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  1. HIPEC MAGDY GHATTAS Consultant of anesthesia and intensive care Ismailia Oncology Teaching Hospital
  2. Presentation includes short notes about • Physiological changes during HIPEC • Patient selection criteria for HIPEC and Cytoreductive Surgery (CRS) • Preoperative concerns • Severe fluid shift • HIPEC and electrolyte balance • Hemodynamic management • Control of body temperature • Postoperative complications • Postoperative/critical care management • Conclusion
  3. PHYSIOLOGICAL CHANGES DURING HIPEC • Cardiovascular: Increase in heart rate and central venous pressure. No significant changes in blood pressure. • Respiratory: Increase in peak airway pressures up to 30 mmHg. Decrease in tissue oxygenation. Increase in end-tidal CO2 levels.
  4. PHYSIOLOGICAL CHANGES DURING HIPEC • Renal: Decreased perfusion to the kidneys. Metabolic acidosis with increased lactate. • Coagulation: Hyperthermia-associated coagulopathy with a decrease in platelet count (Thrombocytopenia) as well as an increase in Prothrombin Time (PT) and International Normalized Ratio (INR). (Coagulopathy is corrected on the 5th PO day).
  5. Selection Criteria for HIPEC and Cyto Reductive Surgery • Medical optimization with no active cardiac or respiratory conditions. • Absence of extra abdominal disease, extensive hepatic metastases, and significant retroperitoneal disease. • Age less than 70 years , however not absolutely indicated. • Peritoneal disease that is amenable to complete or near complete resection.
  6. • It is imperative to perform a detailed preoperative assessment to avoid ORGAN FAILURE that may occur in some patients. • Operative risk assessment for comorbidities like diabetes, hypertension and heart disease. • Assessment of pulmonary system.
  7. Preoperative Concerns • AGAIN Thorough assessment of the patient’s cardiac and pulmonary systems is essential to assess their ability to respond to the physiological challenges faced intraoperatively .
  8. PREOPERATIVE WORKUP • Most patients for elective major abdominal surgery invariably undergo adequate preoperative assessment and evaluation. • Echocardiography and dynamic cardiac assessments • Full blood count • Coagulation studies • Electrolytes, urea and creatinine levels • Review the nutritional status of the patient and to measure a preoperative albumin level • Glomerular filtration rate to identify patients at risk of an acute kidney injury associated with the HIPEC
  9. PREOPERATIVE WORKUP Preoperative SERUM ALBUMIN deserves a special mentioning . • It reflects the nutritional status of the patient. • Albumin levels strongly predicts length of hospital stay and overall survival. • Malnutrition may be present in >50% of patients with ovarian cancer and advanced colorectal cancer with peritoneal metastasis. • Preoperative correction of anemia and hypoalbuminemia is preferable.
  10. VENOUS THROMBO- EMBOLISM PROPHYLAXIS Mechanical pneumatic compression stockings should be applied
  11. OF HIPEC and CRS PERIOPERATIVE CONCERNS OF HIPEC and CRS Perioperative management is complex and is associated with : • Massive fluid shift • Blood loss • Temperature imbalance • Hemodynamic alterations And • Renal toxicity of chemotherapeutic drugs
  12. Chemotherapeutics used during hyperthermic intraperitoneal chemotherapy and possible chemotherapeutic-specific adverse effects Mitomycin C: Nephrotoxicity, pulmotoxicity Cisplatin Peripheral neuropathia, myelotoxicity Cisplatin : Peripheral neuropathia, myelotoxicity Doxorubicin : Cardiotoxicity (arrhythmia, cardiomyopathy), myelotoxicity Oxyliplatin : Neurotoxicity (laryngeal/pharyngeal dysesthesia) Irinotecan : Myelotoxicity
  13. MASSIVE FLUID SHIFT • Significant blood loss associated with the major debulking surgery. • Evaporative losses related to the open abdomen. • Ascites drainage of protein‐rich fluid. • HIPEC causes peritoneal inflammation that can cause perioperative fluid loss.
  14. MASSIVE FLUID SHIFT • Intraoperative fluid losses may be as high as 12-20 ml/kg/hour depending on the degree of debulking i.e. 1800 ml/hour. • Large amount of fluid shift occurs during cytoreductive phase due to large raw surface produced by peritonectomy, ascitic drainage and significant blood loss during this procedure .
  15. MASSIVE FLUID SHIFT • Anesthesiologists need to manage intravenous fluid therapy, blood transfusion and electrolyte balance to maintain optimal end-organ perfusion and prevent renal injury. • Patients with poor cardiac reserve may not tolerate a high volume of intravenous fluid and may require vasopressors and inotropes to be used carefully .
  16. MASSIVE FLUID SHIFT • Fluid replacement is with crystalloid or colloid solutions as well as blood and plasma . • Up to NINE LITERS of blood loss has been reported during Cytoreduction Surgery (CRS) and HIPEC due to surgical reasons and coagulation abnormalities.
  17. RENAL PROTECTION • The best way to preserve renal function is to maintain NORMOVOLEMIA and ADEQUATE URINARY OUTPUT (1mL/kg/h). NO diuretics or dopamine is recommended.
  18. HIPEC AND ELECTROLYTE BALANCE • Chemotherapeutic agents (especially if dissolved in DW5%) may lead to: • Dilutional Hyponatremia ( serum sodium ) ( ? Mechanism) • Lactic acidosis mainly due to increased glucose metabolism and anaerobic metabolism. • Hypomagnesaemia which leads to cardiac arrhythmias . • Electrolyte disturbances like calcium, potassium and magnesium should be replaced if required.
  19. HIPEC AND ELECTROLYTE BALANCE Frequent ABG, and electrolytes (sodium, potassium, calcium and magnesium) are desired to be measured calcium and magnesium) are desired to be measured to detect and manage the abnormalities early. to detect and manage the abnormalities early.
  20. Hemodynamic Management • Hyperthermia during HIPEC leads to peripheral vasodilatation and reduction in peripheral vascular resistance and mean arterial pressure . • There is an increase in heart rate in order to maintain cardiac output . • An arterial line, a central venous catheter and a urinary catheter are useful for monitoring the hemodynamic status of the patient in real time .
  21. CONTROL OF BODY TEMPERATURE • CRS combined with HIPEC can be associated with both hypothermia and hyperthermia. • Hypothermia occurs during CRS and increases the risk of blood loss and surgical wound infections. • Hyperthermia: The carrier solution for HIPEC is heated to 42C-43C and body temperature may rise to up to 40.5 C. (? Effects on abdominal organs)
  22. CONTROL OF BODY TEMPERATURE • Hyperthermia increases the systemic oxygen demand, and may lead to an increased metabolic demand levels and a concomitant metabolic acidosis AKI. • Hyperthermia also puts the patient at risk of coagulopathies, liver dysfunction, neuropathies, and seizures.
  23. CONTROL OF BODY TEMPERATURE • Body temperature is monitored by two probes. • One temperature probe is placed in the esophagus/nasopharynx for core temperature monitoring and the temperature of the abdominal cavity is measured by thermistors present in the inlet and outlet drains of the HIPEC machine. • Thermoregulation plays a significant role in  maintaining the metabolic homeostasis,  coagulation, anti‐inflammatory cascade and  neurological status intact .
  24. CONTROL OF BODY TEMPERATURE • Warming during CRS to prevent hypothermia and to prevent coagulation and metabolic harmful effects . AND • During the HIPEC phase, cooling blankets and cold head-wraps or cooling blocks can be used to help to regulate the temperature.
  25. CONTROL OF BODY TEMPERATURE • Cold intravenous fluids and placement of ice packs in the axillae of the patient may be required to normalize the temperature . • If despite all these measures, core body temperature rises to ≥39°C then the perfusionist should be advised to reduce the instillate temperature .
  26. Postoperative Complications Hypovolemia/Hypoproteinemia as the patient loses  4 – 5 liters of PROTEIN – ENRICHED fluid per day. Bowel perforation Anastomotic  and bile leakage Fistula formation Postoperative  bleeding or  infections Venous‐thromboembolic  complications Postoperative ileus Complications related to  chemotherapy as leukopenia
  27. Postoperative/Critical Care Management REFERENCE • Intensive Care Management of Patient After Cytoreductive Surgery and HIPEC – A Concise Review. Indian J Surg Oncol (June 2016) 7(2):244–248 DOI 10.1007/s13193-016-0511-7.
  28. Postoperative/Critical Care Management • Postoperative fluid loss during the first 72 hours following surgery is still very high with values up to 4 liters per day, whereas most of the fluid loss occurs via abdominal drains (40%) due to the severely wounded surface . • Protein loss is remarkable with decreased albumin levels starting to decline during surgery with the frequent need for exogenous administration . Supplement Albumin if it falls below 3.0 g/dl to maintain adequate intra vascular volume. • Close monitoring of fluid loss and turnover is of critical importance for the patient’s convalescence. REFERENCES : 1.Arakelian E, Gunningberg L, Larsson J, et al. Factors influencing early postoperative recovery after cytoreductive surgery and hyperthermic intraperitoneal chemotherapy. Eur J Surg Oncol 2011; 37:897–903. 2. Cooksley TJ, Haji‐Michael P. Postoperative critical care management of patients undergoing cytoreductive  surgery and Heated Intraperiton al Chemotherapy (HIPEC). World J Surg Oncol 2011; 9:169
  29. Postoperative/Critical Care Management • Vasodilation may occur after HIPEC. • Vasopressors for patients who are not fluid responsive to avoid fluid overload. • Early enteral feeding is recommended, as nutrition is crucial to promote wound healing and improve intestinal health.
  30. Postoperative/Critical Care Management • Maintain an adequate effective circulating volume by supplying sufficient intravenous fluids such as crystalloid & colloid solutions or blood and blood products like fresh frozen plasma. • ANALGEIA .There is increasing evidence that thoracic epidural anesthesia (TEA) with local anesthetics and opioids is superior in the control of dynamic pain, playing a key role in early extubation and mobilization and reducing postoperative pulmonary complications. • TEA Hypotension & Epidural hematoma ? • Multimodal analgesia is a good alternative.
  31. Postoperative/Critical Care  Management • Postoperative respiratory support is not always necessary. It was reported that all the patients were extubated in the OR . • The coagulation profile takes at least 5 days to get back to baseline, eventual transfusions are needed . • Patients with gross ascites often lose in excess of two litters of ascitic fluid rich in protein (0.5–4 g/dL) which is primarily albumin. • Renal Status, Electrolyte Balance, Glycemic Control :  Impairment to these functions is reported to be short lasting. Standard care is needed. • Stress Ulcer Prophylaxis. • Infection Control .
  32. Postoperative Care • Postoperative ileus is a common problem after CRS and HIPEC. • Oral intake, regaining bowel functions and mobilization usually occur between 7 and 11 days postoperatively. • Patients may experience nausea for up to 13 days postoperatively. • Early enteral feeding is both safe and beneficial for these patients. • Epidural anesthesia has been recommended by some as a strategy to reduce postoperative ileus . Arakelian E, Gunningberg L, Larsson J, Norlén K, Mahteme H. Factors influencing early postoperative recovery after cytoreductive surgery and hyperthermic intraperitoneal chemotherapy. Eur J Surg Oncol 2011;37:897–903
  33. Postoperative Care • Anti-emetic prophylaxis using 5-HT3 antagonists should continue for a few days at a regular intervals. • Maintaining Hemoglobin concentration between 8-10 g/dL according to CV risk. • Avoid nephrotoxic medications and diuresis should not fall below 1 mL/kg/hour. • Hemodynamic monitoring until the third postoperative day or discharge from ICU.
  34. Postoperative Care • Drain Management Enhancing early mobilization is an essential element of postoperative enhanced recovery protocols. • Tubes and drains carry the risks of infection and can hinder mobility and cause pain. • Drains should be removed as early as possible. • It is recommended to leave only one abdominal silicone drain for the pelvis, additional drains can be used especially after splenectomy or (partial) gastrectomy.
  35. Postoperative Care • Management of Hemodynamics: REMEMBER that Fluid loss during initial 72 hours after surgery may be as high as 4 liters per day due to oozing of protein-rich fluid from the raw surface area due to peritonectomy . • Most of the patients require vasopressor support in the early postoperative period to counteract the vasodilatation due to HIPEC.
  36. VASOPRESSOR SUPPORT In our case of HIPEC operated on Monday 14th of June 2021 at Ismailia Oncology Teaching Hospital, we have supported the patient`s circulation by Noradrenaline (Levophed) vasopressor , Starting with a dose of 0.05 microgram/kg/minute (that is 210 mic/hour) and raised gradually to 400 mic/hour to support the circulation and maintain B.P.
  37. One mL contains 80 microgram Noradrenaline (Levophed) Starting dose for a 70 kg patient is : 0.025 mic. x 70 kg x 60 min = 105 microgram/hour = 105/80 = 1.3 mL/hour . To be increased gradually according to patient`s response. NORADRENALINE INFUSION (Levophed) 4 mg ampoule = 4 mL 0f 1:1000 Add 4 mL of 1:1000 Noradrenaline to 46 mL Glucose to make 50 mL. Starting dose : 0.025 – 0.05 microgram/kg/min. The rate in infusion/syringe pump in mL/hour.
  38. CONCLUSION Perioperative care of patients undergoing cytoreductive surgery and HIPEC procedure is complex and involves management of excessive fluid and protein losses, thermoregulation, coagulation disturbance and postoperative care.
  39. • Gupta, et al.: Anesthesia for HIPEC Journal of Anaesthesiology Clinical Pharmacology | Volume 35 | Issue 1 | January-March 2019. • Anesthesia tutorial of the week. General anesthesia 379 Dr Rosemarie Kearsley, Dr Sine´ ad Egan, Professor Conan McCaul Anesthesia for cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (HIPEC) (15 May 2019)
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