Hyperthermic intraperitoneal chemotherapy surgery

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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.[1] These cancers include secondary peritoneal carcinomatosis, pseudomyxoma peritonei and primary peritoneal tumors.[1][2]  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.[1][3][4] This may be performed in a closed abdomen via perfusion circuit or an open abdomen +/- cavity expanders (sometimes referred to as the Coliseum technique[5]).[6]  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.[1][3]

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.[7]

Preoperative management

Cytotoxic Agents[1][8]

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 a higher major morbidity[9]
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+)[10]
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[11]
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

References

  1. 1.0 1.1 1.2 1.3 1.4 Webb, Christopher Allen-John; Weyker, Paul David; Moitra, Vivek K.; Raker, Richard K. (2013). "An overview of cytoreductive surgery and hyperthermic intraperitoneal chemoperfusion for the anesthesiologist". Anesthesia and Analgesia. 116 (4): 924–931. doi:10.1213/ANE.0b013e3182860fff. ISSN 1526-7598. PMID 23460568.
  2. Macrì, Antonio (2010-01-15). "New approach to peritoneal surface malignancies". World Journal of Gastrointestinal Oncology. 2 (1): 9–11. doi:10.4251/wjgo.v2.i1.9. ISSN 1948-5204. PMC 2999159. PMID 21160811.
  3. 3.0 3.1 Schmidt, C.; Moritz, S.; Rath, S.; Grossmann, E.; Wiesenack, C.; Piso, P.; Graf, B. M.; Bucher, M. (2009-09-15). "Perioperative management of patients with cytoreductive surgery for peritoneal carcinomatosis". Journal of Surgical Oncology. 100 (4): 297–301. doi:10.1002/jso.21322. ISSN 1096-9098. PMID 19697426.
  4. Al-Shammaa, Hassan-Alaa-Hammed; Li, Yan; Yonemura, Yutaka (2008-02-28). "Current status and future strategies of cytoreductive surgery plus intraperitoneal hyperthermic chemotherapy for peritoneal carcinomatosis". World Journal of Gastroenterology. 14 (8): 1159–1166. doi:10.3748/wjg.14.1159. ISSN 1007-9327. PMC 2690662. PMID 18300340.
  5. Rodríguez Silva, Cristina; Moreno Ruiz, Francisco Javier; Bellido Estévez, Inmaculada; Carrasco Campos, Joaquin; Titos García, Alberto; Ruiz López, Manuel; González Poveda, Ivan; Toval Mata, Jose Antonio; Mera Velasco, Santiago; Santoyo Santoyo, Julio (2017-02-21). "Are there intra-operative hemodynamic differences between the Coliseum and closed HIPEC techniques in the treatment of peritoneal metastasis? A retrospective cohort study". World Journal of Surgical Oncology. 15 (1): 51. doi:10.1186/s12957-017-1119-2. ISSN 1477-7819. PMC 5320712. PMID 28222738.
  6. Witkamp, A. J.; de Bree, E.; Van Goethem, R.; Zoetmulder, F. A. (2001). "Rationale and techniques of intra-operative hyperthermic intraperitoneal chemotherapy". Cancer Treatment Reviews. 27 (6): 365–374. doi:10.1053/ctrv.2001.0232. ISSN 0305-7372. PMID 11908929.
  7. González-Moreno, Santiago; González-Bayón, Luis; Ortega-Pérez, Gloria (2012). "Hyperthermic intraperitoneal chemotherapy: methodology and safety considerations". Surgical Oncology Clinics of North America. 21 (4): 543–557. doi:10.1016/j.soc.2012.07.001. ISSN 1558-5042. PMID 23021715.
  8. Cancer chemotherapy and biotherapy : principles and practice. Bruce Chabner, Dan L. Longo (5th ed.). Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins. 2011. ISBN 1605474312. OCLC 751669717.CS1 maint: others (link)
  9. Seretis, Charalampos; Gill, Jagjit; Malik, Adnan; Elhassan, Ali Mohamed; Shariff, Umar; Youssef, Haney (2020-12). "Low Preoperative Serum Albumin Levels Are Associated With Impaired Outcome After Cytoreductive Surgery and Perioperative Intraperitoneal Chemotherapy for Peritoneal Surface Malignancies". Journal of Clinical Medicine Research. 12 (12): 773–779. doi:10.14740/jocmr4362. ISSN 1918-3003. PMC 7781284. PMID 33447310. Check date values in: |date= (help)
  10. Rothfield, Kenneth P.; Crowley, Kathy (2012). "Anesthesia considerations during cytoreductive surgery and hyperthermic intraperitoneal chemotherapy". Surgical Oncology Clinics of North America. 21 (4): 533–541. doi:10.1016/j.soc.2012.07.003. ISSN 1558-5042. PMID 23021714.
  11. Webb, Christopher; Day, Ryan; Velazco, Cristine S.; Pockaj, Barbara A.; Gray, Richard J.; Stucky, Chee-Chee; Young-Fadok, Tonia; Wasif, Nabil (2020). "Implementation of an Enhanced Recovery After Surgery (ERAS) Program is Associated with Improved Outcomes in Patients Undergoing Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy". Annals of Surgical Oncology. 27 (1): 303–312. doi:10.1245/s10434-019-07900-z. ISSN 1534-4681. PMID 31605328.