Effects of a Single Opioid Dose on Gastrointestinal Motility in Rabbits (Oryctolagus cuniculus): Comparisons among Morphine, Butorphanol, and Tramadol

The aim of this study was to evaluate and compare the effects of single doses of butorphanol, morphine, and tramadol on gastrointestinal motility in rabbits (Oryctolagus cuniculus) using non-invasive imaging methods, such as radiographic barium follow through and ultrasonographic contraction counts. Time-lapse radiographic and ultrasound examinations were performed before and after a single intramuscular dose of 5 mg kg−1 butorphanol, 10 mg kg−1 morphine, or 10 mg kg−1 tramadol. Pyloric and duodenal contraction counts by ultrasonography and radiographic repletion scores for the stomach and caecum were analysed using a mixed linear model. No significant effect was noted on ultrasound examinations of pyloric and duodenal contractions after administration of an opioid treatment. Morphine had a significant effect on the stomach and the caecum repletion scores, whereas butorphanol had a significant effect only on the caecum repletion score. Tramadol had no significant effect on the stomach or caecum repletion scores. The present findings suggest that a single dose of 5 mg kg−1 butorphanol or 10 mg kg−1 morphine temporarily slows gastrointestinal transit in healthy rabbits, preventing physiological progression of the alimentary bolus without the induction of ileus. In contrast, a single dose of 10 mg kg−1 tramadol has no such effects.

Acupuncture for cancer pain: an evidence-based clinical practice guideline

Background This study aims to develop an evidence-based clinical practice guideline of acupuncture in the treatment of patients with moderate and severe cancer pain. Methods The development of this guideline was triggered by a systematic review published in JAMA Oncology in 2020. We searched databases and websites for evidence on patient preferences and values, and other resources of using acupuncture for treatment of cancer pain. Recommendations were developed through a Delphi consensus of an international multidisciplinary panel including 13 western medicine oncologists, Chinese medicine/acupuncture clinical practitioners, and two patient representatives. The certainty of evidence, patient preferences and values, resources, and other factors were fully considered in formulating the recommendations. The Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach was employed to rate the certainty of evidence and the strength of recommendations. Results The guideline proposed three recommendations: (1) a strong recommendation for the treatment of acupuncture rather than no treatment to relieve pain in patients with moderate to severe cancer pain; (2) a weak recommendation for the combination treatments with acupuncture/acupressure to reduce pain intensity, decrease the opioid dose, and alleviate opioid-related side effects in moderate to severe cancer pain patients who are using analgesics; and (3) a strong recommendation for acupuncture in breast cancer patients to relieve their aromatase inhibitor-induced arthralgia. Conclusion This proposed guideline provides recommendations for the management of patients with cancer pain. The small sample sizes of evidence limit the strength of the recommendations and highlights the need for additional research.

Postoperative Respiratory Compromise following Cesarean Birth: The Impact of Obesity and Systemic Opioids

Objective The aim of this study was to measure the effect of obesity and systemic opioids on respiratory events within the first 24 hours following cesarean. Methods Opioid-naive women undergoing cesarean between January 2016 and December 2017 were included in this retrospective cohort study. The primary outcome was the proportion of women experiencing at least one composite respiratory outcome (oxygen saturation less than 95% lasting 30+ seconds or need for respiratory support) within 24 hours of cesarean. The impact of obesity and total systemic opioid dose in 24 hours (measured in morphine milligram equivalents [MMEs]) on the composite respiratory compromise outcome were evaluated. Results Of 2,230 cesarean births, 790 women had at least one composite respiratory event. Predictors of the composite respiratory outcome included body mass index (BMI) as a continuous variable (odds ratio = 1.063 for every one unit increase in BMI [95% confidence interval (CI): 1.021–1.108], p = 0.003), and MME (odds ratio = 1.005 [95% CI: 1.002–1.008], p = 0.003), adjusting for magnesium sulfate use. The interaction between obesity and opioid dose demonstrated an odds ratio of 1.000 (95% CI: 0.999–1.000, p = 0.030). Conclusion The proportion of women experiencing respiratory events following cesarean birth increases with the degree of obesity and opioid dose. Key Points

Opioid use in Older Orthopedic Rehabilitation Inpatients: A Retrospective Study

Background: While there is much evidence about pain management for orthopedic patients in the immediate perioperative setting, little is known about how opioids are used during inpatient rehabilitation in the days and weeks that follow, particularly in older adults. A safe upper limit of 50 oral morphine equivalents (OME) is frequently cited in guidelines. This study’s objective is to characterize the use of opioids in an older adult population undergoing orthopedic rehabilitation. Methods: This is a retrospective observational study of adults aged ≥50 years old admitted for orthopedic rehabilitation between November 2019 and June 2021 at an academic rehabilitation hospital in Toronto, Canada. Acute care admissions preceding rehabilitation were for either a surgical or non-surgical orthopedic indication. Participants were divided into opioid-naïve individuals who received opioids, opioid-naïve individuals who did not receive opioids, and pre-existing chronic users of opioids. Demographic, clinical, and medication administration data were collected through the electronic health record and manual chart review. Average daily opioid dose for the first seven days of each stay was characterized using OME. Linear regression was used to assess for variables independently associated with opioid dose. Results: A total of 643 patients undergoing orthopedic rehabilitation were included: 125 (19.4%) involved chronic opioid users, 416 (64.7%) were opioid-naïve patients who received opioids, and 102 (15.9%) were opioid-naïve patients who did not receive opioids, with median age respectively of 72, 79, and 83. Median daily OME over the first week for chronic users was 30.3 and for opioid-naïve users was 6.9. Opioid dose was significantly positively associated with reported pain as defined by day 3 pain score and knee replacement; it was inversely associated with admission for a non-surgical indication and age. Conclusions: Opioids are frequently but heterogeneously used in older adults undergoing orthopedic rehabilitation. Median OME use in this cohort of older adults was substantially lower than the 50 OME threshold suggested in guidelines. Dedicated guidance for opioid use is warranted for this unique patient population.

“Pain Management in Intensive Care Patients, a Retrospective Observational Research.”

Background Sepsis and septic shock are the most common causes of death in non-cardiac surgery intensive care units. The treatment of sepsis is difficult. Adequate analgesia is essential for a positive outcome. There are differences in pain management between septic and non-septic patients. Septic ICU patients receive higher doses of opioids than non-septic ICU patients. Methods A retrospective observational study was carried out in an anesthesiological intensive care from 1.1.2014 to 30.6.2016. The cases were divided into four different groups according to the criteria: Sepsis “yes/no” and communication ability “yes/no”. After adjusting the number of cases by pairing method, 356 cases were recruited. The endpoint of our study was defined as the "total opioid dose". A statistical evaluation was carried out by T-tests and two-factor variance analyses. Results There is a significant difference in opioid dose between communicative and non-communicative ICU patients. The mean sufentanil dose is significantly higher in the non-communicative patients than in the communicative patients. Sepsis has no significant effect on the dose of sufentanil. Conclusion The hypothesis that sepsis decreases the pain threshold could not be proven in this study. The effect of the higher opioid requirement is not directly caused by sepsis, but by the factor of communication ability. Furthermore, we were able to show through our investigations and especially through the data of the pain recording instruments that the septic and non-septic intensive care patients receive sufficient pain therapy treatment.

Successful Strategies and Areas of Improvement–Lessons Learned from Design and Conduction of a Randomized Placebo-Controlled Trial in Palliative Care, ‘Palliative-D’

Clinical trials in palliative care are challenging to design and conduct. Burden on patients should be minimized, while gatekeeping by professionals and next-of kin needs to be avoided. Clinical deterioration due to disease progression affects attrition unrelated to intervention, and different care settings complicate comparisons and reduce the generalizability of the results. The aim of this review is to provide advice for colleagues planning to perform clinical trials in palliative care based on our own experiences from performing the Palliative-D study and by a thorough literature review on this topic. The Palliative-D study was a double-blind trial with 244 randomized patients comparing the effect of vitamin D3 to placebo in patients with advanced or metastatic cancer in the palliative phase of their disease trajectory who were enrolled in specialized palliative home care teams. Endpoints were opioid and antibiotic use, fatigue, and QoL. Recruitment was successful, but attrition rates were higher than expected, and we did not reach targeted power. For the 150 patients who completed the study, the completeness of the data was exceptionally high. Rather than patient reported pain, we choose the difference in the mean change in opioid dose between groups after twelve weeks compared to baseline as the primary endpoint. In this paper we discuss challenges in palliative care research based on lessons learned from the “Palliative-D” trial regarding successful strategies as well as areas for improvement.

Guideline adherence and reasons for recommending dose reduction in a primary care-based opioid management clinic

Background: To provide Centers for Disease Control and Prevention (CDC) guideline-recommended practices for patients on long-term opioid therapy (LTOT) including individualized decisions about opioid dose reduction, we developed the Power Over Pain (POP) Clinic.Objective: To describe frequency and reasons for opioid dose reduction and pre–post adherence to CDC guideline-recommended practices.Design: Retrospective chart review with qualitative and pre–post analysis.Patients and setting: Patients at an urban internal medicine teaching practice-prescribed LTOT were seen at POP Clinic at least once.Methods: Opioid dose reduction was defined by reduction in morphine-equivalent daily dose (MEDD) at 6 and 12 months after the first POP Clinic visit compared to baseline using paired t-tests. Among patients with a dose reduction, reasons documented in POP Clinic notes were qualitatively examined. Dichotomous measures of receiving four CDC guideline-recommended practices (controlled substance agreement [CSA], urine drug testing [UDT], prescription monitoring program review, and naloxone dispensing) at baseline versus 6 and 12 months were compared using McNemar's tests.Results: Of the 70 patients, most were female (66 percent) and Hispanic (54 percent). Forty-three patients (61 percent) had an opioid dose reduction in 12 months after the first POP Clinic visit. The most frequent reason was low or unclear benefit of continuing the current dose (49 percent). Mean MEDD was reduced from 69 mg to 57 mg at 6 months (p 0.01) and to 56 mg at 12 months (p 0.01). Completing a CSA, UDT, and naloxone distribution increased at 6 and 12 months (p 0.01). Conclusions: Individualized risk assessment in a primary care-based opioid management clinic is feasible and can result in opioid dose reduction and guideline adherence.

Time series-based bibliometric analysis of a systematic review of multidisciplinary care for opioid dose reduction: exploring the origins of the North American opioid crisis

Bibliometric analyses of systematic reviews offer unique opportunities to explore the character of specific scientific fields. In this time series-based analysis, dynamics of multidisciplinary care for chronic pain and opioid prescribing are analyzed over a forty-four year time span. Three distinct periods are identified, each defined by distinct research areas, as well as priorities regarding the use of opioids and the appropriate management of chronic pain. These scientometrically defined periods align with timelines identified previously by narrative historical accounts. Through cross-correlation with a mortality time series, a significant two-year lag between opioid overdose mortality and citation dynamics is identified between 2004 and 2019. This analysis demonstrates a bidirectional relationship between the scientific literature and the North American opioid overdose crisis, suggesting that the scientific literature is both reflective and generative of an important health and social phenomenon. A scientometric phenomenon of memory lapse, namely an overt and prolonged failure to cite older relevant literature, is identified using a metric of mean time to citation. It is proposed that this metric can be used to analyze changes in emerging literature and thus predict the nature of clinical and policy responses to the opioid crisis, and thus potentially to other health and social phenomena.