance

Potentially, better cardiac function 

May be frustrated by activation of the RAAS.

For cystic fibrosis, as an expectorant and mucolytic:
Multiple mechanisms 

Osmotic hydration of the mucus layer (i.e. attracting water into it) and disruption of mucus proteins.

Recommended for CF patients who can tolerate it (Elkins and Bye 2011)

Not very well investigated in other groups, eg. COPD

It's irritant, which the patients will not appreciate; but this promotes cough and improves secretion clearance

Routine frequent use may result in systemic absorption of sodium and chloride, which might not be desirable.


Lazaridis, Christos, et al. "High-Osmolarity Saline in Neurocritical Care: Systematic Review and Meta-Analysis*." Critical care medicine 41.5 (2013): 1353-1360.

Strandvik, G. F. "Hypertonic saline in critical care: a review of the literature and guidelines for use in hypotensive states and raised intracranial pressure." Anaesthesia 64.9 (2009): 990-1003.

Holmes, J. A. "Therapeutic Uses Of Hypertonic Saline In The Critically Ill Emergency Department Patient." EM Critical Care 3.1 (2013).

Oliveira, Roselaine P., et al. "Clinical review: Hypertonic saline resuscitation in sepsis." Critical care 6.5 (2002): 418.

Asfar, Pierre, et al. "Hyperoxia and hypertonic saline in patients with septic shock (HYPERS2S): a two-by-two factorial, multicentre, randomised, clinical trial." The Lancet Respiratory Medicine 5.3 (2017): 180-190.

Pfortmueller, Carmen Andrea, and Joerg C. Schefold. "Hypertonic saline in critical illness-A systematic review." Journal of Critical Care 42 (2017): 168-177.

Paterna, Salvatore, et al. "Short-term effects of hypertonic saline solution in acute heart failure and long-term effects of a moderate sodium restriction in patients with compensated heart failure with New York Heart Association class III (Class C)(SMAC-HF Study)." The American journal of the medical sciences 342.1 (2011): 27-37.

De Crescenzo, Claire, et al. "Prehospital hypertonic fluid resuscitation for trauma patients: A systematic review and meta-analysis." Journal of Trauma and Acute Care Surgery 82.5 (2017): 956-962.

Gunn, Mark L., et al. "Prospective, randomized trial of hypertonic sodium lactate versus lactated Ringer's solution for burn shock resuscitation.Journal of Trauma and Acute Care Surgery 29.9 (1989): 1261-1267.

Elkins, Mark R., and Peter TP Bye. "Mechanisms and applications of hypertonic saline." Journal of the Royal Society of Medicine104.1_suppl (2011): 2-5.