Dose Of Mannitol Research Articles

Brain-Relaxing Effect of Different Diuretic Regimens in Supratentorial Tumor Surgery: A Comparative Study Guided by Optic Nerve Sheath Diameter.

Background:Hyperosmolar therapy is a well-established method to approach brain relaxation during craniotomy. Mannitol is used with a wide range of dosing regimens, combination with loop diuretics exerts a synergistic effect resulting in both reduction of the dose and its complications. Ultrasound measurement of optic nerve sheath diameter (ONSD) gives reliable information about intracranial pressure (ICP) and avoids overdosing and complications of osmotherapy.Aims and Objectives:In this study, we compare the ordinary dose of mannitol with the low dose combined with furosemide and detect the effect on ICP by ONSD.Setting and Design:This is a prospective, randomized, double-blind study involving 60 patients undergoing supratentorial brain tumor surgery.Materials and Methods:Sixty patients were enrolled in this study, divided into two equal groups: Group M received mannitol 1 g.kg−1: while Group F received mannitol 0.25 g.kg−1 and furosemide 0.5 mg.kg−1. Reduction in ONSD measurement was the primary objective, while brain-relaxation score (BRS), hemodynamic changes, urine output, serum lactate, and changes in serum electrolyte were the secondary objectives.Statistical Analysis:Data collected were analyzed using SPSS software, IBM, USA, version 22. P value was considered significant if <0.05.Results:ONSD and BRS showed no statistically significant difference between the studied groups. After diuresis, Group M showed significant reduction in heart rate and mean arterial blood pressure, serum sodium, potassium, and lactate (P = 0.02, P = 0.02, P = 0.001, P = 0.001, P = 0.001, P = 0.001 respectively), with increased urine output (UOP) and fluids replacement (P = 0.00, P = 0.01, respectively).Conclusion:Compared to high dose, adding loop diuretics to low-dose mannitol during supratentorial brain tumor surgeries resulted in comparable BRSs with a lower incidence of hemodynamic and metabolic disturbances.

Assessment of fitness for recreational scuba diving in candidates with asthma: a pilot study

BackgroundAsthma may be regarded as a contraindication to scuba diving.PurposeA clinical algorithm to assess fitness to dive among individuals with asthma was developed and tested prospectively in clinical practice.Study designCohort...

The effect of deep inhalation on mannitol responsiveness.

Mannitol inhalation testing is specific for asthmatics with eosinophilic airway inflammation, a factor that has been negatively correlated with the development of deep inhalation bronchoprotection. To evaluate the effect of deep inhalations on responsiveness to inhaled mannitol in correlation with the degree of airway inflammation. Twenty participants with stable asthma completed this randomized, crossover study. A screening visit assessed responsiveness to methacholine and airway inflammation through fractional exhaled nitric oxide (FeNO) measures and sputum induction. Participants next completed two mannitol challenges, one with deep inhalations (standard method) and one with inhalations to half of total lung capacity, and two methacholine challenges, one with tidal breathing (standard method) and one with deep inhalations. Only the inhalation technique for dose administration differed between repeat mannitol or methacholine challenges. Deep inhalations did not significantly influence the provocative dose of mannitol causing a 15% fall in forced expiratory volume in 1second ((P=.73; n=7) or the mannitol dose-response slope (P=.26; n=20). Deep inhalations produced significant bronchoprotection against methacholine (P=.03; n=20). FeNO levels were significantly correlated to sputum eosinophilia (P=.02; n=15), responsiveness to deep inhalation methacholine (P=.005; n=20), the dose-response slopes from deep inhalation mannitol (P=.01; n=20), and the dose-response slope from non-deep inhalation mannitol (P=.005; n=20). Deep inhalations did not produce significant bronchoprotection against inhaled mannitol. This result is in agreement with past findings linking airway inflammation with loss of deep inhalation bronchoprotection. This study was prospectively registered on clinicaltrials.gov (NCT03505489).

Analysis of influencing factors of trough serum vancomycin concentrations in critically ill neurosurgical patients

To evaluate trough serum vancomycin concentrations and identify their influencing factors in critically ill neurosurgical patients. A retrospective study was conducted. Adult patients who received vancomycin with at least one appropriate monitoring of trough serum vancomycin concentration and admitted to neurosurgical intensive care unit (ICU) of the First Affiliated Hospital of Sun Yat-sen University from November 2017 to July 2019 were enrolled. General information including gender, age, comorbidities, etc., trough serum vancomycin concentrations, vancomycin dosage, duration of vancomycin therapy, urine output, serum creatinine (SCr), concurrent medications (including mannitol,diuretic, vasopressors, non-steroidal anti-inflammatory drugs, polymyxin, aminoglycosides and contrast medium, etc.) were collected for analysis. Trough serum vancomycin concentrations were evaluated and their influencing factors were analyzed by multiple linear regression method. In total, 81 trough serum vancomycin concentration data sets obtained from 28 patients were evaluated. (1) The initial daily dose of vancomycin was 2.00 (2.00, 2.00) g/d. After 4-6 doses, the trough serum vancomycin concentration obtained from initial blood draw was 10.99 (6.98, 16.25) mg/L, of which only 17.9% (5/28) achieving targeted concentrations (15-20 mg/L), 71.4% (20/28) subtherapeutic level and 10.7% (3/28) supratherapeutic level. (2) The duration of vancomycin therapy was 8.0 (6.0, 15.0) days. With average daily dose of 2.00 (1.75, 3.00) g/d, targeted trough vancomycin concentrations were achieved in only 30.9% (25/81) of all cases, subtherapeutic concentrations in 49.4% (40/81) and supratherapeutic concentrations in 19.7% (16/81). (3) There were significant differences in age, comorbidities, vancomycin dosage, diuretics use and mannitol dosage, etc. among different vancomycin concentration groups. Multiple linear regression analysis suggested that the trough serum vancomycin concentration increased by 0.14 mg/L [95% confidence interval (95%CI) was 0.06-0.22] for every 1 year increase in age, increased by 7.22 mg/L (95%CI was 2.08-12.36) in patients with multiple comorbidities (concomitant hypertension, diabetes and coronary heart disease) compared with those without comorbidities, increased by 2.78 mg/L (95%CI was 0.20-5.35) in patients treated with diuretics compared with those without diuretics. The effect of other variables was not statistically significant. It suggested that age, multiple comorbidities (concomitant hypertension, diabetes and coronary heart disease), and diuretic usage affected trough serum vancomycin concentrations. Targeted trough serum vancomycin level is not often achieved in neurosurgical ICU patients following standard dosing. Younger patients are associated with lower trough serum vancomycin concentrations, while diuretic usage, combined with multiple comorbidities are associated with higher trough serum vancomycin concentrations.

Assessment of intracranial pressure monitoring in patients with moderate traumatic brain injury: A retrospective cohort study

Objectivesintracranial pressure (ICP) monitoring has now been a standard technique for the treatment of severe traumatic brain injury (sTBI), while the effect of ICP monitoring for moderate traumatic brain injury (mTBI) is not clear. Moreover, evidence comparing the two types of ICP monitoring: ventricular drainage (VD) catheter and intraparenchymal (IP) catheter is scarce. Patients and methods91 patients with mTBI were reviewed retrospectively. They were divided into VD, IP and Non-ICP group. Baseline parameters were recorded. The clinical outcome was reflected by Glasgow Outcome Scale (GOS) and mortality at discharge and six months after injury. The rate of surgical decompression, refractory intracranial hypertension, neuroworsening, dose of mannitol and cranial CT were recorded. Meningitis and intracranial hematoma, two major complications of ICP monitoring, were also collected. Resultsthe three groups showed no significant difference in GOS at discharge and six months after injury. The mortality was similar among the three groups at six months after injury, while the Non-ICP group had the highest mortality at discharge. The Non-ICP group was administered the most mannitol while the VD group was administered the least. The Non-ICP group also received the most cranial CT scans among the three groups. Incidence of meningitis and intracranial hematoma were not significantly different among the VD and IP group. Conclusionuse of ICP monitoring could hardly improve the functional outcome of mTBI, but may possibly reduce the in-hospital mortality. By using ICP monitoring, the dose of mannitol and cranial CT scan for mTBI patients may be decreased.

The Optimal Dose of Mannitol for Intraoperative Brain Relaxation During the Operation of Aneurysmal Subarachnoid Hemorrhage

The Optimal Dose of Mannitol for Intraoperative Brain Relaxation During the Operation of Aneurysmal Subarachnoid Hemorrhage

Modeling hyperosmotic blood–brain barrier opening within human tissue-engineered in vitro brain microvessels

As the majority of therapeutic agents do not cross the blood–brain barrier (BBB), transient BBB opening (BBBO) is one strategy to enable delivery into the brain for effective treatment of CNS disease. Intra-arterial infusion of the hyperosmotic agent mannitol reversibly opens the BBB; however, widespread clinical use has been limited due to the variability in outcomes. The current model for mannitol-induced BBBO assumes a transient but homogeneous increase in permeability; however, the details are poorly understood. To elucidate the mechanism of hyperosmotic opening at the cellular level, we developed a tissue-engineered microvessel model using stem cell-derived human brain microvascular endothelial cells (BMECs) perturbed with clinically relevant mannitol doses. This model recapitulates physiological shear stress, barrier function, microvessel geometry, and cell-matrix interactions. Using live-cell imaging, we show that mannitol results in dose-dependent and spatially heterogeneous increases in paracellular permeability through the formation of transient focal leaks. Additionally, we find that the degree of BBB opening and subsequent recovery is modulated by treatment with basic fibroblast growth factor. These results show that tissue-engineered BBB models can provide insight into the mechanisms of BBBO and hence improve the reproducibility of hyperosmotic therapies for treatment of CNS disease.

Evidence for Mannitol as an Effective Agent Against Intracranial Hypertension: An Individual Patient Data Meta-analysis.

Mannitol is currently used to reduce intracranial pressure (ICP), but the evidence supporting its usefulness has been questioned. We aim to meta-analyze the effectiveness of mannitol in reducing ICP in adult patients with cerebral injuries and its dependency on baseline ICP values, comparing findings from individual patient data (IPD) and aggregated data (AD) meta-analysis performed on the same studies. We searched the Medline database, with no time limitation, through March 1, 2019. We selected studies for which IPD were available, with a before-after design, concerning adult patients with traumatic cerebral hemorrhages, subarachnoid hemorrhages, or hemorrhagic and ischemic stroke, treated with mannitol for increased intracranial hypertension. We extracted ICP values at baseline and at different time-points, and mannitol doses. We used a multilevel approach to account for multiple measurements on the same patient and for center variability. The AD meta-analysis and meta-regression were conducted using random-effects models. Three studies published IPD, and four authors shared their datasets. Two authors did not own their datasets anymore. Eight authors were unreachable, while 14 did not answer to our request. Overall, 7 studies provided IPD for 98 patients. The linear mixed-effects model showed that ICP decreased significantly after mannitol administration from an average baseline value of 22.1mmHg to 16.8, 12.8, and 9.7mmHg at 60, 120, and 180min after mannitol administration. ICP reduction was proportional to baseline values with a 0.64mmHg decrease for each unitary increment of the initial ICP value. Dose did not influence ICP reduction. The AD meta-analysis, based on data collected between 30 and 60min from mannitol administration not accounting for multiple time-point measurements, overestimated ICP reduction (10mmHg), while meta-regression provided similar results (0.66mmHg decrease for each unitary increase of initial ICP). Mannitol is effective in reducing pathological ICP, proportionally to the degree of intracranial hypertension. IPD meta-analysis provided a more precise quantification of ICP variation than the AD approach.

Usefulness of mannitol challenge testing for diagnosing asthma in everyday clinical practice

Background: The mannitol test is widely used for assessment of airway responsiveness in patients with possible asthma, but our knowledge of the value in everyday clinical practice is limited.Objective: To investigate the diagnostic value of the mannitol test in a clinical setting.Methods: All patients having a mannitol challenge test as part of their diagnostic work-up for asthma at the respiratory outpatient clinic, Hvidovre Hospital, over a 5-year period were included in the present analysis. Case history, including previous diagnoses, spirometry, exhaled nitric oxide (FENO) was obtained. The mannitol challenge was performed according to guidelines, i.e. increasing doses of mannitol (from 5 to 635 mg) until maximum dose or a 15% decline in FEV1 (PD15) was achieved (positive test defined as a PD15 < 635 mg).Results: Our cohort comprised 566 patients (210 men). Post-challenge, 247 patients were diagnosed with asthma by a specialist in respiratory medicine, of whom 138 (56%) had a positive mannitol test. A diagnosis of asthma was ruled out by the specialist in 319 individuals, of whom 18 (6%) had a positive mannitol test and 77 (24%) previous doctor-diagnosed asthma (but with no evidence of a confirmatory test). The specificity and sensitivity of the test was 94% and 56%, respectively. Female gender (p = 0.005), increasing BMI (p < 0.001), exercise-induced cough (p = 0.002), night-time respiratory symptoms (p = 0.002), low FEV1/FVC ratio (p = 0.008) and high FENO (p < 0.001) were determinants for a positive mannitol test.Conclusion: In everyday clinical work-up of patients with possible asthma, the sensitivity and specificity of the mannitol challenge test is comparable to previous controlled trials.

Postmortem evaluation of renal tubular vacuolization in critically ill dogs

To describe the frequency of renal tubular vacuolization (RTV) as a surrogate of osmotic nephrosis and assess hyperosmolar agents as predictors of RTV severity. Retrospective study (February 2004-October 2014). Veterinary teaching hospital. Fifty-three client-owned, critically ill dogs that had a postmortem examination. None. The frequency, severity, and location of RTV were determined in small group of critically ill dogs postmortem. Logistic regression was performed to assess cumulative 6% HES (670/0.75) and mannitol dose as predictors for RTV severity with presenting serum creatinine concentration, cumulative furosemide dose, and duration of hospitalization as covariates. RTV was noted in 45 (85%) of 53 critically ill dogs and was most commonly located to the medullary rays (68%). Cumulative 6% HES (670/0.75) dose (P = 0.009) and presenting serum creatinine concentration (P = 0.027) were significant predictors of RTV severity. For every 1 mL/kg increase in 6% HES (670/0.75) dose that a dog received, there was 1.6% increased chance of having more severe RTV (OR 1.016; 95% CI 1.004-1.029). In addition, for every 88.4 μmol/L (1 mg/dL) increase in presenting serum creatinine, there was a 22.7% increased chance of having more severe RTV (OR 1.227; 95% CI 1.023-1.472). Cumulative mannitol (P = 0.548) and furosemide (P = 0.136) doses were not significant predictors of RTV severity. In a small group of critically ill dogs, there was a high frequency of RTV identified on postmortem examination. Administration of 6% HES (670/0.75) and presenting serum creatinine concentration were significant predictors of RTV severity. Larger prospective studies are needed to determine the etiology and significance of RTV in dogs.

Mannitol Improves Intraoperative Brain Relaxation in Patients With a Midline Shift Undergoing Supratentorial Tumor Surgery: A Randomized Controlled Trial.

Mannitol is widely used to reduce brain tissue swelling and improve brain relaxation during neurosurgery. However, the optimal dosage for patients with midline shift undergoing supratentorial tumor resection remains unclear. In this randomized, controlled double-blinded study, 204 patients with preoperative midline shift who underwent elective supratentorial brain tumor surgery were equally allocated to receive placebo or 0.7, 1.0, or 1.4 g/kg mannitol infusion. The primary outcome was the proportion of satisfactory brain relaxation. Demographics and baseline characteristics were similar among the 4 groups. Trend analysis showed that mannitol infusion increased satisfactory brain relaxation (P<0.0001), relaxed dural tension (P<0.0001) and adequate surgical exposure (P<0.0001), and decreased the requirement for rescue therapy for brain swelling (P<0.0005), all in a dose-dependent manner. Tumor size (odds ratio [OR]: 0.99 per 1 mm, 95% confidence interval [CI]: 0.989-0.998, P=0.004), peritumoral edema classification (OR: 0.60, 95% CI: 0.37-0.97; P=0.038) as well as mannitol dose (OR: 2.81, 95% CI: 1.97-4.02, P<0.0001) were significantly associated with satisfactory brain relaxation. An increased risk of moderate to severe postoperative cerebral edema was found in the group receiving 1.4 g/kg mannitol (P=0.025) in a dose-dependent manner (P=0.018). An optimal mannitol infusion dosage of 1.0 g/kg is recommended to improve brain relaxation with lower risk of moderate to severe postoperative cerebral edema in patients with midline shift undergoing supratentorial tumor resections. The effect of mannitol on brain relaxation is affected by tumor size and severity of peritumoral edema, rather than by midline shift.

Mannitol decreases neocortical epileptiform activity during early brain development via cotransport of chloride and water

Seizures and brain injury lead to water and Cl− accumulation in neurons. The increase in intraneuronal Cl− concentration ([Cl−]i) depolarizes the GABAA reversal potential (EGABA) and worsens seizure activity. Neocortical neuronal membranes have a low water permeability due to the lack of aquaporins necessary to move free water. Instead, neurons use cotransport of ions including Cl− to move water. Thus, increasing the extracellular osmolarity during seizures should result in an outward movement of water and salt, reducing [Cl−]i and improving GABAA receptor-mediated inhibition. We tested the effects of hyperosmotic therapy with a clinically relevant dose of mannitol (20 mM) on epileptiform activity, spontaneous multiunit activity, spontaneous inhibitory post-synaptic currents (sIPSCs), [Cl−]i, and neuronal volume in layer IV/V of the developing neocortex of C57BL/6 and Clomeleon mice. Using electrophysiological techniques and multiphoton imaging in acute brain slices (post-natal day 7–12) and organotypic neocortical slice cultures (post-natal day 14), we observed that mannitol: 1) decreased epileptiform activity, 2) decreased neuronal volume and [Cl−]i through CCCs, 3) decreased spontaneous multi-unit activity frequency but not amplitude, and 4) restored the anticonvulsant efficacy of the GABAA receptor modulator diazepam. Increasing extracellular osmolarity by 20 mOsm with hypertonic saline did not decrease epileptiform activity. We conclude that an increase in extracellular osmolarity by mannitol mediates the efflux of [Cl−]i and water through CCCs, which results in a decrease in epileptiform activity and enhances benzodiazepine actions in the developing neocortex in vitro. Novel treatments aimed to decrease neuronal volume may concomitantly decrease [Cl−]i and improve seizure control.

A Comparative Study of Bolus Dose of Hypertonic Saline, Mannitol, and Mannitol Plus Glycerol Combination in Patients with Severe Traumatic Brain Injury

This prospective randomized controlled study compared the efficacy of an equiosmolar and isovolumetric dose of 3% hypertonic saline, 20% mannitol, and 10% mannitol plus 10% glycerol combination in reducing the raised intracranial pressure (ICP) in patients with severe traumatic brain injury (TBI). A total of 120 patients of severe TBI with increased ICP were randomized to receive an equiosmolar and isovolumetric dose of 3% hypertonic saline, 20% mannitol, and 10% mannitol plus 10% glycerol combination at a defined infusion rate, which was stopped when ICP was <15 mm Hg. A total of 120 patients with severe TBI (aged >18 years, Glasgow Coma Scale ≤8, and had sustained elevated ICP of >20 mm Hg for more than 5 minutes) were randomized during the study. All data were presented as mean (minimum-maximum). A one-way analysis of variance test was used to analyze the effect across the treatment group, and Tukey's method was used for multiple comparisons. A paired t-test was employed to analyze the effect of the medication within each group. All 3 drugs decreased ICP below 15 mm Hg (P < 0.0001). The maximum change in ICP occurred after a bolus dose of 3% hypertonic saline followed by 10% mannitol plus 10% glycerol combination and then 20% mannitol (60% vs. 57% vs. 55%, respectively). Mean arterial pressure and cerebral perfusion pressure were increased after the bolus dose of study medications. Maximum changes occurred after infusion of 3% hypertonic saline followed by 10% mannitol plus 10% glycerol combination and 20% mannitol (P < 0.0349 and <0.0013, respectively). There was no statistically significant change in the hematocrit value noted after the bolus dose of any of the study medications. Serum sodium and osmolarity were raised significantly after the bolus dose of study medications. Maximum changes in serum sodium and osmolarity occurred after the bolus dose of 3% hypertonic saline. The mean dose required to reduce ICP below 15 mm Hg for 3% hypertonic saline: 1.4 mL/kg, for 10% mannitol plus 10% glycerine: 1.7 mL/kg, and for 20% mannitol: 2.0 mL/kg. The mean time required to reduce ICP below 15 mm Hg for 3% hypertonic saline: 16 minutes, for 10% mannitol plus 10% glycerine: 19 minutes, and for 20% mannitol: 23 minutes. The maximum change in the Glasgow Coma Scale occurred after the bolus dose of 3% hypertonic saline, followed by 10% mannitol plus 10% glycerol combination and then 20% mannitol. All 3 osmotic compounds exhibit comparable effectiveness in reducing ICP when a similar osmotic load is administrated, but 3% hypertonic saline appeared to be more effective followed by 10% mannitol plus 10% glycerol combination and 20% mannitol. A dose of 1.4 mL/kg can be recommended as an initial bolus dose for 3% hypertonic saline. Hypertonic saline can be recommended to treat patients with pretreatment hypovolemia, hyponatremia, or renal failure. There is no clear benefit compared with 20% mannitol in regard to neurologic outcome, even though there is a minor positive trend for 3% hypertonic saline and 10% mannitol plus 10% glycerol combination.

Human iPSC-derived blood-brain barrier microvessels: validation of barrier function and endothelial cell behavior

Microvessels of the blood-brain barrier (BBB) regulate transport into the brain. The highly specialized brain microvascular endothelial cells, a major component of the BBB, express tight junctions and efflux transporters which regulate paracellular and transcellular permeability. However, most existing models of BBB microvessels fail to exhibit physiological barrier function. Here, using (iPSC)-derived human brain microvascular endothelial cells (dhBMECs) within templated type I collagen channels we mimic the cylindrical geometry, cell-extracellular matrix interactions, and shear flow typical of human brain post-capillary venules. We characterize the structure and barrier function in comparison to non-brain-specific microvessels, and show that dhBMEC microvessels recapitulate physiologically low solute permeability and quiescent endothelial cell behavior. Transcellular permeability is increased two-fold using a clinically relevant dose of a p-glycoprotein inhibitor tariquidar, while paracellular permeability is increased using a bolus dose of hyperosmolar agent mannitol. Lastly, we show that our human BBB microvessels are responsive to inflammatory cytokines via upregulation of surface adhesion molecules and increased leukocyte adhesion, but no changes in permeability. Human iPSC-derived blood-brain barrier microvessels support quantitative analysis of barrier function and endothelial cell dynamics in quiescence and in response to biologically- and clinically-relevant perturbations.

Effect of a single dose of mannitol on hydration status and electrolyte concentrations in patients with tick-borne encephalitis.

ObjectiveThis study was performed to assess the effect of a single dose of 15% mannitol on the hydration status and electrolyte balance in patients with tick-borne encephalitis (TBE).MethodsForty-one patients with TBE were treated with 0.25 g/kg of 15% mannitol. The electrolyte concentrations (Na, K, and Cl), creatinine concentration, and hydration status were measured before and after mannitol infusion.ResultsAfter mannitol administration, 7 patients had hyponatremia, 3 had hypokalemia, 1 had hyperkalemia, and 17 had hypochloremia. The total body water volume (TBW) changed by 0.44% ± 0.55%, the external body water volume (EBW) changed by 0.12% ± 0.15%, and the internal body water volume (IBW) changed by 0.19% ± 0.40%. The mean ECW/ICW ratio was 0.7694 ± 0.07 before treatment and 0.7699 ± 0.07 after treatment. Age was correlated with the TBW change in men (R = 0.42, p < 0.05) and with the potassium change in women (R = 0.66, p < 0.05).ConclusionsPatients with TBE should receive mannitol two to four times daily depending on the clinical manifestation. Administration of a single dose of mannitol (0.25 g/kg) requires at least 300 mL of fluid supplementation. Bioimpedance might be useful for individual evaluation of dehydration. Additionally, patients require monitoring for potential hyponatremia. Older men may be more prone to dehydration after receiving mannitol.

A case-control study analyzing mannitol dosing for prevention of cisplatin-induced acute nephrotoxicity.

Mannitol is an osmotic diuretic given routinely as part of cisplatin regimens to prevent nephrotoxicity, but there are limited data on the ideal dosage. At our center, three different doses of mannitol are used: 12, 20, and 40 g per cycle for cisplatin doses of ≥50 mg/m2. The primary objective was to determine if variations in mannitol dosing significantly influence the incidence of cisplatin-induced acute nephrotoxicity. A case-control study was performed. Electronic records of 1462 consecutive outpatients who received cisplatin at ≥ 50 mg/m2 per cycle between January 2010 and December 2014 were reviewed. Patients experiencing nephrotoxicity of any grade within 30 days of last cisplatin dose, as defined by NCI CTCAE 4.0, were matched to a minimum of two and maximum of five controls based on the following criteria: age ± 5 years, baseline estimated glomerular filtration rate ± 10 ml/min/1.73 m2, cisplatin dose per cycle, and presence of diabetes. Conditional logistic regression was used to identify baseline predictors of cisplatin-induced acute nephrotoxicity. Of the 1245 included patients, 237 had nephrotoxicity and 1008 were matched controls. Median baseline estimated glomerular filtration rate for cases and controls were 83 and 80 ml/min/1.73 m2, respectively. A total of 3.8% of cases experienced ≥ grade 3 nephrotoxicity. Univariable analysis showed that diabetes, lymphoma, low baseline estimated glomerular filtration rate, and low baseline magnesium level were significantly associated with nephrotoxicity, whereas mannitol dosing did not show any association (odds ratio 1.08; p = 0.29). In multivariable analysis, diabetes and lymphoma retained statistical significance, but baseline estimated glomerular filtration rate and baseline magnesium level showed nonsignificant associations with nephrotoxicity. Cisplatin-induced acute nephrotoxicity remains common in patients with good baseline renal function despite preventive measures. Diabetes and lymphoma are predictors of nephrotoxicity, whereas mannitol dosing has no significant influence, suggesting that doses may be standardized across cisplatin regimens.

Effect of mannitol on globe and orbital volumes in humans.

To determine the effect of intravenous mannitol on globe and orbital volumes. Retrospective chart review of a consecutive series of Cleveland Clinic Neurosurgical Intensive Care Unit patients who underwent computed tomographic imaging before and after intravenous mannitol administration. Volume measurements were performed according to a previously described technique by averaging axial image areas. Measurements before and after mannitol administration were compared using paired t-test. Fourteen patients (28 eyes) met inclusion criteria. Average globe volume decreased 186 mm3 (-2.5%, p = 0.02) after mannitol administration, while average orbital volume increased 353 mm3 (+3.5%, p = 0.04). Average globe volume change for subjects with follow-up scan less than 4.7 hours (mean 1.9 hours; range 0.2-4.5 hours) after mannitol administration was -125 mm3 (-1.7%, p = 0.24) and average orbital volume change was +458 mm3 (+5.1%, p = 0.11). Average globe volume change after mannitol administration for those with follow-up more than 4.7 hours (average 13.9 hours, range 4.9-24.7 hours) was -246 mm3 (-3.3%, p = 0.05) and orbital volume change was +248 mm3 (+2.2%, p = 0.24). Dividing the study population into groups based on mannitol dose did not yield any statistically significant change. Human globe volume decreases after intravenous mannitol administration, while orbital volume increases. These volume changes occur during the time period when intraocular pressure normalizes, after the pressure-lowering effects of the drug. This novel volumetric information improves our understanding of mannitol's mechanism of action and its effects on human ocular and periocular tissues.

Inhaled mannitol for cystic fibrosis.

Inhaled mannitol for cystic fibrosis.

Renal tubular epithelial cells injury induced by mannitol and its potential mechanism

Administration of mannitol with high dose could induce extensive isometric renal proximal tubular vacuolization and acute renal failure in clinic. We previously demonstrated that mannitol-induced human kidney tubular epithelial cell (HK-2) injury. The objective of our present work was to further study the cytotoxicity of mannitol in HK-2 cells and its potential mechanism. Cell viability was assessed by an MTT method. Cell morphological changes were observed. Furthermore, levels of malondialdehyde (MDA) and glutathione (GSH) were measured. Flow cytometry was performed to determine cell apoptosis by using Annexin V-FITC and PI. In addition, the F-actin of cells was labeled by FITC-Phalloidin for observation of cytoskeleton. The MTT assay displayed that the cell viability decreased significantly in a dose- and time-dependent manner. The morphological changes were observed, including cell membrane rapture and cell detachment. The GSH concentration in HK-2 cells decreased dramatically in mannitol treatment group, while MDA content increased significantly. The results of flow cytometry indicated that apoptotic percentages of HK-2 cells increased in 250 mmol/L mannitol treatment group. After treatment with 250 mmol/L mannitol for 48 h, HK-2 cells showed disorganization of cytoskeleton and even exhibited a totally destroyed cytoskeleton. Therefore, high dose of mannitol has a toxic effect on renal tubular epithelial cells, which might be attributed to oxidative stress, destroyed cellular cytoskeleton and subsequent cell apoptosis.

Intraoperative Mannitol Not Essential During Partial Nephrectomy.

Intraoperative mannitol is routinely administered for renoprotection in partial nephrectomy (PN). However, there is a paucity of evidence supporting mannitol's renoprotective effect. We performed a retrospective study of mannitol's efficacy in PN. Using an institutional database, patients undergoing PN from 2006 to 2016 were retrospectively identified and divided into two groups based on mannitol use. Cases with missing serum creatinine measurements were excluded. Mannitol use was dependent on surgeon preference. An independent-samples t-test was used to compare 6-month postoperative estimated glomerular filtration rate (eGFR) between mannitol groups and to compare 6-month eGFR between mannitol dose for patients who received mannitol. Multivariate linear regression was used to estimate 6-month eGFR when adjusting for multiple covariates that were considered clinically relevant to postoperative renal function. Of the patients, 476 patients were eligible for analysis and 286 received mannitol. Preoperative eGFR (7.8 ± 21.4 mL/minute/1.73 m2 vs 75.3 ± 23.1 mL/minute/1.73 m2, p = 0.223) and tumor size (3.5 ± 1.7 cm vs 3.4 ± 1.5 cm, p = 0.532) were matched between the mannitol (M+) and no mannitol (M-) groups, whereas warm ischemic time (22.5 ± 11.2 minutes vs 15.0 ± 10.2 minutes, p < 0.001) was longer in the M+ group. There was no significant difference in 6-month eGFR between mannitol groups (70.6 ± 22.2 mL/minute/1.73 m2 vs 68.0 ± 23.9 mL/minute/1.73 m2, p = 0.225). No significant association between mannitol dose and 6-month eGFR was found. Covariates that significantly predicted 6-month eGFR in our multivariate model were age (β = 0.052, p = 0.042) and preoperative eGFR (β = 0.843, p < 0.001). In addition, neither the use of renal cooling nor the surgical approach (open vs minimally invasive) was significantly associated with 6-month eGFR. Mannitol did not demonstrate renoprotective effects based on analysis of 6-month postoperative eGFR. In addition, neither the surgical approach nor the use of renal cooling significantly predicted postoperative renal function.