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Advanced Drug Delivery Reviews Aug 2018The story of how we came to use inhaled mannitol to diagnose asthma and to treat cystic fibrosis began when we were looking for a surrogate for exercise as a stimulus to... (Review)
Review
The story of how we came to use inhaled mannitol to diagnose asthma and to treat cystic fibrosis began when we were looking for a surrogate for exercise as a stimulus to identify asthma. We had proposed that exercise-induced asthma was caused by an increase in osmolarity of the periciliary fluid. We found hypertonic saline to be a surrogate for exercise but an ultrasonic nebuliser was required. We produced a dry powder of sodium chloride but it proved unstable. We developed a spray dried preparation of mannitol and found that bronchial responsiveness to inhaling mannitol identified people with currently active asthma. We reasoned that mannitol had potential to replace the 'osmotic' benefits of exercise and could be used as a treatment to enhance mucociliary clearance in patients with cystic fibrosis. These discoveries were the start of a journey to develop several registered products that are in clinical use globally today.
Topics: Administration, Inhalation; Asthma; Cystic Fibrosis; Drug Repositioning; Humans; Mannitol
PubMed: 29626547
DOI: 10.1016/j.addr.2018.04.003 -
Cell Transplantation 2014Ischemic brain injury in adults and neonates is a significant clinical problem with limited therapeutic interventions. Currently, clinicians have only tPA available for... (Review)
Review
Ischemic brain injury in adults and neonates is a significant clinical problem with limited therapeutic interventions. Currently, clinicians have only tPA available for stroke treatment and hypothermia for cerebral palsy. Owing to the lack of treatment options, there is a need for novel treatments such as stem cell therapy. Various stem cells including cells from embryo, fetus, perinatal, and adult tissues have proved effective in preclinical and small clinical trials. However, a limiting factor in the success of these treatments is the delivery of the cells and their by-products (neurotrophic factors) into the injured brain. We have demonstrated that mannitol, a drug with the potential to transiently open the blood-brain barrier and facilitate the entry of stem cells and trophic factors, as a solution to the delivery problem. The combination of stem cell therapy and mannitol may improve therapeutic outcomes in adult stroke and neonatal cerebral palsy.
Topics: Animals; Blood-Brain Barrier; Cord Blood Stem Cell Transplantation; Humans; Ischemia; Mannitol; Nerve Growth Factors; Stem Cell Transplantation; Stem Cells; Stroke
PubMed: 24480552
DOI: 10.3727/096368914X678337 -
The Veterinary Record Apr 2023
Topics: Dogs; Animals; Mannitol; Paralysis; Dog Diseases
PubMed: 37000729
DOI: 10.1002/vetr.2910 -
Expert Opinion on Pharmacotherapy Jan 2012Airway hyperresponsiveness (AHR) is a key feature of asthma and can be assessed by the use of bronchial provocation tests. A test using inhaled dry powder mannitol for... (Review)
Review
INTRODUCTION
Airway hyperresponsiveness (AHR) is a key feature of asthma and can be assessed by the use of bronchial provocation tests. A test using inhaled dry powder mannitol for diagnosing asthma is now regulatory approved in 20 countries.
AREAS COVERED
This paper reviews the literature on inhaled mannitol from the first publication in 1997 until present (October 2011). It discusses the current knowledge on the clinical usefulness as a tool for diagnosing and managing asthma.
EXPERT OPINION
Inhaled mannitol can be regarded as a safe, standardized, specific, but less sensitive, tool for the diagnosis of asthma in both children and adults. Discomfort, in terms of cough, during the test occurs in 85.3% of subjects, but rarely (1.3%) leads to discontinuation. Headache (6.1%), pharyngolaryngeal pain (2.6%) and cough (1.3%) are the most frequent adverse events that occur on the day of the test. The test holds several advantages compared with existing tests; there is no need for additional equipment (i.e., a nebulizer) besides a spirometer; it requires no cleaning and has only one standard operating protocol. In a new study using mannitol for monitoring mild and moderate persistent asthma in primary care, the number of mild exacerbations was reduced.
Topics: Administration, Inhalation; Asthma; Bronchial Provocation Tests; Humans; Mannitol
PubMed: 22118547
DOI: 10.1517/14656566.2012.638917 -
European Journal of Clinical... Dec 2022Successful bowel preparation (BP) for colonoscopy depends on the instructions, diet, the laxative product, and patient adherence, which all affect colonoscopy quality....
BACKGROUND
Successful bowel preparation (BP) for colonoscopy depends on the instructions, diet, the laxative product, and patient adherence, which all affect colonoscopy quality. Nevertheless, there are no laxatives which combine effectiveness, safety, easy self-administration, good patient acceptance, and low cost. However, mannitol, a sugar alcohol, could be an attractive candidate for use in clinical practice if it is shown to demonstrate adequate efficacy and safety.
AIMS
The present phase II dose-finding study compared three doses of mannitol (50, 100, and 150 g) to identify the best dose to be used in a subsequent phase III study.
METHODS
The Boston Bowel Preparation Scale, caecal intubation rate, adherence, acceptability, and safety profile, including measurement of potentially dangerous colonic gas concentrations (CH, H, O), were considered in all patients. A weighted algorithm was used to identify the best mannitol dose for use in the subsequent study.
RESULTS
The per-protocol population included 60 patients in the 50 g group, 54 in the 100 g group, and 49 in the 150 g group. The 100 g dose was the best as it afforded optimal colon cleansing efficacy (94.4% of patients had adequate BP), adherence, acceptability, and safety, including negligible gas concentrations.
CONCLUSIONS
The present study demonstrated that the colon cleansing efficacy and safety of mannitol were dose dependent. Conversely, gas concentrations were not dose dependent and negligible in all patients. Combined evaluation of efficacy, tolerability, and safety, using a weighted algorithm, determined that mannitol 100 g was the best dose for the phase III study.
Topics: Humans; Cathartics; Colonoscopy; Laxatives; Mannitol; Administration, Oral
PubMed: 36287232
DOI: 10.1007/s00228-022-03405-z -
New Horizons (Baltimore, Md.) Aug 1995Mannitol has replaced other diuretics as the agent of first choice for control of raised intracranial pressure (ICP) after brain injury. Mannitol should be given as a... (Review)
Review
Mannitol has replaced other diuretics as the agent of first choice for control of raised intracranial pressure (ICP) after brain injury. Mannitol should be given as a bolus intravenous infusion, over 10 to 30 mins, in doses ranging from 0.25 to 1.0 g/kg body weight. It may be given when high ICP is suspected, prior to computed tomography scanning, e.g., in patients who develop a fixed, dilated pupil or neurologic deterioration. This agent may also be used pre- or intraoperatively in patients with intracranial hematomas, and when high ICP is demonstrated in the ICU. It is more effective and safer when administered in bolus doses than as a continuous infusion. Mannitol may be safely used during the early resuscitation phase in hypovolemic patients with concomitant head injury, provided that plasma expanders and/or crystalloid solutions are given to correct the hypovolemia simultaneously. A Foley catheter should always be inserted when mannitol is used. Serum osmolality should be measured frequently after mannitol and maintained < 320 mOsm to avoid renal failure. Its beneficial effects and the rationale for its use are also reviewed.
Topics: Brain Injuries; Cerebrovascular Circulation; Diuretics, Osmotic; Hemodynamics; Humans; Intracranial Pressure; Mannitol; Resuscitation
PubMed: 7496753
DOI: No ID Found -
Nature Protocols Jan 2022The blood-brain barrier (BBB) is the main obstacle to the effective delivery of therapeutic agents to the brain, compromising treatment efficacy for a variety of... (Review)
Review
The blood-brain barrier (BBB) is the main obstacle to the effective delivery of therapeutic agents to the brain, compromising treatment efficacy for a variety of neurological disorders. Intra-arterial (IA) injection of hyperosmotic mannitol has been used to permeabilize the BBB and improve parenchymal entry of therapeutic agents following IA delivery in preclinical and clinical studies. However, the reproducibility of IA BBB manipulation is low and therapeutic outcomes are variable. We demonstrated that this variability could be highly reduced or eliminated when the procedure of osmotic BBB opening is performed under the guidance of interventional MRI. Studies have reported the utility and applicability of this technique in several species. Here we describe a protocol to open the BBB by IA injection of hyperosmotic mannitol under the guidance of MRI in mice. The procedures (from preoperative preparation to postoperative care) can be completed within ~1.5 h, and the skill level required is on par with the induction of middle cerebral artery occlusion in small animals. This MRI-guided BBB opening technique in mice can be utilized to study the biology of the BBB and improve the delivery of various therapeutic agents to the brain.
Topics: Animals; Blood-Brain Barrier; Capillary Permeability; Injections, Intra-Arterial; Magnetic Resonance Imaging; Male; Mannitol; Mice; Mice, SCID; Osmotic Pressure
PubMed: 34903870
DOI: 10.1038/s41596-021-00634-x -
Critical Care (London, England) Feb 2012Hyperosmolar therapy is the principal medical management strategy for elevated intracranial pressure. Mannitol has been the primary hyperosmolar agent for nearly a... (Review)
Review
Hyperosmolar therapy is the principal medical management strategy for elevated intracranial pressure. Mannitol has been the primary hyperosmolar agent for nearly a century and remains the de facto gold standard for medical management of intracranial hypertension. Over the past 25 years, however, hypertonic saline (HTS) has become a progressively more common alternative to mannitol, and several recent studies have suggested its relative superiority. These findings have prompted calls for large-scale comparator trials of mannitol and HTS, but such trials would only be necessary if the designation of mannitol as the gold standard is appropriate and if current evidence suggests its therapeutic equipoise with HTS. Mounting evidence supporting HTS suggests that neither of these conditions is necessarily true and, instead, mandates reassessment of the actual gold-standard agent for hyperosmolar therapy. In the present article I make the case that current evidence supports HTS, not mannitol, as the better choice for gold-standard therapy for medical management of intracranial hypertension. This is accomplished first by examining the evidence on which the apparent designation of mannitol as the presumed gold-standard is based, then by reviewing the recent comparative efficacy data for HTS versus mannitol, and finally by discussing additional clinical considerations for appropriate designation of a gold-standard agent for hyperosmolar therapy. This assessment has important implications both for patient care and for clinical trial design.
Topics: Animals; Disease Management; Humans; Intracranial Hypertension; Mannitol; Reference Standards; Saline Solution, Hypertonic; Treatment Outcome
PubMed: 22353146
DOI: 10.1186/cc11182 -
Urologia Internationalis 2013Paraphimosis is a urologic emergency. Many treatment options have been devised for managing this entity. The osmotic method is one of them. We used an osmotic diuretic,...
INTRODUCTION
Paraphimosis is a urologic emergency. Many treatment options have been devised for managing this entity. The osmotic method is one of them. We used an osmotic diuretic, mannitol, for reducing paraphimosis. Mannitol is commonly used for conditions like head injury to decrease cerebral oedema, partial nephrectomy and hepatorenal syndrome; we attempted using this diuretic for reducing paraphimosis. This is a novel technique and an application of mannitol which has never been reported before.
METHODS
Starting in February 2011, we used mannitol 20% in patients presenting to urologic emergency with uncomplicated paraphimosis. Mannitol-soaked gauzes were wrapped around the oedematous prepuce, followed by minimal intermittent hand compression and frequent resoaking of the gauze with 20% mannitol. No needle punctures were made. The soaked gauze was removed and the paraphimosis was reduced easily.
RESULTS
A complete reduction of paraphimosis occurred after mannitol-soaked gauze had been placed over the oedematous prepuce for about 30-45 min in 6 of our patients. This is a novel agent used for this entity; it reduces paraphimosis in a minimal time with no pain, with the added advantage of the least risk of infection after the procedure as opposed to granulated sugar or 50% dextrose previously used as osmotic agents.
CONCLUSIONS
Mannitol can be applied in clinical practice for reducing paraphimosis. It requires no anaesthesia and is associated with minimal/no patient discomfort unlike that seen with multiple needle punctures and the various other non-osmotic methods of reducing paraphimosis.
Topics: Administration, Cutaneous; Diuretics, Osmotic; Humans; Male; Mannitol; Paraphimosis; Time Factors; Treatment Outcome
PubMed: 23257575
DOI: 10.1159/000343737 -
Neurosurgical Review Oct 2018There is a controversy about the effects of hypertonic saline (HS) used for brain relaxation in patients requiring craniotomies. We conducted a meta-analysis to compare... (Comparative Study)
Comparative Study Meta-Analysis Review
There is a controversy about the effects of hypertonic saline (HS) used for brain relaxation in patients requiring craniotomies. We conducted a meta-analysis to compare the efficacy of equiosmolar hypertonic saline with mannitol on intraoperative brain relaxation in patients undergoing craniotomies. We searched PubMed, EMBASE, Cochrane Library databases, and Web of Science for randomized controlled trials (RCTs). The outcome indicators included brain relaxation, hemodynamic status, fluid volume, and blood chemistry. A total of nine RCTs involving 665 patients were identified and included. There was a greater increase in the odds of good intraoperative brain relaxation in the HS group (odds ratio (OR) 2.05, 95% confidence interval (CI) 1.40~3.01; P = 0.0002) compared with mannitol. In comparison with HS, mannitol slightly reduced the central venous pressure (CVP) (mean difference (MD) 1.03, 95% CI 0.03~2.03; P = 0.04) as well as significantly increasing the diuretic effect regardless of the dosage of HS (standardized mean difference (SMD) -0.86, 95% CI -1.35~-0.37; P = 0.0006). HS increased the plasma sodium level significantly (MD 7.86, 95% CI 2.78 ~ 12.95, P = 0.002) but reduced the intraoperative fluid intake (SMD -0.56, 95% CI -0.98~-0.15, P = 0.008). However, there were no significant differences in plasma osmolality and mean arterial pressure (MAP). Our results suggest that there appears to be better brain relaxation without a significant increase in urine volume in the HS group compared with mannitol in patients requiring craniotomies. High-quality RCTs with larger sample sizes will be required in the future to confirm the conclusions.
Topics: Craniotomy; Diuretics; Humans; Mannitol; Neurosurgical Procedures; Randomized Controlled Trials as Topic; Saline Solution, Hypertonic; Solutions
PubMed: 28258418
DOI: 10.1007/s10143-017-0838-8