Open Liver Resection 2019

Open liver resection-specific evidence

Data table: NSAIDs/COX-2-selective inhibitors for pain management after open liver resection

Arguments for…

• Two placebo-controlled RCTs reported significant pain relief and opioid sparing with pre- and post-operative administration of parecoxib, with rescue analgesia provided by IV-PCA opioid (Wang 2020; Chen 2017).
• Another RCT compared a combination of parecoxib with TAP blocks with placebo and no TAP blocks and reported significantly lower pain scores on postoperative days 1 and 2 in the study group (Qiao 2019).
• A placebo-controlled RCT evaluated the analgesic effects of IV ketorolac initiated postoperatively for 48 hours, and found lower pain scores and an opioid-sparing effect from 6 hours until 36 hours after surgery (Yassen 2012).
• Paracetamol, as co-analgesic, was not used in any of these studies.

PROSPECT Recommendations

• Paracetamol and an NSAID are recommended, unless contraindicated, administered either pre-operatively or intra-operatively and continued postoperatively.
  • Analgesic efficacy was shown for NSAIDs as basic analgesics administered pre-operatively or intra-operatively and continued postoperatively on a “round-the-clock” or scheduled basis.
  • No study investigated the analgesic efficacy of paracetamol in liver resection, although given its relative safe profile and the few side effects, it is considered as basic (i.e. first line) analgesic according to the PROSPECT methodology (Joshi 2019). Paracetamol was used as basic analgesic in several RCTs included in this review.
  • Risk factors for hepatotoxicity that should be considered before using paracetamol include liver disease, age, malnutrition and intra-operative liver ischaemia. The altered pharmacokinetics in patients with liver disease or after major liver resections might influence the paracetamol dose (Galinski 2006; Rudin 2007). Overall, there is a low risk for paracetamol toxicity after liver resection, and therefore, it is recommended as basic analgesic.

Open liver resection-specific evidence

Data table: Magnesium sulphate (MgSO₄)  for pain management after open liver resection

Arguments for…

• A placebo-controlled study reported significantly reduced pain scores and opioid requirements with IV MgSO₄ (a loading dose of 30 mg.kg^-1 followed by a continuous infusion of 10 mg.kg^-1.h^-1) (Mahmoud 2016). Basic analgesics were not administered in the control group.

PROSPECT Recommendations

• Intraoperative use of magnesium sulphate is not recommended due to limited procedure-specific evidence.

Open liver resection-specific evidence

Data table: Dexmedetomidine for pain management after open liver resection

Arguments for…

• A placebo-controlled RCT reported that dexmedetomidine (0.5 µg.kg^-1 over 10 minutes before intubation followed by 0.3 µg.kg^-1.h^-1) reduced postoperative pain scores at rest for eight hours, and on coughing for 48 hours (Zhang 2018).

PROSPECT Recommendations

• Intraoperative use of dexmedetomidine is not recommended due to limited procedure-specific evidence.

Open liver resection-specific evidence

• No procedure-specific evidence was identified that met the inclusion criteria.

PROSPECT Recommendations

• Ketamine is not recommended due to lack of procedure-specific evidence.

Open liver resection-specific evidence

• No procedure-specific evidence was identified that met the inclusion criteria.

PROSPECT Recommendations

• Gabapentinoids are not recommended due to lack of procedure-specific evidence.

Open liver resection-specific evidence

• No procedure-specific evidence was identified that met the inclusion criteria.

PROSPECT Recommendations

• IV lidocaine is not recommended due to lack of procedure-specific evidence.

Open liver resection-specific evidence

• No procedure-specific evidence was identified that met the inclusion criteria.

PROSPECT Recommendations

• Dexamethasone is not recommended due to lack of procedure-specific evidence.

Open liver resection-specific evidence

Data table: Intrathecal morphine for pain management after open liver resection

Arguments for…

• In one RCT, IT morphine 400 µg reduced pain at rest for 30 hours and on coughing for 24 hours compared with control (Ko 2009). Pruritus was more frequent in the IT morphine group. Basic analgesics like paracetamol and NSAIDs were not administered.
• Another RCT compared IT morphine 400 µg with a continuous ropivacaine wound infusion (Lee 2013). Pain scores at rest in the IT morphine group were significantly reduced only for the first 12 hours. However, pain scores on coughing were similar between groups throughout the study period. No differences in side-effects were reported. Basic analgesics like paracetamol and NSAIDs were not administered.

PROSPECT Recommendations

• Intrathecal morphine is not recommended due to limited procedure-specific evidence.

Open liver resection-specific evidence

Data table: TAP blocks for pain management after open liver resection

Arguments for…

• Five RCTs reported reduced pain scores and opioid requirements with the use of bilateral oblique subcostal TAP blocks with or without rectus sheath block (Kıtlık 2017; Guo 2018; Karanicolas 2018; Serag Eldin 2014; Yassen 2019):
  • Single injection bilateral subcostal TAP block reduced pain at rest and with movement and reduced opioid use for 24 hours after surgery compared with no block (Kıtlık 2017). Baseline analgesic consisted of paracetamol every six hours.
  • Another placebo-controlled RCT reported that single injection bilateral oblique subcostal TAP blocks performed before the incision significantly reduced pain scores at rest at 2 and 4 hours (Guo 2018). Baseline analgesia was provided with parecoxib and dexmedetomidine, with opioid as rescue analgesia.
  • A placebo-controlled study reported that bilateral local anaesthetic infusion via catheters placed in the medial TAP space and posterior rectus sheath both reduced pain scores at rest and with coughing and reduced opioid use for three days (i.e., the duration of local anaesthetic infusion) (Karanicolas 2018). Baseline analgesic included celecoxib 200 mg twice a day.
  • Bilateral TAP blocks with bupivacaine administered before surgery followed by postoperative boluses every eight hours via catheters placed by the surgeon provided similar pain control at rest to the control group (Serag Eldin 2014). However, pain on coughing was significantly lower in the TAP group during the first three postoperative days. Basic analgesics (i.e. paracetamol and/or NSAIDs) were not administered.
  • Another placebo-controlled RCT found that pain scores and opioid use were reduced during the first two postoperative days when bupivacaine was administered for eight hours via catheters placed by the surgeon in the TAP space and rectus sheath space (Yassen 2019). No basic analgesics were administered.

Arguments against…

• Local anaesthetic infusion through catheters placed in the TAP space and the posterior rectus sheath was compared with TEA; better pain control was reported in the TEA group immediately after surgery and during the first postoperative day (Bell 2019). After this period, differences in pain scores were less than 1/10 on a NRS. Oral analgesics were mentioned but not specified.
  • It should be noted that the TEA group showed a relatively high rate of technical failure (20%) compared to the abdominal wall catheter group (7%). In one patient, deranged biochemical coagulation led to the delay of removal of the epidural catheter.

PROSPECT Recommendations

• In the absence of contraindications, bilateral oblique subcostal TAP blocks (single shot and/or continuous local anaesthetic infusion) are recommended, depending on evaluation of the potential benefits and harms, and the anaesthesiologists’ familiarity with the technique. This recommendation is based on analgesic efficacy in several studies.

Open liver resection-specific evidence

Data table: Epidural analgesia for pain management after open liver resection

Data table: Epidural analgesia with local anaesthetics alone, only used intraoperatively, for pain management after open liver resection

Arguments for…

• A meta-analysis comparing the analgesic effect of TEA with opioid IV-PCA included four RCTs (n=278 patients) and demonstrated that TEA provided superior pain relief at rest and with movement at 12 and 24 hours after surgery, with no significant difference in hospital length of stay (Li 2019).
  • Of the four RCTs included in the meta-analysis, two RCTs (Revie 2012; Fayed 2014) are also included in our review.
  • Of note, the meta-analysis did not consider the use of basic analgesics in the included RCTs.
• Another four RCTs included in our review but not in the meta-analysis (Li 2019), also reported lower pain scores with TEA compared with opioid IV-PCA (Qi 2018; Atalan 2017; Hausken 2019; Mondor 2010).
  • One RCT compared TEA with ketobemidone (opioid) IV-PCA combined with IV NSAIDs while both groups received paracetamol on a scheduled basis (Hausken 2019).
  • Another placebo-controlled RCT compared intraoperative TEA with sham epidural analgesia and IT morphine (500 µg) and fentanyl (15 µg) (Mondor 2010). Patients in the TEA group suffered less pain at rest and with movements and demonstrated significantly lower opioid use.

PROSPECT Recommendations

• In the absence of contraindications, thoracic epidural analgesia is recommended, depending on evaluation of the potential benefits and harms, and the anaesthesiologists’ familiarity with the technique. This recommendation is based on several studies showing analgesic efficacy, particularly during coughing and deep breathing.

Open liver resection-specific evidence

Data table: Wound infiltration/infusion for pain management after open liver resection

Arguments for…

• Three of five RCTs comparing continuous local anaesthetics infusion via wound catheters (CWI) versus saline infusion or IV analgesics found a clinically significant reduction in pain scores; three studies also reported a reduction in opioid requirements. Of note, the catheters were placed at different anatomical planes.
  • A double-blind placebo-controlled RCT found that local anaesthetic infusion via a subfascial catheter reduced pain intensity after six hours until the second postoperative day; however, the differences were not clinically significant with both groups reporting low absolute pain scores (NRS < 3/10) (Dalmau 2018). There were no differences in opioid consumption between the groups. Baseline analgesia included IV NSAIDs and paracetamol.
  • Another similar study found that local anaesthetic infusion through a subfascial catheter reduced opioid use but did not influence pain scores (Peres-Bachelot 2019). Basic analgesia consisted of paracetamol and nefopam.
  • Another placebo-controlled RCT reported that local anaesthetic infusion through two catheters – one placed in the subfascial plane and the other subcutaneously – resulted in significantly lower pain scores at rest at eight and 16 hours but no difference on pain associated with movement (Xin 2014). The use of basic analgesics was not reported. CWI was associated with an accelerated recovery and discharge compared to placebo.
  • In another study, CWI via two multi-orifice wound catheters buried in the musculofascial layer reduced pain at rest and during spirometry and reduced opioid use from four to 72 hours (Chan 2010).
  • A three-arm study investigated local anaesthetic infiltration of the skin and muscular layers followed by CWI, IV-PCA fentanyl or IV tramadol. Compared with IV tramadol group, wound infusion and IV-PCA fentanyl groups had lower pain scores at six, 12, 24 and 48 hours (Wu 2018). Compared with IV-PCA fentanyl, wound infusion provided superior pain relief in the first 12 hours postoperatively. The use of basic analgesic was not mentioned.
• Local anaesthetic infiltration of the parietal peritoneum, fascia and subcutaneous planes improved pain control at rest and with movement for 12 hours postoperatively; however, the differences in pain scores were not clinically significant (i.e., less than 1/10 on NRS) (Sun 2017). An opioid-sparing effect was also noted. Other analgesics were not used.

Arguments against…

• Two RCTs compared CWI with TEA provided for 48 h after surgery, with inconsistent results:
  • In one study, pain scores were similar in both the groups at rest and with movement (Hughes 2015). Opioid use was higher in the CWI group until first postoperative day, but higher in the TEA group afterwards. Baseline analgesia was provided with IV paracetamol. Time to functional recovery (i.e. independent mobilisation, eating and drinking and need of IV fluids) was reduced in the CWI group.
  • In another study, lower pain scores at rest and with movement were observed in the TEA group and opioid consumption was higher in the CWI group (Revie 2012). All patients received IV paracetamol if no concern for size or quality of the liver remnant existed.
• Two meta-analyses found reduced pain scores with TEA compared with CWI:
  • A subgroup analysis of 4 RCTs (n=684 patients) for open liver surgery within a larger meta-analysis found lower pain scores in the TEA group at two hours at rest and at 12 hours with movement (Li 2018).
  • Another meta-analysis of three RCTs (n=240 patients) showed no significant difference in pain scores between CWI and TEA groups on the first and third postoperative day (Gavriilidis 2019). However, the TEA analgesia group had lower pain scores on the second day after surgery. Opioid consumption was also reduced on the first postoperative day in the TEA group. This meta-analysis incorrectly included a study (Bell 2019) comparing TEA analgesia with interfascial plane blocks (TAP and rectus sheath blocks) rather than CWI. Thus, the conclusions of this meta-analysis are questionable since it may overestimate the beneficial effect of CWI.

PROSPECT Recommendations

• Continuous wound infiltration is not recommended due to limited procedure-specific evidence.
• However, it may be considered as a second-line regional analgesic technique, when TEA and interfascial plane blocks (i.e. subcostal TAP blocks) are not possible.
• It is critical to recognise that, depending upon the mass of liver resected, the pharmacokinetic characteristics of local anaesthetics may be impaired which may increase the potential for systemic local anaesthetic toxicity. Specific studies investigating the pharmacokinetics of CWI after liver surgery are currently lacking.

Open liver resection-specific evidence

Data table: Paravertebral nerve blocks for pain management after open liver resection

Arguments for…

• In a placebo-controlled study, continuous right thoracic PVB showed superior pain control at rest and with movement as well as reduced opioid use on the first postoperative day (Chen 2014). No basic analgesics were used in this study.

Arguments against…

• Compared with bilateral continuous PVB, TEA provided significantly lower pain scores at rest and on deep breathing up to the second postoperative day (Schreiber 2016).
  • Of note, basic analgesics such as IV ketorolac or paracetamol were only used based on the estimated need for supplemental analgesia rather than on a scheduled basis.
  • A mild degree of coagulopathy developed in both groups with an increase in International Normalised Ratio (INR) and a decrease in platelet count, which was most pronounced on the second postoperative day. Although this did not result in a delay in catheter removal in the PVB group, in the TEA group three out of 41 patients had a delay in catheter removal. None of the patients in both groups developed complications related to coagulopathy.

PROSPECT Recommendations

• Continuous paravertebral block is not recommended due to limited procedure-specific evidence.

Open liver resection-specific evidence

Data table: Quadratus lumborum blocks for pain management after open liver resection

Arguments for…

• An RCT reported that QL block (ropivacaine infusion and boluses, if needed) was associated with lower pain scores at rest than no block, but these results were only significant at 48 hours, and the significance was lower when assessed on movement for each time interval (Zhu 2019). IV NSAIDs were administered in both groups at the end of the surgery.

PROSPECT Recommendations

• Quadratus lumborum block is not recommended due to limited procedure-specific evidence.