Fluid Infusion Research Articles

Embracing uncertainty in cerebrospinal fluid dynamics: A Bayesian approach to analysing infusion studies

IntroductionCerebrospinal fluid (CSF) infusion test analysis allows recognizing and appropriately evaluating CSF dynamics in the context of normal pressure hydrocephalus (NPH), which is crucial for effective diagnosis and treatment. However, existing methodology possesses drawbacks that may compromise the precision and interpretation of CSF dynamics parameters. Research questionThis study aims to circumvent these constraints by introducing an innovative analysis method grounded in Bayesian inference. Material and methodsA single-centre retrospective cohort study was conducted on 858 patients who underwent a computerized CSF infusion test between 2004 and 2020. We developed a Bayesian framework-based method for parameter estimation and compared the results to the current, gradient descent-based approach. We evaluated the accuracy and reliability of both methods by analysing erroneous prediction rates and curve fitting errors. ResultsThe Bayesian method surpasses the gradient descent approach, reflected in reduced inaccurate prediction rates and an improved goodness of model fit. On whole cohort level both techniques produced comparable results. However, the Bayesian method holds an added advantage by providing uncertainty intervals for each parameter. Sensitivity analysis revealed significance of the CSF production rate parameter and its interplay with other variables. The resistance to CSF outflow demonstrated excellent robustness. Discussion and conclusionThe proposed Bayesian approach offers a promising solution for improving robustness of CSF dynamics assessment in NPH, based on CSF infusion tests. Additional provision of the uncertainty measure for each diagnostic metric may perhaps help to explain occasional poor diagnostic performance of the test, offering a robust framework for improved understanding and management of NPH.

Anaphylaxis mortality in the perioperative setting: Epidemiology, elicitors, risk factors and knowledge gaps.

Perioperative anaphylaxis (PA) is a severe condition that can be fatal, but data on PA mortality are scarce. The aim of this article is to review the epidemiology, elicitors and risk factors for PA mortality and identify knowledge gaps and areas for improvement regarding the management of severe PA. PA affects about 100 cases per million procedures. Mortality is rare, estimated at 3 to 5 cases per million procedures, but the PA mortality rate is higher than for other anaphylaxis aetiologies, at 1.4% to 4.8%. However, the data are incomplete. Published data mention neuromuscular blocking agents and antibiotics, mainly penicillin and cefazolin, as the main causes of fatal PA. Reported risk factors for fatal PA vary in different countries. Most frequently occurring comorbidities are obesity, male gender, cardiovascular diseases and ongoing treatment with beta-blockers. However, there are no clues about how these factors interact and the impact of individual risk factors. The pathophysiology of fatal PA is still not completely known. Genetic factors such as deficiency in PAF-acetyl hydrolase and hereditary alpha-tryptasemia, have been reported as modulators of severe anaphylaxis and possible targets for specific treatments. Our review underlines unmet needs in the field of fatal PA. Although we confirmed the need for timely administration of an adequate dose of adrenaline and the proper infusion of fluids, there is no evidence-based data on the proper dose of intravenous titrated adrenaline and which clinical manifestations would flag the need for fluid therapy. There are no large clinical studies supporting the administration of alternative vasopressors, such as glucagon and methylene blue. Further research on pathophysiological mechanisms of PA and its severity may address these issues and help clinicians to define new therapeutic approaches.

Peripherally Inserted Central Catheter (PICC) Guidelines - Nursing Perspective

A Peripherally Inserted Central Catheter PICC is a form of intravenous line that grants access to the central venous system. It is inserted through a vein in the arm and then carefully advanced until it reaches a large vein close to the heart. The PICC has one two or three separate channels called lumens that can be used for different purposes such as blood sampling medication administration fluid infusion and other interventions. Each lumen has a cap and a connector that prevents contamination and allows needle-free access. Venous access is crucial for many patients who need frequent or complex treatments such as critically ill patients who require blood tests drugs that affect blood pressure fluid replacement long-term antibiotics and other indications.

A mathematical model for simulation of cardiovascular, renal, and hormonal responses to burn injury and resuscitation.

Treating extensive burn injury requires an individually tailored resuscitation protocol that includes hourly-titrated intravenous fluid infusion to avert both hypovolemic shock and edema. Due to the complexity of burn pathophysiology and significant variability in treatment protocols, there is an ongoing effort to optimize burn resuscitation. The goal of this work is to contribute to this effort by developing a mathematical model of burn pathophysiology and resuscitation for in silico testing of burn resuscitation protocols and decision-support systems. In our previous work, we developed and validated a mathematical model consisting of volume kinetics, burn-induced perturbations, and kidney function. In this work, we expanded our previous mathematical model to incorporate novel mathematical models of cardiovascular system and hormonal system (renin-angiotensin-aldosterone (RAAS) system and antidiuretic hormone) which affect blood volume and pressure regulation. We also developed a detailed mathematical model of kidney function to regulate blood volume, pressure, and sodium levels, including components for glomerular filtration rate, reabsorption rates in nephron tubules, Tubuglomerular feedback, and myogenic mechanisms. We trained and validated the expanded mathematical model using experimental data from 15 pigs and 9 sheep with extensive burns to quantitatively evaluate its prediction accuracy for hematocrit, cardiac output, mean arterial pressure, central venous pressure, serum sodium levels, and urinary output. We then trained and tested the mathematical model using a clinical dataset of 233 human burn patients with demographic data and urinary output measurements. The mathematical model could predict all tested variables very well, while internal variables and estimated parameters were consistent with the literature. To the best of our knowledge, this is the first mathematical model of burn injury and resuscitation which is extensively validated to replicate actual burn patients. Hence, this in silico platform may complement large animal pre-clinical testing of burn resuscitation protocols. Beyond its primary purpose, the mathematical model can be used as a training tool for healthcare providers delivering insight into the pathophysiology of burn shock, and offering novel mathematical models of human physiology which can be independently used for other purposes and contexts.

IOT IV Bag Monitoring and Termination System

Abstract: This paper introduces an innovative IoT-based Intravenous (IV) Bag Monitoring and Termination System designed to address critical challenges in traditional IV therapy. The proposed system leverages advanced sensors and connectivity to monitor IV bag parameters in real-time, ensuring accurate and timely administration of medical fluids. The system comprises a network of smart sensors integrated into IV bags, capable of continuously measuring fluid volume, infusion rate, and temperature. These parameters are wirelessly transmitted to a centralized control unit, providing healthcare professionals with comprehensive and up-to-the-minute data. The IoT IV Bag Monitoring and Termination System offers an intelligent alert mechanism to notify healthcare providers of any deviations from prescribed values, facilitating proactive intervention and minimizing the risk of complications. This ensures patient safety by preventing over-infusion or under-infusion scenarios. The proposed system not only improves the precision of IV therapy but also streamlines healthcare workflows, reducing the burden on medical staff and enhancing overall patient care.

Optimalisasi Alat Monitoring Tetes Infus Kristaloid Berbasis Mikrokontroler ATMega328

In the medical world, supervision of intravenous devices is a priority and the main one to ensure proper and measurable fluid delivery to patients. This research focuses on the development of a crystalloid infusion drip monitoring device using a microcontroller. The background of this research arises from the need for a device that is able to monitor drip infusions automatically, reduce the workload of medical personnel and increase patient safety. The methods used in this study include designing, manufacturing, and testing on tools. Photodiode sensors are selected as the main component in detecting drops of crystalloid liquid. This tool is designed to optimize other supporting sensors to be integrated as instruction modules in counting infusion fluid drops. The application of microcontroller technology in affordable infusion monitoring devices has not been widely adopted in medical practice. This research is driven by the need for reliable monitoring tools in a fast-paced medical environment and requires precision. The results of this study showed that the developed tool succeeded in optimizing the function of the photodiode sensor in counting drops of 99% crystalloid liquid produced accurately. This tool is able to operate in accordance with its original purpose, namely as a monitoring tool as well as a reminder for patient safety. The conclusion is that this microcontroller-based crystalloid infusion drip monitoring device is an innovation and good practice in the medical field. This tool not only increases efficiency in infusion monitoring but also provides additional safety for patients.

Predictive modeling of perioperative blood transfusion in lumbar posterior interbody fusion using machine learning.

Background: Accurate estimation of perioperative blood transfusion risk in lumbar posterior interbody fusion is essential to reduce the number, cost, and complications associated with blood transfusions. Machine learning algorithms have the potential to outperform traditional prediction methods in predicting perioperative blood transfusion. This study aimed to construct a machine learning-based perioperative transfusion risk prediction model for lumbar posterior interbody fusion in order to improve the efficacy of surgical decision-making. Methods: We retrospectively collected clinical data on 1905 patients who underwent lumbar posterior interbody fusion surgery at the Second Hospital of Shanxi Medical University between January 2021 and March 2023. All the data was randomly divided into a training set and a validation set, and the "feature_importances" method provided by eXtreme Gradient Boosting (XGBoost) algorithm was applied to select statistically significant features on the training set to establish five machine learning prediction models. The optimal model was identified by utilizing the area under the curve (AUC) and the probability calibration curve on the validation set. Shapley additive explanations (SHAP) and local interpretable model-agnostic explanations (LIME) were employed for interpretable analysis of the optimal model. Results: In the postoperative outcomes of patients, the number of hospital days in the transfusion group was longer than that in the non-transfusion group. Additionally, the transfusion group experienced higher total hospital costs, 90-day readmission rates, and complication rates within 90days after surgery than the non-transfusion group. A total of 9 features were selected for the models. The XGBoost model performed best with an AUC value of 0.958. The SHAP values showed that intraoperative blood loss, intraoperative fluid infusion, and number of fused segments were the top 3 most important features affecting perioperative blood transfusion in lumbar posterior interbody fusion. The LIME algorithm was used to interpret the individualized prediction. Conclusion: Surgery, ASA class, levels fused, total intraoperative blood loss, operative time, and preoperative Hb are viable predictors of perioperative blood transfusion in lumbar posterior interbody fusion. The XGBoost model has demonstrated superior predictive efficacy compared to the traditional logistic regression model, making it a more effective decision-making tool for perioperative blood transfusion.

Quantitative analysis of microplastics and nanoplastics released from disposable PVC infusion tubes

The exposure of micro- and nanoplastics (MNPs) via medical device is still unknown to us. Herein, a visual quantitative detection of polyvinyl chloride (PVC) MPs and a fluorescent quantitative detection of PVC NPs were developed. To overcome the aggregation of PVC NPs, sodium dodecylbenzene sulfonate was used as the stabilizer of PVC NPs. The brand-new disposable PVC infusion tubes were found to carry PVC MPs with the average total number (ATN) of 931.4 particles and PVC NPs with the average mass of 0.040 μg, respectively. For four typical infusion fluids such as 0.9% sodium chloride, 5% glucose, 5% sodium bicarbonate, hydroxyethyl starch 40 sodium chloride, the released PVC MPs and NPs were ranged from 1003.6 ∼ 3494.6 particles and 0.042 ∼ 0.087 μg, respectively in stimulating normal infusion scenario (room temperature 4 h). The released PVC MPs and NPs were also increased with the infusion duration and temperature. The released PVC MPs are mainly in granular form, accounting for 38 ∼ 49% of the total PVC MPs. Our findings indicate PVC MNPs can enter the blood vessel directly with the infusion fluids during intravenous infusion and the PVC MNPs exposure risk towards patients deserves more attention.

Plasma Volume Oscillations during Fluid Therapy in Humans

Introduction: Oscillations are frequently observed on plasma dilution curves during intravenous fluid therapy. This study aimed to examine how common these oscillations are and what they represent. Methods: Fourier transforms were used to analyze the residuals obtained during fitting of a volume kinetic model to 269 plasma dilution curves. Oscillating patterns were identified in two-thirds of the fluid infusion experiments. Results: The wave frequency usually had a dominating frequency of 1 h or multiples thereof. The wave amplitudes varied between 1% and 4% of the plasma volume. The “peak-to-peak” amplitudes were then twice as large, which corresponded to blood volume changes of 60–240 mL. A population kinetic analysis of the distribution of infused fluid between body fluid compartments was then applied to search for clues that could explain the oscillations. This analysis showed that amplitudes >1.5% were associated with doubled turnover of fluid in a fast-exchange interstitial fluid compartment and, together with data on plasma albumin, suggested that oscillations might represent bursts of efferent lymph. Conclusions: Oscillations with very low frequency were often observed on plasma dilution-time curves obtained during fluid therapy. They were associated with fast turnover of interstitial fluid and can possibly have resulted from accelerated lymphatic flow.

Baseline plethysmographic signal of arterial pulse during polysomnography: a potential insight into venous return and its clinical implications

Pulse oximetry is based on the technique of photoplethysmography. It is known that the pulsatile arterial component can provide a range of information, such as arterial blood oxygen saturation, the response to fluid infusion, and the nature of respiratory events during sleep. Until now, little importance has been given to the venous component of the plethysmographic signal, which is non-pulsatile but subject to volumetric variations in relation to changes in endopleuric pressure.Respiratory-induced intensity variations contained in the baseline of the photoplethysmographic signal have been well documented. We hypothesize that in polysomnography, variations in the baseline of the plethysmographic signal (referred to as the BPS, baseline plethysmographic signal) reflect variations in venous return induced by respiration, and that these variations present morphological aspects that could have clinical utility in the interpretation of polysomnographic signals, particularly regarding respiratory effort associated with respiratory events, their nature (central or obstructive), and the hemodynamic alterations associated with them.This article presents a selection of polysomnographic traces and images with physiopathological considerations that support our hypothesis.

Maldistribution of fluid in preeclampsia: a secondary kinetic analysis

BackgroundHypovolemia and peripheral edema are frequent components of preeclampsia. The level of the dysregulation of the body fluid distribution is unclear, which complicates the choice of infusion fluid during surgery. The present fluid kinetic study challenges whether the maldistribution of fluid is due to increased capillary leakage or to poor return of already distributed fluid, which occurs via lymphatic pathways. MethodsRingeŕs solution was infused in 10 awake non-pregnant women, eight healthy pregnant women, and in eight women with mild-to-moderately severe preeclampsia. Distribution and redistribution of the infused fluid was calculated with mixed models kinetics based on the excreted urine volumes and 675 measurements of hemodilution. Differences in fluid kinetics between the three groups were studied with covariance analysis. ResultsThe return flow of fluid volume to the plasma after distribution (rate parameter k21) was almost zero in women with preeclampsia, while the rate was normal in the other two groups (P< 0.001). By contrast, the capillary leakage rate of fluid in response to the infusion (k12) was normal. The urinary excretion (k10) was moderately accelerated. ConclusionDecreased flow of extravascular fluid to the plasma was the key disturbance in women with preeclampsia. Such decreased flow alone promotes hypovolemia, peripheral edema, and hypoalbuminemia, and may be explained by inhibition of lymphatic pumping and/or a decreased interstitial hydrostatic pressure due to the presence of vasoactive and inflammatory signal molecules. The moderately accelerated urine flow may be due to “pressure diuresis” in response to hypertension.

A 39-Year-Old Woman Presented with Abdominal Pain (colic), Vomiting and Right Lower Quadrant Abdominal Pain

&lt;p&gt;急性腹痛為急診常見主訴之一，其中成人腸套疊診斷著實罕見，以腹部絞痛、噁心嘔吐及腹脹為臨床表現，若未及時處置，病患可能因為腸段套疊造成腸阻塞，導致腸壁缺血、壞死或穿孔，甚至惡化為腹膜炎或敗血症。本文個案為一位39歲女性，因上腹絞痛、嘔吐及右下腹痛至急診求治，藉由病史收集、身體評估、實驗室檢驗無法確立診斷，於腹部電腦斷層檢查後確診為迴腸結腸腸套疊，因此緊急安排腸套疊復位手術，術中發現被套入包覆的闌尾已腫脹發炎，一併執行闌尾切除手術；個案經手術介入後給予充足輸液、傷口照護與多策略方式止痛，恢復漸進式飲食與活動後順利出院。成人腸套疊罕見且缺乏特異性症狀，導因多元且常與腫瘤相關，其次為感染等特發性因素，藉由身體評估困難診斷，因此建議臨床照護人員，當成人病患出現腹部絞痛、噁心嘔吐及腹脹表現時，應考慮納入腸套疊，盡速安排腹部電腦斷層診斷，評估是否需要介入手術治療，以提供病患適切即時的醫療照護。&lt;/p&gt; &lt;p&gt;&amp;nbsp;&lt;/p&gt;&lt;p&gt;Acute abdominal pain is one of the most common complaints of patients admitted to emergency unit but the diagnosis of intussusception in adults is really rare. The clinical symptoms include abdominal pain (colic), nausea, vomiting and distension. Obstruction, ischemia, necrosis, or perforation of the bowel could be induced by intussusception, and even deteriorating into peritonitis or sepsis if not be-ing treated properly. The case in this study is a 39-years-old woman presented with acute abdominal pain (colic), vomiting and right lower quadrant abdominal pain. The diagnosis could not be established by medical history taking, physical examination and laboratory survey. Ileocolic intussusception was diagnosed by abdominal computed tomography, and reduction of intussusception was arranged ur-gently. Swollen appendix with inflammation was also noted during the operation, thus appendectomy was performed. The patient was discharged after progressive diet and treatments such as providing ad-equate fluid infusion, wound and pain management. Adult intussusception is rare and lack of specific symptoms. The causes of intussusception are various and often related to tumors or sometimes idio-pathic factors such as infection. It is difficult to diagnose intussusception through physical examina-tion. Therefore, intussusception should be considered when adult experience abdominal colic, nausea, vomiting and distension. Abdominal computed tomography should be arranged as soon as possible, and surgical intervention should be provided appropriately for immediate medical care for patients.&lt;/p&gt; &lt;p&gt;&amp;nbsp;&lt;/p&gt;

High blood viscosity in acute ischemic stroke.

The changes in blood viscosity can influence the shear stress at the vessel wall, but there is limited evidence regarding the impact on thrombogenesis and acute stroke. We aimed to investigate the effect of blood viscosity on stroke and the clinical utility of blood viscosity measurements obtained immediately upon hospital arrival. Patients with suspected stroke visiting the hospital within 24 h of the last known well time were enrolled. Point-of-care testing was used to obtain blood viscosity measurements before intravenous fluid infusion. Blood viscosity was measured as the reactive torque generated at three oscillatory frequencies (1, 5, and 10 rad/sec). Blood viscosity results were compared among patients with ischemic stroke, hemorrhagic stroke, and stroke mimics diagnosed as other than stroke. Among 112 enrolled patients, blood viscosity measurements were accomplished within 2.4 ± 1.3 min of vessel puncture. At an oscillatory frequency of 10 rad/sec, blood viscosity differed significantly between the ischemic stroke (24.2 ± 4.9 centipoise, cP) and stroke mimic groups (17.8 ± 6.5 cP, p < 0.001). This finding was consistent at different oscillatory frequencies (134.2 ± 46.3 vs. 102.4 ± 47.2 at 1 rad/sec and 39.2 ± 11.5 vs. 30.4 ± 12.4 at 5 rad/sec, Ps < 0.001), suggesting a relationship between decreases in viscosity and shear rate. The area under the receiver operating curve for differentiating cases of stroke from stroke mimic was 0.79 (95% confidence interval, 0.69-0.88). Patients with ischemic stroke exhibit increases in whole blood viscosity, suggesting that blood viscosity measurements can aid in differentiating ischemic stroke from other diseases.

Iatrogenic Hyperhydration in Sickle Cell Disease Patients Admitted for Acute Pain Crisis Management: A Retrospective Analysis from a Single Institution

Background: Parenteral fluids are an important component of acute pain crisis management in sickle cell disease patients. However, lack of uniform guidelines for fluid replacement coupled with underlying host comorbidities result in risk to patients from complications associated with hyperhydration. Contributing factors include inappropriate choice of fluid, rapid fluid infusion rates with prolonged time periods and inadequate monitoring of signs of hyperhydration. Complications of fluid replacement include excessive weight gain, extremity swelling, pulmonary edema and heart failure. In our study we examined the prevalence of hyperhydration in sickle cell anemia patients admitted for acute pain crisis management at our hospital. Methods: We conducted a retrospective chart review on EPIC of sickle cell anemia patients treated for acute pain crisis in the inpatient unit of John Dempsey Hospital, University of Connecticut between January 2022-December 2022, following IRB approval. To capture patients with signs and symptoms of hyperhydration and its clinical consequences, we looked at surrogate markers such as excessive weight gain during admission, signs of fluid retention, charting of patient fluid intake and output, increased oxygen use, diuretic (Lasix) administration, bronchodilator use, abnormal chest x ray findings indicative of fluid overload pattern, activation of rapid response team for patients developing acute symptoms of fluid overload, and urgent patient transfer to a higher level of care including intensive care unit. Results: 256 admitted patient charts were analyzed representing a total of 95 unique sickle cell disease patients. The median length of hospital stay (LOS) was 3 days. 168 patients had LOS from 3 to 10 days. We observed that 10.7% of the patients experienced an increase in oxygen requirements during their hospital stay. Daily weight was collected in only 27 patients (10.5%) for 3 or more days limiting its usefulness to detect subclinical hyperhydration( figure 1). 69 patients (27%) received parenteral Lasix injection for acute symptoms whose chest x rays also showed pulmonary edema or pleural effusions. 13 patients (18%) were transferred to a higher level of care that included 9 patients to step-down unit and 4 to intensive care for endotracheal intubations and ventilatory support. The median hospital stay was 4 days in patients requiring Lasix compared to 3 days in those who did not. Conclusion : Hyperhydration is undesirable complication associated with fluid administration of sickle cell anemia patients admitted with acute vaso-occlusive pain crisis. It occurs in a significant proportion of affected patients that can result in life threatening complications and prolonged hospitalization. Hyperhydration were missed in this retrospective analysis since daily weight measurements were not available in the majority of patients. Strict charting of fluid intake and output, choice of half normal saline for hydration, as well as clinical monitoring of signs and symptoms of subclinical hyperhydration will help reduce this complication and improve patient outcomes. Improving awareness of this complication among health care providers is important towards achieving this goals. Findings from this study are used to design a prospective quality improvement project in our hospital to improve outcomes and reduce hospitalization in sickle cell anemia patients admitted for acute vaso-occlusive pain crisis.

Simulation of gravity- and pump-driven perfusion techniques for measuring outflow facility of ex vivo and in vivo eyes.

Aqueous humor dynamics are commonly assessed by infusing fluid into the eye and measuring intraocular pressure (IOP). From the pressure-flow relationship, conventional outflow facility is estimated to study glaucomatous processes that lower facility or identify therapeutics that enhance facility in hopes of restoring healthy IOP levels. The relative merits and limitations of constant flow (CF), gravity-driven constant pressure (CPg), and pump-driven constant pressure (CPp) infusion techniques were explored via simulations of a lumped parameter viscoelastic model of the eye. Model parameter values were based on published perfusion system properties and outflow facility data from rodents. Step increases in pressure or flow were simulated without and with IOP noise recorded from enucleated eyes, anesthetized animals, and conscious animals. Steady-state response levels were determined using published window and ratio criteria. Model simulations show that all perfusion techniques estimate facility accurately and that ocular fluid dynamics set a hard limit on how fast measurements can be taken. This limit can be approached with CPg and CPp systems by increasing their gain but not with CF systems, which invariably take longest to settle. Facility experiment duration is further lengthened by inclusion of IOP noise, and data filtering is needed for steady-state detection with in vivo noise. The ratio criterion was particularly affected because noise in the flow data is amplified by the higher gain of CPg and CPp systems. A recursive regression method is introduced, which can ignore large transient IOP fluctuations that interfere with steady-state detection by fitting incoming data to the viscoelastic eye model. The fitting method greatly speeds up data collection without loss of accuracy, which could enable outflow facility measurements in conscious animals. The model may be generalized to study response dynamics to fluid infusion in other viscoelastic compartments of the body and model insights extended to optimize experiment design.

Are dynamic measurements of central venous pressure in Fontan circulation during exercise or volume loading superior to resting measurements?

The main objective measure to assess the health of the Fontan circulation is the pressure measurement of the superior vena cava or pulmonary arteries. We reviewed the literature for benefits of measuring resting pressure in the Fontan circuit and explored whether dynamic measurement by volume loading or exercise has the potential to refine this diagnostic tool. PubMed was searched for articles showing a relationship between resting post-operative central venous pressure or pulmonary artery pressure and Fontan failure. Relationships between post-operative central venous pressure or pulmonary artery pressure and volume loading changes, such as during exercise or volume loading during cardiac catheterization, were also queried. A total of 44 articles mentioned relationships between resting central venous pressure or pulmonary artery pressure and Fontan failure. Only 26 included an analysis between the variables and only seven of those articles found pressure to be predictive of Fontan failure. Ten articles examined the relationship between exercise or volume loading and outcomes and demonstrated a large individual variation of pressures under these dynamic conditions. Based on current literature, there is not a lot of strong evidence to show that elevated resting central venous pressure or pulmonary artery pressure is predictive of Fontan failure. Some individuals experience dramatic increases in central venous pressure or pulmonary artery pressure under increased loading conditions with exercise or bolus fluid infusion, while others experience increases closer to that of a healthy control population. Further studies are needed to examine whether more dynamic and continuous monitoring of systemic venous pressures might better predict outcomes in patients with Fontan circulation.

Effect on capillary refill time of volume expansion and increase of the norepinephrine dose in patients with septic shock

BackgroundCapillary refill time (CRT) has been suggested as a variable to follow during the course of septic shock. We systematically investigated the effects on CRT of volume expansion and norepinephrine.MethodsIn 69 septic shock patients, we recorded mean arterial pressure (MAP), cardiac index (CI), and 5 consecutive CRT measurements (video method, standardized pressure applied on the fingertip) before and after a 500-mL saline infusion in 33 patients and before and after an increase of the norepinephrine dose in 36 different patients. Fluid responders were defined by an increase in CI ≥ 15%, and norepinephrine responders by an increase in MAP ≥ 15%.ResultsThe least significant change of CRT was 23%, so that changes in CRT were considered significant if larger than 23%. With volume expansion, CRT remained unchanged on average in patients with baseline CRT < 3 s (n = 7) and in all but one patient with baseline CRT ≥ 3 s in whom fluid increased CI < 15% (n = 13 “fluid non-responders”). In fluid responders with baseline CRT ≥ 3 s (n = 13), CRT decreased in 8 patients and remained unchanged in the others, exhibiting a dissociation between CI and CRT responses. The proportion of patients included > 24 h after starting norepinephrine was higher in patients with such a dissociation than in the other ones (60% vs. 0%, respectively). Norepinephrine did not change CRT significantly (except in one patient) if baseline CRT was ≥ 3 s and the increase in MAP < 15% (n = 6). In norepinephrine responders with prolonged baseline CRT (n = 11), it increased in 4 patients and remained unchanged in the other ones, which exhibited a dissociation between MAP and CRT responses.ConclusionsIn septic shock patients with prolonged CRT, CRT very rarely improves with treatment when volume expansion increases cardiac output < 15% and increasing norepinephrine increases MAP < 15%. When the effects of fluid infusion on cardiac output and of norepinephrine on MAP are significant, the response of CRT is variable, as it decreases in some patients and remains stable in others which exhibit a dissociation between changes in macrohemodynamic variables and in CRT. In this regard, CRT behaves as a marker of microcirculation.Trial registration: ClinicalTrial.gov (NCT04870892). Registered January15, 2021. Ethics committee approval CE SRLF 21-25.

Rehydration Rates and Outcomes in Overweight Children With Diabetic Ketoacidosis.

The Pediatric Emergency Care Applied Research Network Fluid Therapies Under Investigation in Diabetic Ketoacidosis (DKA) (FLUID) Trial found that rapid fluid infusion does not increase the risk of cerebral injury. Concern persists, however, whether fluid rates should be adjusted for overweight or obese patients. We used the FLUID Trial database to evaluate associations between fluid infusion rate and outcomes in these patients. We compared children and youth who were overweight, obese, or normal weight, in regard to protocol adherence, mental status changes, time to DKA resolution, and electrolyte abnormalities. We investigated associations between outcomes and the amount of fluid received in these groups. Obese children and youth were more likely to receive fluids at rates slower than dictated by protocol. Overweight and obese children and youth in the fast fluid arms, who received fluids per the study protocol based on their measured weight, had similar rates of mental status changes or clinically apparent cerebral injury as those with normal weights. Risk of hypophosphatemia was increased in those receiving larger initial bolus volumes and reduced in those receiving higher rehydration rates. No other metabolic outcomes were associated with rehydration. Protocol adherence data in the FLUID Trial suggest that physicians are uncomfortable using weight-based fluid calculations for overweight or obese children. However, higher rates of fluid infusion were not associated with increased risk of mental status changes or cerebral injury, suggesting that physicians should not limit fluid resuscitation in obese children and youth with DKA.

Update Analysis of Central Nervous System Multiple Myeloma Prognosis and Survival: A Real-World Multi-Institutional Study of the Greek Myeloma Study Group

Central Nervous System Multiple Myeloma (CNS-MM) is a rare but aggressive complication of MM, and its treatment remains an unmet clinical need. Herein we present a real-world national analysis of incidence, characteristics, prognostic factors and outcome of a large cohort of patients with CNS-MM. We evaluated 53 patients with CNS-MM (M/F: 23/30; median age: 59, range: 20-96 years; IgG: 27, IgA: 10, light-chain: 11, non-secretory: 4, IgD: 1; ISS1: 22, ISS2: 13, ISS3: 18; RISS1: 15, RISS2: 22, RISS3: 16) out of 4352 MM patients (1.2%), who were treated within the Greek Myeloma Study Group centers from 2000 to 2022 (23% of patients were diagnosed after 2016). A control group of MM patients matched for age, gender, and stage (ISS/RISS) who were treated during the same period was used for comparisons. Presence of soft tissue plasmacytomas (STP) and/or plasma cell leukemia (PCL; circulating plasma cells, cPCs: ≥5%) was determined and analyzed as extramedullary involvement (EMI). Median time to CNS-MM from MM diagnosis was 28 months (range 0-149 months); 6/53 (11.3%) patients experienced CNS-MM at initial MM diagnosis. Clinical manifestations of CNS-MM included visual disturbances/diplopia: 32%, paresis/paraplegia: 22%, lethargy/confusion: 37%, headache: 22%, cranial nerve palsy: 13% and dysarthria: 11%. PCL was present in 16/53 (30%) CNS-MM patients, while 29/53 (54.7%) CNS-MM patients had bone and/or STP vs. 13/53 matched controls (p=0.001); EMI was found in 24/53 (45%) patients with CNS-MM vs. 4/53 (7%) in controls (p&amp;lt;0.001). 35/53 (66%) CNS-MM patients had leptomeningeal infiltration (LMI) and 34% had intraparenchymal lesions. Median number of cells in the cerebrospinal fluid (CSF) was 60/μL (range 10-2550) and almost all of them (80%, range: 20-100%) were clonal plasma cells. Out of 53 CNS-MM patients, 14 (26.4%) had only CNS involvement without marrow infiltration by PCs; 51% had ≥1 high-risk molecular features (i.e., del17p, t4:14, t14:16, 1q+), and this was marginally higher vs. controls (36%; p=0.15). CD56 negative marrow PCs did not differ between groups (33% vs. 37%). A binary logistic regression analysis demonstrated that EMI was the strongest prognostic factor for the development of CNS-MM (p=0.01; HzR: 5.7). Median number of lines of treatment before the development of CNS-MM was 2 (range 0-9). First line anti-myeloma treatment in patients who developed CNS-MM included conventional chemotherapy (CT) or thalidomide-based regimens in 19 patients, bortezomib-based triplets in 27 and daratumumab-based regimens (DBR) in 7; this did not differ from controls. Overall response rate (ORR) in first-line therapy was similar between CNS-MM and controls (85% for both groups; CR 41% vs. 36%, respectively). After a median follow-up of 150 months post-MM diagnosis (95% CI: 107-192), 46 CNS-MM patients (87%) deceased (MM progression: 34, infection/sepsis: 10, cerebral hemorrhage: 2). Median overall survival (OS) of CNS-MM patients vs. matched controls from initial MM diagnosis was 43 months (95% CI: 31-54) vs 60 months (95% CI: 34-86) (p=0.002; Figure). Regarding CNS-MM therapy, 17 patients received IMiD-based regimens and 26 received PI-based regimens, 6 received CT and 4 received DBR. Patients with CNS-MM and marrow infiltration by PCs displayed an ORR of 31% only; CNS symptoms improved in 74% of all patients. Median OS of CNS-MM patients from the time of CNS involvement was 4 months (95% CI: 2.6-5.3), and it was longer in 12 patients treated after 2016 [18 months (95% CI: 7-29) vs. 2 months (95% CI: 1-3)]. Cerebrospinal fluid (CSF) infusions were performed in 28 patients (53%); 9 patients (19%) underwent radiotherapy. A multivariate analysis showed that EMI, either at diagnosis or during MM course, was the strongest negative predictor for post CNS-MM OS (p=0.008; HR: 3.4 95% CI: 1.4-8.0). Moreover, LMI was a negative predictor (p=0.02; HR: 2.7, 95% CI: 1.2-6.3) for OS, whereas treatment after 2016 had a positive impact (p=0.02; HR: 0.28, 95% CI: 0.12-0.8); CSF infusions did not affect OS. In conclusion, our analysis representing one of the largest real-world series of CNS MM patients after 2016, showed that, OS of CNS-MM remains poor however, there is a positive impact of treatment after 2016, reflecting the efficacy of modern anti-myeloma therapy; EMI strongly predicts for CNS-MM and induces a 3-fold increase in the probability of post CNS-MM death indicating a potential need for CNS prophylaxis in these patients.

Rehydration outcomes for freeze-dried red blood cells in reduced gravity

Medical planning for space exploration is based on the “floating” blood bank model to store life-saving red blood cells (RBCs) for emergencies. The “floating” blood bank approach is not sufficient in cases where multiple crewmembers are affected by space anemia. In these situations, long-term preserved RBCs will be vital to guarantee the health and safety of crew members. Transfusable RBC units can only be refrigerated for 42 days or frozen at −80 °C. However, storing frozen RBCs at −80 °C is challenging during the confined condition of long-duration space flight. Freeze-dried, viable RBCs would be an appropriate alternative because they can be stored without cooling, are predicted to have a shelf-life of years, and could be transfused immediately after rehydration. This study explores if freeze-dried RBCs can be rehydrated and transfused in reduced gravity with similar outcomes in recovery as observed at Earth gravity. Experiments analyzing freeze-dried RBC recoveries, rehydration fluid dynamics, and transfusion flow rates were analyzed utilizing an experimental glovebox in simulated 0 g during parabolic flights. RBC recoveries and rehydration fluid dynamics for volumes of 5 mL and 10 mL were the same in simulated 0 g compared to results obtained at 1 g. A clinically acceptable range of flow rates for slow intravenous infusion and rapid fluid resuscitation was possible with the simple augmentation of a hand-pumped clinical pressure bag around a unit of rehydrated RBCs. The results demonstrate the potential feasibility of using freeze-dried cells for healthcare during deep-space exploration.