Background
Over the last two decades, cytoreductive surgery combined with hyperthermic intraoperative chemotherapy (CRS/HIPEC) has become a therapeutic option for selected patients with peritoneal carcinomatosis [
1]. Traditionally, peritoneal carcinomatosis was considered a palliative incurable condition [
2]. Sugarbaker [
3], however, first described that some of these patients may benefit from the surgical removal of all macroscopic tumor, combined with locoregional chemotherapy [
3]. Since then, CRS/HIPEC has increasingly been used to treat patients with peritoneal carcinomatosis of different origin [
4‐
11].
Strict patient selection is crucial and meticulous surgical tumor removal is mandatory for the best clinical outcome [
9,
12‐
14]. Thereby, longterm survival with good quality of life is feasible [
15]. As there is a learning curve when performing CRS/HIPEC, centralization of the procedure to specialized institutions is recommended [
16]. Regarding anaesthesia management and perioperative care, experience is limited and a consensus has yet to be found [
17]. Several authors have shown major changes in body temperature and hemodynamics, alterations in the composition of the blood as well as need for massive transfusion [
18‐
21].
The aim of our study was to retrospectively analyze anaesthesia management and postoperative course of patients undergoing CRS/HIPEC over a 3-year period since introduction of this combined technique at the University Hospital Zurich.
Discussion
Data on anaesthesia management and the outcome of 57 consecutive patients undergoing combined CRS/HIPEC were retrospectively collected and analyzed at our hospital. In addition to the individual surgical complexity, we have shown that several factors may affect patients’ outcome, such as the type and amount of resuscitation fluids used, as well as blood transfusions.
Cytoreductive surgery with HIPEC is a long-lasting, abdominal surgical procedure (median anaesthesia time 715 minutes) with additional hyperthermia and intraoperative chemotherapy. Extensive bleeding and fluid shifts may occur. Therefore, fluid status and cardiac function were continuously assessed with advanced hemodynamic monitoring in most of our patients.
Currently the type and amount of fluid administration is subject to debate [
26‐
28]. Our fluid management consisted of both crystalloids and colloids. In addition to crystalloids, 51 patients received gelatine and 14 were also given HES, in a ratio of approximately 2.5:1. At the time of observation, studies on the potentially harmful effects of HES preparations in septic ICU patients had not yet been published [
29,
30]. Our data are in accordance with these publications: HES administration had a significant negative impact on renal function, especially in younger patients.
Maintaining renal function and prevention of injury is critical for obtaining the best perioperative outcome [
31]. Known risk factors for acute renal injury are hypovolemia, hypotension, major surgery, nephrotoxic drugs, blood transfusions, and systemic inflammation [
32]. Hemodynamic optimization (optimizing cardiac output, tissue perfusion, and oxygenation) is highly recommended to prevent renal injury. The goal is to maintain the effective circulating blood volume by careful fluid and transfusion management, vasopressors, and inotropes [
33]. Most authors recommend liberal fluid regimens [
14,
18,
34]. Our patients received approximately 10 ml kg
−1 hr
−1 of fluids and lost 3 ml kg
−1 hr
−1 (Additional file
3: Table
3). The amount of fluids given was guided by hemodynamic parameters, blood gas analyses, and urinary output. Most patients were given vasopressors to maintain MAP and, although the benefit of its application is questionable, 35 patients were given IV diuretics to force diuresis during HIPEC [
33]. In fact, there is no evidence that a single pharmacological intervention during surgery protects the kidneys from damage [
31,
35].
Our data suggests that the need for a blood transfusion is associated with an increased risk for major complications (grade ≥3b according to the Clavien-Dindo classification [
22]). The amount of bleeding showed a trend towards major complications (
P = 0.05). It is standard procedure for both the surgical and the anaesthesia team to assess and estimate blood loss at the end of surgery. However, differences between both estimates result in inconsistent documentation. Alternatively, the decrease in hemoglobin concentration can be used as an indicator for blood loss. Both methods are widely used in clinics but are known to be of limited accuracy, tending to underestimate actual blood loss [
36]. For future studies it might be useful to refer to a superior, validated blood loss score, taking into account the hemoglobin concentration of suction fluid [
36].
Exposure to blood transfusions is associated with an increased morbidity and mortality in surgical oncology [
37,
38]. It is therefore critical to control surgical bleeding and to diagnose and correct coagulopathy early. Goal-directed, aggressive treatment using algorithms and point-of-care coagulation testing is recommended [
37]. In our study, 28% of patients required intraoperative blood transfusions and 37% of patients were given coagulation factor concentrates. In contrast to other centers, routine FFP administration is not the first-line treatment for established coagulopathy at our institution [
17]. Only 5% of patients received FFPs compared to 45% described in the literature [
17,
18]. The pathophysiology of coagulopathy in patients undergoing CRS/HIPEC is not completely understood [
14,
17]. Besides bleeding, consumption, and dilution, patients are exposed to extreme changes in body temperature (both hypo- and hyperthermia), suffer from metabolic acidosis, and calcium depletion (40% of our patients required calcium supplementation).
The use of TEA is recommended for patients undergoing CRS/HIPEC to provide optimal pain therapy, to reduce length of postoperative ventilation and pulmonary complications, and to allow for early mobilization (getting people moving as soon as possible) [
14,
34]. Critics underline the potential risk of hemodynamic instability, epidural hematoma, and infectious complications due to massive bleeding, impaired coagulation, and chemotherapy-induced immunodeficiency [
39‐
41]. Recently an incidence ratio for infectious complications of 1:2139 has been reported [
17]. One of our patients suffered from an epidural abscess with the need for an operative decompression seven days after placement. To prevent infections we recommend to limit the postoperative use of epidural analgesia to a maximum of five days and to visit patients with TEA daily. Despite the frequent use of TEA, only 28% of CRS/HIPEC centers describe their pain management as excellent [
17]. Most of our patients received TEA for intra- and post-operative analgesia, and we found a significant opiod-sparing effect. However, unlike previous publications, we could not show that TEA was associated with a reduced length of postoperative ventilation and ICU stay, nor shortened time to first bowel passage [
18].
The present observational study has some limitations. The anaesthesia management of patients did not follow strict protocols and there were no predefined exclusion criteria for the study. Furthermore, data were collected retrospectively and some data were missing due to absent documentation, compromising data analysis and reducing power of statistical conclusions.
Competing interests
The authors declare that they have no competing interests.
Authors’ contributions
MTG initiated, planned and designed the study. MTG and MEK obtained ethic committee approval. MEK was responsible for data collection and analysis. RK and UH performed statistical analyses and revised the manuscript. KL was involved in data acquisition and patient recruitment. MEK wrote the first draft of the paper. MTG and BBS revised the manuscript. All authors have read and approved the final manuscript.