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      Dynamic arterial elastance as a predictor of arterial pressure response to fluid administration: a validation study

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          Abstract

          Introduction

          Functional assessment of arterial load by dynamic arterial elastance (Ea dyn), defined as the ratio between pulse pressure variation (PPV) and stroke volume variation (SVV), has recently been shown to predict the arterial pressure response to volume expansion (VE) in hypotensive, preload-dependent patients. However, because both SVV and PPV were obtained from pulse pressure analysis, a mathematical coupling factor could not be excluded. We therefore designed this study to confirm whether Ea dyn, obtained from two independent signals, allows the prediction of arterial pressure response to VE in fluid-responsive patients.

          Methods

          We analyzed the response of arterial pressure to an intravenous infusion of 500 ml of normal saline in 53 mechanically ventilated patients with acute circulatory failure and preserved preload dependence. Ea dyn was calculated as the simultaneous ratio between PPV (obtained from an arterial line) and SVV (obtained by esophageal Doppler imaging). A total of 80 fluid challenges were performed (median, 1.5 per patient; interquartile range, 1 to 2). Patients were classified according to the increase in mean arterial pressure (MAP) after fluid administration in pressure responders (≥10%) and non-responders.

          Results

          Thirty-three fluid challenges (41.2%) significantly increased MAP. At baseline, Ea dyn was higher in pressure responders (1.04 ± 0.28 versus 0.60 ± 0.14; P <0.0001). Preinfusion Ea dyn was related to changes in MAP after fluid administration ( R 2 = 0.60; P <0.0001). At baseline, Ea dyn predicted the arterial pressure increase to volume expansion (area under the receiver operating characteristic curve, 0.94; 95% confidence interval (CI): 0.86 to 0.98; P <0.0001). A preinfusion Ea dyn value ≥0.73 (gray zone: 0.72 to 0.88) discriminated pressure responder patients with a sensitivity of 90.9% (95% CI: 75.6 to 98.1%) and a specificity of 91.5% (95% CI: 79.6 to 97.6%).

          Conclusions

          Functional assessment of arterial load by Ea dyn, obtained from two independent signals, enabled the prediction of arterial pressure response to fluid administration in mechanically ventilated, preload-dependent patients with acute circulatory failure.

          Electronic supplementary material

          The online version of this article (doi:10.1186/s13054-014-0626-6) contains supplementary material, which is available to authorized users.

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          Most cited references33

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          Surviving Sepsis Campaign: International guidelines for management of severe sepsis and septic shock: 2008

          Objective To provide an update to the original Surviving Sepsis Campaign clinical management guidelines, “Surviving Sepsis Campaign guidelines for management of severe sepsis and septic shock,” published in 2004. Design Modified Delphi method with a consensus conference of 55 international experts, several subsequent meetings of subgroups and key individuals, teleconferences, and electronic-based discussion among subgroups and among the entire committee. This process was conducted independently of any industry funding. Methods We used the GRADE system to guide assessment of quality of evidence from high (A) to very low (D) and to determine the strength of recommendations. A strong recommendation [1] indicates that an intervention's desirable effects clearly outweigh its undesirable effects (risk, burden, cost), or clearly do not. Weak recommendations [2] indicate that the tradeoff between desirable and undesirable effects is less clear. The grade of strong or weak is considered of greater clinical importance than a difference in letter level of quality of evidence. In areas without complete agreement, a formal process of resolution was developed and applied. Recommendations are grouped into those directly targeting severe sepsis, recommendations targeting general care of the critically ill patient that are considered high priority in severe sepsis, and pediatric considerations. Results Key recommendations, listed by category, include: early goal-directed resuscitation of the septic patient during the first 6 hrs after recognition (1C); blood cultures prior to antibiotic therapy (1C); imaging studies performed promptly to confirm potential source of infection (1C); administration of broad-spectrum antibiotic therapy within 1 hr of diagnosis of septic shock (1B) and severe sepsis without septic shock (1D); reassessment of antibiotic therapy with microbiology and clinical data to narrow coverage, when appropriate (1C); a usual 7–10 days of antibiotic therapy guided by clinical response (1D); source control with attention to the balance of risks and benefits of the chosen method (1C); administration of either crystalloid or colloid fluid resuscitation (1B); fluid challenge to restore mean circulating filling pressure (1C); reduction in rate of fluid administration with rising filing pressures and no improvement in tissue perfusion (1D); vasopressor preference for norepinephrine or dopamine to maintain an initial target of mean arterial pressure ≥ 65 mm Hg (1C); dobutamine inotropic therapy when cardiac output remains low despite fluid resuscitation and combined inotropic/vasopressor therapy (1C); stress-dose steroid therapy given only in septic shock after blood pressure is identified to be poorly responsive to fluid and vasopressor therapy (2C); recombinant activated protein C in patients with severe sepsis and clinical assessment of high risk for death (2B except 2C for post-operative patients). In the absence of tissue hypoperfusion, coronary artery disease, or acute hemorrhage, target a hemoglobin of 7–9 g/dL (1B); a low tidal volume (1B) and limitation of inspiratory plateau pressure strategy (1C) for acute lung injury (ALI)/acute respiratory distress syndrome (ARDS); application of at least a minimal amount of positive end-expiratory pressure in acute lung injury (1C); head of bed elevation in mechanically ventilated patients unless contraindicated (1B); avoiding routine use of pulmonary artery catheters in ALI/ARDS (1A); to decrease days of mechanical ventilation and ICU length of stay, a conservative fluid strategy for patients with established ALI/ARDS who are not in shock (1C); protocols for weaning and sedation/analgesia (1B); using either intermittent bolus sedation or continuous infusion sedation with daily interruptions or lightening (1B); avoidance of neuromuscular blockers, if at all possible (1B); institution of glycemic control (1B) targeting a blood glucose < 150 mg/dL after initial stabilization ( 2C ); equivalency of continuous veno-veno hemofiltration or intermittent hemodialysis (2B); prophylaxis for deep vein thrombosis (1A); use of stress ulcer prophylaxis to prevent upper GI bleeding using H2 blockers (1A) or proton pump inhibitors (1B); and consideration of limitation of support where appropriate (1D). Recommendations specific to pediatric severe sepsis include: greater use of physical examination therapeutic end points (2C); dopamine as the first drug of choice for hypotension (2C); steroids only in children with suspected or proven adrenal insufficiency (2C); a recommendation against the use of recombinant activated protein C in children (1B). Conclusion There was strong agreement among a large cohort of international experts regarding many level 1 recommendations for the best current care of patients with severe sepsis. Evidenced-based recommendations regarding the acute management of sepsis and septic shock are the first step toward improved outcomes for this important group of critically ill patients.
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            Effective arterial elastance as index of arterial vascular load in humans.

            This study tested whether the simple ratio of ventricular end-systolic pressure to stroke volume, known as the effective arterial elastance (Ea), provides a valid measure of arterial load in humans with normal and aged hypertensive vasculatures. Ventricular pressure-volume and invasive aortic pressure and flow were simultaneously determined in 10 subjects (four young normotensive and six older hypertensive). Measurements were obtained at rest, during mechanically reduced preload, and after pharmacological interventions. Two measures of arterial load were compared: One was derived from aortic input impedance and arterial compliance data using an algebraic expression based on a three-element Windkessel model of the arterial system [Ea(Z)], and the other was more simply measured as the ratio of ventricular end-systolic pressure to stroke volume [Ea(PV)]. Although derived from completely different data sources and despite the simplifying assumptions of Ea(PV), both Ea(Z) and Ea(PV) were virtually identical over a broad range of altered conditions: Ea(PV) = 0.97.Ea(Z) + 0.17; n = 33, r2 = 0.98, SEE = 0.09, p less than 0.0001. Whereas Ea(PV) also correlated with mean arterial resistance, it exceeded resistance by as much as 25% in older hypertensive subjects (because of reduced compliance and wave reflections), which better indexed the arterial load effects on the ventricle. Simple methods to estimate Ea (PV) from routine arterial pressures were tested and validated. Ea(PV) provides a convenient, useful method to assess arterial load and its impact on the human ventricle. These results highlight effects of increased pulsatile load caused by aging or hypertension on the pressure-volume loop and indicate that this load and its effects on cardiac performance are often underestimated by mean arterial resistance but are better accounted for by Ea.
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              Statistical evaluation of a biomarker.

              A biomarker may provide a diagnosis, assess disease severity or risk, or guide other clinical interventions such as the use of drugs. Although considerable progress has been made in standardizing the methodology and reporting of randomized trials, less has been accomplished concerning the assessment of biomarkers. Biomarker studies are often presented with poor biostatistics and methodologic flaws that precludes them from providing a reliable and reproducible scientific message. A host of issues are discussed that can improve the statistical evaluation and reporting of biomarker studies. Investigators should be aware of these issues when designing their studies, editors and reviewers when analyzing a manuscript, and readers when interpreting results.
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                Author and article information

                Contributors
                ignaciomonge@gmail.com
                manuel.graciaromero@hotmail.com
                anselgil@gmail.com
                hollmann.aya@nhs.net
                andyr@sgul.ac.uk
                michael.grounds@stgeorges.nhs.uk
                m.cecconi@nhs.net
                Journal
                Crit Care
                Critical Care
                BioMed Central (London )
                1364-8535
                1466-609X
                19 November 2014
                19 November 2014
                2014
                : 18
                : 6
                : 626
                Affiliations
                [ ]Servicio de Cuidados Intensivos y Urgencias, Hospital SAS de Jerez, C/Circunvalación s/n, 11407 Jerez de la Frontera, Spain
                [ ]Department of Intensive Care Medicine, St George’s Healthcare NHS Trust and St George’s University of London, Blackshaw Road, Tooting, London, SW17 0QT UK
                Article
                626
                10.1186/s13054-014-0626-6
                4271484
                25407570
                7ded7395-4a59-4a77-940f-93ba2b5a56a5
                © García et al.; licensee BioMed Central Ltd. 2014

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

                History
                : 16 August 2014
                : 28 October 2014
                Categories
                Research
                Custom metadata
                © The Author(s) 2014

                Emergency medicine & Trauma
                Emergency medicine & Trauma

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