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American Journal of Respiratory and... Jun 1999Bronchiectasis is a disease characterized by hypersecretion and retention of mucus requiring physical and pharmacologic treatment. Recently we reported that inhalation... (Clinical Trial)
Clinical Trial
Bronchiectasis is a disease characterized by hypersecretion and retention of mucus requiring physical and pharmacologic treatment. Recently we reported that inhalation of dry powder mannitol markedly increases mucociliary clearance (MCC) in asthmatic and in healthy subjects (Daviskas, E., S. D. Anderson, J. D. Brannan, H. K. Chan, S. Eberl, and G. Bautovich. 1997. Inhalation of dry-powder mannitol increases mucociliary clearance. Eur. Respir. J. 10:2449-2454). In this study we investigated the effect of mannitol on MCC in patients with bronchiectasis. Eleven patients 40 to 62 yr of age inhaled mannitol (approximately 300 mg) from a Dinkihaler. MCC was measured over 90 min, in the supine position, on three occasions involving: mannitol or control or baseline, using a radioaerosol technique. On the control day patients reproduced the breathing maneuvers and the number of coughs induced by the mannitol. Mannitol significantly increased MCC over the 75 min from the start of the intervention compared with control and baseline in the whole right lung, central, and intermediate region. Mean (+/- SEM) clearance with mannitol was 34.0 +/- 5.0% versus 17.4 +/- 3.8% with control and 11.7 +/- 4.4% with baseline in the whole right lung (p < 0.0001). The mean number of coughs induced by mannitol was 49 +/- 11. In conclusion, inhalation of dry powder mannitol increased clearance of mucus and thus has the potential to benefit patients with bronchiectasis.
Topics: Administration, Inhalation; Adult; Aerosols; Bronchiectasis; Cough; Dose-Response Relationship, Drug; Female; Humans; Incidence; Male; Mannitol; Middle Aged; Mucociliary Clearance; Powders
PubMed: 10351929
DOI: 10.1164/ajrccm.159.6.9809074 -
Journal of Neurosurgery Oct 1984In a previous paper, the authors showed that mannitol causes cerebral vasoconstriction in response to blood viscosity decreases in cats. The present paper describes the...
In a previous paper, the authors showed that mannitol causes cerebral vasoconstriction in response to blood viscosity decreases in cats. The present paper describes the changes in intracranial pressure (ICP) and cerebral blood flow (CBF) after mannitol administration in a group of severely head-injured patients with intact or defective autoregulation. The xenon-133 inhalation method was used to measure CBF. Autoregulation was tested by slowly increasing or decreasing the blood pressure by 30% and measuring CBF again. Mannitol was administered intravenously in a dose of 0.66 gm/kg; 25 minutes later, CBF and ICP were measured once again. In the group with intact autoregulation, mannitol had decreased ICP by 27.2%, but CBF remained unchanged. In the group with defective autoregulation, ICP had decreased by only 4.7%, but CBF increased 17.9%. One of the possible explanations for these findings is based on strong indications that autoregulation is mediated through alterations in the level of adenosine in response to oxygen availability changes in cerebral tissue. The decrease in blood viscosity after mannitol administration leads to an improved oxygen transport to the brain. When autoregulation is intact, more oxygen leads to decreased adenosine levels, resulting in vasoconstriction. The decrease in resistance to flow from the decreased blood viscosity is balanced by increased resistance from vasoconstriction, so that CBF remains the same. This might be called blood viscosity autoregulation of CBF, analogous to pressure autoregulation. Vasoconstriction also reduces cerebral blood volume, which enhances the effect of mannitol on ICP through dehydration of the brain. When autoregulation is not intact there is no vasoconstriction in response to increased oxygen availability; thus, CBF increases with decreased viscosity. With the lack of vasoconstriction, the effect on ICP through dehydration is not enhanced, so that the resulting decrease in ICP is much smaller. Such a mechanism explains why osmotic agents do not change CBF but decrease ICP in normal animals or patients with intact vasoconstriction, but do (temporarily) increase CBF in the absence of major ICP changes after stroke.
Topics: Brain Injuries; Cerebrovascular Circulation; Homeostasis; Humans; Intracranial Pressure; Mannitol; Phenylephrine
PubMed: 6432972
DOI: 10.3171/jns.1984.61.4.0700 -
Neurological Research Mar 2010Medical management of brain edema and elevated intracranial pressure (ICP) is a crucial challenge in neurosurgical practice. Depending on the cause, the treatments for... (Comparative Study)
Comparative Study
BACKGROUND
Medical management of brain edema and elevated intracranial pressure (ICP) is a crucial challenge in neurosurgical practice. Depending on the cause, the treatments for brain edema fall into three categories: stabilization of the blood-brain barrier, depletion of brain water and surgical decompression. Although mannitol is the mainstay of hyperosmolar therapy, hypertonic saline (HS) is emerging as an effective alternative to traditional osmotic agents.
METHODS
Experimental elevated ICP (50 mmHg) was induced in rabbits using an intracranial balloon. The effects of mannitol and HS (10% NaCl) were compared in this specific physiopathological model. Twelve animals were divided into three groups (control, HS and mannitol) according to intravenous administration of 0.9% NaCl, 10% NaCl or 20% mannitol 5 minutes after the elevation of ICP. The doses of 10% NaCl and 20% mannitol were iso-osmolar. During 90 minutes, continuous recording of ICP, mean arterial pressure (MAP) and cerebral perfusion pressure (CPP) was realized.
RESULTS
The control group had a median survival of only 53 minutes, significantly lower than the treated groups (p=0.0002). There was statistical difference between mannitol and HS; the 10% NaCl group had lower values of ICP (p=0.0116) and higher values of MAP (p<0.0001) and CPP (p<0.0001).
CONCLUSION
The findings demonstrate higher efficacy of the 10% NaCl treatment in this comparison with 20% mannitol. Further efforts should be directed toward development of clinical studies using iso-osmotic doses of mannitol and HS in specific etiologies of intracranial hypertension.
Topics: Animals; Disease Models, Animal; Intracranial Hypertension; Intracranial Pressure; Male; Mannitol; Rabbits; Saline Solution, Hypertonic; Treatment Outcome
PubMed: 19309542
DOI: 10.1179/174313209X405119 -
Journal of Neurosurgery Oct 1992The authors investigated the pharmacokinetics of mannitol administered for treatment of vasogenic cerebral edema. A cortical cold injury was produced in 23 cats...
The authors investigated the pharmacokinetics of mannitol administered for treatment of vasogenic cerebral edema. A cortical cold injury was produced in 23 cats maintained under general anesthesia for 5 or 21 hours. Control animals received no mannitol, while treatment groups received either a single dose or five doses administered at 4-hour intervals of 0.33 gm/kg radiolabeled mannitol. Liquid scintillation counting was carried out to determine the concentrations of mannitol in the cerebral tissue, cerebrospinal fluid, plasma, and urine. Cerebral water content and linear progression of edema were also measured. Rapid plasma clearance prevented accumulation of mannitol after multiple intravenous injections, as 84% +/- 2% (mean +/- standard error of the mean) of the infused mannitol was excreted through the urine. However, there was progressive accumulation of mannitol within the cerebral tissue, especially in the edematous white matter where it reached a level of 0.33 +/- 0.03 mg/gm after five doses, exceeding the trough plasma concentrations by a ratio of 2.69:1. Water content measurement showed that a single dose of mannitol failed to reduce cerebral water content or edema progression at 4 hours postinjection, while multiple doses produced a 3% increase in water content in edematous regions (p greater than 0.0003). The results of this study demonstrated a reversal of the osmotic concentration gradient between edematous brain and plasma following multiple mannitol injections, associated with exacerbation of vasogenic cerebral edema.
Topics: Animals; Body Water; Brain Chemistry; Brain Edema; Cats; Drug Administration Schedule; Mannitol; Monitoring, Physiologic
PubMed: 1527619
DOI: 10.3171/jns.1992.77.4.0584 -
European Journal of Clinical... 1988An i.v. infusion of mannitol was given over 15 min to 12 patients before they underwent intracranial surgery under general anesthesia. Samples of blood, CSF and urine...
An i.v. infusion of mannitol was given over 15 min to 12 patients before they underwent intracranial surgery under general anesthesia. Samples of blood, CSF and urine were taken over 4 h. Mannitol disappeared from plasma in a bi-exponential manner. The mean maximal plasma concentration was 4.08 mg/ml at 15 min, and at 4 h it had declined to 0.53 mg/ml. The mean distribution rate constant was 11.2 h-1, corresponding to a plasma distribution half-life of 0.11 h. The mean elimination rate constant was 0.41 h-1, the plasma half-life was 2.2 h, the central distribution volume was 16.3 l, and total plasma clearance was 100.4 ml/min. The mean concentration of mannitol in CSF during the 4 h period increased up to 0.10 mg/ml. There were marked interindividual differences in the concentration ratio blood/CSF, and the CSF concentration varied 7.5 fold between patients. Optimal use of mannitol during neurosurgery requires further prolonged study of its pharmacokinetics.
Topics: Adult; Aged; Brain; Female; Gas Chromatography-Mass Spectrometry; Humans; Infusions, Intravenous; Male; Mannitol; Middle Aged
PubMed: 3148472
DOI: 10.1007/BF00637601 -
No Shinkei Geka. Neurological Surgery Jul 1991To study the most effective way of mannitol administration for the treatment of raised intracranial pressure (ICP), pharmacokinetics of mannitol were analysed, and the...
To study the most effective way of mannitol administration for the treatment of raised intracranial pressure (ICP), pharmacokinetics of mannitol were analysed, and the relationship among mannitol concentration, serum osmolality and changes of intracranial pressure (ICP) were examined in cats. 10%, 20% and 30% of mannitol were made and intravenously administrated with the same volume and speed (0.667 ml/kg/min) for 15 minutes to each mannitol concentration group of cats. Sequential changes of ICP were monitored and serial mannitol concentration, serum osmolality and electrolytes were then performed. Changes of mannitol concentration showed a biexponential curve and best fitted to the two-compartment model analysis. There was a strong positive correlation (r = 0.9286) between mannitol concentration and extrinsic serum osmolality. The disposition of mannitol in cats was similar to that which had been reported in dogs and humans. The distribution half-time was faster in 30% mannitol, but the elimination half-time was similar in all groups. The integrated values of mannitol concentration difference between the central (Cc) and the peripheral compartment (Pc) were greatly correlated with the changes of ICP reduction during mannitol administration (for 15min). The time to vanish the mannitol concentration difference between Cc and Pc showed strong reverse correlation with the time to reach the lowest ICP level. The result indicates that the more rapidly mannitol was administrated, the more rapidly the concentration difference between the two compartments was created, and, the higher the effective osmolality was developed, then, the more profound and prolonged ICP reduction can be obtained.(ABSTRACT TRUNCATED AT 250 WORDS)
Topics: Animals; Cats; Intracranial Pressure; Mannitol; Osmolar Concentration; Pseudotumor Cerebri
PubMed: 1909772
DOI: No ID Found -
Journal of Pharmaceutical Sciences Jun 1998Due to its strong tendency to crystallize, the glass properties of mannitol cannot be measured directly. However, because mannitol can exist in a fully or partially...
Due to its strong tendency to crystallize, the glass properties of mannitol cannot be measured directly. However, because mannitol can exist in a fully or partially amorphous state in drug formulations, it is important to determine the glass properties of mannitol. We obtained the glass properties of mannitol by introducing a small amount of sorbitol, an isomer of mannitol, to delay the onset of crystallization. Extrapolation to zero sorbitol concentration yielded the following properties for the mannitol glass: Tg onset = 10.7(o)C, Tg midpoint= 12.6( o)C, Tg end = 18.4 degreesC and DeltaCp = 1.27 J/g/K. In addition, we estimated the following parameters of the mannitol glass from the width of glass transition using the results of Moynihan (J. Am. Ceram. Soc. 1993, 76, 1081) and Angell (J. Phys. Chem. 1994, 98, 13780): DeltaH (at Tg onset) = 103 kcal/mol, D = 11, and T0 = 222 K. The value of T0 is consistent with the Kauzmann temperature TK (236 K) obtained calorimetrically. The properties of the mannitol glass may be useful for predicting the behavior of amorphous mixtures containing mannitol.
Topics: Calorimetry, Differential Scanning; Mannitol; Sorbitol
PubMed: 9607958
DOI: 10.1021/js970224o -
Zhonghua Yi Xue Za Zhi Jun 2019
Topics: Mannitol
PubMed: 31207683
DOI: 10.3760/cma.j.issn.0376-2491.2019.23.001 -
The European Respiratory Journal Apr 2008Bronchiectasis is characterised by hypersecretion and impaired clearance of mucus. A 400-mg dose of inhaled mannitol improves mucus clearance however, the effect of... (Clinical Trial)
Clinical Trial
Bronchiectasis is characterised by hypersecretion and impaired clearance of mucus. A 400-mg dose of inhaled mannitol improves mucus clearance however, the effect of other doses is unknown. A total of 14 patients, aged 63.3+/-5.7 yrs, were studied on five visits. Mucus clearance at baseline and with mannitol (160, 320 and 480 mg) was measured using technetium-99m-sulphur colloid and imaging with a gamma camera over 45 min, followed by a further 30 min involving 100 voluntary coughs. A control study assessed the effect of cough provoked by mannitol during the intervention. Whole right lung clearance over 45 min was 4.7+/-1.2 and 10.6+/-2.6% on baseline and control days, respectively, and increased to 16.7+/-4.2, 22.8+/-4.2 and 31+/-4.7% with 160, 320 and 480 mg mannitol, respectively. Clearance over 45 min with 480 mg mannitol was greater than clearance with 320 and 160 mg. Total clearance over 75 min, after mannitol administration and voluntary coughs, was 36.1+/-5.5, 40.9+/-5.6 and 46.0+/-5.2% with 160, 320 and 480 mg mannitol, respectively, all significantly different from baseline (24.1+/-6.0%) and control (13.1+/-3.0%). Total clearance over 75 min with 480 mg mannitol was greater compared with 160 mg. In conclusion, mucus clearance increases with increasing doses of mannitol and can be further increased by cough in patients with bronchiectasis.
Topics: Administration, Inhalation; Aged; Bronchiectasis; Cough; Diuretics, Osmotic; Dose-Response Relationship, Drug; Female; Humans; Male; Mannitol; Middle Aged; Mucus
PubMed: 18057051
DOI: 10.1183/09031936.00119707 -
Medical Hypotheses Dec 2010Inhalation of hydrogen gas has been proved to be an effective treatment for ischemia-reperfusion injury. There has been considerable evidence of hydrogen's protective...
Inhalation of hydrogen gas has been proved to be an effective treatment for ischemia-reperfusion injury. There has been considerable evidence of hydrogen's protective effect to diseases related to oxidative injury, such as the ischemia-reperfusion injury of the brain, liver and heart. Our previous studies demonstrated that intraperitoneal injection of hydrogen-rich saline protected hypoxic-ischemic brain injury, myocardial and intestine ischemia-reperfusion injury in rats. Bacteria in the large intestinal can produce endogenous hydrogen, and our preliminary experiments revealed that oral administration of mannitol in humans and animals can significantly increase the level of endogenous hydrogen. Therefore, we speculated that oral administration of mannitol may be effective against ischemia-reperfusion injury, which is a convenient, effective and unique treatment for ischemia-reperfusion injury.
Topics: Administration, Oral; Bacteria; Humans; Hydrogen; Intestines; Mannitol; Reperfusion Injury
PubMed: 20801581
DOI: 10.1016/j.mehy.2010.07.048