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SKOPE-Study of Ketorolac vs Opioid for Pain after Endoscopy: A Double-Blinded Randomized Control Trial in Patients Undergoing Ureteroscopy.
Fedrigon, D, Faris, A, Kachroo, N, Jain, R, Elia, M, Wilkins, L, Li, J, De, S, Noble, M, Monga, M, et al
The Journal of urology. 2021;(2):373-381
Abstract
PURPOSE Pain is the leading cause of unplanned emergency department visits and readmissions after ureteroscopy, making postoperative analgesic stewardship a priority given the current opioid epidemic. We conducted a double-blinded, randomized controlled trial, with noninferiority design, comparing nonsteroidal anti-inflammatory drugs to opiates for postoperative pain control in patients undergoing ureteroscopy for urolithiasis. MATERIALS AND METHODS Patients were randomized and blinded to either oxycodone (5 mg) or ketorolac (10 mg), taken as needed, with 3 nonblinded oxycodone rescue pills for breakthrough pain. Primary study outcome was visual analogue scale pain score on postoperative days 1-5. Secondary outcomes included medication utilization, side effects, and Ureteral Stent Symptom Questionnaire scores. RESULTS A total of 81 patients were included (43 oxycodone, 38 ketorolac). The 2 groups had comparable patient, stone, and perioperative characteristics. No differences were found in postoperative pain scores, study medication or rescue pill usage, or side effects. Higher maximum pain scores on days 1-5 (p <0.05) and higher questionnaire score (28.1 vs 21.7, p=0.045) correlated with analgesic usage, irrespective of treatment group. Patients receiving ketorolac reported significantly fewer days confined to bed (mean±SD 1.3±1.3 vs 2.3±2.6, p=0.02). There was no difference in unscheduled postoperative physician encounters. CONCLUSIONS This is the first double-blinded randomized controlled trial comparing nonsteroidal anti-inflammatory drugs and opiates post-ureteroscopy, and demonstrates noninferiority of nonsteroidal anti-inflammatory drugs in pain control with similar efficacy, safety profile, physician contact and notably, earlier convalescence compared to the opioid group. This provides strong evidence against routine opioid use post-ureteroscopy, justifying continued investigation into reducing postoperative opiate prescriptions.
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Analgesic Effect of Intraoperative Intravenous S-Ketamine in Opioid-Naïve Patients After Major Lumbar Fusion Surgery Is Temporary and Not Dose-Dependent: A Randomized, Double-Blind, Placebo-Controlled Clinical Trial.
Brinck, ECV, Maisniemi, K, Kankare, J, Tielinen, L, Tarkkila, P, Kontinen, VK
Anesthesia and analgesia. 2021;(1):69-79
Abstract
BACKGROUND Severe pain often accompanies major spine surgery. Opioids are the cornerstone of postoperative pain management but their use can be limited by numerous side effects. Several studies claim that adjuvant treatment with intravenous (IV) ketamine reduces opioid consumption and pain after back surgery. However, the exact role of ketamine for this indication is yet to be elucidated. We compared 2 different doses of S-ketamine with placebo on postoperative analgesic consumption, pain, and adverse events in adult, opioid-naïve patients after lumbar fusion surgery. METHODS One hundred ninety-eight opioid-naïve patients undergoing lumbar spinal fusion surgery were recruited to this double-blind trial and randomly assigned into 3 study groups: Group C (placebo) received a preincisional IV bolus of saline (sodium chloride [NaCl] 0.9%) followed by an intraoperative IV infusion of NaCl 0.9%. Both groups K2 and K10 received a preincisional IV bolus of S-ketamine (0.5 mg/kg); in group K2, this was followed by an intraoperative IV infusion of S-ketamine (0.12 mg/kg/h), while in group K10, it was followed by an intraoperative IV infusion of S-ketamine (0.6 mg/kg/h). Postoperative analgesia was achieved by an IV patient-controlled analgesia (IV PCA) device delivering oxycodone. The primary end point was cumulative oxycodone consumption at 48 hours after surgery. The secondary end points included postoperative pain up to 2 years after surgery, adverse events, and level of sedation and confusion in the immediate postoperative period. RESULTS The median [interquartile range (IQR)] cumulative oxycodone consumption at 48 hours was 154.5 [120] mg for group K2, 160 [109] mg for group K10, and 178.5 [176] mg for group C. The estimated difference was -24 mg between group K2 and group C (97.5% confidence interval [CI], -73.8 to 31.5; P = .170) and -18.5 mg between group K10 and C (97.5% CI, 78.5-29.5; P = .458). There were no significant differences between groups.Postoperative pain scores were significantly lower in both ketamine treatment groups at the fourth postoperative hour but not later during the 2-year study period.The higher ketamine dose was associated with more sedation. Otherwise, differences in the occurrence of adverse events between study groups were nonsignificant. CONCLUSIONS Neither a 0.12 nor a 0.6 mg/kg/h infusion of intraoperative IV S-ketamine was superior to the placebo in reducing oxycodone consumption at 48 hours after lumbar fusion surgery in an opioid-naïve adult study population. Future studies should assess ketamine's feasibility in specific study populations who most benefit from reduced opioid consumption.
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Opioid Management in CKD.
Lu, E, Schell, JO, Koncicki, HM
American journal of kidney diseases : the official journal of the National Kidney Foundation. 2021;(5):786-795
Abstract
Patients with chronic kidney disease (CKD) experience a high pain and symptom burden. Concurrently, opioid prescription and use in patients with CKD continues to increase, leading to concern for opioid-related risks. Nephrologists increasingly face challenging clinical situations requiring further evaluation and treatment of pain, for which opioid use may be indicated. However, nephrologists are not commonly trained in pain management and may find it difficult to compile the necessary information and tools to effectively assess and treat potentially multidimensional pain. In these situations, they may benefit from using an evidence-based stepwise approach proposed in this article. We address current approaches to opioid use for pain management in CKD and offer a stepwise approach to individualized opioid assessment, focusing on kidney-specific concerns. This includes thorough evaluation of the pain experience, opioid use history, and treatment goals. We subsequently discuss considerations when initiating opioid therapy, strategies to reduce opioid-related risks, and recommended best practices for opioid stewardship in CKD. Using this sequential approach to opioid management, nephrologists can thereby gain a broad overview of key patient considerations, the foundation for understanding implications of opioid use, and a patient-tailored plan for opioid therapy.
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The Effects of Intraoperative Caffeine on Postoperative Opioid Consumption and Related Outcomes After Laparoscopic Surgery: A Randomized Controlled Trial.
Vlisides, PE, Li, D, McKinney, A, Brooks, J, Leis, AM, Mentz, G, Tsodikov, A, Zierau, M, Ragheb, J, Clauw, DJ, et al
Anesthesia and analgesia. 2021;(1):233-242
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Abstract
BACKGROUND Surgical patients are vulnerable to opioid dependency and related risks. Clinical-translational data suggest that caffeine may enhance postoperative analgesia. This trial tested the hypothesis that intraoperative caffeine would reduce postoperative opioid consumption. The secondary objective was to assess whether caffeine improves neuropsychological recovery postoperatively. METHODS This was a single-center, randomized, placebo-controlled trial. Participants, clinicians, research teams, and data analysts were all blinded to the intervention. Adult (≥18 years old) surgical patients (n = 65) presenting for laparoscopic colorectal and gastrointestinal surgery were randomized to an intravenous caffeine citrate infusion (200 mg) or dextrose 5% in water (40 mL) during surgical closure. The primary outcome was cumulative opioid consumption through postoperative day 3. Secondary outcomes included subjective pain reporting, observer-reported pain, delirium, Trail Making Test performance, depression and anxiety screens, and affect scores. Adverse events were reported, and hemodynamic profiles were also compared between the groups. RESULTS Sixty patients were included in the final analysis, with 30 randomized to each group. The median (interquartile range) cumulative opioid consumption (oral morphine equivalents, milligrams) was 77 mg (33-182 mg) for caffeine and 51 mg (15-117 mg) for placebo (estimated difference, 55 mg; 95% confidence interval [CI], -9 to 118; P = .092). After post hoc adjustment for baseline imbalances, caffeine was associated with increased opioid consumption (87 mg; 95% CI, 26-148; P = .005). There were otherwise no differences in prespecified pain or neuropsychological outcomes between the groups. No major adverse events were reported in relation to caffeine, and no major hemodynamic perturbations were observed with caffeine administration. CONCLUSIONS Caffeine appears unlikely to reduce early postoperative opioid consumption. Caffeine otherwise appears well tolerated during anesthetic emergence.
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New insights into molecular pathways in colorectal cancer: Adiponectin, interleukin-6 and opioid signaling.
Świerczyński, M, Szymaszkiewicz, A, Fichna, J, Zielińska, M
Biochimica et biophysica acta. Reviews on cancer. 2021;(1):188460
Abstract
Colorectal cancer (CRC) is one of the most common cause of death among neoplasms around the world. The environmental factors, like diet and obesity, are crucial in CRC pathogenesis by creating cancer-favorable microenvironment and hormonal changes. Adiponectin, the adipose tissue-specific hormone, is generally considered to negatively correlate with CRC development. The interleukin 6 (IL-6) is one of the most important pro-inflammatory cytokine connected with CRC, which is strongly inflammation-associated. The opioids are variable group substantially correlated with cancers - the endogenous opioids affect immune system and cell cycle including proliferation and cell death whereas exogenous opioids are leading clinically used analgesics in terminal cancer patients. In this review we discuss the involvement of adiponectin, IL-6 and opioids in CRC pathogenesis, their link with obesity, possible cross-talk and potential novel therapeutic approach in CRC treatment.
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The Effect of Perioperative Ketorolac Administration on Opioid Use After Hip Arthroscopy.
Cunningham, D, Lewis, B
Orthopedics. 2021;(3):e417-e421
Abstract
Patients undergoing hip arthroscopy often have postoperative pain that is managed in part with opioids. The hypothesis of this study was that administration of ketorolac at the conclusion of the case may improve postoperative pain control and reduce opioid use. This investigation was a retrospective, observational study of opioid use, pain, and time spent in the postanesthesia care unit (PACU) among opioid-naïve patients undergoing primary hip arthroscopy (Current Procedural Terminology code 29914 or 29916) for femoroacetabular impingement syndrome before and after the institution of a surgeon-driven policy to administer ketorolac at the end of the case. Baseline characteristics and perioperative ketorolac administration were recorded. Outcomes included opioids used in the PACU through discharge measured in oral morphine equivalents, time spent in the PACU, and pain reported by the patient in the PACU. Comparative statistics, including multivariable main effects linear regression modeling, were performed to determine the effect of ketorolac administration on outcomes. Patients who did not receive ketorolac consumed a median of 22.5 oral morphine equivalents in the PACU through discharge, whereas patients who received ketorolac consumed a median of 17.5 oral morphine equivalents. No significant difference was found in pain reported or time spent in the PACU through discharge, although the results favored ketorolac administration. This study showed a modest but statistically significant reduction in early postoperative opioid use among patients receiving ketorolac at closure. Ketorolac could be part of a multimodal preemptive pain management strategy to help to reduce postoperative opioid use. [Orthopedics. 2021;44(3):e417-e421.].
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Reconceptualizing non-pharmacologic approaches to Neonatal Abstinence Syndrome (NAS) and Neonatal Opioid Withdrawal Syndrome (NOWS): A theoretical and evidence-based approach. Part II: The clinical application of nonpharmacologic care for NAS/NOWS.
Velez, ML, Jordan, C, Jansson, LM
Neurotoxicology and teratology. 2021;:107032
Abstract
There has been increasing emphasis on the importance of the development of self-regulatory capacities of the individual as the cornerstone of development. The caregivers' abilities to manage their own attention, emotions, physiology and behaviors influence the development of the child's self-regulatory and interactive capacities, and thereby their overall development. Newborns prenatally exposed to psychoactive substances and/or to other prenatal stressors such as maternal poor nutrition, increased maternal stress, trauma, difficult and/or impoverished environments, in tandem with genetic predispositions, can result in alterations to their neurodevelopment that predispose them to self-regulatory problems that can be expressed at any stage of life. The care of infants with Neonatal Abstinence Syndrome (NAS)/Neonatal Opioid Withdrawal Syndrome (NOWS) and their mother/caregiver is a window of opportunity to assess the regulatory and co-regulatory capacities of both, and to provide holistic interventions with the goal of empowering the mother/caregiver in their own self-knowledge/self-regulation capacities and their crucial role in promoting the healthy development of their children. Non-pharmacologic care for the infant with NAS/NOWS is the first line of treatment and of paramount importance. Yet, current approaches are based on a limited scope of infant functioning, and the scoring systems in current use do not result in individualized and specific non-pharmacologic care of the infant, which can result in excessive or insufficient medication and a lack of caregiver appreciation for the infant's strengths, difficulties and early development. The interventions described here are based on the infant's signs of dysregulation in four neurobehavioral subsystems that can be dysregulated by NAS/NOWS, the infant's adaptive or maladaptive responses to return to a regulated functioning, and the co-regulatory behaviors of the infant and the mother/caregiver. In Part I of this two-part series on re-conceptualizing non-pharmacologic care for NAS/NOWS we laid the foundation for a new treatment approach, one grounded in developmental theory and evidence-based observations of infant and interpersonal neurobiology. Here, in Part II, we outline actionable, individually tailored evaluations and approaches to non-pharmacologic NAS/NOWS treatment based on strategies to support the regulatory capacities and development of 4 key domains: 1) autonomic; 2) motor/tone; 3) sleep/awake state control; and 4) sensory modulation subsystems.
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The effect of crocin (the main active saffron constituent) on the cognitive functions, craving, and withdrawal syndrome in opioid patients under methadone maintenance treatment.
Abbaszadeh-Mashkani, S, Hoque, SS, Banafshe, HR, Ghaderi, A
Phytotherapy research : PTR. 2021;(3):1486-1494
Abstract
Individuals under methadone maintenance treatment (MMT) programs are susceptible to several complications, including withdrawal syndrome, craving, and cognitive deficits. This study was designed to elevate the effect of crocin administration on withdrawal syndrome, craving, and cognitive function in subjects under MMT programs. It was a clinical trial that was conducted among 60 patients referred to Soltan Mirahmad Clinic for addict patients in Kashan, Iran. The patients were allocated to two groups including placebo and intervention groups. The intervention group received 30 mg/day crocin (n = 30) and placebo (n = 30) once a day, in 12 weeks. Withdrawal syndrome, craving, and cognitive function parameters were measured before and after the intervention in subjects under MMT programs. Compared with the placebo group, crocin resulted in a significant improvement in craving score (p = .03), and withdrawal symptoms score (p = .01) in the intervention group. In addition, crocin supplementation did not affect cognitive function parameters (e.g., TMT, FAS test, and DGSP score). Overall, crocin supplementation for 12 weeks to patients under MMT programs had beneficial effects on craving and withdrawal symptoms score, but did not affect the cognitive function parameters.
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Opioid Use and Misuse in Pregnancy.
Shatil, B, Landau, R
Clinics in perinatology. 2020;(4):769-777
Abstract
The rate of pregnant women with an opioid use disorder has risen drastically in the past 20 years, paralleling that in the general population. Pregnancies associated with opioid use, abuse, or dependence have significantly higher rates of complications, such as neonatal opioid withdrawal syndrome, intrauterine growth restriction, neural tube defects, stillbirth, increased maternal mortality, greater postpartum pain, and longer inpatient stays. Patient education about the risks and benefits of multimodal analgesia and empowering shared decision making may help curb the opioid epidemic. Tailoring pain management to individual needs might be the solution to the problem.
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Nutritional implications of opioid use disorder: A guide for drug treatment providers.
Chavez, MN, Rigg, KK
Psychology of addictive behaviors : journal of the Society of Psychologists in Addictive Behaviors. 2020;(6):699-707
Abstract
The number of Americans seeking treatment for opioid use disorder (OUD) continues to increase. However, there are important nutritional implications of having OUD that often get overlooked by drug treatment providers. OUDs can cause metabolic changes, constipation, and weight loss, or lead to a lifestyle that results in inadequate food intake and unhealthy eating patterns. Nutritional factors associated with OUD can also hinder treatment outcomes and recovery. Addiction providers tend to give little attention to the nutritional implications of OUD, and this knowledge is rarely incorporated into treatment plans. The goal of this article, therefore, is to summarize the existing literature on the connection between OUD and nutrition to help guide treatment programs. This article (a) describes the nutritional consequences associated with misusing opioids, (b) discusses the role that nutrition can play in OUD treatment and recovery, (c) summarizes the nutritional implications of medication treatment for OUD, and (d) recommends nutritional interventions that might aid in the treatment of OUD. This article directly fills a gap in the OUD literature and has the potential to serve as a guide for drug treatment providers to make more informed nutritional recommendations to their clients. Treatment programs may wish to consider the issues raised in this paper before launching nutritional programs at their facility. (PsycInfo Database Record (c) 2020 APA, all rights reserved).