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 fluid 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 influences 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 classifications [16]. ASA scores in our series are however in concordance with recent findings 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 finding, 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 influence on postoperative morbidity (e.g. increased BMI, vascular remodeling or pre-existing renal insufficiency).
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 reflected 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 fluid strategies during major abdominal surgery, differentiating between an either restrictive (median crystalloid + colloid 2177) or liberal (median crystalloid + colloid 3500 ml) net intraoperative fluid balance [5]. Whereas no differences were observed in general postoperative outcome between both fluid approaches, a liberal intraoperative fluid 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 fluid 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 fluid regime, suggesting a more restrictive perioperative fluid balance to be associated with an increased risk of postoperative pancreatic fistula [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 fluid strategy [22]. The optimal intraoperative fluid 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 finding 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, 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 reflect 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 reflect 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 fistula [24]. Average postoperative pain scores during the first postoperative day were higher in RAPD compared to OPD. The reported first 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.