Journal of Current Medical Research and OpinionReceived 15-06-2020 | Accepted 06-07-2020 | Published Online 06-07-2020

DOI: https://doi.org/10.15520/jcmro.v3i07.307 CMRO 03 (07), 503−507 (2020) ISSN (O) 2589-8779 | (P) 2589-8760

CASE REPORT:

Anaesthetic Management of Cytoreductive Surgery with HyperthermicIntraperitoneal Chemotherapy (CRS/HIPEC): A True Challenge To anAnaesthetist

Dr. Roly Mishra1∗ Dr.Kritika Sharma2 Dr Jueeli Barpande3 Dr Nitu Kumari4 Dr.Hemant Mehta5

VIEW COLONY , MANGO ,JAMSHEDPUR-831020,(JHARKHAND) INDIAb-DNB ANAESTHESIA-TATAMOTORS HOSPITAL,TELCOCOLONY,JAMSHEDPUR-831004,(JHARKHAND) INDIAc-ANAESTHESIA AND PAINMANAGEMNENT SIR H NRELIANCE FOUNDATIONHOSPITAL AND RESEARCH

Abstract:Patients diseased with gynecological malignancies were believed un-treatable with poor survival chances till hyperthermic intraperitoneal chemotherapy after capital cytoreductive surgery came into existence. Perioperative management of this patient, for a major surgery like CRS/HIPEC is complex and challenging. Major perioperative concerns in these patients include anesthetic challenges intraoperative fluid man-agement, maintaining mean arterial blood pressure, thermoregulation electrolyte imbalances, significant blood loss and fluid shifts and renal toxicity after chemotherapeutic drugs administration. We report a case of 66 year old female diagnosed with carcinoma ovary with moderate ascites posted for cytoreductive surgery and HIPEC.

Keywords: Gynaecological malignancy, cytoreductive surgery, hyper-thermic intra peritoneal chemotherapy, peritoneal carcinomatosis

CENTRE PRARTHANA SAMAJ,GIRGAON, MUMBAI-400004(MAHARSHTRA) INDIA

5a- DEPARTMENT OFANAESTHESIA AND PAINMANAGEMENT, KEMHOSPITAL AND SGS MEDICALCOLLEGE, MUMBAI-400012(MAHARASHTRA) INDIAb-ANAESTHESIA AND PAINMANAGEMNENT SIR H NRELIANCE FOUNDATIONHOSPITAL AND RESEARCHCENTRE PRARTHANA SAMAJ,GIRGAON, MUMBAI-400004(MAHARSHTRA) INDIAEmail:hemant.mehta@rfhospital.org

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1(MBBS) Netaji Subhash Chandra Bose Medical College And Hospital, Tilwara Road, Jabalpur-482003, (M.P) India(Third Year Dnb Resident) Department Of Anaesthesia And Pain ManagemnentSir H N Reliance Foundation Hospital And Research Centre, Prarthana Samaj, Girgaon, Mumbai-400004 (Maharshtra) India

2(MBBS) Kasturba Medical College,Manipal University,Magalore- 575001 (Karnataka) India(DNB) Narayana Institute Of Cardiac Sciences, Bommasandra Industrial Area,Bengaluru- 560099 (Karnataka) India(CLINICAL ASSOCIATE) Anaesthesia And Pain Managemnent Sir H N Reliance Foundation Hospital And Research Centre Prarthana Samaj, Girgaon, Mumbai-400004 (Maharshtra) India

3(MBBS) MGM Medical College And Hospital Gate No. 2 Mgm Campus N-6 Cidco, Aurangabad- 431003(Maharashtra) India(MD) Department Of Anaesthesia And Pain Management, Kem Hospital And Sgs Medical College, Mumbai-400012 (Maharashtra) India(EUROPEAN DIPLOMA IN ANAESTHESIA AND INTENSIVE CARE SENIOR CONSULTANT) Anaesthesia And Pain Managemnent Sir H N Reliance Foundation Hospital And Research Centre Prarthana Samaj, Girgaon, Mumbai-400004 (Maharshtra) India

4(MBBS) MGM Medical College Dimna Road ,Hill View Colony , Mango, Jamshedpur-831020,(Jharkhand) India(DNB) Anaesthesia-Tata Motors Hospital,Telco Colony,Jamshedpur-831004, (Jharkhand) India(CLINICAL ASSOCIATE) Anaesthesia And Pain Managemnent Sir H N Reliance Foundation Hospital And Research Centre Prarthana Samaj, Girgaon, Mumbai-400004 (Maharshtra) India

5(MBBS, MD, DA) Department Of Anaesthesia And Pain Management, Kem Hospital And Sgs Medical College, Mumbai-400012 (Maharashtra) India(DIRECTOR AND HEAD) Anaesthesia And Pain Managemnent Sir H N Reliance Foundation Hospital And Research Centre Prarthana Samaj, Girgaon, Mumbai-400004 (Maharshtra) India

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1 INTRODUCTION:

Patients suffering from gynaecological neo-plasms, resulting in peritoneal carcinomato-sis, have a high morbidity and poor quality

of life [1, 2] The current treatment method availablefor patients with local cancer spread with the absenceof distant metastases includes cytoreductive surgeryand the continuous hyperthermic peritoneal perfu-sion with chemotherapeutic agents [3] . There areinnumerable perioperative concerns in these patientswhich include optimal fluid management, maintain-ing mean arterial blood pressure, temperature man-agement, coagulation and electrolyte derangementand renal toxicity of chemotherapeutic drugs.

2 CASE REPORT:

This case report describes a 66 year old, hyper-tensive and asthmatic patient, on regular treat-ment for the same, diagnosed with carcinomaovary who was submitted to cytoreductive surgery(CRS) and hyperthermic intraperitoneal chemother-apy (HIPEC), under general anaesthesia combinedwith a non-continuous epidural block after six cyclesof chemotherapeutic drugs namely Pacliaqualip andCarboplatin.On general and systemic examination, no significantabnormality was noted. Preoperative investigationswere performed in which all routine blood investi-gations were normal. Chest x-ray showed increasedBroncho vascular markings and ECG was normal.2D ECHO showed LVEF 60% with no regional mo-tion wall abnormality andmild diastolic dysfunction.Pulmonary function test were indicative of moderateobstructive ventilator defect with poor reversibil-ity post bronchodilator. The diffusion capacity wasseverely reduced with reduced transfer coefficient.Our patient received Salbutamol and Budecort neb-ulisation twice a day with Foracort 400 inhaler twicea day as prescribed by the chest physician.The patient was taken inside the operating theatreafter ensuring adequate fasting, presenting with amoderate ascitic abdomen. A well written detailedInformed Consent was taken from the patient and

her relatives. They were counselled well regard-ing the expected intraop-complications like signifi-cant blood loss and injury to adjoining vessels andorgans, post op prolonged ICU stay and sos me-chanical ventilation. All emergency drugs includ-ing phenylephrine, adrenaline, antiarrhythmic drugs,noradrenaline infusion and defibrillator pads werekept ready. All necessary drugs and equipment forGeneral anaesthesia were kept ready. The patient wasoptimally monitored with electrocardiogram, non-invasive blood pressure, and pulse oximetry. In theoperating room, the baseline heart rate was notedto be 103 beats per minute and, the blood pressurewas 146/92 mmhg and 96% spo2. Two large venouslines in the upper limbs were secured. The patientwas coloaded with ringer lactate. Subsequently, thepatient was given sitting position for an epiduralblock in T9-T10 using 16 g tuohy needle epidural set,epidural catheter was inserted in T7-8 space under allaseptic precautions.Right radial artery was cannulated under local anaes-thesia for beat to beat blood pressure monitoring.Central line was secured in right internal jugular veinunder USG guidance with local infiltration under allaseptic precautions for CVP monitoring.A balanced general anesthesia was induced with100 µg of Fentanyl, 25 mg of Lidocaine, 120mgof propofol and 50mg of Atracurium. Then, themonitoring was complemented with an oesophagealthermometer was used as muscle relaxant. Patientwas intubated with 7 no. Portex endotracheal tubeand it was fixed at 20 cm at the angle of the mouthafter confirming bilaterally equal air entry. Ryle’stube no 14 FG was inserted, position confirmed onauscultation. Eyes were taped and padded. Anaes-thesia was maintained with air+oxygen +Desfluranewith target MAC of 1.1 and Infusion Atracurium

Supplementary information The online version of this article (https://doi.org/10.15520/jcmro.v3i07.307)

contains supplementary material, which is avaiableto authorized users.

Corresponding Author: Dr. Roly MishraThird year DNB Resident Anaesthesia and Pain Man-agement Sir H N Reliance Foundation Hospital andResearch CentreEmail: rolymishra031@gmail.com

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ANAESTHETIC MANAGEMENT OF CYTOREDUCTIVE SURGERY WITH HYPERTHERMICINTRAPERITONEAL CHEMOTHERAPY (CRS/HIPEC): A TRUE CHALLENGE TO ANANAESTHETISTat the rate of 0.6 mg/kg/hr for muscle relaxation.We ensured that DVT stockings were applied on thepatient as a measure to prevent deep vein thrombosis.Body temperature ranged between 34.6 ◦C and 36.6◦C. During the cytoreduction. when the abdominalcavity is open there is a paramount heat loss andsevere hypothermia. To prevent that warming de-vicesweremade available beforehand (i.e., forced airwarming, warmed infusions, hot blankets). Duringthe HIPEC phase of the surgery as the warm infusategets delivered inside the abdominal cavity,the tem-perature of the patient rises. Cold fluids, ice packs,cooling mattress were also kept prepared for thesame. Our patient had pre-existing lung pathology,and it gets worsened during the surgery. We usedlung protective strategy consisting of low tidal vol-ume, optimal positive end expiratory pressure andrecurrent recruitment manoeuvre’s to prevent therespiratory derangements intra op.Inj. Tranexamicacid 20 mg/kg was administered along with theantibiotic prophylaxis before the surgical incision.Maintaining hemodynamics amongst blood and fluidshifts was extremely challenging. We kept an eyeon hourly urinary output and continuous CVP andPPV.Inf. Albumin 20% was continued during thesurgery. Two units of PCV (736 ml) along with fourFFPS(688 ml) were given to counter on going bloodloss along with 3500 ml of crystalloids.To maintainhemodynamic stability Inf.Noradrenaline support of0.05 mcg/kg/min.was started. A continuous infusionof 0.125% Bupivacaine was continued throughoutthe surgery for pain control. Surgery lasted for 5hours 20minutes. After the procedure the patientwas shifted to ICU on mechanical ventilator for fur-ther monitoring and management with noradrenalinesupport of 0.03 mcg/kg/min. The inotropes weretapered and stopped over the next few hours. Anepidural baxter of 0.125% bupivacaine and 2 mcg/mlFentanyl was started for pain control.Also, she re-ceived Inj.Paracetamol round the clock for betterpain management. On the post-operative day 1, shewas extubated.She had mild pain in the abdominalregion. The postoperative period was uneventful oth-erwise. She evolved to leave the ICU after 48 hourshand was discharged from our institution on the 8thpostoperative day, without complaints. She comesnow for a clinical follow up with the Oncology

Service.Figures 1, 2, 3 and 4

FIGURE 1: PREOPERATIVE CHESTXRAY

FIGURE 2: POSTOPERATIVE CHESTXRAY

3 DISCUSSION:

Primary peritoneal neoplasm and metastasis to peri-toneum from gynaecologic or gastrointestinal cancer

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FIGURE 3: POSTOPERATIVE ABG

FIGURE 4: INTRAOPERATIVE VITALS

are associated with a very poor prognosis and wereconsidered incurable for a long time, until, Dr PaulSugarbaker showed that surgical removal of visi-ble tumour for peritoneal mesothelioma combinedwith loco-regional heated chemotherapeutic drugsimproved median survival of these patients. [4]The surgery requires a full-length midline incisionfollowed by cytoreduction involving removal ofmacroscopic tumour which can vary from omentec-tomy to resection of multiple organs depending onthe spread. In our patient, resection included BSOH,splenectomy, omentectomy, +B/L diphragmatic &anterolateral parietal peritoneumThis is followed by the final stage of chemoperfusionwhere the abdominal cavity is rinsed with a heatedchemotherapy solution which can be done by theopen (or Coliseum) or closed techniques. [5]In our centre, we comply with the open approachwhich ensures gold standard distribution of heatand cytotoxic solution due to manual stirring of theabdominal contents; however, it is associated with;with heat loss which requires an increase in thetemperature of the perfusion fluid, as well as the riskof spillage of cytotoxic drugs. [5, 6]The closedmethod prevents heat loss associated withthe open technique, minimizes drug spillage, and

increases drug penetration, however homogeneousdistribution of the perfusion fluid may now not beachieved [5, 6] . The HIPEC phase which can varyfrom 30 minutes to 2 hours is associated with severalphysiological changes including increase in heartrate, central venous pressure, peak airway pressures,end tidal CO2 levels, decrease in PaO2/FiO2 ra-tio, decreased perfusion to kidneys and metabolicacidosis. The hyperthermia is also associated withcoagulopathy with a decrease in platelet count and anincrease in Prothrombin Time (PT) and InternationalNormalised Ratio (INR).Preoperative evaluation involves a thorough evalu-ation of the patient’s cardiopulmonary systems toassess their ability to tolerate intraoperative physio-logical changes. Our patient was found to have mod-erate obstruction with poor reversibility post bron-chodilator and severely reduced diffusion capacityon spirometry which posed significant challenges in-traoperatively. Ovarian neoplasm is associated withmalnutrition and hypoalbuminemia which is asso-ciated with pronged hospitalisation and increasedcomplications.Prehabilitation plays an important role in overalloutcome which includes optimising the nutritionalstatus, spirometry to improve lung function as atelec-tasis is common in these patients due to associatedascites and pleural effusion as well as giving prophy-laxis for venous thromboembolism. Estimation of theglomerular filtration rate may help identify patientsat risk of an acute kidney injury associated with theHIPEC. [7]The degree of peritoneal disease is assessed by Peri-toneal Cancer Index (PCI) score described by DrSugarbaker, which has a high prognostic value [4]. The PCI score in our patient was 29.Cytoreduction is associated with significant bloodloss and third space loss associated with peritonealinflammation. Keeping in mind the large fluid shifts,fluid resuscitation with crystalloids, colloids i.e. al-bumin and blood and blood products was done tomaintain end organ perfusion. We maintained PPV< 13, MAP >80mmhg, haematocrit > 28 and urineoutput more than 0.5ml/kg/hr during CRS phase andmore than 2 ml/kg/hr during HIPEC phase.

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ANAESTHETIC MANAGEMENT OF CYTOREDUCTIVE SURGERY WITH HYPERTHERMICINTRAPERITONEAL CHEMOTHERAPY (CRS/HIPEC): A TRUE CHALLENGE TO ANANAESTHETISTThese patients also develop coagulopathy either dur-ing CRS or HIPEC phase which can be monitoredby TEG. We gave Tranexamic acid 1 gram and alsotransfused four FFP s during the procedure. Thereis an association between the PCI score and risk ofcoagulopathy. [8]A good pain control is important which can includethoracic epidural in the absence of coagulopathy,opioids, Paracetamol and other regional techniqueslike paravertebral block or subcostal TAP block.During the CRS phase there is a risk of hypother-mia due to extensive debulking and third space losswhich further increases the risk of blood loss. Weused warming blanket, forced air warmer and warmfluids to maintain normothermia. During the HIPECphase the solution is heated to 42 -43 degree Celsiuswhich can cause hyperthermia, which can cause anincrease in oxygen demand, with rising end tidalCO2 levels and a concomitant metabolic acidosis.Prior to commencement of HIPEC phase, wechanged to cool intravenous fluids and decreasedroom temperature and switched off the forced airwarmers in anticipation of the hyperthermia.Thus, we should maintain normothermia by switch-ing off the warming device and using the underbodymattress to cool the patient. Cold intravenous fluidsand placing ice packs in the axillae of the patient mayhelp to normalize the temperature.Another challenge in our case was the obstruc-tive pulmonary disease with severe diffusion defectwhich causes ventilation perfusion mismatch. It cancause air trapping and development of intrinsic PEEPwhich can lead to cardiovascular instability due toincreased intrathoracic pressure. Perioperative betablocker therapy and application of PEEP intraopera-tively helped preventing any complications.Thus, the perioperative management of CRS andHIPEC is complex and requires a team approachwith extensive prehabilitation and optimization toensure successful outcome and early recovery anddischarge.

4 CONCLUSION:

Cytoreduction with HIPEC has emerged as a majoradjunct in the treatment of peritoneal surface cancers.

These cases are difficult to the anaesthetist becausethey are associated with huge blood loss, fluid shifts,gaseous disturbances and hypothermia throughoutthe resection with hyperthermia related compli-cations all through the HIPEC procedure.Authorsthereby suggest adequate preparation, pre-operativeoptimisation, close monitoring and prompt interven-tion with multidisciplinary approach for better man-agement of these patients.Conflicts of Interest:The authors declare there wereno conflicts of interest.Funding: There is not any sources of funding.Ethical Approval:This is a case report. Approval by ethics committeewas not required.

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How to cite this article: Mishra D.R., SharmaD.K., Barpande D.J., Kumari D.N., Mehta D.H.Anaesthetic Management of CytoreductiveSurgery with Hyperthermic IntraperitonealChemotherapy (CRS/HIPEC): A True Chal-lenge To an Anaesthetist . Journal of CurrentMedical Research and Opinion. 2020;503−507. https://doi.org/10.15520/jcmro.v3i07.306

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