Selective Inhibition of NaV1.8 with VX-548 for Acute Pain.

BACKGROUND: The NaV1.8 voltage-gated sodium channel, expressed in peripheral nociceptive neurons, plays a role in transmitting nociceptive signals. The effect of VX-548, an oral, highly selective inhibitor of NaV1.8, on control of acute pain is being studied. METHODS: After establishing the selectivity of VX-548 for NaV1.8 inhibition in vitro, we conducted two phase 2 trials involving participants with acute pain after abdominoplasty or bunionectomy. In the abdominoplasty trial, participants were randomly assigned in a 1:1:1:1 ratio to receive one of the following over a 48-hour period: a 100-mg oral loading dose of VX-548, followed by a 50-mg maintenance dose every 12 hours (the high-dose group); a 60-mg loading dose of VX-548, followed by a 30-mg maintenance dose every 12 hours (the middle-dose group); hydrocodone bitartrate-acetaminophen (5 mg of hydrocodone bitartrate and 325 mg of acetaminophen every 6 hours); or oral placebo every 6 hours. In the bunionectomy trial, participants were randomly assigned in a 2:2:1:2:2 ratio to receive one of the following over a 48-hour treatment period: oral high-dose VX-548; middle-dose VX-548; low-dose VX-548 (a 20-mg loading dose, followed by a 10-mg maintenance dose every 12 hours); oral hydrocodone bitartrate-acetaminophen (5 mg of hydrocodone bitartrate and 325 mg of acetaminophen every 6 hours); or oral placebo every 6 hours. The primary end point was the time-weighted sum of the pain-intensity difference (SPID) over the 48-hour period (SPID48), a measure derived from the score on the Numeric Pain Rating Scale (range, 0 to 10; higher scores indicate greater pain) at 19 time points after the first dose of VX-548 or placebo. The main analysis compared each dose of VX-548 with placebo. RESULTS: A total of 303 participants were enrolled in the abdominoplasty trial and 274 in the bunionectomy trial. The least-squares mean difference between the high-dose VX-548 and placebo groups in the time-weighted SPID48 was 37.8 (95% confidence interval [CI], 9.2 to 66.4) after abdominoplasty and 36.8 (95% CI, 4.6 to 69.0) after bunionectomy. In both trials, participants who received lower doses of VX-548 had results similar to those with placebo. Headache and constipation were common adverse events with VX-548. CONCLUSIONS: As compared with placebo, VX-548 at the highest dose, but not at lower doses, reduced acute pain over a period of 48 hours after abdominoplasty or bunionectomy. VX-548 was associated with adverse events that were mild to moderate in severity. (Funded by Vertex Pharmaceuticals; VX21-548-101 and VX21-548-102 ClinicalTrials.gov numbers, NCT04977336 and NCT05034952.).

Predictors of Prolonged Opioid Use Following Colectomy.

BACKGROUND: The United States is in the middle of an opioid epidemic. Gastrointestinal surgery has been ranked in the top 3 surgical subspecialties for highest opioid prescribing. OBJECTIVE: The goal of this study is to determine the rate of and risk factors for prolonged opioid use following colectomy. DESIGN: This study utilized data (2015-2017) from the American College of Surgeons National Surgical Quality Improvement Program from 5 institutions. SETTINGS: This study was conducted at 2 academic and 3 community hospitals. PATIENTS: Included were 1243 patients who underwent colectomy. MAIN OUTCOME MEASURES: The primary outcome was rate of prolonged opioid use defined as a new opioid prescription 90 to 180 days postoperatively. RESULTS: A total of 132 (10.6%) patients were prolonged opioid users. In univariate analysis, patients who were prolonged opioid users were significantly more likely to have had more than one opioid prescription in the prior year, to have a higher ASA classification, to undergo an open procedure, to have an ostomy created, and to be discharged with a high quantity of opioids (all p < 0.05). Prolonged opioid users were significantly more likely to have a complication (p = 0.007) or readmission (p = 0.003) within 30 days of the index procedure. In multivariable analysis, prior opioid use (OR, 2.6; 95% CI, 1.6-4.2; p < 0.001), ostomy creation (OR, 2.1; 95% CI,1.2-3.7; p = 0.01), higher quantity of opioid prescription at discharge (OR, 1.9; 95% CI,1.1-3.3; p = 0.03), higher ASA classification (OR, 1.7; 95% CI, 1.1-2.6; p = 0.02), and hospital readmission (OR, 2.0; 95% CI, 1.2-3.4; p = 0.01) were independent predictors of prolonged opioid use. LIMITATIONS: This study is a retrospective review, and all variables related to prolonged opioid use are not collected in the data. CONCLUSIONS: A significant proportion of patients undergoing colectomy become prolonged opioid users. We have identified risk factors for prolonged postoperative opioid use, which may allow for improved patient education and targets for intervention preoperatively, as well as implementation of programs for monitoring and cessation of opioid use in the postoperative period. See Video Abstract at http://links.lww.com/DCR/A973. PREDICTORES DEL USO PROLONGADO DE OPIOIDES DESPUÉS DE LA COLECTOMÍA: Los Estados Unidos se encuentran en medio de una epidemia de opioides. La cirugía gastrointestinal ha sido clasificada entre las tres subespecialidades quirúrgicas principales para la prescripción más alta de opioides. OBJETIVO: El objetivo de este estudio es determinar la tasa y los factores de riesgo para el uso prolongado de opioides después de la colectomía. DISEÑO:: Este estudio utilizó datos (2015-2017) del Programa Nacional de Mejoramiento de la Calidad Quirúrgica del Colegio Americano de Cirujanos de cinco instituciones. MARCO: Dos hospitales académicos y tres comunitarios. PACIENTES: 1,243 pacientes sometidos a una colectomía. MEDIDAS DE RESULTADO PRINCIPALES: El resultado primario fue la tasa de uso prolongado de opioides, definida como una nueva receta de opioides entre 90 y 180 días después de la operación. RESULTADOS: Un total de 132 (10.6%) pacientes fueron usuarios de opioides por tiempo prolongado. En el análisis univariado, los pacientes que eran usuarios prolongados de opioides tenían una probabilidad significativamente mayor de haber tenido más de una receta de opioides en el año anterior, tenían una clasificación más alta de la Asociación Americana de Anestesiólogos, se sometieron a un procedimiento abierto, se les creó una ostomía y se les dio de alta con una cantidad grande de opioides (todos p < 0.05). Los usuarios de opioides prolongados fueron significativamente más propensos a tener una complicación (p = 0.007) o readmisión (p = 0.003) dentro de los 30 días del procedimiento índice. En el análisis multivariado, el uso previo de opioides (OR, 2.6; IC 95%, 1.6-4.2; p < 0.001), creación de ostomía (OR, 2.1; IC 95%, 1.2-3.7; p = 0.01), mayor cantidad de prescripción de opioides al dar de alta (OR, 1.9; IC 95%, 1.1-3.3; p = 0.03), clasificación más alta de la Asociación Americana de Anestesiólogos (OR, 1.7; IC 95%, 1.1-2.6; p = 0.02) y reingreso hospitalario (OR, 2.0; IC del 95%, 1.2-3.4, p = 0.01) fueron predictores independientes del uso prolongado de opioides. LIMITACIONES: Este estudio es una revisión retrospectiva y todos los variables relacionadas con el uso prolongado de opioides no se colectaron en los datos. CONCLUSIONES: Una proporción significativa de pacientes con colectomía se convierten en usuarios prolongados de opioides. Hemos identificado factores de riesgo para el uso prolongado de opioides postoperatorios, que pueden permitir una mejor educación del paciente y objetivos para la intervención preoperatoria, así como la implementación de programas para la supervisión y cese del uso de opioides en el período postoperatorio. Vea el Video de Resumen en http://links.lww.com/DCR/A973.

Evaluation of the Determinants of Satisfaction With Postoperative Pain Control After Thoracoscopic Surgery: A Single-Center, Survey-Based Study.

BACKGROUND: The need to measure, compare, and improve the quality of pain management is important to patients, payers, and health care providers. Pain after thoracic surgery can be severe, and thoracoscopic approaches have not had the favorable impact on pain as anticipated. The aim of this study was to evaluate the determinants of patient satisfaction with acute pain management and the effectiveness of pain control after video-assisted thoracoscopic surgery using a modified version of the Revised American Pain Society Patient Outcome Questionnaire. METHODS: We performed a single-center, prospective, survey-based study of 300 patients who had undergone elective video-assisted thoracoscopic surgery. Patients were enrolled and completed the survey on postoperative day 1 or 2. The primary outcome variable was patient-reported satisfaction with acute postoperative pain treatment measured on a 1-4 scale. The relationship between the items on the survey and patient satisfaction was analyzed to determine the factors significantly associated with satisfaction. RESULTS: Fifty-one percent of the patients had the highest satisfaction level with pain treatment, and 4% of the patients had the lowest satisfaction level. The mean reported acceptable pain level was 3.8 ± 1.9 (numeric rating scale [NRS], 0-10). The average pain intensity score at the time of the survey was 2.8 ± 2.1 (NRS, 0-10). The median for the most pain in the prior 24 hours was 7 (NRS, 0-10; interquartile range, 5-9). Five items from the survey were significantly associated with the satisfaction level. The predictor with the highest associated odds ratio (OR) with satisfaction was the ability to participate in pain management decisions (OR, 1.45; P < .0001). Another positively associated predictor was receiving helpful information about pain treatment options (OR, 1.31; P = .002). Negatively associated predictors of patient satisfaction included level of pain intensity at time of survey (OR, 0.76; P = .002), lowest pain score in the prior 24 hours (OR, 0.70; P = .0006), and having pain interfere with sleep in the postoperative period (OR, 0.72; P = .037). CONCLUSIONS: Our findings highlight several factors associated with patient satisfaction with acute postoperative pain management. Interventions focused on achieving acceptable pain levels for the majority of the time, ensuring that patients are able to get sleep, providing patients with helpful information about their pain treatment, and, most importantly, allowing patients to participate in decisions about their pain management may improve patient satisfaction with postoperative pain management.

Avoiding Adverse Events Secondary to Opioid-Induced Respiratory Depression: Implications for Nurse Executives and Patient Safety.

BACKGROUND: Guidelines with recommendations for monitoring type and timing of hospitalized patients for opioid-induced respiratory depression have been published, yet adverse events continue to occur. OBJECTIVE: This study reports on the monitoring practices of 8 hospitals that volunteered to pilot test a Centers for Medicare & Medicaid Services e-quality measure that was under development. Recommendations for nurse executives are provided to support patient safety. METHODS: Data on monitoring practices were collected retrospectively from the electronic medical records at 8 hospitals on all patients receiving intravenous (IV) opioids for more than 2.5 continuous hours via patient-controlled analgesia (PCA). Analysis included the percentage of patients who were monitored according to specific standards developed by a panel of technical experts with comparisons of naloxone use to monitoring practices. RESULTS: Recommended patient assessments occurred in only 8.3% of the patients. No patients who were assessed at least every 2.5 hours received naloxone. CONCLUSIONS: Care for patients receiving IV PCA is lacking in adherence to latest safety standards. Nurse executives must implement structures and processes to promote vigilance with evidence-based monitoring practices.

Surgery at the end of life: a pilot study comparing decedents and survivors at a tertiary care center.

BACKGROUND: More than a quarter of medical costs for Medicare beneficiaries are incurred in the last year of life; surgical intensity during this time is significant. This study was performed to determine types of operations patients undergo in their terminal year, and compare characteristics of decedents with those of survivors. METHODS: Population of 747 consecutive all-payer patients seen at the preoperative assessment center of a tertiary care hospital. Patient characteristics were obtained from the electronic medical record. Surgical indication (palliative, curative, diagnostic, elective) was assessed based on procedure performed and underlying diagnosis. Vital status was determined using the electronic medical record with confirmation via social security national death master file. Descriptive statistics were performed to compare patient characteristics and procedures performed on those who died within 1 yr of procedure with those of survivors. RESULTS: Thirty-seven patients (5%) were confirmed dead at 1 yr. Ten (27%) of these had palliative procedures, 11 (30%) diagnostic, 14 (38%) curative, and 2 (5%) elective. Decedents were more likely to have undergone a palliative (27 vs. 3%) or diagnostic (30 vs. 14%) procedure and less likely to have undergone an elective procedure (5 vs. 42%) than survivors (P < 0.0001). Nearly half of decedents did not have an advanced directive by the date of surgical intervention. CONCLUSIONS: Nearly 1 in 20 patients seen at the preoperative assessment clinic of a tertiary care hospital died within 1 yr of their procedure. Patient characteristics and procedure indication for decedents differed from those of survivors. Similar analyses based on institution and region may provide methodologies to compare variation in surgical intensity and assist preoperative care providers in evaluating appropriateness of resource allocation.

Ketamine decreases postoperative pain scores in patients taking opioids for chronic pain: results of a prospective, randomized, double-blind study.

BACKGROUND: Patients prescribed opioids for chronic pain may suffer from inadequate postoperative pain control. Ketamine is an adjuvant demonstrating analgesic and opioid-sparing effects. We hypothesize that an intravenous ketamine infusion in addition to opioid-based patient-controlled analgesia (PCA) improves postoperative pain relief in this patient population. METHODS: We evaluated 64 patients with chronic pain taking opioids undergoing nononcologic surgery. Patients were randomized to receive either postoperative hydromorphone PCA and continuous ketamine (0.2 mg/kg/hour), or hydromorphone PCA and saline. Patients provided numeric rating scale (NRS) pain scores for "worst," "average," and "least" pain following surgery. The primary outcome measure was change in patients' postoperative NRS scores compared with baseline NRS. Secondary and tertiary outcomes included postoperative day one 24-hour opioid use and the amount of opioid used 24 hours prior to hospital discharge. RESULTS: Fifty-nine patients were included in the analysis. Baseline patient characteristics were similar with the exception of age. Patients using ketamine had decreased "average" pain scores (percent change between postoperative and preoperative NRS) after surgery (13.5% decrease in the ketamine group vs 15.5% increase in NRS in the placebo group, P = 0.0057). There were no differences in "worst" or "least" pain scores or postoperative opioid use. Side effects between groups were similar. CONCLUSIONS: Our study demonstrates that a postoperative ketamine infusion at 0.2 mg/kg/hour in addition to opioids results in a statistically significant reduction of "average" pain scores in patients undergoing surgery who take opioids for chronic pain. However, "least" and "worst" pain scores and the amount of opioid used postoperatively did not differ between groups. Thus, the use of a postoperative ketamine infusion at 0.2 mg/kg/hour provides limited benefit in improving pain management for this challenging population.

Exploratory study of VVZ-149, a novel analgesic molecule, in the affective component of acute postoperative pain after laparoscopic colorectal surgery.

STUDY OBJECTIVE: VVZ-149 is a small molecule that inhibits the glycine transporter type 2 and the serotonin receptor 5-hydroxytryptamine 2A. In the present study, we investigated the efficacy and safety of VVZ-149 as a single-use injectable analgesic for treating moderate to severe postoperative pain after colorectal surgery. DESIGN: Randomized, parallel group, double-blind Phase 2 clinical trial (NCT02489526). SETTING: 3 academic institutions in the United States. PATIENTS: 60 patients undergoing laparoscopic colorectal surgery. INTERVENTIONS: A continuous 8-h intravenous infusion of VVZ-149 Injections (n = 40) or placebo (n = 20) administered after emergence from anesthesia. MEASUREMENTS: The outcome measures included pain intensity (PI), opioid consumption via patient-controlled analgesia (PCA), and rescue dosing provided "as needed". Early rescue dosing with opioids postoperatively was associated with preoperative negative affect (anxiety, depression, and pain catastrophizing), enabling it to be used as an indirect measure of the affective component of pain. Efficacy outcomes were compared between treatment groups based on preoperative negative affect and early rescue dosing of opioids. MAIN RESULTS: Postoperative PI was non-significantly lower in patients receiving VVZ-149 compared to those receiving placebo. The VVZ-149 group had a 34.2% reduction in opioid consumption for 24 h post-dose, along with fewer PCA demands. Somnolence and headache was higher in the intervention group. For patients characterized by high levels of preoperative negative affect, the VVZ-149 group experienced a significant pain reduction and 40% less opioid use compared to the placebo group. CONCLUSIONS: VVZ-149 resulted in a non-significant reduction of postoperative pain during the first 8 h after surgery. Post hoc analysis indicates that VVZ-149 may benefit patients with negative affect who otherwise have higher postoperative opioid use. REGISTRATION NUMBER: www.clinicaltrials.gov, ID: NCT02489526.

Education based on publicly-available keyword data is associated with decreased stress and improved trajectory of in-training exam performance.

STUDY OBJECTIVE: This study aimed to assess the impact of data-driven didactic sessions on metrics including fund of knowledge, resident confidence in clinical topics, and stress in addition to American Board of Anesthesiology In-Training Examination (ITE) percentiles. DESIGN: Observational mixed-methods study. SETTING: Classroom, video-recorded e-learning. SUBJECTS: Anesthesiology residents from two academic medical centers. INTERVENTIONS: Residents were offered a data-driven didactic session, focused on lifelong learning regarding frequently asked/missed topics based on publicly-available data. MEASUREMENTS: Residents were surveyed regarding their confidence on exam topics, organization of study plan, willingness to educate others, and stress levels. Residents at one institution were interviewed post-ITE. The level and trend in ITE percentiles were compared before and after the start of this initiative using segmented regression analysis. RESULTS: Ninety-four residents participated in the survey. A comparison of pre-post responses showed an increased mean level of confidence (4.5 ± 1.6 vs. 6.2 ± 1.4; difference in means 95% CI:1.7[1.5,1.9]), sense of study organization (3.8 ± 1.6 vs. 6.7 ± 1.3;95% CI:2.8[2.5,3.1]), willingness to educate colleagues (4.0 ± 1.7 vs. 5.7 ± 1.9;95% CI:1.7[1.4,2.0]), and reduced stress levels (5.9 ± 1.9 vs. 5.2 ± 1.7;95% CI:-0.7[-1.0,-0.4]) (all p < 0.001). Thirty-one residents from one institution participated in the interviews. Interviews exhibited qualitative themes associated with increased fund of knowledge, accessibility of high-yield resources, and domains from the Kirkpatrick Classification of an educational intervention. In an assessment of 292 residents from 2012 to 2020 at one institution, there was a positive change in mean ITE percentile (adjusted intercept shift [95% CI] 11.0[3.6,18.5];p = 0.004) and trajectory over time after the introduction of data-driven didactics. CONCLUSION: Data-driven didactics was associated with improved resident confidence, stress, and factors related to wellness. It was also associated with a change from a negative to positive trend in ITE percentiles over time. Future assessment of data-driven didactics and impact on resident outcomes are needed.

Preoperative Management of Opioid and Nonopioid Analgesics: Society for Perioperative Assessment and Quality Improvement (SPAQI) Consensus Statement.

There is a lack of guidelines for preoperative dosing of opioid and nonopioid pain medications for surgical patients, which can lead to suboptimal preoperative pain control. The Society for Perioperative Assessment and Quality Improvement identified preoperative dosing of opioid and nonopioid analgesics as an area in which consensus could improve patient care. The aim of this guideline is to provide consensus that will allow perioperative physicians to make optimal recommendations regarding preoperative pain medication dosing. Six categories of pain medications were identified: opioid agonists, opioid antagonists, opioid agonist-antagonists, acetaminophen, muscle relaxants, and triptans/headache medications. We then used a Delphi survey technique to develop consensus recommendations for preoperative dosing of individual medications in each of these groups.

Improving efficiency and patient satisfaction in a tertiary teaching hospital preoperative clinic.

BACKGROUND: Clinical and organizational aspects of the preoperative visit can have a significant impact on patient satisfaction. The authors' previous work demonstrated that communication of information from the clinician to the patient was found to be the most positively rated component, whereas organizational issues, particularly waiting time, were the most negative. This study compares two yearly cycles of patient satisfaction surveys to assess the process and impact of implementation of changes. METHODS: The authors distributed a one-page questionnaire, consisting of elements evaluating satisfaction with clinical providers and with organizational aspects of the visit, to patients in their preoperative clinic during two different time periods. Fourteen different questions had five Likert scale options ranging from excellent to poor. Changes implemented included clerical, scheduling, and clinical changes. RESULTS: The overall collection rate of completed questionnaires was 79%. The scores for each question in Cycle 2 were higher for all questions, with 3 of 14 reaching statistical significance (P < 0.01). These questions related to the explanation of the Preoperative Assessment Clinic by the surgeon's office, courtesy and efficiency of the clinic staff, and satisfaction with waiting time. Average waiting time was reduced from 92 to 41 min (P < or = 0.0001). CONCLUSION: Analysis of patient flow and clinic operations led to alterations in clinic processes. Alterations included education of clinic and surgical office staff to improve customer service, and implementation of changes in provider roles. These modifications resulted in an improvement in patient satisfaction and a reduction in waiting time with minimal economic impact.

Academic Interest in Pain: Comparison of Four Specialties With Long-Standing Involvement in Pain Medicine.

PURPOSE: One of the most interesting signs of growth in a medical specialty is the addition of pain medicine as a clinical subspecialty to it. The aim of this study was to analyze publication-based academic interest in pain medicine among clinical specialties with long-standing involvement in pain management. METHODS: We assessed the activity within several specialties in the development of an academic foundation for pain medicine by measuring the frequency of the most common pain topics (1998-2017) in academic journals representing such specialties. The selection of materials for the analysis of publication-based academic interest associated with the development of pain medicine followed a three-step process: (1) Medical specialties, limited to those with accredited fellowship training in pain medicine for more than 20 years - anesthesiology, neurology, physiatry, and psychiatry; (2) Pain topics, based on the degree of topic association with the work of pain clinics - a total of 34 topics; (3) Specialty journals, mostly official journals of societies publishing articles representing all aspects of a specialty - four journals per specialty. Specialty-related academic interest was characterized in two dimensions: its breadth (the number of different topics of interest with distinctly high shares of publications) and its intensity (maximal number of publications on a particular topic). RESULTS: According to the number of topics with a distinctly high share of articles per topic (≥ 5%), the rank order of specialties was as follows (of 34 topics): anesthesiology (22), physiatry (20), neurology (10), and psychiatry (0). Regarding comparative intensity of interest, anesthesiology has prevailing interest in 16 topics (especially in postoperative pain and pharmacologic pain treatment), physiatry in 13 topics (especially in physical methods of pain therapy), and neurology in one topic (headache disorders). CONCLUSION: Publication-based academic interest in pain management was most intensive in two specialties, anesthesiology and physiatry, with anesthesiology being somewhat more multifaceted, especially in the methods of pain treatment.

Preoperative electrocardiograms: patient factors predictive of abnormalities.

BACKGROUND: Age is often the sole criterion for determining the need for preoperative electrocardiograms. However, screening electrocardiograms have not been shown to add value above clinical information. This study was designed to determine whether it is possible to target electrocardiograms ordering to patients most likely to have an abnormality that would affect management and if age alone is predictive of significant electrocardiograms abnormalities. METHODS: A list was developed of electrocardiograms abnormalities considered significant enough to impact management, as well as a list of patient factors believed to increase cardiovascular risk. electrocardiograms in all patients over 50 yr of age presenting for preoperative evaluation during a 2-month period were reviewed. RESULTS: A total of 1,149 electrocardiograms were reviewed, with 89 patients (7.8%) having at least one significant abnormality. These patients were compared with a group of 195 patients who had electrocardiograms that did not contain significant abnormalities. Patients at higher risk of having a significantly abnormal electrocardiograms that would potentially affect management were those older than 65 yr of age or who had a history of heart failure, high cholesterol, angina, myocardial infarction, or severe valvular disease. Five patients (0.44%) had an abnormal electrocardiograms in the absence of risk factors. The sensitivity of the model is 87.6%. CONCLUSION: Age greater than 65 yr remains an independent predictor for significant preoperative electrocardiograms abnormalities. The specific clinical risk factors that were found have a high sensitivity and identified all but 0.44% of patients with electrocardiograms abnormalities that may affect preoperative management.

Problems with Developments of Breakthrough Analgesics: Recent History via Scientometric Analysis.

This study evaluated 13 specific topics representing molecular targets for pain during the period 1982-2016. The evaluation was performed by measuring research efforts via a scientometric approach on one hand and by assessing successful outcomes of these efforts, as indicated by the development of FDA-approved analgesics, on the other. A number of new analgesics were developed during this period, some of them with a completely novel mechanism of action. However, the main problems with approved drugs, as well as drug candidates, are relatively low levels of clinical superiority in effectiveness and narrow spectrum of action in different types of pain, compared to opioids or NSAIDs. The most interesting feature of the scientometric analysis of the 13 analgesic discovery topics is the long-lasting growth in the number of articles. The total number of all PubMed articles persistently increased over each of many 5-year periods in every topic even without any success in the development of new analgesics. Scientometric indices of NIH-supported studies are not better at predicting successes in the discovery of new analgesics than indices applied to all publications without regard to the category of support. Thus, even the highly valued NIH-based funding system did not demonstrate a clear advantage for discovery efforts centered on pain-related molecular targets. The evaluated research efforts did not result in breakthrough analgesics that could demonstrably affect the current use of opioids or NSAIDs. Orthodox thinking-both in research and research funding-might be the main reason for the absence of breakthrough analgesics.

Needs analysis for the development of a preoperative clinic protocol for perioperative beta-blocker therapy.

STUDY OBJECTIVE: To study the development and implementation of a hospital-wide protocol regarding preoperative beta-blocker therapy. DESIGN: Prospective, observational clinical study. SETTING: Preoperative test center at a university hospital. PATIENTS: 1,000 consecutive patients presenting for a preoperative visit and scheduled for same-day admit surgery. INTERVENTIONS: An algorithm of indications and contraindications for beta-blocker therapy was designed. Data were collected prospectively on 1,000 consecutive patients between June 1, 2004 and August 31, 2004. MEASUREMENTS: Data collected included patient demographics, medication history, risk factors, indications and contraindications to beta-blocker therapy, as well as surgical risk stratification and postoperative complications. MAIN RESULTS: 960 of the 1,000 patients underwent surgery and had complete information for the study collected. 169 patients (17.6%) were receiving beta blockers prior to evaluation. Of the patients having high-risk surgery, 72% had a major or minor indication for beta-blocker therapy without contraindication. Of the patients having intermediate or low-risk surgery, 10% had a major indication for beta blockers without contraindication. Overall, 52% (409/791) of the patients who were candidates for perioperative beta blockers were not receiving them. Some type of complication was experienced by 59 (6.1%) patients. CONCLUSIONS: Development, implementation, and monitoring of perioperative beta-blocker therapy protocols is necessary, as a significant number of appropriate patients do not receive this therapy.

Recent History of Publication-Based Academic Interest in General Anesthetics.

PURPOSE: The aim of this study was to determine how interest in various general anesthetics among the authors of academic publications changed over the past 50 years. METHODS: Publication-based academic interest were analyzed using specific scientometric indices: popularity index (PI), top journal selectivity index (TJSI), and index of change (IC). Terms used for searches were the names of drugs belonging to two pharmacological classes of general anesthetics - inhaled and intravenous. Only those that had a PI value > 2.0 during at least one of the 10 five-year periods, from 1967 to 2016, were selected. RESULTS: The PI, an index of comparative popularity, reflects a consistent decline in academic interest over time in both classes of general anesthetics. Over the past 25 years, the PI of inhaled anesthetics decreased by 52 %, and that of intravenous anesthetics fell by 32%. At the same time, the PI of anesthesia management increased by 167%. Among individual anesthetics, the most impressive change was a profound decline in halothane's PI, from 22.9 in 1972-1976 to 0.5 in 2012-2016. The interest in halothane was gradually supplanted by that in new agents, initially by enflurane, followed by isoflurane and finally, sevoflurane. The next meaningful change was the gradual rise in sevoflurane's PI to surpass that of isoflurane. The most dramatic change among the PIs of intravenous anesthetics was associated with the introduction of propofol: an increase from 1.8 to its maximum of 13.6. CONCLUSIONS: The study revealed a constant decline over time in academic interest in the pharmacological basis of general anesthesia relative to all fields of anesthesia combined.

Publication-Based Academic Interest in Drugs and Techniques for Treatment of Postoperative Pain, 1975-2015.

PURPOSE: The aim of this study was to determine how drugs and their administration techniques, introduced over the past 40 years and still popular now, influenced publication-based academic interest in the treatment of postoperative pain. METHODS: Specific scientometric indices-popularity index (PI), top journal selectivity index (TJSI), and index of change (IC)-were used. Of the 61 terms searched, only those that had a PI value ≥1.0 during the 2011-2015 period were selected. They include eight drugs-bupivacaine, fentanyl, ropivacaine, acetaminophen, tramadol, remifentanil, and dexamethasone-and five techniques-patient-controlled analgesia, epidural opioids, ultrasound-guided nerve blocks, continuous nerve blocks, and transversus abdominis plane block (presented according to their decreasing PI value in each category). RESULTS: Four of these drugs or techniques with the highest PI in 2011-2015 also held top positions even 20 years earlier: in 1991-1995, the PI for bupivacaine was 9.1; fentanyl, 6.6; patient-controlled analgesia, 10.4; and epidural opioids, 6.8. Since that time, their PI values slowly decreased, for the first three items by approximately 50% and much more than that (85%) with epidural opioids. Nevertheless, to this day, they continue to hold the highest degree of publication-based academic interest. The TJSI can be regarded as an index of expectations at the time of articles publication. With bupivacaine, fentanyl, patient-controlled analgesia, and epidural opioids, the TJSI exceeded the specific high threshold of 10.0 for a very long time. The TJSIs of acetaminophen, ketamine, and dexamethasone were increased with the advent of new expectations regarding the treatment of postoperative pain using these old agents. CONCLUSIONS: Two important developments related to ultrasound-guided nerve block and continuous nerve block demonstrated only a moderate degree of academic interest. In conclusion, even today, the greatest publication-based academic interest related to postoperative pain is associated with drugs and techniques introduced 40-50 years ago.

Randomised, double-blind, parallel group, placebo-controlled study to evaluate the analgesic efficacy and safety of VVZ-149 injections for postoperative pain following laparoscopic colorectal surgery.

INTRODUCTION: In spite of advances in understanding and technology, postoperative pain remains poorly treated for a significant number of patients. In colorectal surgery, the need for developing novel analgesics is especially important. Patients after bowel surgery are assessed for rapid return of bowel function and opioids worsen ileus, nausea and constipation. We describe a prospective, double-blind, parallel group, placebo-controlled randomised controlled trial testing the hypothesis that a novel analgesic drug, VVZ -149, is safe and effective in improving pain compared with providing opioid analgesia alone among adults undergoing laparoscopic colorectal surgery. METHODS AND ANALYSIS: Based on sample size calculations for primary outcome, we plan to enrol 120 participants. Adult patients without significant medical comorbidities or ongoing opioid use and who are undergoing laparoscopic colorectal surgery will be enrolled. Participants are randomly assigned to receive either VVZ-149 with intravenous (IV) hydromorphone patient-controlled analgesia (PCA) or the control intervention (IV PCA alone) in the postoperative period. The primary outcome is the Sum of Pain Intensity Difference over 8 hours (SPID-8 postdose). Participants receive VVZ-149 for 8 hours postoperatively to the primary study end point, after which they continue to be assessed for up to 24 hours. We measure opioid consumption, record pain intensity and pain relief, and evaluate the number of rescue doses and requests for opioid. To assess safety, we record sedation, nausea and vomiting, respiratory depression, laboratory tests and ECG readings after study drug administration. We evaluate for possible confounders of analgesic response, such as anxiety, depression and catastrophising behaviours. The study will also collect blood sample data and evaluate for pharmacokinetic and pharmacodynamic relationships. ETHICS AND DISSEMINATION: Ethical approval of the study protocol has been obtained from Institutional Review Boards at the participating institutions. Trial results will be disseminated through scientific conference presentations and by publication in scientific journals. TRIAL REGISTRATION NUMBER: NCT02489526; pre-results.

Increasing patient knowledge on the proper usage of a PCA machine with the use of a post-operative instructional card.

OBJECTIVES: The purpose of this study was to see if an instructional card, attached to the PCA machine following total hip arthroplasty describing proper use of the device, would positively affect subjects' understanding of device usage, pain scores, pain medication consumption and satisfaction. METHODS: Eighty adults undergoing total hip replacements who had been prescribed PCA were randomized into two study groups. Forty participants received the standard post-operative instruction on PCA device usage at our institution. The other 40 participants received the standard of care in addition to being given a typed instructional card immediately post-operatively, describing proper PCA device use. This card was attached to the PCA device during their recovery period. On post-operative day one, each patient completed a questionnaire on PCA usage, pain scores and satisfaction scores. RESULTS: The pain scores in the Instructional Card group were significantly lower than the Control group (p = 0.024). Subjects' understanding of PCA usage was also improved in the Instructional Card group for six of the seven questions asked. CONCLUSION: The findings from this study strongly support that postoperative patient information on proper PCA use by means of an instructional card improves pain control and hence the overall recovery for patients undergoing surgery. In addition, through improved understanding it adds an important safety feature in that patients and potentially their family members and/or friends may refrain from PCA-by-proxy. This article demonstrates that the simple intervention of adding an instructional card to a PCA machine is an effective method to improve patients' knowledge as well as pain control and potentially increase the safety of the device use.