Osmotic Therapy Research Articles

Cerebral Edema Monitoring and Management Strategies: Results from an International Practice Survey.

Cerebral edema is a common, potentially life-threatening complication in critically ill patients with acute brain injury. However, uncertainty remains regarding best monitoring and treatment strategies, which may result in wide practice variations. A 20-question digital survey on monitoring and management practices was disseminated between July 2022 and May 2023 to clinicians who manage cerebral edema. The survey was promoted through email, social media, medical conferences, and the Neurocritical Care Society Web site. We used the χ2 test, Fisher's exact test, analysis of variance, and logistic regression to report factors associated with practice variation, diagnostic monitoring methods, and therapeutic triggers based on practitioner and institutional characteristics. Of 321 participants from 160 institutions in 30 countries, 65% were from university-affiliated centers, 74% were attending physicians, 38% were woman, 38% had neurology training, and 55% were US-based. Eighty-four percent observed practice variations at their institutions, with "provider preference" being cited most (87%). Factors linked to variation included gender, experience, university affiliation, and practicing outside the United States. University affiliates tended to use more tests (median 3.87 vs. 3.43, p = 0.01) to monitor cerebral edema. Regarding management practices, 20% of respondents' preferred timing for decompressive hemicraniectomy was after 48h, and 37% stated that radiographic findings only would be sufficient to trigger surgery. Fifty percent of respondents reported initiating osmotic therapy based on radiographic indications or prophylactically. There were no significant associations between management strategies and respondent or center characteristics. Twenty-seven percent of respondents indicated that they acquired neuroimaging at intervals of 24h or less. Within this group, attending physicians were more likely to follow this practice (65.5% vs. 34.5%, p = 0.04). Cerebral edema monitoring and management strategies vary. Features associated with practice variations include both practitioner and institutional characteristics. We provide a foundation for understanding practice patterns that is crucial for informing educational initiatives, standardizing guidelines, and conducting future trials.

Hyperosmolar therapy response in traumatic brain injury: Explainable artificial intelligence based long-term time series forecasting approach

In the neurological intensive care setting implementing tier-based therapy, osmotic therapy serves as an intermediate approach for reducing intracranial pressure (ICP). However, discussions regarding quantitative and specific criteria for the maintenance and transition of treatment remain limited. This study proposes an explainable neural network forecasting of physiological responses after osmotic therapy administration for the purpose of treatment guidance. Recordings of arterial blood pressure and intracranial pressure were obtained from 107 patients with traumatic brain injury. To maintain adequate intracranial pressure, arterial blood pressure, and cerebral perfusion pressure, 20 % mannitol (100 ml; no. infusion, 3,571) and 11.3 % hypertonic saline (40 ml; no. infusion, 574) were administered. The LTSF-NLinear model was used to predict the target signal response for the subsequent 1 h. Six prediction models were derived by combining two agents (mannitol or hypertonic saline) and three target signals (mean arterial blood pressure, mean intracranial pressure and cerebral perfusion pressure). To validate the model’s robustness while considering patient heterogeneity, group (5)-fold cross-validation was implemented. To assess the predictive ability of the proposed model for adverse clinical events, binary classification of hypotension, intracranial hypertension, and cerebral hypoperfusion was performed. The overall function of the model was elucidated using linear weight visualization. Additionally, the DeepSHAP application allows for a detailed investigation of the prediction process for a single case. The relationship between response to osmotic therapy and patient outcomes was statistically significant. The proposed models achieved reasonable performance, with R2 score > 0.8 for physiological signal predictions and accuracy > 0.9 for event predictions. Through global explanation, the recent values of mean arterial blood pressure, mean intracranial pressure, and cerebral perfusion pressure of input signals significantly influenced physiological responses after osmotic treatment. In the context of local explanation (a single case), it was possible to determine how physiological state influenced the response. The proposed model is expected to provide objective and quantitative information on osmotherapy in neurological intensive care environments, enabling guidance for alternative and aggressive treatments. Thus, it can potentially aid in enhancing the prognosis of patients with traumatic brain injury and improving the clinical workflow. Moreover, the global and local explanations of the proposed model can provide valuable insights for future researchers.

Emergency decompressive surgery in patients with transtentorial brain herniation and pupillary abnormalities: the importance of improved pupillary response after osmotherapy and surgery.

The predictors of survival and functional recovery following emergency decompressive surgery in patients with transtentorial brain herniation, particularly those with pupillary abnormalities, have not been established. In this study, the authors aimed to assess the outcome of patients with intracranial mass lesions, transtentorial brain herniation, and nonreactive mydriasis, following emergency surgical decompression. A retrospective chart review was performed of all patients with transtentorial herniation and pupillary abnormalities who underwent craniotomy or craniectomy at two trauma and stroke centers between 2016 and 2022. The functional outcome was determined using the modified Rankin Scale (mRS). Forty-three patients, 34 men and 9 women with a mean age of 47 years (range 16-92 years), were included. The underlying etiology was traumatic brain injury in 33 patients, hemorrhagic stroke in 8 patients, and tumor in 2 patients. The median preoperative Glasgow Coma Scale score was 3 (range 3-8), and the median midline shift was 9 mm (range 1-29 mm). Thirty-two patients (74.4%) had bilaterally fixed and dilated pupils. The median time to surgery (from pupillary changes) was 133 minutes (mean 169 minutes, range 30-900 minutes). Eighteen patients (41.9%) died postoperatively. After a median follow-up of 12 months (range 3-12 months), 11 patients (26.8%) had a favorable functional outcome, while 10 remained severely disabled (mRS score 5). On univariate analysis, younger age (p < 0.001), less midline shift (p = 0.049), and improved pupillary response after osmotic therapy (p < 0.01) or decompressive surgery (p < 0.001) were associated with favorable outcomes at 3 months. With aggressive medical and surgical management, patients with transtentorial brain herniation, including those with bilaterally fixed and dilated pupils, may have considerable rates of survival and functional recovery. Young age, less midline shift, and improved pupillary response following osmotic therapy or decompressive surgery are favorable prognosticators.

A National Survey on Coma Epidemiology, Evaluation, and Therapy in India: Revisiting the Curing Coma Campaign Come Together Survey.

The limited representation from developing countries in the original COME TOGETHER survey gave us an impetus to conduct this survey in the Indian subcontinent. This cross-sectional online survey was conducted from August through September 2022. Participants were health care physicians caring for patients with coma and disorders of consciousness. Fischer's exact test or the Mann-Whitney U-test was used to compare respondents who agreed or disagreed with the preestablished coma definition. Fleiss κ values were calculated to assess agreement among respondents. A p value less than 0.05 was considered statistically significant. The survey was completed by 130 physicians. We found substantial interrater agreement on absence of wakefulness (71.54%; κ = 0.71), Glasgow Coma Score ≤ 8 (78.46%; κ = 0.78), and failure to respond purposefully to visual, verbal, or tactile stimuli (66.15%; κ = 0.66). Reported common etiologies of coma included traumatic brain injury (50.76%), ischemic stroke (30%), and intracerebral hemorrhage (29.23%). The most common clinical assessment tools used for coma included the Glasgow Coma Score (92.3%) and neurological examination (60.8%). Neurological examination was the most commondiagnostic tool used(100%), followed by magnetic resonance imaging (89.2%), basic laboratory studies (88.5%), and head computed tomography/angiography (86.9%). Pharmacological interventions used to stimulate arousal in patients with coma were sedation vacation (91.5%), electrolyte/endocrine correction (65.4%), osmotic therapy with mannitol (60%), hypertonic saline (54.6%), modafinil (46.9%), and antidote for drugs (45.4%). Among the nonpharmacological interventions, sensory stimulation (57.7%) was the most commonly used modality. The most common discharge disposition for comatose patients who survived hospitalization were home with or without services (70.0%). Differences from the global survey were noted regarding the following: traumatic brain injury being the most common etiology of coma in India, more frequent practice of sedation interruption, less frequent use of electroencephalography in India, rare use of pharmacological neurostimulants, and home being the most common discharge disposition in India.

Imaging biomarkers of cerebral edema automatically extracted from routine CT scans of large vessel occlusion strokes.

Volumetric and densitometric biomarkers have been proposed to better quantify cerebral edema after stroke, but their relative performance has not been rigorously evaluated. Patients with large vessel occlusion stroke from three institutions were analyzed. An automated pipeline extracted brain, cerebrospinal fluid (CSF), and infarct volumes from serial CTs. Several biomarkers were measured: change in global CSF volume from baseline (ΔCSF); ratio of CSF volumes between hemispheres (CSF ratio); and relative density of infarct region compared with mirrored contralateral region (net water uptake [NWU]). These were compared to radiographic standards, midline shift and relative hemispheric volume (RHV) and malignant edema, defined as deterioration resulting in need for osmotic therapy, decompressive surgery, or death. We analyzed 255 patients with 210 baseline CTs, 255 24-hour CTs, and 81 72-hour CTs. Of these, 35 (14%) developed malignant edema and 63 (27%) midline shift. CSF metrics could be calculated for 310 (92%), while NWU could only be obtained from 193 (57%). Peak midline shift was correlated with baseline CSF ratio (ρ=-.22) and with CSF ratio and ΔCSF at 24 hours (ρ=-.55/.63) and 72 hours (ρ=-.66/.69), but not with NWU (ρ=.15/.25). Similarly, CSF ratio was correlated with RHV (ρ=-.69/-.78), while NWU was not. Adjusting for age, National Institutes of Health Stroke Scale, tissue plasminogen activator treatment, and Alberta Stroke Program Early CT Score, CSF ratio (odds ratio [OR]:1.95 per 0.1, 95% confidence interval [CI]: 1.52-2.59) and ΔCSF at 24 hours (OR:1.87 per 10%, 95% CI: 1.47-2.49) were associated with malignant edema. CSF volumetric biomarkers can be automatically measured from almost all routine CTs and correlate better with standard edema endpoints than net water uptake.

The Role of Brain Tissue Oxygenation Monitoring in the Management of Subarachnoid Hemorrhage: A Scoping Review.

Monitoring of brain tissue oxygenation (PbtO2) is an important component of multimodal monitoring in traumatic brain injury. Over recent years, use of PbtO2 monitoring has also increased in patients with poor-grade subarachnoid hemorrhage (SAH), particularly in those with delayed cerebral ischemia. The aim of this scoping review was to summarize the current state of the art regarding the use of this invasive neuromonitoring tool in patients with SAH. Our results showed that PbtO2 monitoring is a safe and reliable method to assess regional cerebral tissue oxygenation and that PbtO2 represents the oxygen available in the brain interstitial space for aerobic energy production (i.e., the product of cerebral blood flow and the arterio-venous oxygen tension difference). The PbtO2 probe should be placed in the area at risk of ischemia (i.e., in the vascular territory in which cerebral vasospasm is expected to occur). The most widely used PbtO2 threshold to define brain tissue hypoxia and initiate specific treatment is between 15 and 20mm Hg. PbtO2 values can help identify the need for or the effects of various therapies, such as hyperventilation, hyperoxia, induced hypothermia, induced hypertension, red blood cell transfusion, osmotic therapy, and decompressive craniectomy. Finally, a low PbtO2 value is associated with a worse prognosis, and an increase of the PbtO2 value in response to treatment is a marker of good outcome.

Cortical Superficial Siderosis and Transient Focal Neurological Episode Preceding Lobar Hemorrhage in Cerebral Amyloid Angiopathy.

Cortical Superficial Siderosis and Transient Focal Neurological Episode Preceding Lobar Hemorrhage in Cerebral Amyloid Angiopathy.

Bilaterally Fixed and Dilated Pupils Are Not the Kiss of Death in Patients with Transtentorial Herniation: A Single Surgeon's Experience.

Bilaterally fixed and dilated pupils in the setting of transtentorial herniation have traditionally been considered a sign of futility. Such patients are often denied life-saving surgery based on the premise that meaningful functional recovery would be extremely unlikely. We sought to determine the survival and functional outcome in a cohort of patients who underwent aggressive medical and surgical management. Charts of all patients managed by a single surgeon over a 42-month period were retrospectively reviewed. Functional outcome was determined using modified Rankin Scale (mRS). Outcome was classified as good (mRS score 0-3), acceptable (mRS score 4), or poor (mRS score 5-6). Patients were 7 men and 2 women with a mean age of 36 years (range, 16-66 years). Etiologies included stroke (4 patients), traumatic brain injury (4 patients), and malignant cerebral edema (1 patient). Preoperative Glasgow Coma Scale scores ranged from 3 to 7, and midline shift was 7-16 mm. All patients received emergency osmotic therapy before decompressive surgery. Time to surgery (from pupillary changes) was <150 minutes for all patients (median 94 minutes; range, 50-148 minutes). At 3 months, 5 patients (55.6%) had recovered, achieving a good (n= 3) or acceptable (n= 2) outcome. The other 4 patients failed to recover and ultimately died of their injury. In well-selected patients with transtentorial herniation and bilaterally fixed and dilated pupils, aggressive and timely medical and surgical management may lead to substantial rates of survival and favorable functional outcome. Preconceived notions of a universally grim prognosis in such patients can lead to self-fulfilling prophecies.

Dividing Cells are Most Susceptible to Targeted Osmotic Lysis Cancer Therapy

Voltage‐gated sodium channels (VGSCs) are upregulated in aggressive carcinomas, making these channels a target for novel clinical therapies. Targeted Osmotic Lysis (TOL) is a novel cancer therapy that combines pharmacologically blocking Na+,K+, ATPase (sodium pumps) while stimulating VGSCs with a pulsed electric field. The consequent increase in intracellular Na+ causes an osmotic lysis of the cells that overexpress VGSCs. Noncancerous cells, with fewer VGSCs do not lyse. We hypothesized that variability in efficacy of TOL is due to VGSC expression that varies across the cell cycle. We assessed cell surface expression of VGSCs and Na+,K+‐ATPase during phases of the cell cycle in which there are single copies of DNA compared with phases in which DNA has doubled. For this, DNA was labeled with either propidium iodide (PI) or DAPI and VGSCs were labeled with a pan‐specific VGSC antibody while Na+,K+‐ATPases were labelled with a pan‐specific Na+,K+‐ATPase antibody in eight immortalized cancer and non‐cancer cell lines. With flow cytometry we showed that VGSC expression doubled during phases of cell division (S‐M phases) compared to G0‐G1 phases, whereas Na+,K+‐ATPase expression increased by 1.5‐fold. To investigate whether cells in S‐M phases are more susceptible to TOL due to the increase in VGSCs, cells were treated and immediately fixed and stained with PI for cell cycle analysis. There was a 30% decrease in the percentage of total cells that were treated with TOL compared to cells that did not receive TOL treatment. This finding is evidence that dividing cells are more susceptible to TOL than cells in G0‐G1 phases. It is thus likely that combined therapies will likely lead to better patient outcomes.

Acute Intracranial Hypertension During Pregnancy: Special Considerations and Management Adjustments.

Pregnancy is associated with a number of pathophysiological changes (including modification of vascular resistance, increased vascular permeability, and coagulative disorders) that can lead to specific (eclampsia, preeclampsia) or not specific (intracranial hemorrhage) neurological complications. In addition to these disorders, pregnancy can affect numerous preexisting neurologic conditions, including epilepsy, brain tumors, and intracerebral bleeding from cerebral aneurysm or arteriovenous malformations. Intracranial complications related to pregnancy can expose patients to a high risk of intracranial hypertension (IHT). Unfortunately, at present, the therapeutic measures that are generally adopted for the control of elevated intracranial pressure (ICP) in the general population have not been examined in pregnant patients, and their efficacy and safety for the mother and the fetus is still unknown. In addition, no specific guidelines for the application of the staircase approach, including escalating treatments with increasing intensity of level, for the management of IHT exist for this population. Although some of basic measures can be considered safe even in pregnant patients (management of stable hemodynamic and respiratory function, optimization of systemic physiology), some other interventions, such as hyperventilation, osmotic therapy, hypothermia, barbiturates, and decompressive craniectomy, can lead to specific concerns for the safety of both mother and fetus. The aim of this review is to summarize the neurological pathophysiological changes occurring during pregnancy and explore the effects of the possible therapeutic interventions applied to the general population for the management of IHT during pregnancy, taking into consideration ethical and clinical concerns as well as the decision for the timing of treatment and delivery.

Tier-three therapies for refractory intracranial hypertension in adult head trauma.

Refractory intracranial hypertension after traumatic brain injury (TBI) is defined as recurrent increase of intracranial pressure above 20-22 mmHg for sustained period of time (10-15 min), despite conventional therapies, such as osmotic therapy, cerebral spinal fluid drainage and mild hyperventilation. As such, more aggressive treatments should be taken into consideration. In particular, therapeutic hypothermia, barbiturates administration and decompressive craniectomy are considered as tier-three or "salvage" interventions, as they have shown to be able to control refractory hypertension; however, they are also associated with an increased risk of significant side effects. Therefore, the aim of this review was to describe the evidence supporting the use of these tier-three therapies in the management of refractory intracranial hypertension in TBI patients.

Hemispheric CSF volume ratio quantifies progression and severity of cerebral edema after acute hemispheric stroke

As swelling occurs, CSF is preferentially displaced from the ischemic hemisphere. The ratio of CSF volume in the stroke-affected hemisphere to that in the contralateral hemisphere may quantify the progression of cerebral edema. We automatically segmented CSF from 1,875 routine CTs performed within 96 hours of stroke onset in 924 participants of a stroke cohort study. In 737 subjects with follow-up imaging beyond 24-hours, edema severity was classified as affecting less than one-third of the hemisphere (CED-1), large hemispheric infarction (LHI, over one-third the hemisphere), without midline shift (CED-2) or with midline shift (CED-3). Malignant edema was LHI resulting in deterioration, requiring osmotic therapy, surgery, or resulting in death. Hemispheric CSF ratio was lower on baseline CT in those with LHI (0.91 vs. 0.97, p < 0.0001) and decreased more rapidly in those with LHI who developed midline shift (0.01 per hour for CED-3 vs. 0.004/hour CED-2). The ratio at 24-hours was lower in those with midline shift (0.41, IQR 0.30–0.57 vs. 0.66, 0.56–0.81 for CED-2). A ratio below 0.50 provided 90% sensitivity, 82% specificity for predicting malignant edema among those with LHI (AUC 0.91, 0.85–0.96). This suggests that the hemispheric CSF ratio may provide an accessible early biomarker of edema severity.

Time Series Analysis and Prediction of Intracranial Pressure Using Time-Varying Dynamic Linear Models.

Intracranial pressure (ICP) monitoring is a key clinical tool in the assessment and treatment of patients in a neuro-intensive care unit (neuro-ICU). As such, a deeper understanding of how an individual patient's ICP can be influenced by therapeutic interventions could improve clinical decision-making. A pilot application of a time-varying dynamic linear model was conducted using the BrainIT dataset, a multi-centre European dataset containing temporaneous treatment and vital-sign recordings. The study included 106 patients with a minimum of 27h of ICP monitoring. The model was trained on the first 24h of each patient's ICU stay, and then the next 2h of ICP was forecast. The algorithm enabled switching between three interventional states: analgesia, osmotic therapy and paralysis, with the inclusion of arterial blood pressure, age and gender as exogenous regressors. The overall median absolute error was 2.98 (2.41-5.24) mmHg calculated using all 106 2-h forecasts. This is a novel technique which shows some promise for forecasting ICP with an adequate accuracy of approximately 3mmHg. Further optimisation is required for the algorithm to become a usable clinical tool.

Acute Kidney Injury in Traumatic Brain Injury Patients: Results From the Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury Study.

Acute kidney injury is frequent in polytrauma patients, and it is associated with increased mortality and extended hospital length of stay. However, the specific prevalence of acute kidney injury after traumatic brain injury is less recognized. The present study aims to describe the occurrence rate, risk factors, timing, and association with outcome of acute kidney injury in a large cohort of traumatic brain injury patients. The Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury is a multicenter, prospective observational, longitudinal, cohort study. Sixty-five ICUs across Europe. For the present study, we selected 4,509 traumatic brain injury patients with an ICU length of stay greater than 72 hours and with at least two serum creatinine values during the first 7 days of ICU stay. We classified acute kidney injury in three stages according to the Kidney Disease Improving Global Outcome criteria: acute kidney injury stage 1 equals to serum creatinine × 1.5-1.9 times from baseline or an increase greater than or equal to 0.3 mg/dL in 48 hours; acute kidney injury stage 2 equals to serum creatinine × 2-2.9 times baseline; acute kidney injury stage 3 equals to serum creatinine × three times baseline or greater than or equal to 4 mg/dL or need for renal replacement therapy. Standard reporting techniques were used to report incidences. A multivariable Cox regression analysis was performed to model the cause-specific hazard of acute kidney injury and its association with the long-term outcome. We included a total of 1,262 patients. The occurrence rate of acute kidney injury during the first week was as follows: acute kidney injury stage 1 equals to 8% (n = 100), acute kidney injury stage 2 equals to 1% (n = 14), and acute kidney injury stage 3 equals to 3% (n = 36). Acute kidney injury occurred early after ICU admission, with a median of 2 days (interquartile range 1-4 d). Renal history (hazard ratio = 2.48; 95% CI, 1.39-4.43; p = 0.002), insulin-dependent diabetes (hazard ratio = 2.52; 95% CI, 1.22-5.197; p = 0.012), hypernatremia (hazard ratio = 1.88; 95% CI, 1.31-2.71; p = 0.001), and osmotic therapy administration (hazard ratio = 2.08; 95% CI, 1.45-2.99; p < 0.001) were significantly associated with the risk of developing acute kidney injury. Acute kidney injury was also associated with an increased ICU length of stay and with a higher probability of 6 months unfavorable Extended Glasgow Outcome Scale and mortality. Acute kidney injury after traumatic brain injury is an early phenomenon, affecting about one in 10 patients. Its occurrence negatively impacts mortality and neurologic outcome at 6 months. Osmotic therapy use during ICU stay could be a modifiable risk factor.

Predictive value of the sequential organ failure assessment (SOFA) score for prognosis in patients with severe acute ischemic stroke: a retrospective study.

ObjectiveTo identify the risk factors for early death and determine the predictive value of the sequential organ failure assessment (SOFA) score for prognosis of severe acute ischemic stroke (AIS).MethodsA total of 110 patients with severe AIS were enrolled and divided into the non-survivor (n = 34) and survivor groups (n = 76). Logistic regression analysis was conducted to identify risk factors for early death, while the receiver operator characteristic (ROC) curve was used to determine the predictive effect of the SOFA score on prognosis.ResultsLogistic regression analysis showed that urinary tract infection (odds ratio [OR] = 17.364, 95% confidence interval [CI]: 1.903–158.427), mechanical ventilation (OR = 1.754, 95% CI: 1.648–2.219), and osmotic therapy (OR = 2.835, 95% CI: 1.871–5.102) were significantly correlated with early death of severe AIS. ROC curve analysis of the area under the curve after hospitalization showed that the maximum SOFA and ΔSOFA scores exceeded 0.7.ConclusionOur study shows that urinary tract infection, mechanical ventilation, and osmotic therapy are risk factors for early death of severe AIS. The SOFA score has good predictive value for prognosis of severe AIS. These findings may provide a guideline for improving clinical outcome.

Hyperosmolar Treatment for Patients at Risk for Increased Intracranial Pressure: A Single-Center Cohort Study.

Treatment with osmoactive agents such as mannitol or hypertonic saline (HTS) solutions is widely used to manage or prevent the increase of intracranial pressure (ICP) in central nervous system (CNS) disorders. We sought to evaluate the variability and mean plasma concentrations of the water and electrolyte balance parameters in critically ill patients treated with osmotic therapy and their influence on mortality. This cohort study covered patients hospitalized in an intensive care unit (ICU) from January 2017 to June 2019 with presumed increased ICP or considered to be at risk of it, treated with 15% mannitol (G1, n = 27), a combination of 15% mannitol and 10% hypertonic saline (HTS) (G2, n = 33) or 10% HTS only (G3, n = 13). Coefficients of variation (Cv) and arithmetic means (mean) were calculated for the parameters reflecting the water and electrolyte balance, i.e., sodium (NaCv/NaMean), chloride (ClCv/ClMean) and osmolality (mOsmCv/mOsmMean). In-hospital mortality was also analyzed. The study group comprised 73 individuals (36 men, 49%). Mortality was 67% (n = 49). Median NaCv (G1: p = 0.002, G3: p = 0.03), ClCv (G1: p = 0.02, G3: p = 0.04) and mOsmCv (G1: p = 0.001, G3: p = 0.02) were higher in deceased patients. NaMean (p = 0.004), ClMean (p = 0.04), mOsmMean (p = 0.003) were higher in deceased patients in G3. In G1: NaCv (AUC = 0.929, p < 0.0001), ClCv (AUC = 0.817, p = 0.0005), mOsmCv (AUC = 0.937, p < 0.0001) and in G3: NaMean (AUC = 0.976, p < 0.001), mOsmCv (AUC = 0.881, p = 0.002), mOsmMean (AUC = 1.00, p < 0.001) were the best predictors of mortality. The overall mortality prediction for combined G1+G2+G3 was very good, with AUC = 0.886 (p = 0.0002). The mortality of critically ill patients treated with osmotic agents is high. Electrolyte disequilibrium is the independent predictor of mortality regardless of the treatment method used. Variations of plasma sodium, chloride and osmolality are the most deleterious factors regardless of the absolute values of these parameters

Topical osmotic therapy for a prolapsed incarcerated ostomy

Abstract Introduction Ostomy Prolapses are common complications in ostomized patients with some studies showing a 38% incidence in pediatric population (Husain and Cataldo, 2008; Robertson et al., 2005) [1,2]. Some prolapses remain incarcerated demanding urgent surgery. In the last decades the use of osmotic agents to reduce incarcerated prolapses had been used in adult patients, but although safe, the technique was yet still unused in pediatric patients (Theofanis et al., 2017; Mohammed et al., 2013) [3,4]. Case report Osmotic therapy with 30 g of granulated sugar was used in a five year old patient with a 12 cm long incarcerated ostomy prolapsed ileum. After the ostomic therapy the stoma edema was significantly reduced allowing manual reduction of the incarcerated strap. Discussion The use of sugar as an osmotic agent in this patient, has proven to be effective, since it avoided performing an emergency surgery and the use of both sedation or anesthesia.

Genesis of Antibiotic Resistance LIX: Fluid Resuscitation Induced Aberrant Intracranial Pressure (“Monroe‐Kellie” Doctrine (MKD) Contort Tethered Leucocytes / Platelets Crest “Critical Closing Pressure” (CCP)

NCT01663701 noted that the median volume of iv fluid administered within 6 hours of presenting to ER in the sepsis intervention group was 3.5 L. The mean volume administered during the similar time interval in prior sepsis resuscitation trials were 5.0 L (EGDT); 5.1 L (ProCESS); and 4.5 L (ARISE). Criticisms of NCT01663701 such as a. the suggested vs administered median volume of fluid administered during the initial phase of resuscitation in the sepsis protocol group (3.5L) may have been higher than the 30 mL/kg recommended by SSC guidelines; b.”Each 1‐hour delay in antibiotic administration was associated with an absolute increase in mortality in the range of 5% to 10%”; and c. the median volume of iv fluid administered between ER presentation and 6 hours for BMI 18.5 kg/m2 ~ 70 mL/kg, here we present a plausible pathophysiological sequel as a contributing factor for mortality rate. Within the six hrs. of fluid resuscitation, a surge of fluid bolus mounted an adverse pressure gradient on the sphincters in metarterioles deregulating the pulsatile blood flow into the capillary bed. Based on the “Whole Brain Fluid and Osmolyte Network Model or” or “The whole brain network” approach a mechanistic model inclusive of major cranial compartments simulated the effect of osmotic therapy predicted that critical intracranial pressure (ICP) increased to &gt;30 mmHg, with insufficient cerebral perfusion, and ventriculomegaly. The ventricular enlargement, in turn, reduces extracellular milieu for fluid exchange lead to a chronic increase in ventricular size shifts attributed to osmolyte administered. It is our hypothesis that after fluid resuscitation blood flows against an adverse pressure gradient in the capillary bed. The fluid particles such as activated and/or aggregating Cellular Aggregates near to the endothelial layer due to their low kinetic energy, “Cellular Aggregates” flows in the opposite direction. Such Cellular Aggregates cannot surmount the adverse pressure, lead to the formation of eddies. Such eddies in the arterial end are likely to cause local flow reversal zone and which retard the velocity concurrently the pressure of the blood flow. Under the low velocity and pressure gradient, the cellular eddies start separating from the endothelium referred to as boundary layer separation causing the blood flow to decelerate against an adverse pressure gradient. Then in the upstream part which is the venous end of the capillary bed, where the cellular eddies achieve boundary layer separation, causing blood pressure to drop from that of the arterial end creating the eddies to drag. At this stage, the pressure distribution in the capillary bed is at the stagnation point, where the velocity becomes zero at which cellular eddies form DIC. Sustained fluid bolus with vasopressor likely to form a non‐pulsatile flow pattern forming turbulent eddies in the venous end and disseminate the coagulated eddies leading to an aberration in the “MKD”. Dysregulated ICP, in turn, alter the ARGR leading to hypoperfusion subsequently coma.Support or Funding InformationSupported by pd funds and in part CME activities of Subburaj Kannan MD PhD for www.aaets.org

Abstract 63: Infarct Volume and Rate of Edema Growth Predicts Need for Intervention in Patients With Cerebellar Infarction

Background: Predictors of malignant edema in patients with acute cerebellar infarction are understudied. We hypothesized that greater infarct volume and CT-defined edema growth would predict individuals requiring acute intervention. Methods: Admissions to a tertiary care neurological ICU with acute cerebellar infarction over three year period were identified. Primary endpoint was defined as needing medical and/or surgical “intervention”: osmotic therapy, extra-ventricular drainage, or surgical decompression. Visible regions of infarct-related hypodensity in the cerebellum were manually outlined on serial CTs to ascertain infarct volumes. Infarct ratio was defined as the ratio of infarct volume to posterior fossa volume on initial CT showing ischemia. Rate in infarct-related edema growth was measured as the change in infarct ratio over time between sequential head CTs. Results: Of the 60 patients identified, 27 (45%) received interventions. All except one received osmotic therapy, while 15 patients underwent surgical intervention. Compared with the no-intervention cohort, intervention cohort was more likely to have diabetes (21% vs 48%, p = 0.03) and larger initial infarct ratio (0.12 vs 0.22, p = 0.001). Diabetes (OR, 6.3 95% CI, 1.6-25.3) and infarct ratio (OR, 3.2; 95% Cl, 1.6-6.3) were independent predictors of intervention. The rate of edema growth was faster in the intervention cohort (time*cohort p =0.005) (Fig A). A subgroup analysis of 34 patients with at least 3 CTs showed the intervention cohort had greater edema growth rate (-0.0001/hr vs 0.0044/hr, p = 0.02). Multivariate analysis showed edema growth independently predicted intervention (Fig B) and improved the AUC from 0.78 to 0.90 (Fig C), while diabetes was not retained (p=0.056). Conclusion: Baseline infarct ratio and rate of edema growth within the first 4 days may provide clinically useful markers to select patients with cerebellar infarction who will benefit from intervention.

Complications Associated with Osmotic Therapy in Acute Stroke Patients- A Prospective Longitudinal Observational Study

Introduction: Mannitol is one of the most frequently used drugs to treat cerebral oedema resulting from ischemic and haemorrhagic strokes. Mannitol administration is associated with complications such as Acute Kidney Injury (AKI) and electrolyte imbalance. Aim: To study effect of mannitol therapy on electrolyte levels and renal function in acute stroke patients. Materials and Methods: The present prospective longitudinal observational study was carried out from January 2019 till September 2019 in Father Muller Medical College, Mangalore, India. After taking informed consent, patients with acute stroke who received mannitol were recruited into the study. Nature of the stroke, presence of comorbidities and dosage of mannitol given were recorded. Serum electrolytes, Serum urea and creatinine were recorded at admission and on fifth day. Serum urea was measured by enzymatic photometric method using urease and glutamate dehydrogenase and serum creatinine was measured by Jaffe’s kinetic method. Comparison of data among different groups was performed using student t-test, ANOVA test, Mann-whitney test and Pearson test. The p-values &lt;0.05 were taken as statistically significant. Results: Total of 72 patients were included in the study. Mean age was 57.7±14.6 years and male: female ratio was 2.27:1. Of the total study subjects, 16 suffered from diabetes (22.22%), 40 from hypertension (55.55%). Ischemic stroke was seen in 41.66% patients and haemorrhagic stroke was seen in 58.33% of the patients. The dose of mannitol administered to all the patients was less than 1 gram/kg/day (low dose mannitol). Cumulative dose of mannitol was 180±177.3 grams. Serum sodium levels were significantly lower on fifth day compared to admission (p-value 0.030) whereas serum potassium and chloride levels were not significantly changed during therapy. There was statistically significant elevation in serum urea levels from admission to fifth day (p-value &lt;0.001) whereas creatinine levels were not significantly altered. Total cumulative dose was compared to serum electrolyte levels and urea and creatinine at admission and fifth day and no significant changes were found. On analysing comorbidities, electrolyte fluctuations were more common in diabetics and Chronic Kidney Disease (CKD) patients whereas renal function parameters were abnormal in diabetics, CKD and hypertensive patients. None of the patients needed any corrective measures to treat the dyselectrolytemias or altered renal function. Conclusion: Low dose mannitol therapy does not produce any significant electrolyte or renal function abnormality in patients with acute stroke. Careful monitoring may be required while treating patients with additional comorbidities.