Effects of TIVA Versus Inhalational Anaesthesia on Circulating Tumour Cells in Hepatocellular Carcinoma Patients

Summary

More than 80% of patients with cancer will be exposed to anaesthesia at some point in their treatment. There is increasing evidence that perioperative events, including the type of anaesthesia drugs utilised, have an impact on cancer recurrence and metastases.

Although potentially and theoretically curative, surgical resection, manipulation and trauma may disseminate tumour cells and reduce immunity. There have been a number of suggestions as to why cancer may be, paradoxically, worsened by surgery and what methods may be used to mitigate this. One of these is propofol based total intravenous anaesthesia (TIVA), whereby the traditional inhalational anaesthetic drugs are avoided. Commonly used inhalational drugs, such as sevoflurane and desflurane, are pro-inflammatory.

Propofol, however, has anti-inflammatory and anti-oxidative properties, induces apoptosis and has specific inhibitory effects on tumour cell growth in vitro. Laboratory investigations, animal models, retrospective clinical studies and initial clinical research are producing evidence that inhalational anaesthesia facilitates tumour recurrence and metastasis, whilst TIVA can prolong survival.

This randomised, controlled trial will look at the effects on DNA damage and biomarkers of immunity and inflammation of inhalational anaesthesia versus TIVA in patients undergoing surgery for hepatocellular carcinoma, a common tumour in the Southern Chinese population, for whom surgery is potentially-curative. It will focus on subjects undergoing open and laparoscopic hepatectomy and investigate changes in biomarkers of inflammation, immunity and gene expression from the patients' blood samples taken before, during and after surgery.

Patients will also be followed-up for cancer recurrence, morbidity and five-year mortality. Results could represent a breakthrough in knowledge of how anaesthetic agents impact the results of cancer surgery, and have important implications for a more disease- sensitive approach to improving management and outcomes in these patients.

Conditions

• Circulating Tumor Cell
• Hepatocellular Carcinoma

Interventions

DRUG

Propofol

Monitoring and other anaesthetic procedures including the management of hypertension and hypotension will be the same as SEVO group. Induction and maintenance of general anaesthesia will be conducted using total intravenous infusion of propofol. Sevoflurane will not be used, and oxygen and air would be given to provide a FiO2 of 30-50%. Target controlled infusion (TCI) with a modified Marsh effect site model (Fresenius Kabi) will be used for induction and maintenance of general anaesthesia and titrated to effect. The usual effect site concentration is 1.5-3 mcg.ml-1 and BIS monitoring will also be used to produce a value of between 40-60. As with patients in the SEVO group, remifentanil will be infused at a rate of between 0.1-0.3 mcg.kg.min-1.

DRUG

Sevoflurane

Propofol 1.5-3mg/kg, remifentanil 1mcg/kg, and rocuronium 0.6-1mg/kg or atracurium 0.5mg/kg will be used intravenously for induction of general anaesthesia. Intubation would be performed after induction of general anaesthesia. General anaesthesia monitoring will be used. Sevoflurane, air and oxygen will be used for maintenance of general anaesthesia. FiO2 will be kept between 35-50%. BIS monitoring will be applied and level of anaesthetia will be titrated to maintain a BIS value of between 40-60. Intravenous remifentanil infusion between 0.1-0.2 mcg/kg/min will be given and this will be titrated to provide optimal haemodynamic parameters.

Sponsors & Collaborators

• The University of Hong Kong

  lead OTHER

Principal Investigators

• Michael G. Irwin, M.B. Ch.B · The University of Hong Kong

Study Design

Allocation

RANDOMIZED

Purpose

HEALTH_SERVICES_RESEARCH

Masking

DOUBLE

Model

PARALLEL

Eligibility

Min Age

18 Years

Max Age

80 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2020-03-04

Primary Completion

2024-01-31

Completion

2024-03-31

Countries

• China