Stéphanie Roullet

Management of bleeding and transfusion during liver transplantation before and after the introduction of a rotational thromboelastometry-based algorithm.

Orthotopic liver transplantation (OLT) remains a potentially hemorrhagic procedure. Rotational thromboelastometry (ROTEM) is a point‐of‐care device used to monitor coagulation during OLT. Whether it allows blood loss and transfusions to be reduced during OLT remains controversial. Excellent correlations and predictive values have been found between ROTEM parameters and fibrinogen. We hypothesized that the use of a ROTEM‐based transfusion algorithm during OLT would lead to more fibrinogen transfusion and decreased bleeding and blood transfusion. Sixty adult patients were consecutively included in a prospective, without‐versus‐with study: 30 in the group without ROTEM results and 30 in the group with the ROTEM‐based algorithm. A small and nonsignificant increase in median fibrinogen transfusions was found for the with group (6.0 g versus 4.5 g, P = 0.50). It was not associated with a decrease in blood transfusions or in the number of patients exposed to blood products. Liver Transpl 21:169‐179, 2015.

The ability of pulse pressure variations obtained with CNAP™ device to predict fluid responsiveness in the operating room.

BACKGROUND: Respiratory-induced pulse pressure variations obtained with an arterial line (&Dgr;PPART) indicate fluid responsiveness in mechanically ventilated patients. The Infinity® CNAP™ SmartPod® (Dräger Medical AG & Co. KG, Lübeck, Germany) provides noninvasive continuous beat-to-beat arterial blood pressure measurements and a near real-time pressure waveform. We hypothesized that respiratory-induced pulse pressure variations obtained with the CNAP system (&Dgr;PPCNAP) predict fluid responsiveness as well as &Dgr;PPART predicts fluid responsiveness in mechanically ventilated patients during general anesthesia. METHODS: Thirty-five patients undergoing vascular surgery were studied after induction of general anesthesia. Stroke volume (SV) measured with the Vigileo™/FloTrac™ (Edwards Lifesciences, Irvine, CA), &Dgr;PPART, and &Dgr;PPCNAP were recorded before and after intravascular volume expansion (VE) (500 mL of 6% hydroxyethyl starch 130/0.4). Subjects were defined as responders if SV increased by ≥15% after VE. RESULTS: Twenty patients responded to VE and 15 did not. The correlation coefficient between &Dgr;PPART and &Dgr;PPCNAP before VE was r = 0.90 (95% confidence interval [CI] = 0.84–0.96; P < 0.0001). Before VE, &Dgr;PPART and &Dgr;PPCNAP were significantly higher in responders than in nonresponders (P < 0.0001). The values of &Dgr;PPART and &Dgr;PPCNAP before VE were significantly correlated with the percent increase in SV induced by VE (respectively, r2 = 0.50; P < 0.0001 and r2 = 0.57; P < 0.0001). Before VE, a &Dgr;PPART >10% discriminated between responders and nonresponders with a sensitivity of 90% (95% CI = 69%–99%) and a specificity of 87% (95% CI = 60%–98%). The area under the receiver operating characteristic (ROC) curve was 0.957 ± 0.035 for &Dgr;PPART. Before VE, a &Dgr;PPCNAP >11% discriminated between responders and nonresponders with a sensitivity of 85% (95% CI = 62%–97%) and a specificity of 100% (95% CI = 78%–100%). The area under the ROC curve was 0.942 ± 0.040 for &Dgr;PPCNAP. There was no significant difference between the area under the ROC curve for &Dgr;PPART and &Dgr;PPCNAP. CONCLUSIONS: A value of &Dgr;PPCNAP >11% has a sensitivity of at least 62% in predicting preload-dependent responders to VE in mechanically ventilated patients during general anesthesia.

Continuous non-invasive arterial pressure measurement: Evaluation of CNAP™ device during vascular surgery

OBJECTIVE Standard non-invasive blood pressure (BP) monitoring is an intermittent, discontinuous procedure. Beat-to-beat BP monitoring requires invasive measurement via an arterial catheter and may be associated with serious complications. The Infinity CNAP SmartPod (Dräger Medical AG & Co. KG, Lübeck, Germany) has recently been proposed for non-invasive continuous beat-to-beat BP measurements. The present study was designed to compare BP obtained with the CNAP and with an invasive method in the operating room. STUDY DESIGN Prospective study. PATIENTS AND METHODS Twenty-five patients undergoing major vascular surgery were included. Systolic, mean and diastolic BP were monitored invasively (SAP, MAP and DAP respectively) and not invasively using the CNAP (CNAP-S, CNAP-M and CNAP-D respectively). Measurements were performed intraoperatively every minute during 1 hour. RESULTS One thousand and five hundred pairs of simultaneous CNAP and invasive BP measurements were obtained and 148 were eliminated. The range of BP measurements was 63-205 mmHg for SAP and 57-187 mmHg for CNAP-S, 38-143 mmHg for MAP and 43-142 mmHg for CNAP-M, 29-126 mmHg for DAP and 33-121 mmHg for CNAP-D. Bias and 95% limit of agreement between CNAP and invasive BP measurements were respectively 7.2 and -17.7 to 32.2 mmHg for SAP, -1.8 and -22.0 to 18.3 mmHg for MAP, and -7.5 and -27.3 to 12.4 mmHg for DAP. The percentage of CNAP measurements with a bias <10% with the arterial line was 69%, 86% and 91% for systolic, diastolic and mean pressures, respectively. CONCLUSION Despite low accuracy for SAP and DAP measurements, CNAP system seems more accurate for MAP measurement in patients undergoing vascular surgery.

Evaluation of stroke volume variations obtained with the pressure recording analytic method.

Objective:To investigate whether stroke volume variations obtained with the pressure recording analytic method can predict fluid responsiveness in mechanically ventilated patients with circulatory failure. Design:Prospective study. Setting:Surgical intensive care unit of a university hospital. Patients:Thirty-five mechanically ventilated patients with circulatory failure for whom the decision to give fluid was taken by the physician were included. Exclusion criteria were: Arrhythmia, tidal volume <8 mL/kg, left ventricular ejection fraction<50%, right ventricular dysfunction, and heart rate/respiratory rate ratio <3.6. Interventions:Fluid challenge with 500 mL of saline over 15 mins. Measurements and Main Results:Stroke volume variations and cardiac output obtained with a pressure recording analytic method, pulse pressure variations, and cardiac output estimated by echocardiography were recorded before and after volume expansion. Patients were defined as responders if stroke volume obtained using echocardiography increased by ≥15% after volume expansion. Nineteen patients responded to the fluid challenge. Median [interquartile range, 25% to 75%] stroke volume variation values at baseline were not different in responders and nonresponders (10% [8–16] vs. 14% [12–16]), whereas pulse pressure variations were significantly higher in responders (17% [13–19] vs. 7% [5–10]; p < .0001). A 12.6% stroke volume variations threshold discriminated between responders and nonresponders with a sensitivity of 63% (95% confidence interval 38% to 84%) and a specificity of 69% (95% confidence interval 41% to 89%). A 10% pulse pressure variation threshold discriminated between responders and nonresponders with a sensitivity of 89% (95% confidence interval 67% to 99%) and a specificity of 88% (95% confidence interval 62% to 98%). The area under the receiver operating characteristic curves was different between pulse pressure variations (0.95; 95% confidence interval 0.82–0.99) and stroke volume variations (0.60; 95% confidence interval 0.43–0.76); p < .0001). Volume expansion-induced changes in cardiac output measured using echocardiography or pressure recording analytic method were not correlated (r2 = 0.14; p > .05) and the concordance rate of the direction of change in cardiac output was 60%. Conclusion:Stroke volume variations obtained with a pressure recording analytic method cannot predict fluid responsiveness in intensive care unit patients under mechanical ventilation. Cardiac output measured by this device is not able to track changes in cardiac output induced by volume expansion. (Crit Care Med 2012; 40:–1191)

Uncalibrated Stroke Volume Variations Are Able to Predict the Hemodynamic Effects of Positive End-Expiratory Pressure in Patients with Acute Lung Injury or Acute Respiratory Distress Syndrome after Liver Transplantation

Background:Positive end-expiratory pressure (PEEP) may reduce cardiac output and total hepatic blood flow after liver transplantation. Pulse pressure variation is useful in predicting the PEEP-induced decrease in cardiac output. The aim of the study was to examine the relationships between stroke volume variations (SVV) obtained with the Vigileo monitor (Edwards Lifesciences, Irvine, CA), and the hemodynamic effects of PEEP. Methods:Over 2 yr, patients presenting an acute lung injury or an acute respiratory distress syndrome in the 72 h after liver transplantation were prospectively enrolled. Patients were monitored with a pulmonary artery catheter (stroke volume) and with the Vigileo system (stroke volume and SVV). Measurements were performed in duplicate, first during zero end-expiratory pressure and then 10 min after the addition of 10 cm H2O PEEP. Results:Twenty-six patients were included. Six patients were excluded from analysis. On PEEP, SVV and pulse pressure variation increased significantly and stroke volume decreased significantly. PEEP-induced changes in stroke volume measured by pulmonary artery catheter were significantly correlated with SVV (r2 = 0.69; P < 0.001) and pulse pressure variation on zero end-expiratory pressure (r2 = 0.66, P < 0.001). PEEP-induced decrease in stroke volume measured by pulmonary artery catheter ≥ 15% was predicted by an SVV > 7% (sensitivity = 100%, specificity = 80%) and by a pulse pressure variation > 8% (sensitivity = 80%, specificity = 100%). PEEP-induced changes in stroke volume measured by pulmonary artery catheter and Vigileo device were correlated (r2 = 0.51, P < 0.005). Conclusions:SVV obtained with Vigileo monitor is useful to predict decrease in stroke volume induced by PEEP. Moreover, this device is able to track changes in stroke volume induced by PEEP.

Risk factors for bleeding and transfusion during orthotopic liver transplantation

OBJECTIVE While orthotopic liver transplantation (OLT) can be associated with haemorrhage, the risk factors for bleeding and transfusion remain difficult to predict. Perioperative transfusion has potentially deleterious side effects and impairs graft and patient survival. Preoperative identification of patients at high risk of bleeding is of clinical interest to manage perioperative transfusion and blood product storage. STUDY DESIGN Retrospective study. PATIENTS AND METHODS All OLT conducted between 2004 and 2008 in the University Hospital of Bordeaux were studied. Risk factors for bleeding greater than one blood volume and for massive red blood cell (RBC) transfusion were determined using univariate and multivariate analysis. Thresholds were determined with ROC curve analysis. RESULTS One hundred and forty-eight transplantations were studied. Preoperative haemoglobin and Child class A were independent protective risk factors for bleeding greater than one blood volume (OR 0.81 [0.67-0.98] and 0.27 [0.10-0.72], respectively). Preoperative Hb was a protective risk factor (OR 0.71 [0.58-0.88]) whereas history of oesophageal varicose bleeding was a risk factor (OR 4.67 [1.45-15.05]) for transfusion of more than eight RBC. CONCLUSION Risk factors for bleeding and transfusion during OLT identified in this study were of little clinical usefulness so blood products should always be available during the procedure.

Noninvasive assessment of macrovesicular liver steatosis in cadaveric donors based on computed tomography liver-to-spleen attenuation ratio

Fatty liver disease, including liver steatosis, is a major health problem worldwide. In liver transplantation, macrovesicular steatosis in donor livers is a major cause of graft failure and remains difficult to assess. On one hand, several imaging modalities can be used for the assessment of liver fat, but liver biopsy, which is still considered the gold standard, may be difficult to perform in this context. On the other hand, computed tomography (CT) is commonly used by teams managing cadaveric donors to assess donors and to minimize the risk of complications in recipients. The purpose of our study was to validate the use of CT as a semiquantitative method for assessing macrovesicular steatosis in cadaveric donors with liver biopsy as a reference standard. A total of 109 consecutive cadaveric donors were included between October 2009 and May 2011. Brain death was diagnosed according to French legislation. Liver biopsy and then CT were performed on the same day to determine the degree of macrovesicular steatosis. All liver biopsies and CT scans were analyzed in a double‐blinded fashion by a senior pathologist and a senior radiologist, respectively. For CT, we used the liver‐to‐spleen (L/S) attenuation ratio, which is a validated method for determining 30% or greater steatosis in living liver donors. Fourteen of 109 biopsies exhibited macrovesicular steatosis > 30% upon histologic analysis. A receiver operating characteristic curve was generated for the L/S ratio to identify its ability to predict significant steatosis, which was defined as >30%. A cutoff value of 0.9 for the CT L/S ratio provided a sensitivity of 79% and a specificity of 97% to detect significant steatosis. Liver Transpl 21:690‐695, 2015.

Lysis Timer: a new sensitive tool to diagnose hyperfibrinolysis in liver transplantation

Aims Diagnosis of hyperfibrinolysis in orthotopic liver transplantation (OLT) remains challenging. Euglobulin clot lysis time (ECLT) is not adapted to clinical situations. ROTEM is specific but seldom sensitive to hyperfibrinolysis. The Lysis Timer assesses ‘Global Fibrinolytic Capacity’ in citrated plasma (GFC/LT). GFC/LT associates reagents for in vitro triggering of the clot (thrombin and calcium) and its lysis (tissue-plasminogenactivator (t-PA)), turbidity signal acquisition by the Lysis Timer, and dedicated software converting the digital signal into an optical curve. A visual check of the curves was systematic to ascertain the lysis time values calculated by the software. The primary aim of this prospective observational study was to evaluate the ability of GFC/LT to recognise hyperfibrinolysis during OLT. The secondary aim was to compare its results with ROTEM maximum lysis (EXTEM ML) and with standard laboratory tests. Methods Thirty consecutive adult patients undergoing OLT were included (NCT03012633). Standard laboratory tests, ROTEM, GFC/LT, ECLT and fibrinolysis parameters were assayed at five sample times. Results GFC/LT was correlated with ECLT, plasmin activator inhibitor 1 antigen and activity and t-PA activity (r=0.490, 0.681, 0.643 and –0.359, respectively). Hyperfibrinolysis was defined as ECLT ≤60 min. Receiver operating characteristic curve analysis showed that GFC/LT with a threshold of 31 min detected hyperfibrinolysis with a sensitivity of 0.88 (95% CI 0.73 to 0.96), a specificity of 0.68 (95% CI 0.56 to 0.78) and an area under the curve (AUC) of 0.85 (95% CI 0.74 to 0.94). EXTEM ML >12% did not detect hyperfibrinolysis (sensitivity 0.38 (95% CI 0.24 to 0.55), specificity 0.95 (95% CI 0.86 to 0.99) and AUC 0.60 (95% CI 0.46 to 0.75)). Conclusions GFC/LT recognised hyperfibrinolysis during OLT with a significant agreement with the other tests of fibrinolysis. Trial registration number NCT03012633.

Management of antiplatelet therapy in patients undergoing elective invasive procedures: Proposals from the French Working Group on perioperative hemostasis (GIHP) and the French Study Group on thrombosis and hemostasis (GFHT). In collaboration with the French Society for Anesthesia and Intensive Care (SFAR).

The French Working Group on Perioperative Haemostasis (GIHP) and the French Study Group on Haemostasis and Thrombosis (GFHT) in collaboration with the French Society for Anaesthesia and Intensive Care Medicine (SFAR) drafted up-to-date proposals for the management of antiplatelet therapy in patients undergoing elective invasive procedures. The proposals were discussed and validated by a vote; all proposals but one could be assigned with a high strength. The management of antiplatelet therapy is based on their indication and the procedure. The risk of bleeding related to the procedure can be divided into high, moderate and low categories depending on the possibility of performing the procedure in patients receiving antiplatelet agents (none, monotherapy and dual antiplatelet therapy respectively). If discontinuation of antiplatelet therapy is indicated before the procedure, a last intake of aspirin, clopidogrel, ticagrelor and prasugrel 3, 5, 5 and 7 days before surgery respectively is proposed. The thrombotic risk associated with discontinuation should be assessed according to each specific indication of antiplatelet therapy and is higher for patients receiving dual therapy for coronary artery disease (with further refinements based on a few well-accepted items) than for those receiving monotherapy for cardiovascular prevention, for secondary stroke prevention or for lower extremity arterial disease. These proposals also address the issue of the potential role of platelet functional tests and consider management of antiplatelet therapy for regional anaesthesia, including central neuraxial anaesthesia and peripheral nerve blocks, and for coronary artery surgery.

Position of the French Working Group on Perioperative Haemostasis (GIHP) on viscoelastic tests: What role for which indication in bleeding situations?

PURPOSE Viscoelastic tests (VETs), thromboelastography (TEG®) and thromboelastometry (ROTEM®) are global tests of coagulation performed on whole blood. They evaluate the mechanical strength of a clot as it builds and develops after coagulation itself. The time required to obtain haemostasis results remains a major problem for clinicians dealing with bleeding, although some teams have developed a rapid laboratory response strategy. Indeed, the value of rapid point-of-care diagnostic devices such as VETs has increased over the years. However, VETs are not standardised and there are few recommendations from the learned societies regarding their use. In 2014, the recommendations of the International Society of Thrombosis and Haemostasis (ISTH) only concerned haemophilia. The French Working Group on Perioperative haemostasis (GIHP) therefore proposes to summarise knowledge on the clinical use of these techniques in the setting of emergency and perioperative medicine. METHODS A review of the literature. PRINCIPAL FINDINGS The role of the VETs seems established in the management of severe trauma and in cardiac surgery, both adult and paediatric. In other situations, their role remains to be defined: hepatic transplantation, postpartum haemorrhage, and non-cardiac surgery. They must be part of the global management of haemostasis based on algorithms defined in each centre and for each population of patients. Their position at the bedside or in the laboratory is a matter of discussion between clinicians and biologists. CONCLUSION VETs must be included in algorithms. In consultation with the biology laboratory, these devices should be situated according to the way each centre functions.