Open Liver Resection 2019

An explanation of PROSPECT methodology and Working Group processes can be found at the following link: http://esraeurope.org/prospect-methodology

For the open liver resection review, the Subgroup members were:

• Audrey Dieu¹
• Philippe Huynen²
• Patricia Lavand’homme¹
• Hélène Beloeil³
• Stephan M. Freys⁴
• Esther M. Pogatzki-Zahn⁵
• Girish P. Joshi⁶
• Marc Van de Velde^2,7

1. Department of Anesthesiology, Cliniques universitaires Saint-Luc, Bruxelles, Belgium
2. Department of Cardiovascular Sciences, KULeuven, Leuven, Belgium
3. Anesthesia and Intensive Care Department, University of Rennes, CHU Rennes, Inserm, INRA, CIC 1414 NuMeCan, Rennes, France
4. Department of Surgery, DIAKO Ev. Diakonie-Krankenhaus, Bremen, Germany
5. Department of Anesthesiology, Intensive Care Medicine and Pain Therapy, University Hospital Münster, Münster, Germany
6. Department of Anesthesiology and Pain Management, University of Texas, Southwestern Medical Center, Dallas, Texas, USA
7. Department of Anesthesiology, UZ Leuven, Leuven, Belgium

Open liver resection literature search

• Systematic review of the literature associated with analgesia after liver resection from January 2010 to October 2019.
• The following databases were searched: MEDLINE (PubMed), Embase and Cochrane Databases (Search strategy).
• Included studies were RCTs or systematic reviews/meta-analyses of analgesic, anaesthetic or surgical interventions, in English, assessing postoperative pain management for patients after open liver resection. A study was also required to measure pain intensity using a numerical linear scoring system, such as the numerical rating scale (NRS) or visual analogue scale (VAS).
• RCTs that reported data pooled from patients undergoing simultaneous surgical procedures were excluded as were the RCTs evaluating combinations of different perioperative interventions such as studies comparing ERAS programs to conventional care, because the variability of definitions and protocols can make practical recommendations about a particular intervention impossible. Meta- analyses that reported data on mixed surgical procedures were only included when a subanalysis on liver resection was available.
• Of 4991 unique records screened, 125 full-text articles were reviewed in more detail.
• 31 RCTs and 3 meta-analyses met the inclusion criteria (Summary of literature selection; Included studies).
• 91 studies were excluded after full-text screening.
• The reasons for exclusion were: posters or conference abstracts (n=44), retrospective studies (n=10), not randomised (n=8), not specific (n=9), not focused on pain (n=6), ERAS procedures with mixed analgesic interventions (n=6), laparoscopic approach (n=3), no pain scores (n=2), pharmacokinetic studies (n=2), poor quality with conflicting conclusion (n=1).

• Data extraction and data analysis for the open liver resection review adhered to the PROSPECT methodology (Joshi 2019, http://esraeurope.org/prospect-methodology).
• Pain intensity scores were used as the primary outcome measure.
• We regarded a change of more than 10 mm out of 100 mm on the Visual Analog Scale (VAS) or more than one out of 10 on a Numerical Rating Scale (NRS) as clinically relevant.
• Secondary outcomes included cumulative 24 hours of opioid requirements, other supplementary analgesic use, opioid-related adverse events and patient-related outcome measures.

• Recommendations were made according to PROSPECT methodology (Joshi 2019, http://esraeurope.org/prospect-methodology).
• To be recommended, the intervention must be:
  1. Beneficial in at least two RCTs.
  2. Clinically relevant to current perioperative practice.
  3. Of clinical benefit when added to the ‘basic analgesic regimen’ or if this regimen is not possible or is contraindicated.
• Furthermore, the balance between the invasiveness of the analgesic technique and the consequences of postoperative pain, as well as the balance between the analgesic efficacy and the adverse event profile of the analgesic technique, was considered.
• The opioid-sparing effects of paracetamol and NSAIDs (termed as basic analgesic regimen) are well described for all surgical procedures (Joshi 2019). The PROSPECT group assessed if the addition of an analgesic intervention would further improve pain relief when combined with these simple, effective, non-opioid analgesics.
• Five questions about each recommendation were investigated:
  1. Is the recommended intervention clinically relevant?
  2. Does it add to the ‘basic analgesic technique’?
  3. Does the balance between efficacy and adverse effects allow recommendation?
  4. Does the balance between invasiveness of the analgesic intervention and degree of pain after surgery allow recommendation?
  5. Are the reasons for not recommending an analgesic intervention appropriate?
• The proposed recommendations were sent to the PROSPECT Working Group for review and comments. A modified Delphi approach was used, which included rounds of individual comments followed by round-table discussions.
• Following a round of discussion during the face-to-face meeting, the Working Group unanimously agreed with the proposed recommendations.
• Once a consensus was achieved, the lead authors drafted the final document, which was ultimately approved by the working group.

The limitations of this review are related to those of the included studies:

• Considerable heterogeneity across the studies, such as variable dosing regimens, variable methods of administration, a variable use of analgesics in the control groups, as well as variable time points of pain measurement.
• Many of the included studies suffered from small sample size and therefore it is hard to draw firm conclusions regarding the side-effect profile of the proposed interventions.
• Most RCTs did not include basic analgesics (i.e. paracetamol and NSAIDs) in the control group, thus making it difficult to determine if the positive efficacy of the analgesic interventions studied would yield the same results when combined with basic analgesics.
• Furthermore, while the PROSPECT initiative promotes multimodal, non-opioid analgesic strategies and modern perioperative care, few studies applied the multimodal analgesia or ERAS pathways.
• Future adequately powered studies should assess analgesic interventions in comparison with basic analgesics, as well as assess side effects of analgesic interventions, and it would be optimal if the role of analgesic interventions was assessed in the context of ERAS programs.
• We also initially assessed publications relating to minimally invasive approaches such as the laparoscopic approach. Unfortunately, there were few (i.e. three RCTs) publications investigating these surgical approaches that met the inclusion criteria – too few to draw any relevant conclusions.

The AGREE II instrument (Brouwers 2010) is used internationally to assess the methodological rigour and transparency of practice guidelines. As far as possible, the methodology of the PROSPECT open liver resection review meets the requirements of ‘Domain 3: Rigour of development’ of the AGREE II instrument:

• Systematic methods were used to search for evidence
• The criteria for selecting the evidence are clearly described
• The strengths and limitations of the body of evidence are clearly described
• The methods for formulating the recommendations are clearly described
• The health benefits, side effects, and risks have been considered in formulating the recommendations
• There is an explicit link between the recommendations and the supporting evidence
• The guideline has been externally reviewed by experts prior to its publication. (The evidence and recommendations are made available on the website after peer review and publication)
• A procedure for updating the guideline is provided. (Methodology is provided so that the systematic review can be updated as required)