Systematic review on marine carbon source-mannitol: Applications in synthetic biology.

Mannitol, one of the most widespread sugar alcohols, has been integral to daily human life for two centuries. Global population growth and competition for freshwater, food, and land have prompted a shift in the fermentation industry from terrestrial to marine raw materials. Mannitol is a readily available carbohydrate in brown seaweed from the ocean and possess a higher reducing power than glucose, making it a promising substrate for biological manufacturing. This has spurred numerous explorations into converting mannitol into high-value chemicals. Researchers have engineered microorganisms to utilize mannitol in various synthetic biological applications, including: (1) employing mannitol as an inducer to control the activation and deactivation of genetic circuits; (2) using mannitol as a carbon source for synthesizing high-value chemicals through biomanufacturing. This review summarizes the latest advances in the application of mannitol in synthetic biology. AIM OF REVIEW: The aim is to present a thorough and in-depth knowledge of mannitol, a marine carbon source, and then use this carbon source in synthetic biology to improve the competitiveness of biosynthetic processes. We outlined the methods and difficulties of utilizing mannitol in synthetic biology with a variety of microbes serving as hosts. Furthermore, future research directions that could alleviate the carbon catabolite repression (CCR) relationship between glucose and mannitol are also covered. EXPECTED CONTRIBUTIONS OF REVIEW: Provide an overview of the current state, drawbacks, and directions for future study on mannitol as a carbon source or genetic circuit inducer in synthetic biology.

Sugar lowering in fermented apple-pear juice orchestrates a promising metabolic answer in the gut microbiome and intestinal integrity.

Excessive sugar consumption in young people, who are the major consumers of sugary drinks, combined with limited physical activity, is an important determinant of obesity. Despite their natural appeal, fruit juices have a similar sugar content to that of sugary drinks and once metabolized, they may induce the same biological response. This study aimed to verify whether fermentation processes can make juice consumption healthier and whether reduced-sugar juices have a specific impact on intestinal function. We designed a tailored fermentation of apple-pear juices with lactic acid bacteria and yeasts, which resulted in a reduction of sugar content (27-66%) and caloric intake, and an increase in mannitol content. The impact of newly developed apple-pear juices on gut microbiome composition and functionality was evaluated in vitro using the Simulator of the Human Intestinal Microbial Ecosystem (SHIME). Promising changes were found in the gut microbiota and its metabolic responses and functionality, targeting pathways related to obesity and weight loss (lipopolysaccharide and secondary metabolite biosynthesis, polycyclic aromatic hydrocarbon degradation, and amino sugar and nucleotide sugar metabolism). Additionally, the fermented apple-pear juices positively modulated the intestinal epithelial features. While the simulation of the study simplifies the complex in vivo conditions, it suggests that low-sugar fermented apple-pear juices can elicit targeted responses in the gut ecosystem, contributing to healthier alternatives to traditional fruit juices.

Effectiveness of Mannitol Use on Clinical Outcomes of Severe Traumatic Brain Injury Patients.

Background: Head injuries are considered as a silent epidemic due to the high incidence rate throughout the world. The main cause of morbidity and mortality in patients with head injury is cerebral edema which is defined as abnormal fluid accumulation in the brain parenchyma. Mannitol is a hyperosmolar solution given to reduce fluid volume in the brain. Increased high intracranial pressure can affect prognosis and can be evaluated by assessing clinical outcomes in patients with severe traumatic brain injury using the Glasgow Outcome Discharge Scale (GODS) instrument. Methods: Observational analytical study with a cross sectional design on 50 patients with severe traumatic brain injury at dr. Zainoel Abidin General Hospital Banda Aceh to determine the effect of mannitol use on the clinical outcomes of severe traumatic brain injury patients which used t test analysis. Results: The mean value of the group that received mannitol had a higher GODS score than the group that did not receive mannitol. The results of the T test between groups obtained a p value of 0.000 which is smaller than 0.05, so it can be concluded that the use of mannitol has an effect on the GODS score in Severe traumatic brain injury patients. The results showed that the mean GODS value in patients who received mannitol was higher than those who did not receive mannitol. Conclusion: This concludes that the administration of mannitol is effective in improving the clinical outcomes of patients with severe traumatic brain injury at dr. Zainoel Abidin General Hospital Banda Aceh.

Photoperiod and temperature interactions drive the latitudinal distribution of Laminaria hyperborea (Laminariales, Phaeophyceae) under climate change.

Due to global rises in temperature, recent studies predict marine species shifting toward higher latitudes. We investigated the impact of interacting abiotic drivers on the distribution potential of the temperate kelp Laminaria hyperborea. The ecosystem engineering species is widespread along European coasts but has not yet been observed in the High Arctic, although it can survive several months of low temperatures and darkness. To investigate its ability to extend northward in future, we conducted a long-term multifactorial experiment with sporophytes from Porsangerfjorden, Norway-close to the species' documented northernmost distribution margin. The samples were exposed to three different photoperiods (PolarDay, LongDay, and PolarNight) at 0°C, 5°C, and 10°C for 3 months. Optimum quantum yield of photosynthesis (Fv/Fm), dry weight, pigments, phlorotannins, and storage carbohydrates were monitored. Both physiological and biochemical parameters revealed that L. hyperborea was strongly influenced by the different photoperiods and their interaction with temperature, while temperature alone exerted only minor effects. The Fv/Fm data were integrated into a species distribution model to project a possible northward expansion of L. hyperborea. The combination of extended day lengths and low temperatures appeared to be the limiting reason for northward spread of L. hyperborea until recently. However, with water temperatures reaching 10°C in summer, this kelp will be able to thrive also in the High Arctic. Moreover, no evidence of stress to Arctic winter warming was observed. Consequently, L. hyperborea has a high potential for spreading northward with further warming which may significantly affect the structure and function of Arctic ecosystems.

Mannitol mediates the mummification behavior of Thitarodes xiaojinensis larvae infected with Ophiocordyceps sinensis.

Introduction: Parasites can facilitate their own spread and reproduction by manipulating insect hosts behavior, as seen in the interaction between Thitarodes xiaojinensis and Ophiocordyceps sinensis. Infection by O. sinensis leads to the mummification of T. xiaojinensis larvae, but the underlying mechanisms remain mysterious. Methods: The morphology of O. sinensis infected larvae and fungal growth were first observed. Subsequently, the metabolite changes in the larvae before and after infection with the fungus were analyzed by LC/MS and targeted metabolomics. The expression of mannitol-related genes was detected using RT-qPCR, and morphological changes in larvae were observed after injection of different concentrations of mannitol into the O. sinensis-infected larvae. Results: Significant changes were found in phenotype, fungal morphology in hemocoel, larval hardness, and mannitol metabolites in infected, mummified 0 h larvae and larvae 5 days after mummification behavior. Surprisingly, the occurrence of mummification behavior was accompanied by fungal dimorphism, as well as the absence of mannitol in both infected and non-infected larvae, until the initial accumulation of mannitol and the expression of mannitol-associated genes occurred at the time of mummification behavior. The presence of mannitol may promote fungal dimorphism to mediate changes in fungal toxicity or resistance, leading to the end of the fungus-insect coexistence period and the incidence of mummification behavior. Furthermore, mannitol injections increase the mummification rate of the infected larvae without significant difference from the normal mummification phenotype. Discussion: This finding suggests the importance of mannitol in the mummification of host larvae infected with O. sinensis.

Serial Assessment of Hemodynamic and Cerebrovascular Changes After Administration of Mannitol in Postoperative Neurosurgical Patients in the Intensive Care Unit: A Combined Transthoracic and Transcranial Color Doppler Study.

INTRODUCTION: Mannitol is widely used in neurosurgical units to mitigate raised intracranial pressure and cerebral edema, crucial in postoperative management. Its hyperosmolar properties reduce brain extracellular fluid, thereby altering cerebral perfusion and cardiac dynamics. However, the temporal and combined effects of mannitol on cardiovascular and cerebrovascular parameters remain inadequately explored in postoperative settings. METHODS: This prospective observational study enrolled 20 adult patients who underwent elective craniotomies for tumor excision. Mannitol was administered to the patients at a dose of 0.5 mg/kg/dose as a bolus dose over 20 to 30 minutes. The time interval was eight hours between the doses (scheduled dosing). Patients received their first dose of mannitol in the ICU after eight hours of intraoperative dose. The patients were given mannitol for two postoperative days and followed up for two days in the postoperative period. Transthoracic echocardiography and transcranial color Doppler were used to assess cardiovascular and cerebrovascular parameters at multiple intervals post-mannitol administration. RESULTS: Significant increases in mean flow velocities were observed bilaterally immediately post-mannitol administration on the first postoperative day, indicative of improved cerebral blood flow. However, these changes were transient, with no significant variations noted on the second postoperative day. Cerebrovascular resistance, as measured by the pulsatility index, showed non-significant changes bilaterally across both days. Cardiovascular parameters, including stroke volume and cardiac output, remained stable throughout the study period. CONCLUSION: Mannitol administration at 0.5 g/kg in postoperative neurosurgical patients transiently improves cerebral perfusion without causing significant hemodynamic instability. This study underscores the importance of monitoring both cerebrovascular and cardiovascular parameters post-mannitol administration to optimize patient management and outcomes.

[Recent advances in the bioproduction of mannitol].

D-mannitol is a six-carbon sugar alcohol and one of the most abundant polyols in the nature. With antioxidant and osmotic pressure-regulating effects and non-metabolism by the human body, D-mannitol has been widely used in functional food and pharmaceutical industries. At present, a major way for industrial production of D-mannitol is chemical hydrogenation. In addition, D-Mannitol can be produced by microbial metabolism or catalysis. Compared with the chemical hydrogenation, the microbial methods for synthesizing mannitol do not produce sorbitol as a by-product and have the advantages of mild reaction conditions, strong specificity, and high conversion rate. Microbial fermentation is praised for easy access of strains and raw materials and simple separation of the product. Microbial catalysis usually adopts a multi-enzyme coupling strategy, which uses enzymes produced by engineered bacteria for whole-cell catalysis, and the cofactor recycling pathway is introduced to replenish expensive cofactor. This method can achieve high yields with cheap substrates under mild conditions without the formation of by-products. However, the application of microbial methods in the industrial production of D-mannitol is limited by the high costs of fermentation media and substrates and the long reaction time. This article reviews the reported microbial methods for producing D-mannitol, including the use of high-yielding strains and their fermentation processes, the utilization of low-cost substrates, whole-cell catalytic strategies, and the process control for high productivity. The biosynthesis of mannitol is not only of great significance for promoting industrial upgrading and realizing green manufacturing, but also provides strong support for the development of new bio-based products to meet the growing market demand. With the continuous improvement of technological innovation and industrial chain, it is expected to become one of the main ways of mannitol production in the future.

Comparison of topical 5% NaCl versus 10% Mannitol for the treatment of corneal edema after phacoemulsification.

OBJECTIVE: This study aimed to compare the efficacy of topical 5% Sodium Chloride (NaCl) and 10% Mannitol agents in managing corneal edema following uncomplicated cataract surgery. METHODS: Patients with postoperative corneal edema were enrolled, and they were divided into three groups for comparison. Anterior chamber depth (ACD), axial length (AL), intraocular lens (IOL) power, cumulative dissipated energy (CDE), best-corrected visual acuity (BCVA), central corneal thickness (CCT), and endothelial cell count (ECC) were assessed among the groups. RESULTS: Fifty-eight eyes of 58 patients were included. The study comprised the NaCl group (using topical 5% NaCl, n = 21), Mannitol group (using topical 10% Mannitol, n = 17), and a control group without osmotic agent use (n = 20). Age, gender, ACD, AL, IOL power, and CDE were similar across groups. Postoperative day-1 CCT values showed no significant difference between groups. Additionally, at postoperative 1 week, CCT values were [663.4 ± 100.2] microns in the NaCl group, [640.4 ± 68.9] microns in the Mannitol group, and [760.3 ± 76.7] microns in the Control group. Although CCT and BCVA values were better in the Mannitol group at postoperative 1 week, no statistically significant difference was found between the groups at 1 week and 1 month postoperatively. Furthermore, corneal edema positively correlated with CDE and negatively correlated with AL. CONCLUSION: Topical 5% NaCl and 10% Mannitol agents are effective and reliable agents that showed faster recovery of corneal edema during the early postoperative period after uncomplicated cataract surgery. The choice between these agents may depend on factors such as patient tolerability, cost, and availability.

Development of Root Caries Associated With the Use of Sugar-Free Nicotine Lozenges: A Long-Term Case Report.

The authors present a case concerning an adult male patient who developed multiple sites of root caries adjacent to the area where he habitually held a sugar-free nicotine lozenge that contained mannitol and maltodextrin. The root caries occurred despite the patient's excellent oral hygiene, exemplary dietary habits, and clinically normal salivary flow. Between 1999 and 2008, he had only required two restorations to repair carious lesions. This patient had a 20+-year habit of using smokeless tobacco before switching to a cessation aid nicotine lozenge in May of 2008. A full-mouth series of radiographs taken in November 2009 revealed carious lesions on virtually every posterior tooth. The nicotine lozenge's principal ingredients were mannitol (75.7%) and maltodextrin. According to the United States' current Food and Drug Administration (FDA) guidelines, manufacturers can advertise these lozenges as sugar-free. Thus, it is assumed by the public that these types of products are incapable of "causing a cavity." However, this case report presents evidence suggesting that frequent use of sugar-free nicotine lozenges may be associated with dental caries.

Urinary excretion of gluten immunoreactive peptides as an indicator of gastrointestinal function after fasting and dietary provocation in healthy volunteers.

Introduction: Understanding intestinal permeability is paramount for elucidating gastrointestinal health and pathology. The size and nature of the molecule traversing the intestinal barrier offer crucial insights into various acute and chronic diseases, as well as the evolution of some conditions. This study aims to assess the urinary excretion kinetics of gluten immunogenic peptides (u-GIP), a unique class of dietary peptides detectable in urine, in volunteers under controlled dietary conditions. This evaluation should be compared to established probes like lactulose, a non-digestible disaccharide indicative of paracellular permeability, and mannitol, reflecting transcellular permeability. Methods: Fifteen participants underwent simultaneous ingestion of standardized doses of gluten (10 g), lactulose (10 g), and mannitol (1 g) under fasting conditions for at least 8 hours pre-ingestion and during 6 hours post-ingestion period. Urine samples were collected over specified time intervals. Excretion patterns were analyzed, and correlations between the lactulose-to-mannitol ratio (LMR) and u-GIP parameters were assessed. Results: The majority of u-GIP were detected within the first 12 hours post-ingestion. Analysis of the variability in cumulative excretion across two sample collection ranges demonstrated that lactulose and u-GIP exhibited similar onset and excretion dynamics, although GIP reached its maximum peak earlier than either lactulose or mannitol. Additionally, a moderate correlation was observed between the LMR and u-GIP parameters within the longest urine collection interval, indicating potential shared characteristics among permeability pathways. These findings suggest that extending urine collection beyond 6 hours may enhance data reliability. Discussion: This study sheds light on the temporal dynamics of u-GIP in comparison to lactulose and mannitol, established probes for assessing intestinal permeability. The resemblance between u-GIP and lactulose excretion patterns aligns with the anticipated paracellular permeability pathway. The capacity to detect antigenic food protein fragments in urine opens novel avenues for studying protein metabolism and monitoring pathologies related to the digestive and intestinal systems.

A Rapid and Reliable Spectrofluorimetric Method to Measure the Urinary Lactulose/Mannitol Ratio for Dysbiosis Assessment.

Gut microbiota plays a crucial role in human health homeostasis, and the result of its alteration, known as dysbiosis, leads to several pathologies (e.g., inflammatory bowel disease, metabolic syndrome, and Crohn's disease). Traditional methods used to assess dysbiosis include the dual sugar absorption test and the urinary lactulose/mannitol ratio (LMR) measurement using mass spectrometry. Despite its precision, this approach is costly and requires specialized equipment. Hence, we developed a rapid and reliable spectrofluorimetric method for measuring LMR in urine, offering a more accessible alternative. This spectrofluorimetric assay quantifies the fluorescence of nicotinamide adenine dinucleotide (NADH) and nicotinamide adenine dinucleotide phosphate (NADPH) produced during the enzymatic oxidation of mannitol and lactulose, respectively. The assay requires 100 µL of urine samples and detects LMR values lower (eubiosis) and higher (dysbiosis) than 0.05, ultimately being amenable to high-throughput screening and automatization, making it practical for clinical and research settings. A validation of the method demonstrated its high precision, accuracy, and robustness. Additionally, this study confirmed analyte stability under various storage conditions, ensuring reliable results even with delayed analysis. Overall, this spectrofluorimetric technique reduces costs, time, and the environmental impact associated with traditional mass spectrometry methods, making it a viable option for widespread use in the assessment of dysbiosis.

Preoperative intravenous mannitol administration and its rationale before cataract surgery.

BACKGROUND: The purpose of this study is to assess the variations in anterior chamber depth (ACD), axial length (AXL), and intraocular pressure (IOP) in both phakic and pseudophakic eyes undergoing preoperative intravenous mannitol infusion. The study was conducted at the Ophthalmology Department of IRCSS Humanitas in Milan, Italy. This is a prospective and non-randomized study. METHODS: 40 patients with phakic eyes and 40 patients with pseudophakic eyes scheduled for cataract surgery in their fellow eye were included. Prior to the surgery, comprehensive ophthalmic examinations were conducted, including IOP measurement, and bilateral biometry performed with Anterion® (Heidelberg Engineering GmbH, 69,115, Heidelberg, Germany). All patients received intravenous infusion of mannitol before the surgery. One hour after cataract extraction, the patients underwent the same set of examinations. We analyzed the changes AXL, ACD and IOP in the eye opposite to the one that underwent surgery. RESULTS: The comparison between preoperative and postoperative parameters showed no differences in AXL (p = 0.34 and p = 0.53) and in ACD (p = 0.38 and p = 0.31) in the phakic and in the pseudophakic group, respectively. Instead, a statistically significant difference was found between the mean preoperative and postoperative IOP (p = 0.02) for the phakic group and (p = 0.03) for the pseudophakic group. CONCLUSIONS: The administration of mannitol does not lead to any changes in the ACD and AXL, regardless of whether the eyes are phakic or pseudophakic. However, there is a statistically significant reduction in IOP. Nonetheless, it is important to consider the various side effects associated with mannitol infusion.

Efficacy of Intravenous 20% Mannitol vs 3% Hypertonic Saline in Reducing Intracranial Pressure in Nontraumatic Brain Injury: A Systematic Review and Meta-analysis.

Background: Nontraumatic brain injury encompasses various pathological processes and medical conditions that result in brain dysfunction and neurological impairment without direct physical trauma. The study aimed to assess the efficacy of intravenous administration of 20% mannitol and 3% hypertonic saline to reduce intracranial pressure in nontraumatic brain injury. Materials and methods: The Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines were followed for study selection and data extraction. The search was conducted in the PubMed, Embase, and Scopus databases, including articles published in English from January 2003 to December 2023. Our study included randomized controlled trials, comparative studies, prospective analyses, and retrospective cohort studies. We extracted data on baseline characteristics of patients, intervention details, major outcomes, and complications. Quality assessment was performed using the Jadad scale and the Robvis assessment tool for risk of bias. Results: A total of 14 studies involving 1,536 patients were included in the analysis. Seven studies reported hypertonic saline as more effective in reducing intracranial pressure, while three studies found similar effectiveness for both interventions. Adverse events were reported in only three studies. The studies that reported complication rates ranged from 21 to 79%. A meta-analysis was conducted on five studies, showing varying rates of adverse events associated with mannitol and hypertonic saline. Conclusion: Both hypertonic saline solution and mannitol have been explored as treatment options for decreasing intracranial pressure in nontraumatic brain injuries. While some studies indicate the superiority of hypertonic saline, others report similar effectiveness between the two interventions. How to cite this article: Choudhury A, Ravikant, Bairwa M, Jithesh G, Kumar S, Kumar N. Efficacy of Intravenous 20% Mannitol vs 3% Hypertonic Saline in Reducing Intracranial Pressure in Nontraumatic Brain Injury: A Systematic Review and Meta-analysis. Indian J Crit Care Med 2024;28(7):686-695.

Advancing the Management of Nontraumatic Brain Injuries with Hypertonic Saline and Mannitol.

How to cite this article: Shetty RM. Advancing the Management of Nontraumatic Brain Injuries with Hypertonic Saline and Mannitol. Indian J Crit Care Med 2024;28(7):634-636.

Physiological, transcriptomic and metabolomic insights of three extremophyte woody species living in the multi-stress environment of the Atacama Desert.

MAIN CONCLUSIONS: In contrast to Neltuma species, S. tamarugo exhibited higher stress tolerance, maintaining photosynthetic performance through enhanced gene expression and metabolites. Differentially accumulated metabolites include chlorophyll and carotenoids and accumulation of non-nitrogen osmoprotectants. Plant species have developed different adaptive strategies to live under extreme environmental conditions. Hypothetically, extremophyte species present a unique configuration of physiological functions that prioritize stress-tolerance mechanisms while carefully managing resource allocation for photosynthesis. This could be particularly challenging under a multi-stress environment, where the synthesis of multiple and sequential molecular mechanisms is induced. We explored this hypothesis in three phylogenetically related woody species co-occurring in the Atacama Desert, Strombocarpa tamarugo, Neltuma alba, and Neltuma chilensis, by analyzing their leaf dehydration and freezing tolerance and by characterizing their photosynthetic performance under natural growth conditions. Besides, the transcriptomic profiling, biochemical analyses of leaf pigments, and metabolite analysis by untargeted metabolomics were conducted to study gene expression and metabolomic landscape within this challenging multi-stress environment. S. tamarugo showed a higher photosynthetic capacity and leaf stress tolerance than the other species. In this species, a multifactorial response was observed, which involves high photochemical activity associated with a higher content of chlorophylls and ß-carotene. The oxidative damage of the photosynthetic apparatus is probably attenuated by the synthesis of complex antioxidant molecules in the three species, but S. tamarugo showed the highest antioxidant capacity. Comparative transcriptomic and metabolomic analyses among the species showed the differential expression of genes involved in the biosynthetic pathways of key stress-related metabolites. Moreover, the synthesis of non-nitrogen osmoprotectant molecules, such as ciceritol and mannitol in S. tamarugo, would allow the nitrogen allocation to support its high photosynthetic capacity without compromising leaf dehydration tolerance and freezing stress avoidance.

Synergistic Therapeutic Effects of D-Mannitol-Cerium-Quercetin (Rutin) Coordination Polymer Nanoparticles on Acute Lung Injury.

Acute lung injury (ALI) remains a significant global health issue, necessitating novel therapeutic interventions. In our latest study, we pioneered the use of D-mannitol-cerium-quercetin/rutin coordination polymer nanoparticles (MCQ/R NPs) as a potential treatment for ALI. The MCQ/R NPs, which integrate rutin and quercetin for their therapeutic potential and D-mannitol for its pulmonary targeting, displayed exceptional efficacy. By utilizing cerium ions for optimal nanoparticle assembly, the MCQ/R NPs demonstrated an average size of less than 160 nm. Impressively, these nanoparticles outperformed conventional treatments in both antioxidative capabilities and biocompatibility. Moreover, our in vivo studies on LPS-induced ALI mice showed a significant reduction in lung tissue inflammation. This groundbreaking research presents MCQ/R NPs as a promising new approach in ALI therapeutics.

Mannitol-coated hydroxypropyl methylcellulose as an alternative directly compressible controlled release excipient.

One of the most common forms of controlled release technology for oral drug delivery comprises an active ingredient dispersed in a hydrophilic matrix forming polymer such as hydroxypropyl methylcellulose (HPMC), which is tableted via direct compression. However, HPMC may pose problems in direct compression due to its poor flowability. Hence, mannitol syrup was spray-coated over fluidized HPMC particles to produce co-processed HPMC-mannitol at ratios of 20:80, 50:50, and 70:30. Particles of pure HPMC, co-processed HPMC-mannitol, and their respective physical mixtures were evaluated for powder flowability, compression profiles, and controlled release performance. It was found that co-processed HPMC-mannitol consisted of particles with improved flow compared to pure HPMC particles. Sufficiently strong tablets of >2 MPa could be produced at moderate to high compression forces of 150-200 MPa. The dissolution profile could be tuned to obtain desired release profiles by altering HPMC-mannitol ratios. Co-processed HPMC-mannitol offers an interesting addition to the formulator's toolbox in the design of controlled release formulations for direct compression.

Effectiveness of hypertonic saline infusion in management of traumatic brain injury: an updated systematic review and meta-analysis of randomized controlled trials.

OBJECTIVE: This study aimed to find out the efficacy of using Hypertonic saline solution (HSS) over mannitol in the management of TBI by comparing their performance in improving different outcomes. METHODS: Electronic databases were searched for randomized controlled trials (RCTs) assessing the impact of HSS vs. mannitol on ICP in patients who suffered TBI. Outcomes of interest were mortality, neurologic functional outcomes, risk ratio (RR) of successful ICP treatment, reduction in ICP after 30-60 and 90-120 min, improvement in cerebral perfusion pressure (CPP) at 30-60 and 90-120 min, and also treatment failure. Evaluations were reported as RR or mean difference (MD) with 95% confidence intervals (CIs) using weighted random-effects models. RESULTS: The analysis included 624 patients from 15 RCTs. HSS infusion had a significant impact on the improvement of CPP at 30-60 min [MD = 5.54, 95% CI (3.04, 8.03),p < 0.001] compared to mannitol. However, results yielded no significant difference between HSS and mannitol in terms of mortality, neurologic functional outcomes, successful ICP treatment, reduction in ICP after 30-60 min and 90-120 min, improvement in CPP at 90-120 min, and treatment failure. CONCLUSION: HSS and mannitol are both effective treatments for elevated ICP due to TBI. However, further research is required to derive a better comparison.

Comparing the effects of mannitol and hypertonic saline in severe traumatic brain injury patients with elevated intracranial pressure: a systematic review and meta-analysis.

OBJECTIVES: Controlling elevated intracranial pressure following brain injury with hyperosmolar agents is one of the mainstay treatments in traumatic brain injury patients. In this study, we compared the effects of hypertonic saline (HS) and mannitol in reducing increased intracranial pressure. METHODS: A total of 637 patients from 15 studies were included in our meta-analysis. The primary outcomes were mortality, the length of stay in the hospital and ICU, and the Glasgow Outcome Scale at follow-up. RESULTS: The mortality in the mannitol group was not statistically different compared to the HS group (RR = 1.55; 95% CI = [0.98, 2.47], p = 0.06). The length of stay in the ICU was significantly shorter in the HS group (MD = 1.18, 95% CI = [0.44, 1.92], p < 0.01). In terms of favorable neurological outcomes, there was no significant difference between the two agents (RR = 0.92, 95% CI = [0.11, 7.96], p = 0.94). The duration of the effect was shorter in the mannitol group than in the HS group (MD = -0.67, 95% CI = [-1.00, -0.33], p < 0.01). DISCUSSION: The results showed that HS and mannitol had similar effects in reducing ICP. Although the HS was associated with a longer duration of effect and shorter ICU stay, other secondary outcomes including mortality rate and favorable neurological outcomes were similar between the two drugs. In conclusion, considering the condition of each patient individually, HS could be a reasonable option than mannitol to reduce ICP in TBI patients.