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Experimental Biology and Medicine... Nov 2023The opioid epidemic has become a serious national crisis in the United States. An indepth systematic analysis of opioid-related adverse events (AEs) can clarify the...
The opioid epidemic has become a serious national crisis in the United States. An indepth systematic analysis of opioid-related adverse events (AEs) can clarify the risks presented by opioid exposure, as well as the individual risk profiles of specific opioid drugs and the potential relationships among the opioids. In this study, 92 opioids were identified from the list of all Food and Drug Administration (FDA)-approved drugs, annotated by RxNorm and were classified into 13 opioid groups: buprenorphine, codeine, dihydrocodeine, fentanyl, hydrocodone, hydromorphone, meperidine, methadone, morphine, oxycodone, oxymorphone, tapentadol, and tramadol. A total of 14,970,399 AE reports were retrieved and downloaded from the FDA Adverse Events Reporting System (FAERS) from 2004, Quarter 1 to 2020, Quarter 3. After data processing, Empirical Bayes Geometric Mean (EBGM) was then applied which identified 3317 pairs of potential risk signals within the 13 opioid groups. Based on these potential safety signals, a comparative analysis was pursued to provide a global overview of opioid-related AEs for all 13 groups of FDA-approved prescription opioids. The top 10 most reported AEs for each opioid class were then presented. Both network analysis and hierarchical clustering analysis were conducted to further explore the relationship between opioids. Results from the network analysis revealed a close association among fentanyl, oxycodone, hydrocodone, and hydromorphone, which shared more than 22 AEs. In addition, much less commonly reported AEs were shared among dihydrocodeine, meperidine, oxymorphone, and tapentadol. On the contrary, the hierarchical clustering analysis further categorized the 13 opioid classes into two groups by comparing the full profiles of presence/absence of AEs. The results of network analysis and hierarchical clustering analysis were not only consistent and cross-validated each other but also provided a better and deeper understanding of the associations and relationships between the 13 opioid groups with respect to their adverse effect profiles.
Topics: Analgesics, Opioid; Bayes Theorem; Data Mining; Fentanyl; Hydrocodone; Hydromorphone; Meperidine; Oxycodone; Oxymorphone; Tapentadol; United States
PubMed: 38158803
DOI: 10.1177/15353702231211860 -
Minerva Anestesiologica Oct 2023Shivering is a common side effect after general anesthesia. Risk factors are hypothermia, young age and postoperative pain. Severe complications of shivering are rare... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
Shivering is a common side effect after general anesthesia. Risk factors are hypothermia, young age and postoperative pain. Severe complications of shivering are rare but can occur due to increased oxygen consumption. Previous systematic reviews are outdated and have summarized the evidence on the topic using only pairwise comparisons. The objective of this manuscript was a quantitative synthesis of evidence on pharmacological interventions to treat postanesthetic shivering.
EVIDENCE ACQUSITION
Systematic review and frequentist network meta-analysis using the R package netmeta. Endpoints were the risk ratio (RR) of persistent shivering at one, five and 10 minutes after treatment with saline/placebo as the comparator. Data were retrieved from Medline, Embase, Central and Web of Science up to January 2022. Eligibility criteria were: randomized, controlled, and blinded trials comparing pharmacological interventions to treat shivering after general anesthesia. Studies on shivering during or after any type of regional anesthesia were excluded as well as sedated patients after cardiac surgery.
EVIDENCE SYNTHESIS
Thirty-two trials were eligible for data synthesis, including 28 pharmacological interventions. The largest network included 1431 patients. The network geometry was two-centered with most comparisons linked to saline/placebo or pethidine. The best interventions were after one minute: doxapram 2 mg/kg, tramadol 2 mg/kg and nefopam 10 mg, after 5 minutes: tramadol 2 mg/kg, nefopam 10 mg and clonidine 150 µg and after 10 minutes: nefopam 10 mg, methylphenidate 20 mg and tramadol 1 mg/kg, all reaching statistical significance. Pethidine 25 mg and clonidine 75 µg also performed well and with statistical significance in all networks.
CONCLUSIONS
Nefopam, tramadol, pethidine and clonidine are the most effective treatments to stop postanesthetic shivering. The efficacy of doxapram is uncertain since different doses showed contradictory effects and the evidence for methylphenidate is based on a single comparison in only one network. Furthermore, both lack data on side effects. Further studies are needed to clarify the efficacy of dexmedetomidine to treat postanesthetic shivering.
Topics: Humans; Adult; Shivering; Nefopam; Clonidine; Tramadol; Network Meta-Analysis; Doxapram; Meperidine; Methylphenidate
PubMed: 37458681
DOI: 10.23736/S0375-9393.23.17410-4 -
CJEM Jun 2023The objective of this study was to synthesize indication-based evidence for NO for distress and pain in children. (Meta-Analysis)
Meta-Analysis
OBJECTIVES
The objective of this study was to synthesize indication-based evidence for NO for distress and pain in children.
STUDY DESIGN
We included trials of NO in participants 0-21 years, reporting distress or pain for emergency department procedures. The primary outcome was procedural distress. Where meta-analysis was not possible, we used Tricco et al.'s classification of "neutral" (p ≥ 0.05), "favorable," or "unfavorable" (p < 0.05, supporting NO or comparator, respectively). We used the Cochrane Collaboration's Risk of Bias tool and the Grading of Recommendations Assessment, Development, and Evaluation system to evaluate risk of bias and quality of evidence, respectively.
RESULTS
We included 30 trials. For pain using the Visual Analog Scale (0-100 mm) during IV insertion, 70% NO (delta:-16.5; 95%CI:-28.6 to -4.4; p = 0.008; three trials; I = 0%) and 50% NO plus eutectic mixture of local anesthetics (EMLA) (delta:-1.2; 95%CI:-2.1 to -0.3; p = 0.007; two trials; I = 43%) were superior to EMLA. 50% NO was not superior to EMLA (delta:-0.4; 95%CI:-1.2 to 0.3; p = 0.26; two trials; I = 15%). For distress and pain during laceration repair, NO was "favorable" versus each of SC lidocaine, oxygen, and oral midazolam but "neutral" versus IV ketamine (five trials). For distress and pain during fracture reduction (three trials), NO was "neutral" versus each of IM meperidine plus promethazine, regional anesthesia, and IV ketamine plus midazolam. For distress and pain during lumbar puncture (one trial), NO was "favorable" versus oxygen. For distress and pain during urethral catheterization (one trial), NO was "neutral" versus oral midazolam. For pain during intramuscular injection (one trial), NO plus EMLA was "favorable" versus NO and EMLA alone. Common adverse effects of NO included nausea (4.4%), agitation (3.7%), and vomiting (3.6%) AEs were less frequent with NO alone (278/1147 (24.2%)) versus NO plus midazolam (48/52 (92.3%)) and NO plus fentanyl (123/201 (61.2%)).
CONCLUSIONS
There is sufficient evidence to recommend NO plus topical anesthetic for IV insertion and laceration repair. Adverse effects are greater when combined with other sedating agents.
Topics: Child; Adolescent; Humans; Nitrous Oxide; Midazolam; Ketamine; Lacerations; Pain; Anesthetics, Local; Lidocaine, Prilocaine Drug Combination; Oxygen
PubMed: 37171705
DOI: 10.1007/s43678-023-00507-0 -
International Wound Journal Feb 2023Pain and wound after haemorrhoidectomy constantly bothered the patient's convenience. Recurrently, topical sucralfate is used to treat excoriations and burns. It is... (Meta-Analysis)
Meta-Analysis
The efficacy of topical sucralfate in improving pain and wound healing after haemorrhoidectomy procedure: A systematic review, meta-analysis, and meta-regression of randomised clinical trials.
Pain and wound after haemorrhoidectomy constantly bothered the patient's convenience. Recurrently, topical sucralfate is used to treat excoriations and burns. It is considered to enhance epidermal growth and tissue granulation, thus, alleviating patients' problems. This study evaluated topical sucralfate's feasibility, safety, and superiority after haemorrhoidectomy. We searched randomised controlled trial (RCT) studies in PubMed, Google Scholar, Europe PMC, and ClinicalTrials.gov until March 29th, 2022. We investigated the influence of topical sucralfate on pain score postoperatively (24 hours, 7 days, and 14 days), pethidine usage, diclofenac usage, and wound healing rate compared to placebo. This study was conducted following the PRISMA guidelines. This study sorted the final six studies with 439 patients underwent haemorrhoidectomy. Topical sucralfate demonstrated significant outcomes on VAS 24 hours post-operative [Std. Mean Difference -1.00 (95% CI -1.70, -0.31), P = .005], VAS 7 days post-operative [Std. Mean Difference -2.29 (95% CI -3.34, -1.25), P < .0001], VAS 14 days post-operative [Std. Mean Difference -1.88 (95% CI -2.74, -1.01), P < .0001], pethidine usage within 24 hours post-operative [Std. Mean Difference -0.62 (95% CI -0.96, -0.27), P = .0004], diclofenac usage 7 days post-operative [Std. Mean Difference -1.76 (95% CI -2.61, -0.92), P < .0001], diclofenac usage 14 days post-operative [Std. Mean Difference -1.64 (95% CI -2.38, -0.91), P < .0001], and wound healing rate at 28-day post-operative [RR 1.45 (95% CI 1.25-1.68), P < .00001]. Topical sucralfate alleviated pain, improved wound healing, and minimised the usage of pethidine and diclofenac compared to placebo.
Topics: Humans; Diclofenac; Hemorrhoidectomy; Meperidine; Pain, Postoperative; Randomized Controlled Trials as Topic; Sucralfate; Wound Healing
PubMed: 35864080
DOI: 10.1111/iwj.13901 -
European Journal of Clinical... Jun 2022Catheter-related bladder discomfort (CRBD) is a common complication of intraoperative urinary catheterization. Various studies have evaluated the efficacy of different... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
Catheter-related bladder discomfort (CRBD) is a common complication of intraoperative urinary catheterization. Various studies have evaluated the efficacy of different interventions in postoperative CRBD. The present review was performed to assess the efficacy of these interventions.
METHODS
PubMed, Embase, and CENTRAL (Cochrane Central Register of Controlled Trials) databases were systematically searched to identify randomized controlled trials (RCTs) investigating the efficacy of different drugs for the prevention of postoperative CRBD. This review evaluated the incidence and severity of CRBD after different interventions at 0, 1, 2, and 6 h postoperatively.
RESULTS
Forty-five studies including 31 different drugs were analyzed. Eleven drugs were investigated in more than two RCTs, of which dexmedetomidine, gabapentin, tolterodine, tramadol, ketamine, nefopam, oxybutynin, pregabalin, and pudendal nerve block (PNB) generally showed significantly higher efficacy than controls postoperatively. Solifenacin only showed significant efficacy compared with the control at 0 h, and intravenous lidocaine only showed significant efficacy compared with the control at 6 h. There were insufficient trials to draw conclusions regarding atropine, butylscopolamine, chlorpheniramine, clonidine, darifenacin, diphenhydramine, glycopyrrolate, intravesical bupivacaine, ketamine-haloperidol, pethidine-haloperidol, ketorolac, lidocaine-prilocaine cream, magnesium, hyoscine n-butyl bromide, oxycodone, paracetamol, parecoxib, trospium, resiniferatoxin, or amikacin. However, all but pethidine-haloperidol and chlorpheniramine showed some efficacy at various time points compared with controls.
CONCLUSION
This review suggests that dexmedetomidine, gabapentin, tolterodine, tramadol, ketamine, nefopam, oxybutynin, pregabalin, and PNB are effective in preventing postoperative CRBD. Considering the efficacy and adverse effects of all drugs, dexmedetomidine and gabapentin were ranked best.
Topics: Chlorpheniramine; Dexmedetomidine; Gabapentin; Haloperidol; Humans; Ketamine; Lidocaine; Meperidine; Nefopam; Pain, Postoperative; Pregabalin; Tolterodine Tartrate; Tramadol; Urinary Bladder; Urinary Catheters
PubMed: 35218404
DOI: 10.1007/s00228-021-03251-5 -
Journal of Obstetrics and Gynaecology... Dec 2020This systematic review and meta-analysis assessed the effectiveness and safety of camylofin compared with other antispasmodics (drotaverine, hyoscine, valethamate,... (Review)
Review
This systematic review and meta-analysis assessed the effectiveness and safety of camylofin compared with other antispasmodics (drotaverine, hyoscine, valethamate, phloroglucinol, and meperidine) in labor augmentation. A systematic literature search until March 27, 2018, was performed, and data on the cervical dilatation rate (CDR) and duration of stages of labor reported in 39 eligible articles were analyzed using a random-effects model. CDR was significantly higher (0.38 cm/h, 95% confidence interval (CI) 0.10 to 0.67, = 0.007), and the duration of the first stage of labor was significantly shorter (- 41.21 minutes, 95% CI, - 77.19 to - 5.22, = 0.02) in women receiving camylofin than those receiving other antispasmodics for labor augmentation. CDR was significantly higher with camylofin compared with valethamate (0.6 cm/h, 95% CI 0.4 to 0.9, < 0.0001) and hyoscine (20 mg) (0.5 cm/h, 95% CI 0.1 to 0.8, = 0.02). The duration of the first stage of labor was significantly shorter with camylofin compared with hyoscine (20 mg) (- 59.9 min, 95% CI, - 117.9 to - 1.8, = 0.04). However, CDR and the duration of first stage of labor were not statistically different between camylofin and drotaverine groups. The percentage of women having nausea and vomiting, cervical/vaginal tear, and postpartum hemorrhage were comparable with all antispasmodics, whereas tachycardia was least reported in women receiving camylofin (3, 2.07%) than those receiving other antispasmodics. This meta-analysis demonstrated the benefit of camylofin in labor augmentation with a faster CDR and reduction in the active first stage of labor in Indian women.
PubMed: 33417640
DOI: 10.1007/s13224-020-01343-3 -
BMC Anesthesiology Aug 2020Shivering is a common side effect in women having cesarean delivery (CD) under spinal anesthesia, which can be bothersome to the patient, and it can also interfere with... (Meta-Analysis)
Meta-Analysis
Effect of intrathecal lipophilic opioids on the incidence of shivering in women undergoing cesarean delivery after spinal anesthesia: a systematic review and bayesian network meta- analysis of randomized controlled trials.
BACKGROUND
Shivering is a common side effect in women having cesarean delivery (CD) under spinal anesthesia, which can be bothersome to the patient, and it can also interfere with perioperative monitoring. In several studies, the intrathecal (IT) addition of a lipophilic opioid to local anesthetics has been shown to decrease the incidence of shivering.
OBJECTIVE
We performed this network meta-analysis to evaluate the effects of intrathecal lipophilic opioids in preventing the incidence of shivering in patients undergoing CD.
METHODS
This review was planned according to the PRISMA for Network Meta-Analysis (PRISMA-NMA) guidelines. An English literature search of multiple electronic databases was conducted. We included randomized controlled trials (RCTs) that reported on the incidence of shivering, with study groups receiving either IT fentanyl, sufentanil, or meperidine in women undergoing CD under spinal anesthesia. Quality of the studies was assessed using the modified Oxford scoring system. Using random-effects modeling, dichotomous data were extracted and summarized using odds ratio (OR) with a 95% credible interval (CrI). Statistical analysis was conducted using R studio version 1.0.153 - Inc.
RESULTS
Twenty-one studies consisting of 1433 patients (Control group: 590 patients in twenty-one studies; Fentanyl group:199 patients in seven studies; Sufentanil group: 156 patients in five studies; Meperidine group: 488 patients in ten studies) met the inclusion criteria for this systematic review investigating the effect of intrathecal lipophilic opioids in preventing the incidence of shivering in women undergoing cesarean delivery under spinal anesthesia. Methodological validity scores ranged from 3 to 7. The Bayesian mixed network estimate showed the incidence of shivering was significantly lower with IT fentanyl (pooled odds ratio (OR): 0.13; 95% credible interval (CrI): 0.04 to 0.35; P = 0.0004) and IT meperidine (OR: 0.12; 95% CrI: 0.05 to 0.29; P < 0.00001), but not with IT sufentanil (OR: 0.37; 95% CrI: 0.11 to 1.22; P = 0.23). The IT fentanyl group had a significantly lower incidence of intraoperative discomfort [Risk Ratio (RR): 0.19; 95% CI: 0.10-0.35; P < 0.00001], the IT sufentanil group had a significantly higher incidence of pruritus (RR: 6.18; 95% CI: 1.18-32.46; P = 0.03) The IT meperidine group had a significantly lower incidence of intraoperative discomfort (2.7% vs. 13.6%; RR: 0.22; 95% CI: 0.09-0.55; P = 0.001), but there was a significant increase in nausea and vomiting (IT meperidine group vs. Control group: 42.7% vs. 19.4%; RR: 2.56; 95% CI: 1.14-5.75; P = 0.02). Meta-regression analysis based on the opioid dose and quality of the study did not impact the final inference of our result.
CONCLUSION
IT fentanyl significantly decreased the incidence of shivering in women undergoing CD under spinal anesthesia without increasing maternal adverse events, confirming that routine use in this patient population is a good choice. IT sufentanil did not decrease the incidence of shivering. IT meperidine decreased the incidence and severity of shivering, but its use was also associated with significant nausea and vomiting.
Topics: Analgesics, Opioid; Anesthesia, Obstetrical; Anesthesia, Spinal; Bayes Theorem; Cesarean Section; Female; Fentanyl; Humans; Incidence; Injections, Spinal; Network Meta-Analysis; Postoperative Nausea and Vomiting; Pregnancy; Randomized Controlled Trials as Topic; Shivering; Sufentanil
PubMed: 32847522
DOI: 10.1186/s12871-020-01116-5 -
Anesthesiology and Pain Medicine Apr 2020Spinal anesthesia is the most preferred method for cesarean section. This meta-analysis was performed to determine the effect of minimum and maximum intrathecal doses of...
CONTEXT
Spinal anesthesia is the most preferred method for cesarean section. This meta-analysis was performed to determine the effect of minimum and maximum intrathecal doses of meperidine (pethidine) [5 to 40 mg] on the maternal and newborn outcomes after cesarean section.
EVIDENCE ACQUISITION
The data were collected through the systematic search in the ISI, PubMed, Scopus, Google Scholar, Barakat, MagIran, SID, Irandoc, and EMBASE medical databases. Eighteen clinical trial studies with 1,494 patients were included.
RESULTS
Patients who had received intrathecal meperidine had experienced lower shivering, relative risk [RR] = 0.34 (95% CI = 0.23, 0.48) and longer analgesia, [standard mean difference (SMD)] = 7.67 (95% CI = 1.85, 13.49) after the surgery. Moreover, RR of nausea = 1.37 (95% CI = 1.13, 1.66), vomiting RR = 2.02 (95% CI = 1.28, 3.20), and pruritus RR = 9.26 (95% CI = 4.17, 20.58) was higher in the pethidine group than in the control group. There was no statistically significant difference in the Apgar score at one-minute RR = 0.99 (95% CI = 0.9, 1.09), at five-minute RR = 0.93 (95% CI = 0.87, 1.08), maternal hypotension RR = 1.00 (95% CI = 0.87, 1.15), and maternal sensory and motor blockade durations, SMD = -1.72 (95% CI = -3.78.0.34) and SMD = -4.38 (95% CI = -9.19, 0.44), respectively in the two pethidine and control groups.
CONCLUSIONS
Intrathecal meperidine can reduce shivering and increase the duration of postoperative analgesia, though it increases the relative risk of nausea, vomiting, and pruritus. No significant difference was found both in the Apgar score, maternal hypotension, and duration of the motor and sensory block.
PubMed: 32637349
DOI: 10.5812/aapm.100375 -
Asian Journal of Anesthesiology Sep 2019Shivering is a common postoperative complication that occurs after both general and regional anesthesia even in the cases when hypothermia during surgery has been...
Shivering is a common postoperative complication that occurs after both general and regional anesthesia even in the cases when hypothermia during surgery has been averted. Patients describe it as a highly unpleasant experience, while clinicians are concerned due to its adverse effects such as increased oxygen consumption. In this article, we present a summary of the pathophysiological mechanisms involved in postoperative shivering (POS), risk factors, and inadvertent effects. The major objective of this article was to review the existing literature on the effi ciency of various drug interventions as a prophylactic measure against POS. Since α2-adrenergic, opioid, anticholinergic, and serotonergic pathways are thought to play a role in the pathogenesis of POS, a wide variety of drugs has been investigated in this regard. Although the methodological diversity of the study designs and regimens does not support drawing defi nite conclusions, there is evidence indicating a benefi cial effect of dexmedetomidine, ketamine, tramadol, meperidine, dexamethasone, nefopam, granisetron, and ondansetron in the prevention of POS. The purpose of this review is to provide a thorough insight on various drug options and to serve as an aid for clinicians for careful analysis of the advantages and disadvantages of each regimen to decide which regimen will be ideally suited for the medical profi le of each patient.
Topics: Adrenergic alpha-2 Receptor Agonists; Humans; Nefopam; Postoperative Complications; Prospective Studies; Randomized Controlled Trials as Topic; Receptors, N-Methyl-D-Aspartate; Shivering; Tramadol
PubMed: 31842530
DOI: 10.6859/aja.201909_57(3).0002 -
Pain Physician Nov 2019Opioid medications are frequently used effectively for analgesia in acute settings, however, they are associated with dependence and addiction, and were implicated in...
BACKGROUND
Opioid medications are frequently used effectively for analgesia in acute settings, however, they are associated with dependence and addiction, and were implicated in 47,600 American fatalities in 2017. Evidence suggests that despite guidelines and professional body recommendations, acute prescribing remains highly variable. Educational interventions targeting prescribers have potential to optimize prescribing in-line with evidence-based best practice.
OBJECTIVES
To identify the objective impacts of education interventions on opioid prescribing in the acute care setting.
STUDY DESIGN
A systematic literature review.
SETTING
The electronic databases MEDLINE, Embase, and Cochrane for works published until December 31, 2018. Bibliographies of relevant studies and the gray literature were also searched.
METHODS
Databases were searched for interventional studies (clinical trials and pre- and poststudies). Studies describing an educational intervention delivered to clinicians and reporting at least one objective measure of opioid use in the acute care setting were included. Studies reporting only subjective outcomes and those focused on chronic pain or set in primary care were excluded. Two reviewers (RB, TB) extracted data and assessed the quality of included studies using the Downs and Black Tool.
RESULTS
Nine studies met inclusion criteria; all used pre- and postdesigns. Three studies described stand-alone education, and the others described multifaceted interventions. All 9 interventions significantly reduced at least one of the following: high-risk agent use including meperidine use by up to 71%; total or daily dosage of opioids at discharge, including median morphine milligram equivalence (MME) from 90 mg to 45 mg per patient; and quantity of medications such as oxycodone supplied to patients, halved in one study from 6,170 expected to 2,932 supplied tablets. No increase in pain complaints or prescription refill requests were reported in those studies assessing these outcomes. The longest study examined prescribing 15 months after education delivery, reporting sustained practice changes.
LIMITATIONS
Overall study quality was fair to poor. Significant heterogeneity in settings, patient groups, methodologies, and outcomes prevented pooled quantitative analysis. No studies examined all available opioid agents or formulations.
CONCLUSIONS
These findings support prescriber education as an effective strategy to reduce opioid use and optimize prescribing in acute settings. Further research, particularly high quality randomized studies, describing the impact of education on all available opioid formulations and total MME is required. Reviewing the existing literature has offered useful models that can be implemented to improve care with opioid prescribing in acute settings.
KEY WORDS
Opioids, education, physician education, prescriber education, opioid education, opioid prescribing, systematic review, prescriptions, prevention.
Topics: Analgesics, Opioid; Drug Prescriptions; Humans; Opioid-Related Disorders; Oxycodone; Pain; Practice Patterns, Physicians'; Primary Health Care
PubMed: 31775401
DOI: No ID Found