Hyperosmolar Therapy Alexandra Serafino, PharmD Pharmacy Resident, Intermountain Medical Center, Intermountain Healthcare; Salt Lake City, UT Objectives: • List the more common causes of elevated intracranial pressures (ICP) • Compare and contrast the pharmacokinetics, pharmacodynamics, and therapeutic applications of hypertonic saline and mannitol • Determine if hypertonic saline or mannitol should be used preferentially when given a patient case
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Hyperosmolar Therapy
Alexandra Serafino, PharmD Pharmacy Resident, Intermountain Medical Center, Intermountain
Healthcare; Salt Lake City, UT
Objectives: • List the more common causes of elevated intracranial pressures (ICP) • Compare and contrast the pharmacokinetics, pharmacodynamics,
and therapeutic applications of hypertonic saline and mannitol • Determine if hypertonic saline or mannitol should be used
preferentially when given a patient case
SaltyorSweet‐HowDoYouLikeYourBrain?
ALEXANDRA SERAFINO, PHARM.D.
PGY-2 CRITICAL CARE PHARMACY RESIDENT
INTERMOUNTAIN MEDICAL CENTER
MURRAY, UT
Objectives
» List the more common causes of elevated intracranial pressures (ICP)
» Compare and contrast the pharmacokinetics, therapeutic applications, and administration techniques of hypertonic saline and mannitol
» Given a patient case, determine how to appropriately administer hypertonic saline or mannitol and monitor the patient
ElevatedICP
» Increase in ICP >20 mmHg
» A neurologic emergency
» Potentially devastating
Ropper AH, et al. N Engl J Med 2012; 367:746-52.
CausesofElevatedICP
Traumatic brain injuries
Intracranial bleeding
Brain and CNS tumors
Hydrocephalus
Severe ischemic stroke
Ropper AH, et al. N Engl J Med 2012; 367:746-52.
Epidemiology
» Traumatic brain injuryo ~1.4 million sustained annually in the United States
o ~80,000 severe TBI
» Elevated ICP increases morbidity and mortalityo Mortality of 18% for ICP < 20 mmHg
o Mortality of 56% for ICP > 40 mmHg
» Long term disability is common
Treggiari MM, et al. Neurocrit Care 2007;6:104-12.Thurman DJ, et al. J Head Trauma Rehabil 1999;14:602-15.
Results1 RCT showed improved GOS at 1-year; 6/7 RCTssuggest improved ICP lowering with HTS vs. mannitol
Conclusions
HTS decreases ICP to a greater extent vs. mannitol, whether used as a bolus or continuous infusion, but has been not shown to improve neurologic outcomes
Mortazavi MM, et al. J Neurosurg 2012; 116:210-21
Mortazavi,etal
Mortazavi MM, et al. J Neurosurg 2012; 116:210-21
Meta‐AnalysesandReviews
» Other meta-analyses have made similar conclusionso HTS is more effective at decreasing ICP
o Limited long-term and neurologic outcome data
» Mean difference in ICP lowering is smallo ~1.5-2.5 mmHg
» Less therapeutic failures with HTS vs. mannitol
Kamel H, et al. Crit Care Med 2011; 39:554-9Hinson HE, et al. J Intensive Care Med 2013; 28(1):3-11Lazaridis C, et al. Crit Care Med 2013; 41:1353-60
Rickard AC, et al. Emerg Med J 2013
Bolusvs.ContinuousInfusion
Mortazavi MM, et al. J Neurosurg 2012; 116:210-21
Bolusvs.ContinuousInfusions
Mortazavi MM, et al. J Neurosurg 2012; 116:210-21
Bolusvs.ContinuousInfusion
» No recommendation can be made with regards to continuous infusion vs. bolus mannitol
» Significantly more data on bolus HTS administration
» Available data suggest bolus and continuous infusion HTS is effective at reducing ICP
Mortazavi MM, et al. J Neurosurg 2012; 116:210-21Bullock MR, et al. Neurotrauma 2007;24:Suppl 1: S14-S20.
GuidelineRecommendations
Bullock MR, et al J Neurotrauma. 2007;24 Suppl 1:S14-20
Choices– SaltyorSweet?
» HTS vs. Mannitolo Decreases ICP to a greater extent
o Effects last longer, realized more quickly
o Lower risk of rebound ICP elevations
o Fewer adverse effects
» Clinical outcome data to support the use of one agent over the other is lacking
» Recent study of neurointensivists reports trend in increasing HTS use (55% vs. 45%)
Hays AN,. Neurocrit Care 2011, 14:222-228.
Take‐AwayPoints
» HTS over mannitol in most situations
» Either therapy will require frequent laboratory monitoringo Sodium