We investigated the impact of GDT on intraoperative hemodynamic management and physiologic variables compared with historical controls in patients undergoing PD at Teine Keijinkai Hospital, a 600-bed tertiary care hospital in Sapporo, Japan. The study was reviewed and approved on December 24, 2015, by the Teine Keijinkai Hospital institutional review board. Due to the retrospective design of the study, the need for informed consent was waived by the board.
Study subjects
Perioperative data from consecutive patients who underwent PD electively between July 2013 and June 2015 were analyzed. Patients who underwent an operation for other organs concurrently with PD and patients with renal failure requiring hemodialysis were excluded from the study.
Patients who underwent PD in the 1-year period between July 2014 and June 2015 were designated the GDT group, which represents the first patients who received GDT in this hospital. Patients who underwent PD in the preceding 1-year period (between July 2013 and June 2014) were designated the control group.
Intraoperative management
All patients underwent the operation under general anesthesia with tracheal intubation combined with epidural anesthesia. General anesthesia was maintained with propofol or an inhalational agent (sevoflurane or desflurane), with or without remifentanil. The epidural catheter was placed at Th 8/9, Th 9/10, or Th 10/11 interspace, and 0.2–0.375% ropivacaine was infused during surgery with varying doses at the discretion of the caregiving anesthesiologist. A radial artery cannula was placed after tracheal intubation.
Patients in the GDT group received hemodynamic management based on a predefined GDT protocol. The radial artery cannula was connected to a FloTrac sensor and a FloTrac monitor EV-1000 version 1.5 (Edwards Lifesciences, Irvine, CA, USA). First, fluid was given until the goal of stroke volume variation (SVV) < 12% was achieved. At this point, continuous infusion of dobutamine was started or increased if the cardiac index was < 2.5 L/min/m2. If SVV and cardiac index were within the target ranges but mean arterial pressure (MAP) was < 60 mmHg, continuous infusion of norepinephrine or phenylephrine was started or increased. The patients were monitored and reassessed continuously and catecholamines were titrated, if used, to maintain values within these predefined target ranges during surgery (Fig. 1). The patients were mechanically ventilated with tidal volumes of 7 to 10 mL/kg and positive end-expiratory pressure ≤ 6 cmH2O. Maintenance fluid was restricted to < 5 mL/kg/h.
Patients in the control group received hemodynamic management entirely at the discretion of the caregiving anesthesiologist.
Data collection and statistical analysis
We assessed intraoperative use of fluids, catecholamines, and blood products; intraoperative MAP and heart rate (HR); estimated blood loss; and urine output. Fluid balance was defined as the total volume of administered fluid and blood products minus estimated blood loss during surgery minus urine output. MAP and HR were recorded just before induction of anesthesia as the baseline and every 30 min after the surgical incision. Analysis of intraoperative MAP and HR was restricted to the period of 270 min after the surgical incision during which all patients underwent the operation.
We expressed dichotomous or categorical variables as numbers (percentage) and continuous variables as means ± standard deviation or medians (interquartile range), as appropriate. The amount of fluid administered, urine output, estimated blood loss, and fluid balance were expressed as values divided by body weight, because body weight was 8% lower in the GDT group.
For dichotomous or categorical variables, we compared frequencies using Fisher’s exact test. For continuous variables, we compared differences using Welch’s t test or the Mann–Whitney U test when the data were skewed (i.e., urine output). For MAP and HR, we compared differences using repeated measures analysis of variance (ANOVA) with degrees of freedom correction using the Huynh–Feldt or Greenhouse–Geisser estimates of sphericity, as appropriate. We calculated 95% confidence intervals (CIs) of the mean differences for the main results. As the major contributors to fluid balance, we analyzed the correlation between the amount of fluid administered and urine output, using the scatter plot and Spearman’s rank correlation coefficient method. This statistical method was used because of the skewed distribution of urine output.
All statistical tests were two-sided, and we considered P values < 0.05 to indicate statistical significance. All statistical analyses were performed with EZR version 1.36 (Saitama Medical Center, Jichi Medical University, Saitama, Japan), which is a graphical user interface for R version 3.4.1 (The R Foundation for Statistical Computing, Vienna, Austria) [8].