Identifying Perioperative Anesthetic Factors
associated with Postoperative Morbidity in RobotAssisted vs. Open Pancreatoduodenectomy: A
Cohort Study
Antoon van den Enden ( t.vandenenden@hotmail.com )
Erasmus University Medical Center
Bas Groot Koerkamp
Erasmus University Medical Center
Maya Maranus-Vereen
Erasmus University Medical Center
Markus Klimek
Erasmus University Medical Center
Research Article
Keywords: Pancreatic surgery, robot-assisted surgery, pancreatoduodenectomy, perioperative guidance.
DOI: https://doi.org/10.21203/rs.3.rs-145387/v1
License: This work is licensed under a Creative Commons Attribution 4.0 International License.
Read Full License
Page 1/25
Abstract
Background: Robot-assisted pancreatoduodenectomy (RAPD) is a challenging procedure for the
perioperative anesthesiologist, e.g. because of prolonged pneumoperitoneum exposure and reversedTrendelenburg positioning. Purpose of this retrospective cohort study is to identify differences in
perioperative anesthesia-related factors between RAPD and open pancreatoduodenectomy (OPD) and to
determine perioperative anesthetic factors associated with major morbidity (Clavien Dindo ≥ III) after
RAPD.
Methods: All consecutive patient undergoing pancreatoduodenectomy were retrospectively included
during a two year inclusion period. Anesthesia charts were studied on uid management details, rates of
vasopressor administration and arterial blood gas results. All factors were compared between both
surgical approaches. Within RAPD, factors were subsequently compared between patients with major
(Clavien Dindo ≥ III) vs. without major postoperative morbidity and between procedures with high and
low intraoperative blood loss. Perioperative factors associated with considerable postsurgical morbidity
(Clavien Dindo ≥ III) were identi ed by constructing a logistic regression model.
Results: RAPD was associated with higher administration of intraoperative vasopressors (9.5% of
operative time vs. 0% in OPD, p=0.005) and a higher net intraoperative uid balance (2497.6 vs. 1572.3
ml, p<0.001). OPD patients more frequently and quantitatively received colloids compared to RAPD
patients (79.0% vs. 51.6%, p<0.001, 1000.0 vs. 500.0 ml, p<0.001). Intraoperative erythrocyte transfusion
rate was 6.3% (4/64) for RAPD compared to 30.6% (19/62) for OPD (p<0.001). Colloid administration
during surgery and hyperlactatemia after 12 hour postoperative admission were associated with major
(Clavien Dindo ≥ III) morbidity after RAPD (OR 5.06 with 95% CI 1.49-17.20, p=0.009 and OR 3.18 with
95% CI 1.01-9.91, p=0.047, respectively).
Conclusions: RAPD is a challenging procedure for the perioperative anesthesiologist e.g. considering a
higher perioperative demand for vasopressors. Perioperative anesthetic factors, including hemodynamics
and uid strategy might alter postoperative morbidity. However, current data is insu cient to make
speci c recommendations.
Background
The robot-assisted approach of pancreatoduodenectomy was rst described in 2003 by Giulianotti et al.
and has gained momentum as a minimally invasive technique for pancreatoduodenectomy surgery [1].
Robot-assisted pancreatoduodenectomy (RAPD) was already compared with conventional open
pancreatoduodenectomy (OPD) for surgical outcomes by various cohort studies. Despite longer duration
of surgery, RAPD is characterized by lower intraoperative blood loss with equal postoperative mortality
rates and similar oncological outcome [2–4]. Although the surgical feasibility of RAPD is extensively
reported, little is known about speci c anesthesiologic concerns of RAPD and how perioperative
anesthesia-related factors affect postoperative outcome after RAPD.
Page 2/25
The optimal intraoperative uid regimen during abdominal (including pancreatic) surgery in relation to
postsurgical morbidity is part of ongoing scienti c debate. E.g., the 2018 RELIEF trial described an
association between a more restrictive intraoperative net uid balance (median 3.7 liters) and an
increased rate of postsurgical kidney injury after major abdominal surgery [5]. Grant et al. however
observed no differences in postoperative major morbidity rate after randomizing between either a net
liberal (12 ml kg− 1 hr− 1) vs. net restrictive (6 ml kg − 1 hr− 1) intraoperative uid balance for
pancreatectomy surgery, both in a conventional and minimally-invasive approach [6]. RAPD presents
several speci c perioperative challenges. The patient is exposed to pneumoperitoneum and placed in
reversed-Trendelenburg position during the most of the surgical time. This speci c sequence has
previously been described to alter central venous pressure, to increase blood carbon dioxide levels as well
as to decrease cardiac output [7–9]. Compared to OPD, RAPD is expected to differ in perioperative
vasopressor demands and levels of uid administration.
The objective of this retrospective study was rstly to evaluate anesthesia-related differences of RAPD
compared to OPD and secondly to identify independent anesthesia-related factors associated with postRAPD morbidity.
Methods
Population and study characteristics
The local Medical Ethics Committee approved the study with waiver for informed patient consent with
reference MEC-2019-0090 (Medical Ethics Committee, Erasmus MC University Hospital, Rotterdam, the
Netherlands). The study protocol is performed in accordance with the relevant guidelines.
All consecutive patients who underwent pancreatoduodenectomy (either RAPD or OPD) between January
1st 2017 and December 31st 2018 have been retrospectively included for analysis. RAPD has been
performed in our tertiary referral center since January 2017. All procedures were undertaken by a
dedicated team of two pancreatic surgeons or a pancreatic surgeon together with a pancreatic surgical
fellow. RAPD was executed using the Da Vinci Model S robotic surgical device, which was later switched
to the Model Xi (Intuitive Surgical Inc., Sunnyvale, CA, USA). OP was performed by or under direct
supervision of three experienced consultant pancreatic surgeons. Different consultant anesthesiologists
(n = 39) were involved in both surgical modalities.
RAPD is characterized as full-robotic surgery, meaning both the resection and the reconstruction phase
were conducted robotically-assisted. Patients were assigned to RAPD based on patient preference and
availability of both the robot and the robotic surgical team. Patients were only excluded for RAPD in case
of locally advanced pancreatic cancer. All patients were postoperatively admitted to a High Dependency
Unit (HDU) or incidentally to an Intensive Care Unit (ICU). Protocols for postoperative management were
identical for both units. Digital patient records were reviewed for patient demographics, intra- and
postoperative management and postoperative outcome.
Page 3/25
Demographic and baseline details
Extracted baseline data included age, sex, body mass index (BMI) and medical history (comprising
preoperative diabetes mellitus, any pulmonary, cardiac or vascular disease, any history of cerebrovascular
accident (CVA) or transient ischemic attack (TIA), hypertension or prior kidney or liver failure). Besides,
data were extracted on preoperative rates of any previous malignancy, (non-) abdominal surgery or
neoadjuvant chemotherapy. Baseline comorbidity was graded according to American Society of
Anesthesiologist’s (ASA) score and Charlson Comorbidity Index (CCI) [10]. Laboratory results (including
hemoglobin (Hb), platelet count, estimated glomerular ltration rate (e-GFR) and levels of albumin, total
bilirubin, creatinine and CA 19 − 9) were also extracted.
Perioperative factors and postoperative outcome
According to local protocol norepinephrine (NE) was routinely used as perioperative vasopressor adjunct.
Anesthesia records were screened for NE doses on start and end of surgery as well as the frequency of an
NE dosage exceeding 0.2 µg kg− 1 min− 1 (this dosage was chosen within our center as a cut-off for NEadministration via a central venous catheter instead of via a peripheral intravenous cannula). A central
venous catheter was incidentally inserted based on preoperative anesthesiologist’s assessment. The
amount of times NE dosage exceeded 0.2 µg kg− 1 min− 1 was expressed as time span in minutes and as
percentage of operating room time (time span between entering and leaving the operating theatre).
Operative time was de ned as the time interval between skin incision and wound closure.
Fluid balances, including the necessity of erythrocyte transfusion, were studies up to 24 hours
postoperatively. Results of arterial blood gas (ABG) analyses (including blood pH, partial CO2 (pCO2)
pressure, lactate and Hb count) were evaluated at 3 points in time: rst available sample results during
surgery, rst available results upon HDU/ICU admission and rst available results after a minimum of 12
hour HDU/ICU admission. The perioperative ABG results were also compared with the corresponding end
tidal (et) CO2 level.
Time to detubation was de ned as the time interval between wound closure and removal of the
endotracheal tube. Pain scores, expressed as Numeric Rating Scale (NRS), were analyzed on
postoperative days 1 and 3. Standard postoperative analgesic regimen comprised paracetamol (1000 mg
4 times daily) and naproxen (750 mg 3 times daily). OPD was preferably performed under additional
epidural analgesia (routinely using ropivacaine 0.2% combined with sufentanil 1 µg ml− 1). For RAPD a
patient controlled analgesia (PCA) device (morphine based) was used for postoperative analgesia. Once
oral intake was possible again, epidural or PCA analgesia was if necessary converted to oral oxycodone.
Patient records were analyzed for the total hours of postoperative HDU/ICU stay and the rate of
prolonged HDU/ICU admission (de ned as exceeding 24 hours). Length of hospital stay was determined
starting from the rst day after surgery. Postoperative morbidity was graded on a 90-day postsurgical
interval using the Clavien Dindo (CD) score as well as the Comprehensive Complication Index [11, 12]. A
CD score ≥ III was de ned as major postsurgical morbidity. Kidney failure was graded according to
Page 4/25
European Society of Anesthesiologists’ (ESA) European Perioperative Clinical Outcome (EPCO) standards
[13]. Mortality rates were calculated on postoperative days 30 and 90.
Data processing and statistical analysis
Baseline and perioperative factors were primarily analyzed for RAPD and OPD totals. Factors were
subsequently compared for RAPD patients with major postsurgical morbidity (CD ≥ III) vs. RAPD patients
without major postsurgical morbidity. In order to determine whether anesthetic factors were in uenced by
intraoperative blood loss, factors ware also compared for RAPD patients with above vs. below median
intraoperative blood loss (referred to as groups of high and low blood loss, respectively).
Normal distribution of numerical data was assessed using a combination of visual inspection of
histograms and Q-Q plots and the Shapiro-Wilk test. Numerical data on averages were presented as mean
(standard deviation, SD) or median (interquartile range, IQR) as appropriate. Categorical data were
presented with frequencies and percentages. An independent sample T-test or Mann-Whitney U-test was
performed in comparing numerical data, a χ2 or Fisher’s exact test in categorical data. A logistic
regression model was constructed using a backward stepwise approach to identify independent
prognostic factors of major morbidity (CD ≥ III) after RAPD. Results herein were presented as odds ratio
(OR) with corresponding 95% con dence interval. Throughout the study two-tailed P-values of < 0.05 were
considered statistically signi cant. Statistical analysis was carried out using IBM SPSS Statistics
(version 24.0, Armonk, NY, USA; IBM Corp.).
Results
During the inclusion period, 126 Consecutive patients underwent pancreatoduodenectomy (n = 64 RAPD,
n = 62 OPD).
RAPD vs. OPD
No differences in age, BMI and baseline medical history could be demonstrated between RAPD and OPD
patients (Table 1). Baseline hemoglobin level was lower for OPD (12.6 vs. 13.2 g dl− 1, p = 0.049).
Operative time was 441.5 min. in RAPD compared to 318.0 min. in OPD (p < 0.001, Table 2). No RAPD
procedures were converted to OPD. Net intraoperative uid balance was higher in RAPD (2497.6 vs.
1572.3 ml in OPD, p < 0.001). OPD patients more frequently and quantitatively received colloids compared
to RAPD patients (79.0% vs. 51.6%, p < 0.001, 1000.0 vs. 500.0 ml, p < 0.001). Average intraoperative
blood loss was 250.0 ml for RAPD compared to 1150.0 ml for OPD (p < 0.001) with an intraoperative
erythrocyte transfusion rate of 6.3% (4/64) for RAPD compared to 30.6% (19/62) for OPD (p < 0.001). For
RAPD, Hb levels were higher during surgery, upon HDU/ICU admission and after a minimum of 12 hour
HDU/ICU admission (12.6 vs. 11.9 g dl− 1, p = 0.017, 12.6 vs. 11.3 g dl− 1, p < 0.001 and 12.1 vs. 11.0 g dl−
1
, p < 0.001, respectively).
Page 5/25
Table 1
Demographic and baseline details for RAPD and OPD patients
Variables
RAPD vs. OPD
RAPD (n
= 64)
OPD (n =
62)
Post-RAPD morbidity
P
RAPD without
major morbidity
(CD < III, n = 36)
RAPD with
major
morbidity
P
(CD ≥ III, n =
28)
Age (yr)
67.8 ± 9.8
65.5 ±
10.1
0.188
66.8 ± 9.7
69.1 ± 9.9
0.340
Sex (M:F)
1.0:0.9
1.0:0.9
0.424
1.0:1.0
1.0:0.9
0.806
BMI (kg/m2)
25.0
(18.9–
37.9)
24.6
(16.7–
40.7) 2
0.179
25.9 ± 5.0
26.0 ± 3.3
0.909
Diabetes mellitus
17 (26.6)
22 (35.5)
0.337
12 (33.3)
5 (17.9)
0.254
Pulmonary
disease
13 (20.3)
9 (14.5)
0.484
7 (19.4)
6 (21.4)
1.000
Cardiac disease
17 (26.6)
15 (24.4)
0.839
9 (25.0)
8 (28.6)
0.782
Vascular disease
2 (3.1)
5 (8.1)
0.269
1 (2.8)
1 (3.6)
1.000
CVA or TIA
5 (7.8)
6 (9.7)
0.761
3 (8.3)
2 (7.1)
1.000
Hypertension
28 (43.8)
25 (40.3)
0.721
11 (30.6)
17 (60.7)
0.023
Kidney or liver
failure
10 (15.6)
10 (16.1)
1.000
4 (11.1)
6 (21.4)
0.312
Previous
malignancy
19 (29.7)
18 (29.0)
1.000
9 (25.0)
10 (35.7)
0.256
Previous
abdominal surgery
35 (54.7)
36 (58.1)
0.723
21 (58.3)
14 (50.0)
0.615
Previous nonabdominal surgery
41 (64.1)
43 (69.4)
0.574
22 (61.1)
19 (67.9)
0.610
I
8 (12.5)
4 (6.9) 4
0.543
6 (16.7)
2 (7.1)
0.460
II
45 (70.3)
41 (70.3)
25 (69.4)
20 (71.4)
III
11 (17.2)
13 (22.4)
5 (13.9)
6 (21.4)
Medical history
ASA
4
4
Page 6/25
Variables
RAPD vs. OPD
RAPD (n
= 64)
OPD (n =
62)
Post-RAPD morbidity
P
RAPD without
major morbidity
(CD < III, n = 36)
IV
0
0
Score
5.4 ± 2.0
5.4 ± 1.9
Charlson = 0
0
0
Charlson = 1–3
12 (18.8)
10 (16.1)
Charlson = 4–6
34 (53.1)
Charlson = 7
Preoperative
chemotherapy
RAPD with
major
morbidity
P
(CD ≥ III, n =
28)
0
0
5.1 ± 1.9
5.8 ± 2.0
0.161
-
-
-
8 (22.2)
4 (14.3)
0.492
35 (56.5)
18 (50.0)
16 (57.1)
18 (28.1)
17 (27.4)
10 (27.8)
8 (28.6)
4 (6.3)
11 (17.7)
0.057
2 (5.6)
2 (7.1)
0.593
Hemoglobin level
(mmol/L)
8.2 ± 0.9
7.8 ± 1.0
0.049
8.0 ± 0.9
8.4 ± 0.8
0.116
Platelet count (x
109/L)
266 ± 83
293 ± 78
0.063
264 (114–556)
236 (135–
402)
0.365
e-GFR (ml·min−
1·1.73− 1 m2)
81.3 ±
18.1
82.9 ±
17.5
0.610
84.4 ± 17.2
77.3 ± 18.7
0.123
Albumin level
(g/L)
42.1 ± 7.2
41.8 ± 4.6
0.757
41.0 (24.0–
50.0) 1
42.0 (32.0–
75.0) 1
0.564
Total bilirubin level
(umol/L)
11.5 (3.0214.0)
9.0 (3.0208.0) 1
0.218
12.5 (3.0-214.0)
10.5 (5.0–
51.0)
0.542
Creatinine level
(umol/L)
77.0 ±
23.7
75.4 ±
18.8
0.675
73.5 ± 17.3
81.4 ± 29.7
0.216
Ca 19 − 9 (kU/L)
33.0 (1.05146.0)
29.0 (1.07408.0) 5
0.880
35.0 (1.05146.0)
33.0 (1.01908.0)
0.946
Charlson
Comorbidity Index
0.900
0.332
Baseline
laboratory
2
6
Page 7/25
Variables
RAPD vs. OPD
RAPD (n
= 64)
OPD (n =
62)
Post-RAPD morbidity
P
RAPD without
major morbidity
(CD < III, n = 36)
RAPD with
major
morbidity
P
(CD ≥ III, n =
28)
Values are presented as number (proportion) or depending on normality distribution of cases as
mean ± SD or median (interquartile range). Xn where n represents the number of missing cases. ASA,
American Society of Anesthesiologists Classi cation; BMI, Body Mass Index; CD, Clavien Dindo; CVA,
Cerebro Vascular Accident; e-GFR, Estimated Glomerular Filtration Rate; OPD, Open
Pancreatoduodenectomy; RAPD, Robot-Assisted Pancreatoduodenectomy; TIA, Transient Ischemic
Attack.
Page 8/25
Table 2
Perioperative anesthesia-related factors, RAPD vs. OPD
Variables
RAPD vs. OPD
RAPD (n = 64)
OPD (n = 62)
P
Operating room time (min)
513.5 (377.0-836.0)
392.5 (240.0-802.0)
<
0.001
Operative time (min)
441.5 (326.0-756.0)
318.0 (188.0-753.0)
<
0.001
Net positive uid balance (ml)
2497.6 (544.05535.0) 1
1572.3 (50.025925.2) 3
<
0.001
Crystalloid dose (ml)
2100.0 (51.05137.0) 1
1896.0 (0.0-8337.4)
0.069
500.0 (0.0-2000.0)
1000.0 (0.0-5700.0)
<
0.001
Colloid administration
33.0 (51.6) 1
49.0 (79.0) 3
<
0.001
Blood loss (ml)
250.0 (0.0–2500.0)
1150.0 (0.011585.0) 3
<
0.001
Intraoperative erythrocyte transfusion
4 (6.3)1
19 (30.6)
<
0.001
NE dose on surgery’s start (ug·kg− 1·min− 1)
0.05 (0.00-0.20) 2
0.03 (0.00-0.72) 2
0.021
NE dose on surgery’s end (ug·kg− 1·min− 1)
0.06 (0.00-0.38) 1
0.06 (0.00-0.80)
0.821
NE dose > 0.2 ug·kg− 1·min− 1 (min)
1 (0–5) 1
0 (0–3) 1
0.005
Time span NE dose > 0.2 ug·kg− 1·min− 1 (min)
4.1 (0.0-610.0) 1
0.0 (0.0-393.0) 1
0.002
Operative time NE dose > ug·kg− 1·min− 1 (%)
9.5 (0.0-96.2) 1
0.0 (0.0-56.5) 1
0.005
Blood pH
7.32 ± 0.06 7
7.35 ± .0.06 2
0.021
Partial CO2 pressure (kPa)
6.2 (4.3–24.2) 7
5.6 (4.5–7.1) 2
<
0.001
Corresponding end-tidal CO2 (kPa)
5.0 ± 0.6 15
4.7 ± 0.3 8
0.001
Intraoperative uid balance
Colloid dose (ml)
1
3
3
NE regimen
First arterial BGA during surgery
Page 9/25
Variables
RAPD vs. OPD
RAPD (n = 64)
OPD (n = 62)
P
Lactate level (mmol/L)
0.7 (0.3–1.9) 7
0.7 (0.3–2.7) 2
0.884
Hemoglobin count (mmol/L)
7.8 ± 0.8 7
7.4 ± 1.0 2
0.017
Blood pH
7.33 ± 0.04 1
7.35 ± 0.05
0.013
Partial CO2 pressure (kPa)
5.8 (4.7–20.1) 1
5.5 (4.0-6.7)
0.002
Lactate level (mmol/L)
1.3 (0.1–6.3) 1
1.3 (0.4–11.7)
0.517
Hemoglobin count (mmol/L)
7.8 ± 0.9 1
7.0 ± 1.0
<
0.001
Blood pH
7.39 (7.29–7.48) 4
7.39 (7.23–7.47) 1
0.981
Partial CO2 pressure (kPa)
5.8 (4.7-7.0) 4
5.5 (3.8–7.9) 1
0.019
Lactate level (mmol/L)
1.1 (0.5–2.9) 4
1.0 (0.4–5.6) 1
0.803
Hemoglobin count (mmol/L)
7.5 ± 0.9 4
6.8 ± 1.0 1
<
0.001
First arterial BGA upon HCU/IDU admission
First arterial BGA after ≥ 12 hours HCU/IDU
admission
Values are presented as number (proportion) or depending on normality distribution of cases as
mean ± SD or median (interquartile range). Xn where n represents the number of missing cases. BGA,
Blood Gas Analysis; HDU, High Dependency Unit; ICU, Intensive Care Unit; NE, Norepinephrine; OPD,
Open Pancreatoduodenectomy; RAPD, Robot Assisted Pancreatoduodenectomy.
On average, NE was administered in a higher dose at procedure’s start in RAPD (0.05 vs. 0.03 µg kg− 1
min− 1 in OPD, p = 0.021). During the intraoperative course of RAPD, NE dosage exceeded 0.2 µg kg− 1
min− 1 more frequently compared to OP with a net time span of 48 vs. 0 min (p = 0.002) and 9.5 vs. 0
percent of operating room time (p = 0.005). RAPD was characterized by lower average blood pH during
surgery (7.32 vs. 7.35 in OPD, p = 0.021) with high pCO2 pressures and corresponding etCO2 levels (6.2 vs.
5.6 kPa in OPD, p < 0.001 and 5.0 vs. 4.7 kPa in OPD, p = 0.001, respectively). A similar trend is observed
in RAPD patients upon HDU/ICU arrival (arterial blood pH 7.33 vs. 7.35 in OPD, p = 0.013 and pCO2 5.8 vs.
5.5 kPa in OPD, p = 0.002, Table 2).
No differences were observed in major postoperative morbidity rate (CD ≥ III) between both surgical
modalities (28/64, 43.8% in RAPD vs. 33/62, 53.2% in OPD, p = 0.373, Table 3). An average
Comprehensive Complication Index of 32.7 was observed in RAPD vs. 49.9 in OPD (p = 0.012). Rates of
postoperative acute kidney injury were 9/64 (14.5%) for RAPD vs. 6/92 (9.7%) for OPD (p = 0.583). Six
Page 10/25
patients entered the procedure with pre-existing renal impairment (e-GFR < 60 ml min-1, n = 3 in RAPD and
n = 3 in OPD). No further deterioration of kidney injury was observed in any of these patients. Average
pain score on postoperative day 1 was 3 for RAPD compared to 1 for OPD (p < 0.001). On postoperative
day 3, average pain score was 2 for both RAPD and OPD (p = 0.894).
Table 3
Postoperative outcome after RAPD vs. OPD
Variables
RAPD (n = 64)
OPD (n = 62)
P
Time to detubation (min)
32.0 (0.0-931.0) 11
21.0 (1.0-21714.0) 9
0.381
Stay HCU/IDU (hours)
19.5 (14.6–97.4)
21.6 (15.6-478.4) 1
< 0.001
Prolonged HDU/ICU admission
5 (7.8)
12 (19.7)1
0.069
Hospital stay (days)
11.5 (4.0–61.0)
14.5 (6.0-200.0)`
0.277
Comprehensive Complication Index
32.7 (0.0-100.0)
49.9 (8.7–100.0)
0.012
Grade III
20 (31.1)
23 (37.1)
0.574
Grade IIIA
15 (23.4)
14 (22.6)
1.000
Grade IIIB
5 (7.8)
9 (14.5)
0.268
Grade IV
8 (12.5)
10 (16.1)
0.617
Grade IVA
3 (4.7)
4 (6.5)
0.715
Grade IVB
5 (7.8)
6 (9.7)
0.761
=> Grade III
28 (43.8)
33 (53.2)
0.420
Acute Kidney failure
9 (14.5)
6 (9.4)
0.583
30-day mortality
1 (1.6)
2 (3.2)
0.616
90-day mortality
5 (7.8)
4 (6.5)
1.000
NRS Postoperative day 1
3 (0–7) 8
1 (0–7) 3
< 0.001
NRS Postoperative day 3
2 (0–7) 9
2 (0–5) 16
0.894
CD morbidity rates
Values are presented as number (proportion) or depending on normality distribution of cases as
mean ± SD or median (interquartile range). Xn: where represents the number of missing cases. CD,
Clavien Dindo; HDU, High Dependency Unit; ICU, Intensive Care Unit; NRS, Numeric Rating Scale; OPD,
Open Pancreatoduodenectomy; RAPD, Robot Assisted Pancreatoduodenectomy.
Major (CD ≥ III) vs. without major morbidity after RAPD
Page 11/25
A higher rate of baseline hypertension was observed in the RAPD group with major postoperative
morbidity (17/28, 60.7% vs. 11/36, 30.6% for the RAPD group without major morbidity, p = 0.023, Table 1).
Intraoperative colloid administration and blood loss were higher in the RAPD group with major
postoperative morbidity (500.0 vs. 0.0 ml, p = 0.002 and 350.0 vs. 200.0 ml, p = 0.047, respectively, Table
4). Average NE dose was higher at the end of surgery for the RAPD group with major postoperative
morbidity (0.09 vs. 0.04 µg kg− 1 min− 1 for the RAPD group without major postoperative morbidity, p =
0.726). Upon HDU/ICU admission, lower arterial blood pH as well as higher lactate levels were observed in
the RAPD group with major postoperative morbidity (7.32 vs. 7.34, p = 0.017 and 1.7 vs 1.3 mmol l− 1, in
the RAPD group without major postoperative morbidity, respectively). A similar trend was observed after a
minimum of 12 hour HDU/ICU admission (7.37 vs. 7.39, p = 0.016 and 1.4 vs. 0.9 mmol l− 1, respectively).
Hospital stay was doubled in the RAPD group with major postoperative morbidity compared to the RAPD
group without major postoperative morbidity (18.0 vs. 7.0 days, p < 0.001, Table 5). Within the 90-day
inclusion period, n = 2 (RAPD) patients deceased due to early recurrence of malignant disease.
Page 12/25
Table 4
Perioperative anesthetic factors in RAPD
Variables
RAPD (n
= 64)
Post-RAPD morbidity
Intraoperative blood loss
(RAPD)
RAPD
with
major
morbidity
High
Low
(≥
250 ml,
n = 33)
(<
250 ml,
n = 31)
(CD ≥ III,
n = 28)
RAPD
without
major
morbidity
(CD < III, n
= 36)
P
Operating room
time
513.5
(377.0836.0)
527.5
(397.0749.0)
513.5
(377.0836.0)
0.690
580.0
(397.0750.0)
478.0
(377.0836.0)
0.001
Operative time
441.5
(326.0756.0)
463.5
(353.0691.0)
441.5
(326.0756.0)
0.671
516.0
(353.0691.0)
410.0
(326.0756.0)
0.001
2497.6
(544.05535.0)
2777.1 ±
1046.9 1
2688.0 ±
806.3
0.704
3057.0
(544.05535.0)
2288.9
(1525.64346.9)
0.012
2100.0
(51.05137.0)
2267.4 ±
1110.4 1
2478.7
±
1048.7
2080.6
6 ± 51.6
0.076
500.0
(0.02000.0)
500.0
(0.02000.0) 1
0.0 (1.01000.0)
500.0
(0.02000.0)
0.0 (0.01250.0)
<
0.001
Colloid
administration
33.0
(51.6) 1
20 (71.4)
13 (36.1)
0.005
25
(75.8) 1
8 (25.8)
<
0.001
Blood loss (ml)
250.0
(0.0–
2500.0)
350.0
(0.02500.0)
200.0
(30.02000.0)
0.047
500.0
(250.02500.0)
150.0
(0.0200.0)
<
0.001
Intraoperative
erythrocyte
transfusion
4 (6.3)1
2 (7.1) 1
2 (5.6)
1.000
4 (12.1)
0
0.113
0.05
(0.000.20) 2
0.05
(0.01–
0.20) 1
0.05 (0.000.20) 1
0.472
0.05
(0.000.19) 2
0.05
(0.000.20)
0.692
Intraoperative uid
balance
Net positive uid
balance (ml)
1
1
Crystalloid dose
(ml)
2294.4 ±
702.2
0.906
1
Colloid dose (ml)
1
1
1
0.002
1
1
NE regimen
NE dose on
surgery’s start
(ug·kg− 1·min− 1)
Page 13/25
Variables
RAPD (n
= 64)
Post-RAPD morbidity
Intraoperative blood loss
(RAPD)
RAPD
with
major
morbidity
High
Low
(≥
250 ml,
n = 33)
(<
250 ml,
n = 31)
0.09
(0.000.38) 1
0.04
(0.000.25)
0.518
1 (0–4)
1 (0–5)
0.374
134.0
(0.0600.0)
15.0
(0.0610.0)
0.283
(CD ≥ III,
n = 28)
RAPD
without
major
morbidity
(CD < III, n
= 36)
P
NE dose on
surgery’s end
(ug·kg− 1·min− 1)
0.06
(0.000.38) 1
0.09
(0.000.22) 1
0.04 (0.000.38)
0.726
NE dose > 0.2
ug·kg− 1·min− 1
(min)
1 (0–5)
1 (0–5) 1
1 (0–3)
0.471
Time span NE dose
> 0.2 ug·kg− 1·min− 1
(min)
4.1 (0.0610.0) 1
133.0
(0.0610.0) 1
22.5 (0.0550.0)
0.262
Operative time NE
dose > ug·kg−
1
·min− 1 (%)
9.5 (0.096.2) 1
20.4 (0.096.2) 1
5.0 (0.09.1)
0.298
20.8
(0.086.2) 1
4.0 (0.096.2)
0.431
Blood pH
7.32 ±
0.06 7
7.34 ±
0.06 3
7.31 ± 0.06
0.135
7.31 ±
0.06 3
7.33 ±
0.06 4
0.361
Partial CO2
pressure (kPa)
6.2
(4.3–
24.2) 7
6.1 (4.3–
8.1) 3
6.3 (5.3–
24.2) 4
0.681
6.3
(4.3–
8.4) 3
6.1
(5.1–
24.2) 4
0.695
Corresponding endtidal CO2(kPa)
5.0 ± 0.6
5.0 ± 0.7 5
5.0 ± 0.5 10
0.895
5.0
(3.9–
6.5) 8
5.0
(3.9–
6.6) 7
0.703
Lactate level
(mmol/L)
0.7
(0.3–
1.9) 7
0.8 (0.3–
1.9) 3
0.7 (0.4–
1.3) 4
0.403
0.8
(0.3–
1.6) 3
0.7
(0.4–
1.9) 4
0.411
Hemoglobin count
(mmol/L)
7.8 ± 0.8
7.9 ± 0.8 3
7.8 ± 0.9 4
0.526
7.7 ±
0.9 3
8.0 ±
0.8 4
0.180
7.33 ±
0.04 1
7.32 ±
0.04
7.34 ± 0.04
0.017
7.33 ±
0.05 1
7.33 ±
0.04
0.588
1
1
1
First arterial BGA
during surgery
15
7
4
First arterial BGA
upon HDU/ICU
admission
Blood pH
1
Page 14/25
Variables
RAPD (n
= 64)
Post-RAPD morbidity
Intraoperative blood loss
(RAPD)
RAPD
with
major
morbidity
High
Low
(≥
250 ml,
n = 33)
(<
250 ml,
n = 31)
(CD ≥ III,
n = 28)
RAPD
without
major
morbidity
(CD < III, n
= 36)
P
Partial CO2
pressure (kPa)
5.8
(4.7–
20.1) 1
5.8 (4.8–
20.1)
5.8 (4.6–
10.7) 1
0.241
5.8
(4.7–
20.1) 1
5.8 (5.010.7)
0.588
Lactate level
(mmol/L)
1.3
(0.1–
6.3) 1
1.7 (0.5–
6.3)
1.3 (0.1–
6.3) 1
0.021
1.6
(0.5–
6.3) 1
1.0
(0.1–
3.7)
0.008
Hemoglobin count
(mmol/L)
7.8 ± 0.9
7.8 ± 0.9
7.8 ± 0.9 1
0.874
7.5 ±
0.9 1
8.1 ±
0.8
0.007
Blood pH
7.39
(7.29–
7.48) 4
7.37 ±
0.04 1
7.39 ± 0.03
0.016
7.38 ±
0.04 3
7.40 ±
0.04 1
0.131
Partial CO2
pressure (kPa)
5.8 (4.77.0) 4
5.8 ± 0.5 1
5.6 ± 0.5 3
0.190
5.8
(4.8–
6.3) 3
5.7 (4.97.0) 1
0.906
Lactate level
(mmol/L)
1.1
(0.5–
2.9) 4
1.4 (0.6–
2.8) 1
0.9 (0.5–
2.9) 3
0.014
1.2
(0.7–
2.8) 3
1.0
(0.5–
2.9) 1
0.282
Hemoglobin count
(mmol/L)
7.5 ± 0.9
7.7 (5.2–
8.7) 1
7.6 (6.1–
9.5) 3
0.864
7.1 ±
0.9 3
7.9 ±
0.7 1
<
0.001
1
First arterial BGA
after ≥ 12 hours
HDU/ICU
admission
4
3
Values are presented as number (proportion) or depending on normality distribution of cases as
mean ± SD or median (interquartile range). Xn where n represents the number of missing cases. BGA,
Blood Gas Analysis; HDU, High Dependency Unit; ICU, Intensive Care Unit; NE, Norepinephrine; OPD,
Open Pancreatoduodenectomy; RAPD, Robot Assisted Pancreatoduodenectomy.
Page 15/25
Table 5
Postoperative outcome after RAPD
Variable
RAPD
(n = 64)
Post-RAPD morbidity
RAPD with
major
morbidity
(CD ≥ III, n =
28)
Time to
detubation (min)
RAPD
without
major
morbidity
Intraoperative (RAPD)
blood loss
P
(CD < III, n =
36)
P
High
Low
(≥
250 ml,
n = 33)
(<
250 ml,
n = 31)
55.0
(0.0931.0)
22.5
(0.0185.0)
0.327
32.0
(0.0931.0)
49.5 (0.0403.0) 6
Stay HDU/ICU
(hours)
11.5
(4.0–
61.0)
20.0 (15.3–
97.4)
19.1 (14.6–
44.0)
0.140
18.8
(14.097.4)
19.7
(14.6–
44.9)
0.122
Prolonged
HDU/ICU
admission
5 (7.8)
4 (14.3)
1 (2.8)
0.159
3 (9.1)
2 (6.5)
1.000
Hospital stay
(days)
10.5
(4.0–
61.0)
19.0 (5.0–
61.0)
8.0 (4.0–
37.0)
<
0.001
17.0
(5.061.2)
9.0
(4.0–
48.0)
0.002
Comprehensive
Complication
Index
32.7
(0.0100.0)
64.5 (0.0100.0)
21.8 (0.0100.0)
<
0.001
51.5
(12.2–
100.0)
24.2
(0.099.9)
<
0.001
28
(43.8)
-
-
-
20
(60.6)
8
(25.8)
0.006
NRS
Postoperative
day 1
3 (0–7)
3 (0–7) 1
2 (0–7)7
0.248
3 (0–
7) 3
2 (0–
7) 5
0.255
NRS
Postoperative
day 3
2 (0–7)
2 (0–7) 3
2 (0–4)6
0.071
2 (0–
7) 4
2 (0–
7) 5
0.562
24.0 (0.0931.0) 5
0.316
8
11
CD ≥ Grade III
8
9
3
Values are presented as number (proportion) or median (interquartile range). Xn where n represents
the number of missing cases. CD, Clavien Dindo; HDU, High Dependency Unit; ICU, Intensive Care Unit;
NRS, Numeric Rating Scale; OPD, Open Pancreatoduodenectomy; RAPD, Robot Assisted
Pancreatoduodenectomy.
High vs. low intraoperative blood loss in RAPD
Average intraoperative blood loss was 250 ml in RAPD (Table 2), n = 33 RAPD procedures were
characterized by high (≥ 250 ml) vs. 31 RAPD procedures by low (< 250 ml) intraoperative blood loss.
Both operating room and operative time were longer in the RAPD group with high intraoperative blood
Page 16/25
loss (580.0 vs. 487.0 min., p = 0.001 and 518.0 vs. 410.0 min., p = 0.001, respectively, Table 4) compared
to the RAPD group with low intraoperative blood loss. Average NE dose was higher at the end of surgery
for the RAPD group with high intraoperative blood loss (0.09 vs. 0.04 µg kg− 1 min− 1 in the RAPD group
with low intraoperative blood loss). NE-dose trended to exceed 0.2 µg kg− 1 min− 1 more frequently in the
RAPD group of high intraoperative blood loss (134.0 vs. 15.0 min, p = 0.283, and 20.8% vs. 4.0% of
operative time in the RAPD group of low intraoperative blood loss, p = 0.431). Upon HDU/ICU admission,
lactate levels were higher in the RAPD group of high intraoperative blood loss (1.6 vs. 1.0 mmol l− 1 in the
RAPD group of low intraoperative blood loss, p = 0.008). Length of hospital stay was doubled for the
RAPD group of high intraoperative blood loss (16.0 vs. 8.0 days in the RAPD group of low intraoperative
blood loss, p = 0.002, Table 5). A higher rate of postoperative morbidity was observed in the RAPD group
with high intraoperative blood loss (Comprehensive Complication Index of 51.5 vs. 24.2 in the RAPD
group with low intraoperative blood loss, p < 0.001). Besides, a higher rate of major postoperative
morbidity (CD ≥ III) was observed in the RAPD group of high intraoperative blood loss (20/33, 60.6% vs.
8/31, 25.8% in the RAPD group of low intraoperative blood loss, p = 0.006).
Predictors of major morbidity after RAPD
After univariate logistic regression analysis, anesthesia-related factors independently associated with
major morbidity (CD ≥ III) after RAPD were a baseline medical history of hypertension (OR 3.51, 95% CI
1.24–9.92, p = 0.018), colloid administration during surgery (OR 5.06, 95% CI 1.69–15.14, p = 0.004),
lactate level upon HDU/ICU admission (OR 2.47, 95% CI 1.27–4.82, p = 0.008) and lactate level after 12
hour HDU/ICU admission (OR 3.66, 95% CI 1.29–10.44, p = 0.015, Table 6). After backward stepwise
regression, colloid administration during surgery and lactate level after 12 hour HDU/ICU admission
remained independently associated with major morbidity after RAPD (OR 5.06, 95% CI 1.49–17.2, p =
0.009 and OR 3.18, 95% CI 1.01–9.91, p = 0.047, respectively).
Page 17/25
Table 6
Logistic regression analysis : anesthesia-related factors independently associated with major morbidity
(CD ≥ III) after RAPD
Variable
Univariable analysis
Backward stepwise
regression
OR
95% CI
P
OR
95%
CI
P
Medical history of hypertension
3.51
1.24 to
9.92
0.018
3.28
0.97
to
11.13
0.057
Intraoperative colloid administration
5.06
1.69 to
15.14
0.004
5.06
1.49
to
17.20
0.009
Blood loss during surgery (ml)
1.12
1.00 to
1.26
0.058
Operating room time (min)
1.00
1.00 to
1.01
0.599
Lactate level in rst BGA after HDU/ICU
admisison (mmol/L)
2.47
1.27 to
4.82
0.008
3.66
1.29 to
10.44
0.015
3.18
1.01
to
9.91
0.047
Lactate level in BGA after ≥ 12 hour HDU/ICU
admisison (mmol/L)
BGA, Blood Gas Analysis; CI, con dence interval; CD, Clavien Dindo; HDU, High Dependency Unit; ICU,
Intensive Care Unit; NE, Norepinephrine’ OR, Odds Ratio’ RAPD, Robot Assisted
Pancreatoduodenectomy.
Discussion
After comparing perioperative anesthetic factors for RAPD and OPD, RAPD is characterized by higher
demands of vasopressor support and higher intra- and postoperative pCO2 and Hb-levels. Although net
intraoperative uid balance and vasopressor demands are higher in RAPD, levels of colloid and
erythrocyte transfusion are lower for RAPD compared to OPD. Rates of major postoperative morbidity
(CD ≥ III) were similar for the surgical approaches. Within patients who developed major morbidity (CD ≥
III) after RAPD, vasopressor demands and necessity of colloid administration tended to be higher. The
need for intraoperative colloid administration and increased postoperative lactate levels were
independently associated with major morbidity (CD ≥ III) after RAPD.
Comparing outcomes, the surgical modality itself in uences the development of major morbidity less
than patient-related variables. We report a small fraction of patients marked ASA class III and above
(11/64, 17.2% in RAPD and 13/62, 22.4% in OPD), compared to earlier studies reporting percentages up to
43.1 and 82.4% [14, 15]. This discrepancy might suggest an underrating of ASA grading, in contrast with
the 2017 strengthened ASA classi cations [16]. ASA scores in our series are however in concordance with
Page 18/25
recent ndings of van Roessel et al., reporting 21.8% ASA III patients in a cohort of n = 3341
pancreatoduodenectomy and distal pancreatectomy procedures, using Dutch Nationwide Pancreatic
Cancer Audit data [17, 18]. Van Roessel et al. predict worse outcome after pancreatoduodenectomy in
ASA ≥ III patients (OR 0.59, 95% CI 0.44–0.80, for achieving optimal outcome after pancreatic surgery). In
our study ASA class itself was not an individual predictor for postoperative major morbidity (CD ≥ III)
where baseline hypertension was (OR 3.51, 95% CI 1.24–9.92). This nding, compared with higher
vasopressor demands in RAPD, implies as association between baseline cardiovascular condition and
postoperative outcome after RAPD. However, a medical history of hypertension might comprise several
baseline conditional factors with itself a possible in uence on postoperative morbidity (e.g. increased
BMI, vascular remodeling or pre-existing renal insu ciency).
A higher need for intraoperative vasopressor administration in RAPD could be explained by differences in
patient positioning (reversed-Trendelenburg in RAPD vs. supine in OPD) as well as exposure to
pneumoperitoneum, affecting cardiac afterload and cardiac output [7–9]. Higher demand for vasopressor
administration in RAPD was not necessarily re ected by worse baseline physical condition. Although
OPD patients more often received neoadjuvant chemotherapy and baseline hemoglobin levels were lower,
no differences in baseline medical condition could be demonstrated between both surgical approaches.
Although the intraoperative use of vasopressors was evident, we feel supported by recently published
data that routinely insertion of a central venous catheter is not mandatory in RAPD or OPD patients [19,
20].
The 2018 RELIEF Study reported on postoperative outcome after distinct intraoperative uid strategies
during major abdominal surgery, differentiating between an either restrictive (median crystalloid + colloid
2177) or liberal (median crystalloid + colloid 3500 ml) net intraoperative uid balance [5]. Whereas no
differences were observed in general postoperative outcome between both uid approaches, a liberal
intraoperative uid strategy was associated with lower rates of postoperative kidney failure (17/1439,
5.0% for liberal vs. 124/1443, 8.6% for restrictive, p < 0.001). In comparison, we report a median
intraoperative uid balance of 2800 ml and a 9/64 (14.5%) rate of postoperative acute kidney injury in
RAPD patients. Bannone et al. observed an increased rate of post pancreatoduodenectomy pancreatitis in
patients exposed to a near-zero net perioperative uid regime, suggesting a more restrictive perioperative
uid balance to be associated with an increased risk of postoperative pancreatic stula [21]. On the
contrary, the 2019 meta-analysis by Garland et al. reported an OR of 0.54 (95% CI 0.31–0.94) for major
morbidity post pancreatoduodenectomy surgery after following a more restrictive intraoperative uid
strategy [22]. The optimal intraoperative uid regime in pancreatoduodenectomy remains point of debate
and prospective research should extrapolate this topic to minimally-invasive vs. conventional
pancreatoduodenectomy surgery.
We observed an association between the intraoperative administration of colloids and development of
major morbidity after RAPD (OR 5.06, 95% CI 1.96–15.14, p = 0.009). This nding is in accordance with
Simões, reporting an OR of 1.86 (95% CI 1.03–4307) for development of major postoperative morbidity
after the intraoperative administration of colloids (n = 308 elective surgeries for abdominal malignancies,
Page 19/25
including n = 22 pancreatic surgical procedures) [23]. In our RAPD series of low intraoperative blood loss,
8/31 (25.8%) of patients vs. 25/33 (75.8%) of patients in the RAPD group of high intraoperative blood
loss intraoperative received colloids. It is important to consider which patient category requires
intraoperative colloid transfusion. Since colloid administration is part of therapy for major blood loss in
our center’s protocol, the association of intraoperative colloid administration and development of major
postoperative morbidity (CD ≥ III) does not necessarily have to re ect a direct causative effect.
Over the perioperative course, pH values were higher in RAPD compared to OPD (7.35 vs. 7.32 on
beginning of surgery, p = 0.021 and 7.35 vs. 7.33 upon HDU/ICU arrival, p = 0.013). These differences in
pH levels do not re ect clinical relevance and moderately higher perioperative pH levels in RAPD can well
be explained by exposure to pneumoperitoneum and (retroperitoneal) absorption of CO2. In our series a
higher lactate level after a minimum admission of 12 hours on HDU/ICU was associated with major
morbidity after RAPD (OR 3.18, 95% CI 1.01–9.91, p = 0.047). This is in accordance with De Schryver et
al., reporting an OR of 3.58 (95% CI 1.22–10.18, p = 0.020) for 6-hour post pancreatic (laparotomic)
surgery hyperlactatemia and development of postoperative pancreatic stula [24]. Average postoperative
pain scores during the rst postoperative day were higher in RAPD compared to OPD. The reported rst
postoperative day NRS of 3 in RAPD compared to a NRS of 1 in OPD is of limited clinical relevance and
therefore not attributable to major morbidity. Besides, this moderate difference can well be explained by
the routine application of additional epidural analgesia in OPD, in accordance with previously reported
studies on additional epidural analgesia during pancreatoduodenectomy [25].
Our study comprises several limitations. First the retrospective single-center study design covering a
relatively high, but still limited number of procedures. Due to the limited number of surgeons, the surgical
approach was very standardized. This is in contrast to the perioperative anesthetic care, which was
provided by n = 39 different consultant anesthesiologists who followed available protocols with different
levels of adherence.
Conclusions
Speci c differences exist in perioperative anesthesia-related factors between RAPD and OPD. RAPD is
associated with higher levels of vasopressor drug administration as well as higher net perioperative uid
balance. Besides, levels of colloid and erythrocyte transfusion are lower for RAPD compared to OPD.
Baseline hypertension, perioperative colloid administration and increased lactate levels after surgery were
associated with higher rates of major morbidity (CD ≥ III) after RAPD. A more restrictive intraoperative
uid regime has previously been shown to increase postoperative (nephrogenic) morbidity, present
evidence is however contradictory. Current data is insu cient to make speci c recommendations on
perioperative anesthetic guidance in RAPD. However, intraoperative hemodynamics including uid
strategy might in uence postoperative morbidity and should be the focus of future prospective research.
Abbreviations
Page 20/25
ABG = Arterial Blood Gas
ASA = American Society of Anesthesiologists
BMI = Body Mass Index
CCI = Charlson Comorbidity Index
CD = Clavien Dindo
CVA = Cerebro Vascular Accident
e-GFR = Estimated Glomerular Filtration Rate
EPCO = European Perioperative Clinical Outcome
ESA = European Society of Anesthesiology
ET = End Tidal
Hb = Hemoglobin
HDU = High Dependency Unit
ICU = Intensive Care Unit
IQR = Inter Quartile Range
NE = Norepinephrine
NRS = Numeric Rating Scale
OPD = Open Pancreatodudoenectomy
OR = Odds Ratio
PCA = Patient Controlled Analgesia
pCO2 = Partial Carbon dioxide
pO2 = Partial Oxygen
RAPD = Robot Assisted Pancreatoduodenectomy
SD = Standard Deviation
TIA = Transient Ischemic Attack
Page 21/25
Declarations
Ethics approval and consent to participate
The local Medical Ethics Committee approved the study with waiver for informed patient consent with
reference MEC-2019-0090 (Medical Ethics Committee, Erasmus MC University Hospital, Rotterdam, the
Netherlands).
Consent for publication
Not applicable
Availability of data and materials
The datasets used and analysed during the current study are available from the corresponding author on
reasonable request.
Competing interests
The authors declare that they have no competing interests.
Funding
Funding was provided solely from institutional and/or departmental sources.
Authors’ contributions
AE was responsible for data acquisition, methodology, formal analysis and visualization of data.
Conceptualization was performed by BGK and MK. Writing of the original draft was conducted by AE.
BGK, MMV and MK reviewed and edited the manuscript. The nal manuscript was read and approved by
all authors.
Acknowledgements
The authors thank Khe T.C.K. Tran, MD, consultant surgeon (department of Surgery, Division of
Hepatobiliary, Pancreatic- and Transplant Surgery at Erasmus University MC, Rotterdam, the Netherlands)
for her help in implementing the robot-assisted pancreatoduodenectomy in our university hospital. We
also acknowledge Casper H.J. van Eijck, MD, PhD, professor and consultant surgeon (department of
Surgery, Division of Hepatobiliary, Pancreatic- and Transplant Surgery at Erasmus University MC,
Rotterdam, the Netherlands) for leading and coordinating the pancreatic surgical team in our university
hospital.
References
Page 22/25
1. Giulianotti PC, Coratti A, Angelini M, Sbrana F, Secconi S, Balestracci T et al. Robotics in general
surgery: personal experience in a large community hospital. Arch Surg. 2003 Jul; 138(7): 777 – 84.
https://doi.10.001/archsurg.138.7.777.
2. Chen S, Chen JZ, Zhan Q, Deng XX, Shen BY, Peng CH et al. Robot-assisted laparoscopic versus open
pancreaticoduodenectomy: a prospective, matched, mid-term follow-up study. Surg Endosc. 2015
Dec; 29(12): 3698 – 711. https://doi.10.1007/s00464-015-4140-y.
3. Boggi U, Napoli N, Costa F, Kauffmann EF, Menonna F, Iacopi, S et al. Robotic-assisted pancreatic
resections. World J Surg. 2016 Oct; 40(10): 2497 – 506. https://doi.10.1007/s00268-016-3565-3.
4. Wang SE, Shyr BU, Chen SC, Shyr YM. Comparison between robotic and open
pancreaticoduodenectomy with modi ed Blumgart pancreaticojejunostomy: a propensity scorematched study. Surgery. 2018 Dec; 164(6): 1162-7. https://doi.10.1016/j.surg.2018.06.031.
5. Myles PS, Bellomo R, Corcoran T, Forbes A, Peyton P, Story D et al. Restrictive versus liberal uid
therapy for major abdominal surgery. N Engl J Med. 2018 Jun; 378(24): 2263-74.
https://doi.10.1056/NEJMoa1801601.
6. Grant F, Brennan MF, Allen PJ, DeMatteo RP, Kingham P, D’Angelica M et al. Prospective randomized
controlled trial of liberal vs restricted perioperative uid management in patients undergoing
pancreatectomy. Ann Surg. 2016 Oct; 264(4): 591-8. https://doi.10.1097/SLA.0000000000001846.
7. Odeberg S, Ljungqvist O, Svenberg T, Gannedahl P, Bäckdahl M, von Rosen A et al. Hemodynamic
effects of pneumoperitoneum and the in uence of posture during anesthesia for laparoscopic
surgery. Acta Anesthesiol Scand. 1994 Apr; 38(3): 276 – 83. https://doi.10.1111/j.13996576.1994.tb03889.x.
8. He H, Gruartmoner G, Ince Y, van Berge Henegouwen M, Gisbertz SS, Geerts BF et al. Effect of
pneumoperitoneum and steep reverse-Trendelenburg position on mean systemic lling pressure,
venous return, and microcirculation during esophagectomy. J Thorac Dis. 2018 Jun; 10(6): 3399 –
408. https://doi.10.21037/jtd.2018.05.169.
9. Atkinson TM, Giraud GD, Togioka BM, Jones DB, Cigarroa JE. Cardiovascular and ventilatory
consequences of laparoscopic surgery. Circulation. 2017 Feb; 135(7): 700 – 10.
https://doi.10.1161/CIRCULATIONAHA.116.023262.
10. Charlson ME, Pompei P, Ales KL, MacKenzie CR. A new method of classifying prognostic comorbidity
in longitudinal studies: development and validation. J Chronic Dis. 1987; 40(5): 373 – 83.
https://doi.10.1016/0021-9681(87)90171-8.
11. Dindo D, Demartines N, Clavien PA. Classi cation of surgical complications: a new proposal with
evaluation in a cohort of 6336 patients and results of a survey. Ann Surg. 2004 Aug; 240(2): 205 –
13. https://doi.10.1097/01.sla.0000133083.54934.e.
12. Slankamenac K, Graf R, Barkun J, Puhan MA, Clavien PA. The comprehensive complication index: a
novel continuous scale to measure surgical morbidity. Ann Surg. 2013 Jul; 258(1): 1–7.
https://doi.10.1097/SLA.0b013e318296c732.
Page 23/25
13. Jammer I, Wickboldt N, Sander M, Smith A, Schultz MJ, Paolo P et al. Standards for de nitions and
use of outcome measures for clinical effectiveness research in perioperative medicine: European
Perioperative Clinical Outcome (EPCO) de nitions: a statement from the ESA-ESICM joint taskforce
on perioperative outcome measures. Eur J Anesthesiol. 2015 Feb; 32 (2): 88–105.
https://doi.10.1097/EJA.0000000000000118.
14. Kim JH, Gonzalez-Heredia R, Daskalaki D, Rashdan M, Masrur M, Giulianotti PC. Totally replaced
right hepatic artery in pancreaticoduodenectomy: is this anatomical condition a contraindication to
minimally invasive surgery? HPB (Oxford). 2016 Jul; 18(7): 580-5.
https://doi.10.1016/j.hpb.2016.04.009.
15. Jung JP, Zenati MS, Dhir M, Zureikat AM, Zeh HJ, Simmons RL et al. Use of video review to
investigate technical factors that may be associated with delayed gastric emptying after
pancreaticoduodenectomy. JAMA Surg. 2018 Oct; 153(10): 918 – 27.
https://doi.10.1001/jamasurg.2018.2089.
16. Hurwitz EE, Simon M, Vinta SR, Zehm CF, Shabot SM Minhajuddin A et al. Adding examples to the
ASA-physical status classi cation improves correct assignment to patients. Anesthesiology. 2017
Apr; 126(4): 614 – 22. https://doi.10.1097/ALN.0000000000001541.
17. Van Roessel S, Mackay TM, Van Dieren S, Van der Schelling GP, Nieuwenhuijs VB, Bosscha K et al.
Textbook outcome: nationwide analysis of a novel quality measure in pancreatic surgery. Ann Surg.
2020 Jan; 271(1): 155 – 62. https://doi.10.1097/SLA0000000000003451.
18. Bengt van Rijssen L, Groot Koerkamp B, Zwart MJ, Bonsing BA, Bosscha K, Van Dam RM et al.
Nationwide prospective audit of pancreatic surgery: design, accuracy, and outcomes of the Dutch
Pancreatic Cancer Audit. HPB (Oxford). 2017 Oct; 19(10): 919 – 26.
https://doi.10.1016/j.hpb.2017.06.010.
19. Lewis T, Merchan C, Altshuler D, Papadopoulos J. Safety of the peripheral administration of
vasopressor agents. J Intensive Care Med. 2019 Jan; 34(1): 26–33.
https://doi.10.1177/0885066616686035.
20. Tian DH, Smyth C, Keijzers G, Mackdonald SP, Peake S, Udy A et al. Safety of peripheral
administration of vasopressor medications: a systematic review. Emerg M Australas. 2020 Apr;
32(2): 220-7. https://doi.10.1111/1742-6723.13406.
21. Bannone E, Andrianello S, Marchegiani G, Masini G, Malleo G, Bassi C et al. Postoperative acute
pancreatitis following pancreaticoduodenectomy: a determinant of stula postentially driven by the
intraoperative uid management. Ann Surg. 2018 Nov; 268(5): 815 – 22.
https://doi.10.1097/SLA.0000000000002900.
22. Garland ML, Mace HS, MacCormick AD, McCluskey SA, Lightfoot N. Restrictive versus liberal uid
regimens in patients undergoing pancreaticoduodenectomy: a systematic review and meta-analysis.
J Gastrointest Surg. 2019 Jun; 23(6): 1250-65. https://doi.10.1007/s11605-018-04089-6.
23. Simões CM, Carmona MJC, Hajjar LA, Vincent JL, Landoni G, Belletti A. Predictors of major
complications after elective abdominal surgery in cancer patients. BMC Anesthesiol. 2018 May;
Page 24/25
18(1): 49. https://doi.10.1186/s12871-018-0516-6.
24. De Schryver N, Wittebole X, Hubert C, Gigot JF, Laterre PF, Castanares-Zapatero D. Early
hyperlactatemia predicts pancreatic stula after surgery. BMC Anesthesiol. 2015 Jul; 28(15): 109.
https://doi.10.1186/s12871-015-0093-x.
25. Groen JV, Khawar AAJ, Bauer PA, Bonsing BA, Martini CH, Mungroop TH et al. Meta-analysis of
epidural analgesia in patients undergoing pancreatoduodenectomy. BJS Open. 2019 Apr; 29(5):
559–571. https://doi.10.1002/bjs5.50171.
Page 25/25