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Medicine Aug 2020To compare the effects of 3% hypertonic saline solution and 20% mannitol solution on intracranial hypertension. (Comparative Study)
Comparative Study Meta-Analysis
BACKGROUND
To compare the effects of 3% hypertonic saline solution and 20% mannitol solution on intracranial hypertension.
METHODS
WAN-FANGDATA, CNKI, and CQVIP databases were searched, and relevant literatures of randomized controlled trials comparing 3% hypertonic saline solution with mannitol in reducing intracranial hypertension from 2010 to October 2019 were collected. Meta-analysis was performed using RevMan software.
RESULTS
As a result, 10 articles that met the inclusion criteria were finally included. A total of 544 patients were enrolled in the study, 270 in the hypertonic saline group and 274 in the mannitol group. There was no significant difference in the decrease of intracranial pressure and the onset time of drug between the 2 groups after intervention (all P > .05). There was a statistically significant difference between the hypertonic saline group and the mannitol group in terms of duration of effect in reducing intracranial pressure (95% confidence interval: 0.64-1.05, Z = 8.09, P < .00001) and cerebral perfusion pressure after intervention (95% confidence interval: 0.15-0.92, Z = 2.72, P = .007).
CONCLUSION
Both 3% hypertonic saline and mannitol can effectively reduce intracranial pressure, but 3% hypertonic saline has a more sustained effect on intracranial pressure and can effectively increase cerebral perfusion pressure.
Topics: Brain Injuries, Traumatic; Diuretics, Osmotic; Humans; Intracranial Hypertension; Intracranial Pressure; Mannitol; Saline Solution, Hypertonic
PubMed: 32871879
DOI: 10.1097/MD.0000000000021655 -
Journal of Intensive Care Medicine Jul 2023Acutely elevated intracranial pressure (ICP) may have devastating effects on patient mortality and neurologic outcomes, yet its initial detection remains difficult... (Review)
Review
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.
Topics: Humans; Mannitol; Intracranial Hypertension; Brain Injuries, Traumatic; Brain Injuries; Saline Solution, Hypertonic; Intracranial Pressure
PubMed: 36802976
DOI: 10.1177/08850666231156589 -
Journal of Neurotrauma Jul 2023Increased intracranial pressure (ICP) is one of the most important modifiable and immediate threats to critically ill patients suffering from traumatic brain injury...
Increased intracranial pressure (ICP) is one of the most important modifiable and immediate threats to critically ill patients suffering from traumatic brain injury (TBI). Two hyperosmolar agents (HOAs), mannitol and hypertonic saline (HTS), are routinely used in clinical practice to treat increased ICP. We aimed to assess whether a preference for mannitol, HTS, or their combined use translated into differences in outcome. The Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) Study is a prospective multi-center cohort study. For this study, patients with TBI, admitted to the intensive care unit (ICU), treated with mannitol and/or HTS, and aged ≥16 years were included. Patients and centers were differentiated based on treatment preference with mannitol and/or HTS based on structured, data-driven criteria such as first administered HOA in the ICU. We assessed influence of center and patient characteristics in the choice of agent using adjusted multi-variate models. Further, we assessed the influence of HOA preference on outcome using adjusted ordinal and logistic regression models, and instrumental variable analyses. In total, 2056 patients were assessed. Of these, 502 (24%) patients received mannitol and/or HTS in the ICU. The first received HOA was HTS for 287 (57%) patients, mannitol for 149 (30%) patients, or both mannitol and HTS on the same day for 66 (13%) patients. Two unreactive pupils were more common in patients receiving both (13, 21%), compared with patients receiving HTS (40, 14%) or mannitol (22, 16%). Center, rather than patient characteristics, was independently associated with the preferred choice of HOA (-value <0.05). ICU mortality and 6-month outcome were similar between patients preferably treated with mannitol compared with HTS (odds ratio [OR] = 1.0, confidence interval [CI] = 0.4-2.2; OR = 0.9, CI = 0.5-1.6, respectively). Patients who received both also had a similar ICU mortality and 6-month outcome compared with patients receiving HTS (OR = 1.8, CI = 0.7-5.0; OR = 0.6, CI = 0.3-1.7, respectively). We found between-center variability regarding HOA preference. Moreover, we found that center is a more important driver of the choice of HOA than patient characteristics. However, our study indicates that this variability is an acceptable practice given absence of differences in outcomes associated with a specific HOA.
Topics: Humans; Mannitol; Cohort Studies; Prospective Studies; Brain Injuries, Traumatic; Saline Solution, Hypertonic; Intracranial Hypertension; Intracranial Pressure
PubMed: 37014076
DOI: 10.1089/neu.2022.0465 -
Medicine Sep 2020Mannitol and hypertonic saline (HTS) are effective in reducing intracranial pressure (ICP) after severe traumatic brain injury (TBI). However, their efficacy on the ICP... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Mannitol and hypertonic saline (HTS) are effective in reducing intracranial pressure (ICP) after severe traumatic brain injury (TBI). However, their efficacy on the ICP has not been evaluated rigorously.
OBJECTIVE
To evaluate the efficacy of repeated bolus dosing of HTS and mannitol in similar osmotic burdens to treat intracranial hypertension (ICH) in patients with severe TBI.
METHODS
The authors used an alternating treatment protocol to evaluate the efficacy of HTS with that of mannitol given for ICH episodes in patients treated for severe TBI at their hospital during 2017 to 2019. Doses of similar osmotic burdens (20% mannitol, 2 ml/kg, or 10% HTS, 0.63 ml/kg, administered as a bolus via a central venous catheter, infused over 15 minutes) were given alternately to the individual patient with severe TBI during ICH episodes. The choice of osmotic agents for the treatment of the initial ICH episode was determined on a randomized basis; osmotic agents were alternated for every subsequent ICH episode in each individual patient. intracranial pressure (ICP), mean arterial pressure (MAP), and cerebral perfusion pressure (CPP) were continuously monitored between the beginning of each osmotherapy and the return of ICP to 20 mm Hg. The duration of the effect of ICP reduction (between the beginning of osmotherapy and the return of ICP to 20 mm Hg), the maximum reduction of ICP and its time was recorded after each dose. Serum sodium and plasma osmolality were measured before, 0.5 hours and 3 hours after each dose. Adverse effects such as central pontine myelinolysis (CPM), severe fluctuations of serum sodium and plasma osmolality were assessed to evaluate the safety of repeated dosing of HTS and mannitol.
RESULTS
Eighty three patients with severe TBI were assessed, including 437 ICH episodes, receiving 236 doses of HTS and 221 doses of mannitol totally. There was no significant difference between equimolar HTS and mannitol boluses on the magnitude of ICP reduction, the duration of effect, and the time to lowest ICP achieved (P > .05). The proportion of efficacious boluses was higher for HTS than for mannitol (P = .016), as was the increase in serum sodium (P = .038). The serum osmolality increased immediately after osmotherapy with a significant difference (P = .017). No cases of CPM were detected.
CONCLUSION
Repeat bolus dosing of 10% HTS and 20% mannitol appears to be significantly and similarly effective for treating ICH in patients with severe TBI. The proportion of efficacious doses of HTS on ICP reduction may be higher than mannitol.
Topics: Adult; Brain Injuries, Traumatic; Cerebrovascular Circulation; Diuretics, Osmotic; Female; Humans; Intracranial Hypertension; Intracranial Pressure; Male; Mannitol; Middle Aged; Saline Solution, Hypertonic; Trauma Severity Indices
PubMed: 32957318
DOI: 10.1097/MD.0000000000022004 -
European Journal of Medical Research Nov 2022Traumatic 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... (Meta-Analysis)
Meta-Analysis
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.
Topics: Humans; Young Adult; Intracranial Pressure; Brain Injuries; Saline Solution, Hypertonic; Intracranial Hypertension; Brain Injuries, Traumatic; Mannitol
PubMed: 36404350
DOI: 10.1186/s40001-022-00897-4 -
The Western Journal of Medicine Oct 1979Mannitol may be useful clinically both as a diuretic and as an obligate extracellular solute. As a diuretic it can be used to treat patients with intractable edema... (Review)
Review
Mannitol may be useful clinically both as a diuretic and as an obligate extracellular solute. As a diuretic it can be used to treat patients with intractable edema states, to increase urine flow and flush out debris from the renal tubules in patients with acute tubular necrosis, and to increase toxin excretion in patients with barbiturate, salicylate or bromide intoxication. As an obligate extracellular solute it may be useful to ameliorate symptoms of the dialysis disequilibrium syndrome, to decrease cerebral edema following trauma or cerebrovascular accident, and to prevent cell swelling related to renal ischemia following cross-clamping of the aorta. Largely unexplored uses for mannitol include its use as an osmotic agent in place of dextrose in peritoneal dialysis solutions, its use to maintain urine output in patients newly begun on hemodialysis, and its use to limit infarct size following acute myocardial infarction.
Topics: Acute Kidney Injury; Antidotes; Cardiovascular System; Cerebrovascular Circulation; Cerebrovascular Disorders; Coronary Disease; Diuretics, Osmotic; Humans; Intraocular Pressure; Kidney; Kidney Transplantation; Mannitol; Oliguria; Renal Dialysis; Water-Electrolyte Imbalance
PubMed: 388867
DOI: No ID Found -
Journal of Otolaryngology - Head & Neck... Dec 2017Characterization of the blood labyrinth barrier (BLB) is extremely important to determine whether the BLB can be manipulated pharmacologically. However, experiments to... (Comparative Study)
Comparative Study
BACKGROUND
Characterization of the blood labyrinth barrier (BLB) is extremely important to determine whether the BLB can be manipulated pharmacologically. However, experiments to investigate the BLB are technically difficult to perform. In this report, we demonstrated a unique method of controlling the BLB, and established the pharmacokinetics of gentamicin in perilymph, cerebrospinal fluid (CSF) and blood with and without mannitol.
STUDY DESIGN
Controlled animal research project.
METHODS
Permeability of the BLB and the blood brain barrier (BBB) to gentamicin with and without mannitol was studied by collecting 175 samples from 44 guinea pigs using concentrations relevant to human clinical situations. Samples were taken from two groups of 22 animals, with each animal undergoing sampling at a different time after administration of either 10 mg/ml gentamicin (4 mg/kg) (Gardena, CA) alone or gentamicin with 20% mannitol (250 mg/kg) (Mallinckrodt Inc., KY). The sample times varied from 0.5 to 17.5 h post-infusion. Samples were also taken from 4 animals as negative controls after administration of normal saline. Our goal was to simultaneously assess the pharmacokinetics of gentamicin in each of three different fluid samples in the same animal. Thus at the pre-determined post-infusion sampling time, each animal was sampled once for perilymph, CSF, and blood before being euthanized. Each animal contributed to a single time point on the subsequent pharmacokinetic curves with more than one animal per time point.
RESULTS
Mannitol increased the rate of entry and egress of gentamicin through BLB significantly (p = 0.0044) but the effects on the BBB did not reach statistical significance (p = 0.581). Mannitol did not alter renal clearance of gentamicin from the blood (p = 0.433). The concentration of gentamicin in perilymph and CSF was always significantly lower than in blood.
CONCLUSIONS
Mannitol administration transiently increases the permeability of the BLB. Potential clinical benefits may accrue from selected timing of administration of osmotic agents such as mannitol augmenting the rate of entry and egress of compounds such as gentamicin into and out of perilymph.
Topics: Animals; Blood-Brain Barrier; Cerebrospinal Fluid; Drug Therapy, Combination; Ear, Inner; Enzyme-Linked Immunosorbent Assay; Gentamicins; Guinea Pigs; Mannitol; Models, Animal; Perilymph; Reference Values
PubMed: 29228990
DOI: 10.1186/s40463-017-0245-8 -
The Cochrane Database of Systematic... Jul 2007Mannitol is an osmotic agent and a free radical scavenger which might decrease oedema and tissue damage in stroke. (Review)
Review
BACKGROUND
Mannitol is an osmotic agent and a free radical scavenger which might decrease oedema and tissue damage in stroke.
OBJECTIVES
To test whether treatment with mannitol reduces short and long-term case fatality and dependency after acute ischaemic stroke or intracerebral haemorrhage (ICH).
SEARCH STRATEGY
We searched the Cochrane Stroke Group Trials Register (searched December 2006), MEDLINE (1966 to January 2007), the Chinese Stroke Trials Register (searched November 2006), the China Biological Medicine Database (searched December 2006) and the Latin-American database LILACS (1982 to December 2006). We also searched the database of Masters and PhD degree theses at Sao Paulo University (searched January 2007), and neurology and neurosurgery conference proceedings in Brazil from 1965 to 2006. In an effort to identify further published, ongoing and unpublished studies we searched reference lists and contacted authors of published trials.
SELECTION CRITERIA
We included randomised controlled trials comparing mannitol with placebo or open control in patients with acute ischaemic stroke or non-traumatic intracerebral haemorrhage.
DATA COLLECTION AND ANALYSIS
Two review authors independently selected trials, assessed quality, extracted data, and performed the data analysis.
MAIN RESULTS
Three small trials, involving 226 participants, were included. One trial included patients with presumed ischaemic stroke without computerised tomography (CT) verification, and the other two trials included patients with CT-verified ICH. Data on the primary outcome measure (death and dependency) were not available in any of the trials. Death and disability could be calculated in the larger ICH trial without differences between the mannitol and control groups. Case fatality was not reported in the trial of ischaemic stroke. Case fatality did not differ between the mannitol and control groups in the ICH trials. Adverse events were either not found or not reported. The change in clinical condition was reported in two trials, and the proportion of those with worsening or not improving condition did not differ significantly between mannitol-treated patients and controls. Based on these three trials neither beneficial nor harmful effects of mannitol could be proved. Although no statistically significant differences were found between the mannitol-treated and control groups, the confidence intervals for the treatment effect estimates were wide and included both clinically significant benefits and clinically significant harms as possibilities.
AUTHORS' CONCLUSIONS
There is currently not enough evidence to support the routine use of mannitol in acute stroke patients. Further trials are needed to confirm or refute whether mannitol is beneficial in acute stroke.
Topics: Acute Disease; Brain Edema; Brain Ischemia; Cerebral Hemorrhage; Diuretics, Osmotic; Humans; Mannitol; Randomized Controlled Trials as Topic
PubMed: 17636655
DOI: 10.1002/14651858.CD001153.pub2 -
Current Opinion in Critical Care Apr 2013To discuss trends in the use of osmotic therapy. (Review)
Review
PURPOSE OF REVIEW
To discuss trends in the use of osmotic therapy.
RECENT FINDINGS
Use of osmotic therapy has evolved from bolus administration of mannitol to routine use of hypertonic saline as a bolus as well as in continuous infusions to creating a sustained hyperosmolar state.In a survey of neurointensivists 55% favored hypertonic saline over mannitol. Retrospective studies suggest better intracranial pressure (ICP) control with hypertonic saline. Whereas a prospective study in adults with head injury compared alternating doses of mannitol and hypertonic saline and found no difference in change in ICP control or outcome, two meta-analyses, which did not include this study, favored hypertonic saline for ICP control (although the absolute difference of 2 mmHg is of little clinical value) with no difference in outcome.Hypertonic saline has also been administered by infusions to creating a sustained stable hyperosmolar state. Two studies, using historical controls, suggested benefit of hypertonic saline infusions. In a prospective, randomized study, in children with severe head injury Lactated Ringer's solution was compared to hypertonic saline. Although ICP control was similar, the hypertonic saline group required fewer other interventions.
SUMMARY
The existing data do not support favoring boluses of hypertonic saline over mannitol in terms of ICP control, let alone outcome. The rationale for continuous infusions to create a sustained hyperosmolar state is open to discussion and use of this approach should be curtailed pending further research.
Topics: Brain Ischemia; Cerebral Hemorrhage; Craniocerebral Trauma; Critical Care; Diuretics, Osmotic; Female; Humans; Intracranial Hypertension; Male; Mannitol; Osmolar Concentration; Practice Guidelines as Topic; Saline Solution, Hypertonic; Treatment Outcome
PubMed: 23385373
DOI: 10.1097/MCC.0b013e32835eba30 -
Circulation Research Sep 2023Cardiac conduction is understood to occur through gap junctions. Recent evidence supports ephaptic coupling as another mechanism of electrical communication in the...
BACKGROUND
Cardiac conduction is understood to occur through gap junctions. Recent evidence supports ephaptic coupling as another mechanism of electrical communication in the heart. Conduction via gap junctions predicts a direct relationship between conduction velocity (CV) and bulk extracellular resistance. By contrast, ephaptic theory is premised on the existence of a biphasic relationship between CV and the volume of specialized extracellular clefts within intercalated discs such as the perinexus. Our objective was to determine the relationship between ventricular CV and structural changes to micro- and nanoscale extracellular spaces.
METHODS
Conduction and Cx43 (connexin43) protein expression were quantified from optically mapped guinea pig whole-heart preparations perfused with the osmotic agents albumin, mannitol, dextran 70 kDa, or dextran 2 MDa. Peak sodium current was quantified in isolated guinea pig ventricular myocytes. Extracellular resistance was quantified by impedance spectroscopy. Intercellular communication was assessed in a heterologous expression system with fluorescence recovery after photobleaching. Perinexal width was quantified from transmission electron micrographs.
RESULTS
CV primarily in the transverse direction of propagation was significantly reduced by mannitol and increased by albumin and both dextrans. The combination of albumin and dextran 70 kDa decreased CV relative to albumin alone. Extracellular resistance was reduced by mannitol, unchanged by albumin, and increased by both dextrans. Cx43 expression and conductance and peak sodium currents were not significantly altered by the osmotic agents. In response to osmotic agents, perinexal width, in order of narrowest to widest, was albumin with dextran 70 kDa; albumin or dextran 2 MDa; dextran 70 kDa or no osmotic agent, and mannitol. When compared in the same order, CV was biphasically related to perinexal width.
CONCLUSIONS
Cardiac conduction does not correlate with extracellular resistance but is biphasically related to perinexal separation, providing evidence that the relationship between CV and extracellular volume is determined by ephaptic mechanisms under conditions of normal gap junctional coupling.
Topics: Animals; Guinea Pigs; Dextrans; Connexin 43; Myocytes, Cardiac; Sodium; Gap Junctions; Albumins; Mannitol; Action Potentials
PubMed: 37681314
DOI: 10.1161/CIRCRESAHA.123.322567