Summary of key results from studies evaluating analgesic interventions that are not recommended in patients undergoing open liver resection
| Study | Study design | Pain scores | Cumulative opioid dose | Basic and baseline analgesia |
| Preoperative interventions | ||||
| Intrathecal morphine | ||||
| Ko et al 12 | Procedure: open right liver resection for living donation. Intrathecal morphine 400 µg single preoperative injection (n=20) versus no intrathecal morphine (n=20). | Patients in the intrathecal morphine group had less pain at rest up to 30 hours and when coughing up to 24 hours. | Patients in intrathecal morphine group showed longer time to receive the first rescue meperidine (45.7±23 hours vs <1 hour). The amounts of supplementary meperidine (0 vs 175 mg) and fentanyl intravenous PCA (407.2 µg vs 594.8 µg) required were significantly less in the intrathecal morphine group. Cumulative consumption of meperidine and fentanyl until 72 hours was significantly less in the intrathecal morphine group. | No basic analgesia and no additional baseline analgesia. |
| Lee et al 13 | Procedure: open right liver resection for living donation. CWI (bolus ropivacaine 0.75% 10 mL after catheter placement at the end of surgery followed by ropivacaine 0.5% 4 mL/hour for 72 hours) (n=19) versus intrathecal morphine (400 µg) preoperative+continuous intravenous fentanyl (15 µg/hour) postop (n=21) | During the first 12 hours, VAS score at rest was lower for the intrathecal morphine+intravenous fentanyl group. The VAS scores at rest thereafter were similar between the groups. The VAS scores with coughing were similar between the groups throughout the study time period. | Rescue intravenous fentanyl requirements were significantly higher in the CWI group during the first 24 hours after surgery, but they became similar to the requirements in the intrathecal morphine/intravenous fentanyl group 24–28 hours and 48–72 hours after surgery. | No basic analgesia and no additional baseline analgesia. |
| Intraoperative interventions | ||||
| MgSO4 | ||||
| Mahmoud et al 14 | Procedure: open liver resection for living donation. Intraoperative MgSO4 infusion (30 mg/kg bolus followed by 10 mg/kg infusion until the end of surgery) in living liver donors (n=25) versus placebo (n=25) | Postoperative VAS lower in the MgSO4 group (1.2 vs 3.8). | Postoperative fentanyl intravenous PCA requirement lower (70 µg/hour vs 114 µg/hour). | No basic analgesia and no additional baseline analgesia. |
| Dexmedetomidine | ||||
| Zhang et al 15 | Procedure: open liver resection. Dexmedetomidine (0.5 µg/kg loading dose, 0.3 µg/kg/hour during surgery) combined with postoperative oxycodone+dexmedetomidine intravenous PCA (n=26) versus placebo (n=26) during surgery, postoperative oxycodone intravenous PCA alone. | VAS scores lower in the dexmedetomidine group at rest at 1, 4 and 8 hours postoperatively. VAS scores lower in the dexmedetomidine group at coughing at 24 and 48 hours postoperatively. | Postoperative consumption of oxycodone intravenous PCA was lower in the dexmedetomidine group at 4, 8, 12, 24 and 48 hours. Also, rescue analgesics requirement (parecoxib and tramadol) in PACU higher in the control group (34.62% vs 11.54%). | No basic analgesia and no additional baseline analgesia. |
| QL blocks | ||||
| Zhu et al 22 | Procedure: open liver resection. US-guided continuous QL block (ropivacaine 0.4% 0.6 mL/kg, then a catheter is placed: ropivacaine 0.2%, continuous infusion at 5 mL/hour, bolus 5 mL, 15 min lockout, max 20 mL/hour max) (n=32) versus no continuous QL block (n=31). | Pain scores (NRS) at rest lower in the QL block group but only significant at 48 hours postoperatively. Pain scores (NRS) at movement lower in the QL block group at all times. | No significant difference in the postoperative self-administered analgesic dose. | Basic analgesia: flurbiprofen 100 mg at the end of surgery. No additional baseline analgesia. |
| Paravertebral nerve blocks | ||||
| Schreiber et al 23 | Procedure: open liver resection. EA (5–8 mL/hour ropivacaine 0,2%, bolus 3 mL/hour) (n=41) versus continuous bilateral PVB (n=39) (T7, 15 mL ropivacaine 0.5% bolus each side, followed by 7–12 mL/hour ropivacaine 0.2% each side, bolus 3 mL each side/hour) during 3 days for open liver resection. The infusions were started after resection, before emergence. | VRS lower at rest and during deep inspiration at 24 and 48 hours in the EA group at 48 hours (not clinically relevant at 24 hours, with VAS difference<1/10). | Hydromorphone intravenous PCA until at least POD 3; no difference in opioid administration, no difference in acetaminophen, ketorolac or ketamine-infusion in both groups. | Basic analgesia: acetaminophen and ketorolac. Baseline analgesia: ketamine infusions were used by intraoperative practitioners or added by the acute pain service, but according to those practitioners preference. |
| Chen et al 24 | Procedure: open right liver resection. Continuous right thoracic PVB (T7, ropivacaine 0.2% 10 mL bolus, 6 mL/hour for 24 hours) (n=24) versus placebo (n=24) infusion; first bolus before emergence. | Pain scores (NRS) lower on rest and coughing in the PVB group for each time point but not clinically relevant (VAS difference>1/10) at rest at 24 hours. | Lower cumulative consumption of sufentanil (54.3 µg/24 hours vs 68.1 µg/24 hours). | No basic analgesia and no additional baseline analgesia. |
| Wound infiltration | ||||
| Dalmau et al 25 | Procedure: open liver resection. CWI (ropivacaine 0.23% 10 mL bolus, 5 mL/hour for 48 hours) (n=53) versus placebo (n=46) infusion. | Pain scores (NRS) were lower in the CWI group with significance after 6 hours until POD 2 but not clinically significant (VAS difference between groups<1/10). | No difference in morphine consumption. | Basic analgesia: dexketoprofen and acetaminophen. No additional baseline analgesia. |
| Peres-Bachelot et al 26 | Procedure: open liver resection for liver metastasis. CWI with ropivacaine 0.375%, 40 mL bolus followed by 8 mL/hour for 96 hours (n=42) vs placebo (n=43) infusion. | Non-significantly lower pain score (VAS) in the CWI group. | Less morphine consumption (0.5 mg/kg less) on PODs 1 and 2, no significant difference on PODs 3 and 4. Total median requirements of acetaminophen was reduced but no difference in total median nefopam requirements. | Basic analgesia: acetaminophen 1 g at the end of surgery. No additional baseline analgesia. |
| Xin et al 27 | Procedure: open liver resection. CWI with ropivacaine 0.5%, 20 mL via two catheters 10 min before end of surgery in both groups. On arrival in PACU: ropivacaine 0.3% 2 mL/hour per catheter (=4 mL/hour) for 48 hours (n=20) vs control: saline 4 mL/hour for 48 hours (n=20) | Lower pain score at rest at 8 and 16 hours. No difference in pain score on movement. | Lower sufentanil consumption. Despite increased use of sufentanil in the saline group, no difference in sedation score after 16 hours. | No basic analgesia and no additional baseline analgesia. |
| Chan et al 28 | Procedure: open liver resection. CWI with ropivacaine 0.25% bolus 20 mL at the end of the surgery then 4 mL/hour via two multiorifice catheters placed within the musculofascial layer before skin closure for 68 hours (n=22) vs placebo (n=22). | Ropivacaine group had less pain at rest at 4–72 hours and after spirometry at 4–72 hours. | Ropivacaine group had reduced mean total morphine consumption (58 vs 86 mg). | No basic analgesia and no additional baseline analgesia. |
| Wu et al 29 | Procedure: open liver resection for hepatocellular carcinoma. CWI with ropivacaine 0.25%, 50 mL infiltration followed by ropivacaine 0.25%, 5 mL/hour (n=20) vs fentanyl+tropisetron intravenous PCA 24–30 µg/hour, bolus 6–7.5 µg, lockout 15 min, for 2 days (n=20) versus control with tramadol intravenously according to NRS (n=20). | NRS scores at 6, 12, 24 and 48 hours in both CWI and intravenous PCA groups were significantly lower than those in the control group. NRS scores at 6 and 12 hours lower in the CWI group than those in the intravenous PCA group. | Not mentioned. PONV lower in the CWI group than in the intravenous PCA, no difference between CWI and control. | No basic analgesia and no additional baseline analgesia. |
| Sun et al 30 | Procedure: open liver resection. Surgical wound infiltration (ropivacaine 0.75% 20 mL) (n=26) versus placebo (n=27). | Lower VAS scores at 0, 6 and 12 hours postoperative in the intervention group at rest and movement but not clinically relevant (difference in mean VAS score<1/10 at all time). | Sufentanil consumption lower at 6, 12, 24 and 36 hours. | No basic analgesia and no additional baseline analgesia. |
| Hughes et al 31 | Procedure: open liver resection. Surgically placed catheters (TAP+posterior rectus abdominis space; 40 mL 0.125% L-bupivacaine on closure, elastomeric reservoir 0.375% L-bupivacaine 4 mL/hour for 48 hours) (n=49) versus EA (T8–T9, 10 mL L-bupivacaine+100 µg fentanyl epidural loading and infusion 0.1% L-bupivacaine+2 µg/mL fentanyl for 48 hours) (n=48). | Pain scores (NRS) were not significantly different at rest nor on movement No difference in pain score (NRS), but advantage of CWI in recovery time over EA. | Intraoperative and postoperative opioids (converted to MED); opioid consumption was greater in the CWI group up to POD 1; thereafter, EA received a significantly greater amount of opioids. | Basic analgesia: acetaminophen 1 g every 6 hours on PODs 1 and 2. No additional baseline analgesia. |
| Revie et al 32 | Procedure: open liver resection. CWI+PCA (at the end of the surgical procedure, infiltration with 20 mL L-bupivacaine 0.25% then L-bupivacaine 0.375% 4 mL/hour over 48 hours) (n=33), vs EA at T7–T8 peroperatively bupivacaine 0.1% 7–10 mL/hour+fentanyl 2 µg/mL (n=32). | Pain scores lower in the EP group at rest. Pain scores lower in the EA group with movement. Median pain scores at rest in both groups equally mild. | Opioid use greater in the CWI group as opioid PCA was routine in this group. | Basic analgesia: standardized enhanced recovery protocol; acetaminophen every 6 hours (except if concern regarding remnant liver). POD 2: addition of ibuprofen 400 mg every 8 hours. No additional baseline analgesia. |
| Li et al 33 | Meta-analysis on open abdominal surgeries (subanalysis for open liver resection): EA versus CWI. | Significantly lower pain scores in EA at 2 hours on rest and 12 hours on mobilization than those in the CWI group after liver surgery. | Not mentioned. | NA |
| Gavriilidis et al 34 | Meta-analysis on open liver resection: CWI versus EA. | No statistically significant difference in pain scores between groups on PODs 1 and 3, but on POD 2, patients with had lower pain scores. | On POD 1, patients with EA had significantly lower opioid consumption. On PODs 2 and 3, patients who had CWI had significantly lower opioid consumption. | NA |
| Epidural analgesia with local anesthetics alone, only used intraoperatively | ||||
| Mondor et al 39 | Procedure: open liver resection. Epidural T7–T8 or T8–T9 with local anesthetics without opioids (bupivacaine 0.5%: first bolus of 3 mL followed by an infusion of 3 mL/hour intraoperatively then a bolus of 3 mL at the end of the surgery, before the catheter was removed) (n=22) vs placebo sham epidural (n=21). | VAS score at rest lower in the epidural group. However, the difference was only clinically relevant at 6, 9, 24 and 36 hours (not at 12, 18 and 48 hours). VAS with movements lower in the epidural group and the difference was clinically relevant at each time interval. | The sham group used twice as much morphine as the epidural group. | No basic analgesia. Baseline analgesia: intrathecal morphine 500 µg+intrathecal fentanyl 15 µg before the surgery. |
| Interpleural analgesia | ||||
| Weinberg et al 41 | Procedure: open liver resection. Interpleural analgesia with a 20 mL loading dose of L-bupivacaine 0.5% at the end of the surgery, followed by a continuous infusion of L-bupivacaine 0.125%+multimodal analgesia (n=25) vs multimodal analgesia with morphine intravenous PCA (n=25). | During the first 24 hours postoperatively, the only significant difference in resting pain scores between the groups was found at 6 hours. However, pain intensity using the VAS score was less on movement in the interpleural group compared with the intravenous PCA group for the first 24 postoperative hours. The greatest difference in VAS score on movement was also found at 6 hours postoperatively where the mean VAS score on movement was 42 mm in the interpleural group and 61 mm in the intravenous PCA group (difference 18 mm, 95% CI 4 to 32 mm, adjusted). At 24 hours postoperatively, mean (SD) VAS scores during movement remained lower in the interpleural group compared with the intravenous PCA group 44 (22) mm vs 51 (18) mm, respectively). However, after 48 hours, VAS score for pain at rest and during movement was similar in both groups. | At 24 hours postoperatively, the cumulative mean morphine consumption was similar in the groups. | Basic analgesia: acetaminophen 1 g every 6 hours for the first 24 hours. |
| Postoperative interventions | ||||
| NSAIDs started after completion of the surgery | ||||
| Yassen et al 42 | Procedure: open right liver resection for living donation. Ketorolac 15 mg over 30 min after surgery+48-hour infusion (60 mg ketorolac/240 mL saline=250 µg/mL, 50 µg/kg/hour) (n=28) vs placebo (saline) over 30 min after surgery+48 hour infusion (240 mL saline) (n=29). | VAS pain scores were lower in the ketorolac group compared with the placebo group starting from 6 to 36 hours. | Daily doses of fentanyl were lower in the ketorolac group at 24 and 48 hours. | No basic analgesia and no additional baseline analgesia. |
CWI, continuous wound infiltration; EA, epidural analgesia; MED, morphine equivalent dose; MgSO4, magnesium sulfate; NA, not applicable; NRS, Numerical Rating Scale; NSAID, non-steroidal anti-inflammatory drug; PACU, postoperative care unit; PCA, patient-controlled analgesia; POD, postoperative day; PONV, postoperative nausea and vomiting; PVB, paravertebral block; QL, quadratus lumborum; TAP, transversus abdominis plane; US, ultrasound; VAS, Visual Analog Scale; VRS, Verbal Rating Scale.