Hypertonic saline for craniotomy?

IN this issue of ANESTHESIOLOGY, Rozet et al. present the findings of a comprehensive study comparing two hyperosmolar agents, hypertonic saline (HS) and mannitol, for brain relaxation during craniotomy. This work calls into question whether sufficient information is now available to advocate substitution of mannitol with HS to promote brain relaxation during routine craniotomy. It was discovered in the early 20th century that HS reduces brain bulk in animals. Reports in humans were not forthcoming until the 1980s. The neurosurgical and neuro–critical care communities have since explored the use of HS because of its ability to treat cerebral edema and intracranial hypertension. Although mannitol remains the recommended hyperosmolar therapy in settings such as severe traumatic brain injury, HS is an appealing alternative because its reflection coefficient is superior to that of mannitol (1.0 vs. 0.9; i.e., HS does not cross an intact blood–brain barrier). HS also differs from mannitol in that it has little diuretic effect and thus should better maintain cerebral perfusion pressure. At the same time, HS and mannitol have similarities. Both agents have potential to improve blood rheology. This can serve to either reduce brain blood volume or improve flow through stenotic vessels. In contrast, in the presence of blood–brain barrier breakdown, both agents can accumulate over time in brain parenchyma and negate any beneficial effect or even increase intracranial pressure (ICP). The question, therefore, is whether HS offers efficacy superior to mannitol without adding risk. Numerous studies have investigated the efficacy of different HS formulations (2–30% wt/vol) in the setting of neurologic injury. In contrast to the intraoperative investigation by Rozet et al., the following studies compared mannitol with HS in neuro–critical care populations. Vialet et al. performed a randomized comparative study of 20% mannitol and 7.5% NaCl, administered in equal volumes (not equiosmolar loads; 20% mannitol is approximately equivalent to 3% NaCl), to control ICP in 20 patients with traumatic brain injury. ICP control was better in the HS group, which received the higher osmolar load. Harutjunyan et al. randomly assigned 40 patients at risk for intracranial hypertension to receive 7.2% NaCl–hydroxyethyl starch 200/0.5 or 15% mannitol. Both drugs were continuously infused as required to maintain ICP less than 15 mmHg. 7.2% NaCl–hydroxyethyl starch 200/0.5 was more effective and had a greater osmolar load than 15% mannitol. A similar elevation in cerebral perfusion pressure was seen with both drugs (approximately 10 mmHg). Schwarz et al. compared equiosmolar loads of 20% mannitol versus 7.5% NaCl–6.0% hydroxyethyl starch for control of intracranial hypertension in nine ischemic stroke patients with 30 episodes of elevated ICP. Patients were randomly assigned to one or the other therapy and subsequent doses were alternated, mannitol or HS. The authors found HS to be more efficacious in controlling ICP, but the small sample size and potential crossover effects create limitations in interpreting the data. In a subsequent study, they found that 10% NaCl was effective in controlling ICP refractory to mannitol therapy in ischemic stroke patients. The use of HS as a rescue therapy for ICP refractory to mannitol has been reported by others. These studies, while providing insight, did not adequately assess the comparative efficacy of HS versus mannitol, due to either nonequiosmolar dosing or trial design. In the operative arena, three previous investigations have been reported. These studies either did not use equiosmolar loads of mannitol and HS, or used a nonneurosurgical population. De Vivo et al. studied 30 neurosurgical patients randomly assigned to three groups: 3% HS, HS–mannitol, or 18% mannitol alone. Therapy was started intraoperatively and continued through postoperative day 3. ICP was decreased by all three strategies. Although 3% HS and 20% mannitol have similar osmolarity, the volumes of the respective solutions infused differed (and thus so did the osmolar load). Changes in serum sodium and potassium were inconsequential, but HS alone preserved central venous pressure better, consistent with the larger volume of HS given. Gemma et al. studied 7.5% NaCl versus 20% mannitol in equal volumes of 2.5 ml/kg (but different osmolar loads) in 50 elective craniotomy patients. They found that both therapies had similar effects on mean arterial pressure, central venous pressure, ICP, and brain bulk This Editorial View accompanies the following article: Rozet I, Tontisirin N, Muangman S, Vavilala MS, Souter MJ, Lee LA, Kincaid MS, Britz GW, Lam AM: Effect of equiosmolar solutions of mannitol versus hypertonic saline on intraoperative brain relaxation and electrolyte balance. ANESTHESIOLOGY 2007; 107:697–704.