Serum chymase levels correlate with severe dengue warning signs and clinical fluid accumulation in hospitalized pediatric patients.

Dengue induces a spectrum of severity in humans from the milder dengue fever to severe disease, or dengue hemorrhagic fever (DHF). Chymase is a candidate biomarker that may aid dengue prognosis. This prospective study aimed to identify whether warning signs of severe dengue, including hypovolemia and fluid accumulation, were associated with elevated chymase. Serum chymase levels were quantified prospectively and longitudinally in hospitalized pediatric dengue patients in Sri Lanka. Warning signs were determined based on daily clinical assessments, laboratory tests and ultrasound findings. Chymase was significantly elevated during the acute phase of disease in DHF or Severe dengue, defined by either the 1997 or 2009 WHO diagnosis guidelines, and persisted longer in the most severe patients. Chymase levels were higher in patients with narrow pulse pressure and clinical warning signs such as severe leakage, fluid accumulation, pleural effusion, gall-bladder wall thickening and rapid haematocrit rise concurrent with thrombocytopenia. No association between chymase and liver enlargement was observed. This study confirms that serum chymase levels are associated with DHF/Severe dengue disease in hospitalized pediatric patients. Chymase levels correlate with warning signs of vascular dysfunction highlighting the possible functional role of chymase in vascular leakage during dengue.

Lessons learnt from an old foe.

Neurotuberculosis usually responds well to standard antitubercular therapy. Some; patients have prolonged course A 11 year old boy diagnosed TBM, an immunocompetent patient, had an unusual course of illness in the form of prolonged fever, persistent hyponatremia and CSF; pleocytosis despite adequate treatment. Clinical course in the management of TBM can be; protracted with complications despite adequate therapy.

Relative Change of Protidemia Level Predicts Intradialytic Hypotension.

Background Hemodialysis patients are at risk of intradialytic hypotension (IDH), which is associated with mortality and cardiovascular and neurological events. The use of biomarkers of volemia such as relative change in protidemia and BNP (B-natriuretic peptide) levels to predict IDH remains unknown. Methods and Results We conducted a prospective observational study, which enrolled 170 chronic hemodialysis patients in a single center from September 2015 to March 2016. BNP and the relative change of protidemia level (Δprotidemia=postdialysis protidemia-predialysis protidemia) were measured monthly over 6 months. A logistic mixed regression model was used to define the best biomarkers that predict the 30-day risk of IDH. Receiver operating characteristic analysis area under the curve was used to define the cutoff values of Δprotidemia that predict IDH A logistic mixed model reveals that Δprotidemia predicts the 30-day risk of IDH but not BNP or age; odds ratio=1.12, 95% CI 1.08-1.17), odds ratio=0.81, 95% CI (0.64; 1.07) and odds ratio =0.015 95% CI (0.99; 1.03), respectively. Adding the ultrafiltration rate did not improve the model. A receiver operating characteristic curve analysis showed that Δprotidemia of 10 g/L allowed for discrimination of the patients with IDH (area under the curve= 0.67; 95% CI 0.62-0.72, P<0.05). There was an increase in area under the curve to 0.71 (95% CI 0.63-0.76) in a subgroup of hemodialysis with BNP <300 ng/L, for a cutoff value of 11 g/L, especially for the nondiabetic patients. Conclusions Relative change in protidemia level (Δprotidemia) outperforms BNP and ultrafiltration rate as a predictor for 30-day risk of IDH. These results should be confirmed by a prospective study.

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

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.

Hyponatraemia in patients with community-acquired pneumonia; prevalence and aetiology, and natural history of SIAD.

OBJECTIVE: Hyponatraemia is common in community-acquired pneumonia (CAP) and is associated with increased mortality. The mechanism of hyponatraemia in CAP is not completely understood and treatment is therefore ill-defined. We aimed to define the causation of hyponatraemia in CAP. DESIGN: Prospective, single-centre, observational study of all patients with CAP and hyponatraemia (≤ 130 mmol/L) during a 9-month period. PATIENTS: The prevalence of each subtype of hyponatraemia, and the associated mortality, was determined in 143 admissions with CAP (Study 1). A sub-cohort of patients with SIAD (n = 10) was prospectively followed, to document the natural history of SIAD associated with CAP (Study 2). MEASUREMENTS: In Study 2, blood and urine were collected on day 1, 3, 5 and 7 following admission for measurement of plasma vasopressin, sodium, osmolality and urine osmolality. RESULTS: In study 1, 143/1723(8.3%) of CAP patients had hyponatraemia (≤130 mmol/L). About 66 had SIAD (46%), 60(42%) had hypovolaemic hyponatraemia (HON), 13(9%) had hypervolaemic hyponatraemia (HEN) and 4(3%) patients had hyponatraemia due to glucocorticoid hormone deficiency. Mortality was higher in the HEN than in the HON, SIAD or normonatraemic groups (P < 0.01). In Study 2, plasma sodium concentration normalized in 8/10 (80%) by day 7. Two patients with persistent hyponatraemia were discovered to have underlying bronchiectasis. CONCLUSIONS: Hyponatraemia in CAP is most commonly secondary to SIAD or hypovolaemia. HEN is less common, but has worse prognosis. Prospective observation demonstrates that in SIAD, plasma AVP and sodium concentrations normalize with antimicrobials; failure of reversal of suggests underlying lung disease, such as bronchiectasis.

Evaluation of NT-ProBNP as a marker of the volume status of neurosurgical patients developing hyponatremia and natriuresis: A pilot study.

OBJECTIVE: Post-operative hyponatremia (serum sodium <130 mEq/L) contributes to morbidity and prolongs the hospital stay of patients undergoing neurosurgical procedures. Syndrome of inappropriate anti-diuretic hormone secretion (SIADH) and cerebral salt wasting (CSW) commonly occur in the post-operative setting. While patients with SIADH are either euvolemic or hypervolemic, patients with CSW are always hypovolemic. The treatment of these two conditions is radically different. Patients with SIADH need fluid restriction, while patients with CSW need fluid replacement. As current diagnostic methods do not clearly distinguish between SIADH and CSW, we looked at N-terminal prohormone of brain natriuretic peptide (NT-proBNP) and uric acid as biochemical markers for estimating the volume status of patients developing hyponatremia in the postoperative period. MATERIALS AND METHODS: In this study, we used a cohort design and carried it out in two phases over a period of 30 months (August 2011-February 2014). Thirty-one patients with hyponatremia were recruited into the study. In Phase1, 10 patients were diagnosed to have either SIADH or CSW based on their central venous pressure (CVP). In all of them, blood for NT-proBNP was collected prior to starting treatment. At a later stage, the NT-proBNP results were compared with central venous pressure (CVP) and the clinical diagnosis. Patients diagnosed to have SIADH (CVP >5cm) had NT-proBNP levels <125pg/ml and those with a diagnosis of CSW (CVP <5cm) had NT-proBNP levels >125pg/ml. In Phase2, 21 patients were categorized and treated according to their NT-proBNP levels. Those with NT-proBNP levels <125 pg/ml were treated as SIADH, and those with NT-proBNP levels >125 pg/ml were treated as CSW. RESULTS: In Phase 1, NT-proBNP could detect hypovolemia in patients with CSW with 100% sensitivity and 66.7% specificity (P < 0.07). In Phase 2, NT-proBNP could detect hypovolemia in patients with CSW with 90% sensitivity and 100% specificity (P < 0.001). Combining the results of Phase 1 and Phase 2, NT-proBNP could diagnose CSW with 87.50% sensitivity and 93.33% specificity (P < 0.001). The positive predictive value was 93.33% and the negative predictive value was 87.50%. CONCLUSION: NT Pro-BNP is a quick and convenient assay to differentiate SIADH and CSW. We need a larger sample size to correctly characterize the cut off value. Uric acid cannot be used to distinguish between SIADH and CSW.

Comparisons of Traditional Metabolic Markers and Compensatory Reserve as Early Predictors of Tolerance to Central Hypovolemia in Humans.

Circulatory shock remains a leading cause of death in both military and civilian trauma. Early, accurate and reliable prediction of decompensation is necessary for the most efficient interventions and clinical outcomes. Individual tolerance to reduced central blood volume can serve as a model to assess the sensitivity and specificity of vital sign measurements. The compensatory reserve (CRM) is the measurement of this capacity. Measurements of muscle oxygen saturation (SmO2), blood lactate, and end tidal CO2 (EtCO2) have recently gained attention as prognostic tools for early assessment of the status of patients with progressive hemorrhage, but lack the ability to adequately differentiate individual tolerance to hypovolemia. We hypothesized that the CRM would better predict hemodynamic decompensation and provide greater specificity and sensitivity than metabolic measures. To test this hypothesis, we employed lower body negative pressure on healthy human subjects until symptoms of presyncope were evident. Receiver operating characteristic area under the curve (ROC AUC), sensitivity, and specificity were used to evaluate the ability of CRM, partial pressure of oxygen (pO2), partial pressure of carbon dioxide (pCO2), SmO2, lactate, EtCO2, potential of hydrogen (pH), base excess and hematocrit (Hct) to predict hemodynamic decompensation. The ROC AUC for CRM (0.94) had a superior ability to predict decompensation compared with pO2 (0.85), pCO2 (0.62), SmO2 (0.72), lactate (0.57), EtCO2 (0.74), pH (0.55), base excess (0.59), and Hct (0.67). Similarly, CRM also exhibited the greatest sensitivity and specificity. These findings support the notion that CRM provides superior detection of hemodynamic compensation compared with commonly used clinical metabolic measures.

Resuscitation using less fluid has no negative impact on hydration status in children with moderate sized scalds: a prospective single-centre UK study.

BACKGROUND: After a burn, optimal fluid resuscitation is critical for positive patient outcome. Although national guidelines advocate using resuscitation fluids of 4mL per kg body weight and percent body surface area (%BSA) for paediatric burns of >10% BSA, evidence in adults suggest that such volumes lead to over-resuscitation and related complications. Our aim was to investigate whether children managed with biosynthetic dressings (Biobrane™) and reduced fluid volumes remain well hydrated, as determined by clinical and laboratory parameters. METHODS: At a single UK Burn Centre, children with scalds of 10-19%BSA managed with Biobrane were given 80% maintenance fluids and no formal burn resuscitation (permissive hypovolaemia [PH] group). Urine output (UO), serum sodium, urea, and creatinine were used as 24h markers of hydration and concentrations compared to those in a patient cohort treated within the same centre when traditional resuscitation was used (TR group). RESULTS: Serum sodium concentrations and UO in the PH group were similar to those in the TR group (median sodium: PH=136, TR=136, P=1.00; median UO: PH=1.5, TR=1.8, P=0.25). Urea concentrations were lower and creatinine concentrations higher in the TR group compared to the PH group (median urea: PH=3.2, TR=2.3, P=0.04; median creatinine: PH=21, TR=30, P<0.001). A higher proportion of TR patients than PH patients fell outside the reference ranges for urea (61% vs. 23%; P=0.04) and creatinine (44% vs. 8%; P=0.03). CONCLUSION: Based on markers of hydration, children with moderate-sized scalds managed with Biobrane can be safely managed with less fluid.

Responses of distal nephron Na+ transporters to acute volume depletion and hyperkalemia.

We assessed effects of acute volume reductions induced by administration of diuretics in rats. Direct block of Na+ transport produced changes in urinary electrolyte excretion. Adaptations to these effects appeared as alterations in the expression of protein for the distal nephron Na+ transporters NCC and ENaC. Two hours after a single injection of furosemide (6 mg/kg) or hydrochlorothiazide (HCTZ; 30 mg/kg) Na+ and K+ excretion increased but no changes in the content of activated forms of NCC (phosphorylated on residue T53) or ENaC (cleaved γ-subunit) were detected. In contrast, amiloride (0.6 mg/kg) evoked a similar natriuresis that coincided with decreased pT53NCC and increased cleaved γENaC. Alterations in posttranslational membrane protein processing correlated with an increase in plasma K+ of 0.6-0.8 mM. Decreased pT53NCC occurred within 1 h after amiloride injection, whereas changes in γENaC were slower and were blocked by the mineralocorticoid receptor antagonist spironolactone. Increased γENaC cleavage correlated with elevation of the surface expression of the subunit as assessed by in situ biotinylation. Na depletion induced by 2 h of furosemide or HCTZ treatment increases total NCC expression without affecting ENaC protein. However, restriction of Na intake for 10 h (during the day) or 18 h (overnight) increased the abundance of both total NCC and of cleaved α- and γENaC. We conclude that the kidneys respond acutely to hyperkalemic challenges by decreasing the activity of NCC while increasing that of ENaC. They respond to hypovolemia more slowly, increasing Na+ reabsorptive capacities of both of these transporters.

Isolated Brain Trauma in Cats Triggers Rapid Onset of Hypovolemia.

BACKGROUND: Hemodynamic instability responsive to fluid resuscitation is common after a traumatic brain injury (TBI), also in the absence of systemic hemorrhage. The present study tests if an isolated severe TBI induces a decrease in plasma volume (PV). METHODS: The study was performed in three groups of anesthetized and tracheostomized male cats (n = 21). In one group (n = 8), the cats were prepared with a cranial borehole (10 mm i.d) used to expose the brain to a fluid percussion brain injury (FPI) (1.90-2.20 bar), and two smaller cranial boreholes (4 mm i.d) for insertion of an intracranial pressure (ICP) and a microdialysis catheter. To differentiate the effect of FPI from that of the surgical preparation, a sham group was exposed to the same surgical preparation but no FPI trauma (n = 8). A control group had no brain trauma and no surgical preparation (n = 5). PV was determined by a 125I-albumin dilution technique. PV, electrolytes, pH, BE (base excess), hematocrit (Hct), PaO2, and PaCO2 were measured at baseline and after 3 h. Mean arterial pressure (MAP) was measured continuously. ICP was measured in the FPI and the sham group. RESULTS: In the FPI group, PV decreased by 11.2 mL/kg from 31.7 mL/kg (p < 0.01) with a simultaneous increase in Hct and decrease in pH. In the sham group, PV decreased by 5.7 mL/kg from 32.7 mL/kg (p < 0.01). The control group showed no PV reduction. CONCLUSIONS: The results support that an isolated severe head trauma triggers a significant and rapid reduction in PV, most likely due to vascular leak.

White blood cell concentrations during lower body negative pressure and blood loss in humans.

NEW FINDINGS: What is the central question of this study? Is lower body negative pressure a useful surrogate to study white blood cell responses to haemorrhage in humans? What is the main finding and its importance? We found that lower body negative pressure appears to be a useful surrogate to study the early white blood cell mobilization response during blood loss. Hypovolaemia has been associated with an immune response that might be secondary to sympathoexcitation. We tested the hypothesis that simulated hypovolaemia using lower body negative pressure (LBNP) and real hypovolaemia induced via experimental blood loss (BL) cause similar increases in the white blood cell concentration ([WBC]). We measured [WBC] and catecholamine concentrations in 12 men who underwent an LBNP and a BL protocol in a randomized order. We compared 45 mmHg of LBNP with 1000 ml of BL; therefore, [WBC] and catecholamine concentrations were plotted against central venous pressure to obtain stimulus-response relationships using the linear regression line slopes for both protocols. Mean regression line slopes were similar for total [WBC] (LBNP 183 ± 4 µl-1  mmHg-1 versus BL 155 ± 109 µl-1  mmHg-1 , P = 0.15), neutrophils (LBNP 110 ± 2 µl-1  mmHg-1 versus BL 96 ± 72 µl-1  mmHg-1 , P = 0.15) and lymphocytes (LBNP 65 ± 21 µl-1  mmHg-1  versus BL 59 ± 38 µl-1  mmHg-1 , P = 0.90). Mean regression line slopes for adrenaline were similar (LBNP 15 ± 5 pg ml-1  mmHg-1 versus BL 16 ± 4 pg ml-1  mmHg-1 , P = 0.84) and were steeper during LBNP for noradrenaline (LBNP 28 ± 6 pg ml-1  mmHg-1 versus BL 9 ± 6 pg ml-1  mmHg-1 , P = 0.01). These data indicate that central hypovolaemia elicits a relative leucocytosis with a predominantly neutrophil-based response. Additionally, our results indicate that LBNP models the stimulus-response relationship between central venous pressure and [WBC] observed during BL.

[Hypovolemic hyponatremia at the onset of severe ischemic stroke as a predictor of adverse outcome]. / Gipervolemicheskaya gipernatriemiya v debyute tyazhelogo ishemicheskogo insul'ta kak prediktor neblagopriyatnogo iskhoda.

AIM: To study the prognostic value of disturbances of the water and electrolyte homeostasis in the acute stage of ischemic stroke (II) and their impact on the course and outcome. MATERIAL AND METHODS: Disturbances of the water and electrolyte homeostasis associated with plasma sodium fluctuations were studied in 150 patients with severe II. RESULTS: The poor outcome was associated with plasma osmolarity >297 mOsmol/L and plasma sodium concentration >155 mOsmol/L in the first day of severe II and with >303 mOsmol/L and >161 mOsmol/L, respectively, in the 3rd and 5th days. The prognosis was significantly worse in hypovolemia compared to normo- and hypervolemia. CONCLUSION: Hypovolemic hyponatremia as a presentation of hyperosmolar syndrome at the onset of severe II can be considered as a relatedly independent predictor of the fatal outcome.

Controlled moderate hypovolaemia in healthy volunteers is not associated with the development of oxidative stress assessed by plasma F2-isoprostanes and isofurans.

Hypovolaemia can be associated with substantial morbidity, particularly when it occurs in the setting of trauma and in patients with comorbid diseases. Hypovolaemia and inflammation such as occur in the setting of trauma and surgery, are associated with systemic oxidative stress and free-radical injury. Free-radical injury that results from hypovolaemia-induced organ reperfusion may further augment inflammatory processes. It is unknown exactly what proportion of free-radical injury is associated with isolated hypovolaemia as opposed to the contribution from inflammation from surgery or trauma. In the first human study of its kind, we exposed 8 adult male volunteers to venesection-induced hypovolaemia in progressive aliquots of 5% of total blood volume until 20% had been removed. This blood was subsequently reinfused. Plasma F2-isoprostanes and isofurans, markers of in vivo lipid oxidation, were measured by gas chromatography-mass spectrometry at each 5% aliquot venesected and at each 5% reinfused. Between baseline and maximal blood loss there was a minor fall in haemoglobin concentration from 143.9g/l to 138.8g/l (p=0.004, 95% CI 2.2, 8.0g/L). No significant change from baseline occurred in the concentrations of either plasma F2-isoprostanes or isofurans during venesection (p=0.116 and p=0.152, respectively) or blood reinfusion (p=0.553 and p=0.736, respectively). We can conclude that in healthy adult volunteers, isolated hypovolaemia to 20% total blood volume loss is not associated with detectable systemic oxidative stress. The free-radical injury identified in surgical and trauma patients may represent the effects of tissue damage and inflammation, with an uncertain contribution from tissue ischemia as may occur with hypovolaemia.

Effect of hemorrhage rate on early hemodynamic responses in conscious sheep.

Physiological compensatory mechanisms can mask the extent of hemorrhage in conscious mammals, which can be further complicated by individual tolerance and variations in hemorrhage onset and duration. We assessed the effect of hemorrhage rate on tolerance and early physiologic responses to hemorrhage in conscious sheep. Eight Merino ewes (37.4 ± 1.1 kg) were subjected to fast (1.25 mL/kg/min) and slow (0.25 mL/kg/min) hemorrhages separated by at least 3 days. Blood was withdrawn until a drop in mean arterial pressure (MAP) of >30 mmHg and returned at the end of the experiment. Continuous monitoring includedMAP, central venous pressure, pulmonary artery pressure, pulse oximetry, and tissue oximetry. Cardiac output by thermodilution and arterial blood samples were also measured. The effects of fast versus slow hemorrhage rates were compared for total volume of blood removed and stoppage time (whenMAP < 30 mmHg of baseline) and physiological responses during and after the hemorrhage. Estimated blood volume removed whenMAPdropped 30 mmHg was 27.0 ± 4.2% (mean ± standard error) in the slow and 27.3 ± 3.2% in the fast hemorrhage (P = 0.47, pairedttest between rates). Pressure and tissue oximetry responses were similar between hemorrhage rates. Heart rate increased at earlier levels of blood loss during the fast hemorrhage, but hemorrhage rate was not a significant factor for individual hemorrhage tolerance or hemodynamic responses. In 5/16 hemorrhages MAP stopping criteria was reached with <25% of blood volume removed. This study presents the physiological responses leading up to a significant drop in blood pressure in a large conscious animal model and how they are altered by the rate of hemorrhage.

PlanHab: Hypoxia counteracts the erythropoietin suppression, but seems to exaggerate the plasma volume reduction induced by 3 weeks of bed rest.

The study examined the distinct and synergistic effects of hypoxia and bed rest on the erythropoietin (EPO) concentration and relative changes in plasma volume (PV). Eleven healthy male lowlanders underwent three 21-day confinement periods, in a counterbalanced order: (1) normoxic bed rest (NBR; PIO2: 133.1 ± 0.3 mmHg); (2) hypoxic bed rest (HBR; PIO2: 90.0 ± 0.4 mmHg, ambient simulated altitude of ~4000 m); and (3) hypoxic ambulation (HAMB; PIO2: 90.0 ± 0.4 mmHg). Blood samples were collected before, during (days 2, 5, 14, and 21) and 2 days after each confinement to determineEPOconcentration. Qualitative differences inPVchanges were also estimated by changes in hematocrit and hemoglobin concentration along with concomitant changes in plasma renin concentration.NBRcaused an initial reduction inEPOby ~39% (P = 0.04). By contrast,HBRenhancedEPO(P = 0.001), but the increase was less than that induced byHAMB(P < 0.01). All three confinements caused a significant reduction inPV(P < 0.05), with a substantially greater drop inHBRthan in the other conditions (P < 0.001). Thus, present results suggest that hypoxia prevents theEPOsuppression, whereas it seems to exaggerate thePVreduction induced by bed rest.

Does inferior vena cava respiratory variability predict fluid responsiveness in spontaneously breathing patients?

INTRODUCTION: We have almost no information concerning the value of inferior vena cava (IVC) respiratory variations in spontaneously breathing ICU patients (SBP) to predict fluid responsiveness. METHODS: SBP with clinical fluid need were included prospectively in the study. Echocardiography and Doppler ultrasound were used to record the aortic velocity-time integral (VTI), stroke volume (SV), cardiac output (CO) and IVC collapsibility index (cIVC) ((maximum diameter (IVCmax)- minimum diameter (IVCmin))/ IVCmax) at baseline, after a passive leg-raising maneuver (PLR) and after 500 ml of saline infusion. RESULTS: Fifty-nine patients (30 males and 29 females; 57 ± 18 years-old) were included in the study. Of these, 29 (49 %) were considered to be responders (≥10 % increase in CO after fluid infusion). There were no significant differences between responders and nonresponders at baseline, except for a higher aortic VTI in nonresponders (16 cm vs. 19 cm, p = 0.03). Responders had a lower baseline IVCmin than nonresponders (11 ± 5 mm vs. 14 ± 5 mm, p = 0.04) and more marked IVC variations (cIVC: 35 ± 16 vs. 27 ± 10 %, p = 0.04). Prediction of fluid-responsiveness using cIVC and IVCmax was low (area under the curve for cIVC at baseline 0.62 ± 0.07; 95 %, CI 0.49-0.74 and for IVCmax at baseline 0.62 ± 0.07; 95 % CI 0.49-0.75). In contrast, IVC respiratory variations >42 % in SBP demonstrated a high specificity (97 %) and a positive predictive value (90 %) to predict an increase in CO after fluid infusion. CONCLUSIONS: In SBP with suspected hypovolemia, vena cava size and respiratory variability do not predict fluid responsiveness. In contrast, a cIVC >42 % may predict an increase in CO after fluid infusion.

Coagulation changes during lower body negative pressure and blood loss in humans.

We tested the hypothesis that markers of coagulation activation are greater during lower body negative pressure (LBNP) than those obtained during blood loss (BL). We assessed coagulation using both standard clinical tests and thrombelastography (TEG) in 12 men who performed a LBNP and BL protocol in a randomized order. LBNP consisted of 5-min stages at 0, -15, -30, and -45 mmHg of suction. BL included 5 min at baseline and following three stages of 333 ml of blood removal (up to 1,000 ml total). Arterial blood draws were performed at baseline and after the last stage of each protocol. We found that LBNP to -45 mmHg is a greater central hypovolemic stimulus versus BL; therefore, the coagulation markers were plotted against central venous pressure (CVP) to obtain stimulus-response relationships using the linear regression line slopes for both protocols. Paired t-tests were used to determine whether the slopes of these regression lines fell on similar trajectories for each protocol. Mean regression line slopes for coagulation markers versus CVP fell on similar trajectories during both protocols, except for TEG α° angle (-0.42 ± 0.96 during LBNP vs. -2.41 ± 1.13°/mmHg during BL; P < 0.05). During both LBNP and BL, coagulation was accelerated as evidenced by shortened R-times (LBNP, 9.9 ± 2.4 to 6.2 ± 1.1; BL, 8.7 ± 1.3 to 6.4 ± 0.4 min; both P < 0.05). Our results indicate that LBNP models the general changes in coagulation markers observed during BL.