Study design and settings
Ten patients, who fulfill inclusion and exclusion criteria, were enrolled in this observational study at the University Hospital Tor Vergata in Rome, Italy. The study was approved by the local Ethics Committee of University Hospital Tor Vergata, and the patients gave their written informed consent to participate.
Data collection and protocol
Inclusion criteria were age above 18 years and prescription of OLT or hepatectomy. The exclusion criteria were persistent arrhythmias, arteriosclerosis, and tidal volume less than 8 ml/kg of ideal weight . OLTs were all performed by using piggyback technique, i.e., a venous anastomosis and not a venous-venous bypass.
Sedation was induced using propofol and/or sufentanil (2 mg/kg) and maintained by total intravenous anesthesia (TIVA, 6 to 8 mg/kg/h). Rapid infusions only were analyzed, and they consisted boluses of 100 or 500 ml administered within 30 s or 1 min, respectively. The administered fluid consists mainly of blood recovered by the patient with addition of crystalloid and colloids; such solution is named ‘reservoir’. The fluid was infused by a peristaltic pump (Belmont FMS 2000™, Boston Road Billerica, MA, USA). Each patient was instrumented with an arterial catheter inserted in the brachial artery and placed in the aortic arch, with a central venous catheter inserted in a jugular vein and with an ECG lead. All the patients were monitored by Pulsion PiCCO and GE S/5 Avance Carestation devices.
Measurements and preprocessing
The following signals were continuously recorded during the entire surgery: arterial blood pressure (ABP), air flow (AF), air pressure (AP), central venous pressure (CVP), pulse contour cardiac output (PCCO), and SV. ABP and CVP were recorded at a sample frequency of 100 Hz, AF and AP at 25 Hz, and ECG at 300 Hz. Cardiac output (CO) and all indices provided by Pulsion PiCCO were provided with a sampling frequency of 2.5 Hz.
For each maneuver, the time windows were selected beginning 20 s before the start of infusion and including the following 3 min. Preprocessing of raw recordings of ABP, ECG, CVP, and respiration (AF and AP) was performed in order to extract beat-by-beat series, employing standard and robust algorithms. In particular, R peaks indicative of each cardiac cycle were extracted through ECG processing, hence constructing RR interval series (RRI); beat-by-beat series of systolic blood pressure (SBP), diastolic blood pressure (DBP), mean arterial pressure (MAP), and pulse pressure (PP), computed as the difference between SBP of the current cardiac cycle and DBP of the previous cycle, were extracted from the arterial pressure waveform ; beat-by-beat CVP was calculated as the mean value of continuously recorded CVP over each cardiac cycle, defined as the interval between two consecutive R peaks. The respiratory cycles were identified from the AF signal by applying a threshold to a series obtained from the cross-correlation between the AF signal and a stepwise weight function. The tidal volume Vt was estimated as the area of AF signal between the beginning and the end of a respiratory cycle.
Cardiac output estimators
Two algorithms were implemented to extract beat-to-beat values of CO and SV from the continuous ABP signal: the Liljestrand and Zander method (COLM, SVLM) and the systolic area method (COSA, SVSA). For mathematical details, see .
As the CO and SV estimated on a beat-to-beat basis reflect the respiratory oscillations, a moving average filter was applied and no calibration was performed. In fact, the responsiveness of a maneuver is estimated as a percentage variation of CO, and it was assessed as
where COref is the average of CO values measured during the last 20 s before the start of infusion. CO variation was assessed by using the values obtained from the implemented algorithms and the values provided by PiCCO. The PiCCO is a commercial monitor that can provide both a quantitative measure of CO by means of thermodilution and a continuous estimation of CO. The monitor estimates CO from the peripheral ABP measurement by applying the pulse contour analysis, i.e., a sort of weighted systolic area. Notice that CO variation is equal to cardiac index (CI) variation as the normalizing term of body surface area is canceled.
Fluid responsiveness indices
PPV and SVV were estimated according to the definitions (2) and (3):
where PPmax and PPmin refer to the maximum and minimum values, respectively, obtained in a single respiratory cycle, previously identified by AF signal;
where SVmax and SVmin refer to the maximum and minimum values, respectively, obtained in a single respiratory cycle. The same indices provided by PiCCO monitor were recorded as well (PPVPiCCO and SVVPiCCO), for comparison purposes. Notice that the PiCCO monitor computed these indices without the information on respiratory cycle, but by considering moving windows of 30 s.
SPV was computed too as the difference between the maximum and minimum values of SBP obtained in a single respiratory cycle. The average values of these fluid responsiveness indices were computed in the time interval of 60 s before the fluid administration started.
Criteria for classification of the maneuver
Several approaches were adopted in order to classify the maneuvers into responsive and nonresponsive. Each maneuver was considered individually as the hemodynamic characteristics of a patient can be different at different stages of the surgical procedure and after short time intervals. The maneuvers were classified as responsive by using the values provided by the commercial monitor commonly adopted in the OR (COPCCO) and according to different criteria, i.e., the time of response and the statistics for CO variation values. In particular,
the CO variation, i.e., Δ COPCCO, was assessed in two different time windows: after 1 min of fluid infusion and during the following 2 min;
in each time window, the maximum value and the 75° percentile of Δ COPCCO were estimated. The last case was considered to limit the effects of artifacts or short transitory increase in CO, but not effective.
In all cases, a maneuver was classified as responsive if the CO variation estimated according to that approach was higher than 10%.
The CO variations (Δ CO) obtained from different estimators and on different time intervals or statistics were compared, and a Pearson correlation analysis was performed. The fluid responsiveness indices estimated were compared with the FR indices provided by the commercial monitor PiCCO by the Bland-Altman analysis. After the subdivision of the maneuvers into two groups, i.e., responsive and not responsive, receiver operating characteristic (ROC) curves were estimated to obtain threshold values for each index. The index values were compared between the groups by means of Wilcoxon-Mann–Whitney test.