Summary of key results from studies evaluating analgesic interventions that are recommended in patients undergoing open liver resection
| Study | Study design | Pain scores | Cumulative opioid dose | Basic and baseline analgesia |
| Preoperative interventions | ||||
| NSAIDs | ||||
| Wang et al 9 | Procedure: open liver resection for hepatocellular carcinoma. Parecoxib intravenous 40 mg 30 min before induction followed by 40 mg every 12 hours for 48 hours after the operation (n=40) versus placebo (n=40). | VAS scores lower at rest at 2, 6, 12 and 24 hours in the parecoxib group; no difference at 48 hours. VAS scores during coughing significantly lower at 2, 6, 12, 24 hours in the parecoxib group, no difference at 48 hours. However, VAS difference at 12 and 24 hours is <1/10 (not clinically relevant). | Fentanyl intravenous-PCA consumption lower in the parecoxib group (reduction of about 8%). | No basic analgesia and no additional baseline analgesia. |
| Chen et al 10 | Procedure: open liver resection for hemangioma. Parecoxib intravenous 40 mg before incision and two times per day for 3 days after surgery (n=28) versus placebo (n=28). | Parecoxib provided greater relief than placebo following liver resection with lower VAS scores at 30, 42 and 54 hours after surgery. | Sufentanil intravenous PCA consumption at 54 hours, as well as meperidine as pain supplement for insufficient analgesia, was lower in the parecoxib group than in the control group. | No basic analgesia and no additional baseline analgesia. |
| Qiao et al 11 | Procedure: open liver resection for hepatocellular carcinoma. Parecoxib intravenous 40 mg 30 min before induction (and every 12 hours for 72 hours)+TAP block (150 mg of 0.375% ropivacaine+5 mg dexamethasone) (n=51) versus placebo (n=49) before anesthesia induction without TAP block. | VAS pain scores in the parecoxib+TAP group were lower for POD 1-2-3 (not mentioned if resting/coughing). However, VAS difference between groups on POD 3 is not clinically relevant (<1/10). | Not mentioned. | No basic analgesia and no additional baseline analgesia. |
| Intraoperative interventions | ||||
| Interfascial plane blocks | ||||
| Kıtlık et al 16 | Procedure: open liver resection for living donation. US-guided bilateral subcostal TAP block (1.5 mg/kg bupivacaine diluted with saline to 40 mL volume) (n=25) versus no block (n=25). | VAS lower in the TAP group at 0, 2, 4, 6 and 24 hours both on rest and on movement Difference in pain score always >1/10. | Morphine intravenous PCA consumption lower mean dose over 24 hours: 40 mg (TAP) vs 65 mg (non-TAP). | No basic analgesia and no additional baseline analgesia. |
| Guo et al 17 | Procedure: open liver resection for hepatocellular carcinoma. US-guided bilateral subcostal TAP block (40 mL ropivacaine 0.375%) (n=35) versus placebo (n=35). | NRS at rest significantly lower at 2 hour (median NRS 2 (1–3) vs 2 (1–2)) and 4 hour (median NRS 2 (1–3) vs 1 (1–2)) postoperatively. NRS at coughing significantly lower at 2 hour, 4 hour, 12 hours and 24 hours but not 5 min after extubation. | Intraoperative and postoperative sufentanil dose significantly lower at extubation, 2 hour, 4 hour, 12 hours and 24 hours. | Basic analgesia: parecoxib 40 mg every 12 hours for 3 days No additional baseline analgesia. |
| Karanicolas et al 18 | Procedure: open liver resection for various indications. MOTAP: Surgical placed catheters (TAP and posterior rectus abdominis space); ropivacaine 0.2%, 2×20 mL at conclusion of surgery and 2×5 mL/hour for 72 hours (n=71) vs placebo (n=82). | NRS lower POD 0 until 3 (removal) at rest and movement (cough), higher proportion of patients with pain score of ‘moderate’ (defined as NRS score≥4/10) or higher at rest and when coughing. No difference in reported quality of pain control/satisfaction. | Reduced opioid requirements from 48 and at 72 hours. | Basic analgesia: celecoxib 200 mg every 12 hours No additional baseline analgesia. |
| Serag et al 19 | Procedure: open liver resection in patients with cirrhosis (child A). US-guided bilateral posterior TAP block (bupivacaine 0.375%, 15 mL on both sides, before skin incision)+bolus injections of bupivacaine 0.375% every 8 hours via surgical inserted TAP catheter (n=25) versus no TAP block (n=25). | Similar effective pain score at rest (VAS score<3) Lower pain score when coughing on POD 1–3. | Intraoperative fentanyl dose comparable in both groups, less fentanyl use in TAP+intravenous PCA group. | No basic analgesia and no additional baseline analgesia. |
| Yassen et al 20 | Procedure: open liver resection in patients with cirrhosis (child A). Surgically placed catheters (TAP+RSP 0.2 mL/kg of bupivacaine 0.25% three times a day) (n=30) versus placebo (saline injection via catheter) (n=25). | On movement and early ambulation, VAS score for pain was reduced during the first two postoperative days in the TAP+RSP group. During rest, pain control was equally effective for both groups (VAS score≤3). | Fentanyl consumption was significantly lower on POD 1 and POD 2. | No basic analgesia and no additional baseline analgesia. |
| Bell et al 21 | Procedure: open liver resection for various indications. Catheters in the TAP space and posterior rectus sheath, bolus 20 mL bupivacaine 0,5% followed by 4 mL/hour bupivacaine 0,25%)+intravenous PCA (morphine/oxycodone based) for 60 hours postoperatively (n=42) vs EA (bupivacaine 0,15%+fentanyl 2 µg/mL 6–10 mL/hour) (n=41). | Median pain scores were worse in the CWI group than in the EA group on POD 0, afternoon of POD 1 and morning of POD 2 but not afterwards. However, the only clinical relevant difference in VAS score (>1/10) was noted on POD 0. | Not mentioned. | No basic analgesia and no additional baseline analgesia. |
| Epidural analgesia intraoperatively and postoperatively | ||||
| Fayed et al 35 | Procedure: open liver resection for hepatocellular carcinoma in patients with cirrhosis (child A). EA at T11–T12 (bupivacaine 0.125%+2 µg/mL fentanyl, 6 mL/hour, bolus 3 mL, lockout 15 min) (n=17) versus intravenous PCA (n=17) (fentanyl, bolus 15 µg, 10 min lockout, max 90 µg/hour). | Pain scores at rest similar for POD 0–3 Pain scores with coughing lower on POD 2 (difference<1/10) and POD 3 (difference>1/10) No difference in patient satisfaction. | More sedation on POD 1 in intravenous PCA and fewer PONV in EA (1/17 vs 3/17). | No basic analgesia and no additional baseline analgesia. |
| Qi et al 36 | Procedure: open liver resection. ERAS program with middle thoracic EA (local anesthetics and low-dose opioid, no more details) (n=80) versus conventional care without epidural (n=80) | Lower pain scores in the ERAS group Significantly higher satisfaction in the ERAS group. | Not mentioned. | Not mentioned. |
| Atalan et al 37 | Procedure: open liver resection for living donation. EA (L1–L2, confirmation with epiduroscopy, 10 mL bupivacaine 0.25%+50 µg fentanyl to achieve a sensorial block at T4, then starting an infusion of the same solution at 7 mL/hour before starting anesthesia and until end of operation)+TIVA (propofol only)+EA postoperatively (5 mL/hour) (n=33) versus TIVA (propofol–remifentanil) and postoperative tramadol infusion (0.25 mg/kg bolus+0.15 mg/kg/hour (n=33). | Lower VAS sore at the end of operation up to 24 hours. Pulmonary function tests were better protected with the use of EA, decreased anesthesia requirements (mean propofol dose) and reduced atelectasis score and better pain control (significantly lower VAS score). Total propofol dose, decrease in FEV1 and VAS at end of surgery were associated with atelectasis score, and atelectasis score was associated with LOS. | Not mentioned. | Not mentioned. |
| Hausken et al 38 | Procedure: open liver resection for colorectal metastasis. EA at T8–T9 (bupivacaine 1 mg/mL+fentanyl 2 µg/mL+epinephrine 2 µg/mL, at 5–15 mL/hour Bolus 5 mL, maximum of two per hour) (n=77) vs ketobemidone intravenous PCA (1 mg bolus, lockout 8 min, max 7 mg/hour)+ketorolac 30 mg every 8 hours+local wound infiltration (bupivacaine 0.5% 20 mL or 0.25% 40 mL) (n=66). | No difference in mean pain scores (NRS) for PODs 0–5 (1.7 (intravenous PCA) vs 1.6 (EA), non-inferiority). Lower pain scores (NRS) in EA versus intravenous PCA on POD 0 and POD 1, but higher or equal on PODs 2–5. Significantly less patients with severe pain (NRS score≥4) on POD 0 in EA, no significant difference afterwards. | Intravenous PCA group was associated with earlier discontinuation of pump and with lower consumption of MED. However, both groups received oral oxycodone and epidural fentanyl converted to MED as if intravenous fentanyl. | Basic analgesia: Acetaminophen 1 g every 6 hours. Baseline analgesia: oxycodone 10 mg every 12 hours from POD one to POD 2. |
| Li et al 40 | Systematic review and meta-analysis. Intravenous PCA versus EA after open hepatic resection. | Pain scores at rest at 12 hours no difference, at 24 hours higher pain scores in intravenous PCA group (significant), at 48 hours no statistical significance. Pain scores at movement at 24 and 48 hours: no difference. At 2 and 12 hours: higher scores in the intravenous PCA group (but did not reach statistical significance). | NA | |
CWI, continuous wound infiltration; EA, epidural analgesia; ERAS, enhanced recovery after surgery; FEV1, forced expiratory volume in 1 s; LOS, length of stay; MED, morphine equivalent dose; MOTAP, medial open transversus abdominis plane; NA, not applicable; NRS, Numerical Rating Scale; NSAID, non-steroidal anti-inflammatory drug; PCA, patient-controlled analgesia; POD, postoperative day; PONV, postoperative nausea and vomiting; RSP, rectus sheath plane; TAP, transversus abdominis plane; TIVA, total intravenous anesthesia; US, ultrasound; VAS, Visual Analogue Scale.