Showing papers on "Hypovolemia published in 2022"

How can assessing hemodynamics help to assess volume status?

Abstract: In critically ill patients, fluid infusion is aimed at increasing cardiac output and tissue perfusion. However, it may contribute to fluid overload which may be harmful. Thus, volume status, risks and potential efficacy of fluid administration and/or removal should be carefully evaluated, and monitoring techniques help for this purpose. Central venous pressure is a marker of right ventricular preload. Very low values indicate hypovolemia, while extremely high values suggest fluid harmfulness. The pulmonary artery catheter enables a comprehensive assessment of the hemodynamic profile and is particularly useful for indicating the risk of pulmonary oedema through the pulmonary artery occlusion pressure. Besides cardiac output and preload, transpulmonary thermodilution measures extravascular lung water, which reflects the extent of lung flooding and assesses the risk of fluid infusion. Echocardiography estimates the volume status through intravascular volumes and pressures. Finally, lung ultrasound estimates lung edema. Guided by these variables, the decision to infuse fluid should first consider specific triggers, such as signs of tissue hypoperfusion. Second, benefits and risks of fluid infusion should be weighted. Thereafter, fluid responsiveness should be assessed. Monitoring techniques help for this purpose, especially by providing real time and precise measurements of cardiac output. When decided, fluid resuscitation should be performed through fluid challenges, the effects of which should be assessed through critical endpoints including cardiac output. This comprehensive evaluation of the risk, benefits and efficacy of fluid infusion helps to individualize fluid management, which should be preferred over a fixed restrictive or liberal strategy.

Acute Kidney Injury in Patients with Liver Cirrhosis: Prevalence, Predictors, and In-Hospital Mortality at a District Hospital in Ghana

Abstract: Background Acute kidney injury (AKI) is one of the most severe complications of cirrhosis and portends an ominous prognosis with an estimated mortality of about 50% in a month and 65% within a year. Infection and hypovolemia have been found to be the main precipitating factors of AKI in liver cirrhosis. Early detection and treatment of AKI may improve outcomes. AKI in patients with liver cirrhosis in Ghana and their impact on inpatient mortality are largely unknown. This study was aimed at determining the prevalence, precipitating factors, predictors, and in-hospital mortality of AKI in patients with liver cirrhosis admitted to a district hospital in Ghana. Methods Consecutive hospitalized patients with liver cirrhosis from 1 January 2018 to 30 April 2020 were recruited. Patient's demographic data and clinical features were collected using a standardized questionnaire. Biochemical and haematological tests as well as abdominal ultrasound scans were done for all patients. All patients were then followed up until discharge or death. Results There were 117 (65.4%) males out of the 179 patients with a mean age of 49.94 and 45.84 years for those with and without AKI, respectively. The prevalence of AKI was 27.9% (50/179). Out of 50 participants with AKI, 64.0% (32/50) died, contributing 41.0% of all in-patient mortality amongst participants. There was a significant association between AKI and death (p ≤ 0.001). The major precipitating factors of AKI were infections (60.0%), hypovolemia (20.0%) due to gastrointestinal bleeding and gastroenteritis, and refractory ascites (16.0%). Alkaline phosphatase, INR, model for end-stage liver disease sodium, sodium, and blood urea nitrogen were independent predictors of AKI. Conclusion AKI was common among patients with liver cirrhosis with high in-patient mortality. Identification of these precipitants and independent predictors of AKI may lead to prompt and targeted treatment with reduction in patient mortality.

Quantitative Lung Ultrasonography for the Nephrologist: Applications in Dialysis and Heart Failure

Abstract: Volume overload, and its attendant increase in acute care utilization and cardiovascular morbidity and mortality, represents a critical challenge for the practicing nephrologist. This is particularly true among patients with ESKD on HD, where predialysis volume overload and intradialytic and postdialytic hypovolemia account for almost a third of all cost for the Medicare dialysis benefit. Quantitative lung ultrasound is a tool for assessing the extent of extravascular lung water that outperforms physical exam and plain chest radiography. B-lines are vertical hyperechoic artifacts present in patients with increased extravascular lung water. B-lines have been shown to decrease dynamically during the hemodialysis treatment in proportion to ultrafiltration volume. Among patients with chronic heart failure, titration of diuretics on the basis of the extent of pulmonary congestion noted on lung ultrasonography has been shown to decrease recurrent acute care utilization. Early data from randomized controlled trials of lung ultrasound-guided ultrafiltration therapy among patients with ESKD on HD have shown promise for potential reduction in recurrent episodes of decompensated heart failure and cardiovascular events. Ultimately, lung ultrasound may predict those who are ultrafiltration tolerant and could be used to decrease acute care utilization and, thus, cost in this population.

Cardiorenal Syndrome: An Updated Classification Based on Clinical Hallmarks

Abstract: Cardiorenal syndrome (CRS) is defined as progressive, combined cardiac and renal dysfunction. In this mini review, a historical note on CRS is presented, the pathomechanisms and clinical hallmarks of both chronic heart failure and chronic kidney disease are discussed, and an updated classification of CRS is proposed. The current consensus classification relies on the assumed etiology and the course of the disease, i.e., acute or chronic CRS. Five types are described: type-I CRS presenting as acute cardiac failure leading to acute renal failure; type-II CRS presenting as chronic cardiac failure leading to chronic renal failure; type-III CRS presenting as acute kidney injury aggravating heart failure; type-IV CRS presenting as chronic kidney failure aggravating heart failure; and type-V CRS presenting as concurrent, chronic cardiac and renal failure. For an updated classification, information on the presence or absence of valvular heart disease and on the presence of hyper- or hypovolemia is added. Thus, CRS is specified as “acute” (type-I, type-III or type-V CRS) or “chronic” (type-II, type-IV or type-V) CRS, as “valvular” or “nonvalvular” CRS, and as “hyper-” or “hypovolemia-associated” CRS if euvolemia is absent. To enable the use of this updated classification, validation studies are mandated.

Low-dose fentanyl does not alter muscle sympathetic nerve activity, blood pressure, or tolerance during progressive central hypovolemia

Abstract: Hemorrhage is a leading cause of battlefield and civilian trauma deaths. Several pain medications, including fentanyl, are recommended for use in the prehospital (i.e., field setting) for a hemorrhaging solider. However, it is unknown whether fentanyl impairs arterial blood pressure (BP) regulation, which would compromise hemorrhagic tolerance. Thus, the purpose of this study was to test the hypothesis that an analgesic dose of fentanyl impairs hemorrhagic tolerance in conscious humans. Twenty-eight volunteers (13 females) participated in this double-blinded, randomized, placebo-controlled trial. We conducted a presyncopal limited progressive lower body negative pressure test (LBNP; a validated model to simulate hemorrhage) following intravenous administration of fentanyl (75 µg) or placebo (saline). We quantified tolerance as a cumulative stress index (mmHg·min), which was compared between trials using a paired, two-tailed t test. We also compared muscle sympathetic nerve activity (MSNA; microneurography) and beat-to-beat BP (photoplethysmography) during the LBNP test using a mixed effects model [time (LBNP stage) × trial]. LBNP tolerance was not different between trials (fentanyl: 647 ± 386 vs. placebo: 676 ± 295 mmHg·min, P = 0.61, Cohen’s d = 0.08). Increases in MSNA burst frequency (time: P < 0.01, trial: P = 0.29, interaction: P = 0.94) and reductions in mean BP (time: P < 0.01, trial: P = 0.50, interaction: P = 0.16) during LBNP were not different between trials. These data, the first to be obtained in conscious humans, demonstrate that administration of an analgesic dose of fentanyl does not alter MSNA or BP during profound central hypovolemia, nor does it impair tolerance to this simulated hemorrhagic insult.

Demystifying hyponatremia: A clinical guide to evaluation and management.

Abstract: Hyponatremia (serum sodium <135 mEq/L) is a frequent electrolyte abnormality complicating the clinical care of hospitalized patients. Hyponatremia has been associated with an increased risk of mortality. Hyponatremia can be seen in patients with euvolemia, hypovolemia, or hypervolemia. Evaluation of hyponatremia relies on clinical assessment and estimation of serum sodium, urine electrolytes, and serum and urine osmolality in addition to other case-specific laboratory parameters. In addition, point-of-care ultrasonography is an important adjunct to physical assessment in estimation of volume status. Understanding the pathophysiology of the underlying process can lead to a timely diagnosis and appropriate management of hyponatremia.

AI-Enabled Advanced Development for Assessing Low Circulating Blood Volume for Emergency Medical Care: Comparison of Compensatory Reserve Machine-Learning Algorithms

Abstract: The application of artificial intelligence (AI) has provided new capabilities to develop advanced medical monitoring sensors for detection of clinical conditions of low circulating blood volume such as hemorrhage. The purpose of this study was to compare for the first time the discriminative ability of two machine learning (ML) algorithms based on real-time feature analysis of arterial waveforms obtained from a non-invasive continuous blood pressure system (Finometer®) signal to predict the onset of decompensated shock: the compensatory reserve index (CRI) and the compensatory reserve metric (CRM). One hundred ninety-one healthy volunteers underwent progressive simulated hemorrhage using lower body negative pressure (LBNP). The least squares means and standard deviations for each measure were assessed by LBNP level and stratified by tolerance status (high vs. low tolerance to central hypovolemia). Generalized Linear Mixed Models were used to perform repeated measures logistic regression analysis by regressing the onset of decompensated shock on CRI and CRM. Sensitivity and specificity were assessed by calculation of receiver-operating characteristic (ROC) area under the curve (AUC) for CRI and CRM. Values for CRI and CRM were not distinguishable across levels of LBNP independent of LBNP tolerance classification, with CRM ROC AUC (0.9268) being statistically similar (p = 0.134) to CRI ROC AUC (0.9164). Both CRI and CRM ML algorithms displayed discriminative ability to predict decompensated shock to include individual subjects with varying levels of tolerance to central hypovolemia. Arterial waveform feature analysis provides a highly sensitive and specific monitoring approach for the detection of ongoing hemorrhage, particularly for those patients at greatest risk for early onset of decompensated shock and requirement for implementation of life-saving interventions.

Graded lower body negative pressure induces intraventricular negative pressures and incremental diastolic suction: a pressure volume study in a porcine model.

Abstract: Lower body negative pressure (LBNP) has been a tool to study compensatory mechanisms to central hypovolemia for decades. However, underlying hemodynamic mechanisms were mostly assessed non-invasively and remain unclear. We hypothesized that incremental LBNP reduces diastolic filling and thereby affects left ventricular (LV) diastolic suction (DS). Here, we investigated the impact of graded LBNP at 3 different levels of seal as well as during beta-adrenergic stimulation by invasive pressure-volume (PV) analysis. Eight Landrace pigs were instrumented closed-chest for PV assessment. LBNP was applied at three consecutive locations: I) cranial, 10cm below xiphoid process; II) medial, half-way between cranial and caudal; III) caudal, at the iliac spine. Level III) was repeated under dobutamine infusion. At each level, baseline measurements were followed by application of incremental LBNP of -15, -30 and -45 mmHg. LBNP induced varying degrees of preload-dependent hemodynamic changes, with cranial LBNP inducing more pronounced effects than caudal. According to the Frank-Starling mechanism, graded LBNP progressively reduced LV stroke volume (LV SV) following a decrease in LV end-diastolic volume. Negative intraventricular minimal pressures were observed during dobutamine-infusion as well as higher levels of LBNP. Of note, incremental LV negative pressures were accompanied by increasing DS volumes, derived by extrapolating the volume at zero transmural pressure, the so-called equilibrium volume (V0), related to LV SV. In conclusion, graded preload reduction shifts the PV loop to smaller volumes and end-systolic volume below V0, which induces negative LV pressures and increases LV suction. Accordingly, LBNP induced central hypovolemia is associated with increased DS.

SARS-CoV-2-Infection (COVID-19): Clinical Course, Viral Acute Respiratory Distress Syndrome (ARDS) and Cause(s) of Death

Abstract: SARS-CoV-2-infected symptomatic patients often suffer from high fever and loss of appetite which are responsible for the deficit of fluids and of protein intake. Many patients admitted to the emergency room are, therefore, hypovolemic and hypoproteinemic and often suffer from respiratory distress accompanied by ground glass opacities in the CT scan of the lungs. Ischemic damage in the lung capillaries is responsible for the microscopic hallmark, diffuse alveolar damage (DAD) characterized by hyaline membrane formation, fluid invasion of the alveoli, and progressive arrest of blood flow in the pulmonary vessels. The consequences are progressive congestion, increase in lung weight, and progressive hypoxia (progressive severity of ARDS). Sequestration of blood in the lungs worsens hypovolemia and ischemia in different organs. This is most probably responsible for the recruitment of inflammatory cells into the ischemic peripheral tissues, the release of acute-phase mediators, and for the persistence of elevated serum levels of positive acute-phase markers and of hypoalbuminemia. Autopsy studies have been performed mostly in patients who died in the ICU after SARS-CoV-2 infection because of progressive acute respiratory distress syndrome (ARDS). In the death certification charts, after respiratory insufficiency, hypovolemic heart failure should be mentioned as the main cause of death.

What does the evidence tell us? Revisiting optimal cord management at the time of birth

Abstract: Abstract A newborn who receives a placental transfusion at birth from delayed cord clamping (DCC) obtains about 30% more blood volume than those with immediate cord clamping (ICC). Benefits for term neonates include higher hemoglobin levels, less iron deficiency in infancy, improved myelination out to 12 months, and better motor and social development at 4 years of age especially in boys. For preterm infants, benefits include less intraventricular hemorrhage, fewer gastrointestinal issues, lower transfusion requirements, and less mortality in the neonatal intensive care unit by 30%. Ventilation before clamping the umbilical cord can reduce large swings in cardiovascular function and help to stabilize the neonate. Hypovolemia, often associated with nuchal cord or shoulder dystocia, may lead to an inflammatory cascade and subsequent ischemic injury. A sudden unexpected neonatal asystole at birth may occur from severe hypovolemia. The restoration of blood volume is an important action to protect the hearts and brains of neonates. Currently, protocols for resuscitation call for ICC. However, receiving an adequate blood volume via placental transfusion may be protective for distressed neonates as it prevents hypovolemia and supports optimal perfusion to all organs. Bringing the resuscitation to the mother’s bedside is a novel concept and supports an intact umbilical cord. When one cannot wait, cord milking several times can be done quickly within the resuscitation guidelines. Cord blood gases can be collected with optimal cord management. Conclusion : Adopting a policy for resuscitation with an intact cord in a hospital setting takes a coordinated effort and requires teamwork by obstetrics, pediatrics, midwifery, and nursing. What is Known: • Placental transfusion through optimal cord management benefits morbidity and mortality of newborn infants. • The World Health Organisation has recommended placental transfusion in their guidance. What is New: • Improved understanding of transitioning to extrauterine life has been described. • Resuscitation of newborn infants whilst the umbilical cord remains intact could improve the postpartum adaptation.

Wearable Sensors and Machine Learning for Hypovolemia Problems in Occupational, Military and Sports Medicine: Physiological Basis, Hardware and Algorithms

Abstract: Hypovolemia is a physiological state of reduced blood volume that can exist as either (1) absolute hypovolemia because of a lower circulating blood (plasma) volume for a given vascular space (dehydration, hemorrhage) or (2) relative hypovolemia resulting from an expanded vascular space (vasodilation) for a given circulating blood volume (e.g., heat stress, hypoxia, sepsis). This paper examines the physiology of hypovolemia and its association with health and performance problems common to occupational, military and sports medicine. We discuss the maturation of individual-specific compensatory reserve or decompensation measures for future wearable sensor systems to effectively manage these hypovolemia problems. The paper then presents areas of future work to allow such technologies to translate from lab settings to use as decision aids for managing hypovolemia. We envision a future that incorporates elements of the compensatory reserve measure with advances in sensing technology and multiple modalities of cardiovascular sensing, additional contextual measures, and advanced noise reduction algorithms into a fully wearable system, creating a robust and physiologically sound approach to manage physical work, fatigue, safety and health issues associated with hypovolemia for workers, warfighters and athletes in austere conditions.

Correlation between Angiotensin Serum Levels and Very-Low-Frequency Spectral Power of Heart Rate Variability during Hemodialysis

Abstract: Cardiovascular regulatory mechanisms that fail to compensate for ultrafiltration and cause hypovolemia during hemodialysis (HD) are not completely understood. This includes the interaction between the autonomic nervous system and the biochemistry that regulates blood pressure and modulates cardiac activity and vascular tone in response to hypovolemia in patients treated with HD. The objective was to evaluate the association of spectral indices of heart rate variability (HRV) with serum levels of angiotensin II, angiotensin 1–7, nitric oxide and total antioxidant capacity during HD. Electrocardiographic records were obtained from 20 patients during HD (3 h), from which HRV data and spectral power data in the very-low-frequency (VLF), low-frequency (LF) and high-frequency (HF) bands were generated. Three blood samples per patient were collected during HD (0.0, 1.5, 3.0 h) to determine the levels of biomarkers involved in the pressor response during HD. Angiotensin II had a positive correlation with VLF (r = 0.390) and with LF/HF (r = 0.359) and a negative correlation with LF (r = −0.262) and HF (r = −0.383). There were no significant correlations between HRV and the other biomarkers. These results suggest that during HD, VLF could reflect the serum levels of angiotensin II, which may be associated with the autonomic response to HD.

Burn-Induced Acute Kidney Injury–Two-Lane Road: From Molecular to Clinical Aspects

Abstract: Severe burn injuries lead to acute kidney injury (AKI) development, increasing the mortality risk up to 28–100%. In addition, there is an increase in hospitalization days and complications appearance. Various factors are responsible for acute or late AKI debut, like hypovolemia, important inflammatory response, excessive load of denatured proteins, sepsis, and severe organic dysfunction. The main measure to improve the prognosis of these patients is rapidly recognizing this condition and reversing the underlying events. For this reason, different renal biomarkers have been studied over the years for early identification of burn-induced AKI, like neutrophil gelatinase-associated lipocalin (NGAL), cystatin C, kidney injury molecule-1 (KIM-1), tissue inhibitor of metalloproteinase-2 (TIMP-2), interleukin-18 (IL-18), and insulin-like growth factor-binding protein 7 (IGFBP7). The fundamental purpose of these studies is to find a way to recognize and prevent acute renal injury progression early in order to decrease the risk of mortality and chronic kidney disease (CKD) onset.

Transpulmonary ultrasound dilution is an acceptable technique for cardiac output measurement in anesthetized pigs.

Abstract: OBJECTIVE To evaluate cardiac output (CO) measurements using transpulmonary ultrasound (TPUD) technology and compare results with those of the gold standard, pulmonary arterial catheter thermodilution (PACTD), in 6 healthy anesthetized pigs during acute hemodynamic changes caused by manipulation of the blood volume. ANIMALS 6 healthy male Landrace pigs. PROCEDURES Over a period of 1 week, pigs were anesthetized with isoflurane, mechanically ventilated, and underwent instrumentation in dorsal recumbency. They were subjected to sequential experimental states during which the blood volume was manipulated so that the animals transitioned from normovolemia to hypovolemia (20% and 40% of blood volume depletion), back to normovolemia (autologous blood transfusion), and then to hypervolemia (following colloid bolus). During each volume state, CO measurements were compared between TPUD and PACTD. RESULTS The mean ± SD relative bias between TPUD and PACTD was 7.71% ± 21.2% with limits of agreement -33.9% to 49.3%, indicating TPUD slightly underestimated CO values, compared with values obtained with PACTD. The mean ± SD of the bias between the 2 methods was 0.13 ± 0.5 L/min. Only 5 of 36 (13.9%) TPUD CO measurements had an absolute value of relative bias > 30%. The percentage error calculated for TPUD was 29.4%. CLINICAL RELEVANCE Results suggested that TPUD measurements have acceptable agreement with PACTD measurements. Moreover, TPUD exhibits promising potential in being used interchangeably with PACTD for future hemodynamic research involving swine as species of interest.

Effects of experimental hypovolemia and pain on pre‐ejection period and pulse transit time in healthy volunteers

Abstract: Trauma patients may suffer significant blood loss, and noninvasive methods to diagnose hypovolemia in these patients are needed. Physiologic effects of hypovolemia, aiming to maintain blood pressure, are largely mediated by increased sympathetic nervous activity. Trauma patients may however experience pain, which also increases sympathetic nervous activity, potentially confounding measures of hypovolemia. Elucidating the common and separate effects of the two stimuli on diagnostic methods is therefore important. Lower body negative pressure (LBNP) and cold pressor test (CPT) are experimental models of central hypovolemia and pain, respectively. In the present analysis, we explored the effects of LBNP and CPT on pre‐ejection period and pulse transit time, aiming to further elucidate the potential use of these variables in diagnosing hypovolemia in trauma patients. We exposed healthy volunteers to four experimental sequences with hypovolemia (LBNP 60 mmHg) or normovolemia (LBNP 0 mmHg) and pain (CPT) or no pain (sham) in a 2 × 2 fashion. We calculated pre‐ejection period and pulse transit time from ECG and ascending aortic blood velocity (suprasternal Doppler) and continuous noninvasive arterial pressure waveform (volume‐clamp method). Fourteen subjects were available for the current analyses. This experimental study found that pre‐ejection period increased with hypovolemia and remained unaltered with pain. Pulse transit time was reduced by pain and increased with hypovolemia. Thus, the direction of change in pulse transit time has the potential to distinguish hypovolemia and pain.

Classification of Blood Volume Decompensation State via Machine Learning Analysis of Multi-Modal Wearable-Compatible Physiological Signals

Abstract: This paper presents a novel computational algorithm to estimate blood volume decompensation state based on machine learning (ML) analysis of multi-modal wearable-compatible physiological signals. To the best of our knowledge, our algorithm may be the first of its kind which can not only discriminate normovolemia from hypovolemia but also classify hypovolemia into absolute hypovolemia and relative hypovolemia. We realized our blood volume classification algorithm by (i) extracting a multitude of features from multi-modal physiological signals including the electrocardiogram (ECG), the seismocardiogram (SCG), the ballistocardiogram (BCG), and the photoplethysmogram (PPG), (ii) constructing two ML classifiers using the features, one to classify normovolemia vs. hypovolemia and the other to classify hypovolemia into absolute hypovolemia and relative hypovolemia, and (iii) sequentially integrating the two to enable multi-class classification (normovolemia, absolute hypovolemia, and relative hypovolemia). We developed the blood volume decompensation state classification algorithm using the experimental data collected from six animals undergoing normovolemia, relative hypovolemia, and absolute hypovolemia challenges. Leave-one-subject-out analysis showed that our classification algorithm achieved an F1 score and accuracy of (i) 0.93 and 0.89 in classifying normovolemia vs. hypovolemia, (ii) 0.88 and 0.89 in classifying hypovolemia into absolute hypovolemia and relative hypovolemia, and (iii) 0.77 and 0.81 in classifying the overall blood volume decompensation state. The analysis of the features embedded in the ML classifiers indicated that many features are physiologically plausible, and that multi-modal SCG-BCG fusion may play an important role in achieving good blood volume classification efficacy. Our work may complement existing computational algorithms to estimate blood volume compensatory reserve as a potential decision-support tool to provide guidance on context-sensitive hypovolemia therapeutic strategy.

The reciprocal relationship between cardiac baroreceptor sensitivity and cerebral autoregulation during simulated hemorrhage in humans

Abstract: A reciprocal relationship between the baroreflex and cerebral autoregulation (CA) has been demonstrated at rest and in response to acute hypotension. We hypothesized that the reciprocal relationship between cardiac baroreflex sensitivity (BRS) and CA would be maintained during sustained central hypovolemia induced by lower body negative pressure (LBNP), and that the strength of this relationship would be greater in subjects with higher tolerance to this stress. Healthy young adults (n = 51; 23F/28M) completed a LBNP protocol to presyncope. Subjects were classified as high tolerant (HT; completion of −60 mmHg LBNP stage, ≥20-min) or low tolerant (LT; did not complete −60 mmHg LBNP stage, <20-min). R-R intervals (RRI), systolic arterial pressure (SAP), mean arterial pressure (MAP), and middle cerebral artery velocity (MCAv) were measured continuously. Cardiac BRS was calculated in the time domain (ΔHR/ΔSAP) and frequency domain (RRI-SAP low frequency (LF) transfer function gain), and CA was calculated in the time domain (ΔMCAv/ΔMAP) and frequency domain (MAP-mean MCAv LF transfer function gain). There was a moderate relationship between cardiac BRS and CA for the group of 51 subjects in both the time (R = -0.54, P < 0.0001) and frequency (R = 0.61, P < 0.001) domains; there was a stronger relationship in the HT group (R = 0.73) compared to the LT group (R = 0.31) in the frequency domain (P = 0.08), but no difference between groups in the time domain (HT: R = -0.73 vs. LT: R = -0.63; P = 0.27). These findings suggest that an interaction between BRS and CA may be an important compensatory mechanism that contributes to tolerance to simulated hemorrhage in young healthy adults.

PragmaTic, prospEctive, randomized, controlled, double-blind, mulTi-centre, multinational study on the safety and efficacy of a 6% HydroxYethyl Starch (HES) solution versus an electrolyte solution in trauma patients: study protocol for the TETHYS study

Abstract: Abstract Background Trauma may be associated with significant to life-threatening blood loss, which in turn may increase the risk of complications and death, particularly in the absence of adequate treatment. Hydroxyethyl starch (HES) solutions are used for volume therapy to treat hypovolemia due to acute blood loss to maintain or re-establish hemodynamic stability with the ultimate goal to avoid organ hypoperfusion and cardiovascular collapse. The current study compares a 6% HES 130 solution (Volulyte 6%) versus an electrolyte solution (Ionolyte) for volume replacement therapy in adult patients with traumatic injuries, as requested by the European Medicines Agency to gain more insights into the safety and efficacy of HES in the setting of trauma care. Methods TETHYS is a pragmatic, prospective, randomized, controlled, double-blind, multicenter, multinational trial performed in two parallel groups. Eligible consenting adults ≥ 18 years, with an estimated blood loss of ≥ 500 ml, and in whom initial surgery is deemed necessary within 24 h after blunt or penetrating trauma, will be randomized to receive intravenous treatment at an individualized dose with either a 6% HES 130, or an electrolyte solution, for a maximum of 24 h or until reaching the maximum daily dose of 30 ml/kg body weight, whatever occurs first. Sample size is estimated as 175 patients per group, 350 patients total ( α = 0.025 one-tailed, power 1– β = 0.8). Composite primary endpoint evaluated in an exploratory manner will be 90-day mortality and 90-day renal failure, defined as AKIN stage ≥ 2, RIFLE injury/failure stage, or use of renal replacement therapy (RRT) during the first 3 months. Secondary efficacy and safety endpoints are fluid administration and balance, changes in vital signs and hemodynamic status, changes in laboratory parameters including renal function, coagulation, and inflammation biomarkers, incidence of adverse events during treatment period, hospital, and intensive care unit (ICU) length of stay, fitness for ICU or hospital discharge, and duration of mechanical ventilation and/or RRT. Discussion This pragmatic study will increase the evidence on safety and efficacy of 6% HES 130 for treatment of hypovolemia secondary to acute blood loss in trauma patients. Trial registration Registered in EudraCT, No.: 2016-002176-27 (21 April 2017) and ClinicalTrials.gov, ID: NCT03338218 (09 November 2017).

The Extent of Burn Injury Significantly Affects Serum Micro- and Macroelement Concentrations in Patients on the First Day of Hospitalisation

Abstract: Burns exceeding 30% of total body surface area (TBSA) result in considerable hypovolemia coupled with the formation and release of inflammatory mediators, leading to subsequent systemic effects known as burn shock. Because of plasma exudation and the associated losses of large quantities of minerals, severe burns can lead to nutritional deficiencies and consequently disrupt homeostasis and metabolism of the entire body. The study group comprised 62 patients, who were divided into 3 groups according to the severity of burns. Serum samples were tested for concentrations of Ca, Mg, Mn, P, K, Zn, Cu, Fe, Se, Na, Cr, Ni, and Al. The mineral concentrations in serum of patients with burn injuries differ significantly from reference values, but this is not affected by the extent of the body burn. There are statistically significant decreases in serum concentrations of elements important for antioxidant protection (Zn, Cu, Se), and significant increases in the concentrations of toxic elements (Al and Ni), which may aggravate the effects associated with the state of burn shock. The Spearman rank correlation analysis did not reveal any statistically significant relationships between the serum concentrations of Mn, Ni, Al, K, Na, P, Mg, Zn, Se, Cr and the affected body surface area and severity of the burn—the values were at the lower end of the reference range. The obtained results indicate that proper nutrition, including elements replenishment, is extremely important in the recovery process of burn patients and time to nutrition is an important factor affecting patient survival after severe burn.

Low-Dose Morphine Reduces Tolerance to Central Hypovolemia in Healthy Adults Without Affecting Muscle Sympathetic Outflow.

Abstract: Hemorrhage is a leading cause of preventable battlefield and civilian trauma deaths. Low-dose (i.e., an analgesic dose) morphine is recommended for use in the prehospital (i.e., field) setting. Morphine administration reduces hemorrhagic tolerance in rodents. However, it is unknown whether morphine impairs autonomic cardiovascular regulation and consequently reduces hemorrhagic tolerance in humans. Thus, the purpose of this study was to test the hypothesis that low-dose morphine reduces hemorrhagic tolerance in conscious humans. Thirty adults (15F/15M; 29±6 y; 26±4 kg•m-2, mean ± SD) completed this randomized, crossover, double-blinded, placebo-controlled trial. One minute after intravenous administration of morphine (5 mg) or placebo (saline), we employed a pre-syncopal limited progressive lower-body negative pressure (LBNP) protocol to determine hemorrhagic tolerance. Hemorrhagic tolerance was quantified as a cumulative stress index (mmHg•min), which was compared between trials using a Wilcoxon matched-pairs signed-rank test. We also compared muscle sympathetic nerve activity (MSNA; microneurography) and beat-to-beat blood pressure (photoplethysmography) during the LBNP test using mixed-effects analyses (time [LBNP stage] x trial). Median LBNP tolerance was lower during morphine trials (placebo: 692 [473-997] vs. morphine: 385 [251-728] mmHg•min, p<0.001, CI: -394 to -128). Systolic blood pressure was 8 mmHg lower during moderate central hypovolemia during morphine trials (post hoc p=0.02; time: p<0.001, trial: p=0.13, interaction: p=0.006). MSNA burst frequency responses were not different between trials (time: p<0.001, trial: p=0.80, interaction: p=0.51). These data demonstrate that low-dose morphine reduces hemorrhagic tolerance in conscious humans. Thus, morphine is not an ideal analgesic for a hemorrhaging individual in the prehospital setting.

Where Are We Heading With Fluid Responsiveness and Septic Shock?

Abstract: When hypovolemia is left uncorrected, it can lead to poor tissue oxygenation and organ dysfunction. On the other hand, excessive fluid administration can increase the risk of complications. Assessing volume responsiveness in critically ill patients is therefore crucial. In this article we summarized the literature addressing the most sensitive and specific dynamic predictors for fluid responsiveness, to help clarify the best way to guide clinicians in managing patients with shock. Data were collected from PubMed and EMBASE of high-quality articles, randomized controlled trials (RCTs), retrospective research, and metanalyses; articles were identified from January 2000 to February 2021. We identified and critically reviewed the published peer-reviewed literature investigating the dynamic predictors to assess fluid responsiveness. Evidence suggests that the traditional use of static predictors for fluid responsiveness should be abandoned. Over the last 20 years, a number of dynamic tests have been developed. These tests are based on the principle of inducing short-term changes in cardiac preload using heart-lung interactions. However, in routine practice the conditions to meet the requirements of these dynamic parameters are frequently not met. Therefore, more dynamic predictors that do not depend on heart-lung interaction have developed such as the mini fluid challenge test and passive leg raising test These tests have fewer limitations and higher sensitivity and specificity compared to the other tests.

Can blood loss be assessed by echocardiography? An experimental study on a controlled hemorrhagic shock model in piglets

Abstract: Assessment of the volemic loss is a major challenge during the management of hemorrhagic shock. Echocardiography is an increasingly used noninvasive tool for hemodynamic assessment. In mechanically ventilated patients, some studies suggest that respiratory variations of mean subaortic time-velocity integral (∆VTI) would be predictive of fluid filling response. An experimental model of controlled hemorrhagic shock provides a precise approach to study correlation between blood volume and cardiac ultrasonographic parameters.The main objective was to analyze the ∆VTI changes during hemorrhage in an anesthetized-piglet model of controlled hemorrhagic shock. The secondary objective was to evaluate ∆VTI during the resuscitation process after hemorrhage and other echocardiographic parameters changes during the whole protocol.Twenty-four anesthetized and ventilated piglets were bled until mean arterial pressure reached 40 mm Hg. Controlled hemorrhage was maintained for 30 minutes before randomizing the piglets to two resuscitation groups: fluid filling group resuscitated with saline solution and noradrenaline group resuscitated with saline solution and noradrenaline. Echocardiography and hemodynamic measures, including pulsed pressure variations (PPV), were performed at different stages of the protocol.The correlation coefficient between ΔVTI and PPV with the volume of bleeding during the hemorrhagic phase were respectively 0.24 (95% confidence interval, 0.08-0.39; p < 0.01) and 0.57 (95% CI, 0.44-0.67; p < 0.01). Two parameters had a moderate correlation coefficient with hemorrhage volume (over 0.5): mean subaortic time-velocity index (VTI) and mitral annulus diastolic tissular velocity (E').In this hemorrhagic shock model, ΔVTI had a low correlation with the volume of bleeding, but VTI and E' had a correlation with blood volume comparable to that of PPV.

Prospective, randomized, controlled, double-blind, multi-center, multinational study on the safety and efficacy of 6% Hydroxyethyl starch (HES) sOlution versus an Electrolyte solutioN In patients undergoing eleCtive abdominal Surgery: study protocol for the PHOENICS study

Abstract: Hydroxyethyl starch (HES) solutions are used for volume therapy to treat hypovolemia due to acute blood loss and to maintain hemodynamic stability. This study was requested by the European Medicines Agency (EMA) to provide more evidence on the long-term safety and efficacy of HES solutions in the perioperative setting.PHOENICS is a randomized, controlled, double-blind, multi-center, multinational phase IV (IIIb) study with two parallel groups to investigate non-inferiority regarding the safety of a 6% HES 130 solution (Volulyte 6%, Fresenius Kabi, Germany) compared with a crystalloid solution (Ionolyte, Fresenius Kabi, Germany) for infusion in patients with acute blood loss during elective abdominal surgery. A total of 2280 eligible patients (male and female patients willing to participate, with expected blood loss ≥ 500 ml, aged > 40 and ≤ 85 years, and ASA Physical status II-III) are randomly assigned to receive either HES or crystalloid solution for the treatment of hypovolemia due to surgery-induced acute blood loss in hospitals in up to 11 European countries. The dosing of investigational products (IP) is individualized to patients' volume needs and guided by a volume algorithm. Patients are treated with IP for maximally 24 h or until the maximum daily dose of 30 ml/kg body weight is reached. The primary endpoint is the treatment group mean difference in the change from the pre-operative baseline value in cystatin-C-based estimated glomerular filtration rate (eGFR), to the eGFR value calculated from the highest cystatin-C level measured during post-operative days 1-3. Further safety and efficacy parameters include, e.g., combined mortality/major post-operative complications until day 90, renal function, coagulation, inflammation, hemodynamic variables, hospital length of stay, major post-operative complications, and 28-day, 90-day, and 1-year mortality.The study will provide important information on the long-term safety and efficacy of HES 130/0.4 when administered according to the approved European product information. The results will be relevant for volume therapy of surgical patients.EudraCT 2016-002162-30 . ClinicalTrials.gov NCT03278548.

The role of tricuspite annular plane systolic excursion as a marker of hypovolemia in healthy blood donor volunteers

Abstract: The aim of this study is to compare the diameter of the inferior vena cava with tricuspid annular plane systolic excursion (TAPSE) measurement in order to determine the volume loss before and after blood donation in healthy volunteers.This Institutional Review Board-approved single center, prospective, cross-sectional study included 60 healthy blood donors donating in a tertiary care hospital's blood bank. After obtaining written consent, systolic, diastolic, and mean arterial blood pressures along with pulse rate of the donors were measured in sitting and supine positions by the attending physician, then, inferior vena cava (IVC) and TAPSE measurements were made before and after blood donation.Statistically significant differences was found between standing systolic blood pressure and pulse rate, lying systolic blood pressure and pulse rate, IVC and TAPSE values before and after blood donation (p < 0.05). There was no difference between the other variables before and after blood donation.Our study revealed that, low IVC and TAPSE values correlated in determining blood loss after blood donation. TAPSE may be useful to predict blood loss in early stages of hypovolemic shock.

Detection of a Stroke Volume Decrease by Machine-Learning Algorithms Based on Thoracic Bioimpedance in Experimental Hypovolaemia

Abstract: Compensated shock and hypovolaemia are frequent conditions that remain clinically undetected and can quickly cause deterioration of perioperative and critically ill patients. Automated, accurate and non-invasive detection methods are needed to avoid such critical situations. In this experimental study, we aimed to create a prediction model for stroke volume index (SVI) decrease based on electrical cardiometry (EC) measurements. Transthoracic echo served as reference for SVI assessment (SVI-TTE). In 30 healthy male volunteers, central hypovolaemia was simulated using a lower body negative pressure (LBNP) chamber. A machine-learning algorithm based on variables of EC was designed. During LBNP, SVI-TTE declined consecutively, whereas the vital signs (arterial pressures and heart rate) remained within normal ranges. Compared to heart rate (AUC: 0.83 (95% CI: 0.73–0.87)) and systolic arterial pressure (AUC: 0.82 (95% CI: 0.74–0.85)), a model integrating EC variables (AUC: 0.91 (0.83–0.94)) showed a superior ability to predict a decrease in SVI-TTE ≥ 20% (p = 0.013 compared to heart rate, and p = 0.002 compared to systolic blood pressure). Simulated central hypovolaemia was related to a substantial decline in SVI-TTE but only minor changes in vital signs. A model of EC variables based on machine-learning algorithms showed high predictive power to detect a relevant decrease in SVI and may provide an automated, non-invasive method to indicate hypovolaemia and compensated shock.