We did a post hoc analysis of the multicenter observational and prospective HemoPred study in which 540 ventilated patients admitted between 2012 and 2014 were included in five French ICUs (Amiens, Boulogne-Billancourt, Brest, Limoges, Tours and Suresnes) for circulatory failure. Transthoracic echocardiography (TTE) and transesophageal echocardiography (TEE) were systematically performed within the first 24 hours of ICU admission (11). The investigation conforms with the principles outlined in the Declaration of Helsinki. HemoPred was approved by the Ethics Committee of Limoges (no 85-2012-09). Among the 540 studied patients, 295 were admitted for septic shock, which was not characterized by the Sepsis-3 definition as the HemoPred study was designed before its publication. Diagnosis was based on a suspected infection responsible for sustained hypotension despite adequate fluid loading that required vasopressors, with associated clinical signs of tissue hypoperfusion (mottled skin, encephalopathy, oliguria for more than 2 hours) that were confirmed by laboratory values (pH < 7.38 and base deficit > 5 mmol/L or lactate > 2 mmol/L or central venous oxygen saturation < 70%). 152 patients met the lactate criteria as well as another hypoperfusion sign while 115 did not meet the lactate criteria and 6 only met the lactate criteria.
Clinical and laboratory data
The initial clinical data collected included socio-demographic data, biometric parameters, comorbidities, vital parameters (heart rate, systolic, diastolic and mean arterial blood pressure) and etiology of sepsis. The sequential organ failure assessment score (SOFA) and simplified acute physiology score SAPS2 were recorded.
CVP was obtained by measuring the pressure at the end of a central catheter located at the level of the intrathoracic superior vena cava (SVC) at its entry into the right atrium. Bladder pressure was used as a surrogate of intra-abdominal pressure (IAP) (available in 260/282 – 92.2% patients) and PPV was calculated from the data obtained from the radial or femoral arterial catheter. Arterial blood gas analysis was performed concomitantly with CCE and serum lactate level was reported. Acute respiratory distress syndrome (ARDS) was defined using the Berlin definition (12). Plateau pressure, driving pressure and positive end-expiratory pressure were recorded, and the compliance of the respiratory system was calculated.
As previously described [Vieillard-Baron A, AJRCCM 2003], CCE was performed with continuous ECG and mechanication ventilation monitoring. An end-expiratory beat was defined as the last beat occurring before mechanical lung inflation. Among all variables prospectively recorded in the HemoPred cohort, we especially analyzed tricuspid annular plane systolic excursion (TAPSE), RV size, systolic pulmonary artery pressure (SPAP), and cardiac index (CI). TAPSE was measured at end-expiration with the M-mode study in an apical 4-chamber view as recommended (9). RV size was also evaluated at end-expiration by the ratio of the RV/ LV end-diastolic area (EDA) in a transverse mid-esophageal view (13, 14). Left ventricular stroke volume (LVSV) was calculated by combining the averaged aortic velocity time integral (AoVTI) by pulsed wave Doppler in the whole respiratory cycle with 2-D measurement of the related diameter (15) and CI was calculated as LVSV times heart rate indexed to the body surface area. SPAP was calculated at end-expiration based on the maximal velocity (Vmax) of the tricuspid regurgitation when available, as follows: SPAP = 4xVmax2 + CVP (16).
Detection of fluid responsiveness
Passive leg raising (PLR), as technically validated (17), was performed to mimic fluid expansion. An increase of more than 10% in the AoVTI after 1-minute PLR compared with baseline defined a significant increase in LV stroke volume (17, 18).
The main outcome of the study was to evaluate the incidence of RV failure in septic shock patients.
The secondary outcomes included: 1) the relationship between RV failure and fluid responsiveness and 2) the performance of TAPSE in discriminating patients with and without RV failure.
Continuous variables were reported as medians and categorical data were expressed as numbers and percentages. Continuous variables were compared using a Mann-Whitney test or a Kruskal-Wallis test. Categorical data were compared using a Chi square test or an exact Fisher test when necessary.
Three groups of patients were compared according to RV size and CVP, a good surrogate of venous congestion. Cut-off values of 0.6 for RV/LV EDA (14) and of 8 mmHg for CVP (19, 20) were considered. Patients in group 1 were defined as no RV dilatation (RV/LV ratio < 0.6). Patients in group 2 were defined as exhibiting RV dilatation (RV/LV ratio ≥ 0.6) and CVP < 8 mmHg; we then assumed that these patients did not have RV failure as no congestion was observed. Finally, patients in group 3 were defined as exhibiting RV dilatation (RV/LV ratio ≥ 0.6) associated with elevated CVP (≥ 8 mmHg) and were suspected to have RV failure. Spearman’s correlation coefficients were calculated in the three groups.
Correlation between TAPSE and RV/LV end-diastolic area was evaluated using Spearman’s correlation test. Rho and p-values are provided. The paired Wilcoxon test was used to compare variations of CVP before and after PLR across the three groups. All the analyses were performed using R (R version 3.4.3 (2017-11-30) -- "Kite-Eating Tree" Copyright (C) 2017 The R Foundation for Statistical Computing). A p value < 0.05 was considered significant.