Hyperthermic intraperitoneal chemotherapy surgery

Hyperthermic intraperitoneal chemotherapy surgery

Anesthesia type	General
Airway	ETT
Lines and access	Large bore IV x2 Arterial line Central line NG tube
Monitors	Standard 5-lead ECG ABP
Primary anesthetic considerations
Preoperative	Baseline renal function Electrolyte status Anemia Prehabilitation Nutrition optimization
Intraoperative	Hemodynamic monitoring Active fluid resuscitation Normothermia or mild hypothermia Pre-HIPEC electrolytes HIPEC-phase electrolytes
Postoperative	Maintain urine output Consider ICU admission Prolonged vasoplegia Sodium thiosulfate infusion (12 hrs)
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Hyperthermic intraperitoneal chemotherapy surgery (HIPEC) and cytoreductive surgery is a combined procedure utilized to treat peritoneal surface cancers. These cancers include secondary peritoneal carcinomatosis, pseudomyxoma peritonei and primary peritoneal tumors.  Cytoreductive surgery involves debulking the majority of tumors until the remainder are small enough to ensure adequate efficacy with HIPEC.

HIPEC involves infusing heated cytotoxic chemotherapeutic drugs directly into the surgical site in order to effectively penetrate involved cancer while limiting exposure to normal tissue and decrease systemic uptake. This may be performed in a closed abdomen via perfusion circuit or an open abdomen +/- cavity expanders (sometimes referred to as the Coliseum technique).  Compared to a closed abdomen approach, an open abdomen technique may reduce intraabdominal pressures and prevent reuse of the cytotoxic solution.  However, the closed abdomen technique reduces risk of exposure of the medications to the OR staff.

Important perioperative considerations include temperature management, cardiovascular management, intra-abdominal pressures, metabolic derangements (depending on carrier solution of chemotherapeutic agent), potential chemotherapeutic toxicities (see table below), coagulopathy, fluid/renal management and pain management.

Although HIPEC surgery is generally safe to participate in as an anesthesia provider, intraoperative OR staff may be exposed to cytotoxic agents due to high concentrations of chemotherapeutic medications, long case duration,  and smoke and or mechanical exposure. Pregnant or those actively planning for pregnancy, those with a history of congenital malformations or abortions should carefully consider participation in HIPEC cases. Safety precautions including high-power filtration masks, eye protection, gloves, and standard universal precautions should always be heeded.

Preoperative management

Cytotoxic Agents

Chemotherapeutic agent	End-organ toxicity
Platinum (cisplatin/oxaliplatin)	Nephrotoxicity (hypomagnesemia/hypocalemia) Nausea/Vomiting Neurotoxicity (Peripheral neuropathy, seizure, ototoxcity, blindness) Myelosupression Anaphylaxis
Mitomycin C (MMC)	Myelosupression Pulmonary/interstitial pneumonitis nausea/vomiting/diarrhea cardiomyopathy hemolytic uremic syndrome
5-Fluropyrimidines	GI ulcers myelosuppression rashes, keratitis, ataxia, cognitive dysfunction coronary spasm biliary sclerosis
Anthracyclines (doxorubicin)	Myelosuppression GI mucositis Cardiomyopathy

Patient evaluation

System	Considerations
Neurologic	Neurologic dysfunction risk based upon chemotherapy agents used
Cardiovascular	Cardiomyopathy risk based upon chemotherapy agents used
Pulmonary	Pneumonitis based upon chemotherapy agents used
Gastrointestinal	Hypoalbuminemia associated with higher major mobidity
Hematologic	Risk of profound anemia
Renal	Renal dysfunction based upon chemotherapy used. Monitor creatinine and GFR Abnormal electrolytes
Endocrine
Other	Patients may need nutrition optimization prior to surgery Patients can benefit from active prehabilitation prior to surgery

Labs and studies

• CMP (particularly renal function and electrolytes)
• CBC (identify and correct anemia) - If Hg > 9 g/dL, consider prehabilitation
• Consider pre-albumin to evaluate nutrition status

Operating room setup

• Fluid warmer
• Arterial line setup
• Central line vs. 2 large bore IVs
• ± Cardiac output monitor (i.e. Flowtrack)
• NG or OG tube
• Vasopressor drips
  • Norepinephrine
  • Vasopressin
  • Phenylephrine
• Blood products
  • 2 units pRBCs

Patient preparation and premedication

• Preoperative nutrition consult
• Preoperative prehabilitation plan

Regional and neuraxial techniques

• Epidural or paravertebral blocks (if epidural is contraindicated).
• Erector Spinae block could potentially be used (minimal data at this time; only case reports).

Intraoperative management

Monitoring and access

• Multiple large-bore PIVs (for active fluid resuscitation)
• ± Rapid infusion catheter (RIC)
• Arterial line
• ± Central venous catheter (8 Fr double-lumen, 8.5 Fr single-lumen Cordis, or 9 Fr double-lumen MAC Cordis)

Induction and airway management

• General anesthesia with ETT
• No special precautions
• Paralysis preferred

Surgical Timeout Communication

Operative goals are crucial to delineate with the surgical team prior to incision. Key discussion points include:

1. Patient Risk Factors
2. DVT prophylaxis
3. Fluid Goals
4. Confirm urine output goals for cisplatin only
5. Body Temperature Management plus additional monitors (esophageal, nasopharyngeal, bladder, axillary, etc)
6. Type of chemotherapy agent used, including dilution solution and its implications on electrolytes
7. Consideration for further renal protection therapy
8. Trigger for blood transfusion
9. Preoperative antibiotic choice

Positioning

• Supine

Maintenance and surgical considerations

Pre-cytoreductive phase

• Check baseline electrolytes
• Fluid resuscitation to maintain euvolemia: consider arterial line and cardiac output monitoring to guide fluid resuscitation and avoid over-resuscitation

Cytoreductive Phase

• Check ABG and base deficit q1hour
• Check coagulation status q4 hours
• Resuscitate with lactated ringers or plasma-lyte (Avoid normal saline)
• Consider albumin administration for intravascular fluids
• Maintain normothermia to mild hypothermia (target temp 35-36.5 °C)
• Monitor urine output and evaluate volume status. If UOP less than 0.5 mL/kg/hr - Consider vasopressin or norepinephrine to maintain MAP if patient is hypotensive but not hypovolemic
• Obtain pre-HIPEC chemistries (Na+, K+, Mg2+, Ca2+)

HIPEC Phase

• Maintain good muscle relaxation
• Intra-abdominal pressure may be elevated up to 26 mm Hg
  • Maintain abdominal perfusion pressure of >60 (MAP – IAP)
• Manage ventilation to maintain normocarbia and normoxia
• Avoid hypervolemia during high volume resuscitation
• Check ABG and base deficit q30min to q1hour
  • Treat hyperglycemia (>200) with insulin drip
  • Treat hyponatremia
    • Diuretics for hypervolemia
    • Volume resuscitate for hypovolemia; consider hypertonic saline if Na<130
• Check electrolytes (Na+, K+, Mg2+, Ca2+) during HIPEC phase
• Continue to check coagulation factors q4 hour
• Goal intraperitoneal tissue temperature: 41-43 °C
• Watch for core temperature >39.5 °C
  • Consider passive cooling vs active cooling with ice
  • Consider cooling intraperitoneal fluids
• Cisplatin Perfusion ONLY:
  • sodium thiosulfate bolus at start of chemoperfusion
  • Sodium thiosulfate drip starts immediately after bolus over 12 hrs
  • Crystalloid (avoid NS) to maintain urine output > 100mL/hr through the end of case and into PACU / ICU

Emergence

• After fascia is closed, check twitches and reverse paralysis
• Plan for extubation if hemodynamically stable, normothermic and normoxic.

Postoperative management

Disposition

• Admit to ICU (consider discussion with ICU team and surgeon beforehand)
• UOP Goals: UOP 100 mL/hr (for Cisplatin only)
• May require pressors due to prolonged vasoplegia postoperatively
• Continue Sodium thiosulfate drip over 12 hours from start of perfusion (for cisplatin only)

Pain management

• PCEA
• IV acetaminophen
• ketoralac (if perfusion with MMC, no pre-existing kidney disease)

Potential complications

• variable
• surgical complications: anastomotic leakage, bleeding, infection;
• medical / chemo-related: myelosuppression (MMC),
• nephrotoxicity (Cisplatin)

Procedure variants

	Open Abdominal Perfusion	Closed Abdominal Perfusion	Peritoneal Cavity Expander
Unique considerations		Decreased exposure and inhalation of chemotherapeutic agents High intrabdominal pressures
Position		Supine or low-lithotomy
Surgical time		Variable, dependent on extent of tumor and resection
Perfusion Time		Cisplatin: 90 minutes MMC: 100 minutes
EBL		Variable, dependent on extent of tumor and resection
Postoperative disposition		ICU
Pain management		PCEA, IV acetaminophen Consider ketoralac if: Perfusion with MMC No kidney disease
Potential complications		Surgical complications: Anastomotic leakage Bleeding Infection Medical / chemo-related: Myelosuppression (MMC) Nephrotoxicity (Cisplatin)

Enhanced Recovery After Surgery

Attribute	Mayo Clinic
Nutrition	Protein and carbohydrate supplementation
Intravenous Fluids	Goal directed (UOP of 0.5 mL/kg/h)
Pain Control	Multimodal pain therapy + TAP block
Oral Intake	Clear liquid on POD 0 No NGT tube
Drains & Tubes	Only when indicated
Post-op Disposition	Step-down unit