Mannitol Bolus Research Articles

Cerebral Lactate Uptake After Half-Molar Sodium Lactate Therapy in Traumatic Brain Injury: A Brief Report.

Exogenous sodium lactate has many advantages after traumatic brain injury, including intracranial pressure control and alternative energetic supply. It remains unclear, however, whether half-molar sodium lactate (HSL) is effectively incorporated in brain metabolism, which we can verify using the arteriovenous difference in lactate (AVDlac). Hence we compared the AVDlac in patients with severe traumatic brain injury receiving an equiosmolar bolus of sodium lactate or mannitol for intracranial hypertension (IH) treatment. We included 23 patients: 14 received HSL for 25 IH episodes, and nine received mannitol for 19 episodes (total of 44 IH episodes). We observed that the median variation in AVDlac was positive in the group that received HSL (Δ +0.1 [IQR -0.08-0.2] mmol/L), which suggests a net lactate uptake by the brain. On the other hand, it was negative in the group that received mannitol (Δ -0.0 [IQR -0.1 to 0.0] mmol/L), indicating a net lactate export. Finally, there were more positive AVDlac values in the group that received HSL and more negative AVDlac values in the group that received mannitol (Fisher exact p = 0.04). Our study reports the first evidence of a positive AVDlac, which corresponds to a net lactate uptake by the brain, in patients who received HSL for severe TBI. Our results constitute a bedside confirmation of the integration of lactate into the brain metabolism and pave the way for a wider dissemination of sodium lactate in the daily clinical care of patients with traumatic brain injury.

23Na chemical shift imaging in the living rat brain using a chemical shift agent, Tm[DOTP]5–

ObjectiveIt is well known that the use of shift reagents (SRs) in nuclear magnetic resonance (NMR) studies is substantially limited by an intact blood–brain barrier (BBB). The current study aims to develop a method enabling chemical shift imaging in the living rat brain under physiological conditions using an SR, Tm[DOTP]5−.Materials and methodsHyperosmotic mannitol bolus injection followed by 60 min infusion of a Tm[DOTP]5− containing solution was administered via a catheter inserted into an internal carotid artery. We monitored the homeostasis of physiological parameters, and we measured the thulium content in brain tissue post mortem using total reflection fluorescence spectroscopy (T-XRF). The alterations of the 23Na resonance spectrum were followed in a 9.4T small animal scanner.ResultsBased on the T-XRF measurements, the thulium concentration was estimated at 2.3 ± 1.8 mM in the brain interstitial space. Spectroscopic imaging showed a split of the 23Na resonance peak which became visible 20 min after starting the infusion. Chemical shift imaging revealed a significant decrease of the initial intensity level to 0.915 ± 0.058 at the end of infusion.ConclusionOur novel protocol showed bulk accumulation of Tm[DOTP]5− thus enabling separation of the extra-/intracellular 23Na signal components in the living rat brain while maintaining physiological homeostasis.

The Antiedematous Effect of Exogenous Lactate Therapy in Traumatic Brain Injury: A Physiological and Mechanistic Approach

BackgroundSodium lactate (SL) has been described as an efficient therapy in treating raised intracranial pressure (ICP). However, the precise mechanism by which SL reduces intracranial hypertension is not well defined. An antiedematous effect has been proposed but never demonstrated. In this context, the involvement of chloride channels, aquaporins, or K–Cl cotransporters has also been suggested, but these mechanisms have never been assessed when using SL.MethodsIn a rat model of traumatic brain injury (TBI), we compared the effect of SL versus mannitol 20% on ICP, cerebral tissue oxygen pressure, and brain water content. We attempted to clarify the involvement of chloride channels in the antiedematous effects associated with lactate therapy in TBI.ResultsAn equimolar single bolus of SL and mannitol significantly reduced brain water content and ICP and improved cerebral tissue oxygen pressure 4 h after severe TBI. The effect of SL on brain water content was much longer than that of mannitol and persisted at 24 h post TBI. Western blot and immunofluorescence staining analyses performed 24 h after TBI revealed that SL infusion is associated with an upregulation of aquaporin 4 and K–Cl cotransporter 2.ConclusionsSL is an effective therapy for treating brain edema after TBI. This study suggests, for the first time, the potential role of chloride channels in the antiedematous effect induced by exogenous SL.

Equimolar doses of hypertonic agents (saline or mannitol) in the treatment of intracranial hypertension after severe traumatic brain injury.

Background:Mannitol and hypertonic saline (HTS) are effective in reducing intracranial pressure (ICP) after severe traumatic brain injury (TBI). However, their efficacy on the ICP has not been evaluated rigorously.Objective:To evaluate the efficacy of repeated bolus dosing of HTS and mannitol in similar osmotic burdens to treat intracranial hypertension (ICH) in patients with severe TBI.Methods:The authors used an alternating treatment protocol to evaluate the efficacy of HTS with that of mannitol given for ICH episodes in patients treated for severe TBI at their hospital during 2017 to 2019. Doses of similar osmotic burdens (20% mannitol, 2 ml/kg, or 10% HTS, 0.63 ml/kg, administered as a bolus via a central venous catheter, infused over 15 minutes) were given alternately to the individual patient with severe TBI during ICH episodes. The choice of osmotic agents for the treatment of the initial ICH episode was determined on a randomized basis; osmotic agents were alternated for every subsequent ICH episode in each individual patient. intracranial pressure (ICP), mean arterial pressure (MAP), and cerebral perfusion pressure (CPP) were continuously monitored between the beginning of each osmotherapy and the return of ICP to 20 mm Hg. The duration of the effect of ICP reduction (between the beginning of osmotherapy and the return of ICP to 20 mm Hg), the maximum reduction of ICP and its time was recorded after each dose. Serum sodium and plasma osmolality were measured before, 0.5 hours and 3 hours after each dose. Adverse effects such as central pontine myelinolysis (CPM), severe fluctuations of serum sodium and plasma osmolality were assessed to evaluate the safety of repeated dosing of HTS and mannitol.Results:Eighty three patients with severe TBI were assessed, including 437 ICH episodes, receiving 236 doses of HTS and 221 doses of mannitol totally. There was no significant difference between equimolar HTS and mannitol boluses on the magnitude of ICP reduction, the duration of effect, and the time to lowest ICP achieved (P > .05). The proportion of efficacious boluses was higher for HTS than for mannitol, although which showed a slight difference (p = 0.207), as was the increase in serum sodium (P = .038). The serum osmolality increased immediately after osmotherapy with a significant difference (P = .017). No cases of CPM were detected.Conclusion:Repeat bolus dosing of 10% HTS and 20% mannitol appears to be significantly and similarly effective for treating ICH in patients with severe TBI. The proportion of efficacious doses of HTS on ICP reduction may be slightly higher than mannitol.

Long-term outcome of a surgically resected intracranial vascular hamartoma in a dog

A 13-year-old, 6.25-kg (13.8-lb) female mongrel was referred to the authors’ hospital with an acute-onset left pleurothotonus and intermittent opisthotonus. Neurological examination showed clinical signs consistent with a multifocal brain...

Hematocrit Changes as Parameters for Giving Mannitol in Severe Head Injury

ABSTRACT
 Introduction. Incidence of head injuries is also quite high in Indonesia, around 1.4 million cases per year with a mortality rate of 15-20% in the population aged 5 to 35 years. Head injuries are commonly divided into two separate time periods namely primary and secondary brain injuries. Primary brain injury is physical damage to the parenchyma (tissue and blood vessels) that occurs during a traumatic event, thus causing compression of the surrounding brain tissue. Secondary brain injury is a continuation of the results of primary brain injury with the main complications of brain injury in the following hours and days. This study was aimed to asses the benefits of administration of mannitol in cases of severe head injury in South Sumatra, Indonesia.
 Methods. This research was a clinical trial without comparison by looking at hematocrit levels in patients with severe head injuries with intracranial hypertension before and after given mannitol therapy. Data analysis was performed with IBM SPSS Version 23. Data was presented in the form of narrative tables. Then the paired T test was performed. P value <0.05.
 Results. From 39 research subjects, the age of the subjects ranged between 6-88 years with an average of 33 years. Based on sex there were 28 male sufferers (71.8%) and there were 11 female sufferers 28.2%. GCS varies from 3 to GCS 8 intra-cranial abnormalities. From 39 research subjects with severe head injury without surgery, a hematocrit examination was performed before, after 10 minutes and 6 hours of injection of mannitol bolus 1 g / kg body weight. It was obtained that averaged hematocrit before mannitol administration was 34, after 10 minutes was 33 and after 6 hours was 35.
 Conclusion. There is a decrease in hematocrit levels after administration of bolus mannitol 1 g / kg BW at the beginning of mannitol administration and hematocrit will increase again after 6 hours of mannitol administration

New Insight into the Mechanism of Mannitol Effects on Cerebrospinal Fluid Pressure Decrease and Craniospinal Fluid Redistribution

Intracranial hypertension, which often follows a severe brain injury, is usually treated with intravenous (i.v.) application of hyperosmolar solutions. The mechanism of intracranial cerebrospinal fluid (CSF) pressure decrease after such a treatment is still unclear. The aim of this article was to try to explain the mechanism of CSF pressure reduction after i.v. hyperosmolar mannitol bolus in regard to the changes in CSF volume. Two types of experiments were done on anesthetized cats before and after hyperosmolar mannitol application: ventriculo-cisternal perfusion at different perfusion rates, simultaneously measuring the perfusate outflow volume, and CSF pressure recording in the lateral ventricle before and during artificial CSF infusion. Mannitol application in the first group of cats significantly reduced collected prefusate volume during ventriculo-cisternal perfusion, and in the second group it prevented CSF pressure increase caused by artificial CSF infusion. Our results strongly suggest that the mechanism of hyperosmolar mannitol action after its i.v. application is based on osmotic fluid retrieval from interstitial and cerebrospinal compartments into the microvessels. This shift, without significant volume change inside the cranium, causes a predominant decrease of CSF volume in the spinal part of the system, which in turn leads to lowering of the CSF pressure. Spinal CSF volume decrease is enabled by the extensibility of the spinal dura, this way providing the possibility for CSF volume redistribution inside the CSF system, together with CSF pressure decrease. This mechanism of mannitol action is in accordance with the new hypothesis of CSF physiology.

Malignant Posterior Reversible Encephalopathy Syndrome-An Exacting Challenge for Neurocritical Care Physicians.

We report a case of malignant posterior reversible encephalopathy syndrome (PRES) in a 62-year-old Caucasian female with a complex medical history and comorbidities admitted for bowel resection and lysis of iatrogenic bowel adhesions and enterocutaneous fistulas. Postoperatively, the patient developed sudden bilateral visual loss with no other neurologic deficits. Computed tomography scan showed very severe PRES-like changes, confirmed on magnetic resonance imaging (MRI). Systolic blood pressure remained around 170 mm HG. The patient was obtunded and remained unresponsive after MRI, with minimal response and a deteriorating clinical condition. The patient was given hyperosmolar therapy with a mannitol bolus. She recovered well with near resolution of imaging findings.

Abstract WP351: No Effect of Mannitol on the Course of Perihemorrhagic Edema After Intracerebral Hemorrhage

Introduction: In patients with intracerebral hemorrhage (ICH) perihemorrhagic edema (PHE) seems to play a predictive role besides initial hematoma size, clinical status and intraventricular bleeding (IVH). PHE may exceed the initial hematoma volume by up to 600% thereby leading to increased intracranial pressure (ICP) which may cause severe clinical deterioration. EUSI and ASA guidelines recommend the use of intravenous mannitol or hypertonic saline (HS) in order to reduce elevated ICP. However, clinical data suggest that HS may be superior to mannitol in lowering ICP and clinical data concerning the effect of mannitol on PHE as a cause of elevated ICP is limited. We aimed to investigate the effect of mannitol on PHE after ICH. Methods: Patients with supratentorial spontaneous ICH treated with 20% intravenous mannitol solution (125-250ml every 6h) for 5-10 days and controls matched for ICH volume, age and IVH who did not receive any osmotic agents during the course of treatment were identified retrospectively from our institutional ICH database. PHE volume was calculated on diagnostic CT scans performed on days 1, 2-3, 4-6, 7-9 and 10-12 using a validated volumetric algorithm. Frequency of elevated ICP up to day 12 (ICP burden), modified Rankin Scale (mRS) after rehabilitation (approx. day 90) and PHE evolution were assessed as outcome variables. Results: 44 ICH patients treated with mannitol and 43 controls were included. Basic characteristics did not differ between groups (median ICH volume day 1: 32.9 mL (IQR 16.3 - 54.0) and 27.7 mL (IQR 22.4 - 37.1), p=0.786; median age 71 y (IQR 61.5 - 77) and 72 y (IQR 66 - 81), p=0.269; median PHE volume day 1: 24.3 mL (IQR 16.0 - 38.8) and 24.3 mL (IQR 17.1 - 32.1), p=0.592, respectively). In the mannitol group PHE volume exceeded to a greater extent than in controls (PHE on day 10-12: 60.1 mL (SD 33.6) vs. 36.8 mL (SD 23.2), p=0.005). Median ICP burden was higher in the mannitol group (0 (IQR 0 - 7.75) vs. 0 (IQR 0), p=0.016). Median mRS did not differ between both groups (4 (IQR 4-6) vs. 4 (IQR 3-6), p=0.321). Conclusions: We found no effect of mannitol use on the general evolution of PHE and ICP. Other underlying mechanisms may explain the short-term effect of mannitol bolus administration on ICP in patients with spontaneous supratentorial ICH.

Dexmedetomidine for Refractory Intracranial Hypertension.

Dexmedetomidine (DEX) is a selective α2 adrenergic agonist that is commonly used for sedation in the intensive care unit (ICU). The role of DEX for adjunctive treatment of refractory intracranial hypertension is poorly defined. The primary objective of this study was to determine the effect of DEX on the need for rescue therapy (ie, hyperosmolar boluses, extraventricular drain [EVD] drainages) for refractory intracranial hypertension. Secondary objectives included the number of intracranial pressure (ICP) excursions, bradycardic, hypotensive, and compromised cerebral perfusion pressure episodes. This retrospective cohort study evaluated patients admitted to the neurosurgical ICU from August 1, 2009, to July 29, 2015, and who received DEX for refractory intracranial hypertension. The objectives were compared between the 2 time periods-before (pre-DEX) and during therapy (DEX). Twenty-three patients with 26 episodes of refractory intracranial hypertension met the inclusion criteria. The number of hyperosmolar boluses was decreased after DEX therapy was initiated. Mannitol boluses required were statistically reduced (1 vs 0.5, P = .03); however, reduction in hypertonic boluses was not statistically significant (1.3 vs 0.9, P = .2). The mean number of EVD drainages per 24 hours was not significantly different between the time periods (15.7 vs 14.0, P = .35). The rate of ICP excursions did not differ between the 2 groups (24.3 vs 22.5, P = .62). When compared to pre-DEX data, there was no difference in the median number of hypotensive (0 vs 0), bradycardic (0 vs 0), or compromised cerebral perfusion pressure episodes (0.5 vs 1.0). Dexmedetomidine may avoid increases in the need for rescue therapy when used as an adjunctive treatment of refractory intracranial hypertension without compromising hemodynamics.

Treatment of Acute Liver Failure in Resource-Constrained Settings without Transplantation Facilities Can Be Improved.

Treatment of Acute Liver Failure in Resource-Constrained Settings without Transplantation Facilities Can Be Improved.

Pulse-plethysmographic variables in hemodynamic assessment during mannitol infusion

Plethysmographic signal using pulse oximetry may be used to assess fluid status of patients during surgery as it resembles arterial pressure waveform. This will avoid placement of invasive arterial lines. This study was designed to find out whether intravascular volume changes induced by mannitol bolus in neurosurgical patients are detected by variations in arterial pressure and plethysmographic waveforms and also to assess the strength of correlation between different variables derived from these two waveforms. The time difference between the onset of arterial and plethysmographic waveforms as means of significant hemodynamic changes was also evaluated. Forty one adult ASA I and II neurosurgical patients requiring mannitol infusion were recruited. Arterial line and plethysmographic probe were placed in the same limb. Digitized waveforms were collected before, at the end, and 15, 30 and 60min after mannitol infusion. Using MATLAB, the following parameters were collected for three consecutive respiratory cycles,-systolic pressure variation (SPV), pulse pressure variation (PPV), plethysmographic peak variation (Pl-PV), plethysmographic amplitude variation (Pl-AV) and blood pressure-plethysmographic time lag (BP-Pleth time lag). Changes in above parameters over the study period were studied using repeated measure analysis of variance. Correlation between the parameters was analysed. SPV and Pl-PV showed significant increase at 15, 30 and 60min compared to end of mannitol infusion (P<0.01 for SPV; P<0.05 for Pl-PV). PPV and Pl-AV showed significant increase only at 30min (P<0.05). The correlation between ∆SPV-∆Pl-PV, ∆PPV-∆Pl-AV and ∆SPV-∆BP-Pleth time lag were significant (r=0.3; P<0.01). SPV and time lag had no significant interaction. Pl-PV correlates well with SPV following mannitol infusion and can be used as an alternative to SPV. (BP-Pleth) time-lag promises to be an important parameter in assessing the state of peripheral vascular resistance and deserves further investigation.

Effects of a Single Mannitol Bolus on Cerebral Hemodynamics in Intracerebral Hemorrhage: A Transcranial Doppler Study

Background: Mannitol infusion is widely used in clinical practice to reduce perilesional edema in intracerebral hemorrhage (ICH), though no controlled studies have yet provided evidence of its effects on clinical outcome or on cerebral blood flow impairment following the event. The aim of our study was to evaluate blood flow velocity changes in the middle cerebral arteries (MCA) after a mannitol bolus in patients with ICH. Methods: Transcranial Doppler bilateral monitoring was performed for 90 min in 20 patients with ICH, during 100 ml mannitol bolus i.v. administration. The MCA mean flow velocities (MFVs) and pulsatility index (PI) were recorded. Results: When the ‘healthy’ and the ‘affected’ hemispheres were compared, we observed higher MCA MFV and lower PI on the affected side than on the contralateral side, both at baseline and during the experiment. After the mannitol bolus, we observed a significant MFV increase, starting at the end of the infusion and lasting longer than 60 min in the MCA on the affected side alone. The PI increased after mannitol administration on the healthy side alone. Conclusions: A single bolus of mannitol modified cerebral hemodynamics in our patients with ICH, increasing flow velocities on the affected MCA. This effect may be a consequence of reduced edema in the perilesional areas. The increased PI on the unaffected side may be indicative of preserved pulsatility in the healthy hemisphere.

A young boy with malignant hypertension and intracranial bleed

A 12-year-old male child presented to pediatric emergency with complaints of abnormal movements involving the right side of body, which rapidly progressed to alteration of sensorium along with repeated bouts of vomiting since last one day. He developed all problems acutely and was apparently well before this. In a local hospital he was noted to have weakness of right side of the body and was referred to PGI. There was no history of fever, loose stools, head trauma or excessive bleeding prior to this. The past history was totally unremarkable. The child was born to a gravida 2 mother by full-term normal vaginal delivery and there were no adverse prenatal events. His developmental milestones were normal. He was appropriately immunized. He was born of a non-consanguineous marriage. His elder sibling had died at the age of 1.5 years due to some unknown illness. There was no history of contact with tuberculosis. On examination, he weighed 25 kg, had no pallor, icterus, clubbing, edema or skin bleed. His heart rate was 140 beats/minute, respiratory rate 36 per minute, capillary filling time 2 seconds, blood pressure (BP) 220/160 mm Hg and oxygen saturation was 100% on room air. All the peripheral pulses were palpable. The BP in the upper limbs was 180/130 mm Hg and in the lower limbs was 170/120 mm Hg. Ophthalmoscopic examination showed bilateral disk blurring with hemorrhages. On systemic examination, he had a Glasgow coma score of E2, M4, V2, both the pupils were 2 mm and reacted to light, and there was no cranial nerve palsy. There was hypotonia of all four limbs, more on the right side. The deep tendon reflexes were normally elicitable on the left side; but absent on the right side. Plantars were upgoing in both the legs. Neck rigidity and Kernig’s sign were positive. Cardiovascular, abdominal and respiratory examinations were normal. Investigations are shows in Tables ​Tables11 and ​and22. Table 1 Investigations Table 2 Investigations (Contd.) Blood culture (26/08/06): sterile; Urine RE (28/08/06): protein, nil; sugar, nil; no RBC. Pus cells: 2–3/hpf. Oxalate crystals ++; Urine sugar (30/08/06): ++++; Urine electrolytes (28/08/06): Na, 75 meq/L; K, 28.3 mEq/L; creatinine: 50.4 mg/dL. The child was started on sodium nitroprusside infusion and oral amlodepine. The intracranial pressure (ICP) was 70–80 mm Hg. Measures for raised ICP were instituted. A neurosurgery consultation was obtained and the hematoma was evacuated. Thereafter, he was shifted to intensive care unit. Post-evacuation, the ICP dropped to 30–35 mm Hg, BP came down and nitroprusside drip was discontinued. Later, the BP continued to drop to <5th centile requiring fluid boluses, dopamine and adrenaline infusions were started. Twelve hours postevacuation, ICP began to rise again and reached up to 180 mm Hg. A mannitol bolus was given and a repeat computerized tomography (CT) was done. Anti-edema measures (dexamethasone, lasix, mannitol and hyperventilation) were continued but raised ICP persisted. He had fever in the postoperative period. Ceftriaxone + sulbactum and cloxacillin were started empirically. He also developed hyperglycemia with polyuria, which was treated with insulin infusion and vasopressin. Despite all the measures, the cerebral perfusion pressure continued to remain low. The neurological status and shock progressively deteriorated and he expired on 31.08.06.

A cancer research UK pharmacokinetic study of BPA-mannitol in patients with high grade glioma to optimise uptake parameters for clinical trials of BNCT

This paper describes results to-date from a human pharmacokinetic study which began recruitment in December 2007. Results are presented for a single patient recruited in December 2007. A second patient was recruited in July 2008 but detailed data are not available at the time of writing. The trial is an open-label, non-comparative, non-therapeutic study of BPA-mannitol in patients with high-grade glioma, who will be undergoing stereotactic brain biopsy as part of the diagnostic process before definitive treatment. The study investigates the route of infusion (intra-venous (IV) or intra-carotid artery) and in each case will assess the effect of administration of mannitol as a blood–brain barrier disrupter. All cohorts will receive a 2 h infusion of BPA-mannitol, and for some cohorts an additional mannitol bolus will be administered at the beginning of this infusion. Measurements are made by inductively coupled plasma mass spectrometry (ICP-MS) of 10B concentration in samples of blood, urine, extra-cellular fluid in normal brain (via a dialysis probe), brain tissue around tumour and tumour tissue. Additional analysis of the tumour tissue is performed using secondary ion mass spectrometry (SIMS). The first patient was part of the cohort having intra-venous infusion without mannitol bolus. No serious clinical problems were experienced and the assay results can be compared with available patient data from other BNCT centres. In particular we note that the peak 10B concentration in blood was 28.1 mg/ml for a total BPA administration of 350 mg/kg which is very consistent with the previous experience with BPA-fructose reported by the Helsinki group.

Arsenic Trioxide Entered Cerebrospinal Fluid with the Help of Mannitol Overwhelm the Meningeal Relapse of Acute Promyelocytic Leukemia.

Background and objective Central nervous system (CNS) relapse of acute promyeloytic leukemia (APL) is increasingly reported after treatment with all-trans retinoic acid (ATRA) and arsenic trioxide (As2O3), the optimal therapy for these cases remains unclear. As2O3 highly effective in APL marrow relapse, but its efficacy in APL CNS relapse is undefined. Recent researches showed that little As2O3 could pass through the intact blood- brain-barrier (BBB), which limits its use in prevention and treatment of central nervous system acute promyelocytic leukaemia (CNSAPL). After discovered the different tolarance between NB4 cell line and human cortex neuron to As2O3in vitro, and primarily cleared the safe range of As2O3 level in central nervous system (CNS), we created a non-invasive method to help As2O3 enter into CNS effectively.Methods Five volunteers with isolated meningle APL relapse received the new As2O3 regimen (mannitol helped As2O3 penetration) after accepted the conventional treatment: As2O3 0.16mg/kg/d diluted with 5%glucose 250ml common speed intravenous infusion with intensive intrathecal chemotherapy (MTX 12mg/dose + cytarabine 50mg / dose + Dexamethasone 10mg/dose) and showed chemotherapy resistance. The new regimen included 125ml of 20% mannitol bolus through medial cubital vein with the speed of 12„d'30ml / min, followed by As2O3 0.08mg/kg/d diluted with 250ml-20% mannitol intravenous infusion with the speed of 6ml /min, and then followed by As2O3 0.08mg/kg/d diluted with 5%glucose 250ml intravenous infusion with the speed of 0.5ml/min, meanwhile, associated with intensive intrathecal chemotherapy. The elemental arsenic levels in CSF and plasma during the new regimen performance were dynamic monitored with atomic fluorescence, and the differentiation and apoptosis of the blast cells in CSF were detected with flow cytometry assay.Results The elemental arsenic level in the CSF treated with mannitol helped As2O3 penetration was fluctuated between 0.04 mg /L (0.2 micromol /L) and 0.05mg / L(0.25 micromol /L), which was much higher than that with common speed As2O3 intravenous infusion, and reached to the As2O3 effectively therapeutic level. The blast cells in CSF showed significant differentiation and apoptosis after treated with mannitol helped As2O3 penetration. Three of the five patients obtained complete remission, two of them reached partial remission.Conclusions The new regimen of mannitol helped As2O3 penetration promoted the entrance of elemental arsenic to CNS, which might be benefit to prevent and cure CNS APL, especially to chemotherapy resistant CNS APL.

Evaluation of mannitol effect in patients with acute hepatic failure and acute-on-chronic liver failure using conventional MRI, diffusion tensor imaging and in-vivo proton MR spectroscopy

To evaluate the effect of an intravenous bolus of mannitol in altering brain metabolites, brain water content, brain parenchyma volume, cerebrospinal fluid (CSF) volume and clinical signs in controls and in patients with acute liver failure (ALF) and acute-on-chronic liver failure (ACLF), by comparing changes in conventional magnetic resonance imaging (MRI), in vivo proton magnetic resonance spectroscopy (PMRS) and diffusion tensor imaging (DTI) before and after its infusion. Five patients each with ALF and ACLF in grade 3 or 4 hepatic encephalopathy and with clinical signs of raised intracranial pressure were studied along with five healthy volunteers. After baseline MRI, an intravenous bolus of 20% mannitol solution was given over 10 min in controls as well as in patients with ALF and ACLF. Repeat MRI for the same position was acquired 30 min after completing the mannitol injection. No statistically significant difference was observed between controls and patients with ALF and ACLF in metabolite ratios, DTI metrics and brain volume or CSF volume following 45 min of mannitol infusion. There was no change in clinical status at the end of post-mannitol imaging. The osmotic effect of mannitol did not result in significant reduction of brain water content, alteration in metabolite ratios or any change in the clinical status of these patients during or within 45 min of mannitol infusion.

Effects of Mannitol Bolus Administration on Intracranial Pressure, Cerebral Extracellular Metabolites, and Tissue Oxygenation in Severely Head-Injured Patients

Effects of Mannitol Bolus Administration on Intracranial Pressure, Cerebral Extracellular Metabolites, and Tissue Oxygenation in Severely Head-Injured Patients

Intensive care of patients with acute liver failure: Recommendations of the U.S. Acute Liver Failure Study Group

To provide a uniform platform from which to study acute liver failure, the U.S. Acute Liver Failure Study Group has sought to standardize the management of patients with acute liver failure within participating centers. In areas where consensus could not be reached because of divergent practices and a paucity of studies in acute liver failure patients, additional information was gleaned from the intensive care literature and literature on the management of intracranial hypertension in non-acute liver failure patients. Experts in diverse fields were included in the development of a standard study-wide management protocol. Intracranial pressure monitoring is recommended in patients with advanced hepatic encephalopathy who are awaiting orthotopic liver transplantation. At an intracranial pressure of > or =25 mm Hg, osmotic therapy should be instituted with intravenous mannitol boluses. Patients with acute liver failure should be maintained in a mildly hyperosmotic state to minimize cerebral edema. Accordingly, serum sodium should be maintained at least within high normal limits, but hypertonic saline administered to 145-155 mmol/L may be considered in patients with intracranial hypertension refractory to mannitol. Data are insufficient to recommend further therapy in patients who fail osmotherapy, although the induction of moderate hypothermia appears to be promising as a bridge to orthotopic liver transplantation. Empirical broad-spectrum antibiotics should be administered to any patient with acute liver failure who develops signs of the systemic inflammatory response syndrome, or unexplained progression to higher grades of encephalopathy. Other recommendations encompassing specific hematologic, renal, pulmonary, and endocrine complications of acute liver failure patients are provided, including their management during and after orthotopic liver transplantation. The present consensus details the intensive care management of patients with acute liver failure. Such guidelines may be useful not only for the management of individual patients with acute liver failure, but also to improve the uniformity of practices across academic centers for the purpose of collaborative studies.

Effect of single mannitol bolus in intracerebral hemorrhage

Because of existing controversy about use of mannitol in intracerebral hemorrhage (ICH) this open exploratory trial with blinded outcome assessment of single mannitol bolus in ICH was undertaken. CT proven primary supratentorial ICH patients having midline shift of > or =3 mm were randomized into 20% mannitol (1.5 g/kg) and control groups. Clinical evaluation included Glasgow coma scale (GCS) score, Canadian Neurological scale (CNS) score, pupils, breathing, extensor posturing and contra-lateral pyramidal signs. On cranial MRI horizontal (HS), superior sagittal sinus to pontomesencephalic junction (SSS-PMJ) distance and edema hematoma complex were measured. Twelve patients each were in mannitol and control groups. The age, sex, GCS score, CNS score, pupillary asymmetry, contra-lateral pyramidal signs, HS and SSS-PMJ distance in mannitol and control groups did not differ significantly. Mannitol infusion resulted clinical improvement in five patients, which lasted for 30-60 min. HS and SSS-PMJ distance in mannitol and control groups did not change at 30 or 60 min from the baseline. The change in HS and SSS-PMJ distance were also not significantly different between the two groups both at 30 and 60 min. Mannitol led to transient clinical improvement in five patients without significant reduction in HS or SSS-PMJ distance at 30 and 60 min.