Aandachtspunten bij Anesthesie voor HIPEC. Marleen Verhaegen

Transcription

1 Aandachtspunten bij Anesthesie voor HIPEC Marleen Verhaegen

2 Outline Rationale en techniek van HIPEC Temperatuurbeleid Vochtbeleid Peritoneale perfusie in glucose 5 % (oxaliplatin) Specifieke toxiciteit van cytostatica Veiligheid

3 HIPEC Hyperthermic IntraPEritoneal Chemotherapy 1. Cytoreductive surgery (CRS) 2. Intraperitoneal chemotherapy 3. Intraperitoneal hyperthermia Indications: peritoneal surface malignancies Peritoneal carcinomatosis (colorectal, gastric, ovarian tumors) Pseudomyxoma peritonei Primary peritoneal tumors (mesothelioma) Bidirectional chemotherapy or HIPEC Plus HIPEC + concurrent intravenous chemotherapy

4 HIPEC: Cytoreductive Surgery (CRS) Debulking and cytoreduction Limited (omentectomy) Extensive (omentectomy, stripping of peritoneum and diaphragm, resection of multiple abdominal organs) Complete tumor resection or partial resection with tumor nodules 2.5 mm Peritoneal Cancer Index Estimation of feasibility

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6 Completeness of cytoreduction score

7 HIPEC: Intraperitoneal Chemotherapy Pharmacokinetic advantage Maximal exposure of tumor cells to cytostatic drugs Higher doses than systemic administration: higher than plasma concentrations Minimal systemic drug levels and exposure of healthy tissues Hepatic effect? Peritoneal-plasma barrier: slow rate of movement of chemotherapeutic drugs across the peritoneum Peritoneal-plasma barrier is preserved after extensive peritonectomy Blood from the peritoneal surface drains through the portal vein to the liver First pass detoxifying effect Increased exposure of potential hepatic micrometastases to cytotoxic drugs

8 HIPEC: Intraperitoneal Chemotherapy Pharmacokinetic disadvantage: limited tissue penetration No accurate data Large inter-individual variation Estimated maximum tissue penetration: 3 5 mm? Overestimation? From a few cell layers to a few mm 2.5 mm should be the largest tumor diameter after cytoreduction Cytostatic drug: varies by type of cancer Oxaliplatinum Cisplatinum Mitomycin C

9 HIPEC: Intraperitoneal Chemotherapy Cytostatic drug dosing: based on body surface area Concurrent intravenous chemotherapy Intraperitoneal oxaliplatin: Intravenous 5-FU and folinic acid 1 h prior to HIPEC Optimal duration? min

10 HIPEC: Intraperitoneal Hyperthermia C: synergism of heat and cytotoxic drugs Potentiation of cytotoxicity of chemotherapeutic agents Enhancement of tissue penetration of cytotoxic drugs Cytotoxic effects of hyperthermia (41 43 C) Inhibition of DNA repair mechanisms Denaturing of proteins Activation of heat shock proteins

11 HIPEC: Peritoneal Perfusion Technique Open abdomen technique (Coliseum technique) Better distribution? (manipulation of the viscera) Heat dissipation more difficult to initially achieve a hyperthermic state Closed abdomen technique Uneven distribution and pooling of heat and chemotherapy Increased risk of intraabdominal complications? Increased intraabdominal pressure (12 26 mmhg) Risk of splanchnic hypoperfusion Facilitation of tissue penetration? Cephalad shifting of diaphragm Impaired oxygenation Increased airway pressure No significant differences in outcome

12 Inflow drains / outflow drains Perfusate Temperature probes Cytostatic drugs are added when the perfusate is homogeneously heated to the desired temperature

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14 HIPEC: Carrier Solution Dosing based on body surface area NaCl 0.9 % or D 5 W Generally isotonic saline Oxaliplatin: 5% dextrose Chloride degrades oxaliplatin into less cytotoxic metabolites Absorption of carrier solution from the peritoneal cavity May affect distribution and concentration of cytotoxic drugs in the peritoneal cavity Systemic absorption of 5 % dextrose Severe hyperglycemia Severe hyponatremia Metabolic acidosis

15 HIPEC: Adverse Effects Regional cancer therapy with significant systemic effects Toxic effects of chemotherapeutic agents Systemic absorption is limited Pathophysiologic changes during HIPEC procedure Fluid shifts Body temperature changes Electrolyte disturbances Metabolic disturbances Significant postoperative morbidity/mortality Benefit vs adverse effects

16 De Somer et al., Perit Dial Int 2008: 28: 61-6

17 Baratti et al., World J Gastrointest oncol 2010; 15: 36-43

18 Zhu et al., J Gastrointest Oncol 2013; 4: 62-71

19 HIPEC: Outcome Significant perioperative morbidity and mortality Mortality: 0 9 % Morbidity: % Prolonged survival in selected patients Quality of life in long-term survivors Functional status and pain scores return to baseline 4 6 months after surgery Quality of life scores return to baseline months after surgery

20 HIPEC: Attention Points Temperature management Fluid management D 5 W as a carrier solution Specific toxicity of chemotherapeutic agents Occupational risks

21 HIPEC: Temperature Management (1) Hypothermia during debulking/cytoreduction Extensive surgery Major fluid shifts Exposure of large evaporation surface Risk of coagulopathy, adverse myocardial events, surgical wound infection, altered pharmacokinetics Hyperthermia during HIPEC procedure Warm intra-peritoneal fluids (42 43 C) Rapid rise in temperature Increased O 2 demand, increased CO 2 levels, metabolic acidosis, vasodilation, tachycardia, increased cardiac output, seizures Optimal temperature of peritoneal perfusion fluid? Maximal effect with minimal morbidity

22 Raft et al., Ann Fr Anesth Reanim 2010; 29:

23 HIPEC: Temperature Management (2) Temperature management strategy Before HIPEC: controlled hypothermia Target temperature 35 C Warming measures if indicated During HIPEC No forced air warmer Cold iv fluids Decreased room temperature Active cooling matras?

24 HIPEC: Fluid Management Debulking/cytoreduction Extensive fluid losses Including significant blood loss (coagulopathy) Continues after extensive peritonectomy Protein loss Up to 700 g/d following evacuation of ascites and debulking Non-cardiac pulmonary edema Hyperthermia: vasodilation Increased fluid needs Fluid requirements may be very high Tissue and organ edema Kidney failure Maintain normovolemia and good urine output during HIPEC

25 Arakelian et al., EJSO 2011; 37:

26 Schmidt et al., Anaesthesia 2008; 63:

27 Schmidt et al., J Surg Oncol 2009; 100:

28 HIPEC: Fluid Management Type of fluids Crystalloids Albumin Ascites Loss from extensive raw surface after peritonectomy Fresh frozen plasma Packed red blood cells Artificial colloids? Avoid No good clinical studies

29 HIPEC: Postoperative Care (1) ICU transfer Mechanically ventilated Monitoring of organ functions Monitoring for and management of complications Bowel perforation, anastomotic leakage, bile leakage, fistula formation, pancreatitis, postoperative bleeding, wound problems, deep vein thrombosis, pulmonary embolism Significant fluid losses 72 hours following surgery Up to 4 L/d Protein losses Crystalloids, albumin

30 Arakelian et al., EJSO 2011; 37:

31 Schmidt et al., Anaesthesia 2008; 63:

32 Schmidt et al., Anaesthesia 2008; 63:

33 HIPEC: Postoperative Care (2) Coagulation disturbances Respiratory problems Diaphragm stripping Atelectasis? Prolonged postoperative ileus is common Tissue edema, pain, nausea Toxicity of chemotherapeutic agents Role for epidural analgesia?

34 HIPEC: Postoperative Pain Management Often significant preoperative opioid use Significant postoperative pain First choice: thoracic epidural analgesia Decreased period of postoperative intubation Be aware of postoperative coagulation disturbances

35 D 5 W as a Carrier Solution Hyponatremia Hyperglycemia Hyperlactatemia

36 HIPEC: 30 min Raft et al., Ann Fr Anesth Reanim 2010; 29:

37 De Somer et al., Perit Dial Int 2008: 28: 61-6

38 D 5 W as a Carrier Solution: Hyponatremia Mechanisms Acute hyperglycemia: extracellular shift of water Loss of sodium into the peritoneal perfusion fluid Absorption of free water into the plasma dilutional hyponatremia Acute hyponatremia: [Na + ] 120 meq/l Spontaneous recovery to [Na + ] 130 meq/l within a few hours Cerebral edema Case reports

39 Hillier et al., Am J Med 1999; 106:

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41 De Somer et al., Perit Dial Int 2008: 28: 61-6

42 De Somer et al., Perit Dial Int 2008: 28: 61-6

43 D 5 W as a Carrier Solution: Hyperglycemia Absorption of glucose into the plasma Extreme hyperglycemia Up to 600 mg/dl Hyponatremia Treatment No aggressive treatment during peritoneal perfusion ( open gate effect) After perfusion Insuline bolus + infusion Very frequent glycemia determinations (risk of hypoglycemia)

44 D 5 W as a Carrier Solution: Hyperlactatemia Mechanisms Hyperglycemia-induced glycolysis (specific for D 5 W as a carrier solution) Hypoperfusion

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46 Increasing perfusate temperature seems to enhance glucose transport from the peritoneal cavity into the plasma Increasing perfusate temperature seems to enhance bicarbonate transport from the plasma into the peritoneal cavity Mechanisms Direct effect of temperature on the solute transport across the peritoneal membrane Microvessel dilation resulting in a larger exchange surface

47 HIPEC: Specific Toxicity of Chemotherapeutic Agents Mitomycin C Hematologic toxicity: leucopenia, thrombopenia Cisplatin Up to 28 % of patients Nadir after 2 weeks Renal wasting of intracellular magnesium and prolonged QT interval Case report of episodes of pulseless ventricular tachycardia Renal failure Oxaliplatin Immune-mediated platelet dysfunction Case reports of otherwise unexplained hemoperitoneum 5-Fluorouracil Cardiac toxicity

48 HIPEC: Acute Kidney Injury Incidence: % Generally associated with cisplatin Multifactorial Nephrotoxic chemotherapeutic drugs Cisplatin > 240 mg Abdominal hypertension Intravascular volume depletion Generally reversible

49 HIPEC: Cisplatinum Ventricular tachycardia (CR) Look for perioperative QT interval prolongation due to Direct cardiotoxic effect Selective renal magnesium wasting Check magnesium plasma levels Impaired renal function Prevention Maintain normovolemia Hemodynamic stability, avoid hypotension Adequate urine output (> 2 ml/kg/min?) Avoid nephrotoxic drugs Generally reversible Generally no dialysis required

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51 Owusu-Agyemang et al., Ann Surg Oncol 2012; 19:

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53 5-Fluorouracil: Cardiac Toxicity 5-FU = antimetabolite chemotherapeutic agent Combination therapy: chemotherapy, radiation therapy Prevalence of cardiac toxicity: % During continuous infusion, but also after bolus administration Signs and symptoms Chest pain, ST-T wave changes, arrhythmias (atrial fibrillation, ventricular ectopy, ventricular fibrillation), cardiogenic shock, ventricular dysfunction persisting for days to weeks, acute coronary syndrome Most common: reversible ST-T wave changes (+/- coronary artery disease) Most ischemia-like symptoms are reversible Disappear after the termination of the administration Disappear after pharmacotherapy: nitrates, calcium channel blockers

54 5-Fluorouracil: Cardiac Toxicity Cardiotoxic effects appear generally during the 2 nd or subsequent administrations Case reports during 1 st treatment Cardiac symptoms occur again during repeat administration Rechallenge: pretreatment with calcium channel blockers or nitrates? Mechanism? Not known Coronary vasospasm Endothelial NO is decreased Protein kinase C mediated Toxic myocarditis Myocardiomyopathy

55 Baseline Fradley et al., Tex Heart Inst J 2013; 40:

56 Ventricular fibrillation Atrial fibrillation with rapid ventricular response and ST segment elevation in anterior and inferior leads (after defribrillation) Fradley et al., Tex Heart Inst J 2013; 40:

57 HIPEC: Occupational Risks Exposure of operating room personnel to chemotherapeutic drugs General precautions should be taken when working with and handling cytotoxic drugs Anesthesiologist: 5-FU Low surface contamination Risk of skin contact during HIPEC (surgeon) Powder free latex gloves (double?, long sleeves) protect sufficiently against skin contact and absorption Risk of inhalation: open abdominal, intraperitoneal chemoperfusion (coliseum technique) Very limited data No data on the long-term exposure to low doses