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Hyperosmotic therapy is commonly used to treat intracranial hypertension in traumatic brain injury patients. Unfortunately, hyperosmolality also affects other organs. An increase in plasma osmolality may impair kidney, cardiac, and immune function, and increase blood–brain barrier permeability. These effects are related not only to the type of hype...
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Context 1
... improves the rheological properties of the blood and the osmotic activity of aquaporin receptors in the BBB [21,22]. Clinicians commonly use HTS with different 3%, 7.5%, or 23.4% solutions, and each of those presents a different osmotic activity (Table 1) [21,22]. Regardless of the type of the osmotically active agents, the main target of osmotherapy is to maintain plasma osmolality around 300-320 mOsm/kg H 2 O [1,2]. ...Citations
... Hyperosmotic therapy is used to treat intracranial hypertension in patients with traumatic brain injury [29]. However, even with this treatment, it is recommended to keep the osmolality below 320 mOsm/kg H2O, as higher levels may cause heart and immune system problems [30]. In the first experiment, the volume administered (500 mL) was small compared to the body weight (min: 45 kg, max: 75 kg); therefore, no significant clinical signs or symptoms were observed. ...
Background
Fluid therapy in veterinary medicine is pivotal for treating various conditions in pigs; however, standard solutions, such as Hartmann’s solution, may not optimally align with pig physiology. This study explored the development and efficacy of a customized fluid therapy tailored to the ionic concentrations of pig blood, aiming to enhance treatment outcomes and safety in both healthy and diseased pigs.
Results
The study involved two experiments: the first to assess the safety and stability of customized fluids in healthy pigs, and the second to evaluate the efficacy in pigs with clinical symptoms of dehydration. In healthy pigs, the administration of customized fluids showed no adverse effects, with slight alterations observed in pO2, hematocrit, and glucose levels in some groups. In symptomatic pigs, the customized fluid group did not show any improvement in clinical symptoms, with no significant changes in blood chemistry or metabolite levels compared to controls. The customized fluid group showed a mild increase in some values after administration, yet within normal physiological ranges. The study reported no significant improvements in clinical or dehydration status, attributing the observed variations in blood test results to the limited sample size and anaesthesia effects rather than fluid characteristics.
Conclusions
Customized fluid therapy, tailored to mimic the ionic concentrations of pig blood, appears to be a safe and potentially more effective alternative to conventional solutions such as Hartmann’s solution for treating pigs under various health conditions. Further research with larger sample sizes and controlled conditions is recommended to validate these findings and to explore the full potential of customized fluid therapy in veterinary practice.
... During this phase, his hypernatremia significantly worsened (plasma sodium concentration corrected to glucose by the Hillier formula had a peak of 174 mEq/L on DOH 13) due to excessive electrolyte-free urinary water loss, a well-described phenomenon during this phase of ATN. Serum osmolality was calculated using Smithline and Gardner formula [1,2] (2 × sodium + glucose/18 + BUN/2.8). Measured serum osmolality on DOH 6 was 354 mOsm/kg and calculated serum osmolality was 347 mOsm/kg, indicating that there was no excess osmolar gap (normal osmolar gap < 10 Osm/kg). ...
... Acute increases in serum osmolality can trigger osmotic fluid shifts across the BBB, decreasing the volume of neuronal and glial cells [2]. The BBB prevents the passage of sodium. ...
... The BBB prevents the passage of sodium. Abrupt increases in serum sodium levels can result in significant adjustments to the volumes of neuronal and glial cells, leading to demyelination and programmed cell death (ODS) [2]. Cells can adapt by uptake of intracellular osmoles to prevent shrinkage, although it is unclear how fast this adaptation can occur. ...
... Hyperosmotic therapy is used to treat intracranial hypertension in patients with traumatic brain injury (26). Nevertheless, despite undergoing this treatment, it is advised that the osmolality should not exceed 320 mOsm/kg H2O, as osmolality over 310 mOsm/kg H2O may lead to the development of cardiac and immune system diseases (27). In the rst experiment, the volume administered (500 mL) was small compared to the body weight (min: 45 kg, max: 75 kg); therefore, no signi cant clinical signs or symptoms were observed. ...
Background
Fluid therapy in veterinary medicine is pivotal for treating various conditions in pigs; however, standard solutions, such as Hartmann's solution, may not optimally align with pig physiology. This study explored the development and efficacy of a customized fluid therapy tailored to the ionic concentrations of pig blood, aiming to enhance treatment outcomes and safety in both healthy and diseased pigs.
Results
The study involved two experiments: the first to assess the safety and stability of customized fluids in healthy pigs, and the second to evaluate the efficacy in pigs with clinical symptoms of dehydration. In healthy pigs, the administration of customized fluids showed no adverse effects, with slight alterations observed in pO2, Hematocrit, and glucose levels in some groups. In symptomatic pigs, the customized fluid group did not show any improvement in clinical symptoms, with no significant changes in blood chemistry or metabolite levels compared to controls. The customized fluid group showed a mild increase in some values after administration, yet within normal physiological ranges. The study reported no significant improvements in clinical or dehydration status, attributing the observed variations in blood test results to the limited sample size and anaesthesia effects rather than fluid characteristics.
Conclusions
Customized fluid therapy, tailored to mimic the ionic concentrations of pig blood, appears to be a safe and potentially more effective alternative to conventional solutions such as Hartmann’s solution for treating pigs under various health conditions. Further research with larger sample sizes and controlled conditions is recommended to validate these findings and to explore the full potential of customized fluid therapy in veterinary practice.
... The decision to place invasive neuromonitors was collaborative between pediatric critical care and pediatric neurosurgery based on disease severity, potential for reversibility (regaining of brainstem reflexes with initial ICP lowering therapies), and absence of contraindications (thrombocytopenia, coagulopathy, local infection). Although data are sparse for use of this technology outside of TBI, we anticipated that a tailored approach to treating increased ICP and cerebral hypoxia could minimize secondary neurologic injury, as well as iatrogenic effects of therapies used to treat increased ICP (e.g., hyperventilation, neuromuscular blockade [21,22], and hypernatremia/hyperchloremia [23]). Furthermore, growing appreciation for the potential role for invasive neuromonitoring in neuroinflammatory disease is reflected in the proposed best practice recommendations by the Autoimmune Encephalitis Clinicians Network, which advises consideration in cases with severe edema (24). ...
Background
Myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) is an inflammatory disorder of the CNS with a variety of clinical manifestations, including cerebral edema.
Case Summary
A 7-year-old boy presented with headaches, nausea, and somnolence. He was found to have cerebral edema that progressed to brainstem herniation. Invasive multimodality neuromonitoring was initiated to guide management of intracranial hypertension and cerebral hypoxia while he received empiric therapies for neuroinflammation. Workup revealed serum myelin oligodendrocyte glycoprotein antibodies. He survived with a favorable neurologic outcome.
Conclusion
We describe a child who presented with cerebral edema and was ultimately diagnosed with MOGAD. Much of his management was guided using data from invasive multimodality neuromonitoring. Invasive multimodality neuromonitoring may have utility in managing life-threatening cerebral edema due to neuroinflammation.
... Hyperosmolality persists throughout the procedure (309 mOsm/kg in Gunnar's population) and normalizes only on the first postoperative day. Hyperosmotic environment causes a water shift from the cells to the extracellular compartment, which may damage organs such as the kidneys or the brain and disrupt the immune system's function [94]. Plasma osmolality of 320 mOsm/kg is reported to increase the risk of AKI. ...
... Plasma osmolality of 320 mOsm/kg is reported to increase the risk of AKI. Dąbrowski et al. [94] also mention that hyperosmolality is especially detrimental to the kidneys as it forces osmotic diuresis within the glomerulus, thus reducing medullary blood flow. ...
Introduction: According to different authors, cardiac surgery-associated acute kidney injury (CSA-AKI) incidence can be as high as 20–50%. This complication increases postoperative morbidity and mortality and impairs long-term kidney function in some patients. This review aims to summarize current knowledge regarding alterations to renal physiology during cardiopulmonary bypass (CPB) and to discuss possible nephroprotective strategies for cardiac surgeries. Relevant sections: Systemic and renal circulation, Vasoactive drugs, Fluid balance and Osmotic regulation and Inflammatory response. Conclusions: Considering the available scientific evidence, it is concluded that adequate kidney perfusion and fluid balance are the most critical factors determining postoperative kidney function. By adequate perfusion, one should understand perfusion with proper oxygen delivery and sufficient perfusion pressure. Maintaining the fluid balance is imperative for a normal kidney filtration process, which is essential for preserving the intra- and postoperative kidney function. Future directions: The review of the available literature regarding kidney function during cardiac surgery revealed a need for a more holistic approach to this subject.
... Furthermore, TBI patients with AKI have a higher risk of sepsis. For TBI patients, post-traumatic sympathetic nervous system activation, increased plasma catecholamine level, elevated systolic blood pressure, low blood volume, cytokine cascade reaction, and osmotic therapy of intracranial hypertension will bring a higher risk of kidney injury [27,28]. The changes in intrathoracic pressure related to mechanical ventilation disrupt the systemic hemodynamics, resulting in biological damage such as decreased glomerular filtration rate, decreased creatinine clearance rate, and apoptosis of renal epithelial cells [29]. ...
Purpose
Traumatic brain injury (TBI) patients admitted to the intensive care unit (ICU) are at a high risk of infection and sepsis. However, there are few studies on predicting secondary sepsis in TBI patients in the ICU. This study aimed to build a prediction model for the risk of secondary sepsis in TBI patients in the ICU, and provide effective information for clinical diagnosis and treatment.
Methods
Using the MIMIC IV database version 2.0 (Medical Information Mart for Intensive Care IV), we searched data on TBI patients admitted to ICU and considered them as a study cohort. The extracted data included patient demographic information, laboratory indicators, complications, and other clinical data. The study cohort was divided into a training cohort and a validation cohort. In the training cohort, variables were screened by LASSO (Least absolute shrinkage and selection operator) regression and stepwise Logistic regression to assess the predictive ability of each feature on the incidence of patients. The screened variables were included in the final Logistic regression model. Finally, the decision curve, calibration curve, and receiver operating character (ROC) were used to test the performance of the model.
Results
Finally, a total of 1167 patients were included in the study, and these patients were randomly divided into the training (N = 817) and validation (N = 350) cohorts at a ratio of 7:3. In the training cohort, seven features were identified as key predictors of secondary sepsis in TBI patients in the ICU, including acute kidney injury (AKI), anemia, invasive ventilation, GCS (Glasgow Coma Scale) score, lactic acid, and blood calcium level, which were included in the final model. The areas under the ROC curve in the training cohort and the validation cohort were 0.756 and 0.711, respectively. The calibration curve and ROC curve show that the model has favorable predictive accuracy, while the decision curve shows that the model has favorable clinical benefits with good and robust predictive efficiency.
Conclusion
We have developed a nomogram model for predicting secondary sepsis in TBI patients admitted to the ICU, which can provide useful predictive information for clinical decision-making.
... Current interventions include the use of drugs such as mannitol or bradykinin analog (Cereport/RMP7) to induce disruption of barrier function. Hypertonic mannitol, reduces tight junction integrity through endothelial cell contraction (Dabrowski et al., 2021), but its limitation is that it may cause seizures (Marchi et al., 2007). Cereport/RMP-7 has shown some potential to transiently increase BBB permeability (Borlongan and Emerich, 2003) and has shown some efficacy in animal models for the treatment of CNS pathology, but has not yielded satisfactory results in clinical trials (Prados et al., 2003). ...
This review outlined evidence that purinergic signaling is involved in the modulation of blood-brain barrier (BBB) permeability. The functional and structural integrity of the BBB is critical for maintaining the homeostasis of the brain microenvironment. BBB integrity is maintained primarily by endothelial cells and basement membrane but also be regulated by pericytes, neurons, astrocytes, microglia and oligodendrocytes. In this review, we summarized the purinergic receptors and nucleotidases expressed on BBB cells and focused on the regulation of BBB permeability by purinergic signaling. The permeability of BBB is regulated by a series of purinergic receptors classified as P2Y 1 , P2Y 4 , P2Y 12 , P2X4, P2X7, A 1 , A 2A , A 2B , and A 3 , which serve as targets for endogenous ATP, ADP, or adenosine. P2Y 1 and P2Y 4 antagonists could attenuate BBB damage. In contrast, P2Y 12 -mediated chemotaxis of microglial cell processes is necessary for rapid closure of the BBB after BBB breakdown. Antagonists of P2X4 and P2X7 inhibit the activation of these receptors, reduce the release of interleukin-1 beta (IL-1β), and promote the function of BBB closure. In addition, the CD39/CD73 nucleotidase axis participates in extracellular adenosine metabolism and promotes BBB permeability through A 1 and A 2A on BBB cells. Furthermore, A 2B and A 3 receptor agonists protect BBB integrity. Thus, the regulation of the BBB by purinergic signaling is complex and affects the opening and closing of the BBB through different pathways. Appropriate selective agonists/antagonists of purinergic receptors and corresponding enzyme inhibitors could modulate the permeability of the BBB, effectively delivering therapeutic drugs/cells to the central nervous system (CNS) or limiting the entry of inflammatory immune cells into the brain and re-establishing CNS homeostasis.
... Iatrogenic factors, including exposure to radiocontrast agents, nephrotoxic antibiotics and anti-inflammatory agents [6], must also be considered in brain-injured patients. The treatment of intracranial hypertension may also contribute to the development of AKI [7]. ...
... Overall, 22% were receiving chronic treatment with antiplatelets or anticoagulants. The median Glasgow coma score was 11 (interquartile range [6][7][8][9][10][11][12][13][14]. Up to 26.2% of the patients received prehospital intubation. ...
... In summary, the neuroendocrine pathway, including the central nervous autonomous system and the endocrine system, and the inflammatory and immune responses play a major role in its development [5,6]. Patient-, trauma-, iatrogenic-or treatment-related factors may contribute [5][6][7]. Indeed, the Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) showed that an AKI incidence of 12% of cases in a sample of 1262 TBI patients was associated with patients' previous conditions (renal history and insulin-dependent diabetes), trauma (pupillary reactivity) and treatments received (osmotic therapy and natremia ≥ 150 mmol/L in the initial 3 days after injury) [8]. More recently, Luu et al., in the largest sample of severe TBI patients, found that 2.1% of patients had severe AKI (acute kidney injury network stage 3 or higher) [9]. ...
Our objective was to analyze the contribution of acute kidney injury (AKI) to the mortality of isolated TBI patients and its associated risk factors. Observational, prospective and multicenter registry (RETRAUCI) methods were used, from March 2015 to December 2019. Isolated TBI was defined as abbreviated injury scale (AIS) ≥ 3 head with no additional score ≥ 3. A comparison of groups was conducted using the Wilcoxon test, chi-square test or Fisher’s exact test, as appropriate. A multiple logistic regression analysis was conducted to analyze associated risk factors in the development of AKI. For the result, overall, 2964 (30.2%) had AIS head ≥ 3 with no other area with AIS ≥ 3. The mean age was 54.7 (SD 19.5) years, 76% were men, and the ground-level falls was 49.1%. The mean ISS was 18.4 (SD 8). The in-hospital mortality was 22.2%. Up to 310 patients (10.6%) developed AKI, which was associated with increased mortality (39% vs. 17%, adjusted OR 2.2). Associated risk factors (odds ratio (OR) (95% confidence interval)) were age (OR 1.02 (1.01–1.02)), hemodynamic instability (OR 2.87 to OR 5.83 (1.79–13.1)), rhabdomyolysis (OR 2.94 (1.69–5.11)), trauma-associated coagulopathy (OR 1.67 (1.05–2.66)) and transfusion of packed red-blood-cell concentrates (OR 1.76 (1.12–2.76)). In conclusion, AKI occurred in 10.6% of isolated TBI patients and was associated with increased mortality.
... In humans, cerebral edema resulting from brain injury is frequently treated with hyperosmotic therapy to relieve inter cranial hypertension [11]. However, recent evidence suggests that elevating plasma osmolality can also lead to increased QTc and a higher risk of cardiac arrhythmias [12,13]. We therefore sought to determine what effect osmotic perturbations had on zebrafish ECG patterns. ...
The use of zebrafish to explore cardiac physiology has been widely adopted within the scientific community. Whether this animal model can be used to determine drug cardiac toxicity via electrocardiogram (ECG) analysis is still an ongoing question. Several reports indicate that the recording configuration severely affects the ECG waveforms and its derived-parameters, emphasizing the need for improved characterization. To address this problem, we recorded ECGs from adult zebrafish hearts in three different configurations (unexposed heart, exposed heart, and extracted heart) to identify the most reliable method to explore ECG recordings at baseline and in response to commonly used clinical therapies. We found that the exposed heart configuration provided the most reliable and reproducible ECG recordings of waveforms and intervals. We were unable to determine T wave morphology in unexposed hearts. In extracted hearts, ECG intervals were lengthened and P waves were unstable. However, in the exposed heart configuration, we were able to reliably record ECGs and subsequently establish the QT-RR relationship (Holzgrefe correction) in response to changes in heart rate.
... In humans, cerebral edema resulting from brain injury is frequently treated with hyperosmotic therapy to relieve inter cranial hypertension [32]. However, recent evidence suggests that elevating plasma osmolality can also lead to increased QTc and a higher risk of cardiac arrhythmias [33,34]. We therefore sought to determine what effect osmotic perturbations had on zebrafish ECG patterns. ...
Background
The use of zebrafish to explore cardiac physiology has been widely adopted within the scientific community. Whether this animal model can be used to determine drug cardiac toxicity via electrocardiogram (ECG) analysis, is still an ongoing question. Several reports indicate that the recording configuration severely affects the ECG waveforms and its derived-parameters, emphasizing the need for improved characterization.
Methods
ECGs were recorded from adult zebrafish hearts in 3 different configurations (unexposed heart, exposed heart and extracted heart) to identify the most reliable method to explore ECG recordings at baseline and in response to commonly used clinical therapies.
Results
We found that the exposed heart configuration provided the most reliable and reproducible ECG recordings of waveforms and intervals. We were unable to determine T-wave morphology in unexposed hearts. In extracted hearts, ECG intervals were lengthened and P-waves were unstable. However, in the exposed heart configuration, we were able to reliably record ECGs and subsequently establish the QT-RR relationship (Holzgrefe correction) in response to changes in heart rate.
Conclusions
The exposed heart configuration appears to be the most reliable technique to record ECGs in adult zebrafish. In this configuration, the QT-RR relationship, an important parameter in cardiac toxicity evaluation, can be determined using the Holzgrefe correction.
