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Secondary brain injury after intracerebral hemorrhage (ICH) is the main cause of poor prognosis in ICH patients, but the underlying mechanisms remain less known. The involvement of Piezo1 in brain injury after ICH was studied in a mouse model of ICH. ICH was established by injecting autologous arterial blood into the basal ganglia in mice. After vehicle, Piezo1 blocker, GsMTx4, Piezo1 activator, Yoda-1, or together with mannitol (tail vein injection) was injected into the left lateral ventricle of mouse brain, Piezo1 level and the roles of Piezo1 in neuronal injury, brain edema, and neurological dysfunctions after ICH were determined by the various indicated methods. Piezo1 protein level in neurons was significantly upregulated 24 h after ICH in vivo (human and mice). Piezo1 protein level was also dramatically upregulated in HT22 cells (a murine neuron cell line) cultured in vitro 24 h after hemin treatment as an in vitro ICH model. GsMTx4 treatment or together with mannitol significantly downregulated Piezo1 and AQP4 levels, markedly increased Bcl2 level, maintained more neurons alive, considerably restored brain blood flow, remarkably relieved brain edema, substantially decreased serum IL-6 level, and almost fully reversed the neurological dysfunctions at ICH 24 h group mice. In contrast, Yoda-1 treatment achieved the opposite effects. In conclusion, Piezo1 plays a crucial role in the pathogenesis of brain injury after ICH and may be a target for clinical treatment of ICH., Competing Interests: Declaration of competing interest The author declared no potential conflicts of interest with respect to the research, authorship, and publication of this article., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Objective: A topic of current research is the development of a new approach to the diagnosis and treatment of severe brain injury taking into consideration its main pathophysiological mechanism-idiopathic intracranial hypertension syndrome. The goal of this study was to identify Doppler patterns of unfavorable craniocerebral injury conditions to form a consistent algorithm of treatment measures to reduce secondary brain damage in patients with severe craniocerebral trauma., Methods: Transcranial Doppler imaging is a prospective method, which allows quick and noninvasive assessment of the intracerebral blood flow dynamics right at the patient's bedside. Due to the operator-dependent nature of this method, clinical interpretation can often be contradictory. As a result, no clear criteria for therapy correction have yet been formulated based on this neuroimaging method., Results: Analysis of the therapy performed allowed us to specify the options for the hyperosmolar solutions for the correction of idiopathic intracranial hypertension syndrome., Conclusions: No statistically significant difference in effectiveness was shown between mannitol and hypertonic saline solutions., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Objective: To compare the efficacy and safety of two hyperosmolar agents (hypertonic saline vs. mannitol) used for the reduction of elevated intracranial pressure (ICP) in children., Methods: A meta-analysis of randomized controlled trials (RCTs) was conducted and GRADE system (Grading of Recommendations, Assessment, Development and Evaluation) of evidence was applied. Relevant databases were searched till 31 st May 2022. Primary outcome was mortality rate., Results: Of 720 citations retrieved, 4 RCTs were included in the meta-analysis (n = 365, male = 61%). Traumatic and non-traumatic cases of elevated ICP were included. There was no significant difference in the mortality rate between the two groups [relative risk (RR), 1.09; (95% confidence interval (CI), 0.74 to 1.6)]. No significant difference was found for any of the secondary outcomes, except serum osmolality (being significantly higher in mannitol group). Adverse events like shock and dehydration were significantly higher in the mannitol group, and hypernatremia in the hypertonic saline group. The evidence generated for primary outcome was of "low certainty", and for secondary outcomes, it varied from "very-low to moderate certainty"., Conclusions: There is no significant difference between hypertonic saline and mannitol used for the reduction of elevated ICP in children. The evidence generated for primary outcome (mortality rate) was of "low certainty", and for secondary outcomes, it varied from "very-low to moderate certainty". More data from high-quality RCTs are needed to guide any recommendation., (© 2023. The Author(s), under exclusive licence to Dr. K C Chaudhuri Foundation.)

Acutely elevated intracranial pressure (ICP) may have devastating effects on patient mortality and neurologic outcomes, yet its initial detection remains difficult because of the variety of manifestations that it can cause disease states it is associated with. Several treatment guidelines exist for specific disease processes such as trauma or ischemic stroke, but their recommendations may not apply to other causes. In the acute setting, management decisions must often be made before the underlying cause is known. In this review, we present an organized, evidence-based approach to the recognition and management of patients with suspected or confirmed elevated ICP in the first minutes to hours of resuscitation. We explore the utility of invasive and noninvasive methods of diagnosis, including history, physical examination, imaging, and ICP monitors. We synthesize various guidelines and expert recommendations and identify core management principles including noninvasive maneuvers, neuroprotective intubation and ventilation strategies, and pharmacologic therapies such as ketamine, lidocaine, corticosteroids, and the hyperosmolar agents mannitol and hypertonic saline. Although an in-depth discussion of the definitive management of each etiology is beyond the scope of this review, our goal is to provide an empirical approach to these time-sensitive, critical presentations in their initial stages.

Background: Traumatic brain injury (TBI) causes mortality and long-term disability among young adults and imposes a notable cost on the healthcare system. In addition to the first physical hit, secondary injury, which is associated with increased intracranial pressure (ICP), is defined as biochemical, cellular, and physiological changes after the physical injury. Mannitol and Hypertonic saline (HTS) are the treatment bases for elevated ICP in TBI. This systematic review and meta-analysis evaluates the effectiveness of HTS in the management of patients with TBI., Methods: This study was conducted following the Joanna Briggs Institute (JBI) methods and PRISMA statement. A systematic search was performed through six databases in February 2022, to find studies that evaluated the effects of HTS, on increased ICP. Meta-analysis was performed using comprehensive meta-analysis (CMA)., Results: Out of 1321 results, 8 studies were included in the systematic review, and 3 of them were included in the quantitative synthesis. The results of the meta-analysis reached a 35.9% (95% CI 15.0-56.9) reduction in ICP in TBI patients receiving HTS, with no significant risk of publication bias (t-value = 0.38, df = 2, p-value = 0.73). The most common source of bias in our included studies was the transparency of blinding methods for both patients and outcome assessors., Conclusion: HTS can significantly reduce the ICP, which may prevent secondary injury. Also, based on the available evidence, HTS has relatively similar efficacy to Mannitol, which is considered the gold standard therapy for TBI, in boosting patients' neurological condition and reducing mortality rates., (© 2022. The Author(s).)

Background: Increased intracranial pressure (ICP) occurring after traumatic brain injury (TBI) is associated with increased morbidity and mortality. If appropriate treatments are not initiated, brain herniation can occur and lead to death. Previously, the Brain Trauma Foundation recommended mannitol as the first-choice hyperosmolar agent. However, in 2016, they retracted this recommendation, citing a lack of sufficient supporting evidence. Current research shows that hypertonic saline (HTS) also decreases ICP., Objectives: To compare the efficacy of HTS and mannitol in lowering ICP in patients with TBI., Data Sources: A search was conducted up to June 1, 2019, using PubMed, Embase, CINAHL, and Web of Science. Selected articles compared mannitol and HTS in adults with TBI, with the measured outcome of reduced ICP. Four meta-analyses, three randomized controlled trials, and one retrospective cohort study met the inclusion criteria., Conclusions: Hypertonic saline is an effective alternative to mannitol for increased ICP. Three studies suggested HTS may be superior to mannitol. Conclusions were limited by sample size and methodological differences, such as varying concentrations and doses, and inclusion of patients without TBI in their studies., Implications for Practice: Evidence demonstrates HTS to be as effective as mannitol for ICP reduction. Further research in a large multicenter clinical trial is needed to compare these two agents for superiority in the management of increased ICP. Providers should consider the properties of each agent, adverse effects, and potential benefits when selecting a hyperosmotic agent., Competing Interests: Competing interests: The authors report no conflicts of interest., (Copyright © 2019 American Association of Nurse Practitioners.)

Background: The use of hyperosmolar agents, such as mannitol or hypertonic saline (HTS), to control high intracranial pressure (ICP) in patients with traumatic brain injury has been well studied. However, the role of HTS in the management of aneurysmal subarachnoid hemorrhage (aSAH)-associated increased ICP is still unclear., Methods: We performed a systematic review in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. The primary outcome of this review is to quantify ICP reduction produced by HTS and its effect on clinical outcomes defined by any standardized functional score. Secondary outcomes included HTS versus mannitol in ICP reduction, HTS effects on cerebral vasospasm, and HTS dose concentration, infusion rate, infusion volume, frequency of redosing, and serum sodium/osmolality limits for repeat dosing., Results: Five studies were included in the review encompassing 175 patients. Studies on aSAH included mostly poor grade patients (defined as World Federation of Neurosurgical Societies grade 4 and 5). HTS concentrations ranged from 3%-23.5%. Most studies found that HTS decreased ICP when compared with either baseline or placebo. The mean decrease in ICP from HTS administration was 8.9 mm Hg (range: 3.3-12.1 mm Hg). Only 1 study showed possible improvement in poor grade aSAH outcomes., Conclusions: The current evidence suggests that HTS is as effective as mannitol at reducing increased ICP in aSAH. However, there is not enough data to recommend the optimal and safest dose concentration or whether HTS significantly improves outcomes in aSAH., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Objective: To comparatively evaluate hypertonic sodium (HTS) and mannitol in patients following acute traumatic brain injury (TBI) on the outcomes of all-cause mortality, neurological disability, intracranial pressure (ICP) change from baseline, ICP treatment failure, and serious adverse events., Data Sources: PubMed, EMBASE, CENTRAL, Cochrane Database of Systematic Reviews, ClinicalTrials.gov, and WHO ICTRP (World Health Organization International Clinical Trials Registry Platform) were searched (inception to November 2015) using hypertonic saline solutions, sodium chloride, mannitol, osmotic diuretic, traumatic brain injury, brain injuries, and head injury. Searches were limited to humans. Clinical practice guidelines and bibliographies were reviewed., Study Selection and Data Extraction: Prospective, randomized trials comparing HTS and mannitol in adults (≥16 years) with severe TBI (Glasgow Coma Scale score ≤8) and elevated ICP were included. ICP elevation, ICP reduction, and treatment failure were defined using study definitions., Data Synthesis: Of 326 articles screened, 7 trials enrolling a total of 191 patients met inclusion criteria. Studies were underpowered to detect a significant difference in mortality or neurological outcomes. Due to significant heterogeneity and differences in reporting ICP change from baseline, this outcome was not meta-analyzed. No difference between HTS and mannitol was observed for mean ICP reduction; however, risk of ICP treatment failure favored HTS (risk ratio [RR] = 0.39; 95% CI = 0.18-0.81). Serious adverse events were not reported., Conclusions: Based on limited data, clinically important differences in mortality, neurological outcomes, and ICP reduction were not observed between HTS or mannitol in the management of severe TBI. HTS appears to lead to fewer ICP treatment failures., (© The Author(s) 2016.)

Object: Mannitol is commonly used to treat elevated intracranial pressure (ICP). The authors analyzed mannitol dosing errors at peripheral hospitals prior to or during transport to tertiary care facilities for intracranial emergencies. They also investigated the appropriateness of mannitol use based on the 2007 Brain Trauma Foundation guidelines for severe traumatic brain injury., Methods: The authors conducted a retrospective review of the Shock Trauma Air Rescue Society (STARS) electronic patient database of helicopter medical evacuations in Alberta, Canada, between 2004 and 2012, limited to patients receiving mannitol before transfer. They extracted data on mannitol administration and patient characteristics, including diagnosis, mechanism, Glasgow Coma Scale score, weight, age, and pupil status., Results: A total of 120 patients with an intracranial emergency received a mannitol infusion initiated at a peripheral hospital (median Glasgow Coma Scale score 6; range 3-13). Overall, there was a 22% dosing error rate, which comprised an underdosing rate (<0.25 g/kg) of 8.3% (10 of 120 patients), an overdosing rate (>1.5 g/kg) of 7.5% (9 of 120), and a nonbolus administration rate (>1 hour) of 6.7% (8 of 120). Overall, 72% of patients had a clear indication to receive mannitol as defined by meeting at least one of the following criteria based on Brain Trauma Foundation guidelines: neurological deterioration (11%), severe traumatic brain injury (69%), or pupillary abnormality (25%)., Conclusions: Mannitol administration at peripheral hospitals is prone to dosing error. Strategies such as a pretransport checklist may mitigate this risk.

Objectives: Based on evidence supporting a potential relation between posttraumatic brain hypoxia and microcirculatory derangements with cell edema, we investigated the effects of the antiedematous agent mannitol on brain tissue oxygenation in a model of diffuse traumatic brain injury., Design: Experimental study., Setting: Neurosciences and physiology laboratories., Subjects: Adult male Wistar rats., Interventions: Thirty minutes after diffuse traumatic brain injury (impact-acceleration model), rats were IV administered with either a saline solution (traumatic brain injury-saline group) or 20% mannitol (1 g/kg) (traumatic brain injury-mannitol group). Sham-saline and sham-mannitol groups received no insult., Measurements and Main Results: Two series of experiments were conducted 2 hours after traumatic brain injury (or equivalent) to investigate 1) the effect of mannitol on brain edema and oxygenation, using a multiparametric magnetic resonance-based approach (n = 10 rats per group) to measure the apparent diffusion coefficient, tissue oxygen saturation, mean transit time, and blood volume fraction in the cortex and caudoputamen; 2) the effect of mannitol on brain tissue PO2 and on venous oxygen saturation of the superior sagittal sinus (n = 5 rats per group); and 3) the cortical ultrastructural changes after treatment (n = 1 per group, taken from the first experiment). Compared with the sham-saline group, the traumatic brain injury-saline group had significantly lower tissue oxygen saturation, brain tissue PO2, and venous oxygen saturation of the superior sagittal sinus values concomitant with diffuse brain edema. These effects were associated with microcirculatory collapse due to astrocyte swelling. Treatment with mannitol after traumatic brain injury reversed all these effects. In the absence of traumatic brain injury, mannitol had no effect on brain oxygenation. Mean transit time and blood volume fraction were comparable between the four groups of rats., Conclusion: The development of posttraumatic brain edema can limit the oxygen utilization by brain tissue without evidence of brain ischemia. Our findings indicate that an antiedematous agent such as mannitol can improve brain tissue oxygenation, possibly by limiting astrocyte swelling and restoring capillary perfusion.

Hyperosmolar agents are commonly used as an initial treatment for the management of raised intracranial pressure (ICP) after severe traumatic brain injury (TBI). They have an excellent adverse-effect profile compared to other therapies, such as hyperventilation and barbiturates, which carry the risk of reducing cerebral perfusion. The hyperosmolar agent mannitol has been used for several decades to reduce raised ICP, and there is accumulating evidence from pilot studies suggesting beneficial effects of hypertonic saline (HTS) for similar purposes. An ideal therapeutic agent for ICP reduction should reduce ICP while maintaining cerebral perfusion (pressure). While mannitol can cause dehydration over time, HTS helps maintain normovolemia and cerebral perfusion, a finding that has led to a large amount of pilot data being published on the benefits of HTS, albeit in small cohorts. Prophylactic therapy is not recommended with mannitol, although it may be beneficial with HTS. To date, no large clinical trial has been performed to directly compare the two agents. The best current evidence suggests that mannitol is effective in reducing ICP in the management of traumatic intracranial hypertension and carries mortality benefit compared to barbiturates. Current evidence regarding the use of HTS in severe TBI is limited to smaller studies, which illustrate a benefit in ICP reduction and perhaps mortality., (© 2015 New York Academy of Sciences.)

Object: Increased intracranial pressure (ICP) in patients with traumatic brain injury (TBI) is associated with a higher mortality rate and poor outcome. Mannitol and hypertonic saline (HTS) have both been used to treat high ICP, but it is unclear which one is more effective. Here, the authors compare the effect of mannitol versus HTS on lowering the cumulative and daily ICP burdens after severe TBI., Methods: The Brain Trauma Foundation TBI-trac New York State database was used for this retrospective study. Patients with severe TBI and intracranial hypertension who received only 1 type of hyperosmotic agent, mannitol or HTS, were included. Patients in the 2 groups were individually matched for Glasgow Coma Scale score (GCS), pupillary reactivity, craniotomy, occurrence of hypotension on Day 1, and the day of ICP monitor insertion. Patients with missing or erroneous data were excluded. Cumulative and daily ICP burdens were used as primary outcome measures. The cumulative ICP burden was defined as the total number of days with an ICP of > 25 mm Hg, expressed as a percentage of the total number of days of ICP monitoring. The daily ICP burden was calculated as the mean daily duration of an ICP of > 25 mm Hg, expressed as the number of hours per day. The numbers of intensive care unit (ICU) days, numbers of days with ICP monitoring, and 2-week mortality rates were also compared between the groups. A 2-sample t-test or chi-square test was used to compare independent samples. The Wilcoxon signed-rank or Cochran-Mantel-Haenszel test was used for comparing matched samples., Results: A total of 35 patients who received only HTS and 477 who received only mannitol after severe TBI were identified. Eight patients in the HTS group were excluded because of erroneous or missing data, and 2 other patients did not have matches in the mannitol group. The remaining 25 patients were matched 1:1. Twenty-four patients received 3% HTS, and 1 received 23.4% HTS as bolus therapy. All 25 patients in the mannitol group received 20% mannitol. The mean cumulative ICP burden (15.52% [HTS] vs 36.5% [mannitol]; p = 0.003) and the mean (± SD) daily ICP burden (0.3 ± 0.6 hours/day [HTS] vs 1.3 ± 1.3 hours/day [mannitol]; p = 0.001) were significantly lower in the HTS group. The mean (± SD) number of ICU days was significantly lower in the HTS group than in the mannitol group (8.5 ± 2.1 vs 9.8 ± 0.6, respectively; p = 0.004), whereas there was no difference in the numbers of days of ICP monitoring (p = 0.09). There were no significant differences between the cumulative median doses of HTS and mannitol (p = 0.19). The 2-week mortality rate was lower in the HTS group, but the difference was not statistically significant (p = 0.56)., Conclusions: HTS given as bolus therapy was more effective than mannitol in lowering the cumulative and daily ICP burdens after severe TBI. Patients in the HTS group had significantly lower number of ICU days. The 2-week mortality rates were not statistically different between the 2 groups.

Background: Rising intracranial pressure (ICP) is a poor prognostic indicator in traumatic brain injury (TBI). Both mannitol and hypertonic sodium solutions are used to treat raised ICP in patients with TBI., Objective: This meta-analysis compares the use of mannitol versus hypertonic sodium solutions for ICP control in patients with TBI., Data Sources and Study Eligibility: Randomised clinical trials in adults with TBI and evidence of raised ICP, which compare the effect on ICP of hypertonic sodium solutions and mannitol., Methods: The primary outcome measure is the pooled mean reduction in ICP. Studies were combined using a Forest plot., Results: Six studies were included, comprising 171 patients (599 episodes of raised ICP). The weighted mean difference in ICP reduction, using hypertonic sodium solutions compared with mannitol, was 1.39 mm Hg (95% CI -0.74 to 3.53)., Limitations: Methodological differences between studies limit the conclusions of this meta-analysis., Conclusions: The evidence shows that both agents effectively lower ICP. There is a trend favouring the use of hypertonic sodium solutions in patients with TBI., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)

We used near-infrared spectroscopy technology to monitor and assess the treatment effect of dehydrating agent in injured rat brain in real time style. We employed the brain edema model in rats resulting from Feeney' s freefall damage, then treated with different doses of mannitol, and collected reduced scattering coefficient (p',) and intracranial pressure (ICP) values after the injury and during the treatment. The results showed that brain edema happened 1 h after the injury in rats' brain tissue, peaked around 72 h after injury, and then began to decrease gradually. The reduced scattering coefficient and ICP values of the treatment group injected with mannitol all decreased after administration. Compared with the effect of low-dose mannitol treatment, that of high-dose mannitol treatment was much better. The duration of the plateau was longer and most experiments results declined significantly. From this we conclude that the reduced scattering coefficient and ICP are consistent with the trend changes, and the reduced scattering coefficient could be used as an indicator for monitoring cerebral edema.

Objective: To compare the effects of 15% hypertonic saline and 20% mannitol in doses of similar osmotic burden for treatment of intracranial hypertension in patients with severe traumatic brain injury., Methods: We used an alternating treatment protocol to compare the effects of hypertonic saline with that of mannitol given for episodes of increased intracranial pressure (ICP) in patients with severe brain injury. Standard guidelines for the management of severe traumatic brain injury were followed. For episodes of increased ICP, 20% mannitol (2 ml/kg, infused for over 20 min) and 15% saline (0.42 ml/kg, administered as a bolus via a central venous catheter) of similar osmotic burden were given alternately, with the choice of agent for the initial hypertensive event determined on a randomized basis. Reduction of ICP and duration of the action were recorded after each event., Results: The data were collected from 33 patients with 237 hypertensive events. The mean decrease in ICP was 8.7 mm Hg at 28.7∓9.3 min after mannitol treatment as compared with 9.3 mm Hg at 23.6∓7.1 min after treatment with hypertonic saline (P>0.05). The mean duration of the effect was 270 min for mannitol and 318 min for hypertonic saline (P>0.05)., Conclusions: Treatment with 15% hypertonic saline and 20% mannitol in doses of similar osmotic burden produces similar effects in management of increased ICP in patients with severe traumatic brain injury in terms of the time of action onset, maximum ICP reduction, and duration of action.

Traumatic brain injury (TBI) sustained in a traffic accident or a fall is a major cause of death that affects a broad range of ages. The aim of this study was to investigate the therapeutic effects of intra-arterial transplantation of mesenchymal stem cells (MSCs) combined with hypertonic glycerol (25%) or mannitol (25%) in a TBI model of rats. TBI models were produced with a fluid percussion device. At 24h after TBI, MSCs (1×10(6)cells/100μl) with glycerol or mannitol were administered via the right internal carotid artery. Rats were evaluated behaviorally and immunohistochemically, and hyperpermeability of the blood-brain barrier (BBB) induced by hypertonic solutions was explored. Compared to PBS or glycerol, the administration of mannitol resulted in increased BBB disruption. The mannitol-treated rats showed significant improvement in motor function. Intra-arterial transplantation of MSCs caused no thromboembolic ischemia. Immunohistochemically, more MSCs were observed in the injured brain tissues of mannitol-treated rats than in glycerol or PBS-treated rats at 24h after transplantation. Intra-arterial transplantation of MSCs combined with mannitol is an effective treatment in a TBI model of rats. This technique might be used for patients with diseases of the central nervous system including TBI., (Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.)

Background and Purpose: Intracranial hypertension and cerebral edema are known contributors to secondary brain injury and to poor neurologic outcomes. Small volume solutions of exceedingly high osmolarity, such as 23.4% saline, have been used for the management of intracranial hypertension crises and as a measure to prevent or reverse acute brain tissue shifts. We conducted a systematic literature review on the use of 23.4% saline in neurocritically ill patients and a meta-analysis of the effect of 23.4% saline on intracranial pressure reduction., Design: We searched computerized databases, reference lists, and personal files to identify all clinical studies in which 23.4% saline has been used for the treatment of neurocritical care patients. Studies that did not directly involve either effects on cerebral hemodynamics or the treatment of patients with clinical or radiographic evidence of intracranial hypertension and/or cerebral swelling were eliminated., Measurements and Main Results: We identified 11 clinical studies meeting eligibility criteria. A meta-analysis was performed to evaluate the percent decrease in intracranial pressure and the 95% confidence intervals, from baseline to 60 minutes or nadir from the six studies from which this information could be extracted. A fixed effects meta-analysis estimated that the percent decrease in intracranial pressure from baseline to either 60 minutes or nadir after administration of 23.4% saline was 55.6% (se 5.90; 95% confidence interval, 43.99-67.12; p < 0.0001)., Conclusions: Highly concentrated hypertonic saline such as 23.4% provides a small volume solution with low cost and an over 50% reduction effect on raised intracranial pressure. Side effects reported are minor overall in view of the potentially catastrophic event that is being treated. High quality data are still needed to define the most appropriate osmotherapeutic agent, the optimal dose, the safest and most effective mode of administration and to further elucidate the mechanism of action of 23.4% saline and of osmotherapy in general.

Background: Osmotherapy is a cornerstone for the management of severe Traumatic Brain Injury (TBI). Hypertonic saline (HTS) has advantages as being preferred osmotic agent, but there is inadequte knowledge regarding dose and its saftey in comparison to mannitol. S100B, as a specific neuroinflammatory biomarker in TBI might be a reliable therapeutic index following osmotic therapy., Aim: To compare both administration ways of HTS 5% (bolus and infusion) with mannitol upon S100B as a therapeutic tool for monitoring treatment in TBI patients., Method: Adult patients wih modrate to severe TBI were recruited and have randomly received one of the three protocols: 125 cc of HTS 5% every 6 hrs (N: 11) as bolus; 500 cc of HTS 5% (N: 12) as infusion for 24 hrs; or 1 g/kg mannitol of 20% (N: 10) as a bolus, repeated with a dose of 0.25-0.5 g/kg every 6 hrs based on patient's response for 3 days. Serum S100B, blood pressure, serum sodium and osmolality and Glascow coma score (GCS) were measured at baseline and daily for 3 days., Results: Initial serum S100B level in TBI patients was higher than control group (p < 0.0001). Levels of measured S100B have decreased for all treatment groups, but reduction wasn't significantly after hyperosmolal therapy. GCS level increased significantly in infusion group (p = 0.002) and there were negative and significant correlation between serum S100B level and GCS level in some days. Mean arterial pressure increased significantly in HTS groups (bolus: p = 0.002, infusion < 0.0001)., Conclusions: S100B is closely related to the pathophysiological mechanism in TBI and may be useful as a therapeutic tool for treatment monitoring in TBI patients HTS is a safe and effective osmotic agent in TBI setting.

Purpose: Cerebral blood flow (CBF) is reduced after severe traumatic brain injury (TBI) with considerable regional variation. Osmotic agents are used to reduce elevated intracranial pressure (ICP), improve cerebral perfusion pressure, and presumably improve CBF. Yet, osmotic agents have other physiologic effects that can influence CBF. We sought to determine the regional effect of osmotic agents on CBF when administered to treat intracranial hypertension., Materials and Methods: In 8 patients with acute TBI, we measured regional CBF with positron emission tomography before and 1 hour after administration of equi-osmolar 20% mannitol (1 g/kg) or 23.4% hypertonic saline (0.686 mL/kg) in regions with focal injury and baseline hypoperfusion (CBF <25 mL per 100 g/min)., Results: The ICP fell (22.4 ± 5.1 to 15.7 ± 7.2 mm Hg, P = .007), and cerebral perfusion pressure rose (75.7 ± 5.9 to 81.9 ± 10.3 mm Hg, P = .03). Global CBF tended to rise (30.9 ± 3.7 to 33.1 ± 4.2 mL per 100 g/min, P = .07). In regions with focal injury, baseline flow was 25.7 ± 9.1 mL per 100 g/min and was unchanged; in hypoperfused regions (15% of regions), flow rose from 18.6 ± 5.0 to 22.4 ± 6.4 mL per 100 g/min (P < .001). Osmotic therapy reduced the number of hypoperfused brain regions by 40% (P < .001)., Conclusion: Osmotic agents, in addition to lowering ICP, improve CBF to hypoperfused brain regions in patients with intracranial hypertension after TBI., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Object: Evidence-based guidelines recommend intracranial pressure (ICP) monitoring for patients with severe traumatic brain injury (TBI), but there is limited evidence that monitoring and treating intracranial hypertension reduces mortality. This study uses a large, prospectively collected database to examine the effect on 2-week mortality of ICP reduction therapies administered to patients with severe TBI treated either with or without an ICP monitor., Methods: From a population of 2134 patients with severe TBI (Glasgow Coma Scale [GCS] Score <9), 1446 patients were treated with ICP-lowering therapies. Of those, 1202 had an ICP monitor inserted and 244 were treated without monitoring. Patients were admitted to one of 20 Level I and two Level II trauma centers, part of a New York State quality improvement program administered by the Brain Trauma Foundation between 2000 and 2009. This database also contains information on known independent early prognostic indicators of mortality, including age, admission GCS score, pupillary status, CT scanning findings, and hypotension., Results: Age, initial GCS score, hypotension, and CT scan findings were associated with 2-week mortality. In addition, patients of all ages treated with an ICP monitor in place had lower mortality at 2 weeks (p = 0.02) than those treated without an ICP monitor, after adjusting for parameters that independently affect mortality., Conclusions: In patients with severe TBI treated for intracranial hypertension, the use of an ICP monitor is associated with significantly lower mortality when compared with patients treated without an ICP monitor. Based on these findings, the authors conclude that ICP-directed therapy in patients with severe TBI should be guided by ICP monitoring.

Objectives: To describe patterns of use for mannitol and hypertonic saline in children with traumatic brain injury, to evaluate any potential associations between hypertonic saline and mannitol use and patient demographic, injury, and treatment hospital characteristics, and to determine whether the 2003 guidelines for severe pediatric traumatic brain injury impacted clinical practice regarding osmolar therapy., Design: Retrospective cohort study., Setting: Pediatric Health Information System database, January, 2001 to December, 2008., Patients: Children (age <18 yrs) with traumatic brain injury and head/neck Abbreviated Injury Scale score ≥ 3 who received mechanical ventilation and intensive care., Interventions: : None., Measurements and Main Results: The primary outcome was hospital billing for parenteral hypertonic saline and mannitol use, by day of service. Overall, 33% (2,069 of 6,238) of the patients received hypertonic saline, and 40% (2,500 of 6,238) received mannitol. Of the 1,854 patients who received hypertonic saline or mannitol for ≥ 2 days in the first week of therapy, 29% did not have intracranial pressure monitoring. After adjustment for hospital-level variation, primary insurance payer, and overall injury severity, use of both drugs was independently associated with older patient age, intracranial hemorrhage (other than epidural), skull fracture, and higher head/neck injury severity. Hypertonic saline use increased and mannitol use decreased with publication of the 2003 guidelines, and these trends continued through 2008., Conclusions: Hypertonic saline and mannitol are used less in infants than in older children. The patient-level and hospital-level variation in osmolar therapy use and the substantial amount of sustained osmolar therapy without intracranial pressure monitoring suggest opportunities to improve the quality of pediatric traumatic brain injury care. With limited high-quality evidence available, published expert guidelines appear to significantly impact clinical practice in this area.

Objectives: The purpose of this study was to describe the administration of 3% saline (3%S) during pediatric critical care transport., Methods: A retrospective study was performed on pediatric patients who underwent critical transport to Loma Linda University Children's Hospital from January 1, 2003, to June 30, 2007, and were given 3%S. Patients' demographics, admission diagnosis, route and amount of 3%S administration, serum electrolytes, vital signs, radiographic data, and Glasgow Coma Scale scores were collected and analyzed., Results: A total of 101 children who received 3%S infusions during pediatric critical care transport were identified. Mean patient age was 5.9 years, and mean patient weight was 27.6 kg. The main indications for infusing 3%S were suspected cerebral edema (41%), intracranial bleed with edema (51%), and symptomatic hyponatremia (6%). The amount of 3%S bolus ranged from 1.2 to 24 mL/kg, with a mean of 5.4 mL/kg. Serum electrolytes before and after 3%S infusion demonstrated significant increases in sodium, chloride, and bicarbonate levels (P < 0.05). A significant reduction was also seen in serum urea nitrogen levels and anion gap. Radiographic imaging performed before 3%S infusion demonstrated findings consistent with concerns of increased intracranial pressure such as intracranial bleed and cerebral edema. The route of initial 3%S infusions was mainly through peripheral intravenous lines (96%). No complications related to the 3%S delivery such as local reactions, renal abnormalities, or central pontine myelinolysis were observed., Conclusions: It seems 3%S may be administered safely during pediatric critical transport and administration routes can include peripheral lines. With the importance of initiating therapy early to improve patient outcomes, the use of 3%S may benefit transported children with brain injury and suspected intracranial hypertension.

The potential superiority of hypertonic saline (HTS) over mannitol (MTL) for control of intracranial pressure (ICP) following traumatic brain injury (TBI) is still debated. Forty-seven severe TBI patients with increased ICP were prospectively recruited in two university hospitals and randomly treated with equiosmolar infusions of either MTL 20% (4 mL/kg; n=25 patients) or HTS 7.5% (2 mL/kg; n=22 patients). Serum sodium, hematocrit, ICP, arterial blood pressure, cerebral perfusion pressure (CPP), shear rate, global indices of cerebral blood flow (CBF) and metabolism were measured before, and 30 and 120 min following each infusion during the course of illness. Outcome was assessed at 6 months. Both HTS and MTL effectively and equally reduced ICP levels with subsequent elevation of CPP and CBF, although this effect was significantly stronger and of longer duration after HTS and correlated with improved rheological blood properties induced by HTS. Further, effect of HTS on ICP appeared to be more robust in patients with diffuse brain injury. In contrast, oxygen and glucose metabolic rates were left equally unaffected by both solutions. Accordingly, there was no significant difference in neurological outcome between the two groups. In conclusion, MTL was as effective as HTS in decreasing ICP in TBI patients although both solutions failed to improved cerebral metabolism. HTS showed an additional and stronger effect on cerebral perfusion of potential benefit in the presence of cerebral ischemia. Treatment selection should therefore be individually based on sodium level and cerebral hemodynamics.

Object: The purpose of this study was to compare the effects of mannitol and hypertonic saline in doses of similar osmotic burden for the treatment of intracranial hypertension in patients with severe traumatic brain injury., Methods: The authors used an alternating treatment protocol to compare the effect of hypertonic saline with that of mannitol given for episodes of increased intracranial pressure in patients treated for severe head injury at their hospital during 2006-2008. Standard guidelines for the management of severe traumatic brain injury were followed. Elevated intracranial pressure (ICP) was treated either with mannitol or hypertonic saline. Doses of similar osmotic burden (mannitol 20%, 2 ml/kg, infused over 20 minutes, or saline 15%, 0.42 ml/kg, administered as a bolus via a central venous catheter) were given alternately to the individual patient with severe brain injury during episodes of increased pressure. The dependent variables were the extent and duration of reduction of increased ICP. The choice of agent for treatment of the initial hypertensive event was determined on a randomized basis; treatment was alternated for every subsequent event in each individual patient. Reduction of ICP and duration of action were recorded after each event. Results obtained after mannitol administration were statistically compared with those obtained after hypertonic saline administration., Results: Data pertaining to 199 hypertensive events in 29 patients were collected. The mean decrease in ICP obtained with mannitol was 7.96 mm Hg and that obtained with hypertonic saline was 8.43 mm Hg (p = 0.586, equal variances assumed). The mean duration of effect was 3 hours 33 minutes for mannitol and 4 hours 17 minutes for hypertonic saline (p = 0.40, equal variances assumed)., Conclusions: No difference between the 2 medications could be found with respect to the extent of reduction of ICP or duration of action.

Purpose: The use of hypertonic saline injection in trauma patients is discussed., Summary: Patients with hemorrhage, burns, and traumatic brain injury (TBI) may develop hypovolemic shock and require resuscitation. Compared with conventional isotonic crystalloids, hypertonic saline has several advantages, including hemodynamic, immune-modulating, and antiinflammatory effects, for use in trauma patients for resuscitation. In addition, hypertonic saline is also used in patients with TBI to reduce intracranial pressure (ICP). Overall, studies have not shown a difference in mortality or other clinically important outcomes with the use of hypertonic saline for resuscitation in trauma patients; however, most of these studies were not adequately powered to show significant differences. A recent Cochrane review concluded that there is no evidence that hypertonic crystalloids are better than isotonic or near-isotonic crystalloids for fluid resuscitation in trauma patients. Two recent trials that were adequately powered to investigate a mortality endpoint were halted for futility. A few small randomized controlled studies found that hypertonic saline was more effective than mannitol as a hyperosmolar agent for ICP reduction. Recent guidelines from the American Burn Association have suggested that hypertonic saline may be used for burn shock resuscitation by experienced providers with close monitoring to avoid excessive hypernatremia. One of the main concerns with the use of hypertonic saline is its potential to cause central pontine myelinolysis due to a rapid increase in serum sodium levels., Conclusion: There is no evidence that hypertonic saline provides any additional benefit over isotonic crystalloid solutions for trauma resuscitation. Hypertonic saline may be more effective than mannitol at reducing ICP in patients with TBI.

We retrospectively studied a random cohort of patients with cerebral trauma to investigate the risk factors of acute kidney injury (AKI) following cerebral trauma. AKI was determined using the RIFLE (risk, injury, failure, loss, or end-stage kidney) staging criteria. About 171 patients were chosen in the study, with 53 patients in AKI group and 118 patients without AKI in non-AKI group. By logistic regression analysis, univariate analysis revealed that age, hypertension, emergent surgery, systemic inflammatory response syndrome (SIRS), Glasgow coma score (GCS), sequential organ failure assessment (SOFA) score, the respiration, coagulation, and cardiovascular components of the SOFA score, mechanical ventilation time, red blood cell transfusion, plasma transfusion, and the accumulative doses of furosemide, torsemide, and mannitol were significantly related to AKI after cerebral trauma. Logistic multivariate regression analysis showed that SOFA score [odds ratio (OR) = 1.516, 95% confidence interval (CI) 1.222-1.881, p < 0.001], the accumulative doses of torsemide (OR = 0.016, 95% CI 1.002-1.031, p = 0.016), and the accumulative doses of mannitol (OR = 2.687, 95% CI 1.062-6.800, p = 0.037) were independent risk factors of AKI. This model had a good discrimination for AKI with an area under the receiver operating characteristic (ROC) curve of 0.901 (p < 0.001). The accumulative doses of mannitol as a risk factor of AKI were identified by propensity score match (PSM) method. We concluded that AKI was a common complication in patients with cerebral trauma. SOFA score and the accumulative doses of torsemide and mannitol were independent risk factors of AKI following cerebral trauma.

Background: Oncotic agents are a therapeutic mainstay for the management of intracranial hypertension. Both mannitol and varied concentrations of hypertonic saline (HTS) have been shown to be effective at reducing elevated intracranial pressure (ICP). We compared the safety and efficacy of 23.4% HTS to mannitol for acute management of elevated ICP after traumatic brain injury (TBI)., Methods: After approval from our institutional review board, the records of patients admitted with severe TBI who received mannitol or HTS were reviewed. Demographic and physiologic data were recorded. ICP, cerebral perfusion pressure, reduction of ICP after dose administration, serum sodium, osmolality, and magnitude of dose response during the subsequent 60 minutes were analyzed. Efficacy was determined by comparison of proportion of patients with any response and mean change in ICP after dosing with either agent. Safety was determined by recording any new postinfusion electrolyte or neurologic anomalies. Data were compared using chi2 test, accepting p < 0.05 as significant., Results: Twenty-two patients with severe TBI received 210 doses of either mannitol or HTS. All patients suffered severe blunt injury (mean Injury Severity Score 28 +/- 11). HTS patients had a significantly higher ICP at the initiation of therapy than that of mannitol group (30.7 +/- 7.94 mm Hg vs. 28.3 +/- 8.07 mm Hg, respectively). There was no difference in initial cerebral perfusion pressure. Mean ICP reduction in the hour after administration of 102 doses of mannitol and 108 doses of HTS was greater for patients receiving HTS (9.3 +/- 7.37 mm Hg vs. 6.4 +/- 6.57 mm Hg, respectively; p = 0.0028, chi2). More patients responded to HTS (92.6% HTS vs. 74% mannitol; p = 0.0002, chi2). There was no significant difference between groups in the duration of ICP reduction after dose administration (4.1 hours vs. 3.8 hours, respectively). No adverse events after administration of either agent were identified., Conclusion: Based on this retrospective analysis, 23.4% HTS is more efficacious than mannitol in reducing ICP. If these results are confirmed in a prospective, randomized study, 23.4% HTS may become the agent of choice for the management of elevated ICP after TBI.

Objectives: Traumatic brain injury (TBI) is still a major cause of mortality and morbidity. Recent trials have failed to demonstrate a beneficial outcome from therapeutic treatments such as corticosteroids, hypothermia and hypertonic saline. We investigated the effect of a new hyperosmolar solution based on sodium lactate in controlling raised intracranial pressure (ICP)., Design and Setting: Prospective open randomized study in an adult ICU., Patients: Thirty-four patients with isolated severe TBI (Glasgow Coma Scale

Objectives: The aim of this study was to compare the effects of mannitol and melatonin on brain edema secondary to trauma using magnetic resonance imaging (MRI)., Methods: A mild traumatic brain injury with the Feeney method was performed upon twelve New Zealand rabbits. Three hours after the trauma was inflicted, MRI images were obtained, then the subjects were divided into two groups: a mannitol group and a melatonin group. The mannitol group (n = 6) was given 2 gr/kg of 20% mannitol IV over 10 minutes and the melatonin group (n = 6) received 100 mg/kg of melatonin IV over 30 minutes. Thirty-three hours after the first MRI, MRI was repeated. The 3-hour and 36-hour post-trauma MRI images in both groups were scored regarding signs of edema and extent of brain tissue protrusion in a blinded fashion by a staff radiologist. Intragroup and intergroup comparisons were made using the Fisher exact test and chi square test. Comparison of brain tissue protrusion measurements was done using the Mann Whitney U test., Results: Signs of raised intraventricular pressure, contusion and parenchymal edema were more prevelant, and parenchymal protrusion was more prominent on the 36-hour MRI in both mannitol and melatonin groups. No significant difference was found between the melatonin and mannitol groups in any parameter in the MRI images performed 3 and 36 hours after the head trauma., Conclusions: In this animal model, melatonin and mannitol had similar effects on brain edema, as demonstrated on MRI 3 and 36 hours after head trauma.

Animal and human studies suggest that hypertonic saline is a potential therapeutic agent to assist with the medical treatment of patients with traumatic brain injury. It may have a place as osmotherapy to decrease brain size, predominantly of uninjured brain and has several potential advantages over mannitol. Hypertonic saline has clinically desirable physiological effects on cerebral blood flow, intracranial pressure and inflammatory responses in models of neurotrauma. Animal studies support its use, but definitive human trials using mortality end-points in brain trauma are lacking. Hypertonic saline may be considered a therapeutic adjunct to the medical management of traumatic brain injury, awaiting definitive evidence to support routine use.

Purpose of Review: This review aims to provide an update on recent knowledge gained on hypertonic saline solutions for the treatment of intracranial hypertension. Explanatory approaches to the mechanisms underlying the edema-reducing effects of the solutions are outlined, practical aspects of use are presented, and trials that assessed their clinical utility are highlighted., Recent Findings: With an established trauma system, hypertonic saline added to conventional fluid resuscitation did not improve long-term outcome in multiple injury with hypotension and brain trauma. In intensive care, hypertonic saline reduced intracranial hypertension after subarachnoid haemorrhage, brain trauma, and a variety of other brain diseases, including cerebral edema in acute liver failure., Summary: Hypertonic saline solutions have evolved as an alternative to mannitol or may be used in otherwise refractory intracranial hypertension to treat raised intracranial pressure. With high osmolar loads, the efficacy of the solution is enhanced, but no simple relationship between the saline concentration and the clinical effects of a solution is established. Caution is advised with high osmolar loads because they carry increased risks for potentially deleterious consequences of hypernatremia or may induce osmotic blood-brain barrier opening with possibly harmful extravasation of the hypertonic solution into the brain tissue.

In this study, our objective is to investigate the effects of mannitol and 7.5% hypertonic saline (HS) therapy on the levels of malondialdehyde (MDA), catalase and glutathione peroxidase (GSH-Px) in the early stages of experimental head traumas in rats. Rats included in the study were divided into four groups: Group I Control, Group II Trauma, Group III Mannitol, and Group IV 7.5% Hypertonic Saline. Rats in Group II were subject to head trauma only. Mannitol was injected intraperitoneally to rats in Group III after head trauma and 7.5% HS was injected intraperitoneally to rats in Group IV after head trauma. Rats were sacrificed 4 h after administration of mannitol or 7.5% HS, and the levels of MDA catalase and GSH-Px in brain tissues extracted from rats were determined. MDA levels in the trauma group were significantly increased compared with the control group (p<0.01), whereas there was a reduction in catalase and GSH-Px levels, although these differences were not significant. By contrast, in the mannitol group, MDA, catalase and GSH-Px levels were lower than the levels in the trauma group, and these reductions were statistically significant (p<0.05). The MDA, catalase and GSH-Px levels of the 7.5% HS group were lower than those of the trauma group; however, this reduction was not statistically significant. It was concluded that mannitol and 7.5% HS therapies that are used to reduce intracranial pressure and to increase the use of catalase, an antioxidant enzyme, and GSH-Px, are likely to reduce cellular damage by reducing the formation of MDA, the levels of which are known to be indicative of cellular level oxidant damage.

The objective of the treatment of intracranial hypertension is to decrease intracranial pressure (ICP) while maintaining cerebral blood flow (CBF). Despite numerous treatments, none of them associates total efficiency and security. Systemic secondary cerebral injuries, which are responsible for cerebral ischemia, lead us to administer non specific treatments in order to optimize CBF and cerebral oxygenation. Thus, the goals are: 1) to maintain cerebral perfusion pressure> or =70 mmHg; 2) to control metabolic status by preventing hyperglycaemia, anaemia and hyperthermia; 3) to maintain normoxia and normocapnia (hypercapnia increases ICP and hypocapnia decreases CBF). Beside the neurosurgical evacuation of extra- and intraparenchymatous haematomas, osmotherapy and cerebrospinal fluid (CSF) evacuation are the two specific treatments of intracranial hypertension. Osmotherapy consists in an administration of a hypertonic solution which induces a decrease in cerebral water and finally in ICP. Mannitol (20%), which is the reference, associates osmotic and rheologic effects, and decreases CSF production too. Recent data conduct us to administer larger doses, between 0.7 and 1 g/kg in 15 minutes. Hypertonic saline solution associates osmotic effects and plasma volume loading. Thus, this solution is particularly appropriate in severe head injury with arterial hypotension. CBF evacuation decreases rapidly ICP without any major side-effect. Until now, there is no proof of a superior efficiency of a treatment for intracranial hypertension compared to another. Considering their mechanism of action, all of them are efficient but potentially dangerous too. Indeed, the choice between treatments depends on data which are issued from the multimodal monitoring. General non specific treatments are always necessary. Specific treatments are indicated if ICP is above 20-25 mmHg. Maintaining cerebral perfusion pressure represents the first therapeutic goal. If intracranial hypertension persists, evacuation of CBF or osmotherapy may be advocated. In case of refractory intracranial hypertension, it may be useful to deepen neurosedation. Controlled hypocapnia and barbiturates remain a third line therapy providing to monitor and maintain an appropriate CBF and cerebral oxygenation. Controlled hypothermia and decompressive craniectomy must be individually discussed.

Brain hypothermia treatment (BHT) is an intensive care characterized by simultaneous managements of various vital signs, such as intracranial temperature (ICT) and pressure (ICP), of the severe neuropatient. Medical treatments including therapeutic ambient cooling and diuresis are separately carried out based on the experience of the medical staff involved in the clinical management of various pathophysiological processes, such as thermodynamics, hemodynamics and pharmacokinetics. However, no special attention has been paid to the interactions among these subsystems in therapeutic hypothermia because of the lack of theoretical knowledge. Therefore, quantitative analyses using an integrated model of various physiological processes and their interactions are of pressing need. In the present paper, we propose a general compartmental model to describe the pathophysiological processes of the three aforementioned dynamics, on account of the dynamical analogy of temperature, pressure and concentration. The model is verified by the agreement of model-based simulation results with clinical evidence. Based on responses of the integrated model to various stimuli, a transfer function matrix is identified to linearly approximate the characteristic interrelationships between medical treatments (ambient cooling and diuresis) and the vital signs (ICT and ICP). Then a controller that decouples ambient cooling and diuresis is proposed for efficient management of ICT and ICP, enhancement of hypothermic decompression and reduction of diuretic dosage. Decoupling control simulation indicates that ICT and ICP of the integrated model, representing a patient under BHT, can be simultaneously regulated by a single PID controller for ambient cooling and another for diuresis. The proposed decoupler effectively establishes hypothermic decompression, reduces the dosage of diuretic and improves ICP management. Theoretical analyses of the integrated model and decoupling control of ICT and ICP provide insights into the intensive care of various pathophysiological processes in patients undergoing BHT.

Hypernatremia exerts its main effect on the brain through the osmotic gradient it creates on either side of the blood brain barrier, which is impermeable to sodium. This generates a transfer of water from the intracellular to the vascular sector leading to temporary cell shrinkage. Osmoregulation permits cerebral cells to accumulate osmoactive molecules in order to restore their initial volume. It has been demonstrated in animals with brain injury that intracellular dehydration occurs essentially in the nonlesioned hemisphere. In most experimental studies, the reduction in cerebral volume obtained by hypertonic saline (HS) perfusion is accompanied by an intracranial pressure decrease, even under hemorrhagic shock conditions. Initially, clinical studies successfully used HS, as an alternative to mannitol, in the treatment of acute and refractory intracranial hypertension. Then continuous infusion of HS, with the objective of inducing hypernatremia, had produced encouraging effects on intracranial pressure control. However, these results were limited to non-randomized studies, without control groups and mainly in pediatric patients. Nevertheless, the use of HS on intracranial hypertension, refractory to conventional treatments, could be reasonable under strict monitoring of natremia as well as its adverse effects.

Objective: To compare the respective effects of established measures used for management of traumatic brain injury (TBI) patients on cerebral blood flow (CBF) and cerebral metabolic rates of oxygen (CMRO2), glucose (CMRGlc) and lactate (CMRLct)., Methods: Thirty-six patients suffering from severe traumatic brain injury (TBI) were prospectively evaluated. In all patients baseline assessments were compared with that following moderate hyperventilation (reducing PaCO2 from 36 +/- 4 to 32 +/- 4 mmHg) and with that produced by administration of 0.5 gr/kg mannitol 20% intravenously. Intracranial and cerebral perfusion pressure (ICP, CPP), CBF and arterial jugular differences in oxygen, glucose and lactate contents were measured for calculation of CMRO2, CMRGlc and CMRLct., Results: Following hyperventilation, CBF was significantly reduced (P < 0.0001). CBF remained most often above the ischemic range although values less than 30 ml x 100 gr(-1) x min(-1) were found in 27.8% of patients. CBF reduction was associated with concurrent decrease in CMRO2, anaerobic hyperglycolysis and subsequent lactate production. In contrast, mannitol resulted in significant albeit moderate improvement of cerebral perfusion. However, administration of mannitol had no ostensible effect either on oxidative or glucose metabolism and lactate balance remained mostly unaffected., Conclusions: Moderate hyperventilation may exacerbate pre-existing impairment of cerebral blood flow and metabolism in TBI patients and should be therefore carefully used under appropriate monitoring. Our findings rather support the use of mannitol for ICP control.

The past decade has witnessed a resurgence of interest in the use of hypertonic saline for low-volume resuscitation after trauma. Preliminary studies suggested that benefits are limited to a subgroup of trauma patients with brain injury, but a recent study of prehospital administration of hypertonic saline to patients with traumatic brain injury failed to confirm a benefit. Animal and human studies have demonstrated that hypertonic saline has clinically desirable physiological effects on cerebral blood flow, intracranial pressure, and inflammatory responses in models of neurotrauma. There are few clinical studies in traumatic brain injury with patient survival as an end point. In this review, we examined the experimental and clinical knowledge of hypertonic saline as an osmotherapeutic agent in neurotrauma.

Background: Traumatic brain injury is a major cause of mortality and morbidity, particularly among young men. The efficacy and safety of most of the interventions used in the management of patients with traumatic brain injury remain unproven. Examples include the 'cerebral perfusion pressure-targeted' and 'volume-targeted' management strategies for optimizing cerebrovascular haemodynamics and specific interventions, such as hyperventilation, osmotherapy, cerebrospinal fluid drainage, barbiturates, decompressive craniectomy, therapeutic hypothermia, normobaric hyperoxia and hyperbaric oxygen therapy., Methods: A review of the literature was performed to examine the evidence base behind each intervention., Results: There is no class I evidence to support the routine use of any of the therapies examined., Conclusion: Well-designed, large, randomized controlled trials are needed to determine therapies that are safe and effective from those that are ineffective or harmful.