Mannitol versus furosemide in patients with thoracic malignancies who received cisplatin-based chemotherapy using short hydration: A randomized phase II trial.

BACKGROUND: Mannitol is exclusively recommended in the National Comprehensive Cancer Network guidelines for diuresis in cisplatin (CDDP)-based chemotherapy. The utility of furosemide, a widely used and convenient diuretic, thus requires clarification. METHODS: This is a prospective, single-centered, open-label, noninferiority phase II study. Patients with thoracic malignancies who planned to receive CDDP-based chemotherapy were randomly assigned to receive either mannitol (arm A) or furosemide (arm B). The primary end point was set as the proportion of patients who experienced any grade of "creatinine (Cr) increased" based on the upper limit of the normal range (ULN) during the first cycle as assessed by Common Terminology Criteria for Adverse Events Version 4.0. Secondary end points were Cr increased based on the baseline value during the first cycle, Cr increased after the completion of CDDP, and the proportion of patients with phlebitis. RESULTS: Between April 2018 and March 2022, 115 patients were enrolled and 106 were analyzed. Any grade of Cr increased based on the ULN during the first cycle was 17.3% (arm A) and 24.1% (arm B), respectively (p = 0.34). Therefore, the primary end point was not met. After completion of chemotherapy, any grade of Cr increased was observed in 23.1% (arm A) and 31.5% (arm B), respectively. However, the actual serum Cr level and Cr clearance during the courses were not different between the arms. Phlebitis occurred more frequently in arm A (28.8%) than arm B (16.7%). CONCLUSIONS: Mannitol should remain the standard diuresis in CDDP-based chemotherapy assessed by conventional CTCAE grading, but furosemide can be room for consideration when assessed by actual serum Cr level and Cr clearance.

Comparison of Bretschneider HTK and Blood Cardioplegia (4:1): A Prospective Randomized Study.

BACKGROUND: We compared the effect of intermittent blood and histidine-tryptophan-ketoglutarate (HTK) solution of Bretschneider on myocardial histopathology and perioperative outcome. METHODS: Forty adult cardiac surgery patients were grouped into two (n = 20 for each): (1) Intermittent blood cardioplegia (IBC): had repeated cold 4:1 blood cardioplegia and (2) HTK: had a single dose of cold HTK for cardioprotection. Creatine kinase (CK)-MB, Troponin-I (cTn-I), pH, and lactate were studied in coronary sinus blood before and after aortic cross-clamping (AXC) and systemic blood at postoperative 6th, 24th, and 48th hours. Myocardial biopsy was performed before and after AXC for light microscopy. Vacuolation, inflammation, edema, and glycogen were graded semiquantitatively (from 0 to 3). The myocardial apoptotic index was evaluated via the terminal deoxynucleotidyl transferase dUTP nick end labeling. RESULTS: There were no differences in perioperative clinical outcomes between the groups. The coronary sinus samples after AXC were more acidotic (7.15 ± 0.14 vs. 7.32 ± 0.07, p = 0.001) and revealed higher CK-MB (21.0 ± 12.81 vs. 12.60 ± 11.80, p = 0.008) in HTK compared with IBC. The HTK had significantly a higher amount of erythrocyte suspension intraoperatively compared with IBC (0.21 ± 0.53 vs. 1.68 ± 0.93 U, p = 0.001). Microscopically, myocardial edema was more pronounced in HTK compared with IBC after AXC (2.25 ± 0.91 vs. 1.50 ± 0.04, p = 0.013). While a significant increase in the apoptotic index was seen after AXC in both groups (p = 0.001), no difference was detected between the groups (p = 0.417). CONCLUSION: IBC and HTK have a similar clinical outcome and protective effect, except for more pronounced myocardial edema and increased need for intraoperative transfusion with HTK.

Intensive mannitol slow infusion post-stenting may attenuate stenting-related early adverse effects in patients with cerebral venous sinus stenosis.

AIMS: To analyze intensive slow mannitol poststenting on attenuating stenting-related early adverse effects in cerebral venous sinus stenosis (CVSS). METHODS: This real-world study enrolled subacute or chronic CVSS patients from January 2017 through March 2022 and divided them into DSA only and stenting post-DSA groups. The later group was subdivided into control (without extra mannitol use) and intensive slow mannitol subgroup (immediate extra mannitol 250-500 mL, 2 mL/min infusion post-stenting) after signed informed consent. All data were compared. RESULTS: A total of 95 eligible patients entered into final analysis, in which 37 cases underwent DSA only and 58 cases underwent stenting post-DSA. Finally, 28 patients were entered into intensive slow mannitol subgroup and 30 in control. Stenting group vs. DSA group, HIT-6 scores and WBC counts were higher in the former (both p < 0.001). Intensive slow mannitol subgroup vs. control on the third day post-stenting, a statistically significant reductions were noticed in the former on WBC counts (6.19 ± 1.86 × 109 /L vs. 9.59 ± 2.05 × 109 /L); HIT-6 scores (degree of headache) (40.00 (38.00-40.00) vs. 49.00 (41.75-55.25)) and brain edema surrounding the stent on CT maps (17.86% vs.96.67%), all p < 0.001. CONCLUSIONS: Stenting-related severe headache, inflammatory biomarkers elevation, and brain edema aggravation can be attenuated by intensive slow mannitol infusion.

Is a hyperosmolar pump prime for cardiopulmonary bypass a risk factor for postoperative delirium? A double blinded randomised controlled trial.

Objective: Postoperative delirium (POD) is common after cardiac surgery. We have previously identified plasma sodium concentration and the volume of infused fluids during surgery as possible risk factors. Both are linked to the selection and composition of the pump prime used for cardiopulmonary bypass (CPB). Present study aims to examine whether hyperosmolality increases the risk for POD. Design: Patients ≥65 years (n = 195) scheduled for cardiac surgery were prospectively enrolled into this double blinded randomised clinical trial. Study group received a pump prime containing mannitol and ringer-acetate (966 mOsmol) (n = 98) vs. ringer-acetate (388 mOsmol) (n = 97) in the control group. Postoperative delirium was defined according to DSM-5 criteria based on a test-battery pre- and postoperatively (days 1-3). Plasma osmolality was measured on five occasions and coordinated with the POD assessments. The primary outcome was the POD incidence related to hyperosmolality as the secondary outcome. Results: The incidence of POD was 36% in the study group and 34% in the control group, without intergroup difference (p=.59). The plasma osmolality was significantly higher in the study group, both on days 1 and 3 and after CPB (p<.001). Post hoc analysis indicated that high osmolality levels increased the risk for delirium on day 1 by 9% (odds ratio (OR) 1.09, 95% CI 1.03-1.15) and by 10% on day 3 (OR 1.10, 95% CI 1.04-1.16). Conclusions: Use of a prime solution with high osmolality did not increase the incidence of POD. However, the influence of hyperosmolality as a risk factor for POD warrants further investigation.

Factors influencing the presence of potentially explosive gases during colonoscopy: Results of the SATISFACTION study.

This study tested the hypothesis that bowel preparation with mannitol should not affect the colonic concentration of H2 and CH4 . Therefore, the SATISFACTION study, an international, multicenter, randomized, parallel-group phase II-III study investigated this issue. The phase II dose-finding part of the study evaluated H2 , CH4 , and O2 concentrations in 179 patients randomized to treatment with 50 g, 100 g, or 150 g mannitol. Phase III of the study compared the presence of intestinal gases in 680 patients randomized (1:1) to receive mannitol 100 g in single dose or a standard split-dose 2 L polyethylene glycol (PEG)-Asc preparation (2 L PEG-Asc). Phase II results showed that mannitol did not influence the concentration of intestinal gases. During phase III, no patient in either group had H2 or CH4 concentrations above the critical thresholds. In patients with H2 and/or CH4 levels above detectable concentrations, the mean values were below the risk thresholds by at least one order of magnitude. The results also highlighted the effectiveness of standard washing and insufflation maneuvers in removing residual intestinal gases. In conclusion, bowel cleansing with mannitol was safe as the concentrations of H2 and CH4 were the same as those found in patients prepared with 2 L PEG-Asc. In both groups, the concentrations of gases were influenced more by the degree of cleansing achieved and the insufflation and washing maneuvers performed than by the preparation used for bowel cleansing. The trial protocol was registered with ClinicalTrials.gov (https://clinicaltrials.gov/ct2/show/NCT04759885) and with EudraCT (eudract_number: 2019-002856-18).

Hypertonic saline use in neurocritical care for treating cerebral edema: A review of optimal formulation, dosing, safety, administration and storage.

PURPOSE: Current Neurocritical Care Society guidelines on the management of cerebral edema recommend hypertonic saline (HTS) over mannitol in some scenarios, but practical questions remain regarding the appropriate administration method, concentration/dose, monitoring to ensure safe use, and storage. The aim of this article is to address these practical concerns based on the evidence currently available. SUMMARY: Many different hypertonic solutions have been studied to define the optimal hyperosmolar substance to relieve acute cerebral edema in patients with conditions such as acute ischemic stroke, intracerebral hemorrhage, subarachnoid hemorrhage, and traumatic brain injury. Mannitol and HTS are the main hyperosmolar therapies in use in contemporary neurocritical care practice. Contemporary use of HTS has followed a circuitous path in regards to the practical aspects of dosing and formulation, with evidence mainly consisting of retrospective or observational data. The effectiveness of bolus doses of HTS to lower acutely elevated intracranial pressure is well accepted. Adverse events with use of HTS are often mild and non-clinically significant if appropriate monitoring of serum sodium and chloride concentrations is performed. Available evidence shows that peripheral administration of HTS is likely safe in certain circumstances. Timely utilization of HTS is complicated by regulatory requirements for safe storage, but with appropriate safeguards HTS can be stored in patient care areas. CONCLUSION: HTS formulations, methods of administration, infusion rate, and storage vary by institution, and no practice standards exist. Central intravenous administration may be preferred for HTS, but peripheral intravenous administration is safe provided measures are undertaken to detect and prevent phlebitis and extravasation. The safe use of HTS is possible with proper protocols, education, and institutional safeguards in place.

Moving away from mannitol infusion for partial nephrectomy: has this altered renal function?

In recent years, research has questioned the theorized renal-protective value of mannitol infusion during partial nephrectomy. This study considers whether the cessation of routine mannitol administration has shown any benefit or detriment to patients in the contemporary era. We retrospectively reviewed a multi-institution database for an association between mannitol administration and subsequent renal function during follow-up. These patients were assessed for de novo stage III chronic kidney disease (CKD III) and followed with estimated glomerular filtration rate (eGFR). Statistical analysis included Mann-Whitney-U and Chi-squared tests for comparing baseline and perioperative variables with postoperative outcomes. eGFR changes were evaluated with a mixed-effects linear regression model. Nine hundred and fifteen patients were identified whose operative reports or surgeons' treatment algorithms explicitly described whether or not mannitol was administered. 667 (73%) did not receive mannitol. There were no differences in demographics, age, Charlson comorbidity index, nephrometry score, tumor size, grading, or baseline eGFR from those who received mannitol. Ischemia time and operative time appeared slightly longer with mannitol use. Patients were followed for a median of 5 months (IQR 0.5-19 months), during which mannitol use was associated with an increase in de novo CKD III (14% v. 9%, p = 0.041) and minimally worsened median eGFR on final follow-up (72.82 v. 76.06, p = 0.039). Our analysis of partial nephrectomy patients indicates that mannitol administration likely confers no short- or long-term renal benefit. Mannitol may be used at the surgeon's discretion, but if it prolongs surgery time or ischemia time, it may in fact be detrimental to outcomes.

Computational modelling of cerebral oedema and osmotherapy following ischaemic stroke.

In ischaemic stroke, a large reduction in blood supply can lead to the breakdown of the blood brain barrier and to cerebral oedema after reperfusion therapy. Cerebral oedema is marked by elevated intracranial pressure (ICP), tissue herniation and reduced cerebral perfusion pressure. In clinical settings, osmotherapy has been a common practice to decrease ICP. However, there are no guidelines on the choice of administration protocol parameters such as injection doses, infusion time and retention time. Most importantly, the effects of osmotherapy have been proven controversial since the infusion of osmotic agents can lead to a range of side effects. Here, a new Finite Element model of brain oedema and osmotherapy is thus proposed to predict treatment outcome. The model consists of three components that simulate blood perfusion, oedema, and osmotherapy, respectively. In the perfusion model (comprising arteriolar, venous, and capillary blood compartments), an anatomically accurate brain geometry is used to identify regions with a perfusion reduction and potential oedema occurrence in stroke. The oedema model is then used to predict ICP using a porous circulation model with four fluid compartments (arteriolar blood, venular blood, capillary blood, and interstitial fluid). In the osmotherapy model, the osmotic pressure is varied and the changes in ICP during different osmotherapy episodes are quantified. The simulation results of the model show excellent agreement with available clinical data and the model is employed to study osmotherapy under various parameters. Consequently, it is demonstrated how therapeutic strategies can be proposed for patients with different pathological parameters based on simulations.

Volume replacement is associated with a diminished osmolar effect of mannitol in patients with acute brain injury.

INTRODUCTION: Animal experiments recently demonstrated that replacing urinary loses with crystalloid diminishes the therapeutic effect of mannitol by reducing the increase in osmolality. We aimed to investigate whether this effect is similarly seen in in brain-injured patients by studying the association between total body fluid balance (TBB) and the osmolar response to mannitol. METHODS: We performed a retrospective cohort study of adult patients with acute brain injury between 2015 and 2021 who received ≥ 2 doses of mannitol within 8 hours and no intercurrent concentrated saline solution. We analyzed the association between the change in TBB (∆TBB) and change in osmolality (∆Osm) before and after mannitol in a linear model, both as univariate and after adjustment for common confounding factors. RESULTS: Of 6,145 patients who received mannitol, 155 patients met inclusion criteria (mean age 60 ± 17 years, 48% male, 83% white). The mean total mannitol dose was 2 ± 0.5 g/kg and the mean change in plasma osmolality was 7.9 ± 7.1 mOsm/kg. Each 1 L increase in ∆TBB was associated with a change of -1.1 mOsm/L in ∆Osm (95% CI [-2.2, -0.02], p = 0.045). The magnitude of association was similar to that of total mannitol dose and remained consistent in an adjusted model and after excluding outliers. CONCLUSIONS: In patients with acute brain injury, a positive TBB is associated with a diminished mannitol-induced increase in plasma osmolality. Future prospective studies are needed to confirm these findings and their influence on the therapeutic effect of mannitol.

Oral mannitol for bowel preparation: a dose-finding phase II study.

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 (CH4, H2, O2), 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.

Salted or sweet? Hypertonic saline or mannitol for treatment of intracranial hypertension.

PURPOSE OF REVIEW: The aim of this review article is to present current recommendations regarding the use of hypertonic saline and mannitol for the treatment of intracranial hypertension. RECENT FINDINGS: In recent years, a significant number of studies have been published comparing hypertonic saline with mannitol in patients with acute increased intracranial pressure, mostly caused by traumatic brain injury. Albeit several randomized controlled trials, systematic reviews and meta-analysis support hypertonic saline as more effective than mannitol in reducing intracranial pressure, no clear benefit in regards to the long-term neurologic outcome of these patients has been reported. SUMMARY: Identifying and treating increased intracranial pressure is imperative in neurocritical care settings and proper management is essential to improve long-term outcomes. Currently, there is insufficient evidence from comparative studies to support a formal recommendation on the use of any specific hyperosmolar medication in patients with acute increased intracranial pressure.

Comparative study between manitol and sodium picosulfate with magnesium oxide solutions in the preparation for colonoscopy.

This prospective, randomized and double-blind study aims to compare two different protocols used for bowel preparation in patients scheduled for colonoscopy. The protocols were composed by solutions of Mannitol or sodium picosulfate combined with magnesium oxide. Patients from the proctology outpatient clinic of the General Surgery Unit of the Regional Hospital of Asa Norte (HRAN) comprised the sample of this study. Both the patients and the colonoscopist had no prior knowledge of the substance used to prepare bowel, which was randomly distributed among the participants. Both protocols demonstrated good and similar results regarding the efficiency of colon preparation, although the review of literature shows a difference in favor of preparation made with Mannitol solution regarding the colon neatness during the exam. In line with the literature, patients who used Mannitol solution had more side effects, highlighting the significant difference found for vomiting and sleep impairment. The preparation with Sodium Picosulfate with Magnesium Oxide was significantly superior in relation to the ease of ingestion perceived by the patients.

Mannitol Use is Renal Protective in Patients with Chronic Kidney Disease Requiring Suprarenal Aortic Clamping.

BACKGROUND: Mannitol is often administered during open juxtarenal or suprarenal aortic surgery to prevent ischemic injury to the kidneys. Prior evidence evaluating the benefits of intraoperative mannitol in reducing ischemia/reperfusion injury is conflicting and largely based on small, retrospective series. The aim of this study was to evaluate the effect of mannitol in preventing postoperative hemodialysis in patients undergoing open abdominal aortic aneurysm (AAA) repair where proximal control involved temporary renal ischemia. METHODS: The Society for Vascular Surgery Quality Initiative database was queried for all patients undergoing elective open AAA repair between 2003 and 2020. Patients were included in the current analysis if the proximal aortic clamp was placed above at least one renal artery. Chronic kidney disease (CKD) was defined as Cr > 1.8 mg/dL. Primary end points were 30-day major morbidity (myocardial infarction, respiratory complications, lower extremity or intestinal ischemia, and the need for temporary or permanent hemodialysis) and mortality. Comparisons were made between the mannitol and nonmannitol cohorts and stratified by the presence of preexisting CKD. RESULTS: During the study period, 4,156 patients underwent elective open AAA repair requiring clamp placement more than one (32.7%) or both (67.3%) renal arteries; 182 patients (4.4%) had preexisting CKD. Overall, 69.8% of patients received mannitol during their surgery. Mannitol was more frequently used in cases involving clamp placement above both renal arteries (70.3%) than one renal artery (61.5%). While prolonged ischemia time (more than 40 min) was associated with a higher risk of postoperative dialysis in patients without CKD, it was not significant in patients with baseline CKD. On a univariate analysis, mannitol use in patients with CKD was associated with a lower risk of postoperative dialysis (P = 0.005). This remained significant on a multivariate analysis (P = 0.008). Mannitol use did not appear to confer renal protective effects in patients without baseline CKD. CONCLUSIONS: Mannitol use was associated with a decreased risk of need for postoperative hemodialysis in patients with CKD undergoing suprarenal aortic clamping for open aneurysm repair. In appropriately selected patients, particularly those with underlying renal insufficiency, mannitol may confer a renal protective effect in open repair of pararenal AAA requiring suprarenal clamping.

The Effect of Intravenous Mannitol Combined With Normal Saline in Preventing Cisplatin-Induced Nephrotoxicity: A Randomized, Double-Blind, Placebo-Controlled Trial.

PURPOSE: Nephrotoxicity is a major dose-limiting toxicity among patients with cancer who were treated with cisplatin. Although no standard approach is available to prevent cisplatin-induced nephrotoxicity, administering intravenous isotonic saline is recommended. Additionally, mannitol combined with hydration has been evaluated, but none of them have been established. Our study aimed to determine the efficacy of mannitol combined hydration to prevent cisplatin-induced nephrotoxicity. PATIENTS AND METHODS: This study was a phase II, randomized, placebo-controlled design. All patients with solid cancers who were treated with cisplatin (n = 48) were randomly assigned to receive either placebo (n = 25) or 20 g of mannitol (n = 23) after completing 2 L of prehydration and receiving cisplatin. Serum creatinine, blood urea nitrogen, electrolyte, and glomerular filtration rate (GFR) were measured at baseline and days 2 and 7. Moreover, GFR was calculated based on the 24-hour urine creatinine clearance rate to assess renal function at baseline and 48 hours after receiving cisplatin. Severity of nausea and vomiting was evaluated using Common Terminology Criteria for Adverse Events. RESULTS: No difference was found regarding baseline characteristics between the two groups. Seven of 23 patients (37.4%) in the mannitol group and 10 of 25 patients (40%) in the placebo group increased serum creatinine level ≥ 0.3 mg/dL at 48 hours after intervention (P value = .48). Patients receiving mannitol exhibited significantly lower incidence of 24-hour urine GFR below 60 mL/min/1.73 m than those in the placebo group (13.6% v 48.0% in the placebo group; P value = .012). Univariate analysis showed the greatest benefit for administering mannitol among patients receiving cisplatin > 80 mg/m2, or patients receiving concomitant radiation. CONCLUSION: Mannitol combined with hydration significantly prevented cisplatin-induced nephrotoxicity. Additionally, mannitol should be particularly considered among patients with cancer, treated with cisplatin > 80 mg/m2, or patients receiving concomitant radiation.

The effect of mannitol addition to hydration on acute kidney injury event after high dose cisplatin chemotherapy: an ambispective cohort study.

BACKGROUND: Saline hydration with addition of mannitol have commonly been the strategy to avoid cisplatin induced acute kidney injury (AKI). While the initial reports demonstrated that mannitol diuresis decreased cisplatin induced renal injury, others have shown renal injury to be worsened. OBJECTIVE: To compare the risk of AKI in cancer patients receiving high dose cisplatin with and without addition of mannitol. METHOD: This was an ambispective cohort study based on consecutive sampling at Cipto Mangunkusumo General Hospital (CMGH) and Mochtar Riady Comprehensive Cancer Centre (MRCCC) Siloam Hospitals. The data was obtained from September 2017 to February 2018. The choice of mannitol administration based on attending physician clinical judgement. The primary outcome was increase of serum creatinine more than 0.3 mg/dL or 1.5 times from baseline. Analysis was done by using univariate, bivariate and multivariate logistic regression to obtain crude risk ratio and adjusted risk ratio of cisplatin induced AKI probability caused by mannitol addition on top of usual saline hydration protocol. RESULT: Data from 110 patients (57.3% male) with a median age of 44.5 years (range 19 to 60 years) were collected; 63 received saline with the addition of mannitol and 47 received saline only. Incidence of AKI were higher in mannitol vs saline only group. Bivariate analysis showed higher probability of post chemotherapy AKI in mannitol group, however it was statistically insignificant (RR 2.168; 95% CI 0.839-5.6; p = 0.094). On multivariate analysis the age adjusted RR was 2.852 (95% CI 0.68-11.96; p = 0.152). CONCLUSION: The addition of mannitol to hydration did not reduce the risk of cisplatin induced AKI as compared with saline hydration only. It was also found that risk for acute kidney injury were higher in population ≥ 40 years old.

Inhaled Dry Powder Mannitol Treatment in Pediatric Patients with Cystic Fibrosis: Evaluation of Clinical Data in a Real-World Setting.

Background: Cystic fibrosis (CF) is a genetic disorder, in which defective clearance of airway secretions leads to progressive lung function loss. Inhaled mannitol is used to increase sputum and mucociliary clearance. There are little data from real-world studies on the effectiveness of mannitol in children. Our objective was to evaluate the spirometry and clinical results of mannitol in pediatric patients. Methods: We retrospectively reviewed the records of 30 children and adolescents with CF receiving inhaled mannitol who were already on recombinant human deoxyribonuclease (rhDNase) treatment. The change in forced expiratory volume in 1 second (FEV1) from baseline at 2-4 months was the primary outcome. Secondary measures were other spirometry results, body mass index (BMI), hospital admissions, sputum characteristics, and positive bacterial colonization. Results: Compared to baseline, we found significant improvement in percent predicted FEV1 at 2-4 months of treatment; 84.50 (58.00-99.00) vs. 96.00 (66.00-106.00) (P = 0.0007). The absolute change in FEV1 was +11.5% at 2-4 months, +6.5% at 5-7 months, and +4% at 8-12 months. Also, significant improvements in other spirometry results were observed. Adolescents had significantly lower FEV1 results, but the improvement in their lung function was sustained for a more extended period than children. Mannitol provided easier sputum removal, increased sputum volume, significant decline in hospitalizations, and significantly fewer patients with positive sputum cultures. A significant increase in BMI at 8-12 months was observed. Cough was the most frequent adverse effect. Conclusion: In a real-world setting, our results demonstrated that adding mannitol to rhDNase therapy is tolerable in pediatric patients with CF and may provide improved spirometry and clinical outcomes. In addition, our results showed that mannitol provided recovery in overall lung function at 2-4 months, which was sustained up to 12 months together with improved BMI, easier sputum removal, and a decline in bacterial colonization and hospital admissions. However, cough was the most frequent side effect.

Mannitol Is Associated with Less Postoperative Delirium after Aortic Valve Surgery in Patients Treated with Bretschneider Cardioplegia.

BACKGROUND: Heart surgery with extracorporeal circulation (ECC) often leads to postoperative delirium (POD). This is associated with increased morbidity resulting in longer hospital stay and associated costs. The purpose of our study was to analyze the effect of intraoperative mannitol application on POD in patients undergoing elective aortic valve replacement (AVR). MATERIALS AND METHOD: s In our retrospective single-center study, 259 patients underwent elective AVR, using Bretschneider cardioplegic solution for cardiac arrest, between 2014 and 2017. Patients were divided in mannitol (n = 188) and nonmannitol (n = 71) groups. POD was assessed using the confusion assessment method for the intensive care unit (ICU). Statistical significance was assumed at p < 0.05. RESULTS: Baseline patient characteristics did not differ between the groups. Incidence of POD was significantly higher in the nonmannitol group (33.8 vs. 13.8%; p = 0.001). These patients required longer ventilation time (24.1 vs. 17.1 hours; p = 0.021), higher reintubation rate (11.3 vs. 2.7%; p = 0.009), ICU readmission (12.7 vs. 4.8%; p = 0.026), prolonged ICU (112 vs. 70 hours; p = 0.040), and hospital stay (17.8 vs. 12.6 days; p < 0.001), leading to higher expenses (19,349 € vs. 16,606 €, p < 0.001). A 30-day mortality was not affected, but nonmannitol group showed higher Simplified Acute Physiology Score II score (32.2 vs. 28.7; p < 0.001). Mannitol substitution was independently associated with lower incidence of POD (odds ratio: 0.40; 95% confidence interval: 0.18-0.89; p = 0.02). CONCLUSION: Treatment with mannitol during ECC was associated with decreased incidence of POD. This was accompanied by shorter ventilation time, ICU and hospital stay, and lower treatment expenses.

Laryngeal hypersensitivity and abnormal cough response during mannitol bronchoprovocation challenge.

BACKGROUND AND OBJECTIVE: Inhalational challenge with dry mannitol powder may potentially induce cough by two mechanisms: airway bronchoconstriction or laryngeal irritation. This prospective observational study investigated laryngeal and bronchial components of cough induced by mannitol challenge. METHODS: We recruited consecutive patients referred for clinical mannitol challenge. The Newcastle Laryngeal Hypersensitivity Questionnaire (LHQ) was administered. Throughout testing, coughs were audio-recorded to derive a cough frequency index per time and dose of mannitol. Relationships between cough indices, laryngeal hypersensitivity and bronchial hyperresponsiveness (BHR) were examined. Participants were classified by cough characteristics with k-means cluster analysis. RESULTS: Of 90 patients who underwent challenge, 83 completed both the questionnaire and challenge. Cough frequency was greater in patients with abnormal laryngeal hypersensitivity (p = 0.042), but not in those with BHR. There was a moderate negative correlation between coughs per minute and laryngeal hypersensitivity score (r = -0.315, p = 0.004), with lower LHQ scores being abnormal. Cluster analysis identified an older, female-predominant cluster with higher cough frequency and laryngeal hypersensitivity, and a younger, gender-balanced cluster with lower cough frequency and normal laryngeal sensitivity. CONCLUSION: Cough frequency during mannitol challenge in our cohort reflected laryngeal hypersensitivity rather than BHR. Laryngeal hypersensitivity was more often present among older female patients. With the incorporation of cough indices, mannitol challenge may be useful to test for laryngeal hypersensitivity as well as BHR.

Mannitol Is Comparable to Hypertonic Saline for Raised Intracranial Pressure in Acute Liver Failure (MAHAL Study): A Randomized Controlled Trial.

BACKGROUND: Raised intracranial pressure (ICP) due to cerebral edema (CE) is central to development of hepatic encephalopathy in acute liver failure (ALF). Mannitol (MT) and hypertonic saline (HS) have been shown to improve CE. We compared the efficacy and safety of the 2 modalities. METHODS: ALF with CE was prospectively randomized in an open study to receive either 5 mL/kg of either 3% HS, as continuous infusion; titrated every 6 hourly to achieve serum sodium of <160 (Group A; n = 26) or 1 g/kg of 20% MN as a IV bolus, repeated every 6 hourly (Group B; n = 25) in addition to standard ALF care. Primary end-point was reduction of ICP defined as optic nerve sheath diameter <5 mm and middle cerebral arterial pulsatility index <1.2 at 12 h. RESULTS: Fifty-one patients with ALF, hepatitis E being commonest (33.3%), median jaundice to HE interval of 8 (1-16) days, were randomized to HS (n = 26) or MN (n = 25). Baseline characteristics were comparable including King's college criteria (>2: 38.4% vs.40%). Overall, 61.5% patients in the HS and 56% in the MN group showed reduction in ICP at 12 h (p = 0.25). Rebound increase in ICP indices was noted in 5 (20%) patients in MT and none in HS (p < 0.05) group. New onset acute kidney injury was common in the MT group than in the HS group. The ICU stay and 28-day transplant-free survival were not different between the groups. CONCLUSIONS: While both agents had comparable efficacy in reducing ICP and mortality in ALF patients was comparable, HS was significantly better in preventing reducing rebound CE with lower renal dysfunction.