Intracranial Pressure Effects
As mentioned previously, the primary goals of managing a patient with TBI are to reduce cerebral edema, decrease ICP, and improve CPP. While mannitol has historically been considered the drug of choice for acute intracranial hypertension, it has some drawbacks.54 First, it is believed that the blood-brain barrier may be compromised in TBI, leading to accumulation of mannitol in already edematous tissue, which ultimately causes an increase in cerebral edema and ICP. Additionally, mannitol is an osmotic diuretic and may cause hypotension, which worsens secondary brain injury.
HTS has the theoretical potential to improve both CPP and intracranial hypertension without the deleterious effects of mannitol. The primary effect by which HTS reduces ICP is by setting up an osmotic gradient across an intact blood-brain barrier and dehydrating brain tissue in the mostly uninjured portions.55 It is more attractive than mannitol as a hyperosmotic therapy, as it is less permeable across an intact blood-brain barrier and has a higher osmotic gradient in the vascular compartment.8,9 Because the osmotic effect of HTS alone is transient, it is usually combined with a colloid (hydroxyethyl starch or dextran). This may prolong the clinical effect by 2 to 4 hours.56
Hemodynamic And Microcirculatory Effects
Isotonic crystalloid solutions currently predominate over all other resuscitative fluids for the hypotensive trauma patient. When NaCl or lactated Ringer’s is given, it is rapidly redistributed throughout the entire extracellular space with no preference for the vascular space. Ultimately, only 10% to 20% of the infused isotonic crystalloid remains in the circulation.57-59 This can necessitate large volumes of fluid for resuscitation, potentially worsening hemorrhage and neuronal injury. (See Figure 2.)
In contrast, HTS allows for resuscitation with smaller volumes (4 mL/kg of 7.5% NaCl). The osmotic effect is immediate, and it can increase the intravascular volume by as much as 4 times the infused volume within minutes of infusion.60 That said, it is most likely an oversimplification to consider HTS as a potential treatment for TBI and shock solely from its actions as an osmotic agent. Fortunately, there are many rheological effects by which it may improve microcirculation, including decreasing blood viscosity, endothelial cell edema, and capillary resistance via dehydration of erythrocytes.8-10 Hypertonicity also has a direct relaxant effect on the vascular smooth muscle with resultant arteriolar vasodilation.2 Last but not least, the optimization of blood flow and CPP is supported by the effect of HTS on increasing the MAP.
One of the more intriguing aspects of HTS is its potential to modulate the immune system in the trauma patient. It is well known that dysfunctional activation of the immune system after traumatic injuries and other shock states can cause subsequent tissue and organ injury.61 Basic science studies have confirmed that HTS has marked effects on the immune system.2 It has been shown to blunt neutrophil activation, modify cytokine production,3 and augment T-cell function.4,5 In animal models, it decreases hemorrhage-induced neutrophil activation and is protective against acute lung injury.6,7 To date, no clinical studies have been conducted that demonstrate a patient-oriented benefit from these immunomodulation properties.
As a resuscitative fluid, HTS is cheap, does not transmit infection, and is unlikely to provoke an anaphylactic reaction. It has a strong safety record based on previous clinical trials and reported use. However, it is worthy to note that the patients at the highest risk of being harmed by HTS (such as those with heart failure, pulmonary edema, and kidney failure) were often excluded from these trials.
The largest randomized controlled trial of HTS and TBI (which included 1331 patients) did not find a statistically significant difference in the rate of adverse events between the treatment groups, although they did describe a not statistically significant trend toward a higher nosocomial infection rate in the HTS groups. Importantly, they observed no increase in progression of intracranial hemorrhage in the hypertonic fluid groups.32
One obvious potential complication of HTS is sequelae from unintended iatrogenic-induced hypernatremia (other than ODS). A retrospective analysis of more than 600 neurointensive care unit patients examined upper threshold values of hypernatremia. Unless serum sodium values exceeded 160 mEq/L, no worse outcomes were detected. This is well beyond the value that would commonly be reached after initial treatment in the ED.62
ODS is arguably the most-feared complication from the administration of HTS. Fortunately, it is rare and generally only associated with chronic hyponatremic patients who undergo overrapid correction. There is little evidence from the current literature to support the fear of ODS from treating patients with TBI or hemorrhagic shock with HTS. However, since ODS is a devastating condition, caution should still be exercised when using HTS in a patient who may have chronic hyponatremia (such as an alcoholic patient or a patient with congestive heart failure).
In head-injured patients whose blood-brain barrier is disrupted, the potential exists for HTS to permeate into the injured tissue, raising water content, increasing ICP, and exacerbating brain damage.11 The majority of studies do not report this finding. These effects are more likely to be secondary to changes in serum osmolality.63 Table 3 summarizes the adverse effects of HTS as well as its benefits.
Jeffrey A. Holmes, MD
February 4, 2013