Peritoneal surface malignancies (PSMs) are generally considered the terminal stage of a tumor disease with very poor prognosis. Patients with gynecological and gastrointestinal (GI) tract malignancies, in whom the disease progresses to peritoneal carcinomatosis, experience significant drop in their quality of life, high morbidity, and short survival. The current standard of care (SoC) of people with peritoneal metastases from these cancers is systemic chemotherapy alone or combination with either cytoreductive surgery (CRS) or palliative surgery. CRS + hyperthermic intraoperative peritoneal chemotherapy (HIPEC) is an alternative treatment. The main principle of CRS + HIPEC is to remove all visible (macroscopic) peritoneal metastases followed by HIPEC to treat any remaining microscopic peritoneal metastases. HIPEC involves peritoneal circulation of chemotherapy drugs (usually mitomycin C, 5-fluorouracil, and oxaliplatin or cisplatin) heated to temperatures of 42°C, at which the chemotherapy drugs are potentiated. The surgery involves blood loss, significant fluid mobilization, deterioration of gaseous exchanges, metabolic changes, body temperature changes, and coagulation disorders that must be promptly identified and managed by the anesthesiologists in the intraoperative period.
Our patient is a 52-year-old female without any comorbidities. She underwent transverse colectomy, omentectomy and colocolic anastomosis for primary CA colon one year ago. She presented with secondary metastasis to the peritoneum and ovary (mucinous adenocarcinoma) and underwent CRS and HIPEC, under general anesthesia combined with epidural block.
After thorough pre-anesthetic evaluation and obtaining a written and informed consent, the patient was posted for CRS + HIPEC. She was shifted to the operating room after confirming adequate starvation status. She was conscious, oriented, and had normal breathing. The patient was monitored using an electrocardiogram, a non-invasive blood pressure, and pulse oximetry. IV access was secured with two large bore 18 g cannulas in both the upper limbs. An epidural catheter was placed at T0-11 interspace for intraoperative and postoperative analgesia. A balanced general anesthesia was induced with 100 mcg of fentanyl, 100 mg of propofol, and 6 mg of vecuronium and the patient was intubated with standard single lumen tube. The monitoring was complemented with nasopharyngeal thermometer, invasive arterial pressure monitoring, and central venous access; isoflurane at 1% was started. Antibiotic prophylaxis was given before the surgical incision.
Successive blood gas analyses were done in the intraoperative period for the correction of metabolic disorders and electrolyte disturbances. Volume replacement was done with 5500 ml of crystalloids, two units of red blood cell concentrate (vol. 500 ml) and four units of FFP (vol. 600 ml). A replenishment of calcium with 10% of calcium gluconate and blood sugar monitoring at regular intervals were done for proper glycemic control. All the warming devices were stopped about 45 minutes prior to the commencement of HIPEC. Total duration of the HIPEC phase was 90 minutes. Optimum body temperature was maintained by administration of cold saline and use of ice packs. Body temperature ranged between 34.5°C and 36.9°C and the patient maintained moderate metabolic acidosis during the intraoperative period (pH 7.3–7.21). Urine output at the end of the procedure was 1400 ml.
Intraoperative period was uneventful and the patient was extubated at the end of the procedure. The patient was shifted to the intensive care unit (ICU) without any ongoing vasopressor support but with a complaint of mild pain in the abdominal region.
The patient was electively put on high-flow nasal oxygen for the first six hours postoperatively. She had an uneventful stay in the ICU and was shifted to ward on postoperative day (POD) 3.
CRS + HIPEC is being increasingly performed around the world. But it comes as a huge challenge for the anesthesiologist because patients are submitted to a long surgical procedure with an extensive surgical incision and great loss of fluids.
The acute changes in body temperature associated with an increased intra-abdominal pressure by the administration of the chemotherapeutic fluid (3 to 5 l of solution at 42°C) can promote severe hemodynamic disorders, with increased cardiac output, a reduction of systemic vascular resistance, and an increase in the cardiac index and end tidal carbon dioxide (EtCO2). The maintenance of a proper pre-loading during such intraoperative changes requires a more liberal volume replacement rate—between 1220 ml/h and 1770 ml/h—which enables the provision of an effective circulatory volume despite the reduced systemic vascular resistance and the peripheral vasodilation caused by the increase in temperature because of the chemotherapeutic infusion.
It is also important to consider the nephrotoxicity of the chemotherapeutic agents being used and the need to prevent renal injury. This makes an average diuresis rate of at least 2–3 ml/kg/h desirable during the HIPEC phase. Administration of low doses of furosemide and dopamine are also recommended.
The increase in body temperature also leads to metabolic acidosis and elevation in the serum lactate levels, which was observed in our patient.
The development of coagulation disorders is frequent. Coagulopathy following CRS depends on the duration of surgery, extent of resection, blood loss, and degree of hemodilution which in turn depends on the volume of replacement with crystalloids and colloids, transfusion of packed red cells, and hypothermia. Coagulopathy peaks at 24 h and may persist up to 72 h in the postoperative period. Intraoperative monitoring of coagulation parameters periodically depending on the volume of estimated blood loss is advisable.
Surgical patients are subject to stress hyperglycemia; a good intraoperative glycemic control is therefore recommended. A blood sugar level of 140–180 mg/dl are recommended by the Normoglycemia in Intensive Care Evaluation–Survival Using Glucose Algorithm Regulation (NICE-SUGAR) trial. The intravenous administration of insulin has a more predictable absorption when compared to the subcutaneous use, and it enables faster adjustments with a more accurate glycemic control.
For pain management, intraoperative use of epidural analgesia using local anesthetic agents with or without opioids is frequently done to decrease intraoperative systemic opioid requirement and reducing the need for prolonged mechanical ventilation.
CRS + HIPEC, although a promising alternative in the treatment of primary peritoneal malignancy and malignant neoplasms of gastrointestinal and gynecological origin with peritoneal metastases, is a complex surgery and perioperative management depends on many factors including patient's preoperative health status, disease load, surgical factors, intraoperative events, and chemotherapeutic drugs used for HIPEC; it brings numerous challenges to anesthesiologists.
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The authors certify that they have obtained all appropriate patient consent forms. In the form, the patient has given her consent for her images and other clinical information to be reported in the journal. The patient understands that her name and initials will not be published and due efforts will be made to conceal identity, but anonymity cannot be guaranteed.
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