A 40 year old male was brought into ED following a high speed road traffic accident. The patient was ejected from the vehicle. The patient was managed according to ATLS guidelines. He suffered extensive injuries including facial fractures, traumatic subarachnoid haemorrhage and multiple intra-cerebral haemorrhages, a flail chest and thoracic and cervical spine injuries. Once stabilised, the patient was transferred to the neurosurgical intensive care unit where an intra-cranial pressure (ICP) monitor was inserted to measure intracranial pressures. His ICP was persistently raised despite optimising respiratory parameters, deep sedation, muscle relaxation and then mannitol. A decision was made to commence an infusion of hypertonic saline 2.7% according to the local protocol. The ICP improved rapidly and stabilised and removed the need to proceed with surgical decompressive craniotomy.
What is the evidence for the use of hypertonic saline in the treatment of acutely raised intracranial pressure?
Traumatic brain injury (TBI) is a major cause of morbidity and mortality. The key in managing TBI on an intensive care unit (ICU) is to prevent secondary brain injury, resulting from intracranial hypertension, as this is associated with poorer outcomes. Various methods for controlling intracranial pressure (ICP) are utilised on the ICU.
The two main agents used are mannitol (10% or 20%) and hypertonic saline (HTS). The ideal osmotic agent will exert a strong osmotic gradient, by remaining in the intravascular compartment, as well as having minimal side effects and being non-toxic.
Mannitol is well established in the acute management of intracranial hypertension as recommended by the Brain Trauma Foundation (1) and the European Brain Injury Consortium (2). There are various mechanisms involved in the use of mannitol including the following:(3)
- An increase in cardiac output which increases cerebral perfusion pressure (CPP) and cerebral oxygenation.
- A decrease in cerebral oedema due to the osmotic effect.
- A decrease in cerebrospinal fluid production by up to 50%.
Whilst the beneficial effects are essential in treating intracranial hypertension there are several limitations and side effects. These include:(3)
- Hyperosmolarity beyond 320 mOsmol/L can cause adverse renal and neurological effects.
- Hypovolaemia due to osmotic diuresis which could reduce cardiac output and hence CPP.
- A rebound increased ICP due to accumulation of mannitol in cerebral tissue.
The most recent osmotic agent being used is hypertonic saline of varying concentrations. Indeed, some intensive care units have converted completely to its use over that of mannitol because of increased evidence of its safety. The purpose of this review is to examine the evidence for the use of hypertonic saline for the control of intracranial hypertension in traumatic brain injury. Numerous studies have been performed comparing HTS to Ringers Lactate solution and Mannitol. The main limitations in all the studies are the small sample sizes.
Worthley et al (4) demonstrated an immediate decrease in ICP after administering 29.2% HTS to 2 patients
Einhaus et al (5) demonstrated the same after administration of 7.5% HTS to 1 patient.
Hartl et al (6) demonstrated decreased ICP after 7.5% HTS in 6 patients
Schatzmann et al (7) showed 10% HTS to have a >40% decrease in ICP with a sustained fall for a mean of 93mins
Simma et al (8) demonstrated 1.7% HTS to be more effective than Ringers Lactate in 32 patients.
Ali et al (9) demonstrated safety of a 48 hour infusion of 3% HTS in 30 patients as well as improvement in ICP. Despite sustained hypernatraemia there were no adverse outcomes.
Qureshi et al (10) demonstrated a decrease in ICP following 3% HTS to 27 patients. However this decrease only lasted up to a maximum of 4 hours.
In 1999 Qureshi (11) looked at much larger numbers (36 cases HTS versus 46 controls) and found no difference in outcome. Complimenting Qureshi’s second study was the largest trial comparing HTS to Ringers lactate in the pre-hospital setting by Cooper et al (12). This double-blinded randomised controlled trial compared HTS (114 cases) for fluid resuscitation to Ringers Lactate solution (115 received). There was a statistically insignificant decrease in ICP (P=0.08) and no significant difference in mortality or neurological outcome.
In patients with TBI, following initial pre-hospital resuscitation and treatment of hypotension, the mainstay treatment is prevention of secondary brain injury associated with intracranial hypertension. The evidence currently available does not support using one choice of fluid over another (HTS or mannitol). The side effects of mannitol, in particular rebound intracranial hypertension, were not found in HTS in the majority of studies. This could support the use of HTS over that of mannitol. However the population sizes and significant variations in types of HTS used in the different studies makes it difficult to reach a definitive conclusion. If using HTS, serum sodium, osmolarity and other electrolytes must be monitored to allow early detection of complications. Further research is required in this area of neurosurgery.
1. The Brain Trauma Foundation, The American Association of Neurological Surgeons, The Joint Section on Neurotrauma and Critical Care. Initial management. J Neurotrauma 2000;17:463-9.
2. Maas AI, Dearden M, Teasdale GM, et al. EBIC-guidelines for management of severe head injury in adults: European Brain Injury Consortium. Acta Neurochir (Wien) 1997;139:286-94.
3. White H, Cook D, Venkatesh B: The use of Hypertonic Saline for treating Intracranial Hypertension after Traumatic Brain Injury. Anesthesia and Analgesia 2006;102:1836-46.
4. Worthley LI, Cooper DJ, Jones N. Treatment of resistant intracranial hypertension with hypertonic saline: report of two cases. J Neurosurgery 1998; 68:478-81.
5. Einhaus SL, Croce MA, Watridge CB, Lowery R, Fabian TC. The use of hypertonic saline for the treatment of increased intracranial pressure. Journal of Tennessee Medical Association 1996; 89:81-2.
6. Hartl R, Ghajar J, Hochleuthner H, Mauritz W. Treatment of refractory intracranial hypertension in severe traumatic brain injury with repetitive hypertonic/hyperoncotic infusions. Zentralbi Chir 1997; 122:181-5.
7. Schatzmann C, Heissler HE, Konig K, Klinge-Xhemajli P, Rickels E, Muhling M, Borschel M, Samii M. Treatment of elevated intracranial pressure by infusions of 10% saline in severely head injured patients. Acta Neurochir Suppl (Wien) 1998; 71:31-3.
8. Simma B, Burger R, Falk M. A prospective, randomised and controlled study of fluid management in children with severe head injury: lactated Ringer’s solution versus hypertonic saline. Critical Care Medicine 1998; 26:1265-70.
9. Ali T, Monkhouse A, Madder H. A novel hypertonic saline infusion regime for the treatment of intracranial hypertension following traumatic brain injury. Intensive Care Medicine 2013; Supplement 2, 39:0167.
10.Qureshi AL, Suarez JI, Bhardwaj A, Mirski MA, Schnitzer MS, Hanley DF, Ulatowski JA. Use of hypertonic (3%) saline/acetate infusion in the treatment of cerebral edema: effect on intracranial pressure and lateral displacement of the brain. Critical Care Medicine 1998; 26:440-6.
11.Qureshi AL, Suarez JI, Castro A, Bhardwaj A. Use of hypertonic saline/acetate infusion in the treatment of cerebral edema in patients with head trauma: experience at a single centre. J Trauma 1999; 47:659-65.
12.Cooper DJ, Myles PS, McDermott FT, Murray LJ, Laidlaw J, Cooper G, Tremayne AB, Bernard SS, Ponsford J. Prehospital hypertonic saline resuscitation of patients with hypotension and severe traumatic brain injury: a randomised controlled trial. JAMA 2004; 291:1350-7.