Hypertonic Saline Versus Other Intracranial-Pressure-Lowering Agents for Patients with Acute Traumatic Brain Injury: A Systematic Review and Meta-analysis.

Acute traumatic brain injury (TBI) is a major cause of mortality and disability worldwide. Intracranial pressure (ICP)-lowering is a critical management priority in patients with moderate to severe acute TBI. We aimed to evaluate the clinical efficacy and safety of hypertonic saline (HTS) versus other ICP-lowering agents in patients with TBI. We conducted a systematic search from 2000 onward for randomized controlled trials (RCTs) comparing HTS vs. other ICP-lowering agents in patients with TBI of all ages. The primary outcome was the Glasgow Outcome Scale (GOS) score at 6 months (PROSPERO CRD42022324370). Ten RCTs (760 patients) were included. Six RCTs were included in the quantitative analysis. There was no evidence of an effect of HTS on the GOS score (favorable vs. unfavorable) compared with other agents (risk ratio [RR] 0.82, 95% confidence interval [CI] 0.48-1.40; n = 406; 2 RCTs). There was no evidence of an effect of HTS on all-cause mortality (RR 0.96, 95% CI 0.60-1.55; n = 486; 5 RCTs) or total length of stay (RR 2.36, 95% CI - 0.53 to 5.25; n = 89; 3 RCTs). HTS was associated with adverse hypernatremia compared with other agents (RR 2.13, 95% CI 1.09-4.17; n = 386; 2 RCTs). The point estimate favored a reduction in uncontrolled ICP with HTS, but this was not statistically significant (RR 0.52, 95% CI 0.26-1.04; n = 423; 3 RCTs). Most included RCTs were at unclear or high risk of bias because of lack of blinding, incomplete outcome data, and selective reporting. We found no evidence of an effect of HTS on clinically important outcomes and that HTS is associated with adverse hypernatremia. The included evidence was of low to very low certainty, but ongoing RCTs may help to the reduce this uncertainty. In addition, heterogeneity in GOS score reporting reflects the need for a standardized TBI core outcome set.

Comparison of 20% mannitol and 3% hypertonic saline for intraoperative brain relaxation during supratentorial brain tumour craniotomy in patients with a midline shift / Comparación entre manitol 20% y salino hipertónico 3% para la relajación cerebral intraoperatoria durante craneotomía por tumor cerebral supratentorial en pacientes con desviación de la línea media

Purpose of the study A prospective, randomized, double-blind study was designed to assess differences in brain relaxation between 20% mannitol and 3% hypertonic saline (HS) during elective supratentorial brain tumour surgery in patients with midline shift. Material and methods Sixty patients undergoing supratentorial craniotomy for tumour resection were enrolled to receive either 5mL/kg of 20% mannitol (n=30) or 3% HS (n=30) administered at skin incision. PCO2 in arterial blood was maintained within 35–40mmHg and arterial blood pressure was controlled within baseline values ±20%. The primary outcome was the proportion of satisfactory brain relaxation. The surgeon assessed brain relaxation on a four-point scale (1=excellent with no swelling, 2=minimal swelling, 3=serious swelling not requiring treatment, 4=severe swelling requiring treatment). Postsurgical intracranial changes determined by imaging techniques, postoperative complications, PACU and hospital stay, and mortality at 30 days were also recorded. Appropriate statistical tests were used for comparison; P<0.05 was considered as significant. This trial was registered in Eudract.ema.europa.eu (#2021-006290-40). Results There was no difference in brain relaxation: 2.00 [1.00–2.00] and 2.00 [1.75–3.00] for patients in mannitol and HS groups, respectively (P=0.804). Tumour size (OR: 0.99, 95% CI: 0.99–1.01; P=0.371), peritumoral oedema classification (OR: 0.57, 95% CI: 0.11–2.84; P=0.493), mass effect (OR: 0.86, 95% CI: 0.16–4.87; P=0.864), anaesthesia (OR: 4.88, 95% CI: 0.82–28.96; P=0.081) and midline shift (OR: 5.00, 95% CI: 0.84–29.70; P=0.077) did not have a significant influence on brain swelling in patients treated with either mannitol or HS. No significant differences in perioperative outcomes, mortality and length of PACU and hospital stay were observed (AU)

Objetivos del estudio Estudio prospectivo, aleatorizado y doble ciego diseñado para evaluar diferencias en la relajación cerebral entre manitol 20% y salino hipertónico (SH) 3% durante cirugía supratentorial electiva por tumor cerebral en pacientes con desviación de línea media. Material y métodos Sesenta pacientes sometidos a craneotomía supratentorial para resección tumoral se estudiaron para recibir 5ml/kg de manitol 20% (n=30) o SH 3% (n=30) administrados durante la incisión cutánea. La pCO2 en sangre arterial se mantuvo entre 35-40mmHg y la presión arterial se controló dentro de valores basales±20%. El objetivo principal fue la proporción de relajación cerebral satisfactoria. El cirujano evaluó la relajación cerebral en una escala de 4 puntos (1=excelente sin hinchazón, 2=hinchazón mínima, 3=hinchazón grave que no requiere tratamiento, 4=hinchazón severa que requiere tratamiento). Los cambios intracraneales posquirúrgicos determinados por técnicas de imagen, complicaciones postoperatorias, estancia en reanimación y hospitalaria, así como mortalidad a 30 días fueron registrados. Se usaron test estadísticos para la comparación, siendo considerado p<0,05 como significativo. El ensayo fue registrado en Eudract.ema.europa.eu (#2021-006290-40). Resultados No hubo diferencias en la relajación cerebral: 2,00 [1,00-2,00] y 2,00 [1,75-3,00] en los pacientes del grupo manitol y SH respectivamente (p=0,804). El tamaño tumoral (OR: 0,99: IC 95%:0,99-1,01; p=0,371), nivel de edema peritumoral (OR: 0,57; IC 95%:0,11-2,84; p=0,493), efecto masa (OR: 0,86; IC 95%: 0,16-4,87; p=0,864), anestesia empleada (OR: 4,88; 95% IC: 0,82-28,96; p=0,081) y desviación de la línea media (OR: 5,00; IC 95%: 0,84-29,70; p=0,077) no tuvieron influencia significativa sobre la hinchazón cerebral en los pacientes de ambos grupos. No hubo diferencias significativas en los resultados perioperatorios, mortalidad ni en estancia en reanimación ni hospitalaria (AU)

Fluid therapy and traumatic brain injury: A narrative review / Fluidoterapia y daño cerebral traumático: una revisión narrativa

Traumatic brain injury (TBI) is an important health and social problem. The mechanism of damage of this entity could be divided into two phases: (1) a primary acute injury because of the traumatic event; and (2) a secondary injury due to the hypotension and hypoxia generated by the previous lesion, which leads to ischemia and necrosis of neural cells. Cerebral edema is one of the most important prognosis markers observed in TBI. In the early stages of TBI, the cerebrospinal fluid compensates the cerebral edema. However, if edema increases, this mechanism fails, increasing intracranial pressure. To avoid this chain effect, several treatments are applied in the clinical practice, including elevation of the head of the bed, maintenance of normothermia, pain and sedation drugs, mechanical ventilation, neuromuscular blockade, controlled hyperventilation, and fluid therapy (FT). The goal of FT is to improve the circulatory system to avoid the lack of oxygen to organs. Therefore, rapid and early infusion of large volumes of crystalloids is performed in clinical practice to restore blood volume and blood pressure. Despite the relevance of FT in the early management of TBI, there are few clinical trials regarding which solution is better to apply. The aim of this study is to provide a narrative review about the role of the different types of FT used in the daily clinical practice on the management of TBI. To achieve this objective, a physiopathological approach to this entity will be also performed, summarizing why the different types of FT are used (AU)

El traumatismo craneoencefálico (TCE) es un importante problema sanitario y social. El mecanismo de daño de esta entidad se podría dividir en dos fases: 1) una lesión aguda primaria a causa del evento traumático, y 2) una lesión secundaria por la hipotensión e hipoxia generada por la lesión anterior, que conduce a la isquemia y necrosis de las células neurales. El edema cerebral es uno de los marcadores pronósticos más importantes observados en el TCE. En las primeras etapas de TCE, el líquido cefalorraquídeo compensa el edema cerebral. Sin embargo, si aumenta el edema, este mecanismo falla, aumentando la presión intracraneal. Para evitar este efecto en cadena, en la práctica clínica se aplican varios tratamientos, entre ellos la elevación de la cabecera de la cama, el mantenimiento de la normotermia, los fármacos para el dolor y la sedación, la ventilación mecánica, el bloqueo neuromuscular, la hiperventilación controlada y la fluidoterapia (FT). El objetivo de la FT es mejorar el sistema circulatorio para evitar la falta de oxígeno a los órganos. Por lo tanto, en la práctica clínica se realiza una infusión rápida y temprana de grandes volúmenes de cristaloides para restablecer el volumen sanguíneo y la presión arterial. A pesar de la relevancia de la FT en el manejo temprano del TCE, existen pocos ensayos clínicos sobre qué solución es mejor aplicar. El objetivo de este estudio es proporcionar una revisión narrativa sobre el papel de los diferentes tipos de FT utilizados en la práctica clínica diaria en el manejo del TCE. Para lograr este objetivo, también se realizará un abordaje fisiopatológico de esta entidad, resumiendo por qué se utilizan los diferentes tipos de FT (AU)

Fluid therapy and traumatic brain injury: A narrative review.

Traumatic brain injury (TBI) is an important health and social problem. The mechanism of damage of this entity could be divided into two phases: (1) a primary acute injury because of the traumatic event; and (2) a secondary injury due to the hypotension and hypoxia generated by the previous lesion, which leads to ischemia and necrosis of neural cells. Cerebral edema is one of the most important prognosis markers observed in TBI. In the early stages of TBI, the cerebrospinal fluid compensates the cerebral edema. However, if edema increases, this mechanism fails, increasing intracranial pressure. To avoid this chain effect, several treatments are applied in the clinical practice, including elevation of the head of the bed, maintenance of normothermia, pain and sedation drugs, mechanical ventilation, neuromuscular blockade, controlled hyperventilation, and fluid therapy (FT). The goal of FT is to improve the circulatory system to avoid the lack of oxygen to organs. Therefore, rapid and early infusion of large volumes of crystalloids is performed in clinical practice to restore blood volume and blood pressure. Despite the relevance of FT in the early management of TBI, there are few clinical trials regarding which solution is better to apply. The aim of this study is to provide a narrative review about the role of the different types of FT used in the daily clinical practice on the management of TBI. To achieve this objective, a physiopathological approach to this entity will be also performed, summarizing why the different types of FT are used.

Comparison of 20% mannitol and 3% hypertonic saline for intraoperative brain relaxation during supratentorial brain tumour craniotomy in patients with a midline shift.

PURPOSE OF THE STUDY: A prospective, randomized, double-blind study was designed to assess differences in brain relaxation between 20% mannitol and 3% hypertonic saline (HS) during elective supratentorial brain tumour surgery in patients with midline shift. MATERIAL AND METHODS: Sixty patients undergoing supratentorial craniotomy for tumour resection were enrolled to receive either 5mL/kg of 20% mannitol (n=30) or 3% HS (n=30) administered at skin incision. PCO2 in arterial blood was maintained within 35-40mmHg and arterial blood pressure was controlled within baseline values ±20%. The primary outcome was the proportion of satisfactory brain relaxation. The surgeon assessed brain relaxation on a four-point scale (1=excellent with no swelling, 2=minimal swelling, 3=serious swelling not requiring treatment, 4=severe swelling requiring treatment). Postsurgical intracranial changes determined by imaging techniques, postoperative complications, PACU and hospital stay, and mortality at 30 days were also recorded. Appropriate statistical tests were used for comparison; P<0.05 was considered as significant. This trial was registered in Eudract.ema.europa.eu (#2021-006290-40). RESULTS: There was no difference in brain relaxation: 2.00 [1.00-2.00] and 2.00 [1.75-3.00] for patients in mannitol and HS groups, respectively (P=0.804). Tumour size (OR: 0.99, 95% CI: 0.99-1.01; P=0.371), peritumoral oedema classification (OR: 0.57, 95% CI: 0.11-2.84; P=0.493), mass effect (OR: 0.86, 95% CI: 0.16-4.87; P=0.864), anaesthesia (OR: 4.88, 95% CI: 0.82-28.96; P=0.081) and midline shift (OR: 5.00, 95% CI: 0.84-29.70; P=0.077) did not have a significant influence on brain swelling in patients treated with either mannitol or HS. No significant differences in perioperative outcomes, mortality and length of PACU and hospital stay were observed. CONCLUSIONS: 5mL/kg of 20% mannitol or 3% HS result in similar brain relaxation scores in patients undergoing craniotomy for supratentorial brain tumour with midline shift.

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.

Neuropharmacology in the Intensive Care Unit.

Clinicians must individualize pharmacotherapy for patients with acute neurological injury based on multiple factors, including age, comorbidities, and chronic medication use. Many pharmacokinetic and pharmacodynamic properties are altered during acute illness, particularly absorption, distribution, metabolism, and elimination, which may result in loss of drug effect or toxicity. This article provides clinicians with general pharmacologic knowledge of the following drug regimens commonly prescribed to neurocritically ill adults: sedatives, analgesics, osmotherapy, antiseizure medications, antishivering agents, vasoactive agents, and antithrombotic reversal agents.

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.

Sodium-based osmotherapy for hyponatremia in acute decompensated heart failure.

Acute decompensated heart failure (ADHF) accounts for more than 1 million hospital admissions annually and is associated with high morbidity and mortality. Decongestion with removal of increased total body sodium and total body water are goals of treatment. Acute kidney injury (AKI) or chronic kidney disease (CKD) is present in two-thirds of patients with ADHF. The pathophysiology of ADHF and AKI is bidirectional and synergistic. AKI and CKD complicate the management of ADHF by decreasing diuretic efficiency and excretion of sodium and water. Among patients hospitalized with ADHF, hyponatremia is the most common electrolyte abnormality and is classically encountered with volume overload. ADHF represents an additional therapeutic challenge particularly when oligoanuria is present. Predilution continuous venovenous hemofiltration with sodium-based osmotherapy can safely increase plasma sodium concentration without deleteriously increasing total body sodium. We present a detailed methodology that addresses the issue of hypervolemic hyponatremia in patients with ADHF and AKI.

Efecto de la infusión de lactato de sodio 0.5 molar sobre el medio interno de pacientes críticos / Effect of half-molar sodium lactate infusion on biochemical parameters in critically ill patients

Objetivo Evaluar el impacto de la infusión de lactato de sodio 0,5M sobre variables del medio interno y sobre la presión intracraneana en pacientes críticos. Diseño Estudio prospectivo experimental de cohorte única. Ámbito Unidad de cuidados intensivos de un hospital universitario. Pacientes Pacientes con shock y neurocríticos con hipertensión intracraneana. Intervenciones Se infundió una carga de 500 cc de infusión de lactato de sodio 0,5M en 15 min y se midió el nivel plasmático de sodio, potasio, magnesio, calcio, cloro, lactato, bicarbonato, PaCO2 arterial, pH, fosfato y albúmina en 3 tiempos: T0 preinfusión; T1 a los 30 min y T2 a los 60 min postinfusión. Se midieron la presión arterial media y presión intracraneana en T0 y T2. Resultados Recibieron el fluido N=41: n=19 como osmoagente y 22 como expansor. Se constató alcalosis metabólica: T0 vs. T1 (p=0,007); T1 vs. T2 (p=0,003). La natremia aumentó en los 3 tiempos (T0 vs. T1; p<0,0001; T1 vs. T2; p=0,0001). Se demostró un descenso de la presión intracraneana (T0: 24,83±5,4 vs. T2: 15,06±5,8; p <0,001). El lactato aumentó inicialmente (T1) con un rápido descenso (T2) (p <0,0001), incluso en aquellos pacientes con hiperlactatemia basal (p=0,002). Conclusiones La infusión de lactato de sodio 0,5M genera alcalosis metabólica, hipernatremia, disminución de la cloremia y un cambio bifásico del lactato, y muestra eficacia en el descenso de la presión intracraneana en pacientes con daño encefálico agudo. (AU)

Objective To evaluate the impact of the infusion of sodium lactate 500ml upon different biochemical variables and intracranial pressure in patients admitted to the intensive care unit. Design A prospective experimental single cohort study was carried out. Scope Polyvalent intensive care unit of a university hospital. Patients Critical patients with shock and intracranial hypertension. Procedure A 500ml sodium lactate bolus was infused in 15min. Plasma levels of sodium, potassium, magnesium, calcium, chloride, lactate, bicarbonate, PaCO2, pH, phosphate and albumin were recorded at 3timepoints: T0 pre-infusion; T1 at 30minutes, and T2 at 60minutes post-infusion. Mean arterial pressure and intracranial pressure were measured at T0 and T2. Results Forty-one patients received sodium lactate: 19 as an osmotically active agent and 22 as a volume expander. Metabolic alkalosis was observed: T0 vs. T1 (P=0.007); T1 vs. T2 (P=0.003). Sodium increased at the 3time points (T0 vs. T1, P<0.0001; T1 vs. T2, P=0.0001). In addition, sodium lactate decreased intracranial pressure (T0: 24.83±5.4 vs. T2: 15.06±5.8; P<0.001). Likewise, plasma lactate showed a biphasic effect, with a rapid decrease at T2 (P<0.0001), including in those with previous hyperlactatemia (P=0.002). Conclusions The infusion of sodium lactate is associated to metabolic alkalosis, hypernatremia, reduced chloremia, and a biphasic change in plasma lactate levels. Moreover, a decrease in intracranial pressure was observed in patients with acute brain injury. (AU)

Effect of half-molar sodium lactate infusion on biochemical parameters in critically ill patients.

OBJECTIVE: To evaluate the impact of the infusion of sodium lactate 500ml upon different biochemical variables and intracranial pressure in patients admitted to the intensive care unit. DESIGN: A prospective experimental single cohort study was carried out. SCOPE: Polyvalent intensive care unit of a university hospital. PATIENTS: Critical patients with shock and intracranial hypertension. PROCEDURE: A 500ml sodium lactate bolus was infused in 15min. Plasma levels of sodium, potassium, magnesium, calcium, chloride, lactate, bicarbonate, PaCO2, pH, phosphate and albumin were recorded at 3 timepoints: T0 pre-infusion; T1 at 30min, and T2 at 60min post-infusion. Mean arterial pressure and intracranial pressure were measured at T0 and T2. RESULTS: Forty-one patients received sodium lactate: 19 as an osmotically active agent and 22 as a volume expander. Metabolic alkalosis was observed: T0 vs. T1 (p=0.007); T1 vs. T2 (p=0.003). Sodium increased at the 3 timepoints (T0 vs. T1, p<0.0001; T1 vs. T2, p=0.0001). In addition, sodium lactate decreased intracranial pressure (T0: 24.83±5.4 vs. T2: 15.06±5.8; p<0.001). Likewise, plasma lactate showed a biphasic effect, with a rapid decrease at T2 (p<0.0001), including in those with previous hyperlactatemia (p=0.002). CONCLUSIONS: The infusion of sodium lactate is associated to metabolic alkalosis, hypernatremia, reduced chloremia, and a biphasic change in plasma lactate levels. Moreover, a decrease in intracranial pressure was observed in patients with acute brain injury.

Traumatic Brain Injury-A Review of Intravenous Fluid Therapy.

This manuscript will review intravenous fluid therapy in traumatic brain injury. Both human and animal literature will be included. Basic treatment recommendations will also be discussed.

Effects of Volume Replacement for Urinary Losses from Mannitol Diuresis on Brain Water in Normal Rats.

BACKGROUND/OBJECTIVE: It is frequently recommended that urine output following perioperative mannitol administration be replaced 1:1 with an isotonic crystalloid solution. It is possible that this strategy could increase brain water by reducing the serum osmolality achieved with prior mannitol administration. Therefore, brain water content of rats treated with mannitol alone or mannitol plus normal saline (NS) was studied over a range of urinary replacement ratios. METHODS: Male Wister rats received mannitol 3.2 gm/100 gm infused over 45 min followed by hourly determinations of urine output (UO). Control animals received no additional therapy, whereas animals undergoing intervention received hourly replacement of their urinary losses with 0.9% NS in decreasing NS:UO ratios (1:1, 1:2, 1:3). Three hours after completion of the mannitol infusion, a final tally of UO was made. At that time in all animals, blood was obtained for determination of hemoglobin and electrolyte concentrations and plasma osmolality. Following that, the animals were sacrificed to determine brain water content. Additional groups underwent the same protocol but for 5 h with 1:1 urinary replacement, or received a volume of NS equal to that of the mannitol administered to all other control and intervention animals. RESULTS: 1:1 replacement of urinary loss with NS following mannitol administration was associated with brain water content indistinguishable from control animals receiving only a volume of NS equal to that of the mannitol administered to all other groups. Regression analysis demonstrated a decrease in the final brain water content of 0.67% (CI95 0.43-0.92, p < 0.001) per replacement level as NS:UO replacement ratios were decreased from 1:1 to 1:2 and, finally to 1:3. At the final NS:UO replacement ratio of 1:3, brain water content was indistinguishable from the control group receiving mannitol without NS replacement (p = 0.48) For 1:1 replacement following mannitol, brain water did not differ between experiments of 3 or 5 h duration (p = 0.52). CONCLUSIONS: In rats, NS replacement of UO 1:1 following mannitol administration leads to brain water content no different than if NS had been given in place of mannitol. Only when the NS:UO replacement ratio was 1:3, brain water was similar to that of control animals receiving mannitol alone. The recommendation to replace UO 1:1 with an equal volume of isotonic crystalloid following perioperative mannitol administration must recognize how this strategy could elevate brain water content compared to less vigorous replacement of UO.

Variability in Serum Sodium Concentration and Prognostic Significance in Severe Traumatic Brain Injury: A Multicenter Observational Study.

BACKGROUND/OBJECTIVE: 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. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.

Osmo- and cryotherapy of sugarcane (Saccharum spp. L.) shoot-tips infected with sugarcane mosaic virus (SCMV).

In this work, we investigated the effect of different osmoprotective treatments and of cryopreservation using a droplet-vitrification (D-V) protocol to eliminate sugarcane mosaic virus (SCMV) of shoot-tips excised from in vitro propagated infected plantlets. Shoot-tips of sugarcane (Saccharum spp. L.) were precultured on semisolid MS medium supplemented with 0.3 M sucrose for 1 day, loaded in solution with 0.4 M sucrose and 2 M glycerol for 30 min and exposed to plant vitrification solution 2 for 15 min at room temperature prior to ultra-rapid cooling in liquid nitrogen. Virus indexing was performed by the DAS-ELISA immunoenzymatic test. The presence of SCMV was confirmed in the donor-plantlets derived of infected field material. No virus was detected in the regenerated plantlets from shoot-tips subjected to cryopreservation protocol. The progressive decrease in absorbances occurred from the first preculture treatment and no significant differences (P ≤ 0.05) were found with respect to following steps of D-V protocol. These results indicate that the osmotic dehydration treatments (osmotherapy) and cryopreservation (cryotherapy) may be potentially effective strategies to remove the SCMV from infected plants.

Guidelines for the Acute Treatment of Cerebral Edema in Neurocritical Care Patients.

BACKGROUND: Acute treatment of cerebral edema and elevated intracranial pressure is a common issue in patients with neurological injury. Practical recommendations regarding selection and monitoring of therapies for initial management of cerebral edema for optimal efficacy and safety are generally lacking. This guideline evaluates the role of hyperosmolar agents (mannitol, HTS), corticosteroids, and selected non-pharmacologic therapies in the acute treatment of cerebral edema. Clinicians must be able to select appropriate therapies for initial cerebral edema management based on available evidence while balancing efficacy and safety. METHODS: The Neurocritical Care Society recruited experts in neurocritical care, nursing, and pharmacy to create a panel in 2017. The group generated 16 clinical questions related to initial management of cerebral edema in various neurological insults using the PICO format. A research librarian executed a comprehensive literature search through July 2018. The panel screened the identified articles for inclusion related to each specific PICO question and abstracted necessary information for pertinent publications. The panel used GRADE methodology to categorize the quality of evidence as high, moderate, low, or very low based on their confidence that the findings of each publication approximate the true effect of the therapy. RESULTS: The panel generated recommendations regarding initial management of cerebral edema in neurocritical care patients with subarachnoid hemorrhage, traumatic brain injury, acute ischemic stroke, intracerebral hemorrhage, bacterial meningitis, and hepatic encephalopathy. CONCLUSION: The available evidence suggests hyperosmolar therapy may be helpful in reducing ICP elevations or cerebral edema in patients with SAH, TBI, AIS, ICH, and HE, although neurological outcomes do not appear to be affected. Corticosteroids appear to be helpful in reducing cerebral edema in patients with bacterial meningitis, but not ICH. Differences in therapeutic response and safety may exist between HTS and mannitol. The use of these agents in these critical clinical situations merits close monitoring for adverse effects. There is a dire need for high-quality research to better inform clinicians of the best options for individualized care of patients with cerebral edema.

Standardized Volume Dosing Protocol of 23.4% Hypertonic Saline for Pediatric Critical Care: Initial Experience.

Background: Standardized volume dosing of 23.4% hypertonic saline (HTS) exists for adults, but the concentration, dosing and administration of HTS in pediatrics is variable. With emerging pediatric experience of 23.4% HTS, a standard volume dose approach may be helpful. Objective: To describe initial experience with a standardized 23.4% HTS weight-based volume dosing protocol of 10, 20, or 30 mL in the pediatric intensive care unit. Methods: Standard volume doses of 23.4% HTS were developed from weight dosing equivalents of 3% HTS. Pre and post sodium and intracranial pressure (ICP) measurements were compared with paired t-test or Wilcoxon rank-sum test. The site of administration and complications were noted. Results: A total of 16 pediatric patients received 37 doses of 23.4% HTS, with the smallest patient weighing 11 kg. For protocol compliance, 17 doses (46%) followed recommended dosing, 19 were less volume than recommended (51%), and 1 dose (3%) was more than recommended. Mean increase in sodium was 3.5 mEq/L (95% CI = 2-5 mEq/L); P < 0.0001. The median decrease in ICP was 10.5 mm Hg (interquartile range [IQR] 8.3-19.5) for a 37% (IQR 25%-64%) reduction. Most doses were administered through central venous access, although peripheral intravenous administrations occurred in 4 patients without complication. Conclusion and Relevance: Three standard-volume dose options of 23.4% HTS based on weight increases sodium and reduces ICP in pediatric patients. Standard-volume doses may simplify weight-based dosing, storage and administration for pediatric emergencies, although the optimum dose, and safety of 23.4% HTS in children remains unknown.

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.

Sodium-Based Osmotherapy in Continuous Renal Replacement Therapy: a Mathematical Approach.

Cerebral edema, in a variety of circumstances, may be accompanied by states of hyponatremia. The threat of brain injury from hypotonic stress-induced astrocyte demyelination is more common when vulnerable patients with hyponatremia who have end stage liver disease, traumatic brain injury, heart failure, or other conditions undergo overly rapid correction of hyponatremia. These scenarios, in the context of declining urinary output from CKD and/or AKI, may require controlled elevations of plasma tonicity vis-à-vis increases of the plasma sodium concentration. We offer a strategic solution to this problem via sodium-based osmotherapy applied through a conventional continuous RRT modality: predilution continuous venovenous hemofiltration.