Monitoring the venous circulation: novel techniques and applications.

PURPOSE OF REVIEW: Venous pressure is an often-unrecognized cause of patient morbidity. However, bedside assessment of PV is challenging. We review the clinical significance of venous pressure measurement, existing techniques, and introduce the Venous Excess Ultrasound (VExUS) Score as a novel approach using doppler ultrasound to assess venous pressure. RECENT FINDINGS: Studies show clear associations between elevated venous pressure and adverse outcomes in critically ill patients. Current venous pressure measurement techniques include physical examination, right heart catheterization (RHC), two-dimensional ultrasound, and a variety of labor-intensive research-focused physiological maneuvers. Each of these techniques have specific shortcomings, limiting their clinical utility. To address these gaps, Beaubien-Souligny et al. introduced the VExUS Score, a novel doppler ultrasound-based method that integrates IVC diameter with doppler measurements of the hepatic, portal, and renal veins to generate a venous congestion assesment. Studies show strong correlations between VExUS score and RHC measurements, and well as an association between VExUS score and improvement in cardiorenal acute kidney injury, diuretic response, and fluid status shifts. However, studies in noncardiac populations have been small, heterogenous, and inconclusive. SUMMARY: Early studies evaluating the use of doppler ultrasound to assess venous congestion show promise, but further research is needed in diverse patient populations and clinical settings.

A descriptive study of venous pressures and gradients while awake and both pre- and post-stent under anesthesia in patients with idiopathic intracranial hypertension.

BACKGROUND: This study aims to explore factors that affect venous sinus pressures and associated gradients while awake and under general anesthesia (GA) both before and after venous sinus stenting (VSS) in patients with idiopathic intracranial hypertension (IIH). METHODS: A retrospective analysis was performed examining pressures and gradients in patients with IIH having undergone awake venography followed by VSS under GA. RESULTS: 174 patients were included. Compared with awake, GA superior sagittal sinus (SSS) pressures were 2.6 mmHg lower (p=0.01) resulting in a total cranial gradient reduction of 2.5 mmHg (p=0.002). The transverse-sigmoid gradient, the most commonly stented segment, did not differ under the two conditions (p=0.30). Regression analyses demonstrated that body mass index, gender, blood pressure, and end-tidal carbon dioxide content significantly affected venous pressures (all p<0.05). After stenting, mean total cranial gradients decreased by 13.2 mmHg while skull base gradients increased by 0.8 mmHg. Stenting resulted in an 84% mean reduction in the target gradient and a mean decrease in SSS pressures by 78% of the target gradient. When cardiopulmonary and anesthetic factors were optimized, GA had a limited effect on the target gradient in most patients (p=0.88). CONCLUSIONS: This study is the largest series to date to report on cerebral venous pressure measurements and gradients recorded while awake and under GA both before and after VSS for IIH. In a well-controlled cardiorespiratory and anesthetic setting, GA venography may provide information that is not substantially inequivalent to that obtained while awake.

Intercompartmental communication between the cerebrospinal and adjacent spaces during intrathecal infusions in an acute ovine in-vivo model.

INTRODUCTION: The treatment of hydrocephalus has been a topic of intense research ever since the first clinically successful use of a valved cerebrospinal fluid shunt 72 years ago. While ample studies elucidating different phenomena impacting this treatment exist, there are still gaps to be filled. Specifically, how intracranial, intrathecal, arterial, and venous pressures react and communicate with each other simultaneously. METHODS: An in-vivo sheep trial (n = 6) was conducted to evaluate and quantify the communication existing within the cranio-spinal, arterial, and venous systems (1 kHz sampling frequency). Standardized intrathecal infusion testing was performed using an automated infusion apparatus, including bolus and constant pressure infusions. Bolus infusions entailed six lumbar intrathecal infusions of 2 mL Ringer's solution. Constant pressure infusions were comprised of six regulated pressure steps of 3.75 mmHg for periods of 7 min each. Mean pressure reactions, pulse amplitude reactions, and outflow resistance were calculated. RESULTS: All sheep showed intracranial pressure reactions to acute increases of intrathecal pressure, with four of six sheep showing clear cranio-spinal communication. During bolus infusions, the increases of mean pressure for intrathecal, intracranial, arterial, and venous pressure were 16.6 ± 0.9, 15.4 ± 0.8, 3.9 ± 0.8, and 0.1 ± 0.2 mmHg with corresponding pulse amplitude increases of 2.4 ± 0.3, 1.3 ± 0.3, 1.3 ± 0.3, and 0.2 ± 0.1 mmHg, respectively. During constant pressure infusions, mean increases from baseline were 14.6 ± 3.8, 15.5 ± 4.2, 4.2 ± 8.2, and 3.2 ± 2.4 mmHg with the corresponding pulse amplitude increases of 2.5 ± 3.6, 2.5 ± 3.0, 7.7 ± 4.3, and 0.7 ± 2.0 mmHg for intrathecal, intracranial, arterial, and venous pulse amplitude, respectively. Outflow resistances were calculated as 51.6 ± 7.8 and 77.8 ± 14.5 mmHg/mL/min for the bolus and constant pressure infusion methods, respectively-showing deviations between the two estimation methods. CONCLUSIONS: Standardized infusion tests with multi-compartmental pressure recordings in sheep have helped capture distinct reactions between the intrathecal, intracranial, arterial, and venous systems. Volumetric pressure changes in the intrathecal space have been shown to propagate to the intraventricular and arterial systems in our sample, and to the venous side in individual cases. These results represent an important step into achieving a more complete quantitative understanding of how an acute rise in intrathecal pressure can propagate and influence other systems.

Measurement of the retinal venous pressure with a new instrument in healthy subjects.

BACKGROUND: The retinal venous pressure (RVP) is a determining factor for the blood supply of the retina as well as the optic nerve head and until recently has been measured by contact lens dynamometry (CLD). A new method has been developed, potentially offering better acceptance. The applicability and the results of both methods were compared. METHODS: The type of this study is cross sectional. The subjects were 36 healthy volunteers, age 26 ± 5 years (mean ± s). Tonometry: rebound tonometer (RT) (iCare). The measurements were performed during an increase in airway pressure of 20 mmHg (Valsalva manoeuvre). Principle of RVP measurement: the central retinal vein (CRV) is observed during an increase of intraocular pressure (IOP) and at the start of pulsation, which corresponds with the RVP. Two different instruments for the IOP enhancement where used: contact lens dynamometry and the new instrument, IOPstim. PRINCIPLE: a deflated balloon of 8 mm diameter-placed on the sclera laterally of the cornea-is filled with air. As soon as a venous pulsation occurs, filling is stopped and the IOP is measured, equalling the RVP. Examination procedure: randomization of the sequence: CLD or IOPstim, IOP, mydriasis, IOP three single measurements (SM) of the IOP with RT or of the pressure increase with CLD at an airway pressure of 20 mmHg, 5 min break, IOP, and three SM using the second method at equal pressure (20 mmHg). RESULTS: Spontaneous pulsation of the CRV was present in all 36 subjects. Pressures are given in mmHg. IOP in mydriasis 15.6 ± 3.3 (m ± s). Median RVP (MRVP)) of the three SM: CLD/IOPstim, 37.7 ± 5.2/24.7 ± 4.8 (t test: p < 0.001). Range of SM: 3.2 ± 1.8/2.9 ± 1.3 (t test: p = 0.36). Intraclass correlation coefficient (ICC) of SM: 0.88/0.83. ANOVA in SM: p = 0.48/0.08. MRVP CLD minus MRVP IOPstim: 13.0 ± 5.6. Ratio MRVP CLD/MRVP IOPstim: 1.56 ± 3.1. Cooperation and agreeability were slightly better with the IOPstim. CONCLUSION: This first study with the IOPstim in humans was deliberately performed in healthy volunteers using Valsalva conditions. As demonstrated by ICC and ANOVA, reproducible SM can be obtained by both methods and the range of the SM does not differ greatly. The higher MRVP in CLD could be explained by the different directions of the force vectors.

The Distribution of Retinal Venous Pressure and Intraocular Pressure Differs Significantly in Patients with Primary Open-Angle Glaucoma.

INTRODUCTION: Until now, venous pressure within the eye has widely been equated with intraocular pressure (IOP). Measurements with dynamometers calibrated in instrument units or in force showed that the retinal venous pressure (RVP) may be higher than the IOP in glaucoma patients. In this study, the RVP was measured with a contact lens dynamometer calibrated in mmHg. METHODS: Study type: cross-sectional. SUBJECTS: Fifty consecutive patients with primary open-angle glaucoma (POAG) who underwent diurnal curve measurement under medication. Age: 69 ± 8 years. Measurement of RVP: contact lens dynamometry. IOP measurement: dynamic contour tonometry. RESULTS: Pressures are given in mmHg. In all 50 patients, the IOP was 15.9 (13.6; 17.1) [median (Q1; Q3)], and the RVP was 17.4 (14.8; 27.2). The distribution of the IOP was normal and that of the RVP was right skewed. In the subgroup of 34 patients with spontaneous pulsation of the central retinal vein (SVP), the IOP and therefore, by definition, the RVP was 16.5 (13.7; 17.4). In the subgroup of 16 patients without SVP, the IOP was 14.8 (13.3; 16.4), and the RVP was 31.3 (26.2; 38.8) (p ≤ 0.001). In systemic treatment, the prescribed drugs were (the number of patients is given in parentheses): ACE inhibitors (20), ß-blockers (17), angiotensin II-receptor blockers (13), calcium channel blockers (12), diuretics (7). No difference in RVP was observed between patients receiving these drugs and not receiving them, except in the ß-blocker group. Here, the 17 patients with systemic ß-blockers had a median RVP of 15.6 mmHg and without 20.2 mmHg (p = 0.003). In the 16 patients with a higher RVP than IOP, only one patient received a systemic ß-blocker. The median IOP was 15.7 mmHg with systemic ß-blockers and 16.1 mmHg without (p = 0.85). CONCLUSION: In a subgroup of 16 of the 50 patients studied, the RVP was greater than the IOP by a highly statistically and clinically significant degree. According to the widely accepted thinking on the pathophysiology of retinal and optic nerve head circulation, the blood flow in these tissues may be much more compromised in this group of patients than has been assumed. They may be identified by a missing SVP. Topical and systemic medications showed no statistically significant influence on the RVP, except for the systemic ß-blockers, in which the RVP was lower by 4.6 mmHg than for the patients who did not receive these drugs (p = 0.003).

Episcleral venous pressure response to brain stem stimulation: Effect of topical lidocaine.

Episcleral venous pressure (EVP) is important for steady state intraocular pressure (IOP), as it has to be overcome by aqueous humor in order to leave the eye. Recent evidence suggests a neuronal tone being present, as topical anesthesia lowered EVP. The superior salivatory nucleus in the brainstem could be identified to elicit increases in EVP during electrical stimulation. In the present study the effect of topical anesthesia on the stimulation effect was investigated. 8 Spraque Dawley rats were anesthetized, artificially ventilated with CO2 monitoring and continuous blood pressure monitoring. Intraocular pressure was measured continuously through a cannula in the vitreous body. Episcleral venous pressure was measured by direct cannulation of an episcleral vein via a custom made glass pipette connected to a servonull micropressure system. Electrical stimulation of the superior salivatory nucleus (9 µA, 200 pulses of 1 ms duration) increased EVP from 8.51 ± 1.82 mmHg to 10.97 ± 1.93 mmHg (p = 0.004). After application of topical lidocaine EVP increased from 7.42 ± 1.59 mmHg to 9.77 ± 1.65 mmHg (p = 0.007). The EVP response to stimulation before and after lidocaine application was not statistically significantly different (2.45 ± 0.5 vs 2.35 ± 0.49 mmHg, p = 0.69), while the decrease in baseline EVP was (8.51 vs. 7.42 mmHg, p = 0.045). The present data suggest that distinct neuronal mechanisms controlling the episcleral circulation of rats exist. This is in keeping with previous reports of two distinct arterio-venous anastomoses, one in the limbal circulation and one in the conjunctival/episcleral circulation.

Evaluation of umbilical venous flow volume measured using ultrasound compared to circuit flow volume in the EXTra-uterine Environment for Neonatal Development (EXTEND) system in fetal sheep.

OBJECTIVE: To compare and validate umbilical venous flow volume (UVFV) measured at the intra-abdominal portion using ultrasound with actual flow volume of umbilical vein (UV) in fetal sheep sustained on the EXTrauterine Environment for Neonatal Development (EXTEND) system. METHODS: Circuit flow volume through the oxygenator was obtained using sensors. Ultrasound derived UVFV (ml/min) was calculated as (UV diameter [cm]/2)2 × 3.14 × maximum velocity (cm/s) × 0.5 × 60, measured at approximately the mid portion between its abdominal insertion and the origin of the ductus venosus. UVFV was measured by ultrasound once daily and was compared to the average of daily circuit flow volume directly measured. RESULTS: UVFV was measured 168 times in 15 fetal sheep. The ratio of circuit flow volume to combined cardiac output remained stable within the anticipated physiological range throughout. UVFV measured by ultrasound showed good correlation to directly measured circuit flow (r = 0.72). Interclass correlation coefficients for intra-observer variability was 0.991 (95% confidence interval [CI], 0.979-0.996). CONCLUSION: UVFV measured at the intra-abdominal portion using ultrasound shows a good correlation with directly measured circuit flow volume in UV of fetal sheep on the EXTEND system. Regular incorporation of such validated UVFV measures into clinical use may offer opportunities to better understand conditions of placental dysfunction.

Increase in Free Hepatic Venous Pressure Response to Beta-Blockers Predicts Variceal Bleeding in Cirrhotic Patients.

BACKGROUND AND AIMS: Nonselective beta-blockers (NSBBs) are the main drug to prevent portal hypertension. It could alter free hepatic venous pressure (FHVP); however, the significance is unknown. This prospective study was to explore the change of FHVP after use of NSBBs and its predictive value for gastroesophageal varices (GOV) bleeding in cirrhotic patients. Patients and Methods. Cirrhotic patients with medium-large GOV between September 2014 and January 2019 were enrolled. After initial hepatic venous pressure gradient (HVPG) measurement, patients received oral NSBBs. Seven days later, the secondary HVPG was examined to evaluate the FHVP alteration and hemodynamic response. The variceal bleeding between patients with FHVP increased and decreased/unchanged was compared. RESULTS: A total of 74 patients were enrolled, and 62 patients completed the secondary HVPG measurement and was followed up. The cumulative bleeding rate was significantly higher in patients with FHVP increased ≥ 1.75 mmHg than those with FHVP decreased/unchanged (54.5% vs. 22.5%, p = 0.021), while there was no significant difference in bleeding between HVPG responders and nonresponders (32.6% vs. 37.5%, p = 0.520). For HVPG responders, variceal bleeding in patients with FHVP increased ≥ 1.75 mmHg was significantly more than that in patients with FHVP decreased/unchanged (57.9% vs. 28.6%, p = 0.041). Cox regression analysis showed that change of FHVP was an independent predictor of variceal bleeding. CONCLUSION: Increase ≥ 1.75 mmHg in FHVP responding to beta-blockers in cirrhotic patients with GOV indicates high risk of variceal bleeding. Besides HVPG response, change of FHVP should also be valued in hemodynamic evaluation to beta-blockers. This trial is registered with Chinese Clinical Trial Registry ChiCTR-IPR-17012836.

Splenic non-infarction volume determines a clinically significant hepatic venous pressure gradient response to partial splenic embolization in patients with cirrhosis and hypersplenism.

BACKGROUND: This study aimed to investigate changes in the hepatic venous pressure gradient (HVPG) by partial splenic embolization (PSE) and to identify the determinants of a clinically meaningful postoperative HVPG reduction. METHODS: Sixty-eight patients with cirrhosis and hypersplenism who underwent PSE at our department between September 2007 and June 2020 were included. The HVPG was evaluated pre- and immediately post-PSE. The patients were divided into three groups according to their preprocedural HVPG: low-HVPG (< 10 mmHg, n = 22), intermediate-HVPG (10 mmHg ≤ HVPG < 16 mmHg, n = 33), and high-HVPG (≥ 16 mmHg, n = 13). RESULTS: Overall, PSE significantly reduced HVPG from 12.2 ± 4.0 to 9.4 ± 3.6 mmHg (p < 0.01) with a relative decrease of 22.2 ± 20.4%. In addition, HVPG reductions were 19.4 ± 28.7%, 24.0 ± 15.9%, and 22.5 ± 13.3% in the low-, intermediate-, and high-HVPG groups, respectively, indicating no significant difference in HVPG reduction between the groups. An HVPG decrease of ≥ 20% from the baseline, defined in this study as a clinically significant HVPG response to PSE, was achieved in 55.9% of all patients. Multivariate logistic regression and receiver operating characteristic curve analyses identified splenic non-infarction volume as an independent determinant of a 20% decrease in HVPG (p < 0.05), with a cut-off of 139.2 cm3 (sensitivity, 76.3%; specificity, 60.0%; p < 0.05). CONCLUSIONS: The splenic non-infarction volume, namely the residual functional spleen volume, independently determines a clinically significant HVPG response to PSE in patients with cirrhosis and hypersplenism.

Nanoencapsulated hybrid compound SA-2 with long-lasting intraocular pressure-lowering activity in rodent eyes.

Purpose: Glaucoma is a neurodegenerative disease of the eye with an estimated prevalence of more than 111.8 million patients worldwide by 2040, with at least 6 to 8 million projected to become bilaterally blind. Clinically, the current method of slowing glaucomatous vision loss is to reduce intraocular pressure (IOP). In this manuscript, we describe the in vitro cytoprotective and in vivo long lasting IOP-lowering activity of the poly D, L-lactic-co-glycolic acid (PLGA) nanoparticle-encapsulated hybrid compound SA-2, possessing nitric oxide (NO) donating and superoxide radical scavenging functionalities. Methods: Previously characterized primary human trabecular meshwork (hTM) cells were used for the study. hTM cells were treated with SA-2 (100 µM, 200 µM, and 1,000 µM), SA-2 PLGA-loaded nanosuspension (SA-2 NPs, 0.1%), or vehicle for 30 min. Cyclic guanosine monophosphate (cGMP) and super oxide dismutase (SOD) levels were analyzed using commercial kits. In another experiment, hTM cells were pretreated with tert-butyl hydrogen peroxide (TBHP, 300 µM) for 30 min followed by treatment with escalating doses of SA-2 for 24 h, and CellTiter 96 cell proliferation assay was performed. For the biodistribution study, the cornea, aqueous humor, vitreous humor, retina, choroid, and sclera were collected after 1 h of administration of a single eye drop (30 µl) of SA-2 NPs (1% w/v) formulated in PBS to rat (n = 6) eyes. Compound SA-2 was quantified using high performance liquid chromatography /mass spectrometry (HPLC/MS). For the IOP-lowering activity study, a single SA-2 NPs (1%) eye drop was instilled in normotensive rats eyes and in the IOP-elevated rat eyes (n = 3/group, in the Morrison model of glaucoma), or Ad5TGFß2-induced ocular hypertensive (OHT) mouse eyes (n = 5/group). IOP was measured at various time points up to 72 h, and the experiment was repeated in triplicate. Mouse aqueous humor outflow facility was determined with multiple flow-rate infusion and episcleral venous pressure estimated with manometry. Results: SA-2 upregulated cGMP levels (six- to ten-fold) with an half maximal effective concentration (EC50) of 20.3 µM in the hTM cells and simultaneously upregulated (40-fold) the SOD enzyme when compared with the vehicle-treated hTM cells. SA-2 also protected hTM cells from TBHP-induced decrease in cell survival with an EC50 of 0.38 µM. A single dose of slow-release SA-2 NPs (1% w/v) delivered as an eye drop significantly lowered IOP (by 30%) in normotensive and OHT rodent eyes after 3 h post-dose, with the effect lasting up to 72 h. A statistically significant increase in aqueous outflow facility and a decrease in episcleral venous pressure was observed in rodents at this dose at 54 h. Conclusions: Hybrid compound SA-2 upregulated cGMP in hTM cells, increased outflow facility and decreased IOP in rodent models of OHT. Compound SA-2 possessing an antioxidant moiety provided additive cytoprotective activity to oxidatively stressed hTM cells by scavenging reactive oxygen species (ROS) and increasing SOD enzyme activity. Additionally, the PLGA nanosuspension formulation (SA-2 NPs) provided longer duration of IOP-lowering activity (up to 3 days) in comparison with the free non-encapsulated SA-2 drug. The data have implications for developing novel, non-prostaglandin therapeutics for IOP-lowering and cytoprotective effects with the possibility of an eye drop dosing regimen of once every 3 days for patients with glaucoma.

Algebraic formulas characterizing an alternative to Guyton's graphical analysis relevant for heart failure.

Although Guyton's graphical analysis of cardiac output-venous return has become a ubiquitous tool for explaining how circulatory equilibrium emerges from heart-vascular interactions, this classical model relies on a formula for venous return that contains unphysiological assumptions. Furthermore, Guyton's graphical analysis does not predict pulmonary venous pressure, which is a critical variable for evaluating heart failure patients' risk of pulmonary edema. Therefore, the purpose of the present work was to use a minimal closed-loop mathematical model to develop an alternative to Guyton's analysis. Limitations inherent in Guyton's model were addressed by 1) partitioning the cardiovascular system differently to isolate left ventricular function and lump all blood volumes together, 2) linearizing end-diastolic pressure-volume relationships to obtain algebraic solutions, and 3) treating arterial pressures as constants. This approach yielded three advances. First, variables related to morbidities associated with left ventricular failure were predicted. Second, an algebraic formula predicting left ventricular function was derived in terms of ventricular properties. Third, an algebraic formula predicting flow through the portion of the system isolated from the left ventricle was derived in terms of mechanical properties without neglecting redistribution of blood between systemic and pulmonary circulations. Although complexities were neglected, approximations necessary to obtain algebraic formulas resulted in minimal error, and predicted variables were consistent with reported values.

Liver stiffness measured by two-dimensional shear-wave elastography predicts hepatic vein pressure gradient at high values in liver transplant candidates with advanced liver cirrhosis.

Liver stiffness is a reliable non-invasive predictor of Hepatic Venous Pressure Gradient (HVPG) above 10 mm Hg. However, it failed to predict higher thresholds of HVPG. Our aim was to investigate whether liver stiffness and selected previously published non-invasive blood biomarkers could predict higher HVPG thresholds in liver transplant candidates without ongoing alcohol use. One hundred and nine liver transplant candidates with liver cirrhosis of various aetiologies underwent direct HVPG measurement, liver stiffness measurement by 2D shear-wave elastography (Aixplorer Multiwave, Supersonic Imagine, France) and assessment of blood HVPG biomarkers (osteopontin, VCAM-1, IL-6, TNF-α, IL-1ra/IL-1F3 and ELF score). The correlation between liver stiffness and HVPG was linear up to 30 mm Hg of HVPG (r = 0.765, p < 0.0001). The regression lines had similar slopes for HVPG values below and above 16 mm Hg (p > 0.05) and the correlation in patients with HVPG <16 mm Hg (r = 0.456, p = 0.01) was similar to patients with HVPG ≥ 16 mm Hg (r = 0.499, p < 0.0001). The correlation was similar in the subgroup patients with alcoholic (r = 0.718, p < 0.0001), NASH (r = 0.740, p = 0.008), cryptogenic (r = 0.648, p = 0,0377), cholestatic and autoimmune (r = 0.706, p < 0.0001) and viral cirrhosis (r = 0.756, p < 0.0001). Liver stiffness distinguished patients with HVPG above 16, and 20 mm Hg with AUROCs 0.90243, and 0.86824, sensitivity 0.7656, and 0.7027, and specificity 0.9333, and 0.8750. All studied blood biomarkers correlated better with liver stiffness than with HVPG and their AUROCs did not exceed 0.8 at both HVPG thresholds. Therefore, a composite predictor superior to liver stiffness could not be established. We conclude that liver stiffness is a clinically reliable predictor of higher HVPG thresholds in non-drinking subjects with advanced liver cirrhosis.

Relation of Peripheral Venous Pressure to Central Venous Pressure in Patients With Heart Failure, Heart Transplant, and Left Ventricular Assist Device.

Peripheral venous pressure (PVP) monitoring is a noninvasive method to assess volume status. We investigated the correlation between PVP and central venous pressure (CVP) in heart failure (HF), heart transplant (HTx), and left ventricular assist device (LVAD) patients undergoing right heart catheterization (RHC). A prospective, cross-sectional study examining PVP in 100 patients from October 2018 to January 2020 was conducted. The analysis included patients undergoing RHC admitted for HF, post-HTx monitoring, or LVAD hemodynamic testing. Sixty percent of patients had HF, 30% were HTx patients, and 10% were LVAD patients. The mean PVP was 9.4 ± 5.3 mm Hg, and the mean CVP was 9.2 ± 5.8 mm Hg. The PVP and CVP were found to be highly correlated (r = 0.93, p < 0.00001). High correlation was also noted when broken down by HF (r = 0.93, p < 0.00001), HTx (r = 0.93, p < 0.00001), and LVAD groups (r = 0.94, p < 0.00005). In conclusion, there is a high degree of correlation between PVP and CVP in HF, HTx, and LVAD patients. PVP measurements can be used as a rapid, reliable, noninvasive estimate of volume status in these patient populations.

The Effects of Acute Intracranial Pressure Changes on the Episcleral Venous Pressure, Retinal Vein Diameter and Intraocular Pressure in a Pig Model.

PURPOSE: Orbital veins such as the retinal veins and episcleral veins drain into the cavernous sinus, an intracranial venous structure. We studied the effects of acute intracranial pressure (ICP) elevation on episcleral venous pressure, intraocular pressure and retinal vein diameter in an established non-survival pig model. METHODS: In six adult female domestic pigs, we increased ICP in 5 mm Hg increments using saline infusion through a lumbar drain. We measured ICP (using parenchymal pressure monitor), intraocular pressure (using pneumatonometer), episcleral venous pressure (using venomanometer), retinal vein diameter (using OCT images) and arterial blood pressure at each stable ICP increment. The average baseline ICP was 5.4 mm Hg (range 1.5-9 mm Hg) and the maximum stable ICP ranged from 18 to 40 mm Hg. Linear mixed models with random intercepts were used to evaluate the effect of acute ICP increase on outcome variables. RESULTS: With acute ICP elevation, we found loss of retinal venous pulsation and increased episcleral venous pressure, intraocular pressure and retinal vein pressure in all animals. Specifically, acute ICP increase was significantly associated with episcleral venous pressure (ß = 0.31; 95% CI 0.14-0.48, p < .001), intraocular pressure (ß = 0.37, 95%CI 0.24-0.50; p < .001) and retinal vein diameter (ß = 11.29, 95%CI 1.57-21.00; p = .03) after controlling for the effects of arterial blood pressure. CONCLUSION: We believe that the ophthalmic effects of acute ICP elevation are mediated by increased intracranial venous pressure producing upstream pressure changes within the orbital and retinal veins. These results offer exciting possibilities for the development of non-invasive ophthalmic biomarkers to estimate acute ICP elevations following significant neuro-trauma.

Increased episcleral venous pressure in a mouse model of circumlimbal suture induced ocular hypertension.

PURPOSE: To investigate changes in aqueous humor dynamics during intraocular pressure (IOP) elevation induced by circumlimbal suture in mice. METHODS: Ocular hypertension (OHT) was induced by applying a circumlimbal suture behind the limbus in male adult C57BL6/J mice. In the OHT group, the suture was left in place for an average of 8 weeks (n = 10, OHT group). In the sham control group the suture was cut at 2 days (n = 9, sham group) and in the naïve control group (n = 5) no suture was implanted. IOP was measured at baseline across 3 days, 1 h post-suture implantation, and at the chronic endpoint. Anterior segments were assessed using optical coherence tomography (OCT). Episcleral venous pressure (EVP), total outflow facility (C), uveoscleral outflow (Fu) and aqueous humor flow rate (Fin) were determined using a constant-flow infusion model. RESULTS: All aqueous dynamic and chronic IOP outcome measures showed no difference between sham and naïve controls (p > 0.05) and thus these groups were combined into a single control group. IOP was elevated in OHT group compared with controls (p < 0.01). Chronic suture implantation did not change pupil size, anterior chamber depth or iridocorneal angles (p > 0.05). EVP was significantly higher in OHT eyes compared to control eyes (p < 0.01). There was no statistical difference in C, Fu and Fin between groups (p > 0.05). A significant linear correlation was found between IOP and EVP (R2 = 0.35, p = 0.001). CONCLUSIONS: Circumlimbal suture implantation in mouse eyes results in chronic IOP elevation without angle closure. Chronic IOP elevation is likely to reflect higher EVP.

Sinistral Portal Hypertension Prediction During Pancreatoduodenectomy With Splenic Vein Resection.

BACKGROUND: Pancreaticoduodenectomy with porto-mesenterico-splenic confluence resection can cause sinistral portal hypertension (SPH), which may lead to gastrointestinal bleeding. Nevertheless, it remains difficult to predict SPH development during surgery. The aim of this study is to assess the feasibility of measuring splenic vein (SV) pressure to predict SPH. METHODS: The patients who underwent pancreaticoduodenectomy with porto-mesenterico-splenic confluence resection between January 2016 and December 2017 were included in this study. SV pressure was measured before SV clamping (SVP1) and after SV clamping (SVP2). SPH was defined as varicose vein formation detected by follow-up computed tomography. Incidence of SPH was assessed in patients who had no SV drainage after surgery. RESULTS: SV pressure was measured in 41 patients. Among them, 24 had no SV drainage (13 patients had occluded SV reconstruction, and 11 had SV ligation without an attempt at reconstruction) and were included for the analysis. SPH was observed in 16 of 24 patients (67%). The median ΔSVP (SPV2-SVP1) in patients with SPH was higher than that in patients without SPH (13.5 mmHg versus 7.5 mmHg, P = 0.0237). Most patients with SVP2 >20 mmHg (12/14 [86%]) or ΔSVP >10 mmHg (10/11 [91%]) developed SPH. CONCLUSIONS: For the patients with SV resection, high SV pressure after clamping (≥20 mmHg) and a large SV pressure difference (≥10 mmHg) before and after clamping are feasible indication criteria for SV reconstruction to prevent SPH.

Noninvasive measurement of venous wall deformation induced by changes in transmural pressure shows altered viscoelasticity in patients with chronic venous disease.

OBJECTIVE: The noninvasive measurement of venous wall deformation induced by changes in transmural pressure could allow for the assessment of viscoelasticity and differentiating normal from diseased veins. METHODS: In 57 patients with limbs in the C1s (telangiectasia or reticular veins and symptoms), C3 (edema), or C5 (healed venous ulcer) CEAP (clinical, etiologic, anatomic, pathophysiologic) category of chronic venous disease and 54 matched healthy controls, we measured the changes in the cross-sectional area of the small saphenous vein and a deep calf vein in the supine and standing positions and under compression with an ultrasound probe using ultrasonography. RESULTS: The small saphenous vein, but not the deep calf vein, cross-sectional area was smaller in the limbs of the controls than in the limbs with C3 or C5 disease but was not different from that in C1s limbs. When changing from the supine to the standing position, a greater force was required to collapse the leg veins. Their cross-sectional area increased in most subjects but decreased in 31.5% of them as for the small saphenous veins and 40.5% for the deep calf vein. The small saphenous vein area vs compression force function followed a hysteresis loop, demonstrating viscoelastic features. Its area, which represents the viscosity component, was greater (P < .001) in the pooled C3 and C5 limbs (median, 2.40 N⋅mm2; lower quartile [Q1] to upper quartile [Q3], 1.65-3.88 N⋅mm2) than in the controls (median, 1.24 N⋅mm2; Q1-Q3, 0.64-2.14 N⋅mm2) and C1s limbs (median, 1.15 N⋅mm2; Q1-Q3, 0.71-2.97 N⋅mm2). The area increased (P < .0001) in the standing position in all groups. CONCLUSIONS: Postural changes in the cross-sectional area of the leg veins were highly diverse among patients with chronic venous disease and among healthy subjects and appear unsuitable for pathophysiologic characterization. In contrast, small saphenous vein viscoelasticity increased consistently in the standing position and the viscosity was greater in limbs with C3 and C5 CEAP disease than in controls.

Fluid Resuscitation: History, Physiology, and Modern Fluid Resuscitation Strategies.

Intravenous (IV) fluids are among the most common interventions performed in the emergency department. They are at times lifesaving, but if used recklessly can be harmful. Given their ubiquity, it is important to understand the history, physiology, and current strategies that govern the use of IV fluids during the resuscitation of the critically ill.

Assessment of Upper Extremity Venous Compliance in Patients With Abdominal Aortic Aneurysms.

OBJECTIVE: Abdominal aortic aneurysm (AAA) is associated with morphological and functional changes in both aneurysmal and non-aneurysmal arteries. However, it remains uncertain whether similar changes also exist in the venous vasculature. The aim of this study was to evaluate global venous function in patients with AAA and controls. METHODS: This experimental study comprised 31 men with AAA (mean ± standard deviation age 70.0 ± 2.8 years) and 29 male controls (aged 70.6 ± 3.4 years). Venous occlusion plethysmography (VOP) was used to evaluate arm venous compliance at venous pressures between 10 and 60 mmHg in steps of 5 mmHg. Compensatory mobilisation of venous capacitance blood (capacitance response) was measured with a volumetric technique during experimental hypovolaemia induced by lower body negative pressure (LBNP). RESULTS: The VOP induced pressure-volume curve was significantly less steep in patients with AAA (interaction, p < .001), indicating lower venous compliance. Accordingly, the corresponding pressure-compliance curves displayed reduced venous compliance at lower venous pressures in patients with AAA vs. controls (interaction, p < .001; AAA vs. control, p = .018). After adjusting for arterial hypertension, diabetes mellitus, hyperlipidaemia, chronic obstructive pulmonary disease, and smoking, VOP detected differences in venous compliance remained significant at low venous pressures, that is, at 10 mmHg (p = .008), 15 mmHg (p = .013), and 20 mmHg (p = .026). Mean venous compliance was negatively correlated with aortic diameter (r = -.332, p = .010). Mobilisation of venous capacitance response during LBNP was reduced by approximately 25% in patients with AAA (p = .030), and the redistribution of venous blood during LBNP was negatively correlated with aortic diameter (r = -.417, p = .007). CONCLUSION: Men with AAA demonstrated reduced venous compliance and, as a result, a lesser capacity to mobilise peripheral venous blood to the central circulation during hypovolaemic stress. These findings imply that the AAA disease may be accompanied by functional changes in the venous vascular wall.