Christoph K. Hofer

Coagulation Monitoring : Current Techniques and Clinical Use of Viscoelastic Point-of-Care Coagulation Devices

Perioperative monitoring of blood coagulation is critical to better understand causes of hemorrhage, to guide hemostatic therapies, and to predict the risk of bleeding during the consecutive anesthetic or surgical procedures. Point-of-care (POC) coagulation monitoring devices assessing the viscoelastic properties of whole blood, i.e., thrombelastography, rotation thrombelastometry, and Sonoclot® analysis, may overcome several limitations of routine coagulation tests in the perioperative setting. The advantage of these techniques is that they have the potential to measure the clotting process, starting with fibrin formation and continue through to clot retraction and fibrinolysis at the bedside, with minimal delays. Furthermore, the coagulation status of patients is assessed in whole blood, allowing the plasmatic coagulation system to interact with platelets and red cells, and thereby providing useful additional information on platelet function. Viscoelastic POC coagulation devices are increasingly being used in clinical practice, especially in the management of patients undergoing cardiac and liver surgery. Furthermore, they provide useful information in a large variety of clinical scenarios, e.g., massive hemorrhage, assessment of hypo- and hypercoagulable states, guiding pro- and anticoagulant therapies, and in diagnosing of a surgical bleeding. A surgical etiology of bleeding has to be considered when viscoelastic test results are normal. In summary, viscoelastic POC coagulation devices may help identify the cause of bleeding and guide pro- and anticoagulant therapies. To ensure optimal accuracy and performance, standardized procedures for blood sampling and handling, strict quality controls and trained personnel are required.

Assessing the diagnostic accuracy of pulse pressure variations for the prediction of fluid responsiveness: a "gray zone" approach.

Background:Respiratory arterial pulse pressure variations (PPV) are the best predictors of fluid responsiveness in mechanically ventilated patients during general anesthesia. However, previous studies were performed in a small number of patients and determined a single cutoff point to make clinical discrimination. The authors sought to test the predictive value of PPV in a large, multicenter study and to express it using a gray zone approach. Methods:The authors studied 413 patients during general anesthesia and mechanical ventilation in four centers. PPV, central venous pressure, and cardiac output were recorded before and after volume expansion (VE). Response to VE was defined as more than 15% increase in cardiac output after VE. The following approaches were used to determine the gray zones: resampled and two-graph receiver operator characteristic curves. The impact of changes in the benefit-risk balance of VE on the gray zone was also evaluated. Results:The authors observed 209 responders (51%) and 204 nonresponders (49%) to VE. The area under receiver operating characteristic curve was 0.89 (95% CI: 0.86–0.92) for PPV, compared with 0.57 (95% CI: 0.54–0.59) for central venous pressure (P < 10−5). The gray zone approach identified a range of PPV values (between 9% and 13%) for which fluid responsiveness could not be predicted reliably. These PPV values were seen in 98 (24%) patients. Changes in the cost ratio of VE moderately affected the gray zone limits. Conclusion:Despite a strong predictive value, PPV may be inconclusive (between 9% and 13%) in approximately 25% of patients during general anesthesia.

Assessment of stroke volume variation for prediction of fluid responsiveness using the modified FloTrac™ and PiCCOplus™ system

IntroductionStroke volume variation (SVV) has repeatedly been shown to be a reliable predictor of fluid responsiveness. Various devices allow automated clinical assessment of SVV. The aim of the present study was to compare prediction of fluid responsiveness using SVV, as determined by the FloTrac™/Vigileo™ system and the PiCCOplus™ system.MethodsIn patients who had undergone elective cardiac surgery, SVVFloTrac was determined via radial FloTrac sensor, and SVVPiCCO and pulse pressure variation were assessed via a femoral PiCCO catheter. Stroke volume was assessed by transpulmonary thermodilution. All variables were recorded before and after a volume shift induced by a change in body positioning (from 30° head-up position to 30° head-down position). Pearson correlation, t-test, and Bland-Altman analysis were performed. Area under the curve was determined by plotting receiver operating characteristic curves for changes in stroke volume in excess of 25%. P < 0.05 was considered statistically significant.ResultsBody positioning resulted in a significant increase in stroke volume; SVVFloTrac and SVVPiCCO decreased significantly. Correlations of SVVFloTrac and SVVPiCCO with change in stroke volume were similar. There was no significant difference between the areas under the curve for SVVFloTrac and SVVPiCCO; the optimal threshold values given by the receiver operating characteristic curves were 9.6% for SVVFloTrac (sensitivity 91% and specificity 83%) and 12.1% for SVVPiCCO (sensitivity 87% and specificity 76%). There was a clinically acceptable agreement and strong correlation between SVVFloTrac and SVVPiCCO.ConclusionSVVs assessed using the FloTrac™/Vigileo™ and the PiCCOplus™ systems exhibited similar performances in terms of predicting fluid responsiveness. In comparison with SVVPiCCO, SVVFloTrac has a lower threshold value.

Cardiac output monitoring: an integrative perspective.

Cardiac output monitoring in the critically ill patient is standard practice in order to ensure tissue oxygenation [1] and has been traditionally accomplished using the pulmonary artery catheter (PAC). In recent years, however, the value of PAC has been questioned with some suggesting that its use might not only be unnecessary but also potentially harmful [1]. This notion, together with the availability of new less invasive cardiac output measuring devices, has markedly decreased the widespread use of the PAC [2]. Today, various devices are available to measure or estimate cardiac output using different methods. Some of these less invasive devices track stroke volume (SV) continuously and provide dynamic indices of fluid responsiveness, others allow assessment of volumetric preload variables, and some also provide continuous measurement of central venous saturation via the use of proprietary catheters that are attached to the same monitor. All these variables — together with cardiac output — may result in an improved hemodynamic assessment of the critically ill patient. However, it is important to appreciate that each device has its inherent limitations and that no cardiac output monitoring device can change patient outcome unless its use is coupled with an intervention that by itself has been associated with improved patient outcomes. Therefore, the concept of hemodynamic optimization is increasingly recognized as a cornerstone in the management of critically ill patients and has been shown to be associated with improved outcome in the perioperative [3] and in the intensive care unit (ICU) [4] setting.

Adrenergic receptor genotype but not perioperative bisoprolol therapy may determine cardiovascular outcome in at-risk patients undergoing surgery with spinal block: the Swiss Beta Blocker in Spinal Anesthesia (BBSA) study: a double-blinded, placebo-controlled, multicenter trial with 1-year follow-up

Background:Neuraxial blockade is used as primary anesthetic technique in one third of surgical procedures. The authors tested whether bisoprolol would protect patients at risk for cardiovascular complications undergoing surgery with spinal block. Methods:The authors performed a double-blinded, placebo-controlled, multicenter trial to compare the effect of bisoprolol with that of placebo on 1-yr composite outcome including cardiovascular mortality, nonfatal myocardial infarction, unstable angina, congestive heart failure, and cerebrovascular insult. Bisoprolol was given orally before and after surgery for a maximum of 10 days. Adrenergic receptor polymorphisms and safety outcome measures of bisoprolol therapy were also determined. Results:A total of 224 patients were enrolled. Spinal block could not be established in 5 patients. One hundred ten patients were assigned to the bisoprolol group, and 109 patients were assigned to the placebo group. The mean duration of treatment was 4.9 days in the bisoprolol group and 5.1 days in the placebo group. Bisoprolol therapy reduced mean heart rate by 10 beats/min. The primary outcome was identical between treatment groups and occurred in 25 patients (22.7%) in the bisoprolol group and 24 patients (22.0%) in the placebo group during the 1-yr follow-up (hazard ratio, 0.97; 95% confidence interval, 0.55–1.69; P = 0.90). However, carriers of at least one Gly allele of the β1-adrenergic receptor polymorphism Arg389Gly showed a higher number of adverse events than Arg homozygous (32.4% vs. 18.7%; hazard ratio, 1.87; 95% confidence interval, 1.04–3.35; P = 0.04). Conclusions:Perioperative bisoprolol therapy did not affect cardiovascular outcome in these elderly at-risk patients undergoing surgery with spinal block.

Can Changes in Arterial Pressure be Used to Detect Changes in Cardiac Output during Volume Expansion in the Perioperative Period

Background:Cardiac output (CO) is rarely monitored during surgery, and arterial pressure remains the only hemodynamic parameter for assessing the effects of volume expansion (VE). However, whether VE-induced changes in arterial pressure accurately reflect changes in CO has not been demonstrated. The authors studied the ability of VE-induced changes in arterial pressure and in pulse pressure variation to detect changes in CO induced by VE in the perioperative period. Methods:The authors studied 402 patients in four centers. Hemodynamic variables were recorded before and after VE. Response to VE was defined as more than 15% increase in CO. The ability of VE-induced changes in arterial pressure to detect changes in CO was assessed using a gray zone approach. Results:VE increased CO of more than 15% in 205 patients (51%). Areas under the receiver operating characteristic curves for VE-induced changes in systolic, diastolic, means, and pulse pressure ranged between 0.64 and 0.70, and sensitivity and specificity ranged between 52 and 79%. For these four arterial pressure–derived parameters, large gray zones were found, and more than 60% of the patients lay within this inconclusive zone. A VE-induced decrease in pulse pressure variation of 3% or more allowed detecting a fluid-induced increase in CO of more than 15% with a sensitivity of 90% and a specificity of 77% and a gray zone between 2.2 and 4.7% decrease in pulse pressure variation including 14% of the patients. Conclusion:Only changes in pulse pressure variation accurately detect VE-induced changes in CO and have a potential clinical applicability.

Pulse pressure variation: where are we today?

In the present review we will describe and discuss the physiological and technological background necessary in understanding the dynamic parameters of fluid responsiveness and how they relate to recent softwares and algorithms’ applications. We will also discuss the potential clinical applications of these parameters in the management of patients under general anesthesia and mechanical ventilation along with the potential improvements in the computational algorithms.

Assessment of cardiac output changes using a modified FloTrac/Vigileo™ algorithm in cardiac surgery patients

IntroductionThe FloTrac/Vigileo™ (Edwards Lifesciences, Irvine, CA, USA) allows pulse pressure-derived cardiac output measurement without external calibration. Software modifications were performed in order to eliminate initially observed deficits. The aim of this study was to assess changes in cardiac output determined by the FloTrac/Vigileo™ system (FCO) with an initially released (FCOA) and a modified (FCOB) software version, as well as changes in cardiac output from the PiCCOplus™ system (PCO; Pulsion Medical Systems, Munich, Germany). Both devices were compared with cardiac output measured by intermittent thermodilution (ICO).MethodsCardiac output measurements were performed in patients after elective cardiac surgery. Two sets of data (A and B) were obtained using FCOA and FCOB in 50 patients. After calibration of the PiCCOplus™ system, triplicate FCO and PCO values were recorded and ICO was determined in the supine position and cardiac output changes due to body positioning were recorded 15 minutes later (30° head-up, 30° head-down, supine). Students t test, analysis of variance and Bland-Altman analysis were calculated.ResultsSignificant changes of FCO, PCO and ICO induced by body positioning were observed in both data sets. For set A, ΔFCOA was significantly larger than ΔICO induced by positioning the head down. For set B, there were no significant differences between ΔFCOB and ΔICO. For set A, increased limits of agreement were found for FCOA-ICO when compared with PCO-ICO. For set B, mean bias and limits of agreement were comparable for FCOB-ICO and PCO-ICO.ConclusionsThe modification of the FloTrac/Vigileo™ system resulted in an improved performance in order to reliably assess cardiac output and track the related changes in patients after cardiac surgery.

What technique should I use to measure cardiac output

Purpose of reviewSeveral less invasive cardiac output monitoring techniques are now commercially available and have the potential to replace the pulmonary artery catheter under certain clinical circumstances. The aim of this review is to give a synopsis of the currently available cardiac output measurement methods. This information should help in selecting the appropriate technique in a particular clinical setting. Recent findingsAn overview is given of the currently available techniques for cardiac output monitoring. Recent validation studies demonstrate that pulse wave analysis may be used reliably as an alternative to the pulmonary artery catheter in different clinical settings. The use of transesophageal echocardiography and Doppler measurements is limited due to high operator dependency, the partial carbon dioxide rebreathing technique should be applied in a precisely defined clinical setting to mechanically ventilated patients only, and pulsed dye densitometry as well as the bioimpedance technique are currently primarily applied in an investigational setting. SummaryLess invasive cardiac output monitoring techniques may replace the pulmonary artery catheter in different clinical settings considering the specific properties of these techniques. The pulmonary artery catheter, however, may still be recommended for cardiac output measurement in specific clinical situations when monitoring of pulmonary artery pressures is desirable.

Clinical validation of a new thermodilution system for the assessment of cardiac output and volumetric parameters

IntroductionTranspulmonary thermodilution is used to measure cardiac output (CO), global end-diastolic volume (GEDV) and extravascular lung water (EVLW). A system has been introduced (VolumeView/EV1000™ system, Edwards Lifesciences, Irvine CA, USA) that employs a novel algorithm for the mathematical analysis of the thermodilution curve. Our aim was to evaluate the agreement of this method with the established PiCCO™ method (Pulsion Medical Systems SE, Munich, Germany, clinicaltrials.gov identifier: NCT01405040)MethodsSeventy-two critically ill patients with clinical indication for advanced hemodynamic monitoring were included in this prospective, multicenter, observational study. During a 72-hour observation period, 443 sets of thermodilution measurements were performed with the new system. These measurements were electronically recorded, converted into an analog resistance signal and then re-analyzed by a PiCCO2™ device (Pulsion Medical Systems SE).ResultsFor CO, GEDV, and EVLW, the systems showed a high correlation (r2 = 0.981, 0.926 and 0.971, respectively), minimal bias (0.2 L/minute, 29.4 ml and 36.8 ml), and a low percentage error (9.7%, 11.5% and 12.2%). Changes in CO, GEDV and EVLW were tracked with a high concordance between the two systems, with a traditional concordance for CO, GEDV, and EVLW of 98.5%, 95.1%, and 97.7% and a polar plot concordance of 100%, 99.8% and 99.8% for CO, GEDV, and EVLW, respectively. Radial limits of agreement for CO, GEDV and EVLW were 0.31 ml/minute, 81 ml and 40 ml, respectively. The precision of GEDV measurements was significantly better using the VolumeView™ algorithm compared to the PiCCO™ algorithm (0.033 (0.03) versus 0.040 (0.03; median (interquartile range), P = 0.000049).ConclusionsFor CO, GEDV, and EVLW, the agreement of both the individual measurements as well as measurements of change showed the interchangeability of the two methods. For the VolumeView method, the higher precision may indicate a more robust GEDV algorithm.Trial registrationclinicaltrials.gov NCT01405040.