TELUS in Cardiac Surgery Patients. Effect of CPB and Relation to Postoperative Events (PORE)Events.
TELUS in Cardiac Surgery Patients. Effect of CPB and Relation to Postoperative Events (PORE)Events.
Transesophageal Lung ultrasound (TELUS) was described for the first time in 2016. The
 clinical significance and benefits for the patient of the results of a TELUS examination has
 not been investigated to date.

 Since all cardiac surgery with CPB cases in adult patients are performed using a TEE probe to
 monitor cardiac function, a concomitant TELUS examination is possible in all cases.

 The study seeks to describe the incidence and severity of the modifications of the aeration
 of both lungs assessed by TELUS in the perioperative period of adult cardiac surgery and to
 establish the relation of the TELUS findings with the occurence of postoperative respiratory
 events (PORE).

 Eventually, the study will also provide results about the interobserver variation of the
 TELUS examination for which there no reference to date.
Trans Esophageal Lung Ultrasound (TELUS) score in Cardiac surgery (CS) patients.

 Effect of CPB and relationship between changes on TELUS score and postoperative respiratory
 events (PORE).

 International recommendations for LUS assessment are available as well as the LUS methodology
 and nomenclature are widely accepted (1). Additionally, transthoracic LUS demonstrated a
 predictive value for postoperative pulmonary complication in non-cardiac surgery (2).

 More recently, the Trans Esophageal Lung Ultrasound (TELUS) has been described (3).

 Adult cardiac surgery patients are at special risk of perioperative respiratory complications
 including pulmonary edema, Acute Respiratory Distress Syndrome (ARDS), prolonged ventilation
 and non-invasive ventilation (NIV), tracheotomy and pulmonary infection (4). These
 complications are responsible for a substantial part of the perioperative case fatality rate.
 Prevention of these complications by using low tidal volume and an open lung strategy has
 failed to significantly reduce the incidence of postoperative respiratory events (PORE) (5).

 A worsening of the TELUS imaging occurs after CPB when compared with pre CPB imaging has been
 observed. These observations are consistent with the increase of extra vascular lung water
 during CPB along with specific effects of CPB on lung vessels (6).

 Our primary hypothesis is that CPB induced changes in the TELUS imaging score. Our secondary
 hypothesis is that magnitude of modifications are related to post-operative respiratory
 events (PORE) and postoperative complications. The TELUS modifications could have a
 predictive value for post-operative PORE and thus may help to discriminate patients at risk
 for PORE.

 Objectives 1 - Primary objective :

 1 - 1 Describing the incidence and severity of the changes in TELUS imaging between the pre
 CPB and the post CPB assessment.

 1. - 2 Describing the relation of the post CPB TELUS findings and the occurrence of PORE
 during hospital stay. The primary end-point will be a composite of prolonged NIV (> 12
 hours) and / or return to Mechanical Ventilation (MV) after a first successful
 extubation and / or ICU readmission after a first successful ICU discharge. The
 secondary endpoints will be : total MV duration, total ICU LOS, total hospital LOS, need
 for tracheotomy, death from all cause.

 2. - Secondary objectives

 2 - 1 pre / post CPB TELUS imaging will be assessed by a second examiner allowing us to
 calculate for the first time the pre / post CPB inter-observer variability of TELUS imaging
 in adult cardiac surgery. Intra observer variability will be assessed as well.

 2 - 2 As a standard transthoracic LUS is performed in all CS patients at admission in the ICU
 post-operatively, the respective relation of the admission LUS and post-CPB TELUS scores with
 the first PaO2 / fraction of inspired oxygen (FiO2) (P/F) ratio obtained at admission in the
 ICU.

 Methods This is a single center, non-interventional, observational and prospective study.

 The study will be registered at Clinical trials.gov. The study will be conducted according to
 the STROBE guidelines.

 All patients will be informed orally during the mandatory pre-anesthesia interview usually
 performed the day before surgery. A written information document will be given preoperatively
 to each patient and filed. Patients will be included at the start of the pre-CPB TEE
 examination.

 1. - Anesthesia Briefly, Two standard anesthesia protocols are in use in the institution.
 Anesthesia will be maintained either with Total Intravenous Anesthesia (TIVA)
 (continuous infusion of propofol and remifentanil with titration to keep the Bispectral
 index (BIS) values between 50 and 60) or inhalation anesthesia (remifentanil infusion
 and continuous sevoflurane inhalation including during CPB). Full muscle relaxation will
 be obtained with standard doses of atracurium or cisatracurium. Lungs will be ventilated
 with a low tidal volume of 6 ml.kg-1 (IBW). Standard arterial and central venous
 catheterization will be inserted in all patients. Hemodynamic monitoring will be
 performed with a Flotrac sensor and EV1000 monitor (EDWARDS Life Science - Irvine -
 USA). A continuous airway pressure of 5 cmH2O will be maintained during CPB. After skin
 closure, patients will be transferred to the ICU and anesthesia infusions will be
 discontinued after 2 hours if extubation criteria are met : bleeding < 200 ml, normal
 ECG recording, normal gas exchange, hemodynamic stability with or without low dose
 vasopressive support (norepinephrine < 100 µg.kg-1.h-1 IV).

 2. - CPB CPB will be performed according to institutional standard of care and
 international guidelines (7) CPB flow will be performed using a centrifugal pump after
 caval and aortic canulation. In some cases femoral or bicaval canulation will be used.
 Full anticoagulation will be performed with unfractioned Heparin with POC monitoring
 (target Activated clotting Time (ACT) : 480 sec) according to guidelines. A minimum of
 2.5 l/min CPB flow will be maintained. Cardioplegia will be performed by antegrade
 and/or retrograde normothermic cardioplegia according to the type of surgery.
 Centrifugation of the residual volume of the CPB circuit at the end of the procedure
 will be performed and re-transfused to the patient.

 3. - TEE Comprehensive TEE will be performed in anesthetized patients before skin incision
 (preCPB) and after chest closure (post CPB) using a GE Vivid S7 ultrasound system (GE
 Healthcare, Chicago IL, USA). TEE examination will be performed according to our
 standard procedure, reporting and archiving. Pre and post CPB LV function indices (LVEF,
 E wave, A wave velocities, E' and S'Lat velocities, quantification of Mitral
 Regurgitation (MR) if present).

 4. - TELUS Using the same imaging system, TELUS will be performed pre and post CPB
 according to the method described by previous authors (3). Sagittal (90°) mid-esophageal
 view and rotation of the probe will allow right lung interrogation of the anterior (60°
 rotation), lateral (90° rotation) and posterior (120° rotation) zones and left lung
 interrogation of the anterior (300° rotation), lateral (270° rotation) and posterior
 (240° rotation) zones. For each zone a TELUS score will be defined according to standard
 definitions : TELUS 0 : presence of A lines, TELUS 1 : less than 3 B lines , TELUS 2 :
 more than 3 B lines or confluent B lines, TELUS 3 : sub pleural condensation.
 Additionally, immediate findings (Pleural effusion, Alveolar consolidation,
 Pneumothorax) will be recorded.

 Thus, the maximum LUS score per lung will be 9 and the maximum LUS score per patient
 will be 18.

 5. - LUS A transthoracic LUS examination will be performed immediately after arrival in the
 ICU (standard routine practice). For each lung the anterior, lateral and posterior zones
 will be interrogated. For each zone a LUS score will be defined according to standard
 definitions : LUS 0 : presence of A lines, LUS 1 : less than 3 B lines , LUS 2 : more
 than 3 B lines or confluent B lines, LUS 3 : sub pleural condensation. Additionally,
 immediate findings (Pleural effusion, Alveolar consolidation, Pneumothorax) will be
 recorded.

 Thus the maximum LUS score per lung will be 9 and the maximum LUS score per patient will
 be 18.

 6. - Biological data

 Arterial blood gas are routinely drawn as a standard practice :

 a - After anesthesia and before skin incision b -Immediately after obtaining the CPB
 full flow c - Every 20 - 25 min during CPB d -5 - 10 min after protamine injection. e -
 15 min after arrival in the ICU

 a,d, and e blood gases results will be recorded and P/F ratio will be calculated.

 Troponin will be measured (ROCHE Diagnostics, Basel, Switzerland) in all patients at H24
 as an institution standard practice.

 7. - Recorded data

 All data will be recorded in an anonymous database (EXCEL worksheet). The recorded data
 will be:

 -  Hospital file number, initials, Demographic and procedural data, comorbidities,
 medications, baseline hematocrit and creatinine level

 -  Pre CPB TELUS data and score, TEE data, P/F, MAP, SAP, DAP, Heart Rate, O2 arterial
 saturation

 -  post CPB TELUS data and score, TEE data, P/F, MAP, SAP, DAP, Heart Rate, O2
 arterial saturation, total IV fluid balance during CPB.

 -  LUS data and score, P/F after arrival in the ICU

 -  Post-operative respiratory events (PORE) : time to extubation (hours), total time
 on NIV (hours), return to mechanical ventilation (intubation), total time on
 ventilation (hours),Tracheotomy and duration (hours), length of stay (LOS) in ICU
 (hours), pneumothorax after removal of chest tubes, pleural effusion, pneumonia (≥
 2 criteria including fever> 38.5 ° C or T <36 ° C, leukocytosis> 109/ L , purulent
 tracheal secretions and the appearance or persistence of an infiltrate on the CXR),
 atelectasis, pulmonary embolism, NO inhalation and total duration (hours), ARDS
 (Berlin definition), sternal wound infection, in-hospital LOS (days)

 -  Other in-hospital complications : cardiac ischemia, congestive heart failure,
 ventricular dysrhythmia, new onset of atrial fibrillation (NOAF), Acute kidney
 failure (AKI), Renal replacement therapy (RRT) and total duration (hours), cerebral
 ischemia, sepsis from other origin than the lungs, blood transfusion (units count),
 ICU Readmission, death from all cause.

 8. - Statistical analysis As there is no previous study that have observed TELUS during CPB
 in CS, sample size calculation cannot be done because mean score and standard deviation
 are not known. All patients with complete TELUS and LUS examinations during a four month
 period will be included.

 Inter-observer variability will be assessed using the Bland Altman method (8), Lin test (9),
 and weighted kappa test (10).

 Qualitative variables will be expressed as an absolute value and percentage. Quantitative
 variables will be expressed as a mean and Standard deviation (SD) or median and interquartile
 range depending on the normality of the data distribution.

 Comprehensive descriptive statistics. Comparisons will be made between the pre and post CPB
 TELUS recordings for demographic, procedural and biological data.

 Two groups will be defined according to the value of the PostCPB TELUS Score. Group HITELUS
 with the patients with TELUS score of 12 or higher. Group LOTELUS with the patients with
 TELUS score under 12. The two groups will be compared for the incidence of the primary and
 secondary outcomes and for all comorbidities and procedural variables.

 Comparisons will be made between the post CPB TELUS and ICU LUS recordings for demographic,
 procedural and biological data.

 A composite score of PORE will be built. To determine TELUS / LUS variables associated with
 PORE occurrence, multivariate logistic regression will be performed.

 To determine the predictive performance of TELUS / LUS scores for RE occurrence ROC curves
 will be generated with calculation of Area Under the Curve (AUC) with confidence intervals,
 Se, Sp, positive and Negative predictive values (PPV and NPV), Youden index values.
Inclusion Criteria:

 * Adult cardiac surgery patients with a comprehensive TEE and TELUS examination pre CPB
 will be included.

 Exclusion Criteria:

 -  Previous lung surgery

 -  Previous thoracic radiation therapy for cancer (lung, breast, lymphoma or other)

 -  Mitral valve surgery using a mini thoracotomy and video assistance

 -  Use of an ultrafiltration device during CPB

 -  Mechanical ventilation initiated before arrival in the OR.