Special Article

Society of Onco‑Anaesthesia and Perioperative Care

consensus guidelines for perioperative management
of patients for cytoreductive surgery and hyperthermic
intraperitoneal chemotherapy (CRS-HIPEC)

Address for correspondence: Sohan Lal Solanki, Sudipta Mukherjee1, Vandana Agarwal, Raghu S Thota,
Dr. Sohan Lal Solanki,
Department of
Kalpana Balakrishnan2, Shagun Bhatia Shah3, Neha Desai1, Rakesh Garg4,
Anaesthesiology, Critical Reshma P Ambulkar, Nitin Madhukar Bhorkar5, Viplab Patro1, Snita Sinukumar6,
Care and Pain, 2nd Floor, Meenakshi V Venketeswaran2, Malini P Joshi, Rajesh Holalu Chikkalingegowda7,
Main Building, Tata Memorial
Vijaya Gottumukkala8, Pascal Owusu‑Agyemang8, Avanish P Saklani9,
Hospital, Mumbai ‑ 400 012,
Maharashtra, India. Sanket Sharad Mehta10, Ramakrishnan Ayloor Seshadri11, John C Bell12,
E‑mail: me_sohans@yahoo. Sushma Bhatnagar4, Jigeeshu V Divatia
co.in Department of Anaesthesiology, Critical Care and Pain, Tata Memorial Hospital, Homi Bhabha National
Received: 10 October, 2019
th Institute, 9Gastro-Intestinal Services, Department of Surgical Oncology, Tata Memorial Hospital, Homi
Bhabha National Institute, Departments of 5Anaesthesiology and 10Surgical Oncology, Saifee Hospital,
Revision: 28th October, 2019 Mumbai, 6Surgical Oncology, Jehangir Hospital, Pune, Maharashtra, 1Department of Anaesthesiology,
Accepted: 18th November, Critical Care Medicine and Pain, Tata Medical Center, Kolkata, West Bengal, Department of 2Anaesthesia,
2019 Pain and Palliative Care and 11Surgical Oncology, Cancer Institute, Chennai, Tamil Nadu, 3Department of
Publication: 11th December, Anaesthesiology and Critical Care, Rajiv Gandhi Cancer Institute and Research Centre, Delhi, 4Department
2019 of Onco-Anaesthesiology and Palliative Medicine, Dr BRAIRCH, All India Institute of Medical Sciences,
New Delhi, 7Anaesthesiology, HCG Hospitals, Bengaluru, Karnataka, India, 8Department of Anesthesiology
and Perioperative Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA,
12
Anaesthetics and Intensive Care Medicine, Peritoneal Malignancy Institute, Hampshire Hospitals NHS FT,
Basingstoke, United Kingdom

ABSTRACT

Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS‑HIPEC) for primary

peritoneal malignancies or peritoneal spread of malignant neoplasm is being done at many centres
Access this article online worldwide. Perioperative management is challenging with varied haemodynamic and temperature
Website: www.ijaweb.org instabilities, and the literature is scarce in many aspects of its perioperative management. There
is a need to have coalition of the existing evidence and experts’ consensus opinion for better
DOI: 10.4103/ija.IJA_765_19
perioperative management. The purpose of this consensus practice guideline is to provide
Quick response code
consensus for best practice pattern based on the best available evidence by the expert committee
of the Society of Onco‑Anaesthesia and Perioperative Care comprising perioperative physicians
for better perioperative management of patients of CRS‑HIPEC.

Key words: Consensus, cytoreduction surgical procedures, hyperthermia, induced, peritoneal

neoplasms, peritoneum

This is an open access journal, and articles are distributed under the terms of
INTRODUCTION the Creative Commons Attribution‑NonCommercial‑ShareAlike 4.0 License,
which allows others to remix, tweak, and build upon the work non‑commercially,
as long as appropriate credit is given and the new creations are licensed under
Primary peritoneal malignancy and malignant the identical terms.
neoplasms of gastrointestinal and gynaecological For reprints contact: [email protected]
origin with peritoneal metastases have a poor
prognosis. Traditionally, these types of malignancies How to cite this article: Solanki SL, Mukherjee S, Agarwal V,
were considered incurable conditions suitable for Thota RS, Balakrishnan K, Shah SB, et al. Society of Onco-
Anaesthesia and Perioperative Care consensus guidelines for
palliation. Dr. Paul Sugarbaker showed that surgical perioperative management of patients for cytoreductive surgery and
removal of visible tumour for peritoneal mesothelioma hyperthermic intraperitoneal chemotherapy (CRS-HIPEC). Indian J
combined with locoregional heated chemotherapeutic Anaesth 2019;63:972-87.

972 © 2019 Indian Journal of Anaesthesia | Published by Wolters Kluwer - Medknow

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 Solanki, et al.: SOAPC consensus guidelines of perioperative management of CRS‑HIPEC

drugs improved the quality of life and survival of these such patients. This statement represents the current
patients.[1] Cytoreductive surgery and hyperthermic practice pattern and consensus based on the review
intraperitoneal chemotherapy (CRS‑HIPEC) for of the literature for the best available evidence,
peritoneal malignancies is now done at many centres; individual experience in perioperative management
however, there is no document for best clinical of CRS‑HIPEC patients, inputs from a survey done in
practice related to it. In addition, the literature is India and some centres of England and United States
scarce in many aspects related to the perioperative within a reference group.
management of CRS‑HIPEC. There is immediate
need to have coalition of the existing evidence and The expert committee was divided in nine
experts’ consensus opinion for better perioperative subcommittees (with two experts each) and were
management. assigned a subtopic related to the document. The
experts of each subcommittee also interacted with
CRS‑HIPEC is a complex surgery and perioperative other subcommittees for suggestions and consulted
management depends on many factors including other clinicians as well working in this field during
patient’s preoperative health status, disease the literature review. Each group searched the existing
load, surgical factors, intraoperative events and literature from various search engines including
chemotherapeutic drug/drugs used for HIPEC. HIPEC PubMed, Medline, Cochrane Database, Google Scholar
is a highly concentrated, heated chemotherapy and OVID. The search included randomised controlled
treatment that is delivered directly in the abdomen trials, observational studies, retrospective studies,
after CRS. CRS‑HIPEC with or without systemic review articles, case reports and correspondences
chemotherapy has developed over time as an effective published in English language until August 2019. The
multimodal treatment option for selected patients bibliography of the searched manuscripts was also
with peritoneal surface malignancies. The technique reviewed for any missing relevant articles missed in
involves macroscopic resection of disease burden and initial search and such manuscripts were individually
metastases, followed by infusion of chemotherapy searched from literature. Each expert formulated
heated to 41°C–43°C into the peritoneal cavity by a questions on the subtopic allotted and evidence was
special pump.[2] The efficacy of HIPEC depends on collected accordingly.
a number of patient’s related, clinical and treatment
parameters including class of drug, concentrations of After the collation of evidence from published
drug used, carrier solution, volume of the perfusate, literature, the experts made a survey questionnaire
temperature of the perfusate, treatment duration for the questions for which sufficient literature was
and the technique of delivery.[3,4] There is still high not available or was inconclusive. This questionnaire
variability of HIPEC treatment worldwide based on was discussed in a meeting with all the experts of all
the primary disease and institutional protocol. the subcommittees. After validating the questionnaire
among members of core committee, the final
The purpose of this document is to provide best evidence validated questionnaire was distributed to more than
available and consensus for best clinical practice 60 anaesthesiologists, intensivist, onco‑surgeon and
among perioperative physicians (anaesthesiologists, pain physicians who were actively and regularly
intensivists, surgeons, oncologists and pain physicians) involved in management of CRS‑HIPEC.
and best practice pattern for optimal perioperative
management of CRS‑HIPEC. After the results of the first survey were analysed, the
questionnaire was redistributed to the members of
METHODOLOGY core committee for a total of three rounds for making
consensus as per DELPHI method.[5] Consensus was
This consensus practice guideline document was defined[6] as ‘Strong Consensus’ for 90% or more
prepared by the expert committee of the Society of agreement, ‘Consensus’ for 75%–90% agreement,
Onco‑Anaesthesia and Perioperative Care (SOAPC). ‘Majority Agreement’ for 50%–75% agreement and ‘No
The expert panel included onco‑anaesthesiologists, Consensus’ for less than 50% agreement after three
onco‑surgeons, intensivists and pain physicians, with rounds of discussion on the questionnaire between
inputs from physiotherapists, dietician and oncologists the members of experts’ committee. The proposed
working in the field of peritoneal malignancies and with consensus statement was then presented by select
sufficient experience in perioperative management of members of the expert panel in the ‘HIPEC Consensus

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 Solanki, et al.: SOAPC consensus guidelines of perioperative management of CRS‑HIPEC

Guidelines Session’ in SOAPC annual conference, on with PCI >12 in gastric cancers and PCI >8 in
September 21st 2019 at Hyderabad, India, for wider recurrent ovarian cancer. Although there is no such
discussion and debate. All members of the SOAPC cut‑off for PCI in mesothelioma or pseudomyxoma
and delegates attending the conference were requested peritonei (PMP), a higher PCI is a predictor of poorer
to provide their comments either during the meeting long‑term outcome.[8‑10] It has suggested that for
or later through e‑mail to the first author of this conditions where there is no cut‑off for PCI, CRS‑HIPEC
consensus guideline. The proposed recommendations is contraindicated if complete cytoreduction cannot
were then further revised by the expert panel to be achieved.[9,10] Some sporadic case series suggest
accommodate some of these suggestions. The resulting an extended indication of CRS‑HIPEC with pelvic
consensus guideline document was officially adopted exenteration for rectal cancers.[11]
by members of experts’ committee. When it was
possible to make an evidence‑based recommendation, PREOPERATIVE ASSESSMENT AND OPTIMISATION
the term ‘we recommend’ is used. For other practice
guidelines, the degree of consensus is mentioned. The Preoperative optimisation of CRS‑HIPEC patients
consensus recommendations are mentioned after each should be individualised and depends on patients’
section/subsection but readers are also advised to go age, body mass index, comorbid diseases, functional
through the entire text and not only the consensus status, disease burden, presence or absence of
recommendations. malnutrition (low albumin) and presence or absence
of preoperative anaemia.
SURGICAL FACTORS
Preoperative hypoalbuminaemia can be used
CRS‑HIPEC is a complex procedure with morbidity both as an independent predictor of major
and mortality rates reported between 20%–40% and postoperative complications and as a prognostic
3%, respectively.[7] Over the years, there has been parameter.[12] Perioperative nutrition is a must
a reduction in the morbidity of CRS‑HIPEC which for major cancer surgeries, and enteral nutrition
has been attributed to better patient selection, started preoperatively is the method of choice.[13] In
standardisation of surgical technique, systematic malnourished patients, preoperative sip feed enteral
surgical training and increasing surgical experience. nutrition and in patients with severe metabolic
The Peritoneal Carcinomatosis Index (PCI) provides risk, in whom enteral nutrition cannot provide
a quantitative assessment of the extent of disease adequate energy, preoperative parenteral nutrition is
within the peritoneal cavity [Figure 1]. The PCI is recommended.[14]
an independent predictor of both morbidity and
survival. If the PCI is more than 17–20 in a patient Preoperative malnutrition is prevalent in more than
with colorectal metastases, CRS‑HIPEC should not be 30% patients undergoing CRS‑HIPEC and is associated
offered. No benefit was seen with HIPEC in patients with increased length of stay in hospital and higher

Figure 1: Sugarbaker’s Peritoneal Carcinomatosis Index scoring

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 Solanki, et al.: SOAPC consensus guidelines of perioperative management of CRS‑HIPEC

infectious complications in the postoperative period.[15] chest physiotherapy under the supervision of a
There is a need for preoperative nutrition assessment physiotherapist.[24] Consensus recommendations are
and support if needed.[16] Current guidelines are sparse summarised in Table 1.
in directing nutrition practice in this patient group.
General cancer nutrition guidelines recommend CHEMOTHERAPY
routine preoperative nutrition assessment and
1–2 weeks of oral nutritional optimisation and support The rationale for HIPEC is to maximise the
prior to surgery in nutritional compromised patients exposure of local tissues to high concentrations of
to decrease morbidity.[17,18] The role of perioperative chemotherapeutic agents (20–1000 times greater
immune nutrition in major cancer surgeries is than plasma levels) with minimal effects on normal
controversial; few studies showed benefit,[19] whereas tissue.[25] The most commonly used drugs for
others showed no advantages.[20] intraperitoneal (IP) administration are mitomycin‑C
and the platinum‑based drugs, cisplatin, carboplatin,
Assessment of the functional status in these patients is and oxaliplatin which have synergistic effect with heat.
vital. In addition to routine blood testing, the patient The less commonly used are doxorubicin, docetaxel,
should be screened and optimised according to the paclitaxel, 5‑fluorouracil and irinotecan [Table 2].[4]
preexisting comorbidities. A 12‑lead electrocardiogram Bidirectional intraoperative chemotherapy involves
and a baseline two‑dimensional echocardiogram are concomitant administration of intraoperative
usually enough. Dynamic cardiac testing can be done intravenous and IP chemotherapy, aiming to create
using either exercise testing or dobutamine stress a bidirectional diffusion gradient through the cancer
echocardiography in patients with limited cardiac cells.
reserve or in conditions where functional capacity
cannot be assessed.[21] Preoperative anaemia is The ideal carrier solution should improve exposure
common, and it is associated with increased morbidity of the peritoneal surface, have slow clearance from
and requires massive blood transfusion.[22] Correction the peritoneum, maintain high intraperitoneal
of anaemia should be started as soon as decision for volume and not have any adverse effects on the
surgery is made.[23] peritoneal membranes.[26] Currently, isotonic saline or
dextrose‑based peritoneal solutions are recommended
CRS‑HIPEC is associated with increased incidence with most centres using 1.5% dextrose isotonic
of postoperative pulmonary complications. The peritoneal dialysis solutions.[27] Oxaliplatin was given
factors contributing to this are prolonged operative in 5% dextrose‑based water solution as previously it
time, diaphragmatic splinting, lithotomy position, was thought that chloride ions degrade oxaliplatin
preoperative pleural effusion, ascites or presence of into less cytotoxic metabolites. However, it is
preoperative compromised pulmonary functions. demonstrated that chloride‑containing solutions can
Preoperative incentive spirometry and respiratory be safely used with oxaliplatin and in fact it increases
muscle training and continuation in postoperative its cytotoxicity.[27] The systemic absorption of 5%
period help prevent postoperative pulmonary dextrose solutions can lead to severe hyperglycaemia
complications. These patients should undergo regular and hyponatremia.

Table 1: Consensus recommendations for preoperative assessment and optimisation

Recommendation/suggestion Level of consensus/evidence
We recommend all routine blood investigations and 12‑lead electrocardiogram for all patients. Evidence
We suggest routine preoperative resting 2D echocardiogram. Consensus
Patients should visit perioperative physician 1-4 weeks prior to surgery for optimisation depending on Strong consensus
time availability.
We recommend that preoperative oral or enteral nutrition should be started in all malnourished patients. Strong consensus and evidence
Preoperative oral supplemental nutrition may be considered even if patients are not malnourished. Majority agreement
There is no role of routine perioperative immune nutrition in CRS‑HIPEC patients. Strong consensus
Preoperative physiotherapy and physical exercise should be started Strong consensus
Respiratory exercise training Strong consensus
Muscle training Consensus
Aerobics Majority agreement
2D – Two‑dimensional; CRS‑HIPEC – Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy

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 Solanki, et al.: SOAPC consensus guidelines of perioperative management of CRS‑HIPEC

Table 2: Commonly used chemotherapeutic drugs and their characteristics

Drug Type Dosage (mg/m2 BSA) AUC ratio Common toxicities Common uses
Mitomycin C Antitumour 10-160 23.5 Nephrotoxicity, pulmonary toxicity, Appendix, PMP, colorectal,
antibiotic myelosuppression gastric, ovary
Oxaliplatin Alkylating agent 160-460 16 Neurotoxicity, GI bleeding, nephrotoxicity, Colorectal, appendix, gastric
peripheral neuropathy, myelosuppression
Cisplatin Alkylating agent 50-360 7.8 Nephrotoxicity Ovary, colorectal, gastric, PMP
Carboplatin Alkylating agent 350-800 18 Myelosuppression Appendix, ovary
Doxorubicin Antitumour 15 230 Cardiotoxicity, myelosuppression Appendix, PMP, colorectal,
antibiotic ovary, malignant ascites
Irinotecan Plant alkaloid 100-400 myelotoxicity Colorectal
Paclitaxel Plant alkaloid 60-175 1000 Myelosuppression, peripheral neuropathy Ovary
Docetaxel Plant alkaloid 80 552 Myelosuppression, pulmonary toxicity Gastric
5‑Florouracil Antimetabolite 1000 250 GI, myelosuppression, neurotoxicity GI
AUC – Area under curve; BSA – Body surface area; GI – Gastrointestinal; PMP – Pseudomyxoma peritonei

HIPEC can be delivered by open or closed abdominal overall survival in oncologic patients.[31,32] However,
techniques. The closed abdominal method was a retrospective study of CRS‑HIPEC for appendiceal
the first technique described and still used widely. tumours demonstrated that volatile agent with
The open abdominal is usually performed by the opioid anaesthesia is associated with increased
‘Coliseum technique’. The commonly used perfusate progression‑free survival and 5‑year overall survival
volumes are 1.5–2 L/m2 body surface area. During the when compared with multimodal TIVA group.[33]
HIPEC procedure, the roller pump forces the perfusate The survival benefit of opioid sparing TIVA was only
through the inflow line into the abdomen and pulls demonstrated in low‑volume diseases and lower
it out through the drains at the rate of 1 L/min. The American Society of Anesthesiologists (ASA) physical
heat exchanger keeps the perfusate temperature at status patients.[31,32,34] Use of nitrous oxide during
43°C–45°C, so that the intraperitoneal temperature is CRS‑HIPEC is not evaluated and many researchers
maintained at 41°C–43°C. Once full circulation of the and practitioners are using it routinely. Guidelines for
perfusate in and out of the abdomen is achieved with a anaesthetic management are summarised in Table 3.
temperature of around 41.5°C, the drug is added to the
primer and the timer is set to 30–90 min depending on MONITORING
the drug.
Haemodynamic monitoring
ANAESTHETIC TECHNIQUES AND MONITORING In addition to standard monitoring such as
electrocardiogram, noninvasive blood pressure, pulse
The choice of anaesthesia and analgesia may affect oximetry, end‑tidal CO2 monitoring and core‑body
long‑term cancer outcomes after CRS‑HIPEC. In temperature monitoring, these patients require
animal models, volatile anaesthetic agents and opioids invasive blood pressure monitoring and sometimes
enhance the malignant potential of tumours by central venous pressure monitoring.[35,36] Cardiac
promoting invasion and proliferation of tumour cells output monitoring is being used in many centres in
and by immunosuppression and angiogenesis.[28,29] A high‑volume diseases (PCI >15) or in isolated case
recent meta‑analysis showed that use of propofol‑based reports.[37‑39] Goal‑directed therapy (GDT) in CRS‑HIPEC
total intravenous anaesthesia (TIVA) was associated had shown lower morbidity and postoperative length
with improved recurrence‑free survival and overall of stay with no difference in mortality.[40]
survival after cancer surgeries.[30]
Arterial blood gas monitoring is often needed
Induction of anaesthesia varies with the type of periodically throughout the surgery to assess gas
primary disease. Patients with large PMP and other exchange, electrolyte and lactate levels.[37,38] When 5%
appendiceal tumours may have a large abdomen dextrose is used as a perfusate, it is essential to monitor
due to ascites and disease load and there may be a serum sodium and 1–2 hourly blood glucose levels as
risk of aspiration in these patients and may require hyponatraemia and hyperglycaemia can occur.[41] It
rapid sequence intubation.[2] There are data that is prudent to measure the serum magnesium levels
suggest that use of volatile anaesthetic agents and during surgery especially before the HIPEC phase and
opioids decreases the recurrence‑free survival and also in postoperative period as hypomagnesaemia

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 Solanki, et al.: SOAPC consensus guidelines of perioperative management of CRS‑HIPEC

can result from dilution secondary to fluid infusion monitoring (TEG and thrombocyte function analyser
and following administration of platinum‑based multiplate) can detect complex coagulation disorders
perfusate.[42,43] With massive/significant blood loss such as hyperfibrinolysis, thrombocytopathies/
and transfusion of blood and blood products, ionised penia or factor XIII deficiency.[49] There is no clear
calcium should be monitored and corrected. evidence of timing/phase to do coagulation testing in
perioperative period except preoperative period.[48,50,51]
Goal for intraoperative urine output Consensus recommendations are mentioned in
The incidence of acute kidney injury (AKI) after Table 4.
CRS‑HIPEC ranges from 21.3% to 48%.[44,45] Higher
age, higher BMI, use of preoperative pregabalin, Fluid management
platinum‑based chemotherapy, major blood loss, Fluid management is an important aspect of
hypertension and low intraoperative diuresis were haemodynamic management in patients undergoing
predictors of development of AKI. The incidence of AKI CRS‑HIPEC, but it also one of the most controversial.
was 3.7% following cisplatin‑based (50 mg/m2) HIPEC. During CRS phase, intraoperative fluid loses may
Low intraoperative urine output, use of angiotensin reach as high as 8–12 mL/kg along with significant
II receptor antagonist and hypertension were factors blood loss.[52] Adequate perioperative crystalloids and
associated with development of AKI.[42] Intraoperative colloids are needed to ensure end‑organ perfusion
measurement of urine output is used as a surrogate and maintain haemodynamic goals without causing
marker of renal perfusion. During HIPEC phase, volume overload. There is lot of heterogeneity in the
maintaining optimal urine output is vital. The literature regarding the type of intravenous fluid, that
recommended targets for urine output during various is, crystalloids and colloids, to be used in CRS‑HIPEC.
phases are up to 0.5 mL/kg/h during CRS, 2–4 mL/kg/h Use of hydroxyethyl starch (HES), although extensively
during the HIPEC phase and 1–2 mL/kg/h post‑HIPEC used,[52,53] remains debated because of the association
phase.[13,46,47] However, these thresholds are debatable with AKI and need for renal replacement in critically
in the context of individualised fluid therapy. ill patients[54,55] but not in surgical patients.[56,57]

Debate about hydration and higher diuresis during Table 3: Consensus recommendations for anaesthetic
HIPEC has many reasons. First, chemotherapy is management and monitoring
not administered intravenously. Second, the degree Recommendation/suggestion Level of
consensus/
of absorption and serum concentration may be
evidence
variable depending on the surface area. Third, drug Thoracic epidural analgesia should be used in all Strong
clearance depends on the renal blood flow and not patients if not contraindicated. consensus
the urine output. Fourth, while renal failure can be Intravenous induction of anaesthesia with propofol Strong
and induction dose of opioid should be done. consensus
attributed to platinum, it is often multifactorial. Thus,
Volatile agents (isoflurane/sevoflurane/desflurane) Strong
maintaining euvolaemia in the perioperative period by can be used for maintenance of anaesthesia. consensus
individualising fluid therapy seems prudent. Inhalational anaesthesia vs TIVA can be selected Strong
based on patient’s disease load, tumour grading consensus
Coagulation monitoring and ASA status. Low‑volume disease and lower
ASA physical status patients may be given TIVA.
Coagulopathy following CRS is multifactorial and TIVA – Total intravenous anaesthesia; ASA – American Society of Anesthesiologists
depends on the duration of surgery, extent of resection,
that is, PCI, blood loss and degree of haemodilution Table 4: Consensus recommendations for coagulation
which in turn depends on the volume of replacement monitoring
with crystalloids and colloids, transfusion of packed Recommendation/suggestion Level of consensus/
evidence
red cells and hypothermia. Coagulopathy peaks at 24 h
We recommend PT, aPTT and INR Evidence, consensus
and may persist up to 72 h in the postoperative period.[13] testing in the preoperative period.
Intraoperative monitoring of coagulation parameters We suggest PT, aPTT and INR Consensus
periodically depending on the volume of estimated testing in the postoperative period.
blood loss is advisable. Prothrombin time (PT), PT, aPTT and INR testing should be No consensus, <50%
individualised in intraoperative period agreement
activated partial thromboplastin time (aPTT) and if blood loss is more than 50% of
international normalised ratio (INR) are used in most blood volume and after HIPEC phase.
PT – Prothrombin time; aPTT – Activated partial thromboplastin time;
centres and thromboelastography (TEG or ROTEM) INR – International normalised ratio; HIPEC – Hyperthermic intraperitoneal
in some centres.[48] Use of point‑of‑care coagulation chemotherapy

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HES (130/0.4) was found to have a negative impact Table 5: Consensus recommendations for fluid
on the renal function in patients undergoing HIPEC, management and monitoring
though fewer HIPEC patients received HES.[58] HES Recommendation/suggestion Level of consensus/
evidence
causes increased reduction in maximum amplitude on Balanced salt solutions like Ringer’s lactate Strong consensus
TEG and increased perioperative bleeding compared and acetate‑based solution should be used.
with crystalloids and albumin.[59] Balanced fluids, Albumin should be used as the colloid of Strong consensus
like Ringer’s lactate and acetate‑based solutions, choice
We suggest use of noninvasive cardiac Consensus
have an electrolyte composition close to plasma, output monitoring like arterial‑pressure‑
whereas isotonic normal saline has supraphysiologic based cardiac output monitoring along with
chloride content which induces hyperchloremia and invasive blood pressure monitoring.
Urine output goal of 1 mL/kg/h during CRS Majority agreement
metabolic acidosis.[60,61] Liberal fluid administration and reconstructive phases and 2 mL/kg/h
leads to fluid overload and tissue oedema and causes during HIPEC phase can be considered.
abdominal, cardiac or pulmonary complications. Urine output goal should be accomplished Consensus
Fluid overload has been found to be associated with by use of intravenous fluids and if required
diuretics based on clinical scenario.
an increased morbidity.[46,47] Restrictive fluid regimens CRS – Cytoreductive surgery; HIPEC – Hyperthermic intraperitoneal chemotherapy
have demonstrated decreased perioperative mortality
in other major surgical procedures.[62‑64] However, Temperature management
restricted fluid therapy can cause suboptimal tissue and Normothermia maintenance is an important goal
renal perfusion in the face of extreme haemodynamic in the perioperative period in patients undergoing
changes that occur during the phases of CRS‑HIPEC.[65] CRS‑HIPEC.[13] Extensive CRS and HIPEC can cause
In CRS‑HIPEC procedures, Colantonio et al.[40] found wide variations in temperature.[71] Hyperthermia
that patients in the GDT group received significantly during the HIPEC phase results in increase in the
reduced volume of fluids, had lower morbidity and metabolic rate, consequentially resulting in an
postoperative length of stay with no difference in increase in oxygen demand, heart rate, end‑tidal
mortality. carbon dioxide, lactatemia and worsening metabolic
acidosis. These physiological alterations depend on
GDT with individualised therapeutic end points can be the magnitude of the hyperthermia, which usually
achieved using a combination of colloids, crystalloids reaches a maximum level of 60 min after the infusion
and vasopressors. There is extensive loss of protein in initiation. These hyperdynamic alterations reverse
the ascitic fluid and secondary to surgical dissection. once the temperature normalises. The lactate levels
Hence, albumin replacement has been shown to be after HIPEC should be interpreted with caution as
beneficial in patients requiring extensive debulking they may not be due to hypoperfusion alone and other
and large‑volume ascites drainage.[66] causes should be evaluated.[48] Hyperthermia can also
cause coagulopathies, renal and liver dysfunction,
Early start of vasopressors is advocated to avoid neuropathies and seizures. Hyperthermia can be
hypervolemia. Routine use of furosemide, mannitol or prevented using forced air warmers at ambient
low doses of dopamine to prevent renal dysfunction is temperature, use of cold intravenous fluids <6°C and
not recommended as it does not affect the creatinine use of cooling mattress and ice packs placed in the
values after CRS‑HIPEC.[13,67] Diuretics may be axilla and around the head and neck prior to HIPEC.
required in selected cases wherein urine output is If these measures fail and core temperature continues
inadequate despite adequate intravascular fluid status, to rise, reduction in temperature of perfusate can help.
but it is prudent to avoid diuretics until the patient Cooling (active or passive) the patient before starting
is euvolaemia.[68] Sodium thio‑sulphate is being used the HIPEC phase is another technique that can be used
for prevention of cisplatin‑induced nephrotoxicity to prevent excessive rise in temperature during the
with promising results[69] but is yet to be established HIPEC phase.[25]
as standard of care. Perioperative blood transfusion
policy should be like any other major surgery, and Delta temperature (difference between least and
triggers for blood product transfusion should be highest temperatures) during CRS‑HIPEC was found
individualised. The risk factors for massive transfusion to be a significant predictor of intensive care unit
during CRS‑HIPEC are preoperative anaemia, (ICU) stay >5 days.[38] This is highest in patients with
impaired coagulation profile and high tumour burden high PCI necessitating longer, aggressive resection.
(PCI 16 or more)[70] [Table 5]. The sequential temperature changes exacerbate

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 Solanki, et al.: SOAPC consensus guidelines of perioperative management of CRS‑HIPEC

systemic effect in addition to hypo‑ or hyperthermia. Table 6: Consensus recommendations for temperature
Hypothermia during the CRS phase is associated management and monitoring
with cardiac morbidity, decreased humoral and Recommendation/suggestion Level of consensus/
evidence
cell‑mediated immunity and impaired acid–base We recommend monitoring of core body Evidence
balance thus reflecting prolonged ICU stay.[72] This temperature.
should be managed with forced air warming with We recommend maintenance of Strong consensus
normothermia during CRS phase. and evidence
blankets and blood/fluid warmers [Table 6].
We suggest passive cooling (switching Consensus
off warming devices) of patients before
PAIN MANAGEMENT starting HIPEC (35°C-36°C).
Temperature should/can be controlled
CRS‑HIPEC requires analgesia coverage from T4 down during HIPEC phase by Consensus
Use of ice packs in axilla and neck Consensus
to low lumbar dermatomal segments.[73] These patients
during HIPEC phase Majority agreement
frequently complain of chronic pain, chronic fatigue Use of cool air blankets during HIPEC
and a poor quality of life after surgery.[74,75] Intraoperative Use of cold crystalloids at around 6°C
use of epidural analgesia using local anaesthetic agents during HIPEC phase
with or without opioids is frequently used to decrease We suggest keeping core body Consensus
temperature below 39°C and instruct to
intraoperative systemic opioid requirement. reduce temperature of perfusate if core
body temperature rises above 39°C.
Some centres do not recommend or recommend CRS – Cytoreductive surgery; HIPEC – Hyperthermic intraperitoneal chemotherapy

cautious use of thoracic epidural analgesia as

the resultant hypotension may affect the clinical Table 7: Consensus recommendations for pain
management
determination of fluid status; also, patients may
Recommendation/suggestion Level of
develop coagulopathy which predispose them to consensus/
epidural haematoma, postoperative infections and evidence
sepsis.[50,76,77] The incidence of epidural abscess in this A thoracic epidural catheter should be placed Strong
preoperatively if not contraindicated. consensus
patient group was found to be 1:2139.[48] Clot kinetics
We suggest intraoperative use of epidural analgesia Strong
measured by TEG indicates that epidural catheters consensus
may be safe for postoperative analgesia.[78] Local anaesthetic and opioid‑based epidural Strong
analgesia should be used along with intravenous consensus
paracetamol in postoperative period up to 4-5 days.
The main disadvantages of primary opioid‑based
IVPCA should be used long with TEA if pain relief is Strong
analgesia are increased incidence of respiratory not adequate/all dermatomes are not covered. consensus
complications and need for postoperative ventilatory IVPCA should be used in patients with Strong
support.[64] A recent retrospective review[79] of 215 contraindications for placement of an epidural consensus
catheter, or discontinued epidural catheter.
CRS‑HIPEC patients showed that epidural analgesia
TEA – Thoracic epidural analgesia; IVPCA – Intravenous patient‑controlled
was safe to use in terms of intraoperative and analgesia
postoperative haemodynamic parameters. The median
duration of epidural use is 5 days and it recommends POSTOPERATIVE AND INTENSIVE CARE
daily check of coagulation testing until the fourth MANAGEMENT
postoperative day or on clinical request.[48] A study
showed that only 72% of centres worldwide regularly Tracheal extubation in the operating room (OR)
use epidural analgesia to manage postoperative pain or shifting the patients to ICU with endotracheal
after CRS‑HIPEC.[78] Many centres use a combination tube (ETT) in situ depends on the duration of
of epidural and opioid‑based patient‑controlled surgery, preoperative major cardiac or respiratory
intravenous systemic analgesia (IVPCA) for comorbidities, blood loss and transfusion,
postoperative pain management after CRS‑HIPEC. haemodynamic stability, metabolic derangement
A recent international survey has shown that only and arterial lactate towards end of surgery or any
28% of centres performing CRS‑HIPEC reported other organ failure.[80] All or most of the patients are
postoperative pain control as excellent, despite transferred to ICU in the immediate postoperative
the frequent use (69%) of combined epidural and period (mean 93%, range 20%–100%). The ETT
IVPCA.[62] Other analgesic options include single or was removed in 42%–62% in the OR.[48] Improved
continuous paravertebral or subcostal transverses patient selection, better surgical technique,
abdominis plane blockade [Table 7]. better perioperative management and increasing

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 Solanki, et al.: SOAPC consensus guidelines of perioperative management of CRS‑HIPEC

experience gained by high‑volume centres can Postoperative complications include anastomotic

help in management of certain subgroup of HIPEC leaks, sepsis, ileus, pancreatitis, fistula, pulmonary
patients (e.g. low PCI, minimal blood loss) in a embolism, DVT and reoperation.[84] ASA class higher
non‑ICU setting.[81,82] Immediate or early extubation than 3 and surgical time more than 10 h are the
of the trachea, epidural analgesia, postoperative significant risk factors for grades IV/V morbidity in
monitoring in ICU, immediate initiation of parenteral patients with PMP.[89] Postoperative complications
nutrition in postoperative period and stringent fluid requiring intervention are the only significant risk
status monitoring help in favourable postoperative factor for early recurrence other than the extent of
outcome.[83] peritoneal disease.[90] Early recurrence after CRS‑HIPEC
is associated with a significant reduction in overall
Postoperative stress response involves all major survival.[90] Major morbidity rates range from 12% to
organs such as cardiovascular, respiratory, 52% in high‑volume centres. The mortality rate after
coagulation, renal and endocrine system.[84,85] There CRS‑ HIPEC ranges from 0.9% to 5.8%.[7,91,92] Left upper
can be hyperthermia‑related coagulopathy leading to quadrant peritonectomy and small bowel resection are
increased PT and INR along with low platelet counts. the factors that are predicted for a poor perioperative
Hyperglycaemia is also a common finding because outcome.[93] The most frequent complications are
of physiologic stress and a hypercatabolic state. surgical site infections including intraabdominal
Anticipated postoperative course includes low‑grade abscess, gastric or small intestinal perforation,
fever and moderate to severe pain. Diarrhoea can occur postoperative ileus, anastomotic leakage, urinary
in the first week because of digestive hypersecretion. disturbance, intestinal fistula and postoperative
Leukocyte counts and platelet counts progressively bleeding[91] [Table 8].
decrease in the first 2 weeks followed by progressive
increase. Transient severe hypophosphatemia is PAEDIATRIC CRS‑HIPEC
observed on the first 2–3 postoperative days due to
renal tubulopathy related to hyperthermia. There CRS‑HIPEC in children has been performed in
may be transaminitis with liver function tests being peritoneal tumours of various origins including
elevated 2‑ to 3‑fold during the first 4 postoperative desmoplastic round cell tumour, rhabdomyosarcoma
days, probably due to extensive electrocoagulation and colorectal cancer.[94] Apart from age‑based
of the liver capsule. Inflammatory markers such as variations, the anaesthetic management of children
C‑reactive protein, interleukins and elastase increase undergoing CRS‑HIPEC is similar to that in adults.
during surgery and come back to normal within Monitoring guidelines and practice are the same as an
12–24 h. adult patient except that the arterial‑pressure‑based
cardiac output monitoring is typically not used.
Early postoperative GDT with the help of A central venous catheter may or may not be required.
transthoracic thermodilution technique and In a retrospective study of children and adolescents
arterial‑pressure‑based cardiac output[47,86] had shown who had undergone CRS‑HIPEC, fluid administration
variable results. Abnormalities in coagulation profile at an average rate of 9 mL/kg/h was required to maintain
after CRS‑HIPEC surgery usually take 3‑6 days to urine output.[95] In the absence of contraindications,
resolve. Mechanical and pharmacological deep vein an epidural catheter is usually placed. Similar to
thrombosis (DVT) prophylaxis should be considered CRS‑HIPEC in adults, there is a risk for major blood
as appropriate during the entire perioperative period loss during CRS‑HIPEC in children.[96,97] In general,
if not contraindicated, starting from the preoperative an intraoperative haemoglobin value of less than
period (low‑molecular‑weight heparin) through the 10 g/dL is usually a trigger for discussion about blood
immediate postoperative period. transfusion. Transfusion rates of up to 80% have been
reported.[96]
Preoperative nutritional status influences the
postoperative outcome in terms of length and survival HYPERTHERMIC INTRATHORACIC OR
in patients with cancer undergoing HIPEC.[87] A THORACOABDOMINAL CHEMOTHERAPY
majority of the patients do not tolerate enteral feed
in the first postoperative week, and hence parenteral Pleural malignancies may be of different origin
nutrition may be initiated early and switched to enteral such as malignant pleural mesothelioma, advanced
nutrition whenever acceptable.[88] thymoma with pleural dissemination or spread from

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 Solanki, et al.: SOAPC consensus guidelines of perioperative management of CRS‑HIPEC

Table 8: Consensus recommendations for postoperative and intensive care management

Recommendation/suggestion Level of consensus/evidence
Do not routinely extubate the trachea on operating table. Evidence
Tracheal extubation in the operating room should be attempted in low‑volume (low PCI) cases. Evidence and consensus
We suggest that patients with unstable haemodynamics should be transferred to ICU with Consensus
endotracheal tube in situ.
Patients with massive blood loss, high arterial lactate and diaphragmatic striping may be Majority agreement
considered for transferred to ICU with endotracheal tube in situ.
Decision of transferring patient to ICU with endotracheal tube in situ or with after tracheal No consensus, <50%
extubation in patients who undergone prolonged (>10 h) surgery, presence of preoperative bad agreement
pulmonary functions and major cardiac or non‑cardiac comorbidities should be individualised.
Postoperative fluid therapy should be based on
Mean arterial pressure, heart rate and urine output guided fluid therapy Consensus
Arterial lactate‑guided fluid therapy Majority agreement
We recommend use of early enteral nutrition or parenteral nutrition in patient who cannot Strong consensus and
tolerate enteral nutrition. evidence
PCI – Peritoneal Carcinomatosis Index; ICU – Intensive care unit

PMP.[98] Recently, CRS along with intraoperative connected to a high‑pressure injector and a therapeutic
hyperthermic intrathoracic chemotherapy (HITHOC) capno‑peritoneum is created and maintained for 30 min
perfusion has been advocated to reduce local tumour at a temperature of 37°C.[102] PIPAC is offered mostly in
spread,[99,100] and it significantly increased the median high‑volume disease where complete cytoreduction
survival, tumour‑free survival rate and performance is not possible. At the end of the procedure, the
status.[101] In PMP with limited pleural extension chemotherapy aerosol is exhausted into the OR
of metastasis, thoracoabdominal approach for scavenging setup through a closed system. Perioperative
cytoreduction (removal of pleural metastasis) is usually management of PIPAC is no different from any other
performed followed by heated chemoperfusion. This gastrointestinal procedures with standard general
procedure is called hyperthermic thoracoabdominal anaesthesia. No additional haemodynamic monitoring
chemotherapy (HITAC).[37,98] Preoperative work‑up and is needed. Patients can be extubated in the OR.
optimisation for patients scheduled for CRS and HITHOC
or HITAC are the same for CRS‑HIPEC. We recommend Chemotherapy drugs in the aerosolised form pose
additional preoperative pulmonary function tests apart potential occupational exposure to the OR personnel
from investigations needed for CRS‑HIPEC. For cardiac during PIPAC. Chemotherapy agents have several
output monitoring, pulse pressure variation and stroke adverse effects such as hair loss, headache, acute
volume variation may not work because of open chest; irritation, hypersensitivity, congenital malformations
delta SV protocol can be a better guidance of fluid status in pregnant women, foetal loss, low birthweight,
and therapy.[37] Chemotherapy in the intrathoracic infertility and leukaemia.[103] A laminar flow in the OR is
cavity causes increased fluid load and may lead to recommended, but when PIPAC is done with strict safety
increased airway pressures, increased intrathoracic measures, even without laminar flow, PIPAC seems
pressures, mediastinal shift and decreased functional harmless.[104] N‑95 mask with a tight seal around the
residual capacity. Extubation in the postoperative nose and mouth must be worn by all OR personnel.[105]
unit is preferred in view of large fluid shifts and The injection and nebuliser which produce aerosol
reduction of pulmonary lung volumes after surgery. must be remote‑controlled and should be controlled
Complications of HITHOC are similar to HIPEC, but from outside the OR. No personnel should stay inside
some of the complications are exclusive for HITHOC the OR and the patient should be monitored remotely.
such as pulmonary emboli, chest pain, dyspnoea, The whole system of capnoperitoneum must be airtight
bronchopleural fistula, pneumothorax, empyema and with no leaks. Severe peritoneal sclerosis post repeated
air leak.[37] PIPAC has been observed.[106] There is an elevation of
CRP levels which is a sign of chemical peritonitis.[107]
PRESSURISED INTRAPERITONEAL AEROSOLISED
CHEMOTHERAPY ENHANCED RECOVERY AFTER SURGERY AND
CRS‑HIPEC
In pressurised intraperitoneal aerosolised
chemotherapy (PIPAC), aerosol of chemotherapeutic Prof. Kellet in early 1990s challenged the existing
drug is created with the help of a nebuliser which is dogmas and implemented evidence‑based principles/

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 Solanki, et al.: SOAPC consensus guidelines of perioperative management of CRS‑HIPEC

elements in the perioperative period in colorectal benefits of ERAS in patients undergoing CRS‑HIPEC
surgery and demonstrated reduction in postoperative were evaluated retrospectively before and after ERAS
length of stay. Compliance with enhanced recovery protocol and it was observed that the ERAS pathway
after surgery (ERAS) elements has been favorably was associated with significant reduction in the length
associated with reduced morbidity and length of stay of stay and early gastrointestinal recovery with no
and cost with no impact on readmission across surgical difference in morbidity and mortality.[111]
specialties.[108‑110] Despite these positive results,
evidence regarding ERAS in patients undergoing All consensus recommendations are summarised in
CRS‑HIPEC procedures is lacking. The feasibility and Table 9.

Table 9: Summary of consensus recommendations

Recommendation/suggestion Level of consensus/evidence
Preoperative assessment and management
We recommend all routine blood investigations and 12‑lead electrocardiogram for all patients. Evidence
We suggest routine preoperative resting 2D echocardiogram. Consensus
Patients should visit perioperative physician 1-4 weeks prior to surgery for optimisation depending on Strong consensus
time availability.
We recommend that preoperative oral or enteral nutrition should be started in all malnourished patients Strong consensus and evidence
Preoperative oral supplemental nutrition may be considered even if patients are not malnourished. Majority agreement
There is no role of routine perioperative immune‑nutrition in CRS‑HIPEC patients Strong consensus
Preoperative physiotherapy and physical exercise should be started Strong consensus
Respiratory exercise training Strong consensus
Muscle training Consensus
Aerobics Majority agreement
Anaesthetic management and monitoring
Thoracic epidural analgesia should be used in all patients if not contraindicated. Strong consensus
Intravenous induction of anaesthesia with propofol and induction dose of opioid should be done Strong consensus
Volatile agents (isoflurane/sevoflurane/desflurane) can be used for maintenance of anaesthesia. Strong consensus
Inhalational anaesthesia vs TIVA can be selected based on patient’s disease load, tumour grading and Strong consensus
ASA status. Low‑volume disease and lower ASA physical status patients may be given TIVA.
Coagulation monitoring
We recommend PT, aPTT and INR testing in the preoperative period Evidence, consensus
We suggest PT, aPTT and INR testing in the postoperative period Consensus
PT, aPTT and INR testing should be individualised in intraoperative period if blood loss is more than No consensus, <50% agreement
50% of blood volume and after HIPEC phase.
We recommend PT, aPTT and INR testing in the preoperative period Evidence, consensus
Fluid management and monitoring
Balanced salt solutions like Ringer’s lactate and acetate‑based solution should be used. Strong consensus
Albumin should be used as the colloid of choice. Strong consensus
We suggest use of noninvasive cardiac output monitoring like arterial‑pressure‑based cardiac output Consensus
monitoring along with invasive blood pressure monitoring.
Urine output goal of 1 mL/kg/h during CRS and reconstructive phases and 2 mL/kg/h during HIPEC Majority agreement
phase can be considered.
Urine output goal should be accomplished by use of intravenous fluids and if required diuretics based Consensus
on clinical scenario.
Temperature management and monitoring
We recommend monitoring of core body temperature. Evidence
We recommend maintenance of normothermia during CRS phase. Strong consensus and
evidence
We suggest passive cooling (switching off warming devices) of patients before starting Consensus
HIPEC (35°C-36°C).
Temperature should/can be controlled during HIPEC phase by
Use of ice packs in axilla and neck during HIPEC phase Consensus
Use of cool air blankets during HIPEC Consensus
Use of cold crystalloids at around 6°C during HIPEC phase Majority agreement
We suggest keeping core body temperature below 39°C and instruct to reduce temperature of Consensus
perfusate if core body temperature rises above 39°C.

Contd...

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 Solanki, et al.: SOAPC consensus guidelines of perioperative management of CRS‑HIPEC

Table 9: Contd...
Recommendation/suggestion Level of consensus/evidence
Pain management
A thoracic epidural catheter should be placed preoperatively if not contraindicated. Strong consensus
We suggest intraoperative use of epidural analgesia. Strong consensus
Local anaesthetic and opioid‑based epidural analgesia should be used along with intravenous Strong consensus
paracetamol in postoperative period up to 4-5 days.
IVPCA should be used long with TEA if pain relief is not adequate/all dermatomes are not covered. Strong consensus
IVPCA should be used in patients with contraindications for placement of an epidural catheter, or Strong consensus
discontinued epidural catheter.
Postoperative and intensive care monitoring
Do not routinely extubate the trachea on operating table. Evidence
Tracheal extubation in the operating room should be attempted in low‑volume (low PCI) cases Evidence and consensus
We suggest that patients with unstable haemodynamics should be transferred to ICU with endotracheal Consensus
tube in situ.
Patients with massive blood loss, high arterial lactate and diaphragmatic striping may be considered for Majority agreement
transferred to ICU with endotracheal tube in situ.
Decision of transferring patient to ICU with endotracheal tube in situ or with after tracheal extubation in No consensus, <50% agreement
patients who undergone prolonged (>10 h) surgery, presence of preoperative bad pulmonary functions
and major cardiac or non‑cardiac comorbidities should be individualised.
Postoperative fluid therapy should be based on
Mean arterial pressure, heart rate and urine output guided fluid therapy Consensus
Arterial lactate‑guided fluid therapy Majority agreement
We recommend use of early enteral nutrition or parenteral nutrition in patient who cannot tolerate Strong consensus and evidence
enteral nutrition.
2D – Two‑dimensional; CRS‑HIPEC – Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy; TIVA – Total intravenous anaesthesia; ASA – American
Society of Anesthesiologists; PT – Prothrombin time; aPTT – Activated partial thromboplastin time; INR – International normalised ratio; TEA – Thoracic epidural
analgesia; IVPCA – Intravenous patient‑controlled analgesia; PCI – Peritoneal Carcinomatosis Index; ICU – Intensive care unit

DISCLAIMER AND FUTURE ASPECTS Conflicts of interest

There are no conflicts of interest.
The contents of this publication are current practice
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