Physician adherence to guideline recommendations for the use of opioids to manage chronic pain is often limited.  In February 2018, we administered a 28-item online survey to explore perceptions of the 2017 Canadian guideline for opioid therapy and chronic noncancer pain and if physicians had altered practices in response to recommendations.  We invited 34,322 Canadian physicians to complete our survey, and 1,128 responded for a response rate of 3%; 687 respondents indicated they prescribed opioids for noncancer pain and answered survey questions about the guideline and their practice. Almost all were aware of the guideline, 94% had read the document, and 89% endorsed the clarity as good or excellent. The majority (86%) felt the guideline was feasible to implement, but 66% highlighted resistance by patients, and 63% the lack of access to effective nonopioid treatment as barriers. Thirty-six percent of respondents mistakenly believed the guideline recommended mandatory tapering for patients using high-dose opioid therapy , and 58% felt they would benefit from support for opioid tapering. Seventy percent of respondents had changed practices to align with guideline recommendations, with 51% engaging some high-dose patients in opioid tapering and 43% reducing the number of new opioid starts.  There was high awareness of the 2017 Canadian opioid guideline among respondents, and preliminary evidence that recommendations have changed practice to better align with the evidence. Ongoing education is required to avoid the misunderstanding that opioid tapering is mandatory, and research to identify effective strategies to manage chronic noncancer pain is urgently needed. Canada is the world's second largest per capita prescriber of opioids , and escThe 2017 guidelines were supported by many Canadian medical organizations, including members of the Pan-Canadian Collaborative for Improved Opioid Prescribing , the Association of Faculties of Medicine of Canada, the College of Family Physicians of Canada, the Federation of Medical Regulatory Authorities of Canada, and the Royal College of Physicians and Surgeons of Canada) . To incrhttps://app.magicapp.org/app#/guidelines), an online platform that provides guidelines in an interactive, multilayered format. We further queried if respondents had made any changes to their practices in response to guideline recommendations. We tested the questionnaire with members of the collaborative, and changes were made to include questions regarding supports needed by physicians. We pretested the final questionnaire on a group of 3 physicians who prescribed opioids for chronic noncancer pain, who also commented on its clarity and comprehensiveness and on the time required to complete it (5–8 minutes). No further modifications were suggested by pretest participants , and most were family physicians  practicing in Ontario . Forty-two percent (282 of 676) reported that >10% of their patients sought care for chronic noncancer pain, and 36% (214 of 596) prescribed opioids to >10% of their patients .Almost all respondents were aware of the 2017 Canadian opioid guideline  and had read it thoroughly  or in part . Similar proportions had read the print  and online MAGICapp  versions; 19% (109 of 588) had read both. The large majority of respondents endorsed both print and MAGICapp formats as good or excellent (82% for both); however, twice as many endorsed the online MAGICapp version as excellent (18% vs. 9%).Eighty-nine percent of respondents agreed the clarity of the guideline was excellent  or good . Some respondents  felt the 2017 Canadian opioid guideline had advantages over competing guidelines, whereas 49% (262 of 538) were unsure and 12% disagreed (63 of 538). Those who reported advantages most often highlighted its national scope  and specific guidance . Sixty percent agreed the 2017 Canadian opioid guideline was evidence-based; 32% were unsure, and 8% disagreed.  When askEight-six percent of respondents felt the guideline was either very feasible  or somewhat feasible  to implement. Of the 14% (79 of 553) that felt the guideline was not feasible to implement, the most common concerns were that recommendations were too restrictive regarding the use of opioids  or that recommendations were impractical .Most respondents acknowledged resistance by patients , financial barriers to nonpharmacologic treatment , and lack of availability of nonpharmacologic treatment  as implementation challenges. Many respondents noted inadequate time to manage complex cases , lack of access to addiction management services , and that it was unrealistic for some of their high-opioid dose legacy patients to engage in tapering  . When asMost respondents felt that increased coverage for chronic pain treatment options by insurers , and greater availability of chronic pain treatment services  would facilitate guideline implementation. Forty percent of respondents (235 of 590) indicated that billing incentives were required to encourage physicians to spend more time with their chronic noncancer pain patients. The most requested topics for continuing medical education (CME) among respondents were for assistance managing demanding, resistant, or nonadherent patients on chronic opioids  and instruction on nonopioid options for managing chronic noncancer pain  . The mosThe majority of respondents  agreed there were areas where their practice had differed from recommendations of the 2017 Canadian opioid guideline, and 79% said they had (70%) or intended (9%) to make changes to their practice because of guideline recommendations. Only 16% (96 of 590) reported they did not intend to make any changes to their practice. Specifically, in response to the guideline, 51% (301 of 590) of respondents had engaged some of their legacy patients in opioid tapering, and 43% had reduced the number of new starts of opioid therapy (254 of 590). Approximately a third  had reduced the number of opioid tablets they prescribed at one time, and 32% (191 of 590) had reduced the dose of opioids they prescribed for new starts. A small minority of physicians had either stopped prescribing opioids for chronic noncancer pain  or increased their prescribing of opioids for chronic pain  .Almost all opioid-prescribing survey respondents were aware of the 2017 Canadian opioid guideline and endorsed its clarity and feasibility of implementation; the majority agreed the guideline was evidence-based. Resistance from patients and lack of access to effective nonpharmacologic therapy for chronic pain were the main reported barriers to implementation, and most respondents wanted assistance with tapering high-dose opioid patients. Only half of our respondents were confident that the guideline did not mandate tapering for patients prescribed high-dose opioid, and the majority had altered their practices as a result of the guideline, most often involving tapering legacy patients and reducing the number of new starts of opioid therapy for chronic noncancer pain patients.The 2017 guideline was published with the MAGICapp online platform due to feedback that print versions were cumbersome to use in practice , and twiPhysicians are well-trained in prescribing, but not always in deprescribing, and a number of our survey respondents highlighted this challenge; the third most requested CME topic was strategies to safely taper opioids. There is likely a dose-dependent increase in the risk of nonfatal and fatal opioid overdose , 15. Morhttp://www.magicapp.org/public/guideline/8nyb0E).It is noteworthy that approximately a third of respondents to our survey felt the 2017 guideline endorsed mandatory opioid tapering among patients prescribed high-dose opioid therapy, and this may reflect confusion between weak and strong recommendations. Recommendation 9 of the guideline, which suggests tapering opioids to the lowest effective dose for patients prescribed ≥90 mg MED, potentially including discontinuation, rather than making no change in opioid therapy, is a weak recommendation. This means that while the majority of informed patients would choose the recommended course of action, an appreciable minority would not. With weak recommendations, clinicians should recognize that different choices will be appropriate for individual patients, and they should help patients arrive at decisions consistent with their values and preferences. The online version of the 2017 Canadian guideline includes patient decision aids for all weak recommendations , the Alberta Medical Association Section of Chronic Pain, and the Pain Society of Alberta signed an Agreement in Principle to support chronic pain patients prescribed long-term opioid therapy (https://www.painab.ca/uploads/1/0/8/0/108066059/aip.pdf). This document, which sites the 2017 Canadian Opioid Guideline for support, advises, in part, that no individual on long-term opioid therapy should be abruptly discontinued. Similar agreements in other provinces may be helpful for re-enforcing this message among prescribers.On October 18, 2019, the College of Physicians and Surgeons of Alberta, HELP Alberta's Pain (a patient advocacy group; Many respondents felt that greater access to effective chronic pain management was required; however, while nonopioid alternatives would be expected to reduce harms associated with long-term opioid use, the incremental benefit for chronic pain sufferers is uncertain. Pharmacologic therapies that have been directly compared with opioids show similar, small effects on pain and function . MoreoveStrengths of our study include a comprehensive sampling of Canadian physicians who prescribe opioids for chronic noncancer pain. Moreover, our survey development and administration was consistent with best practices . Our finThere was very high awareness of the 2017 Canadian guideline for opioid therapy and chronic noncancer pain among respondents to our survey, and most physicians reported changing their practices to align with recommendations. Optimizing opioid-prescribing for chronic noncancer pain should reduce opioid-related harms, but confirmation from rigorously conducted observational studies is required. Further education appears needed to ensure appropriate interpretation of weak and strong guideline recommendations, and re-enforcement that forced opioid tapering is inappropriate. The Canadian opioid crisis has highlighted the urgent need for improved management of chronic pain; however, the lack of highly effective therapies suggests that further research is urgently needed versus simply expanding access to existing treatment options.


What are the use patterns and factors associated with combined hormonal contraception (CHC) ineffectiveness or discontinuation due to side-effects in patients with endometriosis and pelvic pain?Worse chronic pelvic pain (CPP) severity and pelvic floor myalgia were associated with continuous CHC ineffectiveness, while poorer quality-of-life was associated with continuous CHC discontinuation due to side-effects.CHC is a first line of therapy for endometriosis-associated pelvic pain in women. However, some patients state that CHC is ineffective for their pain, while others have to discontinue CHC due to side-effects.Analysis of a prospective patient database from a tertiary care referral center for patients with endometriosis and pelvic pain between December 2013 and April 2015 was carried out.A total of 373 patients of reproductive age with endometriosis from the database were included in the study. Data included patient self-reported questionnaires, physical examination findings and validated instruments. There were four variables of interest: history of cyclical CHC ineffectiveness (yes/no), history of cyclical CHC discontinuation due to side-effects (yes/no), history of continuous CHC ineffectiveness (yes/no) and history of continuous CHC discontinuation due to side-effects (yes/no). The primary outcome was CPP severity for the past 3 months (score of 0–10), and secondary outcomes were other pelvic pain scores, quality-of-life on the Endometriosis Health Profile 30 (EHP-30) and underlying conditions including irritable bowel syndrome, painful bladder syndrome, abdominal wall pain, pelvic floor myalgia and depression, anxiety and pain catastrophizing.P < 0.001). Poorer quality-of-life was present in women who reported a history of continuous CHC discontinuation due to side-effects (P = 0.005). Among the underlying conditions, pelvic floor tenderness  was associated with CHC ineffectiveness.Among the 373 cases in the dataset, prior cyclical CHC use was reported by 228 (61.1%) women, of which 103 (27.6%) stated it was ineffective for their pain and 94 (25.2%) stated they discontinued CHC due to side-effects. Previous continuous CHC use was reported by 175 (46.9%) women, of which 67 (18.0%) stated it was ineffective and 59 (15.8%) stated they discontinued due to side-effects. Worse CPP severity in the last 3 months was associated with a history of continuous CHC ineffectiveness .In women with endometriosis, CHC ineffectiveness was associated with worse CPP and pelvic floor myalgia, which suggests myofascial or nervous system contributors to CPP that does not respond to hormonal suppression. A tender pelvic floor, as a sign of pelvic floor myalgia, may be a clinical marker of patients with endometriosis who are less likely to have an optimal response to hormonal suppression. For women who discontinue CHC due to side-effects, research is needed to help alleviate these side-effects as these patients report worse quality-of-life.This work was supported by a Canadian Institutes of Health Research (CIHR) Transitional Open Operating Grant (MOP-142273) as well as BC Women’s Hospital and the Women’s Health Research Institute. PY is also supported by a Health Professional Investigator Award from the Michael Smith Foundation for Health Research. MB/CA has financial affiliations with Abbvie and Allergan; the other authors have no conflicts of interest. Endometriosis and pelvic pain affect more than 1 in 10 women. In endometriosis, tissue that is similar to the tissue that normally lines the inside of the uterus grows outside the uterus and most commonly involves the ovaries, tubes, and the lining of the pelvis. The birth control pill, which contains female hormones, is commonly used as a treatment for pelvic pain in women with endometriosis. In this study, we asked women with endometriosis and pelvic pain about their experiences of using the birth control pill. For women who said that the birth control pill was not effective for their pain, they reported higher levels of pain and more often had muscle pain. It is therefore important to recognize when women with endometriosis actually have muscle pain, as the birth control pill may not be helpful in their treatment. Women who said that they had to stop the birth control pill because of side-effects reported a worse quality-of-life. Ideally, doctors should find ways to help reduce these side-effects of the birth control pill or find new treatments for these women.Chronic pelvic pain (CPP) is defined as a constant or intermittent pain in the lower abdominal or pelvic area for a minimum of 6 months, not exclusively associated with menstruation, intercourse, or pregnancy  with a pCombined hormonal contraception (CHC) is regarded a first line of therapy in treating endometriosis-associated CPP .In this study, we included participants who were referred or re-referred to our center between December 2013 and April 2015, and who had a diagnosis of endometriosis . Exclusion criteria were participants older than 50 years or postmenopausal status.Participants were asked to retrospectively recall whether they have ever taken CHC for their pain (including both past and current use), and whether CHC was taken cyclically and/or continuously. For those who reported having taken CHC cyclically, participants were asked whether CHC was ineffective for their pain and/or whether the CHC was discontinued due to side-effects. Similarly, for those who reported having taken CHC continuously, participants were asked whether CHC was ineffective for their pain and/or whether the CHC was discontinued due to side-effects.Thus, there were four variables of interest: history of cyclical CHC ineffectiveness (yes/no), history of cyclical CHC discontinuation due to side-effects (yes/no), history of continuous CHC ineffectiveness (yes/no) and history of continuous CHC discontinuation due to side-effects (yes/no). Based on the nature of the questions, it was possible for patients to have tried both cyclical and continuous CHC, and to answer ‘yes’ to both ineffectiveness and discontinuation due to side-effects.Primary outcome was CPP severity for the past 3 months assessed using an 11-point numeric rating scale (0–10). Secondary outcomes were other pain symptoms in the past 3 months  , ever symptoms of superficial and deep dyspareunia , and quality of life in the last 4 weeks via the pain subscale of the Endometriosis Health Profile 30 (EHP-30) .Bivariate association was performed between each of the four variables of interest, and the primary and secondary outcomes. For the primary outcome, logistic regression modeling was also carried out, controlling for demographic factors, followed by sequential backward elimination until all variables in the regression model had a We also sought to determine whether the four variables of interest were associated with underlying conditions, which could explain the association with the primary/secondary outcomes. The underlying conditions were a previous surgical confirmation of endometriosis; diagnosis of irritable bowel syndrome (IBS) using the Rome III criteria ; diagnosIn addition, we determined whether a history of CHC ineffectiveness or discontinuation was associated with features of endometriosis: Stage I–II versus Stage III/IV in those who had previous surgery, presence versus absence of a nodule at the initial visit at the center and presence versus absence of an endometrioma at the initial visit at the center.P value <0.05 considered to show significance. Means were provided with SD, medians with ranges and odds ratio with CI. Bivariate testing was carried out using the two sample Student’s t-test (with Welch’s correction if a significant difference in variances using Levene’s test), Fisher’s Exact test, or Chi-square test, depending on the variables involved. The proportion of missing values in anxiety, depression and pain catastrophizing variables were 5.6% in the total cohort and thus were imputed as previously reported  with n = 303), an equal proportion were Stage I–II  and Stage III/IV . The remaining 30 did not have previous surgery, but had a diagnosis of endometriosis through the identification of a nodule or endometrioma on examination/ultrasound at the initial visit at the center. A total of 73 participants had a nodule and 88 participants had an endometrioma at the initial visit .A total of 373 patients from the database met the study criteria . Of the In the study population, 228 (61.1%) reported prior use of cyclic CHC, while 175 participants (46.9%) reported history of using continuous CHC (some patients were in both categories).For the four variables of interest: 103 (27.6% of the study sample) reported cyclical CHC ineffectiveness, 94 (25.2%) reported cyclical CHC discontinuation due to side-effects, 67 (18.0%) reported continuous CHC ineffectiveness and 59 (15.8%) reported continuous CHC discontinuation due to side-effects .P = 0.004) and less likely to be married (P = 0.028). Those who reported continuous CHC to be ineffective were also significantly younger (P < 0.001) and had lower incomes (P = 0.036). No differences were noted for those who reported discontinuing the cyclic or combined CHC due to side-effects   . Multipl< 0.001) .P = 0.025), deep dyspareunia (P = 0.030), and dyschezia (P = 0.025). Cyclic CHC ineffectiveness and discontinuation due to side-effects were associated with worse dysmenorrhea . Those who reported continuous CHC discontinuation due to side-effects had poorer quality-of-life (P = 0.005).For secondary outcomes , continuP = 0.003 and P < 0.001, respectively), and PBS was also associated with continuous CHC ineffectiveness (P = 0.043). There were no associations with IBS, abdominal wall pain or psychological measures.In P = 0.041, P = 0.021) and Stage I–II disease .In In this study of women with endometriosis, 18–28% stated that CHC was ineffective for their pain, and 15–25% discontinued CHC due to side-effects. Our results are consistent with the findings of The main strengths of the study are the use of prospectively consented patients in a large database, and the inclusion of physical examination findings, standardized diagnostic criteria and validated instruments. One limitation is that although patients were prospectively consented for inclusion in the database, this study involved data from the patients’ retrospective recall. In addition, no data were collected on the type of side-effects experienced by the patient, and the medication ineffectiveness was reported subjectively by the patient rather than using standardized criteria. Finally, the diagnosis of endometriosis was based on previous surgery or a current nodule or endometrioma on examination/ultrasound; without prospective surgical data on all the patients, it was not possible to do a sub-analysis by current surgical features (e.g. stage).The association between continuous CHC ineffectiveness and worse CPP may be due to the multifactorial pathophysiology of CPP, which includes nervous system and myofascial mechanisms  tend to have side-effects with a variety of medications and environmental exposures, and thus they are also less likely to tolerate the side-effects of CHC.Another interesting observation was the association between continuous CHC ineffectiveness and lower annual household income. Our study was conducted in a population with a universal province-wide health care plan, but not a universal pharmacare plan, and we do not know whether an individual patient in the study paid for CHC out of pocket or had coverage through third-party insurance. Several studies have identified that female gender, lower income, chronic conditions, and increased drug cost or decreased insurance co-payment can significantly affect patient adherence to treatment .Continuous CHC ineffectiveness was also associated with secondary pain outcomes, such as worse dysmenorrhea, deep dyspareunia and dyschezia. This suggests that pelvic floor myalgia (with or without PBS) may also be associated with these pain symptoms, in addition to CPP. Cyclic CHC ineffectiveness and discontinuation were associated with worse dysmenorrhea, but not with CPP. This raises the question of why continuous CHC ineffectiveness, but not cyclic CHC ineffectiveness, was associated with worse CPP. One explanation may be lack of power, as there was still a nonsignificant trend toward worse CPP in those with cyclic CHC ineffectiveness. An alternative explanation may be that cyclic CHC ineffectiveness is due in part to decreased suppression (during the pill-free week), which would be associated with dysmenorrhea, but not necessarily the myofascial and central nervous system mechanisms underlying CPP.We also found that CHC ineffectiveness and discontinuation due to side-effects were associated with less severe endometriosis disease, in particular the absence of ovarian endometrioma at the initial visit at the center and Stage I–II disease at the time of previous surgery. A possible explanation is that those with more severe endometriosis may be expected to have primarily gynecologic pain that is responsive to hormonal suppression, while those with less severe endometriosis may be more likely to have nervous system or musculoskeletal factors involved in their pain pathophysiology and thus are more likely to report CHC ineffectiveness.In our current research, we are now longitudinally following these patients to assess CHC use patterns prospectively. Future research into the alleviation of CHC side-effects in women with pelvic pain is also important, as these patients report worse quality-of-life; for example, CHC-related mood side-effects could be managed with psychological or pharmacological therapy. Another future research endeavor would be a clinical trial of CHC for pelvic pain, where patients are stratified by the presence of gynecologic and nongynecologic pain generators, in order to confirm that CHC is less effective in those with pelvic floor myalgia.


The optimal analgesia method in video-assisted thoracoscopic surgery (VATS) remains controversial. Intercostal nerve blockade (ICNB) is limited by its duration of action. The erector spinae plane (ESP) block has the potential to provide satisfactory analgesia for VATS; however, the effectiveness of continuous ESP versus surgeon-performed ICNB has not been investigated. The objectives of this study were to establish feasibility of patient recruitment and follow-up before undertaking a fully powered randomized controlled trial (RCT); and, secondarily, to compare opioid usage, pain control, and sensory blockade.2, contraindications to neuraxial analgesia techniques as per the American Society of Regional Anesthesia and Pain guidelines, known allergy to local anesthetics, language or comprehension barriers, procedures with a higher chance of open surgery, and regular opioid use for ≥3 months preoperatively. Patients underwent either continuous ESP (n=12) or surgeon-performed ICNB (n=12). All patients received routine intraoperative anesthesia care and multimodal analgesia. Feasibility criteria were recruitment rate of two patients/week and full follow-up in all patients in-hospital. We compared opioid consumption, postoperative pain scores , adverse events, patient satisfaction, and distribution of sensory blockade as clinical outcomes (secondary).This feasibility RCT was undertaken at St Joseph’s Hospital, Hamilton, Ontario, Canada, and included 24 patients (>18 years) having elective VATS with at least one overnight stay. Exclusion criteria were patient refusal, body mass index >40 kg/mFeasibility of primary outcomes was successfully demonstrated. Five patients had an epidural in anticipation of open surgery. Mean opioid consumption as equivalent morphine units was less in the ESP group over the first 24 h  and 48 h . There were no differences in adverse effects.A fully powered RCT is feasible with modifications. Our results also suggest that continuous ESP is safe and can decrease opioid needs. However, it is important to consider procedures to improve compliance to protocol and adherence to assigned interventions.NCT03176667. Registered June 5, 2017.Clinicaltrials.gov identifier: The online version contains supplementary material available at 10.1186/s40814-021-00801-7. Video-assisted thoracoscopic surgery (VATS) is an increasingly popular technique in thoracic surgery with improvements in technology. VATS provides significant advantages over open thoracotomy procedures including reduced surgical pain, reduced mortality, improved postoperative pulmonary function, and shorter hospital length of stay –4. NeverMost patients receive thoracic epidural analgesia (TEA) to treat postoperative pain in thoracotomy procedures . For VATGiven the importance of providing adequate analgesia in VATS procedures and lack of consensus among surgeons and anesthesiologists for the optimal analgesic technique, we planned to conduct a randomized controlled trial (RCT) to compare continuous ESP blockade versus surgeon-performed ICNBs in patients receiving VATS lobectomy or wedge resections, with the primary objective of assessing the difference in opioid analgesia used. Before conducting the main trial, we conducted a pilot RCT, with the primary objective of establishing feasibility of patient recruitment and follow-up.-1 of epinephrine. Patient enrollment began December 2018.This was a two-arm randomized controlled feasibility trial conducted at St Joseph’s Hospital, Hamilton, Ontario, Canada. The study was registered at clinicaltrials.gov with the registration number NCT03176667, and ethics approval was obtained from the Hamilton Integrated Research Ethics Board on July 18, 2017 (#3012). Due to the unavailability of rupivacaine at the start of the study, as well as input regarding epinephrine from participating anesthesiologists, patients undergoing ESP were administered 30 ml of 0.125% bupivacaine rather than 30 ml of 0.5% ropivacaine with 5 μg ml-2, and contraindications to neuraxial analgesia techniques as per the American Society of Regional Anesthesia and Pain guidelines [Patients were screened for trial inclusion using the preoperative booking list. Adult patients (>18 years) having elective unilateral VATS procedures with at least one overnight stay were included. Patients were excluded if they had one or more of the following: patient refusal, body mass index >40 kg midelines –22; knowPatients were randomized to intervention (US-guided continuous ESP block) and control (surgeon-performed ICNB) groups with a 1:1 allocation ratio using a computerized randomization the day before surgery. Randomization was generated by a statistician not involved with the study, and the list was provided to the pharmacy. The group allocation was concealed and revealed to the anesthesiologist assigned to manage the surgical case the day before to ensure that a trained anesthesiologist was available to perform the pre-operative ESP procedure and catheter placement. Due to the nature of the study interventions, patients and research personnel were not blinded.-1) followed by insertion of a 19 gauge catheter under direct vision 5 cm beyond the needle tip.In the intervention group, patients had a pre-operatively performed US-guided ESP block with catheter placement in a designated block room equipped with monitoring and resuscitation facilities. Intravenous (i.v.) access was established and standard American Society of Anesthesiologists monitors were applied. Sedation and anxiolytics were used as considered appropriate. Patients were placed in a sitting position and the area was sterilized with disposable swabs of 2% chlorhexidine in 70% isopropyl alcohol and then draped in a sterile fashion. A high-frequency linear US transducer  was used in a longitudinal parasagittal orientation 3 cm lateral to the T5 spinous process. The trapezius, rhomboid major, and erector spinae muscles were identified superficial to the tip of the T5 transverse process. The patient’s skin was anesthetized with 2% lidocaine. A B-Braun Contiplex Echo 18 gauge Tuohy needle with the Contiplex Echo 20 gauge catheter  was inserted using an in-plane superior-to-inferior approach to place the tip into the fascial plane on the deep (anterior) aspect of the erector spinae muscle. The location of the needle tip was confirmed by visible fluid spread lifting the erector spinae muscle off the bony shadow of the transverse process. A maximum of 30 ml of 0.125% bupivacaine was injected in 5-ml aliquots through the needle (maximum of 3 mg kg-1) was used.In the control group, the thoracic surgeons performed ICNBs from T4 to T11 on the operated side of the chest, at the end of surgical procedure. The ICNBs were performed using 0.25% bupivacaine with epinephrine and a volume of 5 ml per block  for stabilization as routine practice. If the patient complained of incisional pain of intensity of >4/10 on the numerical rating scale (NRS), the nurse provided boluses of hydromorphone 0.2–0.4 mg i.v. every 7 min as needed to a maximum of 2 mg, after which PCA pumps were initiated. If the patient was allergic to hydromorphone, a morphine PCA was substituted. All patients were enrolled into the Acute Pain Service (APS) and were visited daily by a nurse practitioner and/or an anesthesiologist. In the ESP group, continuous ESP block was provided with a background infusion of 0.125% bupivacaine at 13 ml hThe PCA pump was programmed to administer hydromorphone in boluses of 0.2 to 0.4 mg i.v., with lockout time of 7 to 10 min to a maximum 6 mg over 4 h; or morphine in boluses of 1 to 2 mg i.v., with a lockout time of 7 to 10 min to a maximum of 30 mg over 4 h. Changes to PCA opioid doses was made by the APS team, as necessitated for each patient to target minimal or tolerable pain (NRS <4). In both groups, patients had multimodal analgesia, individualized based on the allergies, comorbidities, and patient tolerance: (1) acetaminophen 975 mg orally/per rectum (PO/PR) for 48 h followed by 650 mg PO/PR every 4 h as needed until discharge and (2) naproxen 500 mg PO twice daily × eight doses (administer with food) or ketorolac 10 mg i.v. four times daily × eight doses if patient is unable to ingest PO medications. PCA was discontinued upon removal of the chest tubes or when patient was ready for discharge, as is the current standard of practice at our hospital. ESP catheter infusion was discontinued 48 h after surgery or under any one or more of the following circumstances: chest drain removal, patient discharge, any signs of local infection or systemic infection, or any sign of mechanical dysfunction including leaking or inadvertent withdrawal of the catheter.To assess the feasibility of conducting a large RCT comparing the ESP versus ICNB, the following outcomes were evaluated: (1) recruitment rate (number of participants recruited per week and (2) proportion of in-hospital follow-up until discharge. The study was considered feasible if the recruitment rate was greater than two patients per week and with complete (100%) in-hospital follow-up until discharge for the clinical outcomes.Differences in total opioid consumption over the first 24 h and 48 h. This was collected using electronic medical records. Opioids will be considered as total hydromorphone equivalents for analysis.Difference in pain scores “at rest” and “at movement” at the following time points: 1 h after entry at PACU, average pain score during the postoperative nights as collected during the morning APS rounds, and pain scores on each morning until discharge. Pain scores at movement were collected by asking patients to cough. Both pain scores were recorded using the patient-reported NRS, an 11-point scale where 0 is no pain and 10 is the worst pain imaginable . The dermatome distribution of the blockade on the patient’s anterior chest, mid-axillary line, mid-clavicular line, and mid-scapular line was assessed using a blunt needle to test for loss of sensation to pinprick. Sensory testing was performed and recorded as shown in Additional file Patient satisfaction with postoperative analgesia on the day of discharge. This was performed using a five-point Likert scale  guidelines for pilot studies . BaselinPatients were noted using a study ID to keep their information anonymous. The patient’s study ID and corresponding hospital medical record number were recorded in an Excel file in a password-encrypted USB that was securely stored in a locked cabinet. Data collection was done using paper forms and transferred to REDCap for secure storage and analysis. Data were collected by research assistants and the APS nurse practitioner (KD). The data collection forms were also kept in the locked cabinet.n=12) and control (n=12) groups , the number of patients recruited per week was >2 and we successfully followed all patients for clinical outcomes during their hospital stay.Clinical outcomes are reported in Table Two individuals (both in the intervention group) experienced at least one adverse event: one event was catheter migration at 24 h, and the second was an accidental catheter disconnection. Nine individuals needed treatment for nausea and vomiting within 24 h, in which three also required treatment in PACU. Among the five categories of patient satisfaction, there were no patients in either group that recorded dissatisfied or completely dissatisfied. In the control group, 58% were very satisfied, 25% were satisfied, and 17% were neutral. In the treatment group, 67% were very satisfied, 25% were satisfied, and 8% were neutral.The presence of sensory blockade on the operative side of the thorax in each group is shown according to dermatome in Fig. In this pilot trial, we were able to demonstrate the feasibility of conducting an RCT comparing continuous ESP analgesia versus ICNB in patients undergoing VATS. We were able to recruit more than two patients per week and follow all patients during their hospital stay. We also observed that the study intervention had a positive influence on the opioid consumption and postoperative pain scores. As a feasibility trial, it was not powered to assess for clinical outcomes. There were no serious adverse clinical events that posed a threat to patient safety or resulted in any known morbidity or mortality. Based on our pilot study, and using the same comparators, we would need a total of 63 patients/group for a difference of 1.63 mg between the groups. We provide estimates of sample size with other variations to mean difference and SDs of the treatment and comparator group in our supplemental table . Possible solutions include reminding physicians that all procedures have a risk of being converted to open thoracotomy, and routinely placed thoracic epidurals are not currently the standard of practice at our institution. Furthermore, thoracic epidurals may also be placed postoperatively if indicated. Tightening the selection criteria so that only suitable patients are randomized can be considered. However, tightening the selection criteria has important implications to study recruitment. There have been suggestions that ITT analysis may not always be appropriate in circumstances such as the above where inappropriate patients were included, and it might be better to go with the recommendations of an adjudication committee for each case inclusion. Finally, another point that should be mentioned is the option to exclude any case that gets converted to open thoracotomy.It has been observed in the literature that the ESP block has variable dermatomal spread. We note that in comparison to ICNB from T4-T8 placed by the surgeon, an ESP placed at T5 covered more dermatomes in our study. Other reports have shown that ESP has the potential for a wider spread. It is probably likely that more obvious blockade at the mid scapular line is explained by predominant blockade of posterior branches. Using computed tomography with contrast, Forero et al.  demonstrWe believe our primary clinical outcome of reduction in opioid usage is more appropriate than pain scores. Since opioid usage was based on PCA needs, it still reflects pain perceived by a patient indirectly if one assumes that opioid needs are based on individual pain tolerance. Opioid usage was observed to be lower in the intervention arm at all points. The decrease in opioid consumption may also explain the decrease in anti-emetic drug administration seen in the ESP and PCA arm. Although we did not intend to limit the inclusion based on the ASA score, all of our patients belonged to either ASA 3 or 4 risk category. We recognize that this might potentially affect the external validity of the study results and hence we plan to ensure inclusion of a wider range of ASA score patients for our main trial.There are a few important limitations of our study. This pilot RCT was not blinded; hence, it carries a higher potential for observation bias. It should also be emphasized that this is a pilot study and it was not designed or powered to provide clinical inference. As mentioned above, there were five patients that had an epidural, indicating non-compliance with study protocol. In view of this, we could consider patient selection criteria as a limitation that needs to be improved in our main trial.In conclusion, we conducted a pilot, non-blinded RCT comparing continuous ESP blockade with surgeon-performed ICNB in patients having VATS resections. Our trial demonstrated that it would be feasible with modifications to conduct a fully powered RCT. We further demonstrate that this type of trial is safe and that there are indications of lower opioid consumption and superior analgesia in the ESP arm. However, more research is required to determine whether this effect is clinically meaningful and statistically significant.Additional file 1: Appendix 1 A supplementary document that contains definitions and scales of each outcome, and diagrams of sensory testing.Additional file 2: Appendix 2 Appendix_Calculation of group sample size. A supplementary document that presents the data for sample size estimates for the main trial .


P < 0.05 and <0.001, respectively). They also scored higher than healthy individuals with disability living with pain (P < 0.001), anxiety (P < 0.001), depression (P < 0.001), and catastrophizing (P < 0.001). The results for anxiety, depression, and catastrophizing have been published earlier, and the reused data in this study are compared with RMS and pain thresholds. The conditional logistic regression model identified catastrophizing  as a significant predictor of TMD patients. The results support this hypothesis and indicate that TMD patients have lower pain thresholds and more disability when living with pain compared to healthy individuals, where the strongest prediction for TMD was catastrophizing. Awareness of psychometric disabilities in TMD patients is of importance when considering the choice of treatment.Temporomandibular disorders (TMDs) are characterized by moderate to severe pain in the masticatory muscles and/or the temporomandibular joint (TMJ). The present study is a part of a multidisciplinary project, initiated by the Norwegian Ministry of Health. The main purpose of this study is to compare a cohort of TMD patients to healthy individuals regarding experimental pain, the degree of disability caused by living with pain and psychometric variables, and to investigate which of these variables is the best predictor for TMD patients. We hypothesised that TMD patients have more disability when living with pain and lower pain thresholds than healthy controls, and those psychometric variables are stronger predictors than pain thresholds provoked by experimental pain. Sixty TMD patients were matched by sex and age to sixty healthy individuals without TMD symptoms or other musculoskeletal symptoms in the head and neck region. All subjects completed a questionnaire that included psychometric characteristics, that is, a one- and two-item version of the Pain Catastrophizing Scale, the Hospital Anxiety and Depression Scale (HADS), and the Roland Morris Scale (RMS), which measures disability when living with pain. They also underwent a clinical examination including the measurement of pain thresholds with electrical and pressure stimuli. The TMD patients had lower pain thresholds for experimental electrical and pressure stimuli compared with the controls ( The conditions that cause pain and/or dysfunction of the temporomandibular joint (TMJ) and muscles that regulate jaw movements are collectively known as temporomandibular disorder (TMD). In a TMD population, the disorder is assumed to be at least three times as common in women as in men , while iUnderstanding the source of pain is important for making a diagnosis and for choosing the appropriate treatment, which may be conservative, psychological, and/or surgical . The patSensitivity of tissues can be assessed by measuring pressure pain thresholds (PPTs) with algometry. It is a valid and reliable method used to measure the PPT in craniocervical muscles . In tensQuestionnaires are often used to assess self-reported symptoms such as pain (subjective pain) and psychometric status. Psychosocial factors are suggested as linked to pain-related disability and duration of pain . Pain isPatients with TMD, who will undergo TMJ surgery, may have a high risk of ultimately experiencing postoperative pain. Among the patients included in this study, seven patients underwent TMJ surgery, and only one of them was pain-free at the follow-up . AccordiThe main purpose of this study is to compare a cohort of TMD patients to healthy controls regarding experimental pain, disability when living with pain and psychometric variables, and to investigate which of these variables was the best predictor for TMD patients. We hypothesised that TMD patients have more disability when living with pain and lower pain thresholds than healthy subjects. We further hypothesised that psychometric variables are stronger predictors for TMD than pain thresholds provoked by experimental pain.Under direction from the Norwegian Directorate of Health, the Oral and Maxillofacial Surgery Department and the Clinic for Pain Treatment and Palliation at Haukeland University Hospital in Bergen, Norway, developed a multidisciplinary investigation programme for patients with severe TMD .n = 22), arthralgia (n = 1), disc derangement (n = 2), and combinations thereof (n = 35).The participants in this study consisted of sixty consecutively referred patients with severe TMD and sixty age- and gender-matched healthy controls. The study groups to be characterized were set at sixty patients by the directive from the health directorate. The sixty TMD patients included in the study were referred from their general medical practitioner during 2013 to 2015 for severe TMD with long-lasting pain. The consecutively included patients were assessed for TMD with a modified DC/TMD, without using the mandatory command, which has previously been shown not to impair diagnostic reliability . InclusiSixty healthy age- and sex-matched subjects without symptoms of TMD were recruited to serve as a control group. The inclusion criteria for the controls were that they were age- and gender-matched to each of the participants in the patient group. The exclusion criteria included TMD symptoms and pain symptoms in the head and neck. The participants in the control group were a convenience sample selected from the Department of Clinical Dentistry at the University in Bergen. All included patients and controls signed a consent form for participating in the study before the investigations. Two different examiners assessed the groups, one for the control group and one for the TMD group. Both examiners underwent specific correlation/synchronisation training before the clinical assessments.Recorded details for all patients were stored in their hospital medical records (DIPS). Data were collected in an anonymised form. The project was approved by the Regional Committee for Medical and Health Professional Research Ethics (2015/930/REK sør-øst).X .All study participants completed a questionnaire, the Roland Morris Scale (RMS), and an additional questionnaire assessing general disability when living with pain . RMS conThe psychometric data from the already published study  included2 and a slope of 30 kPa/s. The algometer was equipped with a warning signal to prevent overload and a green light to indicate correct pressure. The assessment was performed on the TMJ and the most prominent part of the masseter muscle, representing local pain. The patients were asked to occlude their teeth and then relax their jaw to enable the examiner to find the most prominent part of the masseter muscle prior to the algometer measurement. Algometry was also performed on the tip of the pointing finger, representing global pain. The examiner placed the probe on the area being tested, and as soon as the subject perceived pain (PPT), they pushed a button to register the exact value of the weight used. A computer registered and displayed the pressure value. All tests were performed three times bilaterally, and the mean of the measured values was recorded.To assess pain sensitivity and hyperalgesia, pressure and electrical stimuli were used. An algometer assessed pressure pain thresholds (PPTs) on the TMJ, the masseter muscle, and the finger , 40. Theμs to a maximum of 396 μs [The electrical stimuli pain test was performed on the fingers, as for the algometer, representing global pain. We included two measurements, specifically electrical sensibility thresholds (ESTs) and electrical pain thresholds (EPTs), using the PainMatcher . The PainMatcher is a microprocessor, which delivers a constant current of 15 mA with monophasic pulses of 10 Hz to the electrodes. Finger press on the electrode ensures an electrically closed circuit and increased intensity of the pulse, which is sustained for 4 Descriptive data were analysed, and the Wilcoxon signed-rank test was used for bivariate analyses between TMD cases and controls. The results from HADS and catastrophizing have been published earlier as single independent variables, but the present results are novel with respect to the adjusted conditional logistic regression . MultivaP < 0.05 was considered a statistically significant difference.The data analysis was performed in IBM SPSS Statistics for Macintosh, version 25.0 , and Stata Statistical Software: release 14, College Station, TX: StataCorp LLC. n = 45), PainMatcher (n = 58), Roland Morris Scale (n = 59), HADS (n = 59), and catastrophizing (n = 57).The TMD group had a mean age of 45 years (SD 12.6) and included 51 women and 9 men. The mean age of the age- and sex-matched control group was 46 years (SD 12.6), and it consisted of 51 women and 9 men. Because some patients dropped out or moved during the study, we ultimately had a smaller number of participants and matched pairs : pressurP = 0.001 for the finger and masseter muscle and P = 0.003 for the TMJ).The results show that the TMD patients had a lower PPT than the controls (P = 0.014). However, the EST measurements did not differ significantly between the TMD group and the controls . Furthermore, the TMD patients had more anxiety , depression  and catastrophizing  compared to the controls. Descriptive data are shown in The results from the RMS showed increased disability for TMD patients compared to controls (Multivariate conditional logistic regression using an unadjusted Wald test and an adjusted model using stepwise forward procedure included five independent variables: PPT in the masseter muscle and finger as well as scores from catastrophizing, depression, and anxiety scales. Unadjusted and adjusted models are shown in Decreased PPT and higher scorings for psychological factors in TMD patients compared to healthy controls are well known in the literature , 41, 42,In addition to the interesting findings in the multivariable analysis, the bivariate analyses showed significant differences between the TMD group and controls regarding not only catastrophizing but also anxiety, depression, and disability when living with pain and experimental sensitivity/pain thresholds. In this regard, it has previously been suggested that psychological factors are associated with the development of painful TMD , and enhPreviously published data, in the same cohort of patients as presented in this study, show higher scoring on HADS and CSQ compared to healthy individuals, as well as higher levels of cortisol in the saliva, showing an upregulated HPA axis indicating higher levels of stress . These fAn association between psychological distress, a lower threshold in experimentally induced pain, and painful TMD has been found  in analoNot unexpectedly, the TMD patients in the present study had more tenderness measured by the PPT, and previous studies have reported greater sensitivity to experimental pain because of alterations in endocrine, sensory, and psychological processes, as well as central sensitisation , 50. In The surgically treated patients in this cohort, published in 2017, had high scoring of catastrophizing and postoperative pain , possiblOur study had several limitations. First, most of the participants in the control group were selected from the Department of Clinical Dentistry at the University of Bergen and were acquainted with the examiner who evaluated them. The acquaintance between the subjects and the examiner may have affected measurements and given rise to bias. A second limitation was that the exclusion criteria did not include other chronic pain disorders and neurological disorders that might have affected the pain perception or medications such as paracetamol, NSAID's, opioids, and antidepressants that might have affected the pain threshold as well as anxiety and depressive symptoms. Since the patients were recruited consecutively by referrals to the National TMD project at Haukeland University Hospital, other chronic pain disorders, neurological disorders, or medications used by the patients were not considered during the recruitment process but were scrutinized during the thorough multidisciplinary investigation by six different specialists. If there was a need of additional specialist investigation, the patients were further referred before the summation of the investigation was presented for the patient. A third major limitation was that there were two different examiners, one examiner for the control group and one for the TMD patient group. The examiners were trained prior to the examination of participants to minimise variabilities and achieve acceptable interexaminer reliability. Nevertheless, there may still have been interexaminer differences that could have affected the results. A fourth limitation was the drop-out of participants in the algometer test due to either no assessments or healthy individuals not wanting to be exposed to the algometer. A final limitation is that the RMS is originally a questionnaire for low-back pain patients, but since it shows disability when living with pain, and because the questions can apply to any type of body pain, it should not affect the validity. An additional shortcoming is that part of the results was published earlier, the psychometric data, but at this time using single independent variables . This caTo conclude, the TMD patients have lower pain thresholds and a higher disability of pain compared to healthy individuals. The strongest prediction for TMD was catastrophizing. These results are important to be considered when managing TMD patients. Awareness of psychometric disabilities in TMD patients is of importance and should be addressed in the treatment plan.


Effective postoperative pain control remains a challenge for patients undergoing cardiac surgery. Novel regional blocks may improve pain management for such patients and can shorten their length of stay in the hospital.To compare postoperative pain intensity in patients undergoing cardiac surgery with either erector spinae plane (ESP) block or combined ESP and pectoralis nerve (PECS) blocks.This was a prospective, randomized, controlled, double-blinded study done in a tertiary hospital. Thirty patients undergoing mitral/tricuspid valve repair via mini-thoracotomy were included. Patients were randomly allocated to one of two groups: ESP or PECS + ESP group (1:1 randomization). Patients in both groups received a single-shot, ultrasound-guided ESP block. Participants in PECS + ESP group received additional PECS blocks. Each patient had to be extubated within 2 h from the end of the surgery. Pain was treated via a patient-controlled analgesia (PCA) pump. The primary outcome was the total oxycodone consumption via PCA during the first postoperative day. The secondary outcomes included pain intensity measured on the visual analog scale (VAS), patient satisfaction, Prince Henry Hospital Pain Score (PHHPS), and spirometry.p = 0.0004). Moreover, pain intensity was significantly lower in the PECS + ESP group at each of the five measurements during the first postoperative day. Patients in the PECS + ESP group were more satisfied with pain management. No difference was noticed between both groups in PHHPS and spirometry.Patients in the PECS + ESP group used significantly less oxycodone than those in the ESP group: median 12 [interquartile range (IQR): 6–16] mg vs. 20 [IQR: 18–29] mg  on the ClinicalTrials.gov identifier:  Postoperative pain remains a primary challenge in patients undergoing thoracotomy . Poorly Among many regional anesthesia techniques for patients undergoing cardiac surgery, thoracic epidural analgesia (TEA) is associated with reduced incidences of cardiovascular events and infections, lower cost, and shortened length of hospital stay –7. ThoraOur previous, prospective, cohort study demonstrated that the ESP block combined with low-dose intravenous oxycodone was an effective analgesic technique for patients who had undergone mitral or/and tricuspid valve repair via right mini-thoracotomy . In thatThe objective of this study was to compare postoperative pain intensity in patients undergoing cardiac surgery with either ESP block or combined ESP and PECS blocks by assessing oxycodone consumption during the first operative day (primary objective), as well as by comparing patients’ subjective pain intensity by using the visual-analogue scale .This was a randomized, controlled, double-blind trial conducted in a tertiary cardiac surgery department. Before patient recruitment, the study protocol was approved by the Bioethics Committee of the Medical University of Lublin, Lublin, Poland (permit number KE-0254/127/2018), and registered at ClinicalTrials.gov (NCT03592485). Written informed consent was obtained from each patient, and the study was conducted in accordance with the tenets of the Declaration of Helsinki for medical research involving human subjects.The inclusion criteria were as follows: patients who (1) required mitral and/or tricuspid valve repair; (2) underwent surgery via right mini-thoracotomy approach; (3) were more than 18 years of age; and (4) were less than 80 years of age. The exclusion criteria included: (1) coagulopathy, defined as known bleeding disorder; (2) allergy to local anaesthetics; (3) depression, which could significantly influence pain perception; (4) epilepsy; (5) antidepressant or epileptic drug treatment; (6) chronic usage of analgesic drugs; (7) addiction to alcohol or recreational drugs. Data from patients who required endotracheal intubation and respiratory support for > 2 h from the end of surgery were also excluded from the analysis.Patients were randomly allocated to one of two groups  via computer-generated randomization conducted by a team member who was not involved in the surgery or patient assessment. The same team member prepared opaque envelopes in which the intervention type was concealed. These envelopes were opened a few minutes before attempting the regional block. Patients were randomly assigned to the ESP or PECS + ESP group.In the ESP group, ultrasound-guided ESP block at the fourth thoracic level was performed before the surgery and induction of general anesthesia with Ropivacaine  as described in our previous study Fig.  13]. Th. Th13]. − 1 min− 1) , and rocuronium (0.6 mg kg− 1)  were used for the induction of general anesthesia. Maintenance was provided with 0.5 minimum alveolar concentration of sevoflurane , remifentanil, and incremental doses of rocuronium. Remifentanil was continued to achieve a target plasma concentration of 4–8 ng ml− 1 and adjusted to the patient’s heart rate and blood pressure. During the procedure, the right lung was deflated, and the left lung was ventilated with a mixture of air and O2. Residual neuromuscular block was reversed with sugammadex  at the end of surgery.Etomidate , remifentanil (0.5–1.0 mcg kg− 1) was administered 30 min prior to the surgery end. Patients were transferred to the intensive care unit where target plasma concentration of remifentanil was reduced to 0.5–2 ng ml− 1. Ventilation was continued for 60–120 min and patients were observed for occurrence of excessive postoperative bleeding and hemodynamic instability. If no problems were recognized, remifentanil infusion was discontinued, and the patient’s trachea was extubated. Postoperative pain treatment was continued with a patient-controlled analgesia (PCA) pump which supplied oxycodone  during the first 24 postoperative hours.An intravenous bolus of oxycodone  to 100 mm (maximum pain) on the VAS. If pain intensity exceeding 40 mm on the VAS, up to two extra doses of oxycodone  could be administered intravenously by the nurse. Patients were transferred to the surgery ward by the end of the first postoperative day if no complications were present.2 line, and atrial retractor.For mini-invasive mitral and/or tricuspid valve surgery, the patient was placed in the supine position with elevated right hemithorax, and the right upper arm was flexed anteriorly with the forearm in front of the face. Transoesophageal echocardiographic (TEE) monitoring was performed for all patients to confirm the appropriate establishment of cardiopulmonary bypass (CPB), valvular repair, and heart de-airing. The chest was prepared and draped, and the right lung was deflated; a thoracotomy (5 to 7 cm in length) was then performed in the fourth intercostal space in the submammary fold, from the anterior to the medial axillary line. Small accessory incisions were made for the endoscope, aortic clamp, venting tube, COCPB was established via femoral vessel cannulation; if tricuspid valve surgery was also planned, the right jugular vein was cannulated percutaneously. Patients were cooled to 34 °C, the pericardium was opened, and cardioplegia was administered to the aortic root after cross-clamping of the aorta. The mitral and tricuspid valve (if required) was repaired using valvular rings and artificial Gore-Tex chordae, if required. After completion of the repair, patients were rewarmed and weaned from CPB and TEE examination was performed to assure the quality of the repair. The surgery site and the postoperative drain position are presented in Fig. The total consumption of oxycodone during the first 24 postoperative hours. This outcome was presented also as morphine equivalence . SecondThe other measured variables were pain intensity ), patient satisfaction with pain management, and assessment of pulmonary function. PHHPS was used to assess the effect of analgesia provided by regional block and intravenously administered painkillers on deep breathing and coughing. Patients could describe their pain severity using a five-grade scoring system from 0 to 4, in which 0 indicated ‘no pain on coughing’, 1 indicated ‘pain on coughing, but not on deep breathing’, 2 indicated ‘pain on deep breathing, but not at rest’, 3 indicated ‘slight pain at rest’, and indicated 4 ‘severe pain at rest’. PHHPS was assessed at the time of admission, as well as at 1 day and 4 days after surgery. Patient satisfaction with pain management was assessed at the time of discharge from the hospital. Patients could describe their satisfaction with pain management as perfect (5), good (4), moderate (3), poor (2), or very poor (1).Pulmonary function tests were performed by a physician who was not involved in anesthesia or surgery. The physician assessed each study participant by using the SP10W spirometer  before surgery, as well as 1 day and 4 days after surgery.Data are presented as medians [interquartile ranges (IQRs)]. The Mann–Whitney U test was used for nonparametric data. If normal distribution was confirmed, Student’s t-test was used. Parametric data are presented as means with 95% confidence intervals (95% CIs). All analyses were performed in Statistica 13.1 software .The sample size was calculated based on our preliminary results. The mean consumption of oxycodone was 22 mg per day in patients who had the ESP block alone, and 10 mg in patients who had ESP, PECS I, and PECS II blocks. The calculated sample size was 12 individuals per group . Thus, we decided to recruit 15 patients in each group.This study was conducted from July 2018 to August 2018. Overall, 30 patients were analyzed, 15 per group  .Patients in the PECS + ESP group were more satisfied with pain management, compared with patients in the ESP group: 4 [IQR: 4–4] vs. 3 [IQR: 1–4]  to compare ESP block with ESP plus PECS I and II blocks in patients undergoing cardiac surgery comprising valve surgery via right mini-thoracotomy. The results of the current study showed that the inclusion of an additional regional anesthesia technique (PECS I + PECS II blocks) with the ESP block significantly reduced oxycodone consumption and alleviated postoperative pain severity measured on the VAS Figs.  and 7. MESP block provides satisfactory analgesia in patients after mini-thoracotomy procedures. In the current study, of 15 patients in the ESP group, 12 reported that their pain management was perfect or good; only a single participant reported pain management as poor. However, a continuing obstacle to the improvement of postoperative analgesia remains chest pain associated primarily with chest drains. We considered two regional techniques for additional analgesia: PECS and the serratus anterior block. Both methods have been described in patients who have undergone mini-thoracotomy procedures . We chosBoth ESP and PECS blocks are relatively new analgesic techniques. ESP is an interfascial plane block developed by Ferrero et al. in 2016 . The depAlthough PECS and ESP blocks appear to cover similar areas, their clinical efficacy is still under investigation. The results presented in cadaveric studies showed some unpredictably of ESP block , 20. In Other potential techniques that could be used in patients after mitral and/or tricuspid valve repair via mini-thoracotomy include PVB and TEA. PVB seems superior to TEA for this type of surgery because its analgesic area is limited to the operated side , 21. DatThe other regional anesthesia method which could be effective after mini-thoracotomy procedures are the intercostal blockade. This procedure could be performed at the end of surgery by the surgeon under direct vision. However, the intercostal blockade provides the highest plasma ropivacaine concentration of all anesthetic techniques, with the peak plasma concentration at 21 ± 9 min from injection and sensory blockade (measured by pinprick) lasting of 6.0 ± 2.5 h only .Our study had some limitations. Although statistical significance was demonstrated for primary and secondary outcomes, the sample size was relatively small. Thus, the lack of complications could be the result of a low number of participants. The current study showed that the addition of PECS block to ESP block improved postoperative pain control and increased patient satisfaction. However, PECS blocks may be sufficient as a single regional analgesia technique for pain management in patients undergoing valve repair via right mini-thoracotomy. Moreover, PECS blocks could be superior to ESP block for this type of surgery. The current study did not exclude this alternative. Neither ESP nor PECS blocks effectiveness was confirmed in the operating theatre with the loss of sensation technique before the surgery.In conclusion, the current study demonstrated that the addition of PECS blocks to ESP block led to reduced consumption of oxycodone via PCA, reduced pain intensity on VAS, and increased patient satisfaction with pain management in patients undergoing mitral/tricuspid valve repair via mini-thoracotomy. However, there were no differences between the study groups regarding pulmonary function tests.


Adenosine has an analgesic and anti-inflammatory role and its injections are used for perioperative pain management. We aimed to study efficacy of intrathecal injection of adenosine for post-operative radicular pain after lumbar discectomy. Forty patients with unilevel lumbar discectomy who had radicular lower limb pain were treated by 1000 micrograms of intrathecal injection of adenosine in this single-arm prospective open-label trial between November 2015 to October 2016. Radicular pain severity using visual analogue scale (VAS) and pain killer consumption per day were assessed during a 3 months follow up period.Radicular pain severity was significantly reduced in 3 month follow-up period in comparison to the baseline . Further, painkiller medication consumption rate in average during 3 month follow-up period after injection was significantly lower in comparison to baseline . This study suggests that intrathecal injection of 1000 micrograms adenosine is a safe and effective method for post-operative neuropathic pain management after uni-level disk surgeries.Trial registration IRCT201608171772N20, Retrospectively registered on 2016-08-28. Neuropathic pain is a multifaceted pain feature, showing an inconvenient procedure of regular sensory signaling changed so that pain is sensed in the nonexistence of a nociceptive motivation, or replies to ordinarily deleterious stimuli are heightened. The management of persistent postoperative neuropathic pain (PPNP) has preoccupied a multi-discipline approach comprising pharmacological, interventional, and surgical proceeding , 2.Adenosine which has four subtypes of A1, A2a, A2b and A3, is an endogenous protein nucleotide. It modulates physiologic processes that play role in nociception, anti-nociception and central and peripheral analgesia. Its plasma level increases during cell injury, inflammation and ischemic events in order to prevent cell damage from the ischemic-hypoxic reactions , 5.Intravenous injection of adenosine in the surgical procedures has reduced analgesic requirement by 20–50% in studies. It also limits systolic blood pressure fluctuations caused by painful stimuli during a surgery. Studies also have reported a 18–26% reduction of postoperative opioid consumption in the breast and uterine surgical procedures . IntrathSince studies regarding postoperative analgesic effects of adenosine are not sufficient to overcome controversy in the literature, in this study, we aimed to determine the efficacy of intrathecal adenosine injection for relief of neuropathic pain after lumbar uni-level discectom.This is a single-arm prospective open-label trial investigating intrathecal adenosine injection for relief of the neuropathic pain after lumbar uni-level discectomy in 40 patients with history of uni-level lumbar discectomy in the last 3–6 months and chief complaint of postoperative radicular neuropathic pain which was conducted at the Emam Reza Educational Hospital, Tabriz, Iran. Recruitment started in November 2015 and lasted until October 2016. Inclusion criteria were age between 20 and 70 years old; recent history of lumbar uni-level discectomy and history of postoperative radicular pain. Those patients with a history of asthma; liver and renal disease; endocrine and coronary disease; sensitivity to xanthine like dipyridamole and aminophylline; maldigestion of methyl-xanthine; addiction; cardiac arrhythmia and psychogenic disorders were excluded. Recruited patients were seen at 3 visits: initial visit (visit 1), 1-month visit (visit 2), and 3-month visit (visit 3), and their data were collected in a dedicated case report form. This study adhered to the CONSORT guidelines.No Pain and “10” was equal to Most Severe Pain. Finally amount of painkillers consumption per day (number of tablets per day) was recorded.Demographic characteristics of patients and the level of surgery were recorded at the beginning. Before study intervention, radicular pain severity using visual analogue scale (VAS) was assessed. It is a 10 number numerical scale in which “1” indicates In first 48 h after injection with 2 h interval and at the end of 1st, 2nd, 3rd, 4th, 8th and 12th weeks post injection, severity of radicular pain and amount of painkillers per day were recorded. At 1st, 2nd and 3rd month post injection, headache severity and sleep quality were also evaluated. All the measurements and side effects after discharge from hospital were recorded by telephone calls.Under sterile condition and cardiac monitoring, a secure intravenous line for hydration by normal saline was established while patient was seated relaxes. Interlaminar space between 4th (L4) and 5th (L5) lumbar vertebras which is in same level with posterior superior iliac spine protuberances was marked. A 25 gauge spinal needle was used to fenestrate L4–L5 interlaminar space in the midline. Needle was pushed slowly to the intrathecal space. As soon as cerebrospinal fluid was observed in the syringe hub, 1000 micrograms of adenosine were injected to the intrathecal space. The entrance site was bandaged and patient was transferred to recovery unit. If there was no reports of sensorimotor or autonomic dysfunction, patient was transmitted to pain unit in order to be observed for 48 h.Data were analyzed by SPSS . Statistical analyses comprised a report of patient characteristics descriptive analyses. Repeated measures of ANOVA and Chi square tests were also recruited. In this study, p-values less than 0.05 were considered as significant.Forty patients with history of radicular neuropathic pain after lumbar unilevel surgery were included in this trial from November 2015 to October 2016. Mean age of participants was 50.55 ± 10.53 years with a male: female ratio of 21:19. The baseline radicular pain and pain killer consumption were 6.62 ± 0.70 and 4.62 ± 0.70, respectively. Eight patients had unilevel lumbar discectomy plus vertebral fusion. It means that based on surgeon decision they had a more complex condition and needed more comprehensive management. Six patients (15 percent) had done heavy work after the block.Table Painkiller consumption was significantly reduced in first week follow-up period in comparison to the baseline . Although painkiller consumption has an ascending pattern from week 1 to month 3 post injection follow up  but it was still lower than baseline measurements   also had higher level of mean radicular pain in comparison to other patients Fig. . Both ofFortunately during follow-up period of this clinical trial there were no reports of significant complications due to intrathecal adenosine injection. Intrathecal adenosine didn’t affect blood pressure, heart rate and motor or sensory testing. Additionally, there was no report of postspinal headache or superficial wound infections. However, 10 of participants had transient pain localized to the lumbar region at the time of injection for less than 30 min.In this study, forty patients with history of unilateral or bilateral radicular pain after lumbar disc unilevel surgery were treated by 1000 micrograms of adenosine intrathecal injection. In the 3 month period of follow up, pain severity and painkiller consumption rate per day were significantly reduced and fortunately no serious complications were reported. James et al.  had simiN-methyl-d-aspartate transmission [Adenosine as an endogenous porin nucleotide has four subtypes of A1, A2a, a2b and A3. It is elevated in blood plasma during cell inflammatory injury in order to prevent hypoxic-ischemic cell damage. Adenosine receptors mechanism of action is based on G-protein complex. A1 receptor links to G i/o protein and reduces cyclic adenosine monophosphate (cAMP) level. A2 works through Gs protein and promotes adenylate cyclase action. A1 also can bind to Go and inhibits calcium transduction. A2b and A3 bind to Gq and stimulate phospholipase action. So A2a subtype is responsible for anti-inflammatory effects of adenosine. In summary, A1 receptor has analgesic and anti-nociceptive effects while A2a and A3 promote anti-inflammatory mechanisms [smission , 10.Adenosine and Remifentanil analgesic effect for post-operative pain reduction were evaluated in Fukunga et al. study. Pain severity score was 60% lower in adenosine group in comparison to the remifentanil one. Also opioid consumption rate of adenosine treated patients were significantly lower in comparison to the remifentanil treated patients. However, they noted higher blood levels of carbon-dioxide, systolic blood pressure disturbance and higher heart rates in adenosine treated group .Also there were no evidence of complications in current study but clinical trials in literature have reports of headache, back and lower limbs pain , 11. TheSurprisingly, Yamaoka et al. and Sharma et al. who had tried intrathecal injections of adenosine for post-operative pain management could not find any significant analgesic effect , 13. YamThis study suggests that intrathecal injection of adenosine is a safe and effective method for post-operative pain management after uni-level disk surgeries.There are limitations for this study. Firstly, this study did not have a control group. The most important reason for this limitation was lack of eligible cases based on inclusion criteria, but it would be much better if analgesic effects of adenosine have been compared with a control therapy. Secondly, measuring pain killer consumption per day based on number of pills reported by the patient through telephone calls is not completely accurate but since patients were not able to count the milligram of drugs they had consumed, authors had forced to simplify this measurement, for patients of study. Finally an important confounding factor is daily job which could directly impact pain sensation severity reported by the patient. Although authors of current study have recorded heavy labor duties in follow up period but it would be better if results have been classified based on daily job heaviness.


Sufficient analgesia is an obligation, but oligoanalgesia (NRS> 3) is frequently observed prehospitally. Potent analgesics may cause severe adverse events. Thus, analgesia in the helicopter emergency medical service (HEMS) setting is challenging. Adequacy, efficacy and administration safety of potent analgesics pertaining to injured patients in HEMS were analysed.Observational study evaluating data from 14 year-round physician-staffed helicopter bases in Austria in a 12-year timeframe.n=20,051; 76.9%), esketamine , metamizole  and NSAIDs . Monotherapy with opioids or esketamine was the most common regimen , while opioids together with esketamine  or metamizole  were the most common combinations. Females received opioids less frequently than did males . Pain relief was often sufficient (> 95%), but females more often had moderate to severe pain on arrival in hospital . Administration of potent analgesics was safe, as indicated by MEES, SpO2 and respiratory rates. On 10% of all missions, clinical patient assessment was deemed sufficient by HEMS physicians and monitoring was spared.Overall, 47,985 (34.3%) patients received analgesics, 26,059 of whom were adult patients, injured and not mechanically ventilated on site. Main drugs administered were opioids (Opioids and esketamine alone or in combination were the analgesics of choice in physician-staffed HEMS in Austria. Analgesia was often sufficient, but females more than males suffered from oligoanalgesia on hospital arrival. Administration safety was high, justifying liberal use of potent analgesics in physician-staffed HEMS.The online version contains supplementary material available at 10.1186/s13049-021-00839-9. Providing sufficient analgesia in the challenging prehospital emergency setting is an ethical obligation and of clinical relevance . Potent This retrospective study was approved by the Ethics Committee of the Medical University of Innsbruck (AN2015–0068 347/4.13393/5.20) and was registered with Clinical Trials (NCT03760302). In Austria the ÖAMTC  runs 17 year-round helicopter bases. The HEMS team consists of a pilot, a physician (advanced life support (ALS)-certified with several years of clinical practice, most commonly in anaesthesiology and intensive care medicine) and an emergency medical technician with basic life support and mountain rescue skills. After completing a rescue mission, emergency physicians transfer data from their handwritten medical report to a standardized digital database intended for medical documentation and billing purposes. Analysis of this database was performed for a 12-year timeframe from 01/01/2006 to 31/12/2017. Two helicopter bases were excluded for reasons of data protection restrictions, and one helicopter program was launched in May 2020. Consequently, this analysis drew on nationwide data from 14 year-round helicopter bases. The flow chart for the study is outlined in mountain accidents were analysed separately.Data obtained included date, time, helicopter base, type of accident or emergency, sex, age in groups, injury pattern, severity and region of injuries, medication and interventions performed by the emergency team. With regard to emergency classifications, other accidents included work, road traffic and home and leisure accidents. Pain was scaled as no pain, mild pain  ≤3), and moderate to severe pain (NRS > 3). With regard to analgesics, opioids mainly included fentanyl, piritramide, morphine and also seldomly tramadol, nalbuphine, sufentanil and remifentanil. NSAIDs administered included aspirin, mefenamic acid, diclofenac and ketoprofen.The largest group of 2)) [Age documentation was performed in 5- to 10-year scales. With regard to expected weight and required dosages, patients at least 15 years of age were enrolled in the study. When medication dosage was missing or not given accurately, only the type of medication was analysed. Severity and progress of the patient’s condition were evaluated using NACA  scoring and the voluntarily documented MEES ) , 10.Data are presented as median and interquartile range or count and percentage, as appropriate. The Chi-square test was performed to detect group differences in frequencies, and the Mann-Whitney U test for group differences in continuous data. Data were stored with Excel 2019  and processed with RStudio version 1.2.5001 .A total of 176,056 HEMS operations were analysed. Primary missions made up 139,831. Of these, analgesics were administered in 47,985 (34.3%) cases. Exclusion of patients under 15 years of age, uninjured or mechanically ventilated on site resulted in 26,059 patients for further analysis . Sex wasThe adult age group most affected by frequency was the 40- to 59-year-olds. General injury localizations as well as number of affected body regions per patient are depicted in Table Analgesics commonly used are presented as frequencies and median dosages in Table p< 0.001), esketamine in 36.3% (p= 0.002) of all cases  to 26 (25–27) (p< 0.001). Respiratory rates decreased from 15 (14–17) to 14 (12–15) (p< 0.001). Oxygen saturation improved from 96 (94–98) to 98 (97–99) (p< 0.001). Additional mechanical ventilation requirements during transport were present in only 45 (0.2%) patients.Figure p= 0.137), but after treatment and on arrival at hospital females more often suffered from moderate to severe pain . The fraction suffering no or mild pain increased significantly.At the same time, documented pain decreased with respect to the two observed timepoints Fig. . Regardin=1724; 63.3%), younger , orientated  and with moderate to severe pain  from fractures  to the upper or lower limb . Regarding emergency classifications, 2023 (74.3%) cases were mountain accidents and 1877 (68.9%) occurred between December and May. Opioids were administered to 2071 (76.1%) patients and esketamine to 913 (33.5%). Median dosages were 0.2 mg fentanyl, 7.5 mg piritramide and 25 mg esketamine.We identified 2723 missions (10%) conducted without technical monitoring such as pulse oximetry, ECG or blood pressure. The majority of patients were male . Injuries were predominantly fractures, with the upper or lower extremities most often affected. Main substances administered were opioids (fentanyl > piritramide > morphine) followed by esketamine, metamizole and NSAIDs. With analgesic monotherapy being the most common regimen, males proportionally received opioids more often than did females. Following opioids or esketamine only, opioids with esketamine or opioids with metamizole were the most common combination therapies. As shown by the development of MEES, respiratory rates, oxygen saturation and the non-necessity of mechanical ventilation during transport, application of potent analgesics was very safe in the described setting. A total of 10% of the analysed HEMS operations were performed without technical monitoring which could be due to various reasons like short transportation time, cold weather and winter clothes, technical rescue operations or even patient’s medical condition. Regarding pain relief, a higher fraction of females still had moderate to severe pain on hospital arrival. In total, pain levels decreased significantly, and administration seemed safe, thus justifying the liberal use of potent analgesics in HEMS.This study presents a large retrospective analysis of a nationwide registry covering 14 physician-staffed helicopter bases in Austria over a 12-year timeframe. To date, only few studies of this size have been published on prehospital analgesia in HEMS.Current publications on analgesia in HEMS originate in the combat setting, in particular with the U.S. armed forces in Afghanistan –14. AffeAnalgesia administered during EMS may vary depending on type (HEMS/ EMS) and staffing (e.g. paramedic vs. physician) including the training level of the providers . In systems with a large volume of emergency operations staffed at most with BLS/ILS providers, administration of i.v. analgesics is limited . NitrousModerate to severe pain is a frequent finding in the prehospital care of emergency patients , 17, 31.2, respiratory rate) and levels of pain on arrival of the emergency physician and at the time of handover in hospital led us to conclude that the analgesics administered in this study were safe and adequate. The percentage of patients suffering from moderate to severe pain unmistakably decreased from over 87% to under 5%, further justifying liberal use of potent analgesics. Interestingly, while no gender differences were recorded with respect to initially moderate to severe pain, females more often still suffered from moderate to severe pain on arrival in hospital. Documented injury severity was lower in females and, while median analgesic dosages were comparable, decreased opioid but increased esketamine administration was recorded in female adults. Reasons for this difference cannot be derived from the presented data, but this finding stands in contrast to the existing literature, where largely no gender difference or even a female predominance in pain relief is described [While the absence of analgesic administration as well as a higher NACA Score and NRS on site have unsurprisingly been described as risk factors for insufficient pain management, the same is unexpectedly also true of treatment by a female physician . Althougescribed –6, 18.Not previously described is the fact that 10% of the described HEMS missions were conducted without any technical monitoring despite the overwhelming use of opioids and esketamine. These special cases were particularly young, orientated men involved in mountain accidents mainly in winter and suffering from severe pain from fractures to the upper or lower limbs. Obviously, this practice is not uncommon and emergency physicians were not discouraged from administering these potent analgesics in order to relieve severe pain despite the non-availability or cold-related failure of adequate technical monitoring equipment.Although handwritten report forms were primarily documented prospectively and transferred to the digital database in a timely manner and by the emergency physician himself, poor documentation quality is not uncommon in emergency prehospital settings , 34. ErrOpioids and esketamine were frequently administered in physician-staffed HEMS. Analgesia was largely sufficient, with females more often suffering from oligoanalgesia (NRS> 3) on hospital arrival. Administration safety was high, justifying liberal use of potent analgesics in physician-staffed HEMS.Additional file 1 Figure A1. Consort Flowchart.