-
Journal of the American Board of Family... Jun 2024The 2022 Centers for Disease Control's "Clinical Practice Guidelines for Prescribing Opioids for Pain in United States" called for attention and action toward reducing...
BACKGROUND
The 2022 Centers for Disease Control's "Clinical Practice Guidelines for Prescribing Opioids for Pain in United States" called for attention and action toward reducing disparities in untreated and undertreated pain among Black and Latino patients. There is growing evidence for controlled substance safety committees (CSSC) to change prescribing culture, but few have been examined through the lens of health equity. We examined the impact of a primary care CSSC on opioid prescribing, including by patients' race and sex.
METHODS
We conducted a retrospective cohort study. Our primary outcome was a change in prescribed morphine milligram equivalents (MME) at baseline (2017) and follow-up (2021). We compared the differences in MME by race and sex. We also examined potential intersectional disparities. We used paired test to compare changes in mean MME's and logistic regression to determine associations between patient characteristics and MME changes.
RESULTS
Our cohort included 93 patients. The mean opioid dose decreased from nearly 200 MME to 136.1 MME, . Thirty percent of patients had their dose reduced to under 90 MME by follow-up. The reduction rates by race or sex alone were not statistically significant. There was evidence of intersectional disparities at baseline. Black women were prescribed 88.5 fewer MME's at baseline compared with their White men counterparts, .
DISCUSSION
Our findings add to the previously documented success of CSSCs in reducing opioid doses for chronic nonmalignant pain to safer levels. We highlight an opportunity for primary care based CSSCs to lead the efforts to identify and address chronic pain management inequities.
PubMed: 38942449
DOI: 10.3122/jabfm.2023.230220R2 -
Journal of Clinical Anesthesia Jun 2024HR18034, composed of the ropivacaine encapsulated in multi-lamellar, concentric circular structure liposomes as the major component and a small amount of free...
Evaluating the efficacy and safety of perianal injection of liposomal ropivacaine HR18034 for postoperative analgesia following hemorrhoidectomy: A multicenter, randomized, double-blind, controlled phase II clinical trial.
STUDY OBJECTIVE
HR18034, composed of the ropivacaine encapsulated in multi-lamellar, concentric circular structure liposomes as the major component and a small amount of free ropivacaine, has performed well in animal experiments and phase I clinical trials. This trial was to investigate the efficacy, safety, pharmacokinetic profile and the minimum effective dose of HR18034 for postoperative analgesia after hemorrhoidectomy compared with ropivacaine.
DESIGN
A multicenter, randomized, double-blind trial.
SETTING
19 medical centers in China.
PATIENTS
85 patients undergoing hemorrhoidectomy between October 2022 to November 2022.
INTERVENTIONS
Patients were randomly divided into HR 18034 190 mg group, 285 mg group, 380 mg group and ropivacaine 75 mg group, receiving single local anesthetic perianal injection for postoperative analgesia.
MEASUREMENTS
The primary outcome was the area under the resting state NRS score -time curve within 72 h after injection. The second outcomes included the proportion of patients without pain, the proportion of patients not requiring rescue analgesia, cumulative morphine consumption for rescue analgesia, etc. Safety was evaluated by adverse events incidence and plasma ropivacaine concentrations were measured to explore the pharmacokinetic characteristics of HR18034.
MAIN RESULTS
The areas under the NRS score (at rest and moving states)-time curve were significantly lower in HR 18034 380 mg group than ropivacaine 75 mg at 24 h, 48 h, and 72 h after administration. However, this superiority was not observed in HR18034 190 mg group and 285 mg group. There was no difference in cumulative morphine consumption for rescue analgesia between HR 18034 groups and ropivacaine group.
CONCLUSIONS
HR 18034 380 mg showed superior analgesic efficacy and equivalent safety compared to ropivacaine 75 mg after hemorrhoidectomy, thus preliminarily determined as minimum effective dose.
PubMed: 38941870
DOI: 10.1016/j.jclinane.2024.111524 -
Medicine Jun 2024Combining hydromorphone with ropivacaine in ultrasound-guided erector spinae plane blocks enhances postoperative analgesia and reduces interleukin-6 expression in breast... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Combining hydromorphone with ropivacaine in ultrasound-guided erector spinae plane blocks enhances postoperative analgesia and reduces interleukin-6 expression in breast surgery patients.
METHODS
In this study, breast cancer patients undergoing modified radical mastectomy were randomized into 3 groups for anesthesia (30 patients in each group): standard general (group C), Erector Spinae Plane Block (ESPB) with ropivacaine (group R), and ESPB with ropivacaine plus hydromorphone (group HR). Diagnosis: Breast cancer patients. Postsurgery, pain levels, IL-6, anesthetic doses, additional analgesia needs, and recovery milestones were compared to evaluate the efficacy of the ESPB enhancements.
RESULTS
The 3 groups were not significantly different in baseline characteristics, operation time, number of cases with postoperative nausea, and serum IL-6 concentrations at T1 (the time of being returned to the ward after surgery). At T2 (at 6:00 in the next morning after surgery), the serum IL-6 concentration in group HR was significantly lower than that in groups R and C (P < .05); the intraoperative doses of remifentanil, sufentanil, and propofol were significantly lower in groups HR and R than those in group C (P < .05); Groups HR and R had significantly lower visual analog scale scores at T3 (4 hours postoperatively), T4 (12 hours postoperatively), and T5 (24 hours postoperatively) than those in group C (P < .05); the proportions of patients receiving postoperative remedial analgesia were significantly lower in groups HR and R than in group C (P < .05); groups HR and R had significantly lower proportions of patients with postoperative nausea than group C (P < .05); the time to the first anal exhaust and the time to the first ambulation after surgery were significantly shorter in groups HR and R than those in group C (P < .05).
CONCLUSION
Hydromorphone combined with ropivacaine for ESPB achieved a greater postoperative analgesic effect for patients receiving MRM under general anesthesia. The combined analgesia caused fewer adverse reactions and inhibited the expression level of the inflammatory factor IL-6 more effectively, thereby facilitating postoperative recovery. ESPB using hydromorphone with ropivacaine improved pain control post-MRM, reduced adverse effects, and more effectively suppressed IL-6, enhancing recovery.
Topics: Humans; Ropivacaine; Female; Hydromorphone; Middle Aged; Nerve Block; Pain, Postoperative; Prospective Studies; Anesthetics, Local; Breast Neoplasms; Mastectomy, Modified Radical; Analgesics, Opioid; Adult; Interleukin-6; Paraspinal Muscles; Ultrasonography, Interventional; Drug Therapy, Combination; Pain Measurement
PubMed: 38941366
DOI: 10.1097/MD.0000000000038758 -
Anesthesia and Analgesia Jun 2024The aim of this study was to determine the incidence of missed compartment syndrome in tibia fractures treated with and without regional anesthesia.
BACKGROUND
The aim of this study was to determine the incidence of missed compartment syndrome in tibia fractures treated with and without regional anesthesia.
METHODS
A retrospective chart review was performed of patients with operative tibial shaft or plateau fractures at a single level-one trauma hospital between January 2015 and April 2022 with a minimum of 3-month follow-up. Patients under 18 years of age, an ipsilateral knee dislocation, known neurologic injury at presentation, or prophylactic fasciotomy were excluded. We defined missed acute compartment syndrome (ACS) as a postinjury motor deficit still present at the 3-month postoperative appointment. For patients that received a peripheral nerve block, we recorded whether a continuous perineural catheter or one-time single-shot injection was performed, and the number of nerves blocked. Incidence rates for ACS were calculated with exact binomial 95% confidence intervals (CIs). Morphine milligram equivalents (MMEs) consumed 24 hours after surgery, use of nerve block, nerve block timing, and type of block were compared using Mann-Whitney and Kruskal-Wallis nonparametric tests. Statistical significance was defined as P < .05.
RESULTS
The incidence of compartment syndrome diagnosed and treated during index hospitalization was 2.2% (17/791, 95% CI, 1.3%-3.4%). The incidence of missed ACS was 0.9% (7/791, 95% CI, 0.4%-1.8%). The incidence of missed ACS was not different between those who received nerve block 0.7% (4/610, 95% CI, 0.2%-1.7%), and those who did not (1.7% (3/176, 95% CI, 0.4%-4.8%) P = .19). Within patients receiving a nerve block, all patients with missed ACS (n = 4) received a perineural catheter. Similar missed ACS rates were observed between tibial shaft and plateau fractures. Patients receiving a nerve block had lower MME compared to those who did not receive a nerve block (P < .001).
CONCLUSIONS
The results do not provide evidence that perioperative regional anesthesia increases the incidence of missed ACS in patients with operative tibial shaft or plateau injuries. but does decrease postoperative opioid requirements.
PubMed: 38941266
DOI: 10.1213/ANE.0000000000007084 -
Neuropharmacology Jun 2024The direct blockade of CB cannabinoid receptors produces therapeutic effects as well as adverse side-effects that limit their clinical potential. CB negative allosteric...
The direct blockade of CB cannabinoid receptors produces therapeutic effects as well as adverse side-effects that limit their clinical potential. CB negative allosteric modulators (NAMs) represent an indirect approach to decrease the affinity and/or efficacy of orthosteric cannabinoid ligands or endocannabinoids at CB. We recently reported that GAT358, a CB-NAM, blocked opioid-induced mesocorticolimbic dopamine release and reward via a CB-allosteric mechanism of action. Whether a CB-NAM dampens opioid-mediated therapeutic effects such as analgesia or alters other unwanted opioid side-effects remain unknown. Here, we characterized the effects of GAT358 on nociceptive behaviors in the presence and absence of morphine in male rats. We examined the impact of GAT358 on formalin-evoked pain behavior and Fos protein expression, a marker of neuronal activation, in the lumbar spinal cord. We also assessed the impact of GAT358 on morphine-induced slowing of colonic transit, tolerance, and withdrawal behaviors in male mice. GAT358 attenuated morphine antinociceptive tolerance without blocking acute antinociception and reduced morphine-induced slowing of colonic motility without impacting fecal boli production. GAT358 also produced antinociception in the presence and absence of morphine in the formalin model of inflammatory nociception and reduced the number of formalin-evoked Fos protein-like immunoreactive cells in the lumbar spinal cord. Finally, GAT358 mitigated the somatic signs of naloxone-precipitated, but not spontaneous, opioid withdrawal following chronic morphine dosing. Our results support the therapeutic potential of CB-NAMs as novel drug candidates aimed at preserving opioid-mediated analgesia while preventing their unwanted side-effects. Our studies also uncover previously unrecognized antinociceptive properties associated with arrestin-biased CB-NAMs.
PubMed: 38936657
DOI: 10.1016/j.neuropharm.2024.110052 -
Journal of Perianesthesia Nursing :... Jun 2024The perioperative use of gabapentin has been suggested to reduce postoperative pain and opioid consumption. However, there is a variation in clinical practice, the type...
PURPOSE
The perioperative use of gabapentin has been suggested to reduce postoperative pain and opioid consumption. However, there is a variation in clinical practice, the type of surgery and the administration time seem to be distinct between the available studies. We assess whether gabapentin administered before surgery reduces postoperative pain in patients who have undergone inguinal hernioplasty.
DESIGN
This is a double-blind, randomized, and placebo-controlled trial.
METHODS
Seventy-seven patients scheduled for inguinal hernioplasty were randomized in two groups to receive gabapentin (900 mg) or placebo in the perioperative period. The primary outcome was analgesia measured by visual analog scale up to 30 days after surgery. The secondary outcomes such as morphine consumption, nausea, headache, and sedation have been also described.
FINDINGS
Patients who received gabapentin had lower postoperative pain scores compared to the control group, P < .001. The postoperative morphine use was significantly lower in the gabapentin (5.3%) versus placebo group (74.4%), P < .001. No significant difference between groups was observed for the occurrence of adverse events.
CONCLUSIONS
The perioperative administration of gabapentin was effective in reducing postoperative pain and had an important effect in decreasing morphine use. Together, our data reveal a long-lasting opioid-sparing effect of gabapentin in patients who underwent inguinal hernioplasty.
PubMed: 38935013
DOI: 10.1016/j.jopan.2024.01.018 -
Acta Anaesthesiologica Scandinavica Jun 2024Inadequate pain relief with moderate to severe pain remains a challenge after cesarean section and may significantly impair postoperative recovery. However, detailed...
BACKGROUND
Inadequate pain relief with moderate to severe pain remains a challenge after cesarean section and may significantly impair postoperative recovery. However, detailed assessment on the timing of severe pain, opioid consumption, influence on activities such as mobilization, breastfeeding, and caring for the infant are difficult to conduct, especially after discharge. Short message services (SMS)-based questionnaires may offer a low-cost way of providing such data but with the risk of insufficient response rates. We assessed the feasibility of collecting detailed, prospective data on postoperative pain and recovery during the initial hours and days following cesarean section using SMS-based questionnaires.
METHODS
Prospective Danish single-center cohort study involving elective cesarean sections under spinal anesthesia with fentanyl and bupivacaine. The postoperative pain regimen consisted of paracetamol, NSAID and oral morphine by request. Patients received an SMS-based questionnaire at 6, 12, 18, 24, and 48 h postoperatively, as well as on days 7 and 30.
PRIMARY OUTCOME
Response rate and time from receiving the SMS to completion of the questionnaires.
SECONDARY OUTCOMES
Opioid consumption and Patient Reported Outcomes Measures on pain and recovery.
RESULTS
From December 2022 to June 2023; 100 patients were included. The response rate was 78% at 6 h postoperatively, decreasing to 63% at 24 h. The median response time from receiving to answering the SMS-based questionnaire at 6 h after cesarean section was 23 min (IQR 2-72), decreasing to 20 min (IQR 2-78) after 24 h. Severe pain, corresponding to a Numeric Rating Scale (NRS) score >6, was reported by 57% (95% CI 65-84) at 6 h, decreasing to 28% (95% CI 34-58) at 24 h. Median opioid consumption within the first 24 h was 30 mg (IQR 20-50).
CONCLUSION
SMS-based questionnaires on Patient Reported Outcome Measures are a feasible and cost-effective way of prospectively collecting frequent data with acceptable response rates, even shortly after cesarean section. Secondarily 66% of patients reported severe pain during the first 24 h following cesarean section, with the highest pain scores within the initial 12 h. Future studies should focus on optimizing pain-management within this timeframe.
PubMed: 38934683
DOI: 10.1111/aas.14477 -
Journal of Pediatric Orthopedics Jun 2024Posterior spinal fusion (PSF) and hip reconstruction are commonly indicated surgeries in children with cerebral palsy (CP), particularly those functioning at GMFCS...
BACKGROUND
Posterior spinal fusion (PSF) and hip reconstruction are commonly indicated surgeries in children with cerebral palsy (CP), particularly those functioning at GMFCS levels IV and V. These are large and often painful procedures, and previous literature suggests that hip surgery is more painful than spine surgery in this patient population. The purpose of this study is to investigate pain scores and opioid use following hip and spine surgery in a large cohort of children with CP, including many patients who have undergone both types of surgery.
METHODS
A retrospective chart review was performed to identify children with CP who underwent hip reconstruction and/or PSF at a tertiary children's hospital between 2004 and 2022. Charts were reviewed for demographic data, pain scores, pain medication usage, duration of hospital stay, and complications.
RESULTS
Data were collected for 200 patients (101 male, 99 female) who met inclusion criteria. Eighty-seven patients underwent hip reconstruction, 62 spinal fusion, and 51 both hip and spine surgery asynchronously. Median (interquartile range) age at the time of surgery was significantly older for spinal fusion compared with hip surgery [13.1 (4.9) vs. 8.1 (5.7) y, P<0.0001]. Length of stay was significantly longer after PSF, with a median of 6 (4) days compared with 2 (1) days after hip surgery (P<0.0001). Both maximum and average daily pain scores were similar following hip and spine surgery, with the exception that average pain scores for hip surgery were slightly higher on postoperative day 1, hip=1.73 vs. spine=1.0 (P<0.0001). The amount of opioids used, expressed as morphine milligram equivalents (MME)/kg were similar in the hip and spine surgery groups; however, it was significantly lower in the hip surgery group on postoperative day 0, hip=0.06 versus spine=0.17 (P<0.0001). For the 51 patients who underwent both hip and spine surgery, the amount of opioids used mirrored that for the entire group (similar MME/kg, though only statistically significantly less on POD 0 and 3), and pain scores were not significantly different between the 2 groups except in 2 circumstances. The 2 exceptions in these 51 patients both demonstrated lower pain scores in patients after hip surgery, including lower maximum pain scores on POD 1 (P=0.041), and lower average pain scores on POD3 (P=0.043).
CONCLUSIONS
This is the largest series to date comparing postoperative pain in children with CP after hip and spine surgery, including 51 of 200 patients who underwent both types of surgery. The results of this study demonstrate that hip surgery is not more painful than spine surgery in children with CP, and conflict with the traditional belief that hip surgery is more painful. This is important information for health care providers when counseling patients and families regarding these surgeries in children with CP.
LEVEL OF EVIDENCE
Level 3.
PubMed: 38934603
DOI: 10.1097/BPO.0000000000002762 -
IBRO Neuroscience Reports Dec 2024First-line pharmacotherapy for peripheral neuropathic pain (NP) of diverse pathophysiology consists of antidepressants and gabapentinoids, but only a minority achieve...
First-line pharmacotherapy for peripheral neuropathic pain (NP) of diverse pathophysiology consists of antidepressants and gabapentinoids, but only a minority achieve sufficient analgesia with these drugs. Opioids are considered third-line analgesics in NP due to potential severe and unpredictable adverse effects in long-term use. Also, opioid tolerance and NP may have shared mechanisms, raising further concerns about opioid use in NP. We set out to further elucidate possible shared and separate mechanisms after chronic morphine treatment and oxaliplatin-induced and diabetic polyneuropathies, and to identify potential diagnostic markers and therapeutic targets. We analysed thermal nociceptive behaviour, the transcriptome of dorsal root ganglia (DRG) and the metabolome of cerebrospinal fluid (CSF) in these three conditions, in rats. Several genes were differentially expressed, most following oxaliplatin and least after chronic morphine treatment, compared with saline-treated rats. A few genes were differentially expressed in the DRGs in all three models (e.g. and ). Some, e.g. were differentially expressed in both diabetic and oxaliplatin models. Other differentially expressed genes were associated with nociception, inflammation, and glial cells. The CSF metabolome was most significantly affected in the diabetic rats. Interestingly, we saw changes in nicotinamide metabolism, which has been associated with opioid addiction and withdrawal, in the CSF of morphine-tolerant rats. Our results offer new hypotheses for the pathophysiology and treatment of NP and opioid tolerance. In particular, the role of nicotinamide metabolism in opioid addiction deserves further study.
PubMed: 38933596
DOI: 10.1016/j.ibneur.2024.05.006 -
Plants (Basel, Switzerland) Jun 2024The goal of this study was to clarify the role of capsule size and morphology in the alkaloid yield of poppy. In 2023, two industrial varieties from large-scale...
The goal of this study was to clarify the role of capsule size and morphology in the alkaloid yield of poppy. In 2023, two industrial varieties from large-scale cultivation were investigated. Three classes of capsule size (large, medium, and small) and four organelles (wall, placenta, disc, and thalamus) of the seedless capsule were studied for their mass proportions and alkaloid contents. In 'Meara', large capsules had 41% lower total alkaloid levels than smaller ones. In 'Morgana', there was no difference in total alkaloids between size groups, but large capsules had higher contents of codeine and thebaine. Among the four organelles, the wall represented the largest mass in both varieties (60-67%), while the disc and the thalamus gave the lowest proportions (below 9%). In the variety 'Meara', the highest alkaloid contents appeared in the wall (2.69% d.w.), followed by the placenta, and the other two parts. 'Morgana' accumulated the highest alkaloid content (3.72% d.w.) in the placenta. Morphine follows the trend of the total content, while codeine and thebaine may differ. Accurate information on the accumulation of alkaloids in the generative organs may contribute to increasing effectiveness in target-oriented breeding and optimization of cultivation with an appropriate choice of variety.
PubMed: 38931072
DOI: 10.3390/plants13121640