Study design
This retrospective study included consecutive patients who underwent neurological or cardiac surgery, with invasive hemodynamic monitoring consisting of measurements of CVP and CO, from February to March, 2021. The study protocol was approved by the Institutional Review Board of Chungnam National University Hospital (CNUH 2021–04-083) and registered at the Clinical Research Information Service, a clinical trial registry in South Korea (KCT0006187). Patients were excluded if their vital records did not include information on CVP, CO, or MAP. Other data collected from their medical records included patient age, sex, weight, height, type of surgery, and duration of anesthesia.
Data acquisition
All vital data were collected by a free data collection program (Vital recorder [6] version 1.8, accessed at https://vitaldb.net, Seoul, Republic of Korea). CVP and MAP were measured using a central venous or Swan-Ganz catheter (7.5 F Swan-Ganz continuous cardiac output thermodilution catheter: CCOmbo V, model 774F75, Edwards Lifesciences LLC) and an arterial catheter, respectively. In patients who underwent neurosurgery, a FloTrac™/EV1000™ system (Edwards Lifesciences, Irvine, CA, USA) was used, with CO estimated and updated every 20 s. In patients who underwent cardiac surgery, a HemoSphere advanced monitoring platform (Edwards Lifesciences) and a Swan-Ganz catheter were used, with CO estimated and updated every 60 s (continuous CO). The transducers were zeroed and leveled immediately after the insertion of each catheter (i.e. arterial and central). The transducer unit (attached to the multi-transducer holder) was attached on a rod fixed at the side of the operating table. Then the level of the transducer unit was adjusted to the level of 4th intercostal space at the left mid-axillary line of the patient (phlebostatic axis). It is common practice in our institution to adjust the transducer unit if a significant deviation from the phlebostatic axis is noted intraoperatively. However, information about additional intraoperative adjustments of the transducer level was not included in the current study. Mean CVP value obtained over several cardiac and respiratory cycles through the monitor [7] (Intellivue MX700 and MX800 [Philips, Boeblingen, Germany] for neuro- and cardiac surgery, respectively) was recorded and used for the calculation of the actual SVR. As the SVR displayed by the monitoring devices (i.e. EV1000 or HemoSphere) is derived from past CVP (not real-time CVP; displays a same value during the antegrade value processing), the current study used calculated SVR (not displayed value from the device) using real-time CVP and treated it as actual SVR. It was done for comparison between the real-time SVR and the virtual SVR calculated from fixed or random CVP.”
The vital data was recorded in 1 second interval for both MAP and mean CVP and 2 seconds interval for cardiac output. Since these values displayed on the monitor are instantaneous, we extracted mean values for every 10-s interval based on the assumption that at least 10 s of observation is needed for clinical decision. Then the extracted data were filtered for error values so that MAP was > 30 mmHg and < 140 mmHg and mean CVP was > 0 mmHg and < 30 mmHg. After the filtration, as the data processing interval of FloTrac™/EV1000™ system and HemoSphere advanced monitoring platform were 20 and 60 s, respectively, the extracted data was further averaged accordingly (every 20 or 60 s) (Fig. 1).
Hemodynamic variables
SVR was calculated based on actual, fixed, and random values for CVP. Fixed CVP values were set at 0, 5, 10, 15, or 20 mmHg, whereas random CVP values were determined by random sampling between 5 and 15 mmHg, with replacement allowed at every time point; i.e. every 20 s for neurosurgery and every 60 s for cardiac surgery. SVRs for actual CVP (SVRa); for CVPs fixed at 0 mmHg (SVRf0), 5 mmHg (SVRf5), 10 mmHg (SVRf10), 15 mmHg (SVRf15), and 20 mmHg (SVRf20); and for random CVPs (SVRr) were subsequently calculated using the equation: SVR (dynes/sec/cm− 5) = 80 × (MAP [mmHg] – actual, fixed, or random CVP [mmHg]) ÷ CO (L/min).
Statistics
The sample size was based on the available data during the study period. The distribution of continuous variables was assessed by Shapiro–Wilk test and the variables were reported as mean ± SD or median [IQR], accordingly. Differences between actual SVR and SVRs based on fixed and random CVPs were quantified as root mean square error (RMSE) and mean absolute percentage error (MAPE). Actual SVR and SVR derived from the fixed CVP that showed the highest accuracy during the previous stage of analysis, as well as actual SVR and SVR determined from random CVP, were compared using Bland-Altman analysis. The mean biases and the limit of agreements were calculated using a R package ‘SimplyAgree’ which considers adjustment for repeated measurements per patients [8]. Trending ability was assessed by four-quadrant plot analysis, and the concordance rate was calculated [9] after excluding the central zone of each four-quadrant plot, defined as the zone with an absolute difference in SVR < 100 dynes/sec/cm− 5. The border of the central zone of each four-quadrant plot was based on the approximated value of 10% of the mean SVR (actual) in each data set (about 130 and 150 dynes/sec/cm− 5 in cardiac and neurosurgical patients, respectively). The results were stratified by the type of surgery (neurosurgery vs cardiac surgery) to assess potential differences due to surgical characteristics or monitoring modalities. All statistical analyses were performed using R software version 4.0.3 (R Project for Statistical Computing, Vienna, Austria).