Traumatic Brain Injury: Hypertonic Saline or Combination fluids?

The use of fluids prehospital has always been, and will likely continue to be a controversial topic.  The simple notion that we should be replacing the fluids which have been lost is sensible and logical, but not necessarily logistical.  The logistics of carrying blood products make it unfeasible for many services, and certainly on a large scale for widespread use within an ambulance service.

The use of crystalloids has become the mainstay of treatment for most ambulance services.  The crystalloid v colloid debate will inevitably rage on.  There has been increasing interest in hypertonic saline in traumatic brain injury but it is difficult to tease out benefits, due to the heterogeneity amongst trials. There has been interest in the resuscitation of hypotensive, brain injured patients using “small volume resuscitation” – the use of relatively small volumes of hypertonic solutions to draw interstitial and intracellular fluids back into the intravascular space, e.g.

Prehospital Hypertonic Saline Resuscitation of Patients With Hypotension and Severe Traumatic Brain Injury:A Randomized Controlled Trial

D. James Cooper, BMBS, MD et al; 2004 (click here)
This hotly quoted study looked at 229 patients who had traumatic brain injury (TBI) with a Glasgow Coma Scale (GCS) < 9, with hypotension (systolic blood pressure <100 mmHg.  Patients either received 7.5% saline or Ringer’s lactate, both 250mls.  There was no difference in primary endpoints (survival, neurological outcome).  So why all the fuss?
Probably because in-hospital studies have shown promise in the management of ICP in patients with TBI.

Use of hypertonic saline in the treatment of severe refractory posttraumatic intracranial hypertension in pediatric traumatic brain injury.

Crit Care Med. 2000 Apr;28(4):1144-51.

This study in children used infusions of 3% hypertonic saline to reduce ICP in patients in whom other medical therapies had failed including mannitol, sedation, and paralysis.  They reported good results in rises in serum sodium, osmolalities and response of ICP.
So, hypertonic saline may have a beneficial effect, but what about combination fluids such as RescueFlow™?  This fluid purports to expand plasma volume by three times more than the volume given, the company suggest that 250mls is equivalent to between two and three litres of balanced crystalloid solution, so is clearly a logical choice when deciding what to put in your prehospital bag.  But does it work?

Individual Patient Cohort Analysis of the Efficacy of Hypertonic Saline/Dextran in Patients with Traumatic Brain Injury and Hypotension

Wade, C. E. PhD; Grady, J. J. PhD; Kramer, G. C. PhD; Younes, R. N. MD; Gehlsen, K. PhD; Holcroft, J. W. MD

Journal of Trauma-Injury Infection & Critical Care:
14Th Bodensee Symposium On Microcirculation: Small Volume Resuscitation In Head Injury, Bodensee, Germany, June 14-16, 1996: Article

This retrospective short analysis study looked at patients who had received a RescueFlow like solution; the authors suggested a doubling in survival when compared with standard care, but the study design leaves us wondering about potential biases; the cohorts came from previous prospective randomised trials.

An excellent review article by George Kramer et al (2004) explains the development of this sort of fluid, the addition of a colloid to the hypertonic saline should help to retain some of the resorbed water in the intravascular space, so may be helpful in hypovolaemic shock; but warns us of the method of infusion – if 250mls of 7.5% saline with 6% dextran 70 is equivalent to infusing 3000mls of crystalloid, we should be careful with infusion rates, particularly in damage control situations and especially in penetrating chest injury where target blood pressures are even lower (SBP 60-70mmHg).

Is it the Hypertonic Saline, or the Dextran?

So, perhaps these fluids are worth giving in the presence of traumatic brain injury, but do we need the dextran?  One of the concerns over dextran use is the ability to cross-match blood for the patient once in hospital.  The WHO recommend a full crossmatch sample be drawn routinely before administration of dextran 70 since it promotes rouleaux formation, and interferes with the crossmatching process.  The same recommendation raises concerns that in large volumes (>15ml/kg) dextran 70 interferes with platelet function and may increase bleeding time.

Kramer et al states that this may not be a problem, as none of the in vivo studies have seen issues with either crossmatching nor coagulation.  If there is a choice though, do we want to give a drug with the potential for detrimental effects? Can we get away without it?

The effect on ICP is likely the same with hypertonic saline with or without dextran in the absence of hypotension, but as we saw in Wade et al’s study, there was a survival benefit associated with avoiding hypotension.

Best of both worlds?

If you have access to blood products – several UK specialist ambulance resources have begun to carry a mixture of packed red cells, freeze dried plasma, prothrombin complex concentrate, and fibrinogen concentrate, it may be possible to deliver haemostatic resuscitation with these, and use hypertonic saline for ICP management, as might be done in hospital.  This could potentially avoid the theoretical disadvantages of using dextrans.

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