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Background The optimal analgesic strategy for patients with acute pancreatitis (AP) remains unknown. Objective The present systematic review and meta-analysis aims to compare the efficacy of different analgesic modalities trialled in AP. Methods A systematic search of PubMed, MEDLINE, EMBASE, CENTRAL, SCOPUS and Web of Science conducted up until June 2021, identified all randomised control trials (RCTs) comparing analgesic modalities in AP. A pooled analysis was undertaken of the improvement in pain scores as reported on visual analogue scale (VAS) on day 0, day 1 and day 2. Results Twelve RCTs were identified including 542 patients. Seven trial drugs were compared: opiates, non-steroidal anti-inflammatories (NSAIDs), metamizole, local anaesthetic, epidural, paracetamol, and placebo. Across all modalities, the pooled VAS scores showed global improvement from baseline to day 2. Epidural analgesia appears to provide the greatest improvement in VAS within the first 24 h but is equivalent to opiates by 48 h. Within 24 h, NSAIDs offered similar pain-relief to opiates, while placebo also showed equivalence to other modalities but then plateaued. Local anaesthetics demonstrated least overall efficacy. VAS scores for opiate and non-opiate analgesics were comparable at baseline and day 1. The identified RCTs demonstrated significant statistical and methodological heterogeneity in pain-relief reporting. Conclusions There is remarkable paucity of level 1 evidence to guide pain management in AP with small datasets per study. Epidural administration appears effective within the first 24 h of AP although infrequently used and featured in only a single RCT. NSAIDs are an effective opiate sparing alternative during the first 24 h.

BackgroundThe ongoing epidemic of prescription opiate abuse is one of the most pressing health issues in the United States today. Consequently, analgesic adjuncts, such as multimodal drug regimens and regional anesthetic blocks (like transversus abdominis plane (TAP) block), have been introduced to the perioperative period in hopes of decreasing postoperative opiate use. However, the effect of these interventions on intraoperative opiate use has not been examined. We hypothesized that preoperative TAP block would be associated with decreased intraoperative opiate use during minimally invasive cholecystectomy.MethodsThis was a retrospective review of patients undergoing minimally invasive cholecystectomy between June 2018 and January 2021. Perioperative data, operative times, and medication administration data were collected. Intraoperative opiate use was calculated in total morphine equivalent doses (MED) for each patient and adjusted for operative time. Univariate analysis and multivariate linear regression were performed to determine factors affecting intraoperative opiate requirements.Results261 patients were included in this study, of which 62 (23.8%) received preoperative TAP block and 199 (76.2%) did not. Preoperative TAP block was associated with decreased intraoperative opiate use (0.199 vs 0.312, p < 0.001), while there were no statistically significant differences associated with other analgesic adjuncts including preoperative acetaminophen (p = 0.485), celecoxib (p = 0.112), gabapentin (p = 0.165), or intraoperative ketorolac (p = 0.200). On multivariate analysis, preoperative TAP block was independently associated with decreased intraoperative opiate use (< 0.001), while chronic cholecystitis on final pathology was associated with increased intraoperative opiate use (p = 0.002).ConclusionThe use of preoperative TAP block was associated with decreased intraoperative opiate use during minimally invasive cholecystectomy and should be considered for routine use. Future research should investigate whether preoperative TAP blocks and a subsequent decrease of intraoperative opiates, also result in a decrease in postoperative opiate use and improvements in postoperative outcomes.

The impact of agonist dose and of physician, staff and patient engagement on treatment have not been evaluated together in an analysis of treatment for opioid use disorder. Our hypotheses were that greater agonist dose and therapeutic engagement would be associated with reduced illicit opiate use in a time-dependent manner. Publicly-available treatment data from six buprenorphine efficacy and safety trials from the Federally-supported Clinical Trials Network were used to derive treatment variables. Three novel predictors were constructed to capture the time weighted effects of buprenorphine dosage (mg buprenorphine per day), dosing protocol (whether physician could adjust dose), and clinic visits (whether patient attended clinic). We used time-in-trial as a predictor to account for the therapeutic benefits of treatment persistence. The outcome was illicit opiate use defined by self-report or urinalysis. Trial participants (N = 3022 patients with opioid dependence, mean age 36 years, 33% female, 14% Black, 16% Hispanic) were analyzed using a generalized linear mixed model. Treatment variables dose, Odds Ratio (OR) = 0.63 (95% Confidence Interval (95%CI) 0.59–0.67), dosing protocol, OR = 0.70 (95%CI 0.65–0.76), time-in-trial, OR = 0.75 (95%CI 0.71–0.80) and clinic visits, OR = 0.81 (95%CI 0.76–0.87) were significant (p-values < 0.001) protective factors. Treatment implications support higher doses of buprenorphine and greater engagement of patients with providers and clinic staff.

Pancreaticoduodenectomy is the only curative option for patients with pancreatic cancer; however, pain remains a considerable problem postoperatively. With many centres moving away from using epidural analgesia, there is the need to evaluate alternative opiate sparing techniques for postoperative analgesia. We sought to determine if rectus sheath catheters (RSCs) had an opiate sparing and analgesic effect compared with standard care alone (opiate analgesia). We conducted a retrospective pre- and postintervention cohort study of patients undergoing pancreaticoduodenectomy at a single tertiary academic hospital in Toronto, Canada, between April 2018 and December 2019. All patients undergoing a pancreaticoduodenectomy were eligible for inclusion. Among the 101 patients identified, 84 (61 control, 23 RSCs) were analyzed after exclusion criteria were applied (epidural analgesia, admission to intensive care intubated or reintubated within the first 96 hours). The pre-intervention group received a semi-standardized course of analgesics, including intravenous hydromorphone, acetaminophen, ketamine, with or without nonsteroidal anti-inflammatory, and with or without intravenous lidocaine; the latter 2 drugs were at the individual anesthesiologist and surgeon’s preference. For the postintervention group, the same course of analgesics were used, with the addition of RSCs. These were inserted at the end of the operation, with a loading dose of ropivacaine administered and followed by a programmed intermittent bolus regime for 72–96 hours. The primary outcome measure was total postoperative opiate consumption (oral morphine equivalents). Secondary outcomes included pain scores (numeric rating scale) and treatment-related adverse effects. Opiate consumption (oral morphine equivalents) at 96 hours was significantly lower (median 188 mg, interquartile range [IQR] 112–228 v. 242.4 mg, IQR 166.8–352) with and without RSC, respectively (p = 0.01). The RSC group used significantly less opiates at each time point from 24 hours postoperatively, with no significant difference in pain scores between the groups and no significant catheter-related complications. The use of RSCs was associated with significant reductions in postoperative opiate consumption. Given the ease of placement and management, with minimal complications, RSCs should be incorporated into a course of postoperative multimodal analgesia. A large scale randomized controlled trial should be conducted to further investigate these findings. La pancréatoduodénectomie est la seule option à visée curative pour les personnes atteintes d’un cancer du pancréas; toutefois, la douleur postopératoire reste un problème de taille. Étant donné que de nombreux centres abandonnent peu à peu l’analgésie épidurale, il est nécessaire d’explorer d’autres modalités d’épargne opiacée pour l’analgésie postopératoire. Nous avons voulu vérifier si le bloc de gaine des grands droits (BGD) exerçait un effet analgésique et un impact sur l’épargne opiacée, comparativement aux soins standard seuls (analgésie opiacée). Nous avons procédé à une étude de cohorte rétrospective préet postintervention regroupant des personnes soumises à une pancréatoduodénectomie dans 1 seul centre hospitalier universitaire de soins tertiaires à Toronto, au Canada, entre avril 2018 et décembre 2019. Toutes les personnes soumises à une pancréatoduodénectomie étaient admissibles. Parmi les 101 cas identifiés, 84 (61 témoins, 23 BGD) ont été analysés après application de critères d’exclusion (analgésie épidurale, admission à l’unité des soins intensifs, intubation ou réintubation au cours des 96 premières heures). Le groupe pré-intervention a reçu un protocole semi-standardisé d’analgésiques, incluant de l’hydromorphone IV, de l’acétaminophène, de la kétamine avec ou sans anti-inflammatoires non stéroïdiens, et avec ou sans lidocaïne intraveineuse; ces 2 derniers agents étaient administrés à la discrétion des services d’anesthésiologie et de chirurgie. Pour le groupe post-intervention, le même cycle d’analgésiques a été utilisé avec le BGD. Le cathéter de BGD était inséré en fin d’intervention avec une dose de charge de ropivacaïne, suivie d’une série de bolus intermittents programmés sur une période de 72–96 heures. Le paramètre principal était le volume total d’opiacés postopératoires administrés (en équivalence de morphine orale). Les paramètres secondaires incluaient les scores d’évaluation de la douleur (échelle numérique) et les effets indésirables des traitements. La prise d’opiacés (en équivalence de morphine orale) au bout de 96 heures était significativement moindre avec le BGD (médiane 188 mg, éventail interquartile [ÉI] 112–228 c. 242,4 mg, ÉI 166,8–352) avec et sans BGD, respectivement (p = 0,01). Le groupe sous BGD a effectivement utilisé significativement moins d’opiacés à chaque étape de mesure à partir de 24 heures suivant l’intervention, sans différence significative quant aux scores d’évaluation de la douleur entre les groupes ni complications notables liées au cathéter. L’utilisation du BGD a été associée à des réductions significatives de la consommation postopératoire d’opiacés. Étant donné que le BGD est facile à installer et à gérer et qu’il donne lieu à peu de complications, il gagnerait à être intégré aux protocoles d’analgésie postopératoire multimodale. La réalisation d’un grand essai randomisé et contrôlé permettrait d’explorer la question plus avant.

Studies have demonstrated the benefits of INF in reducing pain scores in pediatric patients with VOC due to sickle cell disease (SCD) and in adult patients with chronic pain conditions other than VOC, such as cancer. However, there is limited literature that exists describing the role of INF in adult patients with VOC due to SCD. Current literature demonstrates that the use of IV morphine for VOC patients leads to reduced pain. Therefore, comparing the use of INF with IV morphine will establish the degree of effectiveness of INF for VOC patients. To determine if intranasal fentanyl is equally as effective as IV morphine for treating VOC-associated pain in adult SCD patients. This study was a retrospective non-inferiority cohort study. Electronic health records were utilized to identify eligible patients between January 1, 2021 to February 28, 2022. Patients who received INF as an initial opioid upon presentation to the ED where allocated to the intervention group. On the other hand, individuals who received IV morphine as an initial opioid upon presentation to the ED were allocated to the control group. A multi-site healthcare system containing five hospitals. Patients 18 years of age or older, admitted to the ED with VOC due to SCD, and received INF or IV morphine as an initial opioid upon presentation to the ED. The primary outcome was to evaluate the percent change in pain reduction after the initial dose of opiate between groups. Secondary outcomes include time to first rescue medication, total morphine milligram equivalent (MME) of IV opiates, hypotension, bradycardia, respiratory distress requiring opiate reversal within 6 h post- study drug administration, readmission within 48 h, and ED disposition. A total of 230 patients were reviewed within the study period, 95 subjects met inclusion criteria, 31 subjects were included in the INF arm and 64 subjects in the IV morphine arm. The primary outcome showed an average percent pain reduction of 17.25% in the INF arm and 17.15% in the IV morphine arm. The point estimate difference was 0.1% (95% CI −9.3%–9.5%; non-inferiority (p < 0.0001). The median dose of IV opiates was 8 MME in the INF group, and 6 MME in the IV morphine group (p = 0.0268). The time from study drug to first rescue medication administration was 22.4 min and 27.3 min in the INF and IV morphine groups, respectively (p = 0.2231). There was no incidence of hypotension or respiratory distress requiring opiate reversal in either arm. Bradycardia occurred in 12.9% and 7.7% (p = 0.2042), readmission rates within 48 h due to VOC was 6.5% and 20.9% (p = 0.0553), and discharge from the ED to home was 16% and 66% (p = 0.0196) in INF and IV morphine arms, respectively. INF provided similar pain reduction compared to IV morphine in the treatment of adults with VOC presenting to the ED. IV morphine arm showed a statistically significant difference in discharge to home from the ED, however there was a trend in readmission within 48 h. The study showed no significant difference in hypotension, respiratory distress, or bradycardia between the groups. The INF group had no significant impact on time to drug administration compared to IV morphine, however it was within 1 h of patient presentation which complies with American Society of Hematology (ASH) guidelines. In conclusion, our study showed that INF was non-inferior when compared to IV morphine in reducing pain scores after drug administration. Therefore, INF is an effective alternative to IV morphine for pain management in adults presenting to the ED for VOC particularly in those with limited IV access. •Intranasal fentanyl (INF) is non-inferior to intravenous (IV) morphine in the treatment of adults with vaso-occlusive crisis•IV morphine arm showed statistically significant difference in discharge to home, however there was a trend in readmission•The study showed no difference in hypotension, respiratory distress, or bradycardia between the groups.•INF had a shorter time to drug administration compared to IV morphine, but was not found to be statistically significant.

Background and Aims Multiple medications are associated with an increased risk of incident hepatic encephalopathy. Despite this known risk, medications such as opioids, benzodiazepines, gabapentin/pregabalin, and/or proton pump inhibitors are increasingly prescribed to persons with cirrhosis. Deprescribing is a promising intervention to reduce the burden of hepatic encephalopathy. Given that deprescribing has not been trialed in cirrhosis, we evaluated the barriers and facilitators to safe and successful deprescribing in cirrhosis. Methods We conducted, transcribed, and analyzed semi‐structured interviews using qualitative methodology with 22 subjects. This included eight patients with cirrhosis and recent use of opiates, benzodiazepines, gabapentin/Lyrica, and/or proton pump inhibitors as well as 14 providers (primary care, transplant surgery, transplant hepatology). Interviews explored opinions, behaviors, and understanding surrounding the risks and benefits of deprescribing. Results Major provider‐specific barriers included deferred responsibility of the deprescribing process, knowledge gaps regarding the risk of hepatic encephalopathy associated with medications (e.g., proton pump inhibitors) as well as the safe method of deprescription (i.e., benzodiazepines), and time constraints. Patient‐specific barriers included knowledge gaps regarding the cirrhosis‐specific risks of their medications and anxiety about the recurrence of symptoms after medication discontinuation. Patients uniformly reported trust in their provider's opinions on risks and wished for more comprehensive education during or after visits. Providers uniformly reported support for deprescription resources including pharmacist or nurse outreach. Conclusion Given knowledge of medication risks related to hepatic encephalopathy in patients with cirrhosis, deprescribing is universally seen as important. Knowledge gaps, inaction, and uncertainty regarding feasible alternatives prevent meaningful implementation of deprescription. Trials of protocolized pharmacy‐based deprescribing outreach and patient‐facing education on risks are warranted. Key Summary Summarize the established knowledge on this subject Hepatic encephalopathy (HE) is a morbid complication of cirrhosis. The risk of HE may be increased by psychoactive medications and proton pump inhibitors. Deprescribing is felt to be a promising approach to HE prevention. What are the significant and/or new findings of this study? Patients are unaware of how their medications influence the risk of HE. Patients are willing to follow physician recommendations regarding deprescribing but are afraid of worsening symptoms. Physicians do not feel comfortable deprescribing opioids or benzodiazepines. Physicians do not feel responsible or equipped with the resources for deprescribing.

Using a mobile research facility, we enrolled 141 opioid users from a neighborhood of Philadelphia, an urban epicenter of the opioid epidemic. Nearly all (95.6%) met DSM-5 criteria for severe opioid use disorder. The prevalence of HIV infection (8.5%) was more than seven times that found in the general population of the city. Eight of the HIV-positive participants (67.0%) reported receiving antiretroviral treatment but almost all of them had unsuppressed virus (87.5%). The majority of participants (57.4%) reported symptoms consistent with major depressive disorder. Severe economic distress (60.3%) and homelessness were common (57%). Polysubstance use was nearly universal, 72.1% had experienced multiple overdoses and prior medication for opioid use disorder (MOUD) treatment episodes (79.9%), but few currently engaged in addiction care. The prevalence, multiplicity and severity of chronic health and socioeconomic problems highlight consequences of the current opioid epidemic and underscore the urgent need to develop integrated models of treatment.

Proximal femoral fractures are characterized as one of the most common and most painful injuries sustained by patients of all ages and are associated with high rates of oligoanalgesia in the prehospital setting. Current treatments include oral and parenteral opiates and sedative agents, however regional anesthesia techniques for pain relief may provide superior analgesia with lower risk of side effects during patient transportation. The fascia iliaca compartment block (FICB) is an inexpensive treatment which is performed with minimal additional equipment, ultimately making it suitable in prehospital settings. In adult patients sustaining proximal femoral fractures in the prehospital setting, what is the effect of the FICB on non-verbal pain scores (NVPS), patient satisfaction, success rate, and adverse events compared to traditional analgesic techniques? A librarian-assisted literature search was conducted of the Cochrane Database, Ovid MEDLINE, PubMed, Ovid EMBASE, Scopus, and Web of Science indexes. Additionally, reference lists for potential review articles from the , the , the , , and the were reviewed. Databases and journals were searched during the period from January 1, 1980 through July 1, 2022. Each study was scrutinized for quality and validity and was assigned a level of evidence as per Oxford Center for Evidence-Based Medicine guidelines. Five studies involving 340 patients were included (ie, two randomized control trials [RCTs], two observational studies, and one prospective observational study). Pain scores decreased after prehospital FICB across all included studies by a mean of 6.65 points (5.25 - 7.5) on the NVPS. Out of the total 257 FICBs conducted, there was a success rate of 230 (89.3%). Of these, only two serious adverse events were recorded, both of which related to local analgesia toxicity. Neither resulted in long-term sequelae and only one required treatment. Use of FICBs results in a significant decrease in NVPS in the prehospital setting, and they are ultimately suitable as regional analgesic techniques for proximal femur fractures. It carries a low risk of adverse events and may be performed by health care practitioners of various backgrounds with suitable training. The results suggest that FICBs are more effective for pain management than parenteral or oral opiates and sedative agents alone and can be used as an appropriate adjunct to pain management.

Administration of a widely used 5‐hydroxytryptamine receptor (5HT3AR) antagonist (ondansetron) potently inhibited the development of experimentally induced opioid dependence and withdrawal responses in mice and humans. However, in several studies examining withdrawal symptoms in subjects with chronic opioid use disorders (OUDs), ondansetron exhibited reduced or absent efficacy. Because attenuation of opioid withdrawal symptomatology is mediated within the brain, this study examined single‐dose ondansetron pharmacokinetics in the blood and brain of mice. We demonstrate that ondansetron concentrations in the brain (Cbrain ng/mg) are 1000‐fold lower than the blood concentrations (Cblood ng/ml) and decrease rapidly after ondansetron administration; and that a large percentage of brain ondansetron remains in the ventricular fluid. These results indicate that the ondansetron dose, and the time window between ondansetron and opioid administration, and when withdrawal is assessed are critical considerations for clinical studies involving subjects with chronic OUD. The pharmacokinetic results and the dosing considerations discussed here can be used to improve the design of subsequent clinical trials, which will test whether a more prolonged period of ondansetron administration can provide a desperately needed therapy that can prevent the development of neonatal opioid withdrawal syndrome in babies born to mothers with chronic OUD.