Hypertonic saline versus mannitol for the treatment of elevated intracranial pressure: A meta-analysis of randomized clinical trials

Department of Neurology, University of California, San Francisco, CA, USA.
Critical care medicine (Impact Factor: 6.31). 03/2011; 39(3):554-9. DOI: 10.1097/CCM.0b013e318206b9be
Source: PubMed


Randomized trials have suggested that hypertonic saline solutions may be superior to mannitol for the treatment of elevated intracranial pressure, but their impact on clinical practice has been limited, partly by their small size. We therefore combined their findings in a meta-analysis.
We searched for relevant studies in MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials (CENTRAL), Scopus, and ISI Web of Knowledge.
Randomized trials were included if they directly compared equiosmolar doses of hypertonic sodium solutions to mannitol for the treatment of elevated intracranial pressure in human subjects undergoing quantitative intracranial pressure measurement.
Two investigators independently reviewed potentially eligible trials and extracted data using a preformed data collection sheet. Disagreements were resolved by consensus or by a third investigator if needed. We collected data on patient demographics, type of intracranial pathology, baseline intracranial pressure, osms per treatment dose, quantitative change in intracranial pressure, and prespecified adverse events. Our primary outcome was the proportion of successfully treated episodes of elevated intracranial pressure.
Five trials comprising 112 patients with 184 episodes of elevated intracranial pressure met our inclusion criteria. In random-effects models, the relative risk of intracranial pressure control was 1.16 (95% confidence interval, 1.00-1.33), and the difference in mean intracranial pressure reduction was 2.0 mm Hg (95% confidence interval, -1.6 to 5.7), with both favoring hypertonic saline over mannitol. A mild degree of heterogeneity was present among the included trials. There were no significant adverse events reported.
We found that hypertonic saline is more effective than mannitol for the treatment of elevated intracranial pressure. Our meta-analysis is limited by the small number and size of eligible trials, but our findings suggest that hypertonic saline may be superior to the current standard of care and argue for a large, multicenter, randomized trial to definitively establish the first-line medical therapy for intracranial hypertension.

  • Source
    • "It is administered either as a bolus to treat acute elevations of intracranial pressure (ICP) or infused as osmolar therapy in an attempt to prevent central nervous system (CNS) edema. Bolus HTS, in high concentrations, has proven to be as effective as mannitol in treating elevated ICP [1] [2]. At 3% concentration, HTS infusion maintains relatively high serum sodium (Na) levels in patients with CNS pathology [3] [4]. "
    [Show abstract] [Hide abstract]
    ABSTRACT: We aimed to investigate the incidence of electrolyte abnormalities, acute kidney injury (AKI), deep venous thrombosis (DVT) and infections in patients with traumatic brain injury (TBI) treated with hypertonic saline (HTS) as osmolar therapy. We retrospectively studied 205 TBI patients, 96 with HTS and 109 without, admitted to the surgical/trauma intensive care unit between 2006 and 2012. Hemodynamics, electrolytes, length of stay (LOS), acute physiological assessment and chronic health evaluation II (APACHE II), injury severity scores (ISS) and mortality were tabulated. Infection, mechanical ventilation, DVT and AKI incidence were reviewed. HTS was associated with increased LOS and all infections (p=0.0001). After correction for the Glasgow coma scale (GCS) and ventilator need, pulmonary infections (p=0.001) and LOS remained higher with HTS (p=0.0048). HTS did not result in increased blood pressure, DVT, AKI or neurological benefits. HTS significantly increased the odds for all infections, most specifically pulmonary infections, in patients with GCS<8. Due to these findings, HTS in TBI should be administered with caution regardless of acuity. Copyright © 2015 Elsevier Ltd. All rights reserved.
    Full-text · Article · Jun 2015 · Journal of Clinical Neuroscience
  • Source
    • "More recently, hypertonic saline (HTS) has become popular [5] [6] [7]. While there is as yet no definitive evidence to support one agent as clearly superior, one meta-analysis suggests that equi-osmolar HTS may be more effective than mannitol [8]. At our institution, HTS is regularly used as the firstline hyperosmolar therapy as part of a larger tiered protocol. "
    [Show abstract] [Hide abstract]
    ABSTRACT: In patients with severe traumatic brain injury, increased intracranial pressure (ICP) is associated with poor functional outcome or death. Hypertonic saline (HTS) is a hyperosmolar therapy commonly used to treat increased ICP; this study aimed to measure initial patient response to HTS and look for association with patient outcome. Patients >17 years old, admitted and requiring ICP monitoring between 2008 and 2010 at a large urban tertiary care facility were retrospectively enrolled. The first dose of hypertonic saline administered after admission for ICP >19mmHg was recorded and correlated with vital signs recorded at the bedside. The absolute and relative change in ICP at 1 and 2h after HTS administration was calculated. Patients were stratified by mortality and long-term (≥6 months) functional neurological outcome. We identified 46 patients who received at least 1 dose of HTS for ICP>19, of whom 80% were male, mean age 34.4, with a median post-resuscitation GCS score of 6. All patients showed a significant decrease in ICP 1h after HTS administration. Two hours post-administration, survivors showed a further decrease in ICP (43% reduction from baseline), while ICP began to rebound in non-survivors (17% reduction from baseline). When patients were stratified for long-term neurological outcome, results were similar, with a significant difference in groups by 2h after HTS administration. In patients treated with HTS for intracranial hypertension, those who survived or had good neurological outcome, when compared to those who died or had poor outcomes, showed a significantly larger sustained decrease in ICP 2h after administration. This suggests that even early in a patient's treatment, treatment responsiveness is associated with mortality or poor functional outcome. While this work is preliminary, it suggests that early failure to obtain a sustainable response to hyperosmolar therapy may warrant greater treatment intensity or therapy escalation.
    Full-text · Article · Sep 2014 · Injury
  • Source
    • "mannitol in the reduction of quantitative intracranial pressure (ICP) measurements (Kamel et al., 2011). Together, these studies suggest that high-osmolarity solutions are superior to low-osmolarity solutions in reducing cerebral edema, potentially identifying AVP as a common pathway through which osmotherapy reduces cerebral edema. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Although many approaches have been tried in the attempt to reduce the devastating impact of stroke, tissue plasminogen activator for thromboembolic stroke is the only proved, effective acute stroke treatment to date. Vasopressin, an acute-phase reactant, is released after brain injury and is partially responsible for the subsequent inflammatory response via activation of divergent pathways. Recently there has been increasing interest in vasopressin because it is implicated in inflammation, cerebral edema, increased intracerebral pressure, and cerebral ion and neurotransmitter dysfunctions after cerebral ischemia. Additionally, copeptin, a byproduct of vasopressin production, may serve as a promising independent marker of tissue damage and prognosis after stroke, thereby corroborating the role of vasopressin in acute brain injury. Thus, vasopressin antagonists have a potential role in early stroke intervention, an effect thought to be mediated via interactions with aquaporin receptors, specifically aquaporin-4. Despite some ambiguity, vasopressin V1a receptor antagonism has been consistently associated with attenuated secondary brain injury and edema in experimental stroke models. The role of the vasopressin V2 receptor remains unclear, but perhaps it is involved in a positive feedback loop for vasopressin expression. Despite the encouraging initial findings we report here, future research is required to characterize further the utility of vasopressin antagonists in treatment of stroke. © 2014 Wiley Periodicals, Inc.
    Full-text · Article · Sep 2014 · Journal of Neuroscience Research
Show more