UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: This is a prospective, randomized, double-blind study involving 60 patients undergoing supratentorial brain tumor surgery.
UNASSIGNED: 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.
UNASSIGNED: Data collected were analyzed using SPSS software, IBM, USA, version 22. P value was considered significant if <0.05.
UNASSIGNED: 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).
UNASSIGNED: 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.

Dysnatremia is common in severe traumatic brain injury (TBI) patients and may contribute to mortality. However, serum sodium variability has not been studied in TBI patients. We hypothesized that such variability would be independently associated with mortality.
We collected 6-hourly serum sodium levels for the first 7 days of ICU admission from 240 severe TBI patients in 14 neurotrauma ICUs in Europe and Australia. We evaluated the association between daily serum sodium standard deviation (dNaSD), an index of variability, and 28-day mortality.
Patients were 46 ± 19 years of age with a median initial GCS of 6 [4-8]. Overall hospital mortality was 28%. Hypernatremia and hyponatremia occurred in 64% and 24% of patients, respectively. Over the first 7 days in ICU, serum sodium standard deviation was 2.8 [2.0-3.9] mmol/L. Maximum daily serum sodium standard deviation (dNaSD) occurred at a median of 2 [1-4] days after admission. There was a significant progressive decrease in dNaSD over the first 7 days (coefficient - 0.15 95% CI [- 0.18 to - 0.12], p < 0.001). After adjusting for baseline TBI severity, diabetes insipidus, the use of osmotherapy, the occurrence of hypernatremia, and hyponatremia and center, dNaSD was significantly independently associated with 28-day mortality (HR 1.27 95% CI (1.01-1.61), p = 0.048).
Our study demonstrates that daily serum sodium variability is an independent predictor of 28-day mortality in severe TBI patients. Further prospective investigations are necessary to confirm the significance of sodium variability in larger cohorts of TBI patients and test whether attenuating such variability confers outcome benefits to such patients.

The optimal osmotic agent to treat intracranial hypertension in patients with severe traumatic brain injury (TBI) remains uncertain. We aimed to test whether the choice of mannitol or hypertonic saline (HTS) as early (first 96 h) osmotherapy in these patients might be associated with a difference in mortality. We retrospectively analyzed data from 2015 from 14 tertiary intensive care units (ICUs) in Australia, UK, and Europe treating severe TBI patients with intracranial pressure (ICP) monitoring and compared mortality in those who received mannitol only versus HTS only. We performed multi-variable analysis adjusting for site and illness severity (Injury Severity Score, extended IMPACT score, and mean ICP over the first 96 h) using Cox proportional hazards regression. We collected data on 262 patients and compared patients who received early osmotherapy with mannitol alone (n = 46) with those who received HTS alone (n = 46). Mannitol patients were older (median age, 49.2 (19.2) vs. 40.5 (16.8) years; p = 0.02), with higher Injury Severity Scores (42 (15.9) vs. 32.1 [11.3]; p = 0.001), and IMPACT-TBI predicted 6-month mortality (34.5% [23-46] vs. 25% [13-38]; p = 0.02), but had similar APACHE-II scores, and mean and maximum ICPs over the first 96 h. The unadjusted hazard ratio for in-hospital mortality in patients receiving only mannitol was 3.35 (95% confidence interval [CI], 1.60-7.03; p = 0.001). After adjustment for key mortality predictors, the hazard ratio for in-hospital mortality in patients receiving only mannitol was 2.64 (95% CI, 0.96-7.30; p = 0.06). The choice of early osmotherapy in severe TBI patients may affect survival, or simply reflect clinician beliefs about their different roles, and warrants controlled investigation.

BACKGROUND: Aneurysmal subarachnoid hemorrhage (aSAH) is a life-threatening condition that results from a ruptured cerebral vessel. Cerebral edema and vasospasm are common complications and frequently require treatment with hypertonic solutions, in particular hypertonic sodium chloride (NaCl). We have previously shown that hyperchloremia in patients with aSAH given hypertonic NaCl is associated with the development of acute kidney injury (AKI), which leads to higher morbidity and mortality. Our current trial aims to study the effect of two hypertonic solutions with different chloride content on serum chloride concentrations in patients with aSAH who are at risk for AKI.
METHODS: A low ChloridE hyperTonic solution for brain Edema (ACETatE) is a single center, double-blinded, double-dummy pilot trial comparing bolus doses of 23.4% NaCl and 16.4% NaCl/Na-Acetate for the treatment of cerebral edema in patients with aSAH. All patients will be enrolled within 36 h following admission. Randomization will occur once patients who receive hypertonic treatment for cerebral edema develop hyperchloremia (serum Cl- concentration ≥ 109 mmol/L). Subsequent treatment will consist of either NaCl 23.4% or NaCl/Na-Acetate 16.4%. The primary outcome of this study will be the change in serum Cl- concentrations during treatment. Secondary outcomes will include incidence of AKI, mortality, changes in intracranial pressure, and extent of hypernatremia.
CONCLUSIONS: In patients with aSAH, hyperchloremia is a known risk factor for subsequent development of AKI. The primary goal of this pilot study is to determine the effect of two hypertonic solutions with different Cl- content on serum Cl- concentrations in patients with aSAH who have already developed hyperchloremia. Data will be collected prospectively to determine the extent to which the choice of hypertonic saline solution affects subsequent serum Cl- concentrations and the occurrence of AKI. This approach will allow us to obtain preliminary data to design a large randomized trial assessing the effects of chloride-sparing hypertonic solutions on development of AKI in patients with SAH. This pilot study is the first to prospectively evaluate the relationship between hypertonic solution chloride content and its effect on serum electrolytes and renal function in aSAH patients at risk of AKI due to hyperchloremia.
BACKGROUND: Clinicaltrials.gov, NCT03204955 . Registered on 28 June 2017.

Background: A prospective, randomized, double-blind study was designed to assess differences in brain relaxation between 2 doses of 3% HS during elective supratentorial brain tumour surgery.Methods: 60 patients undergoing supratentorial craniotomy for tumour resection were enrolled to receive either 3 mL/kg (group L) or 5 mL/kg (group H) of 3% HS administered at skin incision. Brain relaxation was assessed after dura opening on a scale ranging 1-4 (1 = perfectly relaxed, 2 = satisfactorily relaxed, 3 = firm brain, 4 = bulging brain). Hemodynamic variables and laboratory values (blood gases, osmolarity, haematocrit, and lactate) were collected before HS infusion and 30, 120 and 360 min after it. Presence of midline shift, postoperative complications, PCU and hospital stay, and mortality after 30 days were also recorded.Results: There was no difference in brain relaxation, with 2.0 (1.0-3.0) and 2.0 (1.0-2.3) (P = 0.535) for patients in groups L and H, respectively. If adjusted for the presence of midline shift, 50% of patients had adequate brain relaxation scores (grades 1 and 2) in group L and 61% in group H (OR 0.64, CI = 0.16-2.49, P = 0.515). No significant differences in perioperative outcome, mortality and length of PCU and hospital stay were observed.Conclusion: 3 mL/kg of 3% HS result in similar brain relaxation scores as 5 mL/kg in patients undergoing craniotomy for supratentorial brain tumour. This study reveals that both high and low doses of 3% HS may be less effective on intraoperative brain relaxation in patients with midline shift.

BACKGROUND: Hyperosmolar therapy with either mannitol or hypertonic saline (HTS) is commonly used in the treatment of intracranial hypertension (ICH). In vitro data indicate that both mannitol and HTS affect coagulation and platelet function in dogs. The aim of this study was to compare the effects of 20% mannitol and 7.2% HTS on whole blood coagulation using rotational thromboelastometry (ROTEM®) and platelet function using a platelet function analyzer (PFA®) in dogs with suspected ICH. Thirty client-owned dogs with suspected ICH needing osmotherapy were randomized to receive either 20% mannitol (5 ml/kg IV over 15 min) or 7.2% HTS (4 ml/kg IV over 5 min). ROTEM® (EXTEM® and FIBTEM® assays) and PFA® analyses (collagen/ADP cartridges) were performed before (T0), as well as 5 (T5), 60 (T60) and 120 (T120) minutes after administration of HTS or mannitol. Data at T5, T60 and T120 were analyzed as a percentage of values at T0 for comparison between groups, and as absolute values for comparison between time points, respectively.
RESULTS: No significant difference was found between the groups for the percentage change of any parameter at any time point except for FIBTEM® clotting time. Within each group, no significant difference was found between time points for any parameter except for FIBTEM® clotting time in the HTS group, and EXTEM® and FIBTEM® maximum clot firmness in the mannitol group. Median ROTEM® values lay within institutional reference intervals in both groups at all time points, whereas median PFA® values were above the reference intervals at T5 (both groups) and T60 (HTS group).
CONCLUSIONS: Using currently recommended doses, mannitol and HTS do not differ in their effects on whole blood coagulation and platelet function in dogs with suspected ICH. Moreover, no relevant impairment of whole blood coagulation was found following treatment with either solution, whereas a short-lived impairment of platelet function was found after both solutions.