Association of postoperative complications with persistent post-surgical pain: a multicentre prospective cohort study.

BACKGROUND: Persistent post-surgical pain is an important and under-recognised problem that is difficult to treat. Postoperative complications have been identified as possible risk factors for persistent post-surgical pain. We conducted a secondary analysis of the Measurement of Exercise Tolerance before Surgery (METS) cohort study to characterise the association of major postoperative complications with post-surgical pain at 30 days and 1 yr after major surgery. METHODS: The analysis included 1313 participants (≥40 yr old) who had inpatient noncardiac surgery and survived for 1 yr. The co-primary outcomes were 30-day post-surgical pain and 1-yr post-surgical pain. Post-surgical pain was defined as pain or discomfort that was of moderate or severe intensity (EuroQoL-5D [EQ-5D] instrument) and unimproved compared with preoperative pain or discomfort. The principal exposure was major in-hospital complications (moderate or severe by modified Clavien-Dindo criteria). Multivariable logistic regression modelling was used to characterise the adjusted association of major complications with outcomes. RESULTS: Of the cohort, 12% (n=163) experienced major complications, 51% (n=674) reported 30-day post-surgical pain, and 42% (n=545) reported 1-yr post-surgical pain. Major complications were associated with 30-day post-surgical pain (adjusted odds ratio [aOR]=1.54; 95% confidence interval [CI], 1.05-2.23) and possibly 1-yr post-surgical pain (aOR=1.42; 95% CI, 0.98-2.06). When analyses were repeated after multiple imputation of missing covariate and outcome data, complications were associated with both 30-day and 1-yr post-surgical pain. CONCLUSIONS: Patients who developed major complications were more likely to report pain at 30 days and possibly 1 yr after surgery. Research is necessary to validate these findings and delineate underlying mechanisms.

The Association between Recent Cannabis Use and Suicidal Ideation in Adults: A Population-based Analysis of the NHANES from 2005 to 2018.

OBJECTIVE: With the increasing prevalence of cannabis use, there is a growing concern about its association with depression and suicidality. The aim of this study was to examine the relationship between recent cannabis use and suicidal ideation using a nationally representative data set. METHODS: A cross-sectional analysis of adults was undertaken using National Health and Nutrition Examination Survey data from 2005 to 2018. Participants were dichotomized by whether or not they had used cannabis in the past 30 days. The primary outcome was suicidal ideation, and secondary outcomes were depression and having recently seen a mental health professional. Multiple logistic regression was used to adjust for potential confounders, and survey sample weights were considered in the model. RESULTS: Compared to those with no recent use (n = 18,599), recent users (n = 3,127) were more likely to have experienced suicidal ideation in the past 2 weeks (adjusted odds ratio [aOR] 1.54, 95% CI, 1.19 to 2.00, P = 0.001), be depressed (aOR 1.53, 95% CI, 1.29 to 1.82, P < 0.001), and to have seen a mental health professional in the past 12 months (aOR 1.28, 95% CI, 1.04 to 1.59, P = 0.023). CONCLUSIONS: Cannabis use in the past 30 days was associated with suicidal thinking and depression in adults. This relationship is likely multifactorial but highlights the need for specific guidelines and policies for the prescription of medical cannabis for psychiatric therapy. Future research should continue to characterize the health effects of cannabis use in the general population.

Bioactive Chemical Composition of Cannabis Extracts and Cannabinoid Receptors.

Cannabis is widely used as a therapeutic drug, especially by patients suffering from psychiatric and neurodegenerative diseases. However, the complex interplay between phytocannabinoids and their targets in the human receptome remains largely a mystery, and there have been few investigations into the relationship between the chemical composition of medical cannabis and the corresponding biological activity. In this study, we investigated 59 cannabis samples used by patients for medical reasons. The samples were subjected to extraction (microwave and supercritical carbon dioxide) and chemical analyses, and the resulting extracts were assayed in vitro using the CB1 and CB2 receptors. Using a partial least squares regression analysis, the chemical compositions of the extracts were then correlated to their corresponding cannabinoid receptor activities, thus generating predictive models that describe the receptor potency as a function of major phytocannabinoid content. Using the current dataset, meaningful models for CB1 and CB2 receptor agonism were obtained, and these reveal the insignificant relationships between the major phytocannabinoid content and receptor affinity for CB1 but good correlations between the two at CB2 receptors. These results also explain the anomalies between the receptor activities of pure phytocannabinoids and cannabis extracts. Furthermore, the models for CB1 and CB2 agonism in cannabis extracts predict the cannabinoid receptor activities of individual phytocannabinoids with reasonable accuracy. Here for the first time, we disclose a method to predict the relationship between the chemical composition, including phytocannabinoids, of cannabis extracts and cannabinoid receptor responses.

Recommendations for the Prescription of Opioids at Discharge After Abdominopelvic Surgery: A Systematic Review.

Importance: The prescription of opioids at discharge after abdominopelvic surgery is variable and often excessive. A lack of guidance for abdominopelvic surgeons may explain the suboptimal nature of current prescribing practices. Objective: To systematically review existing recommendations on the prescription of opioids at discharge, the appropriate disposal of opioids, and the prevention of chronic postsurgical opioid use after abdominopelvic surgery. Evidence Review: This systematic review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. From January 2010 to December 2018, a search of MEDLINE, PsycINFO, HealthSTAR, Embase, and the difficult to locate and unpublished (ie, gray) literature was performed using a peer-reviewed strategy with variations of the terms opioid, surgery, and guideline to identify English-language documents that contained recommendations published by professional societies or health care institutions. The quality of clinical practice guidelines was assessed using the Appraisal of Guidelines Research and Evaluation II (AGREE II) tool. A descriptive synthesis of results was performed. Findings: Of 5530 citations screened, 41 full-text documents were included in the systematic review. Fifteen clinical practice guidelines were identified. AGREE II domain scores varied substantially. Identified among the 41 included documents were 98 recommended interventions for the prescription of opioids at discharge, 8 interventions for the disposal of opioids, and 8 interventions for the prevention of chronic postsurgical opioid use. Only 13 of 114 interventions (11.4%) were supported by an assessment of strength or level of evidence, and the amount of opioid recommended after specific abdominopelvic surgical procedures varied widely between guidance documents, even for the same procedure. Conclusions and Relevance: Current guidance for the prescription of opioids at discharge after abdominopelvic surgery is heterogeneous and rarely supported by evidence. More research is needed on this topic to guide the development of future recommendations.

Consensus Statement for the Prescription of Pain Medication at Discharge after Elective Adult Surgery.

This Consensus Statement provides recommendations on the prescription of pain medication at discharge from hospital for opioid-naïve adult patients who undergo elective surgery. It encourages health care providers (surgeons, anesthesiologists, nurses/nurse practitioners, pain teams, pharmacists, allied health professionals, and trainees) to (1) use nonopioid therapies and reduce the prescription of opioids so that fewer opioid pills are available for diversion and (2) educate patients and their families/caregivers about pain management options after surgery to optimize quality of care for postoperative pain. These recommendations apply to opioid-naïve adult patients who undergo elective surgery. This consensus statement is intended for use by health care providers involved in the management and care of surgical patients. A modified Delphi process was used to reach consensus on the recommendations. First, the authors conducted a scoping review of the literature to determine current best practices and existing guidelines. From the available literature and expertise of the authors, a draft list of recommendations was created. Second, the authors asked key stakeholders to review and provide feedback on several drafts of the document and attend an in-person consensus meeting. The modified Delphi stakeholder group included surgeons, anesthesiologists, residents, fellows, nurses, pharmacists, and patients. After multiple iterations, the document was deemed complete. The recommendations are not graded because they are mostly based on consensus rather than evidence.

Cette déclaration de consensus fait des recommandations pour la prescription d'analgésiques à la sortie de l'hôpital pour les patients adultes n'ayant jamais pris d'opiacés et qui subissent une intervention chirurgicale non urgente. Elle encourage les prestataires de soins de santé (chirurgiens, anesthésiologistes, infirmières et infirmiers, infirmières et infirmiers praticiens, équipes antidouleur, pharmaciens, professionnels de la santé et stagiaires) à (1) utiliser des traitements non opiacés et à réduire la prescription d'opiacés afin de réduire le nombre de pilules opiacées pouvant être détournées; et (2) à éduquer les patients, ainsi que leurs familles et soignants, sur les options de prise en charge de la douleur après l'opération afin d'optimiser la qualité des soins pour la douleur postopératoire.Ces recommandations s'appliquent aux patients adultes n'ayant jamais pris d'opioïdes et qui subissent une intervention chirurgicale non urgente. Cette déclaration de consensus est destinée à être utilisée par les prestataires de soins de santé impliqués dans la prise en charge des patients opérés et les soins qui leur sont apportés.Un processus Delphi modifié a été utilisé pour parvenir à un consensus sur les recommandations. Tout d'abord, les auteurs ont procédé à une de la portée de la littérature afin de déterminer les pratiques exemplaires actuelles et les lignes directrices existantes. À partir de la littérature disponible et de l'expertise des auteurs, une liste provisoire de recommandations a été créée. Ensuite, les auteurs ont demandé aux principales parties prenantes d'examiner et de commenter plusieurs versions préliminaires du document et d'assister à une réunion de consensus en personne. Le groupe des parties prenantes du processus Delphi modifié comprenait des chirurgiens, des anesthésiologistes, des résidents, des fellows, des infirmières et infirmiers, des pharmaciens et des patients. Après de multiples itérations, le document a été jugé complet. Les recommandations n'ont pas été notées car elles étaient fondées sur un consensus plutôt que sur des données probantes.

A Systematic Review of Behavioral Interventions to Decrease Opioid Prescribing After Surgery.

OBJECTIVE: The aim of this study was to summarize strategies to reduce postsurgical opioid prescribing at discharge. SUMMARY BACKGROUND DATA: Current practices for the prescription of opioids at discharge after surgery are highly variable and often excessive. We conducted a systematic review to identify behavioral interventions designed to improve these practices. METHODS: We searched MEDLINE, EMBASE, CINAHL, and PsycINFO until December 14, 2018 to identify studies of behavioral interventions designed to decrease opioid prescribing at discharge among adults undergoing surgery. Behavioral interventions were defined according to the Cochrane Effective Practice and Organisation of Care (EPOC) taxonomy. We assessed the risk of bias of included studies using criteria suggested by Cochrane EPOC and the Newcastle-Ottawa scale. RESULTS: Of 8048 citations that were screened, 24 studies were included in our review. Six types of behavioral interventions were identified: local consensus-based processes (18 studies), patient-mediated interventions (2 studies), clinical practice guidelines (1 study), educational meetings (1 study), interprofessional education (1 study), and clinician reminder (1 study). All but one study reported a statistically significant decrease in the amount of opioid prescribed at discharge after surgery, and only 2 studies reported evidence of increased pain intensity. Reductions in prescribed opioids ranged from 34.4 to 212.3 mg morphine equivalents. All studies were found to have medium-to-high risks of bias. CONCLUSIONS: We identified 6 types of behavioral strategies to decrease opioid prescription at discharge after surgery. Despite the risk of bias, almost all types of intervention seemed effective in reducing opioid prescriptions at discharge after surgery without negatively impacting pain control.

Smoking, Pain Intensity, and Opioid Consumption 1-3 Months After Major Surgery: A Retrospective Study in a Hospital-Based Transitional Pain Service.

Introduction: The present study investigated the associations between smoking, pain, and opioid consumption in the 3 months after major surgery in patients seen by the Transitional Pain Service. Current smoking status and lifetime pack-years were expected to be related to higher pain intensity, more opioid use, and poorer opioid weaning after surgery. Methods: A total of 239 patients reported smoking status in their presurgical assessment (62 smokers, 92 past smokers, and 85 never smokers). Pain and daily opioid use were assessed in hospital before postsurgical discharge, at first outpatient visit (median of 1 month postsurgery), and at last outpatient visit (median of 3 months postsurgery). Pain was measured using numeric rating scale. Morphine equivalent daily opioid doses were calculated for each patient. Results: Current smokers reported significantly higher pain intensity (p < .05) at 1 month postsurgery than never smokers and past smokers. Decline in opioid consumption differed significantly by smoking status, with both current and past smokers reporting a less than expected decline in daily opioid consumption (p < .05) at 3 months. Decline in opioid consumption was also related to pack-years, with those reporting higher pack-years having a less than expected decline in daily opioid consumption at 3 months (p < .05). Conclusions: Smoking status may be an important modifiable risk factor for pain intensity and opioid use after surgery. Implications: In a population with complex postsurgical pain, smoking was associated with greater pain intensity at 1 month after major surgery and less opioid weaning 3 months after surgery. Smoking may be an important modifiable risk factor for pain intensity and opioid use after surgery.

Cannabis sativa (Hemp) Seeds, Δ9-Tetrahydrocannabinol, and Potential Overdose.

Introduction:Cannabis sativa (hemp) seeds are popular for their high nutrient content, and strict regulations are in place to limit the amount of potentially harmful phytocannabinoids, especially Δ9-tetrahydrocannabinol (Δ9-THC). In Canada, this limit is 10 µg of Δ9-THC per gram of hemp seeds (10 ppm), and other jurisdictions in the world follow similar guidelines. Materials and Methods: We investigated three different brands of consumer-grade hemp seeds using four different procedures to extract phytocannabinoids, and quantified total Δ9-THC and cannabidiol (CBD). Discussion: We discovered that Δ9-THC concentrations in these hemp seeds could be as high as 1250% of the legal limit, and the amount of phytocannabinoids depended on the extraction procedure employed, Soxhlet extraction being the most efficient across all three brands of seeds. Δ9-THC and CBD exhibited significant variations in their estimated concentrations even from the same brand, reflecting the inhomogeneous nature of seeds and variability due to the extraction method, but almost in all cases, Δ9-THC concentrations were higher than the legal limit. These quantities of total Δ9-THC may reach as high as 3.8 mg per gram of hemp seeds, if one were consuming a 30-g daily recommended amount of hemp seeds, and is a cause for concern for potential toxicity. It is not clear if these high quantities of Δ9-THC are due to contamination of the seeds, or any other reason. Conclusion: Careful consideration of the extraction method is very important for the measurement of cannabinoids in hemp seeds.

Chemical Profiling of Medical Cannabis Extracts.

Medical cannabis has been legally available for patients in a number of countries. Licensed producers produce a variety of cannabis strains with different concentrations of phytocannabinoids. Phytocannabinoids in medical cannabis are decarboxylated when subjected to heating for consumption by the patients or when extracted for preparing cannabis derivative products. There is little understanding of the true chemical composition of cannabis extracts, changes occurring during heating of the extracts, and their relevance to pharmacological effects. We investigated the extract from a popular commercial strain of medical cannabis, prior to and after decarboxylation, to understand the chemical profiles. A total of up to 62 compounds could be identified simultaneously in the extract derived from commercial cannabis, including up to 23 phytocannabinoids. Upon heating, several chemical changes take place, including the loss of carboxylic group from the acidic phytocannabinoids. This investigation attempts to reveal the chemical complexity of commercial medical cannabis extracts and the differences in the chemical composition of the native extract and the one subjected to heat. Comprehensive chemical analyses of medical cannabis extracts are needed for standardization, consistency, and, more importantly, an informed employment of this substance for therapeutic purposes.

Acute pain trajectories and the persistence of post-surgical pain: a longitudinal study after total hip arthroplasty.

PURPOSE: The aim of this study was to explore acute movement-evoked postoperative pain intensity trajectories over the first 5 days after total hip arthroplasty (THA) and to examine how these pain trajectories are associated with pain-related outcomes 6 weeks and 6 months later. METHODS: A total of 150 adult patients [72 women (48.0 %); mean age 60.0 ± 9.2 (standard deviation) years] completed pain questionnaires preoperatively, several times daily postoperatively until hospital discharge, and 6 weeks and 6 months after surgery. RESULTS: Results showed that the best model had four different acute postoperative pain trajectories and a significant quadratic term. The trajectories varied in terms of initial pain intensity levels and rates of decline/increase in pain over the first 4 postoperative days. Significant predictors of pain trajectory membership were preoperative pain disability and anxiety as well as cumulative morphine consumption 24 h following surgery. Pain trajectories were significantly associated with levels of pain intensity and anxiety at 6 weeks but not at 6 months postoperatively. CONCLUSION: This study showed that during the postoperative period patients differed in terms of pain intensity profiles and that these differences were associated with outcomes for up to 6 weeks following surgery. Pain trajectories were not predictive of persistent postoperative pain status at 6 months. Nonetheless, these results highlight the importance of patient heterogeneity in acute postoperative pain and pain-related outcomes months after THA.

Hyperbaric Oxygen Therapy: A New Treatment for Chronic Pain?

BACKGROUND AND OBJECTIVE: Hyperbaric oxygen therapy (HBOT) is a treatment providing 100% oxygen at a pressure greater than that at sea level. HBOT is becoming increasingly recognized as a potential treatment modality for a broad range of ailments, including chronic pain. In this narrative review, we discuss the current understanding of pathophysiology of nociceptive, inflammatory and neuropathic pain, and the body of animal studies addressing mechanisms by which HBOT may ameliorate these different types of pain. Finally, we review clinical studies suggesting that HBOT may be useful in treating chronic pain syndromes, including chronic headache, fibromyalgia, complex regional pain syndrome, and trigeminal neuralgia. DATABASE AND DATA TREATMENT: A comprehensive search through MEDLINE, EMBASE, Scopus, and Web of Science for studies relating to HBOT and pain was performed using the following keywords: hyperbaric oxygen therapy or hyperbaric oxygen treatment (HBOT), nociceptive pain, inflammatory pain, neuropathic pain, HBOT AND pain, HBOT AND headache, HBOT AND fibromyalgia, HBOT AND complex regional pain syndrome, and HBOT AND trigeminal neuralgia. RESULTS: Twenty-five studies examining the role of HBOT in animal models of pain and human clinical trials were found and reviewed for this narrative review. CONCLUSIONS: HBOT has been shown to reduce pain using animal models. Early clinical research indicates HBOT may also be useful in modulating human pain; however, further studies are required to determine whether HBOT is a safe and efficacious treatment modality for chronic pain conditions.

Distinguishing problematic from nonproblematic postsurgical pain: a pain trajectory analysis after total knee arthroplasty.

The goal of this study was to follow a cohort of patients undergoing total knee arthroplasty over time to: (1) identify and describe the various pain trajectories beginning preoperatively and for up to 12 months after surgery, (2) identify baseline predictors of trajectory group membership, and (3) identify trajectory groups associated with poor psychosocial outcomes 12 months after surgery. One hundred seventy-three participants (female = 85 [49%]; mean age [years] = 62.9, SD = 6.8) completed pain and psychological questionnaires and functional performance tests preoperatively and 4 days, 6 weeks, and 3 and 12 months after total knee arthroplasty. Using growth mixture modeling, results showed that a 4-group model, with a quadratic slope and baseline pain data predicting trajectory group membership, best fit the data (Akaike information criterion = 2772.27). The first 3 pain trajectories represent various rates of recovery ending with relatively low levels of pain 12 months after surgery. Group 4, the constant high pain group, comprises patients who have a neutral or positive pain slope and do not show improvement in their pain experience over the first year after surgery. This model suggests that preoperative pain levels are predictive of pain trajectory group membership and moderate preoperative pain, as opposed to low or high pain, is a risk factor for a neutral or positive pain trajectory postoperatively. Consistent with previous studies, these results show that postoperative pain is not a homogeneous condition and point to the importance of examining intraindividual pain fluctuations as they relate to pain interventions and prevention strategies.

Acute and chronic postsurgical pain after living liver donation: Incidence and predictors.

Despite its prominence as a concern among potential surgical candidates, there is little information in the literature regarding the short- and long-term pain experience after living liver donation. We undertook a prospective study to examine (1) the nature and incidence of acute and chronic pain after living donor hepatectomy and (2) the factors associated with an increased or decreased risk of adverse pain outcomes. Before donation, a comprehensive assessment of potential predictors of acute and chronic pain outcomes was conducted; this included donors' pain expectations, psychosocial factors, medical histories, and demographic factors. Detailed data regarding pain outcomes were collected postoperatively (days 1 and 2) and again during 6- and 12-month follow-up telephone interviews. Sixty-five adults (32 females and 33 males) scheduled for donor hepatectomy participated. Substantial proportions of the donors reported a moderate-to-severe level of pain intensity (≥4 on a 0-10 scale) at rest and after movement on day 1 (42% and 74%, respectively) and day 2 (33% and 32%, respectively). Persistent postsurgical pain was reported by 31% of the donors at the 6-month follow-up and by 27% of the donors at the 12-month follow-up. Generally, this pain was mild, and pain-related life interference was minimal. Female sex, a younger age, and several predonation measures of pain-related anxiety were associated with a significantly greater risk of developing persistent postsurgical pain. In conclusion, this study has identified a subset of patients who experience persistent pain after living liver donation. Additional prospective research using larger samples of liver donors is needed to replicate this work, to obtain a more detailed account of the acute and long-term pain experience, and to determine whether targeted interventions can minimize the frequency and severity of chronic pain.

Use of preoperative antidepressants is not associated with postoperative hospital length of stay.

PURPOSE: Antidepressant medications are commonly prescribed for the treatment of depression, anxiety, and chronic pain. Their use may lead to a number of side effects with important implications in the perioperative period. Our aim was to examine the effect of preoperative antidepressant administration on post-surgical hospital length of stay (LOS) in elective non-cardiac surgery patients. DESIGN: Historical cohort study. METHODS: Demographic and preoperative data were collected by chart review for all non-cardiac surgery patients who were assessed in the preoperative consult clinic from April 2008 through February 2009. Patients were grouped according to whether or not they were taking antidepressant medications. Median length of stay was compared between patients who took antidepressants preoperatively and those who did not. RESULTS: Data were collected for 3,692 patients. Two hundred eighty-nine (7.8%) patients were taking antidepressants preoperatively. Use of antidepressants was not associated with an increased hospital LOS. The median LOS was four days both for patients who took antidepressants preoperatively (95% confidence interval [CI] 4 to 4) and for those who did not (95% CI 3 to 5) (P = 0.13). CONCLUSIONS: The preoperative use of antidepressant medications was not associated with increased postoperative hospital LOS following elective non-cardiac surgery.