Cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) has emerged as an acceptable treatment modality for patients with peritoneal surface malignancies. This combined treatment can be considered standard of care for pseudomyxoma peritonei (PMP) and peritoneal mesothelioma, as well as for select patients with peritoneal metastasis from colorectal and advanced epithelial ovarian cancers.1,2 Since the late-1990s, this treatment modality has grown in practice significantly throughout the U.S.3
In addition to the normal physiologic responses after CRS, administration of intra-abdominal chemotherapy and patient hyperthermia lead to myriad biologic responses, including exaggerated fluid and electrolyte shifts, hemodynamic derangements, bone marrow suppression, and inhibited wound healing.4,5 Consequently, HIPEC procedures traditionally have resulted in high rates of postoperative complications.6-8 Contemporary approaches to perioperative care have included liberal use of intravenous fluids to mitigate against chemotherapy-induced nephrotoxicity, routine use of feeding/nasogastric tubes for anticipated ileus, delayed feeding, transabdominal drains, and use of intensive care units—all associated with prolonged lengths of stay.9-12
The Mayo Clinic in Arizona, Phoenix, implemented the HIPEC program in 2010. Morbidity, mortality, and length of stay (LOS) were carefully monitored from the outset. The research team prospectively maintained a database of patients undergoing HIPEC as part of a quality monitoring and improvement initiative. Our initial experience of 49 cases had an overall complication rate of 63 percent with a grade III/IV complication rate of 24 percent. The mean LOS was 10.3 ± 8.9 days, the rate of unplanned surgical intervention was 12 percent, and the rate of 30-day readmission was 16 percent. The surgical oncology group decided to implement an Enhanced Recovery After Surgery (ERAS) program for patients undergoing HIPEC to try to improve on these outcomes.
Implementing the initiative
The Mayo Clinic in Arizona is a 270-bed hospital with 21 operating rooms (ORs). The hospital started operations in 1998 and employs close to 6,000 people. The institution focuses heavily on quality of care and achieving value-based care. Employees have the option of becoming bronze-, silver-, or gold-certified in quality by participating in quality initiatives and projects within their clinical realm. The hospital already has a robust ERAS program in place for colorectal operations, which facilitated implementation of a new program.
The author identified major stakeholders in the HIPEC practice, partnering with anesthesiologists, nursing staff, OR pharmacists, perfusion staff, allied health staff, and general surgery residents. A review of the literature related to perioperative management of patients undergoing CRS and HIPEC was undertaken to identify areas of intervention. Traditional management of HIPEC patients involves large-volume resuscitation, prolonged durations of no peroral intake, and liberal use of narcotic pain medicines. These patients have high rates of morbidity and mortality and prolonged LOS leading to significant use of hospital resources and costs of care.
A literature review yielded no prior studies on implementation of ERAS principles in HIPEC patients, so our team developed interventions that we believed would be safe and efficacious based on published literature on implementation of ERAS principles in patients undergoing colon surgery.13 The physician lead discussed relevant interventions with each stakeholder. Changes to practice were clearly outlined, and written protocols were disseminated and placed on the institutional Intranet for access. Buy-in was not an issue as ERAS pathways were well established in the institution, and all participants appreciated the opportunity to potentially reduce morbidity, mortality, and LOS in HIPEC patients.
Implementing the quality improvement activity
Table 1 outlines the major interventions made following implementation of an ERAS pathway in patients undergoing CRS and HIPEC at our institution. Traditional management prior to implementation also is shown for purposes of comparison. Our program was launched over several months in early 2016.
Only one surgeon at Mayo Clinic in Arizona performs CRS and HIPEC procedures, and he served as the project lead. Two anesthesiologists served as the leads for the institution’s other ERAS programs and were responsible for training related to preoperative performance of transversus abdominus plane (TAP) blocks under ultrasound guidance. No additional costs were incurred beyond the normal operating expenses associated with clinical care of these patients, and no dedicated funding was required for the project.
Table 1. Implemented ERAS principles vs. traditional perioperative management
Our study population consisted of 130 CRS and HIPEC procedures, 49 (38 percent) in the pre-ERAS group, and 81 (62 percent) in the post-ERAS group. There was no significant difference in mean Peritoneal Cancer Index, operating time, and patient demographics between both groups. Our primary outcome measure was 30-day morbidity and mortality. Secondary outcome metrics were LOS, 30-day rates of unplanned readmission and reoperation, and rates of acute kidney injury (see Figure 1).
Figure 1. Outcomes comparison, pre-ERAS vs. ERAS
Only one patient in the cohort in the ERAS cohort (0.8 percent) died, secondary to respiratory failure. After implementation of ERAS, the rate of serious grade III/IV complications decreased from 24 percent to 15 percent, p = 0.243. The rate of all grade I–IV complications fell from 63 percent pre-ERAS to 37 percent post-ERAS, p = 0.004.
Length of hospital stay decreased significantly from a mean of 10.3 ± 8.9 days in the pre-ERAS group to 6.9 ± 5.0 days in the ERAS group (p = 0.007). Rates of 30-day readmission and acute kidney injury did not change significantly. Total opioid use measured in oral morphine equivalents decreased from a median of 272.6 to 159.7 mg, a difference that was statistically significant in the open but not the laparoscopic group. Net total hospital fluid balance decreased from a mean of 6.07 ± 16.8 liters to 3.00 ± 6.3 liters. On multivariable analyses implementation of an ERAS program was associated with a reduction in LOS (β = –2.89 days, 95 percent CI –0.94 to –4.84) and a reduction in complications (OR 0.22, 95 percent CI 0.08-0.57).
A formal cost analysis was not conducted, but as a ballpark estimate, reduction in mean LOS from 10 to seven days results in savings of $9,095 per HIPEC case.
The team encountered no significant barriers related to implementation, which may be attributable to the small size of the team involved and the fact that there was no significant variation in practice, as only one surgeon performed these procedures. Furthermore, a robust ERAS program for colorectal surgery was already in place at our institution so that existing clinical pathways and electronic health record order sets were easily customizable to suit our needs. The most technical aspect of our program—the TAP blocks—required little training as they already were being used by the anesthesiologists on the team.
A formal cost analysis was not conducted, but one is in development. As a ballpark estimate, we cut our mean LOS from 10 to seven days. The average cost for a one-day stay in an Arizona not-for-profit hospital is $2,675,14 which translates to an average savings of $9,095 per CRS and HIPEC performed. This estimate does not take into account the 38 percent reduction in complication rates.
Tips for others
Other institutions interested in conducting similar quality improvement programs are advised to do the following:
- Sell the ERAS project to the C-suite as a quality improvement project with potential for significant cost savings and decreased resource utilization.
- Find a physician lead who is motivated and invested in taking care of this group of patients.
- Keep the core implementation team small, with one representative from each stakeholder.
- Start with interventions that can be easily implemented and do not require additional training, such as decreasing intraoperative and postoperative fluids.
- Move on to more difficult interventions after successful baseline implementation, such as administering intraoperative TAP blocks.
- Monitor outcomes closely and implement or maintain a database.
- Develop and disseminate a patient information booklet setting expectations early. Most patients will obtain outdated or incorrect information off the Internet.
- O’Dwyer S, Verwaal VJ, Sugarbaker PH. Evolution of treatments for peritoneal metastases from colorectal cancer. J Clin Oncol. 2015;33(18):2122-2123.
- Van Driel WJ, Koole SN, Sikorska K, et al. Hyperthermic intraperitoneal chemotherapy in ovarian cancer. N Engl J Med. 2018;378(3):230-240.
- Dehal A, Smith JJ, Nash GM. Cytoreductive surgery and intraperitoneal chemotherapy: An evidence-based review-past, present and future. J Gastrointestinal Oncol. 2016;7(1):143-157.
- Webb CA, Weyker PD, Moitra VK, Raker RK. An overview of cytoreductive surgery and hyperthermic intraperitoneal chemoperfusion for the anesthesiologist. Anesth Analg. 2013;116(4):924-931.
- Sheshadri DB, Chakravarthy MR. Anaesthetic considerations in the perioperative management of cytoreductive surgery and hyperthermic intraperitoneal chemotherapy. Indian J Surg Oncol. 2016;7(2):236-243.
- Votanopoulos KI, Russell G, Randle RW, Shen P, Stewart JH, Levine EA. Peritoneal surface disease (PSD) from appendiceal cancer treated with cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC): Overview of 481 cases. Ann Surg Oncol. 2015;22(4):1274-1279.
- Chua TC, Yan TD, Smigielski ME, et al. Long-term survival in patients with pseudomyxoma peritonei treated with cytoreductive surgery and perioperative intraperitoneal chemotherapy: 10 years of experience from a single institution. Ann Surg Oncol. 2009;16(7):1903-1911.
- Sugarbaker PH. Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy in the management of gastrointestinal cancers with peritoneal metastases: Progress toward a new standard of care. Cancer Treat Rev. 2016;48(7):42-49.
- Bell JC, Rylah BG, Chambers RW, Peet H, Mohamed F, Moran BJ. Perioperative management of patients undergoing cytoreductive surgery combined with heated intraperitoneal chemotherapy for peritoneal surface malignancy: A multi-institutional experience. Ann Surg Oncol. 2012;19(13):4244-4251.
- Colantonio L, Claroni C, Fabrizi L, et al. A randomized trial of goal directed vs. standard fluid therapy in cytoreductive surgery with hyperthermic intraperitoneal chemotherapy. J Gastrointest Surg. 2015;19(4):722-729.
- Dineen SP, Robinson KA, Roland CL, et al. Feeding tube placement during cytoreductive surgery and heated intraperitoneal chemotherapy does not improve postoperative nutrition and is associated with longer length of stay and higher readmission rates. J Surg Res. 2016;200(1):158-163.
- Cooksley TJ, Haji-Michael P. Postoperative critical care management of patients undergoing cytoreductive surgery and heated intraperitoneal chemotherapy (HIPEC). World J Surg Oncol. 2011;9(1):169.
- Ljungqvist O, Scott M, Fearon KC. Enhanced Recovery After Surgery: A review. JAMA Surg. 2017;152(3):292-298.
- Ellison A. Average hospital expenses per inpatient day across 50 states. January 4, 2019. Becker’s Hospital Review. Available at: www.beckershospitalreview.com/finance/average-hospital-expenses-per-inpatient-day-across-50-states.html. Accessed November 4, 2019.