Perioperative management of cytoreductive surgery and hyperthermic intraoperative thoraco-abdominal chemotherapy (HITAC) for pseudomyxoma peritonei.

Peritoneal carcinomatosis is intraperitoneal spread of gastrointestinal and gynaecological cancers. Cytoreductive surgeries and hyperthermic intraperitoneal chemotherapy offers survival benefits in these cases. Spread of peritoneal carcinomatosis to thorax pose challenges to surgeon and anaesthesiologist. Haemodynamic, temperature and coagulopathy monitoring as well as intraoperative airway pressure, pre- and postoperative pulmonary function test monitoring is required in these cases where diaphragm excision is done and intraoperative intra peritoneal as well as pleural chemotherapy is given. We are reporting a case of pseudomyxoma peritonei involving the abdomen and left side of pleura and lung, posted for cytoreductive surgery and hyperthemic chemotherapy to abdomen and thorax, i.e., hyperthemic intraoperative thoraco-abdominal chemotherapy.

INTRODUCTION

Pseudomyxoma peritonei (PMP) is characterised by intraperitoneal disseminated mucous produced by adenomucinous tumor cells implanted on peritoneal surfaces. Clinically, it is mainly expressed as “jelly belly,” caused by the abundant intraperitoneal mucous. As PMP progresses, gastrointestinal function is compromised and eventually obstruction is imminent and results in the death of the patient unless radically treated. Cytoreductive surgery (CRS) in combination with intraoperative hyperthermic intraperitoneal chemotherapy (HIPEC) is a feasible treatment strategy for operable peritoneal carcinomatosis in terms of survival.[1] Peritoneal carcinomatosis (PC) not amenable to surgery can be offered pressurised intraperitoneal aerosolised chemotherapy (PIPAC) with the aim to prolong the life.[2] Disease involving both the abdominal and thoracic cavities needs special treatment such as hyperthemic intraoperative thoraco-abdominal chemotherapy (HITAC).[3] These cases pose an immense challenge to the anaesthesiologist in terms of haemorrhage, systemic inflammatory response syndrome, multi-organ dysfunction, acid-base imbalances, electrolytic disturbances, coagulopathy and potential systemic toxicity of the chemotherapeutic agents. We report a case of PMP involving the whole abdomen and peritoneum along with left pleura and lung which was treated with CRS and HITAC.

CASE REPORT

A 53-year-old, 56 kg weight and 154 cm height female was having pseudomyxoma peritonei, diffusely deposited in the abdomen and peritoneal surfaces as well as in the left lung and pleural space. She was a case of hypothyroidism since last 4 years on oral thyroxine 50 mcg once a day. Her laboratory investigations were within normal limits except that liver function test showed serum albumin of 2.1 g/L initially which improved to 3.4 g/L with high protein formula feed for 1-month period of evaluation and optimization. Preoperative electrocardiogram and 2D-echocardiogram were normal. Her effort tolerance was more than 4 METs. Preoperative pulmonary function test (PFT) showed FEV1 1.13 Litres (47.3% of predicted) with moderate restriction due to the lung metastases with small airway obstruction. Patient was started on bronchodilator therapy for the same. Diffusion capacity (DLCO) was 81% of predicted. A written informed consent was taken for surgery and anaesthesia. She was kept fasting for solid food for 8 hours. She received clear carbohydrate drink in previous evening and morning of surgery as per institutional protocol. In the operating room, ECG, non-invasive blood pressure and pulse oximetry were attached and base line parameters noted. A 16G intravenous cannula was secured and epidural catheter was placed in T7-8 interspace in left lateral position. Anaesthesia was induced with fentanyl (100 mcg), propofol (110 mg) and vecuronium (6mg) and was maintained on sevoflurane in a gaseous mixture of oxygen with nitrous oxide. The monitoring was then advanced to include invasive arterial blood pressure with pulse pressure variation (PPV), central venous pressure and monitoring with the help of FloTrac including cardiac output, cardiac index, stroke volume (SV), stroke volume index and stroke volume variation (SVV), as well as oesophageal temperature monitoring. CRS phase was started and total peritonectomy with total abdominal hysterectomy plus omenectomy, splenectomy, cholecystectomy and liver portal metastasis clearance was done. Bilateral diaphragmatic stripping was done for metastatic deposits. Debulking surgery of left thorax (large deposits over left lung) through left phrenotomy was done for pleural and lung PMP. A small part of left lower lobe was also resected. During debulking of thorax, a very low tidal volume (4 ml/kg) ventilation was started. CRS phase lasted for 12 hours with a total volume loss (blood mixed) during CRS phase was 6.5 liter, mostly constituted by jelly-like mucinous material. During abdominal debulking, fluid therapy was guided by PPV and SVV but after opening of pleura fluid therapy was guided by delta SV with optimum SV and target SV (10% less than optimum SV) calculation. Six units of packed red cells, 4 units of fresh frozen plasma and 500 ml of 20% albumin was given along with 6 liters of crystalloids and low dose (<0.1 μg/kg/min) nor-adrenaline support was needed toward end of CRS phase. Urine output target during CRS was more than 0.5 ml/kg/h. Total peritoneal carcinomatosis index (PCI) was 39 with completion cytoreduction score of 1. HITAC in form of adriamycin 15 mg/m2 and mitomycin 15 mg/m2 was given in left side of thorax with open diaphragm and whole abdomen for 60 minutes with help of Belmont pump. A urine output of more than 2 ml/kg/h was targeted during HITAC phase by use of cold fluids. Temperature control was done with cold fluids at 6°C and ice packs on neck and axilla. The maximum temperature reached was 37.8°C after 40 minutes of starting HITAC. ScvO2 at end of CRS was 75.6% and at the end of HITAC phase it was 83.4%. Serum lactates increased from 1.10 mmol/L at the end of CRS phase to 8.02 mmol/L at the end of 60 minutes HITAC phase. Peak airway pressure increased from 23 to 30 cm of H2O during HITAC phase. At the end of procedure loop ileostomy was done and diaphragm was closed, drains were put in abdomen and bilateral chest tubes were placed and abdomen was closed. The patient maintained a moderate metabolic acidosis of pH 7.2-7.3 throughout the HITAC. The patient was transferred to the intensive care unit (ICU) mechanically ventilated and sedated. In the ICU, she was electively ventilated for 48 hours. The trachea was extubated on high flow nasal oxygenation by Optiflow™. On postoperative day (POD) 1, parenteral nutrition was started. Adequate pain relief was achieved by epidural infusion of local anaesthetic for 4 days along with intravenous paracetamol 1 g 6 hourly. She was shifted out from ICU on POD 7. PFT repeated on POD 13 showed severe restriction with small airway obstruction, FEV1 0.91 Liter (38% of predicted), and fall in DLCO from preoperative 81% to 59% in postoperative period. She was discharged from hospital on POD 15.

DISCUSSION

Cytoreductive surgery involving resections of abdominal as well as thoracic viscera followed by HITAC is a complex surgery associated with extensive resection, blood loss, fluid shifts and temperature extremes. Such surgeries have major effect on cardiovascular, gastrointestinal, renal, neurological and respiratory systems of body.

Major intraabdominal viscera and peritoneal resection and chemotherapy causes hypoalbuminemia due to a combination of ascitic drainage, debulking surgery, and increase capillary leakage is common.[4]

The main anaesthetic challenges during cytoreduction are substantial fluid losses due to exposure of peritoneum to the environment, and drainage of large amount of ascitic fluid on opening the abdomen.[5] Excessive fluid administration can cause postoperative lung edema contributing to respiratory failure which is seen more in patient's undergoing lung surgery.[67] On the other hand, an adequate perioperative fluid therapy is important to reduce the risk of chemotherapy-related postoperative renal insufficiency. In our case, during open thorax, fluid management was guided by delta SV because PPV and SVV during open chest are not reliable parameters. Hyperthermic intrathoracic chemotherapy (HITHOC) is being used for malignant pleural mesothelioma and thymoma. In a retrospective analysis of 20 patients, HITHOC was considered to be well tolerated but they needed one lung ventilation because HITHOC needs thoracotomy.[8]

Temperature management is of utmost importance in a case of CRS and HITAC (or even HIPEC/HITHOC). During the CRS, patients tend to get hypothermic and develop platelet abnormalities', coagulation dysfunction, impaired surgical wound healing and also life threatening arrhythmias. Hyperthermia during the chemotherapy infusion phase on the other hand increases the basal metabolic rate and oxygen consumption leading to metabolic acidosis.[9] It can cause multiple organ dysfunction due to disturbance of the oxygen demand-supply balance leading to myocardial ischemia, ventilator induced lung injury or neurocognitive dysfunction.[10]

Coagulopathy is another common issue to be tackled during CRS and HITAC. Major resection during CRS stage causes excessive blood loss requiring transfusion. Temperature rise during the HIPEC stage, combined with toxicity of the chemotherapeutic agents and protein loss cause increased coagulopathy.[1112] Standard coagulation monitoring like PT/INR and sometimes thromboelastography may be needed intraoperatively.

Concerns with regards to intrathoracic hyperthermic chemotherapy can be classified as those related to physiological alterations in respiratory systems and cardiovascular system. Physiological alterations in lung would include chemotherapy fluid loading causing rise in intrathoracic pressure, increased airway pressure, mediastinal shift and decreased functional residual capacity.[41113] Postoperative PFTs in our patient showed a decreased FEV1 from 1.13 Liter of baseline to 0.91 Liter and DLCO of 59% from baseline of 81% on POD 13. This may be attributed to poor diaphragmatic functions and pain after surgery despite a good postoperative pain management. Physiological alterations in the heart would include reduced preload due to obstruction of superior and inferior vena cava causing hypotension, direct compression of the heart by the chemotherapy fluid and myocardial irritation causing arrhythmias. Occupational hazards by aerosols, although more common in PIPAC,[2] of chemotherapeutic agents should be protected by personal protective measures.

CONCLUSION

Cytoreductive surgery and hyperthermic intraoperative thoraco-abdominal chemotherapy is an upcoming approach for treatment of patients with intraperitoneal and pleural malignancies and require special anaesthetic management and perioperative care.

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Conflicts of interest

There are no conflicts of interest.