Hypertonic Saline (HTS) is experiencing a moment in the ER and critical care circles. This is likely related to a reverence for the endothelial glycocalyx, and concern for high volume fluid therapy induced damage. There are several human trials evaluating the effectiveness of standard crystalloid fluid bolus therapy that call into question the therapeutic benefits of traditional high volume fluid therapy. HTS may be indicated in the management of cerebral edema and elevated intracranial pressure (such as in the patient with a traumatic brain injury), treatment of hyponatremic seizures and resuscitation of hypovolemic shock. There are theoretical benefits of this fluid type in patients with septic shock and systemic inflammatory conditions, with possible positive effects on the endothelial glycocalyx. Strong evidence in support of positive changes in serum biomarker concentrations reflecting improved inflammatory condition and glycocalyx function is lacking. When used judiciously and with careful planning, there are minimal risks to the administration of hypertonic saline, up to 7.2% NaCl. This practice pearl will focus on the use of HTS as a hyperosmolar agent, highlighting the most common and practical indications as well as contraindications or complications that may arise with use.

Hypertonic Saline and Elevated Intracranial Pressure?

Elevated intracranial pressure can be a life-threatening emergency, developing secondary to a variety of both acute and chronic disease processes. The most common causes of intracranial hypertension (ICH) include traumatic brain injury (TBI), intracranial neoplasia/mass, inflammatory brain disease, intracranial hemorrhage, and seizures. One of the pillars to non-surgical treatment of ICH is early administration of hyperosmolar fluids, like hypertonic saline or mannitol. Both hypertonic saline and mannitol relieve ICH within 15-20 minutes of administration and have effects that persist as long as 4-6 hours in humans. One experimental dog study described effective water movement from CSF into intravascular space following HTS administration that persisted for 90 minutes. Hypertonic saline does not decrease blood volume or contribute to hypovolemia like the osmotic diuretic mannitol does. In multiple human and animal studies, hypertonic saline has outperformed mannitol in terms of degree of ICH resolution and fewer treatment failures. These hyperosmolar agents work by osmotic movement of intracellular and interstitial water from tissues (example: brain) into the intravascular space. Once this occurs in the skull with ICH, osmotic shifts decrease the intracranial volume, decrease the intracranial pressure, and improve perfusion to the brain.

Hypertonic Saline for Hypovolemia?

Hypertonic saline has been used for rapid, robust intravascular fluid expansion in situations of severe hypovolemic shock. The mechanism of action is by way of its hyperosmolar effects, pulling water from tissues into the intravascular compartment. This results in rapid plasma volume expansion, increased cardiac contractility (inotrope), variable vagally-mediated heart rate reduction, and transient increase in cardiac output. Given these properties, hypertonic saline is a good choice as part of the fluid resuscitation plan for any patient with severe hypovolemia and possible ICH. There is experimental evidence of improved endothelial cell function in states of systemic inflammation and CPR as well.

When and How to Use Hypertonic Saline?

The most readily available formulation of hypertonic saline in veterinary medicine is 7.2% NaCl. Many of the experimental studies report on 7.2% or 3% slow infusions. Extrapolated dosing that can be considered for use in dogs is 2 – 4 ml/kg 7.2% NaCl IV slow bolus (over 2 minutes) for suspected ICH or hypovolemia. When using this hyperosmolar agent in treatment of hypovolemia, it is essential to include an isotonic crystalloid as part of the fluid replacement plan to minimize risk of intracellular dehydration and severe electrolyte imbalance. A good rule of thumb is to aim for no greater than a 1mEq/L change in serum sodium per hour. When using hyperosmolar therapies, it is recommended to monitor serum sodium levels before and after infusion. If multiple infusions of hypertonic saline are performed in a short period of time, exceeding 6ml/kg in a 4-hour period, the author recommends measuring blood electrolytes. If sodium has increased too quickly, the clinician can adjust the fluid therapy plan to ameliorate a further rise and adjust the sodium closer to baseline range while observing a slow decrease and avoiding a change faster than 1mEq/h. If sodium rises too quickly, osmotic demyelination syndrome can occur. The symptoms of this may take days to manifest and can range from mild gait abnormalities to severe impairment that may be permanent. Conversely, lowering serum sodium too quickly once the brain has adapted to high sodium levels can lead to osmotic shifting of water into the cells and subsequent cell swelling (cerebral edema). The symptoms of cerebral edema often occur acutely and may range from mild ataxia to severe neurological decompensation. The clinician reaching for hyperosmolar agents should be aware that complications can arise with therapy and know where to look for guidance and be prepared for intervention if necessary.

Why use HTS

• to ameliorate ICH, to rapidly expand intravascular volume in states of shock, to ameliorate endothelial cell swelling and endothelial glycocalyx function, to augment inflammatory mediator profiles in systemic inflammatory conditions

How to use HTS

• 2-4 ml/kg IV 7.2% or 3% NaCl over 2 minutes, consider baseline serum sodium and repeat q 4-6 hours pending trend of sodium measurement

When to reach for HTS

• Traumatic Brain Injury
• Post CPR
• Status epilepticus
• Heat Stroke **carefully monitor serum sodium in these patients**
• Hypovolemic shock and time sensitive need to proceed with anesthesia, such as GDV or unstable hemoperitoneum
• Septic shock on their way to pressor therapy
• Canine parvovirus

References:

Smart L, Macdonald SPJ, Bosio E, Fatovich D, Neil C, Arendts G. Bolus therapy with 3% hypertonic saline or 0.9% saline in emergency department patients with suspected sepsis: A pilot randomised controlled trial. J Crit Care. 2019 Aug;52:33-39. 

Fletcher DJ, Boller M. Fluid Therapy During Cardiopulmonary Resuscitation. Front Vet Sci. 2021 Jan 28;7:625361.

Mekonnen M, Ong V, Florence TJ, Mozaffari K, Mahgerefteh N, Rana S, Duong C, Plurad DS, Yang I. Hypertonic Saline Treatment in Traumatic Brain Injury: A Systematic Review. World Neurosurg. 2022 Jun;162:98-110. 

Ito N, Suzuki K, Koie H, Tsumagari S, Kanayama K, Miyahara M, Asano R. The effect of 7.2% hypertonic saline solution on the duration of sodium gradient between the cerebrospinal fluid and the venous circulation in the dog. J Vet Med Sci. 2006 Feb;68(2):183-5.

About the Guide: Raegan J Wells, DVM, MS, DACVECC


Dr. Wells attended Arizona State University where she earned a Bachelor of Science degree in Life Sciences. She then earned a Doctor of Veterinary Medicine degree from the Colorado State University College of Veterinary Medicine and Biomedical Sciences in Fort Collins, CO and a Master of Science in Clinical Sciences. She went on to complete a rotating medicine and surgery internship at the Veterinary Specialty Hospital of San Diego in San Diego, CA. Following her internship, she returned to the Colorado State University College of Veterinary Medicine and Biomedical Sciences where she completed a Critical Care Residency. She went on to become an Assistant Professor for one year. Raegan has worked in private specialty practice in Maricopa County AZ for 15 years.