Julia Y. Wagner

Measurement of blood pressure

Blood pressure is overwhelmingly the most commonly measured parameter for the assessment of haemodynamic stability. In clinical routine in the operating theatre and in the intensive care unit, blood pressure measurements are usually obtained intermittently and non-invasively using oscillometry (upper-arm cuff method) or continuously and invasively with an arterial catheter. However, both the oscillometric method and arterial catheter-derived blood pressure measurements have potential limitations. A basic technical understanding of these methods is crucial in order to avoid unreliable blood pressure measurements and consequential treatment errors. In the recent years, technologies for continuous non-invasive blood pressure recording such as the volume clamp method or radial artery applanation tonometry have been developed and validated. The question in which patient groups and clinical settings these technologies should be applied to improve patient safety or outcome has not been definitively answered. In critically ill patients and high-risk surgery patients, further improvement of these technologies is needed before they can be recommended for routine clinical use.

Tracking Changes in Cardiac Output: Statistical Considerations on the 4-quadrant Plot and the Polar Plot Methodology

When comparing 2 technologies for measuring hemodynamic parameters with regard to their ability to track changes, 2 graphical tools are omnipresent in the literature: the 4-quadrant plot and the polar plot recently proposed by Critchley et al. The polar plot is thought to be the more advanced statistical tool, but care should be taken when it comes to its interpretation. The polar plot excludes possibly important measurements from the data. The polar plot transforms the data nonlinearily, which may prevent it from being seen clearly. In this article, we compare the 4-quadrant and the polar plot in detail and thoroughly describe advantages and limitations of each. We also discuss pitfalls concerning the methods to prepare the researcher for the sound use of both methods. Finally, we briefly revisit the Bland-Altman plot for the use in this context.

Hemodynamic management of septic shock: is it time for "individualized goal-directed hemodynamic therapy" and for specifically targeting the microcirculation?

ABSTRACT Septic shock is a life-threatening condition in both critically ill medical patients and surgical patients during the perioperative phase. In septic shock, specific alterations in global cardiovascular dynamics (i.e., the macrocirculation) and in the microcirculatory blood flow (i.e., the microcirculation) have been described. However, the presence and degree of microcirculatory failure are in part independent from systemic macrohemodynamic variables. Macrocirculatory and microcirculatory failure can independently induce organ dysfunction. We review current diagnostic and therapeutic approaches for the assessment and optimization of both the macrocirculation and the microcirculation in septic shock. There are various technologies for the determination of macrocirculatory hemodynamic variables. We discuss the data on early goal-directed therapy for the resuscitation of the macrocirculation. In addition, we describe the concept of “individualized goal-directed hemodynamic therapy.” Technologies to assess the local microcirculation are also available. However, adequate resuscitation goals for the optimization of the microcirculation still need to be defined. At present, we are not ready to specifically monitor and target the microcirculation in clinical routine outside studies. In the future, concepts for an integrative approach for individualized hemodynamic management of the macrocirculation and in parallel the microcirculation might constitute a huge opportunity to define additional resuscitation end points in septic shock.

Radial artery applanation tonometry for continuous non-invasive arterial pressure monitoring in intensive care unit patients: comparison with invasively assessed radial arterial pressure

BACKGROUND Radial artery applanation tonometry technology can be used for continuous non-invasive measurement of arterial pressure (AP). The purpose of this study was to evaluate this AP monitoring technology in intensive care unit (ICU) patients in comparison with invasive AP monitoring using a radial arterial catheter. METHODS In 24 ICU patients (German university hospital), AP values were simultaneously recorded on a beat-to-beat basis using radial artery applanation tonometry (T-Line system; Tensys Medical, San Diego, CA, USA) and a radial arterial catheter (contralateral arm). The primary endpoint of the study was to investigate the accuracy and precision of the non-invasively assessed AP measurements with the Bland-Altman method based on averaged 10 beat AP epochs (n=2993 10 beat epochs). RESULTS For mean AP (MAP), systolic AP (SAP), and diastolic AP (DAP), we observed a bias (±standard deviation of the bias; 95% limits of agreement; percentage error) of +2 mm Hg (±6; -11 to +15 mm Hg; 15%), -3 mm Hg (±15; -33 to +27 mm Hg; 23%), and +5 mm Hg (±7; -9 to +19 mm Hg; 22%), respectively. CONCLUSIONS In ICU patients, MAP and DAP measurements obtained using radial artery applanation tonometry show clinically acceptable agreement with invasive AP determination with a radial arterial catheter. While the radial artery applanation tonometry technology also allows SAP measurements with high accuracy, its precision for SAP measurements needs to be further improved.

When should we adopt continuous noninvasive hemodynamic monitoring technologies into clinical routine

The introduction of new technologies for noninvasive continuous hemodynamic monitoring requires the conduction of well-planned clinical studies in order to assess the technology’s measurement performance and to evaluate the potential benefit for the patient. But what is the right way to go with regard to clinical validation and evaluation studies from the technology’s first introduction to its medically useful application on a routine basis? From the article by Benes et al. [1] a general recommendation for a reasonable approach in order to answer this question can be derived. The existence of methodologically and statistically solid validation studies must be the prerequisite for any further scientific investigation of a potential clinical benefit of noninvasive continuous hemodynamic monitoring technologies. In order to assess a new technology’s accuracy and precision and thus its measurement performance in validation studies, we need the comparison with invasive arterial catheter-derived measurements as the clinical criterion standard method. However, invasive hemodynamic monitoring is usually reserved for critically ill and highrisk surgical patients. Therefore, the first step on the path towards establishing a new noninvasive technology must be the performance of validation studies in these patient groups equipped with invasive hemodynamic monitoring that can be used as a reference method [2, 3]. We should then carefully and critically check a new noninvasive technology’s validation data in order to avoid misinterpretation of the technology’s measurement performance. We must avoid performing premature outcome-oriented studies using devices and algorithms that have not been meticulously validated or that are simply not precise enough. Sometimes we might have to take a step back after the first validation data and try to improve the technology’s algorithms and technical shortcomings before proceeding to the next level of studies. Only when meticulously performed validation studies are available it will make sense—from a scientific and clinical point of view—to proceed to the second step. This next step is to precisely define the right target patient groups and clinical scenarios for the sensible application of the noninvasive continuous hemodynamic monitoring technology. At present, a recommendation to use a noninvasive continuous blood pressure measurement technology instead of an arterial catheter in critically ill patients treated in the intensive care unit or in high-risk surgical patients would not be appropriate. Instead, we should rather focus on patients who do not receive continuous hemodynamic monitoring but intermittent blood pressure measurements using oscillometry. Benes et al. [1] rightly decided to include low and intermediate-risk surgical patients during thyroid surgery in beach chair position. Thereby they offer us an excellent example for the possible use of noninvasive continuous blood pressure monitoring as a reasonable alternative to intermittent oscillometric blood pressure measurements in the perioperative setting. Other scenarios in which continuous noninvasive blood pressure measurement might contribute to the patient’s safety have been recently proposed [4, 5]. After having precisely defined patient groups and clinical scenarios for the new technology’s application, the third important step is conducting studies that are related to patient safety and outcome. Such studies might assess hospital mortality, hospital length of stay, or complication J. Y. Wagner (&) B. Saugel Department of Anesthesiology, Center of Anesthesiology and Intensive Care Medicine, University Medical Center HamburgEppendorf, Martinistrasse 52, 20246 Hamburg, Germany e-mail: jwagner.science@gmail.com

Radial Artery Applanation Tonometry for Continuous Noninvasive Cardiac Output Measurement: A Comparison With Intermittent Pulmonary Artery Thermodilution in Patients After Cardiothoracic Surgery.

Objectives:Radial artery applanation tonometry allows completely noninvasive continuous cardiac output estimation. The aim of the present study was to compare cardiac output measurements obtained with applanation tonometry (AT-CO) using the T-Line system (Tensys Medical, San Diego, CA) with cardiac output measured by intermittent pulmonary artery thermodilution using a pulmonary artery catheter (PAC-CO) with regard to accuracy, precision of agreement, and trending ability. Design:A prospective method comparison study. Setting:The study was conducted in a cardiosurgical ICU of a German university hospital. Patients:We performed cardiac output measurements in 50 patients after cardiothoracic surgery. Interventions:None. Measurements and Main Results:Three independent sets of three consecutive thermodilution measurements (i.e., PAC-CO) each were performed per patient, and AT-CO was measured simultaneously. The average of the three thermodilution cardiac output measurements was compared with the average of the corresponding three AT-CO values resulting in 150 paired cardiac output measurements. In 13 patients, cardiac output–modifying maneuvers performed for clinical reasons additionally allowed to evaluate trending ability. For statistical analysis, we used Bland-Altman analysis, the percentage error, four-quadrant plot, and concordance analysis. Mean PAC-CO was 4.7 ± 1.2 L/min and mean AT-CO was 4.9 ± 1.1 L/min. The mean of differences was –0.2 L/min with 95% limits of agreement of –1.8 to + 1.4 L/min. The percentage error was 34%. The concordance rate was 95%. Conclusions:Continuous cardiac output measurement using the noninvasive applanation tonometry technology is basically feasible in ICU patients after cardiothoracic surgery. The applanation tonometry technology provides cardiac output values with reasonable accuracy and precision of agreement compared with intermittent pulmonary artery thermodilution measurements in a clinical study setting and is able to reliably track cardiac output changes induced by cardiac output–modifying maneuvers.

Personalized hemodynamic management

Purpose of review To describe personalized hemodynamic management of critically ill patients in the operating room and the ICU. Recent findings Several recent clinical studies have investigated different strategies for optimizing blood pressure (BP) and flow in the operating room and in the ICU. In the past, (early) goal-directed hemodynamic treatment strategies often used predefined fixed population-based ‘normal’ values as hemodynamic targets. Most hemodynamic variables, however, have large interindividual variability and are dependent on several biometric factors. Personalized BP management aims to set specific BP targets for a given patient taking into account blood flow autoregulation and any history of chronic hypertension. To optimize cardiac output and oxygen delivery, individualized hemodynamic management based on functional assessment of fluid responsiveness is used. Innovative noninvasive technologies now enable preoperative assessment of a patients personal normal hemodynamic values, which can then be targeted in the perioperative phase. In critically ill patients admitted to the ICU, adaptive multiparametric hemodynamic monitoring can help to personalize hemodynamic management. Summary Personalized hemodynamic management targets personal normal values of hemodynamic variables, which are adjusted to biometric data and adapted to the clinical situation (i.e., adequate values). This approach optimizes cardiovascular dynamics based on the patients personal hemodynamic profile.

Advanced Hemodynamic Management in Patients with Septic Shock.

In patients with sepsis and septic shock, the hemodynamic management in both early and later phases of these “organ dysfunction syndromes” is a key therapeutic component. It needs, however, to be differentiated between “early goal-directed therapy” (EGDT) as proposed for the first 6 hours of emergency department treatment by Rivers et al. in 2001 and “hemodynamic management” using advanced hemodynamic monitoring in the intensive care unit (ICU). Recent large trials demonstrated that nowadays protocolized EGDT does not seem to be superior to “usual care” in terms of a reduction in mortality in emergency department patients with early identified septic shock who promptly receive antibiotic therapy and fluid resuscitation. “Hemodynamic management” comprises (a) making the diagnosis of septic shock as one differential diagnosis of circulatory shock, (b) assessing the hemodynamic status including the identification of therapeutic conflicts, and (c) guiding therapeutic interventions. We propose two algorithms for hemodynamic management using transpulmonary thermodilution-derived variables aiming to optimize the cardiocirculatory and pulmonary status in adult ICU patients with septic shock. The complexity and heterogeneity of patients with septic shock implies that individualized approaches for hemodynamic management are mandatory. Defining individual hemodynamic target values for patients with septic shock in different phases of the disease must be the focus of future studies.

Cardiac output monitoring : less invasiveness, less accuracy?

Measuring and optimizing cardiac output (CO) as one major determinant of oxygen delivery is a mainstay in the treatment of hemodynamically unstable patients in intensive care and perioperative medicine. Advanced hemodynamic monitoring using technologies allowing the assessment of stroke volume and thus CO is therefore highly recommended in these patients [1–3]. Although intermittent pulmonary artery thermodilution using a pulmonary artery catheter is still supposed to be the clinical gold standard for the assessment of CO [4], lessinvasive and even non-invasive technologies have been developed in growing numbers in recent years and proposed for CO monitoring—including single-indicator transpulmonary thermodilution and calibrated or uncalibrated pulse contour analysis [3, 5]. While lessand non-invasive hemodynamic monitoring is certainly a striking concept in terms of patient safety and clinical applicability, the ‘‘measurement performance’’ of those monitoring technologies with regard to accuracy and precision of CO measurements in comparison with intermittent pulmonary artery thermodilution has repeatedly been questioned. Therefore, the question arises whether ‘‘less invasiveness’’ necessarily means ‘‘less accuracy’’. Cho et al. [6] need to be commended for aiming to answer this clinically relevant question by performing a very elegant study published in this issue of the journal. In their method comparison study, they compared agreement and trending ability between different methods for CO assessment with different degrees of invasiveness in patients undergoing off-pump coronary artery bypass surgery. As the reference method they used intermittent pulmonary artery thermodilution and evaluated the measurement performance of different test methods, namely continuous pulmonary artery thermodilution, transpulmonary thermodilution, pulse contour analysis calibrated to transpulmonary thermodilution, and uncalibrated pulse contour analysis. Interestingly, the percentage error of CO measurements using continuous versus intermittent pulmonary artery thermodilution was 27 %. The percentage errors observed for transpulmonary thermodilution, pulse contour analysis calibrated to transpulmonary thermodilution, and uncalibrated pulse contour analysis were 13, 29, and 34 %, respectively. Only transpulmonary thermodilution showed a good ability to follow CO changes as determined by intermittent pulmonary artery thermodilution. We don’t want to discuss statistical problems related to the percentage error [7, 8], the trending analysis [9, 10], and the definition of ‘‘acceptable agreement’’ in CO method comparison studies in this editorial. Yet the findings of Cho and colleagues warrant some further discussion regarding the selection of monitoring technologies for our patients. Of note, the authors’ findings show better agreement between pulse contour analysisderived CO and CO assessed with pulmonary artery thermodilution than most previous studies [11–13]. But yet, the study demonstrates that ‘‘invasive’’ transpulmonary thermodilution shows better agreement with pulmonary artery thermodilution compared with calibrated pulse contour analysis (that in turn showed better agreement than & Bernd Saugel bernd.saugel@gmx.de

Innovative noninvasive hemodynamic monitoring: curb your enthusiasm after initial validation studies and evaluate the technologies' clinical applicability.

The continuous monitoring of cardiovascular function seems reasonable in hemodynamically unstable patients. This holds true for a variety of clinical settings in both critically ill patients treated in the intensive care unit and patients undergoing major surgery under general anesthesia. Therefore, advanced hemodynamic monitoring—including the assessment of stroke volume and thus cardiac output—in addition to arterial pressure might be indicated in these settings [1, 2]. Numerous studies on new technologies published during the recent years support the notion that there is a fundamental interest in lessand noninvasive hemodynamic monitoring allowing for the continuous monitoring of arterial pressure [3] or cardiac output [4]. From the flood of data on the measurement performance of innovative lessand noninvasive hemodynamic monitoring technologies several critical problems arise: First, as discussed in detail previously [4–6], there are numerous unresolved problems regarding the design and interpretation of validation studies, including the interpretation of statistical methods [7, 8] and the definition of poor, acceptable, and good agreement with established reference methods (such as pulmonary artery or transpulmonary thermodilution). However, even if we pretend that we theoretically know how to define ‘‘clinical acceptable agreement’’ in validation studies, a second major problem arises, namely: Can the results from positive validation studies be indiscriminately transferred to our daily clinical practice? Therefore, the next step following initial validation studies should be to perform evaluation studies aiming to precisely define in which clinical situations measurements with a certain technology are reliable or not. Although these considerations hold true for all noninvasive hemodynamic monitoring technologies—because each and every one of these has specific limitations restricting their clinical applicability [4]—we might exemplarily discuss the bioreactance method. In short, with this technology one can calculate stroke volume and cardiac output from the voltage phase shift induced by changes in intrathoracic blood volume over the cardiac cycle that is assessed with skin surface electrodes [4]. Although a validation study in 110 post cardiac surgery patients showed promising results [9], subsequent studies revealed contradicting results on the accuracy and precision of the bioreactance technique [4]. In this issue, Zhang et al. [10] report the results of an elegant study in which they examined the effect of head-up tilt positioning on cardiac output measurements obtained with the bioreactance technique (and with external doppler) in young healthy volunteers. According to their results, the bioreactance method did not reliably track changes in stroke volume and cardiac output induced by head up tilting. This is of high clinical relevance because—as the authors explain—one can conclude that bioreactance measurements during a ‘‘passive leg raising test’’ might in turn also not be reliable. Because the continuous assessment of hemodynamic variables during such tests is of utmost importance, this is a major limitation of a continuous noninvasive cardiac output monitoring technique. The study by Zhang et al. therefore contributes to the understanding of basic limitations of this technology. When using bioreactance, a variety of clinical factors can disturb cardiac output measurements & Bernd Saugel bernd.saugel@gmx.de