Showing papers on "Hypovolemia published in 2019"

The independent effects of hypovolaemia and pulmonary vasoconstriction on ventricular function and exercise capacity during acclimatisation to 3800 m.

Abstract: KEY POINTS We sought to determine the isolated and combined influence of hypovolaemia and hypoxic pulmonary vasoconstriction on the decrease in left ventricular (LV) function and maximal exercise capacity observed under hypobaric hypoxia. We performed echocardiography and maximal exercise tests at sea level (344 m), and following 5-10 days at the Barcroft Laboratory (3800 m; White Mountain, California) with and without (i) plasma volume expansion to sea level values and (ii) administration of the pulmonary vasodilatator sildenafil in a double-blinded and placebo-controlled trial. The high altitude-induced reduction in LV filling and ejection was abolished by plasma volume expansion but to a lesser extent by sildenafil administration; however, neither intervention had a positive effect on maximal exercise capacity. Both hypovolaemia and hypoxic pulmonary vasoconstriction play a role in the reduction of LV filling at 3800 m, but the increase in LV filling does not influence exercise capacity at this moderate altitude. ABSTRACT We aimed to determine the isolated and combined contribution of hypovolaemia and hypoxic pulmonary vasoconstriction in limiting left ventricular (LV) function and exercise capacity under chronic hypoxaemia at high altitude. In a double-blinded, randomised and placebo-controlled design, 12 healthy participants underwent echocardiography at rest and during submaximal exercise before completing a maximal test to exhaustion at sea level (SL; 344 m) and after 5-10 days at 3800 m. Plasma volume was normalised to SL values, and hypoxic pulmonary vasoconstriction was reversed by administration of sildenafil (50 mg) to create four unique experimental conditions that were compared with SL values: high altitude (HA), Plasma Volume Expansion (HA-PVX), Sildenafil (HA-SIL) and Plasma Volume Expansion with Sildenafil (HA-PVX-SIL). High altitude exposure reduced plasma volume by 11% (P < 0.01) and increased pulmonary artery systolic pressure (19.6 ± 4.3 vs. 26.0 ± 5.4, P < 0.001); these differences were abolished by PVX and SIL respectively. LV end-diastolic volume (EDV) and stroke volume (SV) were decreased upon ascent to high altitude, but were comparable to sea level in the HA-PVX trial. LV EDV and SV were also elevated in the HA-SIL and HA-PVX-SIL trials compared to HA, but to a lesser extent. Neither PVX nor SIL had a significant effect on the LV EDV and SV response to exercise, or the maximal oxygen consumption or peak power output. In summary, at 3800 m both hypovolaemia and hypoxic pulmonary vasoconstriction contribute to the decrease in LV filling, but restoring LV filling does not confer an improvement in maximal exercise performance.

Episodes of hypovolemia/dehydration in baboons with pig kidney transplants: A new syndrome of clinical importance?

Abstract: To the Editor, We have carried out four kidney transplants from genetically modi‐ fied pigs in baboons, details of three of which have been reported.1,2 In all four, at various time intervals after renal transplantation, and on more than one occasion in three baboons, we have observed the development of features of hypovolemia and dehydration, manifest by an increase in serum creatinine (Figure 1). The baboons remained fully active, maintained a steady weight, and did not drink or urinate more or less than usual. However, when anesthetized, they were found to have a very low central venous pressure (initially <2 mm Hg), a low systolic arterial blood pressure (initially <60 mm Hg), and de‐ hydrated skin (loss of turgor) and tissues. The intravenous infusion of several hundred milliliters of normal saline (approximately 100 mL/kg body weight) was required to raise and maintain the venous pressure to normal levels. The intravenous infusion of normal saline was administered to the baboons under anesthesia over several hours. We discontinued administering fluid when the venous pressure and the systolic blood pressure had in‐ creased and were maintained at >5 and >80 mm Hg, respectively. No features of fluid overload, for example, pulmonary edema, were observed during or after fluid administration. The observation that the state of hypovolemia/dehydration occurred intermittently is presumably because, having corrected the volemic state of the ba‐ boon, it took some days or weeks for hypovolemia and dehydration to recur. We subsequently maintained a state of good hydration for sev‐ eral days by the subcutaneous administration of normal saline (ap‐ proximately 150‐200 mL × 2‐3 weekly for 1‐3 weeks). In some cases, when the serum creatinine again began to increase, daily subcutane‐ ous saline infusions alone proved sufficient to correct the situation.

Role of inferior vena cava collapsibility index in the prediction of hypotension associated with general anesthesia: an observational study

Abstract: Intraoperative hypotension increases 30-day mortality and the risks of myocardial injury and acute renal failure. Patients with inadequate volume reserve before the induction of anesthesia are highly exposed. The identification of latent hypovolemia is therefore crucial. Ultrasonographic measurement of the inferior vena cava collapsibility index (IVCCI) is able to detect volume responsiveness in circulatory shock. No current evidence is available regarding whether preoperative measurement of the IVCCI could identify patients at high risk for hypotension associated with general anesthesia. A total of 102 patients undergoing elective general surgery under general anesthesia with standardized propofol induction were recruited for this prospective observational study. The IVCCI was measured under spontaneous breathing. A collapsing (IVCCI≧50%) (CI+) and a noncollapsing (CI-) group were formed. Immediate postinduction changes in systolic and mean blood pressure were compared. The performance of the IVCCI as a diagnostic tool for predicting hypotension (systolic pressure < 90 mmHg or a ≥ 30% drop from the baseline) was evaluated by ROC curve analysis. A total of 83 patients were available for analysis, with 20 in the CI+ and 63 in the CI- group, we excluded 19 previously eligible patients due to inadequate visualization of the IVC (7 cases), lack of adherence to the protocol (8 cases), missing data (2 cases) or change in anesthesiologic management (2 cases). The mean decrease in systolic pressure in the CI+ group was 53.8 ± 15.3 compared to 35.8 ± 18.1 mmHg in CI- patients (P = 0.0001). The relative mean arterial pressure change medians were 34.1% (IQR 23.2–43.0%) and 24.2% (IQR 17.2–30.2%), respectively (P = 0.0029). The ROC curve analysis for IVCCI showed an AUC of 64.8% (95% CI 52.1–77.5%). The selected 50% level of the IVCCI had a sensitivity of only 45.5% (95% CI 28.1–63.7%), but the specificity was high at 90.0% (78.2–96.7%). The positive predictive value was 75.0% (95% CI 50.9–91.3%), and the negative predictive value was 71.4% (95% CI 58.7–82.1%). In spontaneously breathing preoperative noncardiac surgical patients, preoperatively detected IVCCI≧50% can predict postinduction hypotension with high specificity but low sensitivity. Despite moderate performance, IVCCI is an easy, noninvasive and attractive option to identify patients at risk and should be explored further.

Albumin infusion rate and plasma volume expansion: A randomized clinical trial in postoperative patients after major surgery

Abstract: Optimal infusion rate of colloids in patients with suspected hypovolemia is unknown, and the primary objective of the present study was to test if plasma volume expansion by 5% albumin is greater if fluid is administered slowly rather than rapidly. Patients with signs of hypoperfusion after major abdominal surgery were randomized to intravenous infusion of 5% albumin at a dose of 10 ml/kg (ideal body weight) either rapidly (30 min) or slowly (180 min). Plasma volume was measured using radiolabeled albumin at baseline, at 30 min, and at 180 min after the start of infusion. Primary outcome was change in plasma volume from the start of infusion to 180 min after the start of infusion. Secondary outcomes included the change in the area under the plasma volume curve and transcapillary escape rate (TER) for albumin from 180 to 240 min after the start of albumin infusion. A total of 33 and 31 patients were included in the analysis in the slow and rapid groups, respectively. The change in plasma volume from the start of infusion to 180 min did not differ between the slow and rapid infusion groups (7.4 ± 2.6 vs. 6.5 ± 4.1 ml/kg; absolute difference, 0.9 ml/kg [95%CI, − 0.8 to 2.6], P = 0.301). Change in the area under the plasma volume curve was smaller in the slow than in the rapid infusion group and was 866 ± 341 and 1226 ± 419 min ml/kg, respectively, P < 0.001. TER for albumin did not differ and was 5.3 ± 3.1%/h and 5.4 ± 3%/h in the slow and in the rapid infusion groups, respectively, P = 0.931. This study does not support our hypothesis that a slow infusion of colloid results in a greater plasma volume expansion than a rapid infusion. Instead, our result of a smaller change in the area under the plasma volume curve indicates that a slow infusion results in a less efficient plasma volume expansion, but further studies are required to confirm this finding. A rapid infusion has no effect on vascular leak as measured after completion of the infusion. EudraCT2013-004446-42 registered December 23, 2014.

Acute Postpartum Hemorrhage

Abstract: Obstetric hemorrhage is the most common and dangerous complication of childbirth. Traditionally, postpartum hemorrhage (PPH) has been traditionally defined as greater than 500 mL estimated blood loss in a vaginal delivery or greater than 1000 mL estimated blood loss at the time of cesarean delivery. This was redefined in 2017 by the American College of Obstetrics and Gynecology as cumulative blood loss greater than 1000 mL with signs and symptoms hypovolemia within 24 hours of the birth process, regardless of the route of delivery. While this was change was made with the knowledge that blood loss at the time of delivery is routinely underestimated, blood loss at the time of vaginal delivery greater than 500 mL should be considered abnormal with the potential need for intervention. Primary postpartum hemorrhage is bleeding that occurs in the first 24 hours after delivery, while secondary postpartum hemorrhage is characterized as bleeding that occurs 24 hours to 12 weeks postpartum.

Hemostatic responses to exercise, dehydration, and simulated bleeding in heat-stressed humans

Abstract: Heat stress followed by an accompanying hemorrhagic challenge may influence hemostasis We tested the hypothesis that hemostatic responses would be increased by passive heat stress, as well as exer

Acute Kidney Injury in Nephrotic Syndrome.

Abstract: Nephrotic syndrome (NS) is one of the commonest kidney diseases seen in childhood and is characterized by a relapsing remitting course. Various complications have been reported in children with NS, including infections, thromboembolism, hypovolemia, and acute kidney injury (AKI). There is often a modest decrease in renal function in patients with active proteinuria due to decreased glomerular permeability that improves when they go into remission. However, more pronounced AKI in NS is multifactorial in origin. It is most often secondary to hypovolemia, nephrotoxic medications, and infections, although other reasons may also be seen. Recent years have seen an increase in the incidence of AKI in NS. There is limited data on the correlation between AKI in pediatric NS and long-term outcomes. A better understanding of this increasingly common condition will help improve patient outcomes.

Cerebral Blood Flow Response to Simulated Hypovolemia in Essential Hypertension: A Magnetic Resonance Imaging Study.

Abstract: Hypertension is associated with raised cerebral vascular resistance and cerebrovascular remodeling. It is currently unclear whether the cerebral circulation can maintain cerebral blood flow (CBF) d...

Trigeminal Nerve Stimulation: A Novel Method of Resuscitation for Hemorrhagic Shock

Abstract: OBJECTIVES To determine if trigeminal nerve stimulation can ameliorate the consequences of acute blood loss and improve survival after severe hemorrhagic shock. DESIGN Animal study. SETTING University research laboratory. SUBJECTS Male Sprague-Dawley rats. INTERVENTIONS Severe hemorrhagic shock was induced in rats by withdrawing blood until the mean arterial blood pressure reached 27 ± 1 mm Hg for the first 5 minutes and then maintained at 27 ± 2 mm Hg for 30 minutes. The rats were randomly assigned to either control, vehicle, or trigeminal nerve stimulation treatment groups. The effects of trigeminal nerve stimulation on survival rate, autonomic nervous system activity, hemodynamics, brain perfusion, catecholamine release, and systemic inflammation after severe hemorrhagic shock in the absence of fluid resuscitation were analyzed. MEASUREMENTS AND MAIN RESULTS Trigeminal nerve stimulation significantly increased the short-term survival of rats following severe hemorrhagic shock in the absence of fluid resuscitation. The survival rate at 60 minutes was 90% in trigeminal nerve stimulation treatment group whereas 0% in control group (p < 0.001). Trigeminal nerve stimulation elicited strong synergistic coactivation of the sympathetic and parasympathetic nervous system as measured by heart rate variability. Without volume expansion with fluid resuscitation, trigeminal nerve stimulation significantly attenuated sympathetic hyperactivity paralleled by increase in parasympathetic tone, delayed hemodynamic decompensation, and improved brain perfusion following severe hemorrhagic shock. Furthermore, trigeminal nerve stimulation generated sympathetically mediated low-frequency oscillatory patterns of systemic blood pressure associated with an increased tolerance to central hypovolemia and increased levels of circulating norepinephrine levels. Trigeminal nerve stimulation also decreased systemic inflammation compared with the vehicle. CONCLUSIONS Trigeminal nerve stimulation was explored as a novel resuscitation strategy in an animal model of hemorrhagic shock. The results of this study showed that the stimulation of trigeminal nerve modulates both sympathetic and parasympathetic nervous system activity to activate an endogenous pressor response, improve cerebral perfusion, and decrease inflammation, thereby improving survival.

Comparison between men and women of volume regulating hormones and aquaporin-2 excretion following graded central hypovolemia.

Abstract: Central hypovolemia induced by orthostatic loading causes reno-vascular changes that can lead to orthostatic intolerance. In this study, we investigated volume regulating hormonal responses and reno-vascular changes in male and female subjects as they underwent central hypovolemia, induced by graded lower body negative pressure (LBNP). Aquaporin-2 (AQP2) excretion was measured as a biomarker for the renal system response to vasopressin. 37 young healthy subjects (n = 19 males; n = 18 females) were subjected to graded LBNP until − 40 mmHg LBNP. Under resting conditions, males had significantly higher copeptin (a stable peptide derived from vasopressin) levels compared with females. Adrenocorticotropin (ACTH), adrenomedullin (ADM), vasopressin (AVP) and brain natriuretic peptide (BNP) were not affected by our experimental protocol. Nevertheless, an analysis of ADM and BNP with the data normalized as percentages of the baseline value data showed an increase from baseline to 10 min after recovery in the males in ADM and in the females in BNP. Analysis of BNP and ADM raises the possibility of a preferential adaptive vascular response to central hypovolemia in males as shown by the normalized increase in ADM, whereas females showed a preferential renal response as shown by the normalized increase in BNP. Furthermore, our results suggest that there might be a difference between men and women in the copeptin response to alterations in orthostatic loading, simulated either using LBNP or during posture changes.

Differentiating compensatory mechanisms associated with low tolerance to central hypovolemia in women.

Abstract: We compared hemodynamic and metabolic responses in men and women to experimentally controlled reductions in central blood volume at physiologically equivalent levels of compensatory reserve. We cor...

Effect of intravenous ondansetron on spinal anesthesia-induced hypotension and bradycardia: A randomized controlled double-blinded study

Abstract: Background: Spinal anesthesia is a safe anesthetic technique commonly practiced. However, it is associated with hypotension (33%), bradycardia (13%), and shivering which are induced by hypovolemia, sympathetic blockade, and Bezold–Jarisch reflex through intracardiac serotonin (5HT3) receptors and vagus nerve. Aim: To study the effect of intravenous (i.v.) ondansetron on hypotension and bradycardia induced by spinal anesthesia. Setting and Design: This was a randomized controlled double-blinded study done in a tertiary care teaching hospital. Methods: Of 140 patients, 70 in Group A received 2 mL of i.v. ondansetron 4 mg and 70 in the Group B received 2 mL of i.v. normal saline. 3 mL of 0.5% hyperbaric bupivacaine was injected intrathecally. Measurements of blood pressure and heart rate (HR) were taken every 3 min for 30 min after spinal anesthesia was performed. Mean arterial pressure (MAP) drop more than 20% was considered as incidence of hypotension and ephedrine 6 mg i.v. was given. HR drop >20% was regarded as bradycardia and atropine 0.5 mg i.v. was given. Statistical Tests: Quantitative data were analyzed using ANOVA test and qualitative data were analyzed using Chi-square test. Results: Both groups are comparable in demographic data. Four (5.7%) patients in Group B and no patients in Group A had incidence of bradycardia and atropine requirement (P = 0.120). There was no statistically significant difference in systolic blood pressure, diastolic blood pressure, and MAP. 19 (27%) patients in Group A and 33 (47.1%) in Group B required ephedrine with P = 0.029. 12 (17.1%) in Group B and no patients in Group A had shivering with P = 0.0001. Conclusion: Our study indicates that prophylactic use of ondansetron before spinal anesthesia significantly reduces the requirement of ephedrine and shivering.

1D Convolutional Neural Networks for Estimation of Compensatory Reserve from Blood Pressure Waveforms

Abstract: We propose a Deep Convolutional Neural Network (CNN) architecture for computing a Compensatory Reserve Metric (CRM) for trauma victims suffering from hypovolemia (decreased circulating blood volume). The CRM is a single health indicator value that ranges from 100% for healthy individuals, down to 0% at hemodynamic decompensation – when the body can no longer compensate for blood loss. The CNN is trained on 20 second blood pressure waveform segments obtained from a finger-cuff monitor of 194 subjects. The model accurately predicts CRM when tested on data from 22 additional human subjects obtained from Lower Body Negative Pressure (LBNP) emulation of hemorrhage, attaining a mean squared error (MSE) of 0.0238 over the full range of values, including those from subjects with both low and high tolerance to central hypovolemia.

Treatment of combined traumatic brain injury and hemorrhagic shock with fractionated blood products versus fresh whole blood in a rat model.

Abstract: Treatment of combined traumatic brain injury and hemorrhagic shock, poses a particular challenge due to the possible conflicting consequences. While restoring diminished volume is the treatment goal for hypovolemia, maintaining adequate cerebral perfusion pressure and avoidance of secondary damage remains a treatment goal for the injured brain. Various treatment modalities have been proposed, but the optimal resuscitation fluid and goals have not yet been clearly defined. A growing body of evidence suggests that in hypovolemic shock, resuscitation with fresh whole blood (FWB) may be superior to component therapy without platelets (which are likely to be unavailable in the pre-hospital setting). Nevertheless, the effects of this approach have not been studied in the combined injury. Previously, in a rat model of combined injury we have found that mild resuscitation to MABP of 80 mmHg with FWB is superior to fluid resuscitation or aggressive resuscitation with FWB. In this study, we investigate the physiological and neurological outcomes in a rat model of combined traumatic brain injury (TBI) and hypovolemic shock, submitted to treatment with varying amounts of FWB, compared to similar resuscitation goals with fractionated blood products—red blood cells (RBCs) and plasma in a 1:1 ratio regimen. 40 male Lewis rats were divided into control and treatment groups. TBI was inflicted by a free-falling rod on the exposed cranium. Hypovolemia was induced by controlled hemorrhage of 30% blood volume. Treatment groups were treated either with fresh whole blood or with RBC + plasma in a 1:1 ratio, achieving a resuscitation goal of a mean arterial blood pressure (MAP) of 80 mmHg at 15 min. MAP was assessed at 60 min, and neurological outcomes and mortality in the subsequent 24 h. At 60 min, hemodynamic parameters were improved compared to controls, but not significantly different between treatment groups. Survival rates at 48 h were 100% for both of the mildly resuscitated groups (MABP 80 mmHg) with FWB and RBC + plasma. The best neurological outcomes were found in the group mildly resuscitated with FWB and were better when compared to resuscitation with RBC + plasma to the same MABP goal (FWB: Neurological Severity Score (NSS) 6 ± 2, RBC + plasma: NSS 10 ± 2, p = 0.02). In this study, we find that mild resuscitation with goals of restoring MAP to 80 mmHg (which is lower than baseline) with FWB, provided better hemodynamic stability and survival. However, the best neurological outcomes were found in the group resuscitated with FWB. Thus, we suggest that resuscitation with FWB is a feasible modality in the combined TBI + hypovolemic shock scenario, and may result in improved outcomes compared to platelet-free component blood products.

Cardiovascular biomarkers and echocardiographic findings at rest and during graded hypovolemic stress in women with recurrent vasovagal syncope.

Abstract: Introduction: Vasovagal reflex is the most common type of syncope but its etiology is not fully elucidated. Venous return and cardiac output are key in hemodynamic control. The aim of the study was to assess cardiovascular biomarkers and echocardiographic measures at rest and during hypovolemia in women with and without a history of vasovagal syncope. Methods: Fourteen women (aged 18-30) suffering from recurrent vasovagal syncope and 15 age-matched healthy women were included. Graded lower body negative pressure (LBNP) was used to create central hypovolemic stress until signs of presyncope occurred. Echocardiography was applied at rest and throughout LBNP. Cardiovascular biomarkers: copeptin, mid-regional proadrenomedullin, mid-regional pro-ANP, C-terminal proendothelin-1, and plasma norepinephrine were measured both at rest and throughout graded hypovolemia to presyncope. Results: Women prone to vasovagal syncope presented with a narrower right ventricle (RV) (29 ± 1 vs 32 ± 1 mm, P <.05), smaller left atrium (36 ± 2 vs 47 ± 3 cm3, P <.01) and lower cardiac output at rest (3.1 ± 0.2 vs 3.7 ± 0.2 L/min, P <.05) and during graded hypovolemia (P <.05). Copeptin was elevated at rest (4.3 ± 0.8 vs 2.5 ± 0.2 pmol/L, P <.05) and increased more in women with vasovagal syncope during progression of LBNP (P <.01). At rest, lower C-terminal proendothelin-1 (35 ± 5 vs 46 ± 2 pmol/L, P <.05) and higher norepinephrine levels (1.1 ± 0.1 vs 0.8 ± 0.1 nmol/L, P <.01) were seen in women with vasovagal syncope. Conclusion: Women prone to vasovagal syncope demonstrate reduced cardiac preload, lower cardiac output, as well as increased release of vasopressin in rest and during hypovolemic challenge. The results emphasize the importance of venous return and cardiac output in the pathogenesis of vasovagal syncope. (Less)

Bioimpedance spectroscopy-guided ultrafiltration normalizes hydration and reduces intradialytic adverse events in hemodialysis patients

Abstract: Chronic fluid overload as well as excessive fluid removal are associated with increased morbidity and mortality in hemodialysis (HD) patients. The clinical method to probe the dry weight is often inaccurate and the bioimpedance spectroscopy (BIS) is shown to improve the accuracy. We compared the impact of BIS and clinical methods to guide ultrafiltration (UF) in a randomized controlled study on the intradialytic complications and blood pressure control in prevalent HD patients. Fifty patients on maintenance HD were randomized to BIS method (BIS-group) and clinical method (CL-group) to guide UF. The body composition monitor (BCM) was done post-HD in all patients at baseline and 2-weeks interval during the study period of 6 months to determine the hydration status, but the result was revealed only to the nephrologist managing the patients in BIS-group to probe the dry weight. The endpoints of the study were blood pressure control, intradialytic complications and anti-hypertensive drug burden. The mean age was 56.0 ± 12.0 years and 70% were male. There was significant increase in patients with normal hydration in BIS-group (20% vs. 88%, p = 0.0001), but remained similar to baseline in CL-group (40% vs. 48%, p = 0.3) at 6 months. The incidence of intradialytic hypotension was significantly reduced in BIS-group (4.84 ± 3.0 vs. 2.8 ± 3.13 events/patient/6 months, p = 0.003). There was 35% reduction in hypertensive pill burden in BIS-group with similar blood pressure, compared to CL-group. Post-dialysis underhydration was more common than over or normal hydration at baseline in our population, indicating that clinical method to probe dry weight often resulted in hypovolemia. BIS method to determine dry weight resulted in normalization in volume status and consequently resulted in significant reduction in intradialytic hypotension and anti-hypertensive pill burden over 6-month period.

Acute resuscitation with polyethylene glycol-20k: A thromboelastographic analysis.

Abstract: BACKGROUND Previous ex vivo studies have shown that polyethylene glycol-20,000 Da (PEG-20k), a novel synthetic polymer that is highly effective for resuscitation, has a hypocoagulable effect on human blood. This study's objective was to determine the in vivo effects of PEG-20k-based resuscitation solutions on coagulation and platelet function in a porcine model of hemorrhagic shock. METHODS Anesthetized pigs underwent controlled hemorrhage until the lactate reached 7 mmol/L or 50% to 55% of their estimated blood volume was removed. A laparotomy was performed to simulate tissue injury. Low volume resuscitation (LVR) was given with fluorescein isothiocyanate-labeled 10% PEG-20k solution (100 mg/mL) or Lactated Ringers, both delivered at volumes equal to 10% of the estimated blood volume (n = 5). Thromboelastography was performed after surgery (baseline), after hemorrhage, and 15 minutes, 120 minutes, and 240 minutes postresuscitation. Hemoglobin was measured to determine changes in plasma volume. Plasma PEG-20k concentration was measured by indicator dilution. RESULTS Pigs given PEG-20k survived 2.6-fold longer than controls (p < 0.001) and had a significant increase in plasma volume demonstrated by the sustained drop in hemoglobin, relative to controls. Pigs resuscitated with LR died from hypotension an average of 90 minutes after resuscitation compared to the PEG-20k pigs, which all survived 240 minutes and were then euthanized with normal blood pressure and lactate. Administration of PEG-20k primarily decreased the thromboelastograph maximum amplitude, however this began to return toward baseline by 240 minutes. Peak plasma concentration of PEG-20k after LVR were 40% lower than predicted, based on simple dilution (5.7 mg/mL vs. 10 mg/mL) and the half-life was 59.6 minutes. CONCLUSION These data demonstrate that acute resuscitation with PEG-20k significantly improves tolerance to hypovolemia but also decreases platelet function in the coagulation cascade, which was due, in part, to its volume expanding effects.

Hemodynamic and Pulmonary Permeability Characterization of Hantavirus Cardiopulmonary Syndrome by Transpulmonary Thermodilution.

Abstract: Hantavirus cardiopulmonary syndrome (HCPS) is characterized by capillary leak, pulmonary edema (PE), and shock, which leads to death in up to 40% of patients. Treatment is supportive, including mechanical ventilation (MV) and extracorporeal membrane oxygenation (ECMO). Hemodynamic monitoring is critical to titrate therapy and to decide ECMO support. Transpulmonary thermodilution (TPTD) provides hemodynamic and PE data that have not been systematically used to understand HCPS pathophysiology. We identified 11 HCPS patients monitored with TPTD: eight on MV, three required ECMO. We analyzed 133 measurements to describe the hemodynamic pattern and its association with PE. The main findings were reduced stroke volume, global ejection fraction (GEF), and preload parameters associated with increased extravascular lung water and pulmonary vascular permeability compatible with hypovolemia, myocardial dysfunction, and increased permeability PE. Lung water correlated positively with heart rate (HR, r = 0.20) and negatively with mean arterial pressure (r = −0.27) and GEF (r = −0.36), suggesting that PE is linked to hemodynamic impairment. Pulmonary vascular permeability correlated positively with HR (r = 0.31) and negatively with cardiac index (r = −0.49), end-diastolic volume (r = −0.48), and GEF (r = −0.40), suggesting that capillary leak contributes to hypovolemia and systolic dysfunction. In conclusion, TPTD data suggest that in HCPS patients, increased permeability leads to PE, hypovolemia, and circulatory impairment.

Hypovolemia and reduced hemoglobin mass in patients with heart failure and preserved ejection fraction.

Abstract: A fundamental tenet of heart failure (HF) pathophysiology hinges on a propensity for fluid retention leading to blood volume (BV) expansion and hemodilution. Whether this can be applied to heart failure patients with preserved ejection fraction (HFpEF) remains uncertain. The present study sought to determine BV status and key hormones regulating fluid homeostasis and erythropoiesis in HFpEF patients. BV and hemoglobin mass (Hb$_{mass}$ ) were determined with high-precision, automated carbon monoxide (CO) rebreathing in 20 stable HFpEF patients (71.5 ± 7.3 years, left ventricular ejection fraction = 55.7 ± 4.0%) and 15 healthy age- and sex-matched control individuals. Additional measurements comprised key circulating BV-regulating hormones such as pro-atrial natriuretic peptide (proANP), copeptin, aldosterone and erythropoietin (EPO), as well as central hemodynamics and arterial stiffness via carotid-femoral pulse wave velocity (PWV). Carotid-femoral PWV was increased (+20%) in HFpEF patients versus control individuals. With respect to hematological variables, plasma volume (PV) did not differ between groups, whereas BV was decreased (-14%) in HFpEF patients. In consonance with the hypovolemic status, Hb$_{mass}$ was reduced (-27%) in HFpEF patients, despite they presented more than a twofold elevation of circulating EPO (+119%). Plasma concentrations of BV-regulating hormones, including proANP (+106%), copeptin (+99%), and aldosterone (+62%), were substantially augmented in HFpEF patients. HFpEF patients may present with hypovolemia and markedly reduced Hb$_{mass}$ , underpinned by a generalized overactivation of endocrine systems regulating fluid homeostasis and erythropoiesis. These findings provide a novel perspective on the pathophysiological basis of the HFpEF condition.

Use of a modified passive leg-raising maneuver to predict fluid responsiveness during experimental induction and correction of hypovolemia in healthy isoflurane-anesthetized pigs.

Abstract: OBJECTIVE To evaluate the use of a modified passive leg-raising maneuver (PLRM) to predict fluid responsiveness during experimental induction and correction of hypovolemia in isoflurane-anesthetized pigs. ANIMALS 6 healthy male Landrace pigs. PROCEDURES Pigs were anesthetized with isoflurane, positioned in dorsal recumbency, and instrumented. Following induction of a neuromuscular blockade, pigs were mechanically ventilated throughout 5 sequential experimental stages during which the blood volume was manipulated so that subjects transitioned from normovolemia (baseline) to hypovolemia (blood volume depletion, 20% and 40%), back to normovolemia, and then to hypervolemia. During each stage, hemodynamic variables were measured before and 3 minutes after a PLRM and 1 minute after the pelvic limbs were returned to their original position. The PLRM consisted of raising the pelvic limbs and caudal portion of the abdomen to a 15° angle relative to the horizontal plane. RESULTS Hemodynamic variables did not vary in response to the PLRM when pigs were normovolemic or hypervolemic. When pigs were hypovolemic, the PLRM resulted in a significant increase in cardiac output and decrease in plethysomographic variability index and pulse pressure variation. When the pelvic limbs were returned to their original position, cardiac output and pulse pressure variation rapidly returned to their pre-PLRM values, but the plethysomographic variability index did not. CONCLUSIONS AND CLINICAL RELEVANCE Results suggested a modified PLRM might be useful for identification of hemodynamically unstable animals that are likely to respond to fluid therapy. Further research is necessary to validate the described PLRM for prediction of fluid responsiveness in clinically ill animals.

Capacity to Compensate for Central Hypovolemia and Effects of Menstrual Cycle Phases.

Abstract: BACKGROUND: Tolerance to central hypovolemia is dictated by exhaustion of the physiological capacity to compensate called the compensatory reserve. Such physiological compromise can have detrimental impact on performance in aerospace environments as well as survival from hemorrhage on the battlefield. We induced central hypovolemia using progressively stepwise lower body negative pressure (LBNP) in women during various phases of the menstrual cycle to test the hypothesis that similar tolerance across all menstrual cycle phases would be reflected by similar changes in compensatory reserve.METHODS: Based on self-reporting of the last menstrual period, 40 healthy women, matched by demographics, were classified into 1 of 5 menstrual cycle phases: early follicular (EF, Days 1-7; N = 10), late follicular and ovulatory (LF, Days 9-15, N = 6), early luteal (EL, Days 16-18, N = 6), midluteal (ML, Days 19-25, N = 8), and late luteal (LL, Days 26-30, N = 10). All subjects had a 28-30 d menstrual cycle and were not taking oral contraceptives. Tolerance to central hypovolemia was measured as time (seconds) from baseline to the onset of presyncopal symptoms induced by LBNP.RESULTS: Time to presyncope as well as hemodynamic and compensatory reserve responses were statistically indistinguishable across all menstrual cycle phases.DISCUSSION: Consistent with our hypothesis, compensatory reserve with associated hemodynamic responses and tolerance to central hypovolemia was not affected by menstrual cycle phases. Our findings indicate experimental comparisons of responses to central hypovolemia involving the participation of healthy women with normal menstrual cycles and not taking oral contraceptives can be conducted independent of menstrual cycle phase.Convertino VA, Schlotman TE, Stacey W, Hinojosa-Laborde C. Capacity to compensate for central hypovolemia and effects of menstrual cycle phases. Aerosp Med Hum Perform. 2019; 90(4):378-383.

Associations between changes in precerebral blood flow and cerebral oximetry in the lower body negative pressure model of hypovolemia in healthy volunteers.

Abstract: Reductions in cerebral oxygen saturation (ScO2) measured by near infra-red spectroscopy have been found during compensated hypovolemia in the lower body negative pressure (LBNP)-model, which may reflect reduced cerebral blood flow. However, ScO2 may also be contaminated from extracranial (scalp) tissues, mainly supplied by the external carotid artery (ECA), and it is possible that a ScO2 reduction during hypovolemia is caused by reduced scalp, and not cerebral, blood flow. The aim of the present study was to explore the associations between blood flow in precerebral arteries and ScO2 during LBNP-induced hypovolemia. Twenty healthy volunteers were exposed to LBNP 20, 40, 60 and 80 mmHg. Blood flow in the internal carotid artery (ICA), ECA and vertebral artery (VA) was measured by Doppler ultrasound. Stroke volume for calculating cardiac output was measured by suprasternal Doppler. Associations of changes within subjects were examined using linear mixed-effects regression models. LBNP reduced cardiac output, ScO2 and ICA and ECA blood flow. Changes in flow in both ICA and ECA were associated with changes in ScO2 and cardiac output. Flow in the VA did not change during LBNP and changes in VA flow were not associated with changes in ScO2 or cardiac output. During experimental compensated hypovolemia in healthy, conscious subjects, a reduced ScO2 may thus reflect a reduction in both cerebral and extracranial blood flow.

A Two Parameters for the Evaluation of Hypovolemia in Patients with Septic Shock: Inferior Vena Cava Collapsibility Index (IVCCI), Delta Cardiac Output

Abstract: BACKGROUND The aim of this study was to determine the correlation between inferior vena cava collapsibility index and changes in cardiac output measured during passive leg raising test in patients with spontaneous breathing and septic shock. MATERIAL AND METHODS Fifty-six patients were included in the study. All of these 56 patients were diagnosed with septic shock and had spontaneous breathing under continuous positive airway pressure. Patients exclusions included: patients with cardiac pathology, not septic shock, pregnant, spontaneous breathing, increased intra-abdominal pressure, inferior vena cava could not be visualized, arrhythmia and pulmonary hypertension. Exclusion criteria for the study were as follows: 1) left ventricular systolic dysfunction, 2) cardiomyopathy, 3) medium severe heart valve disease, 4) patients with arrhythmia; 5) pulmonary hypertension, 6) patients without spontaneous breathing (for inferior vena cava collapsibility index, it is not evaluated), 7) patients with >60 mmHg CO₂ in arterial blood gas; 8) pregnant patients; 9) patients with neurogenic shock, cerebrovascular incident or traumatic brain injury, 10) patients whose inferior vena cava and parasternal long axis cannot be visualized, and 11) patients with increased intra-abdominal pressure. Patients were placed in neutral supine position, and the inferior vena cava collapsibility index and cardiac output 1 were recorded. In passive leg raising test, after which the cardiac output 2 is recorded in terms of L/min. The percentage increase between the 2 cardiac outputs was calculated and recorded. RESULTS A moderately positive correlation was also observed between the inferior vena cava collapsibility index and delta cardiac output (r=0.459; r2=0.21), which was statistically significant (P<0.001). The cutoff value for the delta cardiac output was 29.5. CONCLUSIONS In conclusion, we found that the inferior vena cava collapsibility index, which is one of the dynamic parameters used in the diagnosis of hypovolemia in patients with septic shock, is correlated with delta cardiac output after leg raising test. We believe that, based on a clinician's experience, looking at 1 of these 2 parameters is sufficient for the identification of hypovolemia in patients diagnosed with septic shock.

Comparison of Intraosseous, Arterial, and Venous Blood Sampling for Laboratory Analysis in Hemorrhagic Shock.

Abstract: Background Intraosseous (IO) access is often indicated for administration of drugs and fluids in emergencies when venous access is challenging. There is no consensus regarding whether and which laboratory analyses may be performed on IO aspirates, and research on hemodynamically unstable subjects is limited. Methods Twelve anesthetized pigs were sampled from IO, venous, and arterial accesses during stable circulation and after hemorrhage corresponding to 20% and 40% of the blood volume. Samples were analyzed for blood gases and acid-base status, electrolytes, hematocrit, creatinine, glucose, alanine aminotransferase (ALT), aspartate aminotransferase (AST), γ-glutamyltransferase (γ-GT), alkaline phosphatase (ALP), and creatine kinase (CK). Results Average differences of blood gases and acid-base parameters, sodium, creatinine, hematocrit, ALT, and γ-GT and between IO and venous samples were small at baseline and after hemorrhage while differences for lactate and glucose increased with hypovolemia. Both IO-arterial and venoarterial differences in acid-base parameters increased with hypovolemia. Dispersions of differences were often large. Conclusions Average levels of blood gases, acid base parameters, hematocrit, CK, AST, γ-GT, creatinine, and ALT, but not lactate and glucose, were similar in IO and venous samples in hypovolemia. However, precision was limited, indicating that IO test results should be confirmed when other vascular access is established, and that analysis of IO samples should be limited to acute situations and not used for detailed diagnostics in this setting.

Prolonged albumin administration in patients with decompensated cirrhosis: the amount makes the difference

Abstract: Systemic inflammation and cardiovascular dysfunction represent the main pathophysiological features of decompensated cirrhosis. The “peripheral vasodilation hypothesis” published in 1988 (1) has identified in the arterial vasodilation, mainly occurring in the splanchnic area, the primary cause of the effective hypovolemia, which characterizes the cardiovascular status of patients with decompensated cirrhosis.

The bioimpedance spectroscopy as useful tool for measuring the fluid excess and fluid management in severe polytrauma patients.

Abstract: Although the fluid therapy plays a fundamental role in the management of polytrauma patients (PP), a tool which could determine it appropriately is still lacking. The aim of this study was to evaluate the application of a bioimpedance spectroscopy (BIS) for body fluids volume and distribution monitoring in these patients. This prospective, observational study was performed on 25 severe PP and 25 healthy subjects. The body fluids composition was repeatedly assessed using BIS between days 3 to 11 of intensive care unit stay while the impact of fluid intake and balance was evaluated. Fluid intake correlated significantly with fluid excess (FE) in edemas, and their values were significantly higher in comparison with the control group. FE was strongly associated with cumulative fluid balance (p<0.0001; r=0.719). Furthermore, this parameter was associated with the entire duration of mechanical ventilation (p=0.001, r=0.791) independently of injury severity score. In conclusion, BIS measured FE could be useful in PP who already achieved negative fluid balance in prevention the risk of repeated hypovolemia through inappropriate fluid restriction. What is more, measured FE has a certain prognostic value. Further studies are required to confirm BIS as a potential instrument for the improvement of PP outcome.