Optimising postoperative care after cytoreductive surgery and hyperthermic intraperitoneal chemotherapy

Intended learning outcomes

1. Describe the common complications that may occur following cytoreductive surgery with hyperthermic intraperitoneal chemotherapy.

2. Discuss the strategies aimed at minimising and mitigating the common complications and improving postoperative recovery.

3. Describe how Enhanced Recovery After Surgery protocols can be employed following cytoreductive surgery with hyperthermic intraperitoneal chemotherapy.

4. Outline the importance of cytotoxic precautions in the perioperative period.

Clinical vignette

A 62-year-old woman was electively admitted to the postoperative high dependency unit following interval cytoreductive surgery (CRS) during which she received hyperthermic intraperitoneal chemotherapy (HIPEC) for FIGO (International Federation of Gynecology and Obstetrics) Stage IIIC high-grade serous tubo-ovarian carcinoma. Her past medical history included hypertension and hyperlipidaemia, treated with amlodipine and atorvastatin. Apixaban had been commenced for venous thromboembolism prophylaxis during neoadjuvant chemotherapy and was withheld 72 h before surgery.

She underwent an extensive debulking surgery with total abdominal hysterectomy, bilateral salpingo-oophorectomy, peritonectomy, right diaphragmatic stripping and resection, and excision of nodules from the mesentery of the small bowel, transverse colon, distal ileum and ascending colon. The debulking stage was followed by administration of hyperthermic intraperitoneal chemotherapy. The surgical time was 9.5 hours. The estimated blood loss was 1.3 litres, for which she received two units of packed red blood cels intraoperatively. The HIPEC closed technique was utilised that required temporary closure of the abdomen and a drain in each abdominal quadrant, two for input and two for output. Cisplatin 100 mg/m² was delivered to the peritoneal cavity. Sodium thiosulphate infusion was started for renal protection. The mean intra-abdominal temperature was approximately 40.8°C for 1.5 hour with a 5-minute rinsing period.

Question to be answered

What measures ought to be employed following hyperthermic intraperitoneal chemotherapy to optimise recovery and improve patient outcomes?

Discussion

Cytoreductive surgery with hyperthermic intraperitoneal chemotherapy is an increasingly utilised treatment option for metastatic ovarian malignancy with peritoneal deposits. Cisplatin hyperthermic intraperitoneal chemotherapy has been demonstrated to improve survival in patients with ovarian cancer who have responded to neoadjuvant chemotherapy [1].

Cytoreductive part of the surgery removes the macroscopic disease via laparotomy. The HIPEC stage is aimed at targeting microscopic residual disease by infusing heated chemotherapy solution into the abdominal cavity [2].

Cisplatin is highly nephrotoxic, the mechanism of which is multi-factorial. Pre-existing co-morbidities, hydration status as well as intra-operative fluid management may contribute to the nephrotoxic effect [1]. The direct nephrotoxic effect of cisplatin is caused by its accumulation within the kidney and subsequent DNA damage [1].

As is the case for a number of major surgeries, Enhanced Recovery After Surgery (ERAS) protocols should be adopted as the standard approach for gynaecological oncology surgery, including CRS with HIPEC, as evidence shows that adherence to ERAS protocols reduces hospital length of stay and minimises complications without increasing readmission or mortality rates [3]. Common complications following CRS and HIPEC include large fluid shifts, hypovolaemia, coagulopathy and massive cytokine release, resulting in systemic inflammatory response syndrome, which can mimic sepsis. Most centres have developed local protocols for the management of these patients to try to minimise complications, as well as allow early recognition and intervention when complications occur.

Following CRS and HIPEC, patients typically arrive extubated to the high dependency unit or post-anaesthesia care unit (PACU), depending on local pathways of care. The remainder of the sodium thiosulphate infusion, which will have been started in theatre for renal protection, should be completed over the subsequent 6 hours. It is thought that sodium thiosulphate offers renal protection by acting as a chelating agent and binding platinum, a central component of cisplatin, thereby reducing its renal excretion [1].

As part of ongoing effort to prevent an acute kidney injury, relative diuresis is maintained for at least the first 6 hours, whilst maintaining normovolaemia.

Prophylactic enoxaparin should be started 6 hours postoperatively, provided there are no bleeding concerns. Intrathecal diamorphine, wound infiltration with local anaesthetic and transversus abdominis plane (TAP) blocks, are generally favoured over thoracic epidural due to lower side effect profiles and complication rates [4]. Multimodal analgesia is recommended postoperatively to optimise pain control [5]; this includes patient-controlled analgesia (PCA). Pain scores should be checked at least 4-hourly. Early resumption of enteral feeding ought to be the aim. This usually begins with sips of water on day 0 and is then built up over the subsequent days. Patients should be nursed in a side room with cytotoxic precautions, which should be continued for 6 days postoperatively. Regular blood gas measurements are performed to ensure metabolic stability.

Intraoperatively, during the HIPEC phase, patients become hyperthermic, as heat is absorbed from the abdomen from the warmed chemotherapy fluid. The body temperature, therefore, should be checked hourly during the first 24 hours postoperatively. If hyperthermia ensues, cooling options include a Bair Hugger (3M Company, Bracknell, UK) on cooling mode or cool intravenous fluids.

Early formal laboratory blood testing is paramount to ensuring close monitoring for manifestations of organ injury, coagulopathy and blood loss.

Large fluid shifts and hypovolaemia secondary to surgical resection, peritoneal inflammation and altered capillary dynamics are common following this procedure. The degree of fluid shift varies depending on tumour type, disease burden and duration of surgery.

Maintaining good cardiac output and adequate organ perfusion, which is guided by both invasive and non-invasive monitoring is paramount. Most centres have recommended maintaining mean arterial pressure within 20% of the patient’s preoperative baseline [2] and keeping stroke volume variation below 10% through the appropriate administration of fluids and vasopressors [6]. There is a particular focus on patient-specific goal-directed fluid therapy for CRS and HIPEC [2, 5]. Accurate fluid balance charts are essential for early recognition of hypovolaemia. Following major abdominal surgery, patients can experience large decrements in serum albumin levels. Significant changes in albumin levels following CRS and HIPEC have been directly associated with higher rates of postoperative complications [7]. Regular IV albumin 20% is sometimes administered in the first 48 hours postoperatively; however, there is currently a lack of good outcome evidence to support this practice.

On postoperative day 1, the patients usually progress to a light diet. Pain scores should be assessed with all observations. In anticipation of increasing pain 18–24 hours following the intrathecal opioid administration, opioid optimisation and multimodal approach to analgaesia are essential. Background fluids can be continued, if required, to target a positive fluid balance. A proactive approach to early mobilisation should be adopted by the whole multidisciplinary team looking after the patient.

On postoperative day 2 following HIPEC, cytokine release typically occurs and can cause systemic inflammatory response syndrome and significant vasodilation, which can mimic sepsis [2]. Patients can become tachycardic, febrile and hypotensive, often requiring a period of vasopressor support. If pyrexia occurs, a full septic screen should be taken to rule out infection.

Coagulopathy can develop early postoperatively. Its mechanism is poorly understood, but it is thought to be a combination of consumption and the dilution of coagulation factors. Risk factors include tumour type, e.g. mesothelioma and pseudomyxoma peritonei (PMP), specific procedures, e.g. deep pelvic surgery or liver capsulectomy, and prolonged surgical time [2]. Coagulation studies should be performed at least 12-hourly for the first 48 hours during the postoperative period.

The timing of ward step down is guided by the clinical condition of the patient and the availability of a side room, whilst cytotoxic precautions are in place. By postoperative day 3, most patients will have typically progressed to a light diet and should be encouraged to mobilise as much as possible. If pain is well controlled, proactive approach to reducing opiates should focus on introducing short acting oral opiates in favour of PCA, with regular pain scoring to monitor effects of changes to the analgaesic regime.

Cytotoxic agents pose risks to the operating theatre team and wider clinical team involved in patient care. Personal protective equipment must be used. Cytotoxic agents may remain in body fluids for between one and seven days [2], hence the need for cytotoxic precautions to continue postoperatively, with the patient nursed in a side room. All fluids (urine, drain effluents, blood) should be disposed of in designated cytotoxic fluid bins. A chemotherapy spillage kit should be available in the unit whilst cytotoxic precautions are in place. Due to the risk of teratogenicity posed by cytotoxic agents, pregnant as well as breastfeeding staff members should not be involved in direct care of these patients during the period when cytotoxic precautions are indicated [8].

Conclusion

Cytoreductive surgery with hyperthermic intraperitoneal chemotherapy carries significant perioperative challenges. Adherence to ERAS protocols, goal-directed fluid management, vigilant monitoring and multidisciplinary care is essential to optimise recovery and reduce complications postoperatively.

Declarations and conflicts of interest

Artificial intelligence declaration

No AI tools were used in the writing or development of the manuscript.