title: Standard Clinical Protocol for Bidirectional Hyperthermic Intraperitoneal Chemotherapy (HIPEC): Systemic Leucovorin, 5-Fluorouracil, and Heated Intraperitoneal Oxaliplatin in a Chloride-Containing Carrier Solution.
abstract: BACKGROUND
  Intraperitoneal chemotherapy has an established role in the treatment of selected patients with colorectal peritoneal metastases. Oxaliplatin is highly suitable as a chemotherapeutic agent for hyperthermic intraperitoneal chemotherapy (HIPEC), but its use to date has been limited because of the morbidity caused by severe electrolyte and glycemic imbalances associated with 5% glucose as its carrier solution. This report provides an overview of the development, rationale, and application of intraperitoneal chemotherapy and the use of various drugs and carrier solutions. A novel, evidence-based protocol for bidirectional oxaliplatin-based HIPEC in a physiologic carrier solution (Dianeal PD4 dextrose 1.36%) is presented, and its impact on electrolyte and glucose levels is demonstrated.
  
  
  METHODS
  After implementation of the new protocol, the serum electrolyte (sodium, potassium, and chloride) levels, glucose levels, and intravenous insulin requirements were intensively measured in eight consecutive cases immediately before HIPEC (T = 0), immediately after HIPEC (T = 30), 1 h after HIPEC (T = 60), and 3 h after HIPEC (T = 180).
  
  
  RESULTS
  The median sodium levels were 140 mmol/L at T = 0, 138 mmol/L at T = 30, 140 mmol/L at T = 60, and 140 mmol/L at T = 180. The respective median potassium levels were 4.6, 4.2, 3.7, and 3.9 mmol/L, and the respective median chloride levels were 112, 111, 111, and 112 mmol/L. The respective median glucose levels were 9, 11.5, 10.7, and 8.6 mmol/L. The median insulin requirements were respectively 0.5, 1.5, 1.2, and 0 U/h. None of the patients were diabetic.
  
  
  CONCLUSIONS
  Using a novel protocol for bidirectional oxaliplatin-based HIPEC in Dianeal instead of 5% glucose, the observed fluctuations in this study were minimal and not clinically relevant compared with historical values for electrolyte and glycemic changes using 5% glucose as a HIPEC carrier solution. This novel protocol leads to only minimal and clinically irrelevant electrolyte and glycemic disturbances, and its adoption as the standard protocol for oxaliplatin-based HIPEC should be considered.
authors.affiliation: Department of Surgery, Peritoneal Malignancy Institute, Basingstoke & North Hampshire Hospital, Basingstoke, UK. akash.mehta@hhft.nhs.uk.
authors.forename: Akash M
authors.initials: AM
authors.lastname: Mehta
authors.affiliation: Department of Pharmacy and Pharmacology, The Netherlands Cancer Institute, Amsterdam, The Netherlands.
authors.forename: Alwin D R
authors.initials: AD
authors.lastname: Huitema
authors.affiliation: Department of Surgery, Erasmus MC, Rotterdam, The Netherlands.
authors.forename: Jacobus W A
authors.initials: JW
authors.lastname: Burger
authors.affiliation: Department of Surgery, Erasmus MC, Rotterdam, The Netherlands.
authors.forename: Alexandra R M
authors.initials: AR
authors.lastname: Brandt-Kerkhof
authors.affiliation: Department of Anaesthesiology, Erasmus MC, Rotterdam, The Netherlands.
authors.forename: Sander F
authors.initials: SF
authors.lastname: van den Heuvel
authors.affiliation: Department of Surgery, Aarhus University Hospital, Aarhus, Denmark.
authors.forename: Victor J
authors.initials: VJ
authors.lastname: Verwaal
mesh_terms: D061605:Administration, Intravenous; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage*; D001786:Blood Glucose / Q000378:metabolism; D002712:Chlorides / Q000008:administration & dosage / Q000097:blood; D015179:Colorectal Neoplasms / Q000473:pathology*; D065426:Cytoreduction Surgical Procedures; D015314:Dialysis Solutions / Q000008:administration & dosage / Q000737:chemistry; D019317:Evidence-Based Medicine; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D006801:Humans; D006979:Hyperthermia, Induced; D007263:Infusions, Parenteral; D002955:Leucovorin / Q000008:administration & dosage; D008297:Male; D008875:Middle Aged; D009944:Organoplatinum Compounds / Q000008:administration & dosage; D000077150:Oxaliplatin; D010534:Peritoneal Neoplasms / Q000556:secondary / Q000628:therapy*; D011188:Potassium / Q000097:blood; D012964:Sodium / Q000097:blood
chemical_list: D001786:Blood Glucose; D002712:Chlorides; D015314:Dialysis Solutions; D009944:Organoplatinum Compounds; D000077150:Oxaliplatin; D012964:Sodium; D002955:Leucovorin; D011188:Potassium; D005472:Fluorouracil