Steph Tilston Anaesthetic SpR Hurstwood Park Neurological Centre Hyperosmolar/Low Volume Resuscitation and Head Injury – A review of Current Evidence Steph Tilston Anaesthetic SpR Hurstwood Park Neurological Centre

Background Osmotherapy used since early 20thC to treat raised ICP First systemic studies in 1960’s Military use Much animal based research Increased interest over last 20 years Clinical trial evidence emerging Sheep bled out to shocked state in original study..CO and MAP restores with as little as 10% vol lost given Easier for army medics to carry small bags of fluids Found those soldiers receiving this had better outcomes Early volume restoration

Originally hypertonic saline used Effects found to be relatively short lived Combined with colloid solution Volume effects substantially additive to that of colloid alone Best risk/benefit ratio 7.2-7.5% NaCl with 6-10% dextran 60/70 or 6-10% hydroxyethylstarch 200,000

‘Rescueflow’ by vitaline pharmaceuticals 6% dextran 70 in 7.5% NaCl ‘Hyperhaes’ (HHES) Focus is on pre-hospital treatment of severe hypovolaemia/shock

Uses of hypertonic solutions Primary volume resuscitation from severe hypovoleamia and shock Head injury with raised ICP Spinal shock Sepsis Burns Pre CPB priming AAA

Body fluid compartments total body water 42l

Proposed mechanisms of action Rapid mobilisation endogenous water from intracellular compartment – large reserve Increases plasma volume by 3-4 x volume infused Normalising endothelial and red blood cell volume and microvascular blood flow Reperfusion ischaemic areas Endothelial cell volume esp increases in shock/ ischaemia because of cell ATP loss and cell membrane exchange dysfunction Leads to water accumulation within cells

Increased pulmonary gas exchange, R shift oxy-Hb dissociation curve Increaded preload, cardiac index,PCWP Direct myocardial stimulation Peripheral vasodilatation, haemodilution Redistribution blood flow esp mesenteric Emerging evidence of immune modulation; decreased sticking and rolling leukocytes

Characteristics of hypertonic solutions High crysalloid conc, eg Na, glucose, bicarb Substantial but short lasting rise in plasma osmolarity Normal range 280-295 Eg sodium, mannitol, glucose,bicarbonate previosly urea

evidence Huge amounts of animal studies Human trials slow to show benefit. Difficulty in randomisation.crossover. but increasing numbers of studies showing benefit Large North and South America multi-centre trial on pre hospital saline/dextran v crystalloid for post traumatic hypotention Increased survival in penetrating injuries / those requiring immediate surgery Fewer complications

Meta-analysis of 8 trials, 1170 patients significant improvement in 30 day survival esp.. sub-groups with severe trauma ..head injury with raised ICP European research shows CVS benefits in Sepsis Also in management of emergency AAA CAB priming

In Raised ICP / cerebral oedeme Prospective RCT 32 German neurosurgical patients 7.2%NaCl/starch v 15%mannitol Statistically significant speed and degree of normalisation of elevated ICP 6.0 mins v 8.7 mins 57% v 48% No clinically relevant effect on osmolarity Mean dose 1.4 mls/kg

Severe sepsis Prospective bouble-blind RCT Brazilian ITU Improvement in all CVS parameters Few complications But dubious study

Many animal studies show less MODS

Numerous animal studies effectively stays outwith BBB Direct osmotic effect Initial effect lasts aprox 2 hrs Maintained with infusion ^perfusion decreased oedema and volume of contusion

Caution Patients with low cardiac reserve Hyperosmotic states/electrolyte disturbances Uncontrolled bleeding phlebitis Immunodilution? Central pontine myelinolysis?? DKA, severe dehydration, alchohol poisoning CPM too rapid correction low NA, delerium, spastic quadplegia…animal studies only

Further Research Exact MOA in humans Best mode of administration Best dose More quality trials!

The Future? Hyperosmolar solutions with artificial O2 carriers