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Hypertonic saline: a clinical review

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Abstract

Literature suggest that hypertonic saline (HTS) solution with sodium chloride concentration greater than the physiologic 0.9% can be useful in controlling elevated intracranial pressure (ICP) and as a resuscitative agent in multiple settings including traumatic brain injury (TBI). In this review, we discuss HTS mechanisms of action, adverse effects, and current clinical studies. Studies show that HTS administered during the resuscitation of patients with a TBI improves neurological outcome. HTS also has positive effects on elevated ICP from multiple etiologies, and for shock resuscitation. However, a prospective randomized Australian study using an aggressive resuscitation protocol in trauma patients showed no difference in amount of fluids administered during prehospital resuscitation, and no differences in ICP control or neurological outcome. The role of HTS in prehospital resuscitation is yet to be determined. The most important factor in improving outcomes may be prevention of hypotension and preservation of cerebral blood flow. In regards to control of elevated ICP during the inpatient course, HTS appears safe and effective. Although clinicians currently use HTS with some success, significant questions remain as to the dose and manner of HTS infusion. Direct protocol comparisons should be performed to improve and standardize patient care.

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  1. Department of Neurological Surgery, Temple University, 3401 N. Broad St., Suite C540, Philadelphia, PA, 19140, USA

    R. Tyagi, K. Donaldson, C. M. Loftus & J. Jallo

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  1. R. Tyagi
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  2. K. Donaldson
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  3. C. M. Loftus
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  4. J. Jallo
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Attila Schwarcz, Pécs, Hungary

Traumatic brain injury (TBI) imposes severe problems in developed countries since it disables a huge number of healthy and young individuals every year. TBI is also one of the leading causes of mortality among young adults. The primary TBI is often complicated with diverse pathological processes that result in increased intracranial pressure (ICP) decreasing cerebral perfusion severely. The management of raised ICP is still an open field for improvements. Tyagi et al. review literature data of a promising alternative aimed at ICP reduction: hypertonic saline solution (HTS). It appears that use of HTS in the prehospital management of patients with TBI does not result in either better neurological outcome or in lower rate of mortality. However, application of HTS in intensive care units causes prompt and significant ICP decrease. It is also suggested that HTS can be effective in cases refractory to standard mannitol therapy. The inverse relationship between ICP and serum Na+ levels is well documented both in animals and humans. The often observed rebound effect after bolus injection of HTS may be prevented by continuous infusion targeted toward a high level of serum Na+.

As it is obvious from the up-to-date review of Tyagi et al., class I evidence (i.e., double blind, prospective, multicenter study) is still missing as concerns application of HTS (e.g., dose, duration of treatment, ideal serum Na+ level, etc.). However, based on the literature data, application of HTS may be recommended to lower ICP in intensive care units not only as an ultimum refugium but also as a regular treatment.

Oliver W. Sakowitz, Andreas W. Unterberg, Heidelberg, Germany

In their review, Tyagi et al. discuss the mechanisms of action, adverse effects, and current clinical studies on the use of hypertonic saline (HTS) in patients with traumatic brain injury (TBI). Osmotherapy with HTS (and in combination with colloids for small-volume resuscitation) is a promising concept which has been investigated experimentally and clinically for the past two decades. However, so far only one large prospective, randomized clinical study has been conducted by Cooper and coworkers [1]. Prehospital treatment of patients with TBI and hypotension with HTS did not influence outcome when compared to conventional fluid therapy.

Clinical experience from neurointensive care, however, is different, and especially for pediatric TBI promising results have been published. It may be argued that outcome parameters, such as Glasgow Outcome Scale scores after 6 or 12 months, may not adequately reflect the clinical value of HTS. Surrogate parameters, such as brain tissue oxygenation, metabolism, and regional cerebral blood flow, more and more commonly used in multimodality monitoring, could be used alternatively to directly assess “tissue outcome” [2, 3].

The authors are to be commended for their thorough literature review and discussion not only limited to TBI, but also stroke and resuscitation medicine. Their approach of a protocol-based comparison is especially helpful to gain an overview of the different hypertonic fluid regimens currently in use. It also shows the difficulty of comparing these heterogeneous treatments with a “conventional” mannitol-based regimen if equiosmolar doses are not strictly used.

More prospective and randomized clinical studies are needed to elucidate the value of hypertonic fluid therapy in the neurointensive care unit.

References

1. Cooper et al. (2004) Prehospital hypertonic saline resuscitation of patients with hypotension and severe traumatic brain injury. A randomized controlled trial. JAMA 291:1350–1357

2. Hartl et al. (1997) Mannitol decreases ICP but does not improve brain-tissue pO2 in severely head-injured patients with intracranial hypertension. Acta Neurochir Suppl 70:40–42

3. Sakowitz et al. (2007) Effects of mannitol bolus administration on intracranial pressure, cerebral extracellular metabolites, and tissue oxygenation in severely head-injured patients. J Trauma 62:292–298

Ignacio J. Previgliano, Buenos Aires, Argentina

This excellent review by Dr. Tyagi and coworkers provides an analysis of the role of hypertonic saline (HTS) in different types of brain injuries. The first conclusion one can make is that there is not sufficient evidence to favor the routine use of HTS either in the prehospital setting or in the emergency room or in the intensive care unit (ICU).

Most of the prospective papers showed no difference between HTS regimens (3% or 7% plus dextran) and conventional resuscitation with lactated Ringer’s solution in the prehospital setting and long-term neurological recovery assessed by the Extended Glasgow Outcome Scale, specially the Australian research performed by Cooper et al. and Wade et al.’s meta-analysis that showed that HTS is not different from the standard of care and that HTS plus dextran may be superior.

Prospective randomized trials in the ICU have an insufficient number of patients to achieve either a standard or a guideline in HTS use. There is also a lack of uniformity in dosage and concentration, with a wide range from 3 to 29% and variations in volume from 100 ml/bolus to continuous infusion.

An important issue is the development of osmotic demyelination syndrome (ODS), previously known as pontine (PM) or extrapontine myelinolysis (EPM). This syndrome, first described by Adams in chronic alcoholics in 1959, includes tetraplegia, pseudobulbar palsy, and acute changes in mental status leading to coma or death without intervention. Anatomopathological findings of symmetric, demyelinating focus prominent in the central pons were associated with this clinical picture. Similar histologic symmetric lesions were later identified in extrapontine locations, including the white matter of the cerebellum, thalamus, globus pallidus, putamen, and lateral geniculate body, a condition termed EPM. There is an increased risk of PM or EPM development when hyponatremia correction is higher than 2 mmol/h or 8 mmol/day.

Diagnosis is possible by clinical symptoms and by MRI studies (“bat wings” sign in the pons). In the setting of severe brain injury patients, differential diagnosis should be made with primary brain stem lesions, critical care polyneuropathy, or hypoxic anoxic encephalopathy among others.

Only Khanna et al.’s papers addressed the lack of incidence of ODS, but both papers pertain to a pediatric population and one of them is retrospective.

So the risk of ODS is not established and the odds of developing it is high.

The choice of the osmotic agent in our practice is based in the patient’s sodium: if it is normal or high we use mannitol in a 0.5 g/kg per bolus, if it is below 130 mEq/l we use 3% HTS in a 2 ml/kg per bolus. Both boluses are repeated at a 4-h interval according to the intracranial pressure. The other potential use of 3% or 7% HTS in our unit is refractory intracranial hypertension, before using indomethacin, barbiturates, or decompressive craniotomy.

I agree with the author’s statement “it may be that adequate volume and hemodynamic resuscitation is in fact the critical factor in improving neurological outcome.” It could be achieved either with HTS or mannitol under expert intensivist surveillance.

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Tyagi, R., Donaldson, K., Loftus, C.M. et al. Hypertonic saline: a clinical review. Neurosurg Rev 30, 277–290 (2007). https://doi.org/10.1007/s10143-007-0091-7

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