Finger photopletysmography detects early acute blood loss in compensated blood donors: a pilot study.

Objective.Diagnosis of incipient acute hypovolemia is challenging as vital signs are typically normal and patients remain asymptomatic at early stages. The early identification of this entity would affect patients' outcome if physicians were able to treat it precociously. Thus, the development of a noninvasive, continuous bedside monitoring tool to detect occult hypovolemia before patients become hemodynamically unstable is clinically relevant. We hypothesize that pulse oximeter's alternant (AC) and continuous (DC) components of the infrared light are sensitive to acute and small changes in patient's volemia. We aimed to test this hypothesis in a cohort of healthy blood donors as a model of slight hypovolemia.Approach.We planned to prospectively study blood donor volunteers removing 450 ml of blood in supine position. Noninvasive arterial blood pressure, heart rate, and finger pulse oximetry were recorded. Data was analyzed before donation, after donation and during blood auto-transfusion generated by the passive leg-rising (PLR) maneuver.Main results.Sixty-six volunteers (44% women) accomplished the protocol successfully. No clinical symptoms of hypovolemia, arterial hypotension (systolic pressure < 90 mmHg), brady-tachycardia (heart rate <60 and >100 beats-per-minute) or hypoxemia (SpO2< 90%) were observed during donation. The AC signal before donation (median 0.21 and interquartile range 0.17 a.u.) increased after donation [0.26(0.19) a.u;p< 0.001]. The DC signal before donation [94.05(3.63) a.u] increased after blood extraction [94.65(3.49) a.u;p< 0.001]. When the legs' blood was auto-transfused during the PLR, the AC [0.21(0.13) a.u.;p= 0.54] and the DC [94.25(3.94) a.u.;p= 0.19] returned to pre-donation levels.Significance.The AC and DC components of finger pulse oximetry changed during blood donation in asymptomatic volunteers. The continuous monitoring of these signals could be helpful in detecting occult acute hypovolemia. New pulse oximeters should be developed combining the AC/DC signals with a functional hemodynamic monitoring of fluid responsiveness to define which patient needs fluid administration.

Non-invasive biomarkers for detecting progression toward hypovolemic cardiovascular instability in a lower body negative pressure model.

Occult hemorrhages after trauma can be present insidiously, and if not detected early enough can result in patient death. This study evaluated a hemorrhage model on 18 human subjects, comparing the performance of traditional vital signs to multiple off-the-shelf non-invasive biomarkers. A validated lower body negative pressure (LBNP) model was used to induce progression towards hypovolemic cardiovascular instability. Traditional vital signs included mean arterial pressure (MAP), electrocardiography (ECG), plethysmography (Pleth), and the test systems utilized electrical impedance via commercial electrical impedance tomography (EIT) and multifrequency electrical impedance spectroscopy (EIS) devices. Absolute and relative metrics were used to evaluate the performance in addition to machine learning-based modeling. Relative EIT-based metrics measured on the thorax outperformed vital sign metrics (MAP, ECG, and Pleth) achieving an area-under-the-curve (AUC) of 0.99 (CI 0.95-1.00, 100% sensitivity, 87.5% specificity) at the smallest LBNP change (0-15 mmHg). The best vital sign metric (MAP) at this LBNP change yielded an AUC of 0.6 (CI 0.38-0.79, 100% sensitivity, 25% specificity). Out-of-sample predictive performance from machine learning models were strong, especially when combining signals from multiple technologies simultaneously. EIT, alone or in machine learning-based combination, appears promising as a technology for early detection of progression toward hemodynamic instability.

RELATIONSHIP BETWEEN SHOCK INDEX, MODIFIED SHOCK INDEX, AND AGE SHOCK INDEX AND 28-DAY MORTALITY AMONG PATIENTS WITH PREHOSPITAL SEPTIC SHOCK.

BACKGROUND: A relative hypovolemia occurs during septic shock (SS); the early phase is clinically reflected by tachycardia and low blood pressure. In the prehospital setting, simple objective tools to assess hypovolemia severity are needed to optimize triaging. OBJECTIVE: The aim of this study was to evaluate the relationship between shock index (SI), diastolic SI (DSI), modified SI (MSI), and age SI (ASI) and 28-day mortality of patients with SS initially cared for in a prehospital setting of a mobile intensive care unit (MICU). METHODS: From April 6, 2016 through December 31, 2021, 530 patients with SS cared for at a prehospital MICU were analyzed retrospectively. Initial SI, MSI, DSI, and ASI values, that is, first measurement after MICU arrival to the scene were calculated. A propensity score analysis with inverse probability of treatment weighting (IPTW) method was used to assess the relationship between SI, DSI, MSI, and ASI and 28-day mortality. RESULTS: SS resulted mainly from pulmonary, digestive, and urinary infections in 44%, 25%, and 17% of patients. The 28-day overall mortality was 31%. IPTW propensity score analysis indicated a significant relationship between 28-day mortality and SI (adjusted odds ratio [aOR] 1.13; 95% CI 1.01-1.26; p = 0.04), DSI (aOR 1.16; 95% CI 1.06-1.34; p = 0.03), MSI (aOR 1.03; 95% CI 1.01-1.17; p = 0.03), and ASI (aOR 3.62; 95% CI 2.63-5.38; p < 10-6). CONCLUSIONS: SI, DSI, MSI, and ASI were significantly associated with 28-day mortality among patients with SS cared for at a prehospital MICU. Further studies are needed to confirm the usefulness of SI and SI derivates for prehospital SS optimal triaging.

A Comparison of Normalization Techniques for Individual Baseline-Free Estimation of Absolute Hypovolemic Status Using a Porcine Model.

Hypovolemic shock is one of the leading causes of death in the military. The current methods of assessing hypovolemia in field settings rely on a clinician assessment of vital signs, which is an unreliable assessment of hypovolemia severity. These methods often detect hypovolemia when interventional methods are ineffective. Therefore, there is a need to develop real-time sensing methods for the early detection of hypovolemia. Previously, our group developed a random-forest model that successfully estimated absolute blood-volume status (ABVS) from noninvasive wearable sensor data for a porcine model (n = 6). However, this model required normalizing ABVS data using individual baseline data, which may not be present in crisis situations where a wearable sensor might be placed on a patient by the attending clinician. We address this barrier by examining seven individual baseline-free normalization techniques. Using a feature-specific global mean from the ABVS and an external dataset for normalization demonstrated similar performance metrics compared to no normalization (normalization: R2 = 0.82 ± 0.025|0.80 ± 0.032, AUC = 0.86 ± 5.5 × 10-3|0.86 ± 0.013, RMSE = 28.30 ± 0.63%|27.68 ± 0.80%; no normalization: R2 = 0.81 ± 0.045, AUC = 0.86 ± 8.9 × 10-3, RMSE = 28.89 ± 0.84%). This demonstrates that normalization may not be required and develops a foundation for individual baseline-free ABVS prediction.

The Edwards Acumen IQ system using peripheral arterial catheter-based waveforms to estimate cardiac output is not accurate as compared to thermodilution in dogs.

OBJECTIVE: To assess the agreement between cardiac output (CO) estimated via evaluation of the arterial pressure waveform by a novel monitoring system (Edwards Acumen IQ sensor and HemoSphere Advanced Monitor Platform [HS-IQ]; Edwards LifeSciences) and measured by thermodilution (TD) in anesthetized, normovolemic, and hypovolemic dogs. To assess the agreement between the HS-IQ CO measurements in the radial artery and dorsal metatarsal artery. ANIMALS: 8 purpose-bred Beagles. METHODS: Dogs were placed under general anesthesia. CO was measured via TD and via the HS-IQ at radial and dorsal metatarsal arterial catheters. CO measurements were obtained at 4 time points including normovolemic and multiple hypovolemic states. Paired measurements of CO were evaluated via the method of Bland and Altman with acceptable limits of agreement (LOA) defined as < 30%. RESULTS: A total of 24 (dorsal metatarsal) and 21 (radial) paired measurements were collected in 8 dogs. The overall bias (CI) for comparison of TD to radial arterial HS-IQ CO measurements was -0.09 L/min. LOA and proportional LOA were -2.66 to 2.49 L/min and -140.72% to 104.94%. The overall bias (CI) for comparison of TD to dorsal metatarsal arterial HS-IQ CO measurements was -0.26 L/min. LOA and proportional LOA were -2.76 to 2.24 L/min and -135.96% to 93.25%. The overall proportional error for radial arterial was -17.9% and for dorsal metatarsal was -21.4%. CLINICAL RELEVANCE: CO measurements with the HS-IQ were easy to obtain but did not produce results within a clinically acceptable range for either measurement site, with a very wide LOA. The CO estimations from the HS-IQ are not appropriate for clinical use at this time.

Blood volume and hemodynamics during treatment of major hemorrhage with Ringer solution, 5% albumin, and 20% albumin: a single-center randomized controlled trial.

BACKGROUND: Volume replacement with crystalloid fluid is the conventional treatment of hemorrhage. We challenged whether a standardized amount of 5% or 20% albumin could be a viable option to maintain the blood volume during surgery associated with major hemorrhage. Therefore, the aim of this study was to quantify and compare the plasma volume expansion properties of 5% albumin, 20% albumin, and Ringer-lactate, when infused during major surgery. METHODS: In this single-center randomized controlled trial, fluid replacement therapy to combat hypovolemia during the hemorrhagic phase of cystectomy was randomly allocated in 42 patients to receive either 5% albumin (12 mL/kg) or 20% albumin (3 mL/kg) over 30 min at the beginning of the hemorrhagic phase, both completed by a Ringer-lactate replacing blood loss in a 1:1 ratio, or Ringer-lactate alone to replace blood loss in a 3:1 ratio. Measurements of blood hemoglobin over 5 h were used to estimate the effectiveness of each fluid to expand the blood volume using the following regression equation: blood loss plus blood volume expansion = factor + volume of infused albumin + volume of infused Ringer-lactate. RESULTS: The median hemorrhage was 848 mL [IQR: 615-1145]. The regression equation showed that the Ringer-lactate solution expanded the plasma volume by 0.18 times the infused volume while the corresponding power of 5% and 20% albumin was 0.74 and 2.09, respectively. The Ringer-lactate only fluid program resulted in slight hypovolemia (mean, - 313 mL). The 5% and 20% albumin programs were more effective in filling the vascular system; this was evidenced by blood volume changes of only + 63 mL and - 44 mL, respectively, by long-lasting plasma volume expansion with median half time of 5.5 h and 4.8 h, respectively, and by an increase in the central venous pressure. CONCLUSION: The power to expand the plasma volume was 4 and almost 12 times greater for 5% albumin and 20% albumin than for Ringer-lactate, and the effect was sustained over 5 h. The clinical efficacy of albumin during major hemorrhage was quite similar to previous studies with no hemorrhage. TRIAL REGISTRATION: ClinicalTrials.gov NCT05391607, date of registration May 26, 2022.

Predicting fluid responsiveness in spontaneously breathing parturients undergoing caesarean section via carotid artery blood flow and velocity time integral measured by carotid ultrasound: a prospective cohort study.

BACKGROUND: Present evidence suggests that the Doppler ultrasonographic indices, such as carotid artery blood flow (CABF) and velocity time integral (VTI), had the ability to predict fluid responsiveness in non-obstetric patients. The purpose of this study was to assess their capacity to predict fluid responsiveness in spontaneous breathing parturients undergoing caesarean section and to determine the effect of detecting and management of hypovolemia (fluid responsiveness) on the incidence of hypotension after anaesthesia. METHODS: A total of 72 full term singleton parturients undergoing elective caesarean section were enrolled in this study. CABF, VTI, and hemodynamic parameters were recorded before and after fluid challenge and assessed by carotid artery ultrasonography. Fluid responsiveness was defined as an increase in stroke volume index (SVI) of 15% or more after the fluid challenge. RESULTS: Thirty-one (43%) patients were fluid responders. The area under the ROC curve to predict fluid responsiveness for CABF and VTI were 0.803 (95% CI, 0.701-0.905) and 0.821 (95% CI, 0.720-0.922). The optimal cut-off values of CABF and VTI for fluid responsiveness was 175.9 ml/min (sensitivity of 74.0%; specificity of 78.0%) and 8.7 cm/s (sensitivity of 67.0%; specificity of 90.0%). The grey zone for CABF and VTI were 114.2-175.9 ml/min and 6.8-8.7 cm/s. The incidence of hypotension after the combined spinal-epidural anaesthesia (CSEA) was significantly higher in the Responders group 25.8% (8/31) than in the Non-Responders group 17.1(7/41) (P < 0.001). The total incidence of hypotension after CSEA of the two groups was 20.8% (15/72). CONCLUSIONS: Ultrasound evaluation of CABF and VTI seem to be the feasible parameters to predict fluid responsiveness in parturients undergoing elective caesarean section and detecting and management of hypovolemia (fluid responsiveness) could significantly decrease incidence of hypotension after anaesthesia. TRIAL REGISTRATION: The trial was registered at the Chinese Clinical Trial Registry (ChiCTR) ( www.chictr.org ), registration number was ChiCTR1900022327 (The website link: https://www.chictr.org.cn/showproj.html?proj=37271 ) and the date of trial registration was in April 5, 2019. This study was performed in accordance with the Declaration of Helsinki and approved by the Research Ethics Committee of Women's Hospital, Zhejiang University School of Medicine (20,180,120).

Impaired cardiopulmonary baroreflex function and altered cardiovascular responses to hypovolemia in patients with heart failure with preserved ejection fraction.

Heart failure with preserved ejection fraction (HFpEF) is associated with autonomic dysregulation, which may be related to baroreflex dysfunction. Thus, we tested the hypothesis that cardiac and peripheral vascular responses to baroreflex activation via lower-body negative pressure (LBNP; -10, -20, -30, -40 mmHg) would be diminished in patients with HFpEF (n = 10, 71 ± 7 yr) compared with healthy controls (CON, n = 9, 69 ± 5 yr). Changes in heart rate (HR), mean arterial pressure (MAP, Finapres), forearm blood flow (FBF, ultrasound Doppler), and thoracic impedance (Z) were determined. Mild levels of LBNP (-10 and -20 mmHg) were used to specifically assess the cardiopulmonary baroreflex, whereas responses across the greater levels of LBNP represented an integrated baroreflex response. LBNP significantly increased in HR in CON subjects at -30 and -40 mmHg (+3 ± 3 and +6 ± 5 beats/min, P < 0.01), but was unchanged in patients with HFpEF across all LBNP levels. LBNP provoked progressive peripheral vasoconstriction, as quantified by changes in forearm vascular conductance (FVC), in both groups. However, a marked (40%-60%) attenuation in FVC responses was observed in patients with HFpEF (-6 ± 8, -15 ± 6, -16 ± 5, and -19 ± 7 mL/min/mmHg at -10, -20, -30, and -40 mmHg, respectively) compared with controls (-15 ± 10, -22 ± 6, -25 ± 10, and -28 ± 10 mL/min/mmHg, P < 0.01). MAP was unchanged in both groups. Together, these data provide new evidence for impairments in cardiopulmonary baroreflex function and diminished cardiovascular responsiveness during hypovolemia in patients with HFpEF, which may be an important aspect of the disease-related changes in autonomic cardiovascular control in this patient group.NEW & NOTEWORTHY Data from the current study demonstrate diminished cardiovascular responsiveness during hypovolemia induced by incremental lower-body negative pressure in patients with heart failure with preserved ejection fraction (HFpEF). These diminished responses imply impaired cardiopulmonary baroreflex function and altered autonomic cardiovascular regulation which may represent an important aspect of HFpEF pathophysiology.

Sex Differences in Sympathetic Responses to Lower-Body Negative Pressure.

INTRODUCTION: Trauma-induced hemorrhage is a leading cause of death in prehospital settings. Experimental data demonstrate that females have a lower tolerance to simulated hemorrhage (i.e., central hypovolemia). However, the mechanism(s) underpinning these responses are unknown. Therefore, this study aimed to compare autonomic cardiovascular responses during central hypovolemia between the sexes. We hypothesized that females would have a lower tolerance and smaller increase in muscle sympathetic nerve activity (MSNA) to simulated hemorrhage. METHODS: Data from 17 females and 19 males, aged 19-45 yr, were retrospectively analyzed. Participants completed a progressive lower-body negative pressure (LBNP) protocol to presyncope to simulate hemorrhagic tolerance with continuous measures of MSNA and beat-to-beat hemodynamic variables. We compared responses at baseline, at two LBNP stages (-40 and -50 mmHg), and at immediately before presyncope. In addition, we compared responses at relative percentages (33%, 66%, and 100%) of hemorrhagic tolerance, calculated via the cumulative stress index (i.e., the sum of the product of time and pressure at each LBNP stage). RESULTS: Females had lower tolerance to central hypovolemia (female: 561 ± 309 vs male: 894 ± 304 min·mmHg [time·LBNP]; P = 0.003). At LBNP -40 and -50 mmHg, females had lower diastolic blood pressures (main effect of sex: P = 0.010). For the relative LBNP analysis, females exhibited lower MSNA burst frequency (main effect of sex: P = 0.016) accompanied by a lower total vascular conductance (sex: P = 0.028; main effect of sex). CONCLUSIONS: Females have a lower tolerance to central hypovolemia, which was accompanied by lower diastolic blood pressure at -40 and -50 mmHg LBNP. Notably, females had attenuated MSNA responses when assessed as relative LBNP tolerance time.

Sodium-Glucose Cotransporter 2 Inhibitors Should Be Avoided for the Inpatient Management of Hyperglycemia.

OBJECTIVE: Hyperglycemia in patients with type 2 diabetes mellitus is frequently encountered in the hospital setting. The recent guidelines for the management of inpatient hyperglycemia have included the use of dipeptidyl peptidase 4 inhibitors as an alternative to standard insulin therapy in select patients. This raises the question of the inpatient use of sodium-glucose cotransporter 2 inhibitors (SGLT2i), which have gained increasing popularity in the outpatient setting because of beneficial cardiovascular and renal outcomes. This article describes the risks associated with the use of SGLT2i for the management of inpatient hyperglycemia. METHODS: A literature review was performed using PubMed and Google Scholar for studies assessing the inpatient use of SGLT2i. Search terms included "SGLT2 inhibitors," "euglycemic DKA," "inpatient hyperglycemia," "DPP4 inhibitors," "hypovolemia," and "urinary tract infections." Studies not written in English were excluded. Forty-eight articles were included. RESULTS: Review of the literature showed significant safety concerns with the use of SGLT2i for the inpatient management of hyperglycemia. Hospitalized patients treated with SGLT2i were at increased risk of diabetic ketoacidosis, euglycemic diabetic ketoacidosis, hypovolemia, and urinary tract infections. When compared head-to-head, SGLT2i were not more effective for inpatient glycemic control than dipeptidyl peptidase 4 inhibitors and did not reduce insulin requirements when used in combination with insulin. Although SGLT2i can be considered for the treatment of congestive heart failure, they should be started close to or at the time of discharge. CONCLUSION: Although SGLT2i are a preferred pharmacotherapy class for the outpatient management of type 2 diabetes mellitus, there are considerable safety concerns when using them in a hospital setting, and avoidance is recommended.

Assessment of changes in blood volume during lower body negative pressure-induced hypovolemia using bioelectrical impedance analysis.

BACKGROUND: Lower body negative Pressure (LBNP)-induced hypovolemia is simulating acute hemorrhage by sequestrating blood into lower extremities. Bioelectrical Impedance Analysis (BIA) is based on the electrical properties of biological tissues, as electrical current flows along highly conductive body tissues (such as blood). Changes in blood volume will lead to changes in bioimpedance. This study aims to study changes in upper (UL) and lower (LL) extremities bioimpedance during LBNP-induced hypovolemia. METHODS: This was a prospective observational study of healthy volunteers who underwent gradual LBNP protocol which consisted of 3-minute intervals: at baseline, -15, -30, -45, -60 mmHg, then recovery phases at -30 mmHg and baseline. The UL&LL extremities bioimpedance were measured and recorded at each phase of LBNP and the percentage changes of bioimpedance from baseline were calculated and compared using student's t-test. A P-value of < 0.05 was considered significant. Correlation between relative changes in UL&LL bioimpedance and estimated blood loss (EBL) from LBNP was calculated using Pearson correlation. RESULTS: 26 healthy volunteers were enrolled. As LBNP-induced hypovolemia progressed, there were a significant increase in UL bioimpedance and a significant decrease in LL bioimpedance. During recovery phases (where blood was shifted from the legs to the body), there were a significant increase in LL bioimpedance and a reduction in UL bioimpedance. There were significant correlations between estimated blood loss from LBNP model with UL (R = 0.97) and LL bioimpedance (R = - 0.97). CONCLUSION: During LBNP-induced hypovolemia, there were reciprocal changes in UL&LL bioimpedance. These changes reflected hemodynamic compensatory mechanisms to hypovolemia.

Diagnostic Adjunct Techniques in the Assessment of Hypovolemia: A Prospective Pilot Project.

INTRODUCTION: Measuring the hypovolemic resuscitation end point remains a critical care challenge. Our project compared clinical hypovolemia (CH) with three diagnostic adjuncts: 1) noninvasive cardiac output monitoring (NICOM), 2) ultrasound (US) static IVC collapsibility (US-IVC), and 3) US dynamic carotid upstroke velocity (US-C). We hypothesized US measures would correlate more closely to CH than NICOM. METHODS: Adult trauma/surgical intensive care unit patients were prospectively screened for suspected hypovolemia after acute resuscitation, excluding patients with burns, known heart failure, or severe liver/kidney disease. Adjunct measurements were assessed up to twice a day until clinical improvement. Hypovolemia was defined as: 1) NICOM: ≥10% stroke volume variation with passive leg raise, 2) US-IVC: <2.1 cm and >50% collapsibility (nonventilated) or >18% collapsibility (ventilated), 3) US-C: peak systolic velocity increase 15 cm/s with passive leg raise. Previously unknown cardiac dysfunction seen on US was noted. Observation-level data were analyzed with a Cohen's kappa (κ). RESULTS: 44 patients (62% male, median age 60) yielded 65 measures. Positive agreement with CH was 47% for NICOM, 37% for US-IVC and 10% for US-C. None of the three adjuncts correlated with CH (κ -0.045 to 0.029). After adjusting for previously unknown cardiac dysfunction present in 10 patients, no adjuncts correlated with CH (κ -0.036 to 0.031). No technique correlated with any other (κ -0.118 to 0.083). CONCLUSIONS: None of the adjunct measurements correlated with CH or each other, highlighting that fluid status assessment remains challenging in critical care. US should assess for right ventricular dysfunction prior to resuscitation.

Use of POCUS for the assessment of dehydration in pediatric patients-a narrative review.

In pediatric practice, POCUS (point-of-care ultrasound) has been mostly implemented to recognize lung conditions and pleural and pericardial effusions, but less to evaluate fluid depletion. The main aim of this review is to analyze the current literature on the assessment of dehydration in pediatric patients by using POCUS. The size of the inferior vena cava (IVC) and its change in diameter in response to respiration have been investigated as a tool to screen for hypovolemia. A dilated IVC with decreased collapsibility (< 50%) is a sign of increased right atrial pressure. On the contrary, a collapsed IVC may be indicative of hypovolemia. The IVC collapsibility index (cIVC) reflects the decrease in the diameter upon inspiration. Altogether the IVC diameter and collapsibility index can be easily determined, but their role in children has not been fully demonstrated, and an estimation of volume status solely by assessing the IVC should thus be interpreted with caution. The inferior vena cava/abdominal aorta (IVC/AO) ratio may be a suitable parameter to assess the volume status in pediatric patients even though there is a need to define age-based thresholds. A combination of vascular, lung, and cardiac POCUS could be a valuable supplementary tool in the assessment of dehydration in several clinical scenarios, enabling rapid identification of life-threatening primary etiologies and helping physicians avoid inappropriate therapeutic interventions.   Conclusion: POCUS can provide important information in the assessment of intravascular fluid status in emergency scenarios, but measurements may be confounded by a number of other clinical variables. The inclusion of lung and cardiac views may assist in better understanding the patient's physiology and etiology regarding volume status. What is Known: • In pediatric practice, POCUS (point-of-care ultrasound) has been mostly implemented to recognize lung conditions (like pneumonia and bronchiolitis) and pleural and pericardial effusions, but less to evaluate fluid depletion. • The size of the IVC (inferior vena cava) and its change in diameter in response to respiration have been studied as a possible screening tool to assess the volume status, predict fluid responsiveness, and assess potential intolerance to fluid loading. What is New: • The IVC diameter and collapsibility index can be easily assessed, but their role in predicting dehydration in pediatric age has not been fully demonstrated, and an estimation of volume status only by assessing the IVC should be interpreted carefully. • The IVC /AO(inferior vena cava/abdominal aorta) ratio may be a suitable parameter to assess the volume status in pediatric patients even though there is a need to define age-based thresholds. A combination of vascular, lung, and cardiac POCUS can be a valuable supplementary tool in the assessment of intravascular volume in several clinical scenarios.

Acute fasting reduces tolerance to progressive central hypovolemia in humans.

Potential health benefits of an acute fast include reductions in blood pressure and increases in vagal cardiac control. These purported health benefits could put fasted humans at risk for cardiovascular collapse when exposed to central hypovolemia. The purpose of this study was to test the hypothesis that an acute 24-h fast (vs. 3-h postprandial) would reduce tolerance to central hypovolemia induced via lower body negative pressure (LBNP). We measured blood ketones (ß-OHB) to confirm a successful fast (n = 18). We recorded the electrocardiogram (ECG), beat-to-beat arterial pressure, muscle sympathetic nerve activity (MSNA; n = 7), middle cerebral artery blood velocity (MCAv), and forearm blood flow. Following a 5-min baseline, LBNP was increased by 15 mmHg until -60 mmHg and then increased by 10 mmHg in a stepwise manner until onset of presyncope. Each LBNP stage lasted 5-min. Data are expressed as means ± SE ß-OHB increased (ß-OHB; 0.12 ± 0.04 fed vs. 0.47 ± 0.11, P < 0.01 mmol/L fast). Tolerance to central hypovolemia was decreased by ∼10% in the fasted condition measured via total duration of negative pressure (1,370 [Formula: see text] 89 fed vs. 1,229 ± 94 s fast, P = 0.04), and was negatively associated with fasting blood ketones (R = -0.542, P = 0.02). During LBNP, heart rate and MSNA increased similarly, but in the fasted condition forearm vascular resistance was significantly reduced. Our results suggest that acute fasting reduces tolerance to central hypovolemia by blunting increases in peripheral resistance, indicating that prolonged fasting may hinder an individual's ability to compensate to a loss of blood volume.NEW & NOTEWORTHY An acute 24 h fasting reduces tolerance to central hypovolemia, and tolerance is negatively associated with blood ketone levels. Compared with a fed condition (3-h postprandial), fasted participants exhibited blunted peripheral vasoconstriction and greater reductions in stroke volume during stepwise lower body negative pressure. These findings suggest that a prolonged fast may lead to quicker decompensation during central hypovolemia.

Maldistribution of fluid in preeclampsia: a secondary kinetic analysis.

BACKGROUND: Hypovolemia 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. METHODS: Ringers 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. RESULTS: The 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. CONCLUSION: Decreased 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.

Towards a Lightweight Classifier to Detect Hypovolemic Shock.

Predicting the ability of an individual to compensate for blood loss during hemorrhage and detect the likely onset of hypovolemic shock is necessary to permit early clinical intervention. Towards this end, the compensatory reserve metric (CRM) has been demonstrated to directly correlate with an individual's ability to maintain compensatory mechanisms during loss of blood volume from onset (one-hundred percent health) to exsanguination (zero percent health). This effort describes a lightweight, three-class predictor (good, fair, poor) of an individual's compensatory reserve using a linear support-vector machine (SVM) classifier. A moving mean filter of the predictions demonstrates a feasible model for implementation of real-time hypovolemia monitoring on a wearable device, requiring only 408 bytes to store the models' coefficients and minimal processor cycles to complete the computations.

Near-Infrared Spectroscopy Monitoring to Detect Changes in Cerebral and Renal Perfusion During Hypovolemic Shock, Volume Resuscitation, and Vasoconstriction.

INTRODUCTION: Rapidly changing hemodynamic conditions, such as uncontrolled hemorrhage and the resulting hypovolemic shock, are a common contributor to active duty military deaths. These conditions can cause cerebral desaturation, and outcomes may improve when regional cerebral oxygen saturation (CrSO2) is monitored using near-infrared spectroscopy (NIRS) and desaturation episodes are recognized and reversed. The purpose of this porcine study was to investigate the ability of NIRS monitoring to detect changes in regional cerebral and regional renal perfusion during hypovolemia, resuscitation by volume infusion, and vasoconstriction. MATERIALS AND METHODS: Hemorrhagic shock was induced by removing blood through a central venous catheter until mean arterial pressure (MAP) was <40 mmHg. Each blood removal step was followed by a 10-minute stabilization period, during which cardiac output, blood pressure, central venous pressure, blood oxygen saturation, and CrSO2 and regional renal oxygen saturation (RrSO2) were measured. Shock was reversed using blood infusion and vasoconstriction separately until MAP returned to normal. Statistical comparisons between groups were performed using the paired t-test or the Wilcoxon signed-rank test. RESULTS: Using volume resuscitation, both CrSO2 and RrSO2 returned to normal levels after hypovolemia. Blood pressure management with phenylephrine returned CrSO2 levels to normal, but RrSO2 levels remained significantly lower compared to the pre-hemorrhage values (P < .0001). Comparison of the percent CrSO2 as a function of MAP showed that CrSO2 levels approach baseline when a normal MAP is reached during volume resuscitation. In contrast, a significantly higher MAP was required to return to baseline CrSO2 during blood pressure management with phenylephrine (P < .0001). Evaluation of carotid blood flow and CrSO2 indicated that during induction of hypovolemia, the two measures are strongly correlated. In contrast, there was limited correlation between carotid blood flow and CrSO2 during blood infusion. CONCLUSIONS: This study demonstrated that it is possible to restore CrSO2 by manipulating MAP with vasoconstriction, even in profound hypotension. However, MAP manipulation may result in unintended consequences for other organs, such as the kidney, if the tissue is not reoxygenated sufficiently. The clinical implications of these results and how best to respond to hypovolemia in the pre-hospital and hospital settings should be elucidated by additional studies.

Intraoperative Use of Compensatory Reserve Measurement in Orthotopic Liver Transplant: Improved Sensitivity for the Prediction of Hypovolemic Events.

INTRODUCTION: The compensatory reserve measurement (CRM) is a continuous non-invasive monitoring technology that measures the summation of all physiological mechanisms involved in the compensatory response to central hypovolemia. The CRM is displayed on a 0% to 100% scale. The objective of this study is to characterize the use of CRM in the operative setting and determine its ability to predict hypovolemic events compared to standard vital signs. Orthotopic liver transplant was used as the reference procedure because of the predictable occurrence of significant hemodynamic shifts. METHODS: A prospective observational cohort study was conducted on 22 consecutive patients undergoing orthotopic liver transplant. The subjects were monitored in accordance with the standard of care. The CRM data were collected concurrently with intraoperative staff blinded to the outputs. The data were stored on secure devices on encrypted files. Based on prior literature, subgroup analysis was performed for high-tolerance (good compensators) and low-tolerance (poor compensators) groups, which was based on a shock index threshold of 0.9. Threshold events were defined as follows: CRM below 60% (CRM60), systolic blood pressure (SBP) below 90 mmHg (SBP90), and heart rate (HR) above 100 beats per minute (HR100). RESULTS: Complete data were captured in 22 subjects as a result of device malfunction or procedure cancellation. Sensitivity analysis was performed for the detection of hypovolemia at the time of the event. CRM60 was the most sensitive (62.6%) when compared to other threshold measures such as SBP90 (30.6%), HR100 (23.1%), elevated lactate (54.6%), and a drop in hemoglobin (41.7%). The number of patients meeting the CRM60 threshold at the time of the first transfusion (TFX) was higher when compared to SBP90 and HR100 in the overall group (P = .001 and P < .001, respectively) and both the high-tolerance (P = .002 and P = .001, respectively) and low-tolerance groups (P = .016 and P = .001, respectively). Similar results supporting the higher sensitivity of CRM were observed when comparing the number of patients below the threshold at the time of the first vasopressor administration. Start time was standardized so that the time-to-threshold signals for hemodynamic and laboratory parameters could be compared. The median time-to-CRM signal detection before the TFX event was -15.0 minutes (i.e., 15 minutes before TFX). There was no difference when compared to the SBP threshold (median time -5.0 minutes, P = .64) but was significantly sooner when compared to HR (P = .006), lactate (P = .002), and hemoglobin (P < .001). CONCLUSIONS: At the time of the first TFX, the CRM had a higher rate of detection of a hypovolemic event compared to SBP and HR, indicating a higher sensitivity for the detection of the first hypovolemic event. When combined with all hypovolemic events, sensitivity analysis showed that CRM60 provides the earlier predictive capability. Given that SBP is the clinical standard of care for the initiation of TFX, the finding that median time to event detection was statistically similar between CRM60 and SBP90 was not unexpected. When compared to other measures of hypovolemia, the CRM consistently showed earlier detection of hypovolemic events. Although this study had a small sample size, it produced significant results and can serve as a proof of concept for future large-scale studies.

Diagnosis and Management of Sodium Disorders: Hyponatremia and Hypernatremia.

Hyponatremia and hypernatremia are electrolyte disorders that can be associated with poor outcomes. Hyponatremia is considered mild when the sodium concentration is 130 to 134 mEq per L, moderate when 125 to 129 mEq per L, and severe when less than 125 mEq per L. Mild symptoms include nausea, vomiting, weakness, headache, and mild neurocognitive deficits. Severe symptoms of hyponatremia include delirium, confusion, impaired consciousness, ataxia, seizures, and, rarely, brain herniation and death. Patients with a sodium concentration of less than 125 mEq per L and severe symptoms require emergency infusions with 3% hypertonic saline. Using calculators to guide fluid replacement helps avoid overly rapid correction of sodium concentration, which can cause osmotic demyelination syndrome. Physicians should identify the cause of a patient's hyponatremia, if possible; however, treatment should not be delayed while a diagnosis is pursued. Common causes include certain medications, excessive alcohol consumption, very low-salt diets, and excessive free water intake during exercise. Management to correct sodium concentration is based on whether the patient is hypovolemic, euvolemic, or hypervolemic. Hypovolemic hyponatremia is treated with normal saline infusions. Treating euvolemic hyponatremia includes restricting free water consumption or using salt tablets or intravenous vaptans. Hypervolemic hyponatremia is treated primarily by managing the underlying cause (e.g., heart failure, cirrhosis) and free water restriction. Hypernatremia is less common than hyponatremia. Mild hypernatremia is often caused by dehydration resulting from an impaired thirst mechanism or lack of access to water; however, other causes, such as diabetes insipidus, are possible. Treatment starts with addressing the underlying etiology and correcting the fluid deficit. When sodium is severely elevated, patients are symptomatic, or intravenous fluids are required, hypotonic fluid replacement is necessary.

Incidence and risk factors of acute kidney injury in patients with malignant tumors: a systematic review and meta-analysis.

BACKGROUND: There are significant differences in the incidence and risk factors of tumor patients, and there is no relevant statistical data. Therefore, this study aims to clarify the incidence and risk factors of acute kidney injury (AKI) in malignant tumor patients and compare critically ill patients with non-critically ill patients. METHODS: Relevant literature on the occurrence of AKI in malignant tumors was retrieved from databases. Two authors independently screened and evaluated the eligibility and quality of the literature and extracted the data. The Stata 12.0 software was used for meta-analysis. RESULTS: A total of 3922 articles were initially retrieved, and 24 articles were finally included, 8 of which were about critically ill malignant tumor patients, and 16 were about malignant tumor patients. Among the 4107 patients included in the 8 studies on critically ill malignant tumors, 1932 developed AKI, with an incidence rate of 52% (95%CI 34-70%, I2 = 99%). The risk factors for AKI in critically ill malignant tumor patients were sepsis and hypovolemia, which were different from those in non-critically ill patients. Among the 292,874 patients included in the 16 studies on malignant tumors, 51,211 developed AKI, and the combined incidence rate was 24% (95%CI 17-30%, I2 = 100%). The risk factors for AKI in critical malignant tumor patients were sepsis and hypovolemia. CONCLUSION: This meta-analysis shows that the incidence of AKI in critically ill malignant tumor patients is consistent with that in other critically ill patients, and independent risk factors are sepsis and hypovolemia. The incidence of AKI in malignant tumor patients is higher than that in other patients, and tumor is a risk factor for AKI. This study has been registered in INPLASY (INPLASY202320079),Registered February 18,2023.