The study adheres to the STROBE statement. The retrospective study design and protocol were approved by the Ethics Committee of Hirosaki University Graduate School of Medicine and publicized on our hospital homepage (2021-039). As the study was retrospective, the requirement of patients’ written informed consent was waived by the Ethics Committee. The patient characteristics and peri-operative data were collected from anesthetic and medical records of patients with gynecological cancer (≥ 20 years old) who received ANH during open abdominal surgery at Hirosaki University Hospital during the period from April 1, 2013, to March 31, 2016. Patients who did not receive ANH or were infused with both Saviosol® and Voluven® during surgery were excluded from the study. We divided the patients into two groups based on the colloid solutions: the Saviosol® (DEX) group and the Voluven® (HES) group.
Data collection
We collected the following data from the patients’ medical records: age, height, body weight, body mass index (BMI), and the use of peri-operative allogeneic blood transfusion (red blood cells, fresh frozen plasma, and platelet concentration until postoperative day [POD] 3). The following data were collected from the patients’ anesthesia records: the American Society of Anesthesiologists-Physical Status (ASA-PS); the amounts of ephedrine and/or phenylephrine administered; the amount of ANH blood; the intra-operative total fluid volume of crystalloid and colloid, i.e., Voluven® and Saviosol®; the intra-operative urine out; the intra-operative estimated blood loss; and the durations of surgery and anesthesia. Peri-operative laboratory values including the hemoglobin concentration (Hb), platelet count, serum sodium (Na), potassium (K), chloride (Cl), and base excess (BE) were obtained at three time points: before the induction of anesthesia, after acute hemodilution, and after the surgery (after a re-transfusion of ANH blood) in the post-anesthesia care unit.
We also collected the data of the patients’ peri-operative kidney function (serum creatinine [sCre] and the estimated glomerular filtration rate [eGFR]) within 14 days before surgery and on POD-1 from the electronic medical records. The primary outcomes were the changes in Hb and changes in electrolytes during ANH.
Calculation of blood volume and changes in blood volume
Blood volume (BV) was calculated using the formula [11]:
$$ \mathrm{BV}\ \left(\mathrm{dL}\right)=\left(0.0003561\times {\mathrm{height}}^3\ \left(\mathrm{cm}\right)+\left[33.08\times \mathrm{body}\ \mathrm{weight}\ \left(\mathrm{kg}\right)+183\right]\right)/100 $$
The patient’s BV after surgery was calculated by first estimating the total Hb mass in the circulation at baseline “Hbmass(0)” as being equal to the product of BV(0) and the Hb concentration at baseline, “Hb(0).” Losses from Hb mass were then subtracted for measurement, and the BV(1) was obtained by dividing this difference by a freshly taken Hb value after surgery [12, 13].
$$ \mathrm{Hb}\mathrm{mass}(0)=\mathrm{BV}(0)\times \mathrm{Hb}(0) $$
$$ \mathrm{Hb}\mathrm{mass}\left(\mathrm{loss}\right)=\mathrm{blood}\ \mathrm{loss}\times \mathrm{Hb}(1) $$
$$ \mathrm{BV}(1)=\left[\mathrm{Hbmass}(0)-\mathrm{Hbmass}\left(\mathrm{loss}\right)\right]/\mathrm{Hb}(1) $$
$$ \mathrm{Changes}\ \mathrm{in}\ \mathrm{BV}=\mathrm{BV}(1)-\mathrm{BV}(0) $$
General anesthesia and ANH
All open abdominal gynecological surgeries were managed under total intravenous anesthesia: propofol, ketamine, remifentanil and/or fentanyl, and rocuronium. ANH was conducted in patients who were at risk of a blood loss of ≥ 500 mL during surgery, at the request of the gynecological surgeon.
Blood withdrawal from the patients was started just after induction of anesthesia and before skin incision. The whole blood from a central venous line was collected into standard blood collection bags containing a citrate phosphate dextrose solution. To maintain the patient’s euvolemia and mean arterial pressure ≥ 60 mmHg, the withdrawn whole blood was replaced by the same volume of colloid solution (Voluven® or Saviosol®). To maintain mean arterial pressure ≥ 60 mmHg, ephedrine and/or phenylephrine were administered during blood withdrawal. The withdrawn blood volume for ANH was targeted at 400–800 mL and decided by the attending anesthesiologist and supervisor of the operating theater to prevent Hb < 8.0 g/dL after acute hemodilution. ANH procedure took about 20 to 25 min to collect 800 mL of blood. ANH blood bags were shaken 60–80 rpm in the room temperature. Subsequently, all patients received acetate Ringer’s solution and/or colloid solution during anesthesia. When a specimen was removed or surgical hemostasis was performed, all of the collected ANH blood was reinfused to the patient in the operating theater.
Statistical analyses
We used the D’Agostino and Pearson normality test to determine whether all variables showed a Gaussian distribution. Continuous data are presented as the mean ± standard deviation (SD) or the median [interquartile range, IQR]. Categorical data are presented as the number (%). Student’s t-test or the Mann-Whitney U-test was used for analyzing continuous variables, and the Chi-squared test or Fisher’s exact test was used for analyzing categorical variables. We conducted a repeated two-way analysis of variance (ANOVA) with Tukey’s multiple comparisons tests to evaluate the changes in all variables in the peri-operative period. A repeated two-way ANOVA with Sidak’s multiple comparisons test was conducted to assess the difference in each time point between the two groups. Probability (p)-values < 0.05 were considered significant. All reported p-values are two-tailed. Statistical analyses were performed using GraphPad Prism 7.02 (GraphPad Software, San Diego, CA, USA).
No prior sample size calculation was performed in this study. However, our sample size (111 vs 67) had 99.1% power to detect 300 mL absolute difference in BV after surgery between the DEX and the HES group at the 0.05 level. Sample size calculation was performed using EZR software ver. 1.37 (Saitama Medical Center, Jichi Medical University, Saitama, Japan).
