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HIPEC (Hyperthermic Intraperitoneal Chemotherapy) & Cytoreductive Surgery (CRS)

Key points summarized from Dr. Healey Shulman's Grand Rounds presentation (Nov 1, 2024). Dr. Awad and Dr. Maclean have also provided very helpful practical pointers.

Indications

HIPEC is indicated for the treatment of certain peritoneal surface malignancies:
  • Peritoneal carcinomatosis: secondary to cancers of the stomach, colorectal, ovary, and cervix.
  • Pseudomyxoma peritonei
  • Malignant peritoneal mesothelioma
  • Sarcoma of the peritoneum.
  • Adjunct for palliative managing uncontrolled malignant ascites.
Historically, peritoneal malignancies were considered incurable and only suitable for palliation. The goal of HIPEC combined with CRS is curative for certain peritoneal surface malignancies. CRS is to surgically remove all visible tumor mass, while HIPEC aims to eradicate any remaining microscopic disease.
The heated chemotherapy solution (usually between 40°C - 43°C) is intended to increase the penetration of the chemotherapy drugs into tumor tissue. Delivering chemotherapy directly to the peritoneal cavity allows for higher local concentrations of the drug, while limiting its systemic absorption / toxicity. Heat also enhances the cytotoxicity of the chemotherapy.
Nonetheless, CRS and HIPEC still represent a radical treatment modality with high perioperative morbidity and mortality. Appropriate patient selection is key to a successful outcome. Patients should have a good baseline health / functional status / nutritional status without significant cardiac or respiratory disease and ideally be under 70 years of age. The tumor should be confined to the abdominal cavity and the patient should have no disease progression on chemotherapy.
Surgical team also looks at tumor characteristics (load, organs involved, histopathology) during patients selection. 
At Sunnybrook, HIPEC is done in OR 5 for Gynecologic Oncology service.

Anesthetic Managements

Overarching

goals

are

to

maintain

hemodynamic

stability,

optimize organ perfusion, manage temperature fluctuations, and provide adequate analgesia, while also considering the potential side effects of chemotherapeutic agents.
Preoperative Assessment and Optimization:
  • Baseline cardiac, respiratory, and renal function, as well as nutritional status
  • Patients with ascites / pleural effusions may have compromised respiratory function, requiring assessment and management
  • Nutritional status should be evaluated, including albumin levels and any signs of sarcopenia
  • Preoperative labs CBC, extended electrolytes, renal function, LFTs, coagulation profile, G&S
  • Minimize nephrotoxins preoperatively, including NSAIDs and certain antibiotics
Intraoperative Management:
  • Hemodynamic Monitoring and Fluid Management
    • Large bore IVs & arterial line, central venous access in selected cases
    • The initial CRS phase involves significant fluid loss due to evaporative losses from exposed tissue and ascitic fluid drainage & potential significant blood loss
    • The HIPEC phase can cause further fluid shifts due to peritoneal inflammation
    • Goal directed fluid therapy to maintain euvolemia, optimize cardiac output and organ perfusion
    • Hemodynamics during HIPEC Phase:
      • Hyperdynamic State: hypermetabolic state due to the increased body temperature from the heated chemotherapeutic solution leading to an increase in heart rate, central venous pressure (CVP), and cardiac index (CI)
      • Vasodilation and Decreased Systemic Vascular Resistance (SVR): hyperthermia during HIPEC causes peripheral vasodilation, leading to a decrease in SVR and mean arterial pressure (MAP)
      • Increased Cardiac Output: The increase in heart rate is a compensatory response to the decreased SVR, aimed at maintaining cardiac output
      • Reduced Venous Return: The increased intra-abdominal pressure from the chemotherapeutic solution and the surgical procedure can decrease venous return, which may further exacerbate hemodynamic instability. The filling of the abdomen with saline and chemotherapy during the closed technique of HIPEC has a similar effect to a pneumoperitoneum, raising intra-abdominal pressure
      • Potential for Myocardial Dysfunction The use of certain chemotherapeutic agents during HIPEC, such as intraperitoneal cisplatin, may cause cardiac toxicity and arrhythmias
      • Vasopressor may be necessary to maintain adequate MAP, particularly during the vasodilatory phase of HIPEC
      • Patients with poor cardiac reserve may require inotropic support to improve cardiac output and maintain tissue perfusion
    • Urine output particularly important during the HIPEC phase due to the potential nephrotoxic effects of chemotherapeutic drugs and hyperthermia
      • During cytoreduction (CRS): A minimum urine output of 0.5 mL/kg/hr
      • During HIPEC: The target urine output increases to 2-4 mL/kg/hr to ensure adequate renal perfusion and to help flush out nephrotoxic agents. Some sources recommend an even higher rate of at least 100 mL every 15 minutes
      • Post-HIPEC: The target urine output is reduced to 1-2 mL/kg/hr to maintain adequate perfusion and prevent fluid overload
  • Temperature Management
    • Patients are at risk of hypothermia during the CRS phase due to large surgical exposure and fluid losses. Thus, active warming measures i.e. forced-air warmers and fluid warmer
    • During the HIPEC phase, patients are at risk of hyperthermia (increases the body's metabolic rate, leading to increased oxygen demand, heart rate, and end-tidal CO2 levels, metabolic acidosis) due to the heated chemotherapy solution. Nasopharyngeal temperature probe and additional probes in the abdominal cavity, in the inlet and outlet drains of the HIPEC machine are used
    • The core body temperature during HIPEC is to be kept below 39°C. Some sources specify a range of 37–38.8 °C as an appropriate target. Turn forced air blanket to cool, turn off fluid warmer and apply cold head wrap if needed
    • Intraperitoneal Temperature: The temperature of the chemotherapeutic perfusate within the abdominal cavity should be maintained between 41–43°C  to optimize the cytotoxic effect of the chemotherapy
    • The heat exchanger on the HIPEC machine maintains the infusate temperature at 44–46°C at the machine level to ensure the intraperitoneal temperature remains within the 41–43°C range
  • Analgesia:These procedures typically require large incisions and extensive tissue manipulation, causing significant pain [33-35].
  • Thoracic epidural analgesia is often used for perioperative pain management, as it can reduce the need for intravenous opioids and improve bowel function [33, 34, 36, 37].
  • Epidural infusions of local anesthetics and opioids may be administered for an extended period of 5-7 days [33, 37].
  • Multimodal analgesia is recommended, including the use of intravenous opioids, regional blocks, and non-opioid analgesics, such as acetaminophen [7, 37, 38].
  • Coagulation Management:Patients are at risk of coagulopathy due to blood loss, surgical trauma, and the effects of hyperthermia and chemotherapeutic agents [21, 39-41].
  • Coagulation abnormalities may range from a decrease in platelet count to prolongation of prothrombin time [39].
  • Close monitoring of coagulation parameters, such as platelet count, prothrombin time, and international normalized ratio (INR), is needed [13, 39].
  • Transfusion of blood products, such as fresh frozen plasma, may be necessary [42].
  • The placement and removal of epidural catheters should be coordinated with the coagulation status of the patient [43].
  • Respiratory Management:Patients may have decreased functional residual capacity (FRC) due to increased intra-abdominal pressure, predisposing them to rapid oxygen desaturation [44].
  • Adequate preoxygenation and a rapid sequence induction may be needed, especially in patients with ascites [44].
  • Ventilator strategies may include smaller tidal volumes and positive end-expiratory pressure (PEEP), with recruitment maneuvers [44].
  • During the HIPEC phase, increased airway pressures may occur due to cephalad displacement of the diaphragm, which usually reverses partially after the completion of HIPEC and evacuation of the peritoneal instillate [22, 44].
  • Chemotherapy Considerations:The chemotherapeutic agents used in HIPEC can have various systemic side effects, including nephrotoxicity, cardiotoxicity, myelosuppression, and electrolyte imbalances [1, 4, 26, 45, 46].
  • Close monitoring of electrolytes, glucose, and acid-base balance is necessary during and after HIPEC [26, 47, 48].
  • Awareness of the specific side effects of the chemotherapeutic agents used (such as cisplatin, oxaliplatin, mitomycin C, doxorubicin) is important for the anesthesiologist [45, 49, 50].
  • Some agents may cause hyponatremia, hypomagnesemia, and lactic acidosis [26, 51].
  • Surgical Considerations:
  • Open abdomen or 'Coliseum' technique for HIPEC is recommended when a preoperative evaluation reveals a reduction in FRC with altered pulmonary function tests [44].
  • The open abdomen technique can reduce intra-abdominal pressures but may lead to increased heat loss and potential for drug spillage [52, 53].
  • A closed abdomen technique minimizes drug spillage and increases drug penetration but may not achieve homogenous drug distribution [52, 53].
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