Hyperosmolar therapy in the treatment of Traumatic Brain Injury Mannitol vs. Hypertonic saline benefits and adverse effects

Traumatic brain injury (TBI) is a major cause of disability, death, and economic cost to the U.S  society. One of the central concepts that emerged from research is that all neurological damage from TBI doe not occur at the moment of impact, but evolves over the following  hours and days. Furthermore improved outcome results when these secondary, delayed insults, resulting in reduced 

cerebral perfusion to the injured brain, are prevented .

Cerebral edema due to brain injury compromises the delivery of essential nutrients and alters normal intracranial 

pressure. Treatment for intracranial hypertension is aimed at reducing the volume of 1 of the 3 intracranial compartments, brain tissue, blood, and cerebrospinal fluid. Hyperosmolar therapy is one treatment intervention in the care of patients with severe traumatic brain injury resulting in cerebral edema and intracranial hypertension. The effect of hyperosmolar solutions on brain tissue was first studied nearly 90 years ago. Since that time, mannitol has become the most widely used hyperosmolar solution to treat elevated intracranial pressure. Increasingly, hypertonic saline solutions are being used as an adjunct to mannitol in basic science research and clinical studies. Hyperosmolar solutions are effective in reducing elevated intracranial pressure through 2 distinct mechanisms: plasma expansion with a resultant decrease in blood hematocrit, reduced blood viscosity, and decreased cerebral blood volume; and the creation of an osmotic gradient that draws cerebral edema fluid from brain tissue into the circulation.

hyperosmolar agents currently in clinical use for traumatic brain injury TBI are mannitol and hypertonic salin (HS)

Mannitol:

 Mannitol is widely used in the control of raised ICP following TBI. Its use is advocated in tow circumstances. First, a single administration can have short term beneficial effects, during which further diagnostic procedures and interventions can be accomplished. Seconed, mannitol has been used as a prolonged therapy for raised ICP. There is however , a lack of evidence to recommend repeated, regular administration of mannitol over several days. Although there are data regarding it's basic mechanism of action, there are few human studies that validate different regimens of mannitol administration.

 Hypertonic salin (HS):

current therapies used for ICP control (mannitol, barbiturates) bear the risk of further reducing perfusion to the brain either by lowering blood pressure and cerebral perfusion pressure or by causing cerebral vasoconstriction(hyperventilation). Ideally, a therapeutic intervention should effectively reduce ICP while preserving or improving CPP.

   the use of HS for ICP control was discovered from studies on small volume resuscitation. Hypertonic saline solutions were tested in poly-traumatised patients with hemorrhagic shock. The subgroup with accompanying TBI showed the greatest benefit in terms of survival and hemodynamic parameters were restored effectively . the finding that HS may benefit patients with TBI while preserving or even improving hemodynamic parameters stimulated further research on the effects of HS solutions on increased Intracranil pressure in patients with TBI subarachnoid hemorrhage stroke and other pathologies.

Adverse Effects Of Osmothyrapy

 There are few studies that focus on the adverse effects of HTS as the primary outcome measure. However, all the studies have reported these as part of their findings.

 One of the worst potential complications related osmotherapy is central pontine myelinolysis or osmotic demyelination syndrome, which is clinically evident as lethargy and quadraparesis. The risk is generally associated with rapid correction of hyponatremia with HS . 

Osmotherapy may also cause electrolyte disturbances. Mannitol may result in hyponatremia and hypokalemia, followed by hypernatremia, due to its strong osmotic diuretic effect. On the other hand, repeated infusion of HS may increase sodium and chloride concentrations to values far above the normal, resulting in hypernatremia and hyperchloremic acidosis. Additionally, large amounts of potassium may be lost in the urine, resulting in hypokalemia. HS appears to exert its diuretic effect more from atrial natriuretic peptide (ANP) release than through osmotic effect . In the bolus-dose studies, the mean highest serum sodium concentration was 170.7 mmol/L, but there were no adverse effects though to be related to HS. 

Strandvik et al. thought it would be prudent that serum sodium level should be measured within 6h of administration if bolus doses are given. Volume overload is a common side effect of all hyperosmolar solutions and is potentially problematic among patients with cardiopulmonary disease. HS administration naturally expands in volume, whereas mannitol initially expands, then dehydrates. For patients in whom volume expansion must be maintained, such as those with SAH, HS provides an elegant solution to both issues of ICP treatment and prophylaxis/treatment of vasospasm. In this population, mannitol is potentially hazardous but can be used with central venous pressure (CVP) monitoring and careful matching of fluid intake and output. Renal insufficiency or renal failure can not be neglected with osmotherapy. Mannitol, which is excreted unchanged across the glomerular membranes, may cause serious renal failure. Though the mechanism is not known, it may be related to high osmolality in tubuli, resulting in acute tubular necrosis. Mannitol has been shown to be an independent risk factor for acute renal failure after severe head injury. As a similar or even higher increase in osmolality from hypertonic saline or urea causes less renal failure.

CONCLUSION

 The management of patients with acutely elevated ICP remains a major challenge. Osmotherapy is a key protocol in numerous treatment, including sedation, controlled ventilation, and decompressive surgery. It safely and effectively lowers acutely raised ICP in a variety of neurological conditions. Although mannitol remains osmotic agent the most frequently used, recent evidence suggests the superiority of hypertonic saline to mannitol. However, further research into the precise mechanisms of action and into the neurohumoral and immunologic effects is needed. Randomized clinical trials should assess the impact of osmotherapy not only on short-term outcome but also on quality of life in the longer run.

  

References :

● National Center for Biotechnology Information 

http://www.ncbi.nlm.nih.gov/

● Guidelines for the management of sever traumatic brain injury  3^rd edition 

brain trauma foundation 

http://www.braintrauma.org/

● International Journal of Anesthesiology Research, 2013, 1, 56-61 

http://www.pharmapublisher.com/jms/index.php/ijar/article/download/105/75

from Yamin Sallowm, MS4