Use of Salt-Water Solution to Improve Symptoms in Concussion
Condition: Brain Concussion; Post-Concussion Symptoms
MeSH terms: Brain Concussion; Post-Concussion Syndrome
Study type: Interventional

Summary: 
      The purpose of this study is to find out if 3% hypertonic saline (salt-water solution) given
      in a vein improves the headache that may be caused by a concussion. 3% hypertonic saline may
      also improve some of the other symptoms that may be caused by concussion (for example:
      confusion, nausea, vomiting).

      This research is being done because there have been previous experience which suggests that
      3% hypertonic saline has been beneficial in the treatment of children with more severe brain
      injury.
    

Detailed description: 
      A concussion is formally described as a clinical syndrome characterized by immediate and
      transient changes in brain function including alteration of mental status and level of
      consciousness, resulting from mechanical force or trauma. Despite its prevalence, its
      pathophysiology remains a mystery as does its spectrum of clinical presentation.

      A concussion, sometimes described as a mild traumatic brain injury (TBI), can often present
      with initial loss of consciousness, change in behavior, confusion, amnesia, or aphasia which
      all result in a Glasgow Coma Scale (GCS) that is less than normal. As the time from the
      initial injury lengthens, these symptoms can progressively worsen and new symptoms such as
      vomiting and headaches can also develop. Usually, there is no evidence of a significant
      intracranial injury by computed tomography (CT) imaging and these symptoms often improve with
      a gradual progression towards a normal neurologic baseline; in fact, the risk of complication
      in this population is very rare. The time for this improvement varies greatly and can occur
      over a period ranging from hours to days. During this transient time, the patient is often
      very uncomfortable due to persistent headaches, inability to tolerate oral intake due to
      nausea and/or vomiting, confusion, and episodes of amnesia. In some instances, the combative
      behavior of the patient can be difficult to tolerate both by the family and the medical
      staff.

      Just as the symptoms caused by a concussion vary greatly in presentation and duration, so do
      the theories behind the pathophysiology of mild TBI. The transient loss of cerebral function
      after a head injury was formally differentiated from severe head injury for the first time by
      the Persian physician Rhazes in 900 AD and has since caused much speculation and varying
      clinical descriptions throughout history. It took another 500 years before a "commotion" or
      shaking of the brain was theorized to be responsible for clinical signs. Presently, the exact
      cause of concussive symptoms continue to remain an enigma; a major question however, is
      whether a concussion is due to a lesser degree of diffuse structural change seen in severe
      traumatic brain injury, or if it is in fact a mechanism caused by reversible functional
      changes of the neurons and axons.

      Animal models have demonstrated altered metabolic profiles of the brain tissue which resolves
      within hours of initial insult. Other animal models have demonstrated a change in the
      integrity of the microvascular endothelium after TBI. It can be hypothesized that there are
      areas of "microcontusion" and pericontusional edema that maybe responsible for alterations in
      brain chemistry which may ultimately lead to the clinical symptoms associated with mild TBI.
      Multiple other studies have theorized that the direct and indirect effects of trauma on
      cerebral vasculature may lead to a vasoconstrictive phenomenon that may be responsible for
      postconcussive symptoms.

      Currently, the management of patients with mild traumatic brain injuries includes observation
      and symptomatic therapies including analgesia without obscuring a neurologic exam
      (acetaminophen) and antiemetic measures (ondansetron). While many patients are often
      discharged home after initial evaluation in the Emergency Department, some are admitted to
      the hospital for supportive care. The symptoms may resolve in a period of hours to days.

      There has been substantial retrospective data and limited prospective data in children which
      suggests that hypertonic saline (HTS) can improve the control of intracranial pressure (ICP)
      in patients with acute brain injury. In 1992, a report published by the Journal of
      Neurosurgical Anesthesiology indicated that HTS reduced elevated ICP in children after head
      injury. This study looked at a single intravenous bolus of HTS in comparison to the same
      volume of normal saline and demonstrated a clear difference. Subsequently, it was
      demonstrated that HTS appears to be efficacious in controlling ICP. In a retrospective chart
      review, 68 children with closed head injury were cared for using a standardized protocol and
      the intravenous infusion of 3% HTS in quantities designed to drive the serum sodium to levels
      that would reduce the ICP to less than 20 mmHg. Of the patients in who HTS was used, only 3
      patients (4%) died of uncontrolled ICP. Of note, there were no adverse effects of
      super-physiologic hyperosmolarity such as renal failure, pulmonary edema, or central pontine
      demyelination.

      The use of 3% hypertonic saline in traumatic brain injury has recently been investigated by
      many centers and is now included as first tier therapy in the management of decreasing
      intracranial pressure (ICP) secondary to severe traumatic brain injury in the pediatric
      population. Its mechanism in ICP reduction lies in its favorable rheologic and osmolar
      gradient effects; it concomitantly augments intravascular volume and increase mean arterial
      pressure to provide optimum cerebral perfusion pressure. Again, multiple studies have shown
      the direct effect of HTS in lowering ICP along with its safety in a pediatric population. HTS
      has also been used to treat altered mental status in diabetic ketoacidosis.

      Many of the symptoms associated with mild traumatic brain injury may be due to mild
      elevations in intracranial pressure, minimal cerebral edema, and/or vasospasm of the cerebral
      vasculature. Hypertonic saline may be instrumental in improving the symptoms of concussion by
      addressing the commonly suspected mechanisms responsible for these symptoms. By reducing mild
      cerebral edema and/or improving cerebral perfusion pressure, cerebral vasospasm may be
      overcome by reversal or by improved flow; thus, 3% HTS may allow favorable treatment of
      postconcussive symptoms.
    

Intervention name(s): 3% Hypertonic saline; Placebo
Intervention type(s): Drug; Drug
Intervention description(s): Normal saline
Allocation: Randomized
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Treatment
Keywords: Brain Concussion; Post-Concussion Syndrome; Closed Head Injury; Traumatic Brain Injury; Hypertonic Saline Solution