Neurosurgery notes/Trauma/Management of trauma/Non surgical/Head injury ICP management/Hyperosmolar therapy

Hyperosmolar therapy

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Head injury ICP management
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Mannitol
Furosemide
Hypertonic saline (HS)
Hypertonic lactate solutions

Control of ICP in head injury

  • Despite intensive therapeutic measures, intractable ICP is the primary cause of 46% of TBI deaths.
  • Efficacy of mannitol studied in series of reasonably sized RCTs:
    • Shwartz et al 1984 – mannitol vs pentobarbital
    • Sayre et al 1996 – mannitol vs normal saline
    • Smith et al., 1986 – two mannitol regimens, administration guided by either ICP or physiological measurements
  • Also 3 Brazilian studies assess effects of early high dose mannitol in three different groups of severely head injured patients (Cruz et al 2001, 2002 & 2004) (evacuated aSDH, acute temporal ICHs, and severe diffuse injury).
  • Hypertonic saline compared to Ringer’s lactate in Melbourne study (Cooper et al 2004)
  • Small French study compared hypertonic with mannitol (Vialet et al 2003)
  • The brazalian trial might be lying

Trials conclusion

  • Schwartz et al 1984
    • No difference between mannitol and pentobarbital in treatment of intracranial hypertension post head injury
    • Pentobarbital may be harmful in head injured patients without intracranial haematomas
  • Smith et al 1986
    • Regular, frequent administration of mannitol may lead to better overall ICP control than waiting until ICP rises >25mmHg
  • Sayre et al 1986
    • OOH administration of 1g/kg of mannitol to multiple trauma head injured patients is not associated with significant hypotension
  • Cruz et al (2001, 2002, 2004)
    • Early administration of high dose mannitol leads of significant improvements and better clinical outcomes in patients with ASDH, traumatic temporal IPH, and DBI
  • Cooper et al 2004
    • Hypertonic saline in pre hospital setting for several head injured patients is no better than conventional fluids alone for resuscitating hypotensive patients or improving neurological outcomes at 6 months
  • Vialet et al 2003
    • Hypertonic saline was more effective in controlling refractory intracranial hypertension than mannitol in patients with severe head injury

Critique of studies

  • Utility of mannitol in controlling ICP well established but effect on outcome more variable (similar for HTS)
  • Schwartz – cross over between groups. However finding that pentobarbital potentially harmful has contributed to widespread use of mannitol for ICP control
  • Smith – looked at whether benefit to ICPM to guide mannitol use in severe head injury. No significant difference in mortality or neurological outcome with ICPM but possible better ICP control with regular small doses mannitol
  • Sayre – not powered to detect survival difference at 2h but powered to detect sysBP drop to <90mmHg, reasonable endpoint given mortality doubles with hypotension in severe head injury
  • Cooper – weakness is that included polytrauma, so not clear if findings can be extrapolated to those with isolated head injury. Landmark in that it is first resuscitation fluid trial with neurological outcome (GOS) as primary outcome
  • Also Cooper study powered for 20% improvement in GOSE, at lower end this is dead to PVS – not most meaningful outcome. Furthermore, higher serum Na+ on arrival in hospital in HTS could affect blinding
  • Serious concerns expressed about integrity of Cruz’s work
  • Vialet – small number of patients → case heterogeneity concerns. Very poor 90 day outcomes (all dead or severely disabled) raises questions about how representative study group was and how well they were managed

Hyperosmolar conclusion

  • Evidence limited in terms of number of studies and in delineating several aspects of use
  • Little evidence on bolus vs infusion, optimal dose, optimal rate, whether to replace diuresis losses, and whether clinical threshold should be guided by ICP or according to fixed schedules, and whether serum osmo changes affect outcome
  • Mechanism of action not fully elucidated
  • Osmotic tissue dehydration seems less important than immediate rheological effects – blood dilution and increased RBC deformability → decreased blood viscosity and promoting CBF
  • Mechanistic studies therefore suggest bolus administration and replacing urinary losses best practice
  • Limited evidence that successive mannitol boluses accumulate in brain tissue and exacerbate ICP and that cumulative hyperosmolar effects lead to neurological sequelae (Wakai et al 2007)
  • Limited evidence to support concerns about central pontine myelinolysis with HTS