Efficacy of Ultrasound-Guided Serratus Anterior Plane Block for Postoperative Analgesia in Patients Undergoing Breast Surgery: A Systematic Review and Meta-Analysis of Randomised Controlled Trials

Objective. Serratus anterior plane block (SAPB) provides effective thoracic analgesia. This systematic review and meta-analysis was conducted to assess the safety and efficacy of SAPB for postoperative analgesia after breast surgery. Methods. A systematic literature search was performed using Embase, PubMed, Web of Science, and the Cochrane Library for eligible randomised controlled trials. The primary outcomes involved the administration of intraoperative and postoperative opioids. The Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach was used for rating the quality of evidence for making recommendations. Results. Overall, 13 studies comprising 826 patients met the inclusion criteria (412 in the SAPB group and 414 in the control group). Patients treated with SAPB exhibited a significantly lower postoperative opioid consumption (mean difference, −38.51 mg of oral morphine equivalent; 95% confidence interval (CI), −60.97 to −16.05; P < 0.01 ; I2 = 100%), whereas no difference was observed in the intraoperative opioid consumption (mean difference, −9.85 mg of oral morphine equivalent; 95% CI, −19.52 to −0.18; P = 0.05 ; I2 = 94%). In addition, SAPB significantly decreased the occurrence of postoperative nausea and vomiting (risk ratio, 0.32; 95% CI, 0.19–0.55; P < 0.05 ;I2 = 38%) and reduced pain scores during the postoperative period (1 h: standardised mean difference (SMD), −1.23; 95% CI, −2.00 to −0.45; I2 = 92%; 2 h: SMD, −0.71; 95% CI, −1.00 to −0.41; I2 = 48%; 4 h: SMD, −1.52; 95% CI, −2.77 to −0.27; I2 = 95%; 6 h: SMD, −0.80; 95% CI, −1.51 to −0.08; I2 = 81%; 8 h: SMD, −1.12; 95% CI, −1.98 to −0.27; I2 = 92%; 12 h: SMD, −0.78; 95% CI, −1.21 to −0.35; I2 = 83%; and 24 h: SMD, −0.71; 95% CI, −1.20 to −0.23; I2 = 87%; P < 0.05 for all). Conclusion. SAPB was safe and effective after breast surgery to relieve postsurgical pain. However, additional well-developed trials are required to validate these findings.

Persistent Postoperative Opioid Prescription Fulfillment and Peripheral Nerve Blocks for Ambulatory Shoulder Surgery: A Retrospective Cohort Study

Background There is need to identify perioperative interventions that decrease chronic opioid use. The authors hypothesized that receipt of a peripheral nerve block would be associated with a lower incidence of persistent postoperative opioid prescription fulfillment. Methods This was a retrospective population-based cohort study examining ambulatory shoulder surgery patients in Ontario, Canada. The main outcome measure was persistent postoperative opioid prescription fulfillment. In opioid-naive patients (no opioid prescription fulfillment in 90 days preoperatively), this was present if an individual fulfilled an opioid prescription of at least a 60-day supply during postoperative days 90 to 365. In opioid-exposed (less than 60 mg oral morphine equivalent dose per day within 90 days preoperatively) or opioid-tolerant (60 mg oral morphine equivalent dose per day or above within 90 days preoperatively) patients, this was classified as present if an individual experienced any increase in opioid prescription fulfillment from postoperative day 90 to 365 relative to their baseline use before surgery. The authors’ exposure was the receipt of a peripheral nerve block. Results The authors identified 48,523 people who underwent elective shoulder surgery from July 1, 2012, to December 31, 2017, at one of 118 Ontario hospitals. There were 8,229 (17%) patients who had persistent postoperative opioid prescription fulfillment. Of those who received a peripheral nerve block, 5,008 (16%) went on to persistent postoperative opioid prescription fulfillment compared to 3,221 (18%) patients who did not (adjusted odds ratio, 0.90; 95% CI, 0.83 to 0.97; P = 0.007). This statistically significant observation was not reproduced in a coarsened exact matching sensitivity analysis (adjusted odds ratio, 0.85; 95% CI, 0.71 to 1.02; P = 0.087) or several other subgroup and sensitivity analyses. Conclusions This retrospective analysis found no association between receipt of a peripheral nerve block and a lower incidence of persistent postoperative opioid prescription fulfillment in ambulatory shoulder surgery patients. Editor’s Perspective What We Already Know about This Topic What This Article Tells Us That Is New

Rescue-free laxation response with methylnaltrexone treatment in cancer patients with opioid-induced constipation: The impact of baseline ECOG status.

e24083 Background: Opioid-induced constipation (OIC) is a common side effect of opioid treatment for cancer-related pain. Methylnaltrexone (MNTX) is a peripherally active µ-opioid receptor antagonist indicated for OIC that does not affect opioid central analgesia. We assessed if baseline Eastern Cooperative Oncology Group (ECOG) status impacted the rescue-free laxation (RFL) responses among cancer patients with OIC treated with repeated doses of MNTX. Methods: This pooled post hoc analysis from 2 randomized, placebo-controlled, institutional review board–approved clinical studies included cancer patients with OIC (study 302, NCT00402038; study 4000, NCT00672477). Study 302 compared subcutaneous MNTX 0.15 mg/kg vs placebo and study 4000 compared body weight‒based subcutaneous MNTX 8 mg (38–< 62 kg) or 12 mg (³ 62 kg) vs placebo. The data were stratified by baseline ECOG status (< 2 vs ≥ 2). Endpoints included the number of patients with RFL responses within 4 hours after ≥ 2 of the first 4 doses and the number of patients with RFL response within 4 hours of treatment for patients who received all 7 doses. Results: The intent-to-treat analysis included 43 patients with an ECOG < 2 (placebo = 20; MNTX = 23) and 187 patients with an ECOG ≥ 2 (placebo = 94; MNTX = 93). Those with an ECOG < 2 were younger (mean age 58 vs 65 years), predominantly male (60.5% vs 51.3%), and used a higher daily dose of oral morphine equivalent (190.7 vs 180.0 mg/d) compared with those with an ECOG ≥ 2. Cancer patients with an ECOG < 2 treated with MNTX had a significantly greater RFL response within 4 hours after ≥ 2 of the first 4 doses compared with placebo (56.5% vs 5.0%, P = 0.0003). Similar results were reported for patients with an ECOG ≥ 2 (57.0% vs 5.3%, P < 0.0001). Compared with placebo, the MNTX group had a greater proportion of patients with an RFL response, whether they had at least 1 RFL response or up to 7 RFL responses out of 7 doses, with significant treatment differences with each additional RFL per 7 doses among cancer patients with an ECOG ≥ 2 (Table). Conclusions: RFL response rates in cancer patients were significantly greater in the MNTX group vs the placebo group regardless of baseline ECOG status; responses were similar between the 2 groups despite a higher daily dose of opioids in the group with an ECOG > 2. Clinical trial information: NCT00402038; NCT00672477. [Table: see text]

The Prevalence and Characteristics of Breakthrough Cancer Pain in Patients Receiving Low Doses of Opioids for Background Pain

The aim of this study was to assess the prevalence and characteristics of breakthrough cancer pain (BTcP) in patients receiving low doses of opioids for background pain. A consecutive sample of advanced cancer patients receiving less than 60 mg/day of oral morphine equivalent (OME) was selected. Epidemiological data, background pain intensity, and current analgesic therapy were recorded. The presence of BTcP was diagnosed according to a standard algorithm. The number of BTcP episodes, intensity of BTcP, its predictability and triggers, onset duration, interference with daily activities, BTcP medications, satisfaction with BTcP medication, and time to meaningful pain relief were collected. A total of 126 patients were screened. The mean intensity of background pain was 2.71 (1.57), and the mean OME was 28.5 mg/day (SD15.8). BTP episodes were recorded in 88 patients (69.8%). The mean number/day of BTP episodes was 4.1 (SD 7.1, range 1–30). In a significant percentage of patients, BTcP was both predictable and unpredictable (23%). The BTcP onset was less than 20 min in the majority of patients. The mean duration of untreated episodes was 47.5 (SD 47.6) minutes. The mean time to meaningful pain relief after taking a BTcP medication was >20 min in 44.5% of patients. The efficacy of BTcP medication was not considered good in more than 63% of patients. Gender (females) (OR = 4.16) and lower Karnofsky (OR = 0.92) were independently associated with BTcP. A higher number of BTcP episodes/day was associated with gender (females) (p = 0.036), short duration of BTcP (p = 0.005), poorer efficacy of BTcP medication (none or mild) (p = 0.001), and late meaningful pain relief (p = 0.024). The poor efficacy of BTcP medication was independently associated with a higher number of episodes/day (OR = 0.22). In patients who were receiving low doses of opioids, BTcP prevalence was 69.8%. Many patients did not achieve a sufficient level of satisfaction with BTcP medications, particularly with oral morphine. Data also suggest that better optimization of background analgesia, though apparently acceptable, may limit the number of BTcP episodes.

Percutaneous cervical cordotomy for cancer-related pain: prospective multimodal outcomes evaluation

BackgroundPercutaneous cervical cordotomy (PCC) offers pain relief to patients with unilateral treatment-refractory cancer-related pain. There is insufficient evidence about any effects of this intervention on patients’ quality of life.MethodComprehensive multimodal assessment to determine how PCC affects pain, analgesic intake and quality of life of patients with medically refractory, unilateral cancer-related pain.This study was set in a multidisciplinary, tertiary cancer pain service. Patient outcomes immediately following PCC were prospectively recorded. Patients were also followed up at 4 weeks.ResultsOutcome variables collected included: background and breakthrough pain numerical rating scores before PCC, at discharge and 4 weeks postprocedure; oral morphine equivalent opioid dose changes, Patient’s Global Impression of Change, Eastern Cooperative oncology group performance status and health related quality of life score, that is, EuroQol-5 dimension-5 level (EQ-5D).ConclusionsDespite significant improvement in pain and other standard outcomes sustained at 4 weeks, there was little evidence of improvement in EQ-5D scores. In patients with terminal cancer, improved pain levels following cordotomy for cancer-related pain does not appear to translate into improvements in overall quality of life as assessed with the generic EQ-5D measure.

Postoperative Analgesic Effectiveness of Quadratus Lumborum Block for Cesarean Delivery under Spinal Anesthesia

Background Spinal morphine is the mainstay of postcesarean analgesia. Quadratus lumborum block has recently been proposed as an adjunct or alternative to spinal morphine. The authors evaluated the analgesic effectiveness of quadratus lumborum block in cesarean delivery with and without spinal morphine. Methods Randomized trials evaluating quadratus lumborum block benefits in elective cesarean delivery under spinal anesthesia were sought. Three comparisons were considered: spinal morphine versus spinal morphine and quadratus lumborum block; spinal morphine versus quadratus lumborum block; and no block or spinal morphine versus quadratus lumborum block. The two coprimary outcomes were postoperative (1) 24-h cumulative oral morphine equivalent consumption and (2) pain at 4 to 6 h. Secondary outcomes included area under the curve pain, time to analgesic request, block complications, and opioid-related side effects. Results Twelve trials (924 patients) were analyzed. The mean differences (95% CIs) in 24-h morphine consumption and pain at 4 to 6 h for spinal morphine versus spinal morphine and quadratus lumborum block comparison were 0 mg (−2 to 1) and −0.1 cm (−0.7 to 0.4), respectively, indicating no benefit. For spinal morphine versus quadratus lumborum block, these differences were 7 mg (−2 to 15) and 0.6 cm (−0.7 to 1.8), respectively, also indicating no benefit. In contrast, for no block or spinal morphine versus quadratus lumborum block, improvements of −18 mg (−28 to −7) and −1.5 cm (−2.4 to −0.6) were observed, respectively, with quadratus lumborum block. Finally, for no block or spinal morphine versus quadratus lumborum block, quadratus lumborum block improved area under the 48-h pain curve by −4.4 cm · h (−5.0 to −3.8), exceeding the clinically important threshold (3.96 cm · h), but no differences were observed in the other comparisons. Conclusions Moderate quality evidence suggests that quadratus lumborum block does not enhance analgesic outcomes when combined with or compared with spinal morphine. However, the block improves postcesarean analgesia in the absence of spinal morphine. The clinical utility of this block seems limited to situations in which spinal morphine is not used. Editor’s Perspective What We Already Know about This Topic What This Article Tells Us That Is New

Patients With Fibrotic Interstitial Lung Disease Receive Supportive and Palliative Care Just Prior to Death

Background: Fibrotic interstitial lung diseases (f-ILDs) are often progressive and incurable. As patients experience significant symptoms and have a poor prognosis, early palliative care referral is recommended. Objective: To examine the care delivered to patients with f-ILD during the terminal hospital admission and the past 2 years of life. Methods: A retrospective audit was performed for consecutive patients who died from f-ILD at 2 Australian teaching hospitals between January 1, 2012, and December 31, 2016. Results: Of 67 patients, 44 (66%) had idiopathic pulmonary fibrosis. Median age was 78 years. Median respiratory function: forced expiratory volume in 1 second 69.0% predicted (interquartile range [IQR]: 58.0%-77.0%), forced vital capacity 64.0% predicted (IQR = 46.8%-74.3%), and diffusing capacity of carbon monoxide 36.0% predicted (IQR = 31.0%-44.0%). In the 2 years prior to the terminal admission, 38 (57%) patients reported severe breathlessness and 17 (25%) used opioids for symptom relief. Twenty-four (36%) patients received specialist palliative care (SPC) and 11 (16%) completed advance care planning. During the terminal admission, 10 (15%) patients were admitted directly under SPC. A further 33 (49%) patients were referred to SPC, on average 1 day prior to death. Sixty-three (94%) patients received opioids and 49 (73%) received benzodiazepines for symptom management. Median starting and final opioid doses were 10 and 23 mg oral morphine equivalent/24 hours, respectively. Opioids were commenced on average 2 (IQR 1-3) days prior to death. Conclusions: Although most patients were identified as actively dying in the final admission, referral to SPC and use of palliative medications occurred late. Additionally, few patients accessed symptom palliation earlier in their illness.

Opioid rotation from transdermal fentanyl to continuous subcutaneous hydromorphone in a cachectic patient: A case report and review of the literature

Opioid rotation from transdermal fentanyl to an alternate opioid is often necessitated in advanced disease, but is fraught with uncertainty due to variable absorption from the patch in end-stage illness and the lack of a clearly established opioid rotation ratio. The manufacturer of transdermal fentanyl provides opioid rotation recommendations only for rotation from the oral morphine equivalent daily dose (MEDD) of opioid to the patch, not in the opposite direction. This is a case report of a single patient with cancer and cachexia admitted to the palliative care unit of a large academic medical centre in Canada. The patient is a 50-year-old female with widely metastatic breast cancer who developed opioid toxicity when maintenance transdermal fentanyl patch therapy (100 μg patch applied every 72 h) was rotated to subcutaneous hydromorphone infusion to improve pain control. Hydromorphone was initiated at a rate of 1 mg/h by continuous infusion based on an opioid rotation ratio for transdermal fentanyl (μg/h):MEDD (mg/day) of 1:2.4. Opioid toxicity eventually resolved with downward titration of hydromorphone to only 30% of the initially estimated equianalgesic dose. This case highlights the need for close follow-up of all patients undergoing opioid rotation from transdermal fentanyl and reinforces the need to reduce the initial dose of the new opioid by 30%–50% of the calculated MEDD, especially when rotating from a high dose of transdermal fentanyl, or if there are factors potentially impairing absorption from the patch such as age, cachexia and weight loss, or if rotation is performed for reasons other than uncontrolled pain.

OP0088 INITIATING TNF INHIBITORS IN INFLAMMATORY ARTHRITIS DOES NOT DECREASE THE AVERAGE OPIOID ANALGESIC CONSUMPTION

Background:TNFα-inhibitor (TNFi) therapy is effective in controlling several rheumatic diseases and has been shown to reduce pain in patients with arthritis. Opioids are often prescribed for chronic pain, a common issue in inflammatory joint disease.Objectives:To explore the impact of the initiation of TNFi therapy as a first-line biologic disease-modifying anti-rheumatic drug (DMARD) on the prescription rates of opioids in patients with rheumatoid arthritis (RA), psoriatic arthritis (PsA), ankylosing spondylitis (AS) and undifferentiated arthritis (UA) in Iceland.Methods:All patients receiving biologic DMARD therapy for rheumatic diseases in Iceland are registered in a nationwide database (ICEBIO). The Icelandic Directorate of Health operates a Prescription Medicines Register that includes over 90% of all drug prescriptions in Iceland. The study group included patients with RA, PsA, AS, and UA registered in ICEBIO and for each of them five randomly selected comparators from the general population matched on age, sex, and calendar time. On February 1st2016 we extracted data on all filled opioid analgesic prescriptions two years before and two years after the date of TNFi initiation.Results:Data from 359 RA, 217 AS, 251 PsA and 113 UA patients and 4700 comparators were collected. In total, 75% of patients compared to 43% of comparators received ≥1 opiate prescription during the study period. The proportion of patients using opioids (regardless of dose) two years prior to TNFi initiation was 41%, increasing to 49% the following year. After TNFi initiation the proportion returned to 40% (Figure 1). Despite this, the mean yearly opiate dose used by the patients followed a rising trajectory throughout the study period (Figure 2). In total, patients were prescribed nearly 6 times more opioids than the comparators, corresponding to a bootstrapped mean (95% CI) dose of 818 (601-1073) mg MED per patient and year compared to 139 (111-171) mg for comparators.Figure 1.Percental distributions of opioid analgesic use by dose (according to dispensed prescriptions) among patients with inflammatory arthritis (A) and matched comparators (B). All doses are oral morphine equivalent dose (MED) in milligrams.Figure 2.Bootstrapped mean oral morphine equivalent dose per person per year for patients with inflammatory arthritis (above) and age and sex matched comparators (below). Box edges represent 25-75thpercentiles and whiskers 95% confidence intervals.Conclusion:Three out of four patients with inflammatory arthritis in Iceland use opioid analgesics in the two years prior to and/or after the initiation of TNFi therapy and the mean doses were significantly higher than in matched comparators. The proportion of patients receiving opioids increased before TNFi therapy and then decreased again to the previous level. The initiation of the first-line TNFi did not reduce opioid consumption by dose at the group level. On the contrary, there was a trend towards increasing doses over time in both patients and comparators, possibly reflecting the development of opiate tolerance.Table 1.Baseline demographic data. Mean ± SD unless specified. * defined from diagnosis to baselAll patientsRheumatoid arthritisPsoriatic arthritisAnkylosing spondylitisUndifferentiated arthritisTotal n (%)940 (100)359 (38)251 (27)217 (23)113 (12)Age (years)49 ± 1453 ± 1449 ± 1343 ± 1344 ± 15Disease duration (years)*7.8 ± 8.58.2 ± 8.27.4 ± 7.88.3 ± 10.26.3 ± 6.6Female58%73%59%34%52%Disclosure of Interests:Olafur Palsson: None declared, Thorvardur Love: None declared, Johan K Wallman Consultant of: Consultant for AbbVie, Celgene, Eli Lilly, Novartis and UCB Pharma., Meliha C Kapetanovic: None declared, Petur S Gunnarsson: None declared, Björn Gudbjornsson Speakers bureau: Novartis and Amgen

Analgesic efficacy of cannabinoids for acute pain management after surgery: a systematic review and meta-analysis

BackgroundEvidence regarding the role of cannabinoids in managing acute postoperative pain is conflicting. The purpose of this systematic review and meta-analysis was to determine the analgesic efficacy of perioperative cannabinoid compounds for acute pain management after surgery.MethodsOriginal research articles evaluating the addition of cannabinoids to standard opioid-based systemic analgesia (Control) in the postoperative period were sought. Our primary outcomes were cumulative oral morphine equivalent consumption and rest pain severity at 24 hours postoperatively. We also assessed analgesic consumption in the postanesthesia care unit (PACU), pain scores in PACU, 6 and 12 hours postoperatively, and opioid-related and cannabinoid-related side effects, patient satisfaction, and quality of recovery as secondary outcomes.ResultsEight randomized controlled trials (924 patients) and four observational studies (4259 patients) were analyzed and included. There were insufficient data to pool for quantification of differences in cumulative oral morphine equivalent consumption and rest pain severity at 24 hours postoperatively with the addition of cannabinoids in comparison to Control. Qualitative synthesis revealed no differences in cumulative oral opioid consumption or pain at rest 24 hours postoperatively with the addition of cannabinoids in comparison to Control. Patients receiving cannabinoids appeared to have an increased weighted mean difference 95% CI of pain at 12 hours by 0.83 cm (0.04 to 1.63) (p=0.04). Patients receiving cannabinoids also appeared to have 3.24 times increased odds of developing hypotension postoperatively (95% CI 1.12 to 9.36) (p=0.03). Qualitative and quantitative synthesis revealed no differences in any other secondary outcomes.ConclusionsOur quantitative and qualitative review of the literature suggests that the analgesic role of perioperative cannabinoid compounds is limited, with no clinically important benefits detected when cannabinoids are added to traditional systemic analgesics compared with traditional systemic analgesics alone. Notably, there appears to be a signal towards increased postoperative pain and hypotension associated with the addition of perioperative cannabinoids to traditional systemic analgesics. These results do not support the routine use of cannabinoids to manage acute postoperative pain at the present time.