Is TIVA associated with reduced mortality following hepatectomy?

Lai HC, Lee MS, Lin C et al. Propofol-based total intravenous anaesthesia is associated with better survival than desflurane anaesthesia in hepatectomy for hepatocellular carcinoma: a retrospective cohort study. Br J Anaesth. 2019 Aug; 123(2): 151-160.

Take Home Message

This paper is unlikely to convince our HPB anaesthetists to switch to TIVA from desflurane once our new BIS enabled anaesthetic machines are in use.

Background

  • Animal models and human cell lines suggest anaesthetic agents can affect the immune system in different ways
  • Previous studies have suggested propofol based anaesthesia may be associated with a lower risk of cancer recurrence although results in liver surgery have been conflicting

Aim

Does the choice of desflurane vs propofol anaesthesia was associated with long-term survival, local recurrence, and distant metastasis after hepatectomy for HCC.

Design

  • Retrospective, propensity score matched
  • Single centre in Taipei, Taiwan
  • January 2005 – December 2014

Eligibility criteria

  • ASA 2-3
  • TNM stage I-IV HCC
  • Propofol or desflurane maintenance anaesthesia
  • Exclusion criteria: Combined propofol with inhalational anaesthesia, incomplete data, age <20yrs, undergoing liver transplant

Methodology

  • Retrospective database review
  • Data collected on demographics, functional status, anaesthetic method, surgical complications, recurrence, metastasis and survival
  • Induction: No pre-med, routine monitoring including arterial and central venous pressures, Fentanyl, propofol & rocuronium / cisatracurium
  • Prop group: TCI aiming Ce 3-4 mg mL-1, PRN Fent / CisTrac, 100% O2 at 0.3 L min-1
  • Des Group: Vapouriser at 4-10 vol% in 100% O2 at 300 mL min-1, PRN Fent / CisTrac
  • Post-op: PACU / ICU
  • Study size: Power calculation based on Wigmore et al, estimating 213 patients per group based on a propofol mortality 13.5% & des mortality 24%
  • Statistical analysis: Students t-test / χ2, Cox proportional hazards to guide propensity scoring, Kaplan-Meier

Outcomes

  • Primary: Overall survival (date of surgery to date of death or Aug 2017 for those censored)
  • Subgroups: TNM stage, local recurrence & distal metastasis

Results

  • Multiple statistical differences between groups, reduced but not excluded following propensity matching (blood transfusion, retroviral therapy)
  • Primary outcome: Mortality higher in the desflurane group (75.0%) than in the propofol group (30.8%) during follow-up (P<0.001) confirmed following regression analysis and propensity matching  (HR 0.32; 95% CI, 0.26–0.39; P<0.001)
  • Subgroups: Patients who received propofol anaesthesia had less local recurrences and distant metastases than those who received desflurane anaesthesia: crude HR was 0.32 (95% CI, 0.27–0.38; P<0.001), PS-adjusted HR was 0.43 (95% CI, 0.36–0.52; P<0.001), and PS-matched HR was 0.44 (95% CI, 0.36–0.54; P<0.001)

Study Limitations

  • Retrospective
  • Non-random
  • There may be unmeasured confounders
  • No NSAID use although their use may be protective
  • Opiate data not available, known to have an immune effect

Discussion

  • Difficult to interpret the results given the large differences in baseline variables
  • Propensity scoring and matching can help reduce the limitations of retrospective analysis but can’t exclude them completely
  • Probably doesn’t apply to our population given the prevalence of Hep B/C compared to our local population (ETOH)
  • Several similar studies suggest similar, although prospective studies have not confirmed the results (breast surgery in particular)
  • Paper likely to be used as evidence by local pro-TIVA cancer centres to justify their technique
  • Equally paper can also be used by other pro-inhalational centres (including ours – desflurane preferred) given the limitations & confounders
  • There may be environmental concerns that increase the use of TIVA irrespective of oncogenic differences

Summary by Dr Timothy A C Snow

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