Traumatic Brain Injury and the Use of Hypertonic Solutions
Abstract & Commentary
By Roger Härtl, MD, Leonard and Fleur Harlan Clinical Scholar in Neurological Surgery, Associate Professor, Neurological Surgery, Weill Cornell Medical College. Dr. Härtl reports that he is a consultant for Synthes and Brainlab..
Synopsis: Current research does not support the use of hypertonic solutions for initial resuscitation of patients with acute traumatic brain injury, but it remains an option for subsequent treatment.
Source: Bulger EM, et al. and ROC Investigators. Out-of-hospital hypertonic resuscitation following severe traumatic brain injury: A randomized controlled trial. JAMA 2010;304:1455-1464.
Early in the 20th century, hypertonic saline (hs) solutions were noted to affect brain volume after systemic administration. Weed and McKibben had reported on the "alteration of brain bulk" by administration of hypertonic solutions, such as 30% saline, in 1919.1 Harvey Cushing was among the first to use hypertonic saline for reduction of intracranial pressure (ICP) in patients he operated on for brain tumors.2 The first measurements of intracranial pressure dynamics in response to different sodium chloride solutions were made by Wilson et al in 1951.3 These early findings remained largely unrecognized. However, numerous hypertonic solutions other than hypertonic saline, such as glucose, urea, glycerol, sorbitol, and mannitol, were used to treat brain edema and elevated intracranial pressure. The rediscovery of HS and its introduction into neurocritical care was mediated by promising results using small volumes of hypertonic solutions for the resuscitation of patients in severe hemorrhagic shock. In shock and reperfusion injury, small volumes of hypertonic saline solutions were demonstrated to improve tissue microcirculation; thus the concept of "small- volume-resuscitation" was born.4 How these solutions would affect traumatic brain injury (TBI), a condition frequently associated with hemorrhagic shock, was unknown. Subsequent animal studies indicated a potentially beneficial effect of HS on the cerebral microcirculation, brain oxygenation, and intracranial pressure in the setting of hemrorrhagic shock and TBI.4-8
The principle effect of HS on intracranial hemodynamics is probably due to osmotic mobilization of water across the intact blood-brain barrier (BBB) which reduces cerebral water content. HS has been shown to decrease water content of mainly non-traumatized brain tissue, due to an osmotic effect after building up a gradient across the intact BBB.9 Effects on the microcirculation also may play an important role. HS dehydrates endothelial cells and erythrocytes, which increases the lumen of the vessels and deformability of erythrocytes and leads to plasma volume expansion with improved blood flow.10,11 HS reduces leukocyte adhesion in traumatized brain.4 Despite widespread practice and numerous case series indicating a beneficial effect of HS in the treatment of patients with elevated ICP and intractable intracranial hypertension, the current adult TBI Guidelines make no recommendation regarding the use of HS bolus injections for control of elevated ICP.12 However, continuous HS infusion currently is recommended as an option for the control of intracranial hypertension after severe TBI in the pediatric guidelines.13 In our practice, we currently use HS bolus and continuous infusion in patients with elevated intracranial pressure (ICP) or at risk of developing intracranial hypertension and we have demonstrated its safety in a large patient cohort.14
The idea to combine hypertonic saline with colloids was born out of the desire to prolong the transient effect of hypertonic saline on the cardiovascular system when used for resuscitation from hypovolemic shock. Addition of a hyperoncotic colloid increases the effect on cardiovascular parameters such as blood pressure and cardiac output from around one to several hours.7 Hydroxyethyl starch and dextran are the colloids most widely used. In combination with hypertonic saline they have been in clinical use for fluid resuscitation since 1991 and have regulatory approval in several European countries. They exert their beneficial effect primarily by expanding volume of the intravascular compartment.
The well-planned and conducted study by Bulger et al tries to address the important remaining question of how HS with and without dextran component may impact patients with isolated TBI without hemorrhagic compromise. In this multicenter, randomized, controlled trial, patients with isolated TBI with a GCS in the field of 8 or less received either a single 250 ml bolus of 7.5% saline/6% dextran 70, 7.5% saline, or normal saline in the out-of-hospital setting. The primary outcome measure was 6-month neurological outcome. The study was terminated prematurely after inclusion of 1,331 patients because it met prespecified futility criteria and no difference in outcome was seen between the groups. As expected, serum sodium levels on admission were higher in the HS groups but the initial ICP, the highest ICP within the first 12 hours, and the total time of ICP elevation within the first 12 hours were not different between treatments. The patients also were well-balanced in terms of their initial GCS, CT-based criteria, and other indicators of TBI severity.
In essence, the authors confirm that there is, as has been previously shown, no "magic bullet" for the treatment of severe TBI.15 The significant drop in mortality and overall improvement in the outcome from severe TBI that has been achieved over the past decade should be attributed primarily to our better understanding of the pathophysiology of TBI; this led to an emphasis on aggressive and early treatment of systemic hypotension and hypoxia, direct rapid transport of these patients to dedicated trauma centers, and the implementation of treatment protocols in the ICU setting with early nutrition, infection prophylaxis, and ICP monitoring and treatment.16-19 Nonetheless, the current study adds a missing link to the puzzle of how hypertonic solutions should or should not be used in our management of severe TBI. The current "Guidelines for Pre-Hospital Management of TBI" recommend hypertonic saline with or without colloids as an "option" for initial resuscitation in the field.20 ■
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2. Cushing H, Foley F. Alterations of intracranial tension by salt solutions in the alimentary tract. Proc Soc Exper Biol 1920;17:217-218.
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20. Badjatia N, et. al. Brain Trauma Foundation; BTF Center for Guidelines Management. Guidelines for prehospital management of traumatic brain injury. 2nd ed. Prehosp Emerg Care 2008;12(Suppl 1):S1-S52.