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PloS One 2024Opioids administered in hospital during the immediate postoperative period are likely to influence post-surgical outcomes, but inpatient prescribing during the admission...
BACKGROUND
Opioids administered in hospital during the immediate postoperative period are likely to influence post-surgical outcomes, but inpatient prescribing during the admission is challenging to access. Modified-release(MR) preparations have been especially associated with harm, whilst certain populations such as the elderly or those with renal impairment may be vulnerable to complications. This study aimed to assess postoperative opioid utilisation patterns during hospital stay for people admitted for major/orthopaedic surgery.
METHODS
Patients admitted to a teaching hospital in the North-West of England between 2010-2021 for major/orthopaedic surgery with an admission for ≥1 day were included. We examined opioid administrations in the first seven days post-surgery in hospital, and "first 48 hours" were defined as the initial period. Proportions of MR opioids, initial immediate-release(IR) oxycodone and initial morphine milligram equivalents (MME)/day were calculated and summarised by calendar year. We also assessed the proportion of patients prescribed an opioid at discharge.
RESULTS
Among patients admitted for major/orthopaedic surgery, 71.1% of patients administered opioids during their hospitalisation. In total 50,496 patients with 60,167 hospital admissions were evaluated. Between 2010-2017 MR opioids increased from 8.7% to 16.1% and dropped to 11.6% in 2021. Initial use of oxycodone IR among younger patients (≤70 years) rose from 8.3% to 25.5% (2010-2017) and dropped to 17.2% in 2021. The proportion of patients on ≥50MME/day ranged from 13% (2021) to 22.9% (2010). Of the patients administered an opioid in hospital, 26,920 (53.3%) patients were discharged on an opioid.
CONCLUSIONS
In patients hospitalised with major/orthopaedic surgery, 4 in 6 patients were administered an opioid. We observed a high frequency of administered MR opioids in adult patients and initial oxycodone IR in the ≤70 age group. Patients prescribed with ≥50MME/day ranged between 13-22.9%. This is the first published study evaluating UK inpatient opioid use, which highlights opportunities for improving safer prescribing in line with latest recommendations.
Topics: Humans; Analgesics, Opioid; Male; Female; Middle Aged; Aged; Retrospective Studies; Pain, Postoperative; Orthopedic Procedures; Adult; Electronic Prescribing; Inpatients; England; Hospitalization; Aged, 80 and over; Oxycodone; Adolescent
PubMed: 38917135
DOI: 10.1371/journal.pone.0305531 -
Global Spine Journal Jun 2024Meta-analysis. (Review)
Review
STUDY DESIGN
Meta-analysis.
OBJECTIVE
To compare the effectiveness of postoperative pain control between erector spinae plane block (ESPB) and thoracolumbar interfascial plane (TLIP) block in lumbar spine surgery.
METHODS
PubMed, Embase, and MEDLINE electronic databases were searched for articles containing randomized controlled trials (RCTs) published between January 1900 and January 2024. We extracted the postoperative mean pain score, the first 24-h postoperative morphine consumption, and their standard deviation from the included studies. Meta-analysis was performed using the functions available in the metafor package in R software. We pooled continuous variables using an inverse variance method with a random-effects model and summarized them as standardized mean differences.
RESULTS
Five RCTs that directly compared the ESPB and TLIP block in lumbar spine surgery were included, enrolling 432 participants randomly into the two groups with 216 participants in each group. The pooled analyses showed that there was no significant difference between the ESPB and TLIP groups in terms of lower pain scores during the early (1 h) (standardized mean difference [SMD] -1.49, 95% confidence interval [CI], -3.10; 0.11), middle (12 h) (SMD -3.12, 95% CI, -6.86; 0.61), and late (24 h) (SMD -1.38, 95% CI, -3.01; 0.24) postoperative periods. There was also no significant difference in the first 24-h postoperative morphine equivalent consumption between the ESPB and TLIP groups (SMD -0.46 mg, 95% CI -1.23; 0.31).
CONCLUSION
No significant difference was observed between the ESPB and TLIP block in terms of postoperative pain control and 24-h morphine equivalent consumption for lumbar spine surgery.
PubMed: 38914010
DOI: 10.1177/21925682241266518 -
Addiction Neuroscience Jun 2024Adolescence marks a sensitive period for neurodevelopment wherein exposure to drugs of abuse may disrupt maturation and induce persistent changes in neurophysiology...
Adolescence marks a sensitive period for neurodevelopment wherein exposure to drugs of abuse may disrupt maturation and induce persistent changes in neurophysiology which may exacerbate the risk for developing substance use disorders in adulthood. Adolescent nicotine exposure (ANE) enhances motivation to obtain drugs of abuse, particularly opioids, and increases vulnerability for the development of opioid use disorder (OUD). Here, we characterized ANE effects on learning about the adverse consequences of opioid consumption in adulthood in the absence of further nicotine administration. First, we show that ANE engenders punishment resistant fentanyl self-administration in a heterogenous seeking-taking chain schedule of reinforcement at least at the tested dose of fentanyl (0.75 μg/kg). We found that ANE rats consumed significantly more fentanyl and contingent foot shock punishment was less efficacious in limiting fentanyl seeking in ANE rats, relative to nicotine-naïve controls. Next, we demonstrated that ANE limits learning about the deleterious consequences of acute opioid intoxication in adulthood. In a combined conditioned taste avoidance and place preference paradigm we found that ANE resulted in significant reductions in the strength of morphine-induced CTA, and a simultaneous enhancement of CPP at a higher dose that was less capable of driving reinforcement in naïve controls. Finally, we examined the expression of perineuronal nets (PNNs) within insular cortex (IC) and found ANE rats to have increased density of PNNs across the anterior IC and significantly more parvalbumin-labeled IC cells relative to naïve controls. Together, these data lay the framework for a mechanistic explanation of the extreme comorbidity between nicotine use and development of OUDs.
PubMed: 38911872
DOI: 10.1016/j.addicn.2024.100150 -
Clinica Chimica Acta; International... Jun 2024The number of xylazine-involved overdose deaths tremendously increased from 2019 onwards in the US. This is due to the "tranq-dope" trend consisting in mixing opioids...
BACKGROUND AND AIMS
The number of xylazine-involved overdose deaths tremendously increased from 2019 onwards in the US. This is due to the "tranq-dope" trend consisting in mixing opioids with the sedative to reduce drug manufacturing costs and enhance their effects. In this study, we report the first fatality involving xylazine-adulterated heroin in the EU.
MATERIALS AND METHODS
The subject was a 33-year-old Caucasian male with a documented history of drug abuse who was found dead in a public area with puncture marks at the elbow. Peripheral blood and urine were collected at the autopsy and analyzed by liquid chromatography-high-resolution tandem mass spectrometry (LC-HRMS/MS) after protein precipitation.
RESULTS
6-Monoacetylmorphine, total/free morphine, and codeine blood concentrations of 20.3, 236/105, and 38.3 ng/mL, respectively, indicated recent heroin consumption. Methadone blood concentration was below 10 ng/mL. Alprazolam, nordiazepam, and flurazepam blood concentrations were 23.9, 61.4, and 55.0 ng/mL, respectively. Benzoylecgonine blood concentration was below 5 ng/mL. Xylazine blood and urine concentrations were 105 and 72.6 ng/mL, respectively.
CONCLUSION
The combination of central nervous system depressants, i.e., opioids, benzodiazepines, and xylazine, was the principal cause of death by cardiorespiratory failure. The case was promptly reported to the UE Early Warning System on drugs.
PubMed: 38909977
DOI: 10.1016/j.cca.2024.119826 -
Journal of Plastic, Reconstructive &... Jun 2024Protocols surrounding opioid reduction have become commonplace in plastic surgery to improve peri-operative outcomes. Within such protocols, opioid requirement is a... (Review)
Review
INTRODUCTION
Protocols surrounding opioid reduction have become commonplace in plastic surgery to improve peri-operative outcomes. Within such protocols, opioid requirement is a frequently analyzed outcome. Though often examined, there is no literature standard conversion for morphine milligram equivalents (MME) at present, leading to questionable external validity. We hypothesized significant heterogeneity in MME reporting would exist within plastic surgery literature.
METHODS
Following the PRISMA guidelines, the authors conducted a systematic review of 16 journals. Clinical studies focused on opioid reduction within plastic surgery were identified. Primary outcomes included reporting of morphine equivalents (ME) delivery (IV/oral), operative ME, inpatient ME, outpatient ME, timeline, and method of calculation.
RESULTS
Among the 101 studies analyzed, 73% reported opioid requirements in the form of ME. Among those that used ME, 3% reported IV ME, 41% reported oral, 32% reported both, and 25% gave no indication of either. Operative ME were reported in 19% of studies. Furthermore, 54% of studies reported inpatient ME whereas 32% of studies reported outpatient ME. Only 19% reported the number of days opioids were consumed postoperatively. Moreover, 27% of the studies reported the actual method of ME conversion, with 17 unique methods described. Only 8 studies (8%) reported using the Center for Disease Control and Prevention guidelines for ME conversion.
CONCLUSION
There is significant variability among the reported ME conversion methodology within plastic surgery literature. Highlighting these discrepancies is an essential step in creating and implementing a single, standard method to mitigate opioid morbidity in plastic surgery and to optimize enhanced recovery protocols.
PubMed: 38909598
DOI: 10.1016/j.bjps.2024.06.001 -
Redox Biology Jun 2024Morphine, a typical opiate, is widely used for controlling pain but can lead to various side effects with long-term use, including addiction, analgesic tolerance, and...
Morphine, a typical opiate, is widely used for controlling pain but can lead to various side effects with long-term use, including addiction, analgesic tolerance, and hyperalgesia. At present, however, the mechanisms underlying the development of morphine analgesic tolerance are not fully understood. This tolerance is influenced by various opioid receptor and kinase protein modifications, such as phosphorylation and ubiquitination. Here, we established a murine morphine tolerance model to investigate whether and how S-nitrosoglutathione reductase (GSNOR) is involved in morphine tolerance. Repeated administration of morphine resulted in the down-regulation of GSNOR, which increased excessive total protein S-nitrosation in the prefrontal cortex. Knockout or chemical inhibition of GSNOR promoted the development of morphine analgesic tolerance and neuron-specific overexpression of GSNOR alleviated morphine analgesic tolerance. Mechanistically, GSNOR deficiency enhanced S-nitrosation of cellular protein kinase alpha (PKCα) at the Cys78 and Cys132 sites, leading to inhibition of PKCα kinase activity, which ultimately promoted the development of morphine analgesic tolerance. Our study highlighted the significant role of GSNOR as a key regulator of PKCα S-nitrosation and its involvement in morphine analgesic tolerance, thus providing a potential therapeutic target for morphine tolerance.
PubMed: 38901102
DOI: 10.1016/j.redox.2024.103239 -
Journal of Orthopaedic Surgery (Hong... 2024Local infiltration analgesia (LIA), adductor canal block (ACB), and infiltration between the popliteal artery and the capsule of the posterior knee (IPACK) are popular...
Efficacy of adding infiltration between the popliteal artery and the capsule of the posterior knee (IPACK) to adductor canal block and local infiltration analgesia in total knee arthroplasty: A retrospective cohort study.
OBJECTIVE
Local infiltration analgesia (LIA), adductor canal block (ACB), and infiltration between the popliteal artery and the capsule of the posterior knee (IPACK) are popular multimodal analgesia techniques used during total knee arthroplasty (TKA). This study aimed to explore the efficacy of adding the IPACK technique to ACB and LIA in patients undergoing TKA.
METHODS
In this retrospective cohort study, patients who underwent primary unilateral TKA were divided into two groups based on their date of admission. Sixty-three patients underwent IPACK, ACB and LIA (IPACK group) during surgery, while 60 patients underwent ACB and LIA (control group). The primary outcome was the postoperative administration of morphine hydrochloride as a rescue analgesic. Secondary outcomes included time to first rescue analgesia, postoperative pain assessed using the visual analog scale (VAS), functional recovery assessed by knee range of motion and ambulation distance, time until hospital discharge, and complication rates.
RESULTS
The two groups were similar in average postoperative 0-to-24-h morphine consumption (11.8 mg for the control group vs 12.7 mg for the IPACK group, = .428) and average total morphine consumption (18.2 mg vs 18.0 mg, = .983) during hospitalization. There were also no significant differences in the secondary outcomes.
CONCLUSIONS
The addition of IPACK to ACB and LIA did not provide any clinical analgesic benefits. Orthopedic surgeons and anesthesiologists are justified in using ACB and LIA without IPACK for TKA.
Topics: Humans; Retrospective Studies; Arthroplasty, Replacement, Knee; Male; Female; Aged; Popliteal Artery; Nerve Block; Pain, Postoperative; Middle Aged; Analgesics, Opioid; Morphine; Anesthetics, Local; Pain Measurement; Anesthesia, Local; Analgesia; Pain Management
PubMed: 38896879
DOI: 10.1177/10225536241265445 -
Journal of Clinical Medicine May 2024: Our understanding of dexmedetomidine, as an adjuvant to nerve blocks in cancer surgery, is characterized by a current lack of compelling evidence, and it remains... (Review)
Review
: Our understanding of dexmedetomidine, as an adjuvant to nerve blocks in cancer surgery, is characterized by a current lack of compelling evidence, and it remains unknown whether the potential benefits of use outweigh the risks. The aim of the study was to evaluate the benefit and safety profiles of dexmedetomidine as an adjuvant to nerve blocks in cancer surgery. : Systematic searches were conducted in MEDLINE, ScienceDirect, Cochrane Library, Springer, medRxiv, and Scopus up to 17 May 2024. Risk ratios (RR) for binary outcomes and standardized mean differences (SMDs) for continuous outcomes were quantified. : Twenty studies were identified. In breast cancer surgery, the use of dexmedetomidine reduced 24 h total morphine consumption (SMD = -1.99 [95% CI -3.01 to -0.98], = 0.0001, I2 = 91%, random effects) and prolonged the requirement for morphine rescue analgesia (SMD = 2.98 [95% CI 0.01 to 5.95], = 0.05, I2 = 98%, random effects). In abdominal cancer surgery, the dexmedetomidine group had lower total sufentanil consumption (SMD = -1.34 [95% CI -2.29 to -0.40], = 0.005, I2 = 84%, random effects). Dexmedetomidine reduced the VAS score and decreased postoperative nausea and vomiting (PONV). No studies using dexmedetomidine reported serious adverse events. : Using dexmedetomidine as an adjuvant to nerve blocks in cancer surgery could lower the VAS pain score and prolong the regional anesthesia duration, which would lead to a decrease in total opioid consumption and possibly contribute to fewer PONV events. Furthermore, the reports of no serious adverse events indicate its good safety profile.
PubMed: 38892876
DOI: 10.3390/jcm13113166 -
Journal of Clinical Medicine May 2024Post-operative urinary retention (POUR) is a common complication following total hip arthroplasty (THA) and total knee arthroplasty (TKA). Spinal anaesthetic has been...
Post-operative urinary retention (POUR) is a common complication following total hip arthroplasty (THA) and total knee arthroplasty (TKA). Spinal anaesthetic has been associated with an increased risk of POUR, whilst other risk factors remain unclear. This study aims to identify modifiable and non-modifiable risk factors of POUR for THA and TKA patients. A single-centre retrospective cohort study of patients admitted to our hospital over the course of 6 weeks from September to October 2021 for a THA or TKA. All patients who underwent elective THA/TKA were included, and trauma cases were excluded. Ninety-two consecutive patients were included in this study. The overall rate of POUR was 17%. A shorter operative duration resulted in a reduced risk of POUR (median duration of non-retention patients, 88 min vs. 100 min POUR patients; odds ratio, 0.97; 95% CI, 0.95-0.99, = 0.018). The median bladder volume of patients with urinary retention at the point of diagnosis was 614 mL (range, 298-999 mL). The arthroplasty type, anaesthetic technique, pre-operative morphine use, body mass index, age, cardiovascular disease, and renal disease were found to have no significant association with POUR. A reduced operative time of arthroplasty surgery is associated with a decreased risk of POUR. Patients with a prolonged operative time should have an increased frequency of micturition monitoring in the immediate post-operative period.
PubMed: 38892812
DOI: 10.3390/jcm13113102 -
Animals : An Open Access Journal From... Jun 2024Noxious chemicals, coupled with morphine treatment, are often used in studies on pain in vertebrates. Here we show that injection of morphine caused several behavioural...
Noxious chemicals, coupled with morphine treatment, are often used in studies on pain in vertebrates. Here we show that injection of morphine caused several behavioural changes in the crab, , including reduced pressing against the sides of the enclosure and more rubbing and picking at the mouth parts and, at least for a short time, more defensive displays. Subsequent injection of acetic acid into one rear leg caused rubbing of the injected leg and the injected leg was held vertically off the ground. These activities directed at or involving the specific leg are consistent with previous observations of directed behaviour following noxious stimuli and are consistent with the idea that decapods experience pain. Further, acetic acid but not injection of water induced autotomy of the injected leg in these animals. Because autotomy is temporally associated with directed behaviour, it is possible that the autotomy is a pain-related response. Acetic acid is clearly a noxious substance when applied to decapods. However, morphine had no effect on the activities associated with acetic acid injection and thus there is no evidence for an analgesic effect. Further, the injection of acetic acid did not interfere with behavioural effects of morphine. The activities directed towards the site of injection are like those observed with injection, or with external application, of various noxious substances and the present study adds to a growing body of knowledge about possible pain in decapods.
PubMed: 38891753
DOI: 10.3390/ani14111705