Perioperative pain management with regional analgesia techniques for visceral cancer surgery: A systematic review and meta-analysis.

STUDY OBJECTIVE: Regional analgesia following visceral cancer surgery might provide an advantage but evidence for best treatment options related to risk-benefit is unclear. DESIGN: Systematic review of randomized controlled trials (RCT) with meta-analysis and GRADE assessment. SETTING: Postoperative pain treatment. PATIENTS: Adult patients undergoing visceral cancer surgery. INTERVENTIONS: Any kind of peripheral (PRA) or epidural analgesia (EA) with/without systemic analgesia (SA) was compared to SA with or without placebo treatment or any other regional anaesthetic techniques. MEASUREMENTS: Primary outcome measures were postoperative acute pain intensity at rest and during activity 24 h after surgery, the number of patients with block-related adverse events and postoperative paralytic ileus. MAIN RESULTS: 59 RCTs (4345 participants) were included. EA may reduce pain intensity at rest (mean difference (MD) -1.05; 95% confidence interval (CI): -1.35 to -0.75, low certainty evidence) and during activity 24 h after surgery (MD -1.83; 95% CI: -2.34 to -1.33, very low certainty evidence). PRA likely results in little difference in pain intensity at rest (MD -0.75; 95% CI: -1.20 to -0.31, moderate certainty evidence) and pain during activity (MD -0.93; 95% CI: -1.34 to -0.53, moderate certainty evidence) 24 h after surgery compared to SA. There may be no difference in block-related adverse events (very low certainty evidence) and development of paralytic ileus (very low certainty of evidence) between EA, respectively PRA and SA. CONCLUSIONS: Following visceral cancer surgery EA may reduce pain intensity. In contrast, PRA had only limited effects on pain intensity at rest and during activity. However, we are uncertain regarding the effect of both techniques on block-related adverse events and paralytic ileus. Further research is required focusing on regional analgesia techniques especially following laparoscopic visceral cancer surgery.

Regional anaesthesia for postoperative pain management following laparoscopic, visceral, non-oncological surgery a systematic review and meta-analysis.

BACKGROUND: Postoperative pain management following laparoscopic, non-oncological visceral surgery in adults is challenging. Regional anaesthesia could be a promising component in multimodal pain management. METHODS: We performed a systematic review and meta-analysis with GRADE assessment. Primary outcomes were postoperative acute pain intensity at rest/during movement after 24 h, the number of patients with block-related adverse events and the number of patients with postoperative paralytic ileus. RESULTS: 82 trials were included. Peripheral regional anaesthesia combined with general anaesthesia versus general anaesthesia may result in a slight reduction of pain intensity at rest at 24 h (mean difference (MD) - 0.72 points; 95% confidence interval (CI) - 0.91 to - 0.54; I2 = 97%; low-certainty evidence), which was not clinically relevant. The evidence is very uncertain regarding the effect on pain intensity during activity at 24 h (MD -0.8 points; 95%CI - 1.17 to - 0.42; I2 = 99%; very low-certainty evidence) and on the incidence of block-related adverse events. In contrast, neuraxial regional analgesia combined with general anaesthesia (versus general anaesthesia) may reduce postoperative pain intensity at rest in a clinical relevant matter (MD - 1.19 points; 95%CI - 1.99 to - 0.39; I2 = 97%; low-certainty evidence), but the effect is uncertain during activity (MD - 1.13 points; 95%CI - 2.31 to 0.06; I2 = 95%; very low-certainty evidence). There is uncertain evidence, that neuraxial regional analgesia combined with general anaesthesia (versus general anaesthesia) increases the risk for block-related adverse events (relative risk (RR) 5.11; 95%CI 1.13 to 23.03; I2 = 0%; very low-certainty evidence). CONCLUSION: This meta-analysis confirms that regional anaesthesia might be an important part of multimodal postoperative analgesia in laparoscopic visceral surgery, e.g. in patients at risk for severe postoperative pain, and with large differences between surgical procedures and settings. Further research is required to evaluate the use of adjuvants and the additional benefit of regional anaesthesia in ERAS programmes. PROTOCOL REGISTRATION: PROSPERO CRD42021258281.

Erector spinae plane block for postoperative pain.

BACKGROUND: Acute and chronic postoperative pain are important healthcare problems, which can be treated with a combination of opioids and regional anaesthesia. The erector spinae plane block (ESPB) is a new regional anaesthesia technique, which might be able to reduce opioid consumption and related side effects. OBJECTIVES: To compare the analgesic effects and side effect profile of ESPB against no block, placebo block or other regional anaesthetic techniques. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase and Web of Science on 4 January 2021 and updated the search on 3 January 2022. SELECTION CRITERIA: Randomised controlled trials (RCTs) investigating adults undergoing surgery with general anaesthesia were included. We included ESPB in comparison with no block, placebo blocks or other regional anaesthesia techniques irrespective of language, publication year, publication status or technique of regional anaesthesia used (ultrasound, landmarks or peripheral nerve stimulator). Quasi-RCTs, cluster-RCTs, cross-over trials and studies investigating co-interventions in either arm were excluded. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed all trials for inclusion and exclusion criteria, and risk of bias (RoB), and extracted data. We assessed risk of bias using the Cochrane RoB 2 tool, and we used GRADE to rate the certainty of evidence for the primary outcomes. The primary outcomes were postoperative pain at rest at 24 hours and block-related adverse events. Secondary outcomes were postoperative pain at rest (2, 48 hours) and during activity (2, 24 and 48 hours after surgery), chronic pain after three and six months, as well as cumulative oral morphine requirements at 2, 24 and 48 hours after surgery and rates of opioid-related side effects. MAIN RESULTS: We identified 69 RCTs in the first search and included these in the systematic review. We included 64 RCTs (3973 participants) in the meta-analysis. The outcome postoperative pain was reported in 38 out of 64 studies; block-related adverse events were reported in 40 out of 64 studies. We assessed RoB as low in 44 (56%), some concerns in 24 (31%) and high in 10 (13%) of the study results. Overall, 57 studies reported one or both primary outcomes. Only one study reported results on chronic pain after surgery. In the updated literature search on 3 January 2022 we found 37 new studies and categorised these as awaiting classification. ESPB compared to no block There is probably a slight but not clinically relevant reduction in pain intensity at rest 24 hours after surgery in patients treated with ESPB compared to no block (visual analogue scale (VAS), 0 to 10 points) (mean difference (MD) -0.77 points, 95% confidence interval (CI) -1.08 to -0.46; 17 trials, 958 participants; moderate-certainty evidence). There may be no difference in block-related adverse events between the groups treated with ESPB and those receiving no block (no events in 18 trials reported, 1045 participants, low-certainty evidence). ESPB compared to placebo block ESPB probably has no effect on postoperative pain intensity at rest 24 hours after surgery compared to placebo block (MD -0.14 points, 95% CI -0.29 to 0.00; 8 trials, 499 participants; moderate-certainty evidence). There may be no difference in block-related adverse events between ESPB and placebo blocks (no events in 10 trials reported; 592 participants; low-certainty evidence). ESPB compared to other regional anaesthetic techniques Paravertebral block (PVB) ESPB may not have any additional effect on postoperative pain intensity at rest 24 hours after surgery compared to PVB (MD 0.23 points, 95% CI -0.06 to 0.52; 7 trials, 478 participants; low-certainty evidence). There is probably no difference in block-related adverse events (risk ratio (RR) 0.27, 95% CI 0.08 to 0.95; 7 trials, 522 participants; moderate-certainty evidence). Transversus abdominis plane block (TAPB) ESPB may not have any additional effect on postoperative pain intensity at rest 24 hours after surgery compared to TAPB (MD -0.16 points, 95% CI -0.46 to 0.14; 3 trials, 160 participants; low-certainty evidence). There may be no difference in block-related adverse events (RR 1.00, 95% CI 0.21 to 4.83; 4 trials, 202 participants; low-certainty evidence). Serratus anterior plane block (SAPB) The effect on postoperative pain could not be assessed because no studies reported this outcome. There may be no difference in block-related adverse events (RR 1.00, 95% CI 0.06 to 15.59; 2 trials, 110 participants; low-certainty evidence). Pectoralis plane block (PECSB) ESPB may not have any additional effect on postoperative pain intensity at rest 24 hours after surgery compared to PECSB (MD 0.24 points, 95% CI -0.11 to 0.58; 2 trials, 98 participants; low-certainty evidence). The effect on block-related adverse events could not be assessed. Quadratus lumborum block (QLB) Only one study reported on each of the primary outcomes. Intercostal nerve block (ICNB) ESPB may not have any additional effect on postoperative pain intensity at rest 24 hours after surgery compared to ICNB, but this is uncertain (MD -0.33 points, 95% CI -3.02 to 2.35; 2 trials, 131 participants; very low-certainty evidence). There may be no difference in block-related adverse events, but this is uncertain (RR 0.09, 95% CI 0.04 to 2.28; 3 trials, 181 participants; very low-certainty evidence). Epidural analgesia (EA) We are uncertain whether ESPB has an effect on postoperative pain intensity at rest 24 hours after surgery compared to EA (MD 1.20 points, 95% CI -2.52 to 4.93; 2 trials, 81 participants; very low-certainty evidence). A risk ratio for block-related adverse events was not estimable because only one study reported this outcome. AUTHORS' CONCLUSIONS: ESPB in addition to standard care probably does not improve postoperative pain intensity 24 hours after surgery compared to no block. The number of block-related adverse events following ESPB was low. Further research is required to study the possibility of extending the duration of analgesia. We identified 37 new studies in the updated search and there are three ongoing studies, suggesting possible changes to the effect estimates and the certainty of the evidence in the future.

Peripheral Regional Anesthetic Techniques in Cardiac Surgery: A Systematic Review and Meta-Analysis.

OBJECTIVE: The aim of this systematic review was to investigate postoperative pain outcomes and adverse events after peripheral regional anesthesia (PRA) compared to no regional anesthesia (RA), placebo, or neuraxial anesthesia in children and adults undergoing cardiac surgery. DESIGN: A systematic review and meta-analysis with an assessment of the risk of bias (Cochrane RoB 1) and certainty of evidence (Grading of Recommendations, Assessment, Development, and Evaluation). SETTING: Randomized controlled trials (RCTs). PARTICIPANTS: Adults and children undergoing heart surgery. INTERVENTIONS: Any kind of PRA compared to no RA or placebo or neuraxial anesthesia. MEASUREMENTS AND MAIN RESULTS: In total, 33 RCTs (2,044 patients) were included-24 of these had a high risk of bias, and 28 were performed in adults. Compared to no RA, PRA may reduce pain intensity at rest 24 hours after surgery (mean difference [MD] -0.81 points, 95% CI -1.51 to -0.10; I2 = 92%; very low certainty evidence). Peripheral regional anesthesia, compared to placebo, may reduce pain intensity at rest (MD -1.36 points, 95% CI -1.59 to -1.13; I2 = 54%; very low certainty evidence) and during movement (MD -1.00 points, 95% CI -1.34 to -0.67; I² = 72%; very low certainty evidence) 24 hours after surgery. No data after pediatric cardiac surgery could be meta-analyzed due to the low number of included trials. CONCLUSIONS: Compared to no RA or placebo, PRA may reduce pain intensity at rest and during movement. However, these results should be interpreted cautiously because the certainty of evidence is only very low.

Efficacy and safety of perioperative ketamine for the prevention of chronic postsurgical pain: A meta-analysis.

STUDY OBJECTIVE: Assessment of the efficacy and safety of perioperative intravenous ketamine in reducing incidence and severity of chronic postsurgical pain. STUDY DESIGN: A systematic review and meta-analysis of randomized controlled trials (RCTs). DATA SOURCES: The following data sources were systematically searched: MEDLINE, CENTRAL, and EMBASE (till 02/2021). PATIENTS: Adult patients undergoing any surgery. INTERVENTIONS: Perioperative use of intravenous ketamine as an additive analgesic drug compared to placebo, no active control treatment, and other additive drugs. MEASUREMENTS: Primary outcomes were number of patients with chronic postsurgical pain after 6 months and ketamine related adverse effects. Secondary outcomes were chronic postsurgical pain incidence after 3 and 12 months, chronic postsurgical neuropathic pain incidence, chronic postsurgical moderate to severe pain incidence, intensity of chronic postsurgical pain at rest, and during movement, oral morphine consumption after 3, 6, and 12 months and incidence of opioid-related adverse effects. MAIN RESULTS: Thirty-six RCTs were included with a total of 3572 patients. Ketamine compared to placebo may result in no difference in the number of patients with chronic postsurgical pain after 6 months (risk ratio (RR) 0.86, 95% confidence interval (CI) 0.71-1.05; I2 = 34%; 16 studies; low-certainty evidence). Ketamine may reduce the incidence of chronic postsurgical neuropathic pain after 3 months in comparison to placebo (RR 0.78, 95% CI 0.62-0.99, I2 = 31%, seven trials, low-certainty evidence). Ketamine compared to placebo may increase the risk for postoperative nystagmus (RR 9.04, 95% CI 1.15-70.90, I2 30%, two trials, low-certainty evidence) and postoperative visual disturbances (RR 2.29, 95% CI 1.05-4.99, I2 10%, seven trials, low-certainty evidence). CONCLUSIONS: There is low-certainty evidence that perioperative ketamine has no effect on chronic postsurgical pain in adult patients. Low-certainty evidence suggests that ketamine compared to placebo may reduce incidence of chronic postsurgical neuropathic pain after 3 months. Questions like ideal dosing, treatment duration and more patient-related outcome measures remain unanswered, which warrants further studies. PROTOCOL REGISTRATION: Prospero CRD42021223625, 07.01.2021.

Erector spinae plane block for postoperative pain.

BACKGROUND: Acute and chronic postoperative pain are important healthcare problems, which can be treated with a combination of opioids and regional anaesthesia. The erector spinae plane block (ESPB) is a new regional anaesthesia technique, which might be able to reduce opioid consumption and related side effects. OBJECTIVES: To compare the analgesic effects and side effect profile of ESPB against no block, placebo block or other regional anaesthetic techniques. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase and Web of Science on 4 January 2021 and updated the search on 3 January 2022. SELECTION CRITERIA: Randomised controlled trials (RCTs) investigating adults undergoing surgery with general anaesthesia were included. We included ESPB in comparison with no block, placebo blocks or other regional anaesthesia techniques irrespective of language, publication year, publication status or technique of regional anaesthesia used (ultrasound, landmarks or peripheral nerve stimulator). Quasi-RCTs, cluster-RCTs, cross-over trials and studies investigating co-interventions in either arm were excluded. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed all trials for inclusion and exclusion criteria, and risk of bias (RoB), and extracted data. We assessed risk of bias using the Cochrane RoB 2 tool, and we used GRADE to rate the certainty of evidence for the primary outcomes. The primary outcomes were postoperative pain at rest at 24 hours and block-related adverse events. Secondary outcomes were postoperative pain at rest (2, 48 hours) and during activity (2, 24 and 48 hours after surgery), chronic pain after three and six months, as well as cumulative oral morphine requirements at 2, 24 and 48 hours after surgery and rates of opioid-related side effects. MAIN RESULTS: We identified 69 RCTs in the first search and included these in the systematic review. We included 64 RCTs (3973 participants) in the meta-analysis. The outcome postoperative pain was reported in 38 out of 64 studies; block-related adverse events were reported in 40 out of 64 studies. We assessed RoB as low in 44 (56%), some concerns in 24 (31%) and high in 10 (13%) of the study results. Overall, 57 studies reported one or both primary outcomes. Only one study reported results on chronic pain after surgery. In the updated literature search on 3 January 2022 we found 37 new studies and categorised these as awaiting classification. ESPB compared to no block There is probably a slight but not clinically relevant reduction in pain intensity at rest 24 hours after surgery in patients treated with ESPB compared to no block (visual analogue scale (VAS), 0 to 10 points) (mean difference (MD) -0.77 points, 95% confidence interval (CI) -1.08 to -0.46; 17 trials, 958 participants; moderate-certainty evidence). There may be no difference in block-related adverse events between the groups treated with ESPB and those receiving no block (no events in 18 trials reported, 1045 participants, low-certainty evidence). ESPB compared to placebo block ESPB probably has no effect on postoperative pain intensity at rest 24 hours after surgery compared to placebo block (MD -0.14 points, 95% CI -0.29 to 0.00; 8 trials, 499 participants; moderate-certainty evidence). There may be no difference in block-related adverse events between ESPB and placebo blocks (no events in 10 trials reported; 592 participants; low-certainty evidence). ESPB compared to other regional anaesthetic techniques Paravertebral block (PVB) ESPB may not have any additional effect on postoperative pain intensity at rest 24 hours after surgery compared to PVB (MD 0.23 points, 95% CI -0.06 to 0.52; 7 trials, 478 participants; low-certainty evidence). There is probably no difference in block-related adverse events (risk ratio (RR) 0.27, 95% CI 0.08 to 0.95; 7 trials, 522 participants; moderate-certainty evidence). Transversus abdominis plane block (TAPB) ESPB may not have any additional effect on postoperative pain intensity at rest 24 hours after surgery compared to TAPB (MD -0.16 points, 95% CI -0.46 to 0.14; 3 trials, 160 participants; low-certainty evidence). There may be no difference in block-related adverse events (RR 1.00, 95% CI 0.21 to 4.83; 4 trials, 202 participants; low-certainty evidence). Serratus anterior plane block (SAPB) The effect on postoperative pain could not be assessed because no studies reported this outcome. There may be no difference in block-related adverse events (RR 1.00, 95% CI 0.06 to 15.59; 2 trials, 110 participants; low-certainty evidence). Pectoralis plane block (PECSB) ESPB may not have any additional effect on postoperative pain intensity at rest 24 hours after surgery compared to PECSB (MD 0.24 points, 95% CI -0.11 to 0.58; 2 trials, 98 participants; low-certainty evidence). The effect on block-related adverse events could not be assessed. Quadratus lumborum block (QLB) Only one study reported on each of the primary outcomes. Intercostal nerve block (ICNB) ESPB may not have any additional effect on postoperative pain intensity at rest 24 hours after surgery compared to ICNB, but this is uncertain (MD -0.33 points, 95% CI -3.02 to 2.35; 2 trials, 131 participants; very low-certainty evidence). There may be no difference in block-related adverse events, but this is uncertain (RR 0.09, 95% CI 0.04 to 2.28; 3 trials, 181 participants; very low-certainty evidence). Epidural analgesia (EA) We are uncertain whether ESPB has an effect on postoperative pain intensity at rest 24 hours after surgery compared to EA (MD 1.20 points, 95% CI -2.52 to 4.93; 2 trials, 81 participants; very low-certainty evidence). A risk ratio for block-related adverse events was not estimable because only one study reported this outcome. AUTHORS' CONCLUSIONS: ESPB in addition to standard care probably does not improve postoperative pain intensity 24 hours after surgery compared to no block. The number of block-related adverse events following ESPB was low. Further research is required to study the possibility of extending the duration of analgesia. We identified 37 new studies in the updated search and there are three ongoing studies, suggesting possible changes to the effect estimates and the certainty of the evidence in the future.

Determinants of satisfaction with acute pain therapy during and after childbirth.

BACKGROUND: An important task in obstetrics is to offer patients adequate pain management after vaginal delivery (VD) and after cesarean section (CS). The aim of the present analysis was to assess pain intensity at the day after childbirth, after 3 and 6 months in women after VD and after CS. Additionally, it was planned to identify determinants of maternal satisfaction with acute pain therapy following VD and CS. METHODS: This secondary analysis of a single-center prospective cohort study included 210 parturients. The women gave birth in the University Hospital of Wuerzburg. They completed a survey before childbirth (P), on the first day (D1), 3 and 6 months after VD and CS. The survey included questions about the expected pain, the experienced pain, the birth, the pain afterwards and also psychological questionnaires. In addition, information was collected from the patient records. Women with planned CS received spinal anesthesia. A secondary CS was performed with an epidural, spinal or general anesthesia. Pain therapy on the ward was standardized. The primary outcomes were acute and chronic pain intensity at rest, during movement, determinants of satisfaction with pain therapy and the wish to have received more pain medication during and after VD and CS (D1). RESULTS: A total of 175 women completed the survey at all time points and were available for the analysis (drop-out 16.8%). The results confirmed high pain levels at D1 after CS (median pain intensity during movement: 8 NRS points, interquartile range, IQR 6-9 points). After VD pain scores were much lower (median pain intensity during movement: 4 points, IQR 2-5 points). Of the mothers 7.4% reported pain at rest at all time points after VD or CS but pain intensity was low after 3 and 6 months (median pain intensity at rest: 2 points, IQR 0-3 points), 28% received extended-release opioids after CS and 33% of women (VD and CS) had an epidural. The most important influencing factor for lower satisfaction with pain therapy after CS or VD was inadequate pain relief. Women with VD who had an epidural, were more satisfied during delivery than women without but there was no difference at D1. DISCUSSION: This study confirmed high acute pain levels following CS and an incidence of chronic pain of around 7% but pain intensity was low and one third received strong opioids after CS. Around 11% of women after primary CS (8% epidural, 3% combined spinal/epidural) and around 55% of women after secondary CS had an epidural, which could be used for pain therapy after birth. Women without an epidural or without opioids may not have had good pain management. The received pain relief appeared to be the most relevant predictor for satisfaction and the wish to have received more pain medication. Mothers having a VD with an epidural catheter were more satisfied with pain therapy during birth than those without. Therefore, a better multimodal pain management (including opioids, epidural and nonopioids) might provide better pain relief and might improve overall satisfaction with pain treatment following CS. Finally, the received pain relief might be a better patient-related outcome measure for satisfaction with pain treatment after childbirth than pain intensity alone.

Robotic-Assisted Esophagectomy Leads to Significant Reduction in Postoperative Acute Pain: A Retrospective Clinical Trial.

BACKGROUND: Robot-assisted minimally invasive esophagectomy (RAMIE) shows promising results regarding postoperative complications in patients with esophageal cancer. To date, no data are available regarding postoperative analgesic consumption. The aim of this work is to evaluate analgesic consumption after esophagectomy. METHODS: A total of 274 Ivor Lewis esophageal resections performed sequentially from January 2012 to December 2020 were evaluated. RAMIE cases (n = 51) were compared with the hybrid technique (laparoscopic abdominal phase followed by open thoracotomy, n = 59) and open abdominothoracic esophagectomy (OTE) (n = 164). Data were collected retrospectively. The primary endpoint was the overall postoperative morphine consumption, which represents a reliable indirect measurement of pain. Pain levels recorded on the first, third, and fifth postoperative days were assessed as secondary endpoints. RESULTS: A total of 274 patients were included. The postoperative opioid consumption rate for patients who underwent RAMIE (quartiles: 0.14, 0.23, 0.36 mg morphine milligram equivalents (MME)/kg body weight (bw)/day) was significantly lower than in the open group (0.19, 0.33, 0.58 mg MME/kg bw/day, p = 0.016). The overall postoperative opioid consumption for patients who underwent RAMIE was significantly lower (2.45, 3.63, 7.20 mg MME/kg bw/day; morphine milligram equivalents per kilogram body weight) compared with the open (4.85, 8.59, 14.63 MME/kg bw/day, p < 0.0001) and hybrid (4.13, 6.84, 11.36 MME/kg bw/day, p = 0.008) groups. Patients who underwent RAMIE reported lower pain scores compared with the open group on the fifth postoperative day, both at rest (p = 0.004) and while performing activities (p < 0.001). CONCLUSIONS: This study shows that patients who underwent RAMIE experienced similar postoperative pain while requiring significantly lower amounts of opioids compared with patients who underwent open and hybrid surgery. Further studies are required to verify the results.

Perioperative ketamine for postoperative pain management in patients with preoperative opioid intake: A systematic review and meta-analysis.

STUDY OBJECTIVE: Postoperative pain management in opioid users remains challenging. The perioperative administration of ketamine might lead to favourable pain outcomes in these patients. STUDY DESIGN: A systematic review of randomised controlled trials (RCT) with meta-analysis and assessment of the quality of evidence by GRADE was performed. SETTING: Perioperative pain treatment. PATIENTS: Adult opioid users undergoing surgery. INTERVENTIONS: Perioperative administration of ketamine. MEASUREMENTS: Primary outcomes were postoperative acute pain at rest/during movement after 24 h and number of patients with ketamine-related adverse events. MAIN RESULTS: Nine RCTs (802 patients with at least two weeks opioid-intake) were included. There is low-quality evidence that ketamine may slightly reduce postoperative pain during movement after 24 h (mean difference: -0.79; 95% confidence interval (CI): -1.22 to -0.36). Based on a very low-quality of evidence, we are uncertain on any effect of ketamine on pain at rest after 24 h and incidences of adverse events like hallucinations and confusion within 48 h. However, perioperative ketamine reduced cumulative mean opioid consumption by 97.3 mg (95%CI: -164.8 to -29.7) after 24 h and 186.4 mg (95%CI: -347.6 to -25.2) after 48 h. The relative risks (RR) for opioid-related adverse events were significantly different for sedation within 24 h (RR: 0.54; 95%CI 0.37 to 0.78). CONCLUSIONS: There is currently limited evidence for a reduced postoperative pain intensity using perioperative ketamine in preoperative opioid-consuming patients. However, a clinically relevant opioid-sparing effect was evident associated with a reduced risk for postoperative sedation and without increased harm. Therefore, ketamine might be a useful anti-hyperalgesic adjuvant in these patients. Nevertheless, with clinical heterogeneity being considerable, it's too premature to suggest any specific ketamine protocol. Furthermore, many questions (like ideal dosing, treatment duration and more favourable patient-related outcome measures including long-term effects) remain open and need to be addressed in future studies. PROTOCOL REGISTRATION: Prospero CRD42020185497.

Efficacy and adverse events of selective serotonin noradrenaline reuptake inhibitors in the management of postoperative pain: A systematic review and meta-analysis.

STUDY OBJECTIVE: Selective-serotonin-noradrenaline-reuptake inhibitors (SSNRI) might be an interesting option for postoperative pain treatment. Objective was to investigate postoperative pain outcomes of perioperative SSNRI compared to placebo or other additives in adults undergoing surgery. DESIGN: Systematic review of randomised controlled trials (RCT) with meta-analysis and GRADE assessment. SETTING: Acute and chronic postoperative pain treatment. PATIENTS: Adult patients undergoing surgery. INTERVENTIONS: Perioperative administration of SSNRI. MEASUREMENTS: Primary outcomes were postoperative acute pain at rest/during movement (measured on a scale from 0 to 10), number of patients with chronic postsurgical pain (CPSP) and with SSNRI-related adverse events. MAIN RESULTS: Fourteen RCTs (908 patients) were included. We have high-quality evidence that duloxetine has no effect on pain at rest at 2 h (MD: -0.02; 95% confidence interval (CI) -0.51 to 0.47), but probably reduces it at 48 h (MD: -1.16; 95%CI -1.78 to -0.54). There is low- and moderate-quality evidence that duloxetine has no effects on pain during movement at 2 h (MD: -0.42; 95%CI -1.53 to 0.69) and 48 h (MD: -0.91; 95% CI -2.08 to 0.26), respectively. We have very low-quality evidence that duloxetine might reduce pain at rest (MD: -0.45; 95%CI -0.74 to -0.15) and movement (MD: -1.19; 95%CI -2.32 to -0.06) after 24 h. We have low-quality evidence that duloxetine may reduce the risk of CPSP at 6 months (RR:0.35; 95%CI 0.14 to 0.90). There is moderate-quality evidence that duloxetine increases the risk of dizziness (RR:1.72; 95%CI 1.26 to 2.34). CONCLUSION: At the expense of a higher risk for dizziness, SSNRI may be effective in reducing postoperative pain between 24 and 48 h after surgery. However, the results of the meta-analyses are mostly imprecise and duloxetine might only be used in individual cases. Protocol registration: CRD42018094699.

Pectoral nerve blocks for breast surgery: A meta-analysis.

BACKGROUND: Pectoral nerve blocks (PECS block) might be an interesting new regional anaesthetic technique in patients undergoing breast surgery. OBJECTIVE: The aim of this meta-analysis was to investigate postoperative pain outcomes and adverse events of a PECS block compared with no treatment, sham treatment or other regional anaesthetic techniques in women undergoing breast surgery. DESIGN: We performed a systematic review of randomised controlled trials (RCT) with meta-analysis and risk of bias assessment. DATA SOURCES: The databases MEDLINE, CENTRAL (until December 2019) and clinicaltrials.gov were systematically searched. ELIGIBILITY CRITERIA: All RCTs investigating the efficacy and adverse events of PECS compared with sham treatment, no treatment or other regional anaesthetic techniques in women undergoing breast surgery with general anaesthesia were included. RESULTS: A total of 24 RCTs (1565 patients) were included. PECS (compared with no treatment) block might reduce pain at rest [mean difference -1.14, 95% confidence interval (CI), -2.1 to -0.18, moderate quality evidence] but we are uncertain regarding the effect on pain during movement at 24 h after surgery (mean difference -1.79, 95% CI, -3.5 to -0.08, very low-quality evidence). We are also uncertain about the effect of PECS block on pain at rest at 24 h compared with sham block (mean difference -0.83, 95% CI, -1.80 to 0.14) or compared with paravertebral block (PVB) (mean difference -0.18, 95% CI, -1.0 to 0.65), both with very low-quality evidence. PECS block may have no effect on pain on movement at 24 h after surgery compared with PVB block (mean difference -0.56, 95% CI, -1.53 to 0.41, low-quality evidence). Block-related complications were generally poorly reported. CONCLUSION: There is moderate quality evidence that PECS block compared with no treatment reduces postoperative pain intensity at rest. The observed results were less pronounced if patients received a sham block. Furthermore, PECS blocks might be equally effective as PVBs. Due to mostly low-quality or very low-quality evidence level, further research is warranted. PROTOCOL REGISTRATION: CRD42019126733.

Predicting poor postoperative acute pain outcome in adults: an international, multicentre database analysis of risk factors in 50,005 patients.

BACKGROUND: The aim of this study was to determine simple risk factors for severe pain intensity (≥7 points on a numeric rating scale [NRS]), to analyse their relation to other patient-reported outcome measures and to develop a simple prediction model. METHODS: We used data from 50,005 patients from the PAIN-OUT project. Within a first data set (n = 33,667), relevant risk factors were identified by logistic binary regression analysis, assessed for additional patient-reported outcome measures beyond pain intensity and summed up for developing a simple risk score. Finally, sum of factors was plotted against postoperative pain outcomes within a validation data set (n = 16,338). RESULTS: Odds ratios (OR) for the following risk factors were identified: younger age (<54 years, OR: 1.277), preoperative chronic pain at the site of surgery (OR: 1.195), female sex (OR: 1.433), duration of surgery (>90 minutes, OR: 1.308), preoperative opioid intake (OR: 1.250), feeling anxious (OR: 1.239) and feeling helpless due to pain (OR: 1.198), and the country of the recruiting centre (OR: 1.919). Patients with ≥3 risk factors had more severe pain intensity scores, spent a longer time in severe pain, and wished to have received more pain treatment (P < 0.001). A simple risk score was created with 4 risk factors showing a moderate prediction level. CONCLUSIONS: Patients with ≥3 risk factors are at higher risk for poor postoperative acute pain outcome after surgery. Future studies using this score might show that preventive strategies might decrease pain intensity, pain-related postoperative dysfunction, and the development of chronic pain.

Adductor canal blocks for postoperative pain treatment in adults undergoing knee surgery.

BACKGROUND: Peripheral regional anaesthesia techniques are well established for postoperative pain treatment following knee surgery. The adductor canal block (ACB) is a new technique, which can be applied as a single shot or by catheter for continuous regional analgesia. OBJECTIVES: To compare the analgesic efficacy and adverse events of ACB versus other regional analgesic techniques or systemic analgesic treatment for adults undergoing knee surgery. SEARCH METHODS: We searched CENTRAL, MEDLINE, and Embase, five other databases, and one trial register on 19 September 2018; we checked references, searched citations, and contacted study authors to identify additional studies. SELECTION CRITERIA: We included all randomized controlled trials (RCTs) comparing single or continuous ACB versus other regional analgesic techniques or systemic analgesic treatment. Inclusion was independent of the technique used (landmarks, peripheral nerve stimulator, or ultrasound) and the level of training of providers. DATA COLLECTION AND ANALYSIS: We used Cochrane's standard methodological procedures. Our primary outcomes were pain intensity at rest and during movement; rate of accidental falls; and rates of opioid-related adverse events. We used GRADE to assess the quality of evidence for primary outcomes. MAIN RESULTS: We included 25 RCTs (1688 participants) in this review (23 trials combined within meta-analyses). In 18 studies, participants underwent total knee arthroplasty (TKA), whereas seven trials investigated patients undergoing arthroscopic knee surgery. We identified 11 studies awaiting classification and 11 ongoing studies. We investigated the following comparisons. ACB versus sham treatment We included eight trials for this comparison. We found no significant differences in postoperative pain intensity at rest (2 hours: standardized mean difference (SMD) -0.56, 95% confidence interval (CI) -1.20 to 0.07, 4 trials, 208 participants, low-quality evidence; 24 hours: SMD -0.49, 95% CI -1.05 to 0.07, 6 trials, 272 participants, low-quality evidence) or during movement (2 hours: SMD -0.59, 95% CI -1.5 to 0.33; 3 trials, 160 participants, very low-quality evidence; 24 hours: SMD 0.03, 95% CI -0.26 to 0.32, 4 trials, 184 participants, low-quality evidence). Furthermore, they noted no evidence of a difference in postoperative nausea between groups (24 hours: risk ratio (RR) 1.91, 95% CI 0.48 to 7.58, 3 trials, 121 participants, low-quality evidence). One trial reported that no accidental falls occurred 24 hours postoperatively (low-quality evidence). ACB versus femoral nerve block We included 15 RCTs for this comparison. We found no evidence of a difference in postoperative pain intensity at rest (2 hours: SMD -0.74, 95% CI -1.76 to 0.28, 5 trials, 298 participants, low-quality evidence; 24 hours: SMD 0.04, 95% CI -0.09 to 0.18, 12 trials, 868 participants, high-quality evidence) or during movement (2 hours: SMD -0.47, 95% CI -1.86 to 0.93, 2 trials, 88 participants, very low-quality evidence; 24 hours: SMD 0.56, 95% CI -0.00 to 1.12, 9 trials, 576 participants, very low-quality evidence). They noted no evidence of a difference in postoperative nausea (24 hours: RR 1.22, 95% CI 0.42 to 3.54, 2 trials, 138 participants, low-quality evidence) and no evidence that the rate of accidental falls during postoperative care was significantly different between groups (24 hours: RR 0.20, 95% CI 0.04 to 1.15, 3 trials, 172 participants, low-quality evidence). AUTHORS' CONCLUSIONS: We are currently uncertain whether patients treated with ACB suffer from lower pain intensity at rest and during movement, fewer opioid-related adverse events, and fewer accidental falls during postoperative care compared to patients receiving sham treatment. The same holds true for the comparison of ACB versus femoral nerve block focusing on postoperative pain intensity. The overall evidence level was mostly low or very low, so further research might change the conclusion. The 11 studies awaiting classification and the 11 ongoing studies, once assessed, may alter the conclusions of this review.

[Placebo Effects in Acute Pain Therapy]. / Placeboeffekte in der Akutschmerztherapie.

Placebo and nocebo effects are currently within the focus of clinical and experimental pain research. Neurophysiological and psychophysiological mechanisms might play an important role. Placebo and nocebo effects might be mediated through the descendent inhibitory pain pathway via endogenous opioids. Apart from that three different psychological mechanisms might be relevant for placebo and nocebo effects: classical conditioning, social learning and pain expectation. An open analgesic drug application, detailed patient information about efficacy and possible adverse events (without an extensive focus on it) of perioperative analgesic drugs and interventions and an active involvement of the patient in pain therapy (e.g. by using patient-controlled analgesia) might improve acute pain therapy via an additive placebo effect (by around 30%).

Efficacy and safety of dexmedetomidine in peripheral nerve blocks: A meta-analysis and trial sequential analysis.

BACKGROUND: The duration of analgesia provided by nerve blocks is limited if local anaesthetics are administered alone. Therefore, several additives, including dexmedetomidine (DEX), have been investigated in order to prolong postoperative analgesia following single-shot regional anaesthesia. OBJECTIVES: The aim of this meta-analysis was to assess the efficacy and safety of the addition of perineural DEX to local anaesthetics compared with local anaesthetics alone or local anaesthetics combined with systemic administration of DEX. DESIGN: A systematic review of randomised controlled trials (RCT) with meta-analysis, trial sequential analysis and assessment of the quality of evidence by the GRADE approach. DATA SOURCES: The databases MEDLINE, CENTRAL and EMBASE (to May 2017) were systematically searched. ELIGIBILITY CRITERIA: All RCTs investigating the efficacy and safety of perineural DEX combined with local anaesthetics compared with local anaesthetics alone or local anaesthetics in combination with systemic DEX in peripheral nerve blocks of adults undergoing surgery were included. RESULTS: A total of 46 RCTs (3149 patients) were included. Patients receiving perineural DEX combined with local anaesthetics had a longer duration of analgesia than local anaesthetics alone [mean difference 4.87 h; 95% confidence interval (95% CI) 4.02 to 5.73; P < 0.001; I = 100%; moderate-quality evidence]. The most important adverse events in the DEX group were intraoperative bradycardia [risk ratio 2.83; 95% CI 1.50 to 5.33; P = 0.035; I = 40%; very low-quality evidence] and hypotension (risk ratio 3.42; 95% CI 1.24 to 9.48; P = 0.002; I = 65%; very low quality evidence). In contrast, there were no differences in the duration of analgesia between perineural or intravenous DEX combined with local anaesthetics (mean difference 0.98 h; 95% CI -0.12 to 2.08; P = 0.08; I = 0%). CONCLUSION: This meta-analysis demonstrated that DEX in combination with local anaesthetics increases postoperative analgesia for around 5 h. However, there are higher risks of intraoperative hypotension and bradycardia. Findings on side effects are associated with high uncertainty. Initial evidence suggests no difference in the duration of analgesia associated with systemic or perineural DEX. TRIAL REGISTRATION: CRD42016042486.