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Journal of Palliative Medicine May 2023The objective of this systematic review is to consolidate the existing evidence on opioid use, including administration, dosing, and efficacy, for the relief of dyspnea... (Review)
Review
The objective of this systematic review is to consolidate the existing evidence on opioid use, including administration, dosing, and efficacy, for the relief of dyspnea at end of life. The overarching goal is to optimize clinical management of dyspnea by identifying patterns in opioid use, improving opioid management of dyspnea, and to prioritize future research. Opioids are commonly used in the management of dyspnea at end of life, yet specific administration guidelines are limited. A greater understanding of the effectiveness of opioids in relieving end-of-life dyspnea with consideration of study design, patients, and opioids, including dyspnea evaluation tools and outcomes, will leverage development of standardized administration and dosing. A PRISMA-guided systematic review using six databases identified quality studies of opioid management for patients with dyspnea at end of life. Twenty-three references met review inclusion criteria, which included terminally ill cancer and noncancer patients with various diagnoses. Studies included two randomized controlled trials, and three nonrandomized experimental, three prospective observational, one cross-sectional, and one case series. Thirteen retrospective chart reviews were also included due to the limited rigorous studies rendered by the search. Thirteen studies evaluated morphine, followed by fentanyl (6), oxycodone (5), general opioid use (4), and hydromorphone (2). Routes of administration were parenteral, oral, combination, and nebulization. Dyspnea was evaluated using self-reporting and non-self-reporting evaluation tools. Sedation was the most reported opioid-related adverse effect. Challenges persist in conducting end-of-life research, preventing consensus on standardization of opioid treatment for dyspnea within this specific palliative time frame. Future robust prospective trials using specific, accurate assessment with reassessment of dyspnea/respiratory distress, and consideration of opioid tolerance, polypharmacy, and comorbidities are required.
Topics: Humans; Analgesics, Opioid; Prospective Studies; Retrospective Studies; Cross-Sectional Studies; Drug Tolerance; Morphine; Dyspnea; Death; Observational Studies as Topic
PubMed: 36453988
DOI: 10.1089/jpm.2022.0311 -
Journal of Dental Research Apr 2023This study compares the effectiveness of pharmacological treatments to develop guidelines for the management of acute pain after tooth extraction. We searched Medline,... (Meta-Analysis)
Meta-Analysis
This study compares the effectiveness of pharmacological treatments to develop guidelines for the management of acute pain after tooth extraction. We searched Medline, EMBASE, CENTRAL, and US Clinical Trials registry on November 21, 2020. We included randomized clinical trials (RCTs) of participants undergoing dental extractions comparing 10 interventions, including acetaminophen, nonsteroidal anti-inflammatory drugs (NSAIDs), opioids, and combinations to placebo. After duplicate screening and data abstraction, we conducted a frequentist network meta-analysis for each outcome at 6 h (i.e., pain relief, total pain relief [TOTPAR], summed pain intensity difference [SPID], global efficacy rating, rescue analgesia, and adverse effects). We assessed the risk of bias using a modified Cochrane RoB 2.0 tool and the certainty of evidence using the Grading of Recommendations, Assessment, Development, and Evaluation approach. We implemented the analyses in RStudio version 3.5.3 and classified interventions from most to least beneficial or harmful. We included 82 RCTs. Fifty-six RCTs enrolling 9,095 participants found moderate- and high-certainty evidence that ibuprofen 200 to 400 mg plus acetaminophen 500 to 1,000 mg (mean difference compared to placebo [MDp], 1.68; 95% confidence interval [CI], 1.06-2.31), acetaminophen 650 mg plus oxycodone 10 mg (MDp, 1.19; 95% CI, 0.85-1.54), ibuprofen 400 mg (MDp, 1.31; 95% CI, 1.17-1.45), and naproxen 400-440 mg (MDp, 1.44; 95% CI, 1.07-1.80) were most effective for pain relief on a 0 to 4 scale. Oxycodone 5 mg, codeine 60 mg, and tramadol 37.5 mg plus acetaminophen 325 mg were no better than placebo. The results for TOTPAR, SPID, global efficacy rating, and rescue analgesia were similar. Based on low- and very low-certainty evidence, most interventions were classified as no more harmful than placebo for most adverse effects. Based on moderate- and high-certainty evidence, NSAIDs with or without acetaminophen result in better pain-related outcomes than opioids with or without acetaminophen (except acetaminophen 650 mg plus oxycodone 10 mg) or placebo.
Topics: Adult; Humans; Acetaminophen; Ibuprofen; Oxycodone; Network Meta-Analysis; Anti-Inflammatory Agents, Non-Steroidal; Pain, Postoperative; Analgesics, Opioid; Tooth Extraction; Acute Pain
PubMed: 36631957
DOI: 10.1177/00220345221139230 -
The Cochrane Database of Systematic... Jun 2022Many people with cancer experience moderate to severe pain that requires treatment with strong opioids, such as oxycodone and morphine. Strong opioids are, however, not... (Review)
Review
BACKGROUND
Many people with cancer experience moderate to severe pain that requires treatment with strong opioids, such as oxycodone and morphine. Strong opioids are, however, not effective for pain in all people, neither are they well tolerated by all people. The aim of this review was to assess whether oxycodone is associated with better pain relief and tolerability than other analgesic options for adults with cancer pain. This is an updated Cochrane review previously published in 2017.
OBJECTIVES
To assess the effectiveness and tolerability of oxycodone by any route of administration for pain in adults with cancer.
SEARCH METHODS
For this update, we searched the Cochrane Central Register of Controlled Trials (CENTRAL) in the Cochrane Library, MEDLINE and MEDLINE In-Process (Ovid), Embase (Ovid), Science Citation Index, Conference Proceedings Citation Index - Science (ISI Web of Science), BIOSIS (ISI), and PsycINFO (Ovid) to November 2021. We also searched four trial registries, checked the bibliographic references of relevant studies, and contacted the authors of the included studies. We applied no language, date, or publication status restrictions.
SELECTION CRITERIA
We included randomised controlled trials (parallel-group or cross-over) comparing oxycodone (any formulation or route of administration) with placebo or an active drug (including oxycodone) for cancer background pain in adults by examining pain intensity/relief, adverse events, quality of life, and participant preference.
DATA COLLECTION AND ANALYSIS
Two review authors independently sifted the search, extracted data and assessed the included studies using standard Cochrane methodology. We meta-analysed pain intensity data using the generic inverse variance method, and pain relief and adverse events using the Mantel-Haenszel method, or summarised these data narratively along with the quality of life and participant preference data. We assessed the overall certainty of the evidence using GRADE.
MAIN RESULTS
For this update, we identified 19 new studies (1836 participants) for inclusion. In total, we included 42 studies which enrolled/randomised 4485 participants, with 3945 of these analysed for efficacy and 4176 for safety. The studies examined a number of different drug comparisons. Controlled-release (CR; typically taken every 12 hours) oxycodone versus immediate-release (IR; taken every 4-6 hours) oxycodone Pooled analysis of three of the four studies comparing CR oxycodone to IR oxycodone suggest that there is little to no difference between CR and IR oxycodone in pain intensity (standardised mean difference (SMD) 0.12, 95% confidence interval (CI) -0.1 to 0.34; n = 319; very low-certainty evidence). The evidence is very uncertain about the effect on adverse events, including constipation (RR 0.71, 95% CI 0.45 to 1.13), drowsiness/somnolence (RR 1.03, 95% CI 0.69 to 1.54), nausea (RR 0.85, 95% CI 0.56 to 1.28), and vomiting (RR 0.66, 95% CI 0.38 to 1.15) (very low-certainty evidence). There were no data available for quality of life or participant preference, however, three studies suggested that treatment acceptability may be similar between groups (low-certainty evidence). CR oxycodone versus CR morphine The majority of the 24 studies comparing CR oxycodone to CR morphine reported either pain intensity (continuous variable), pain relief (dichotomous variable), or both. Pooled analysis indicated that pain intensity may be lower (better) after treatment with CR morphine than CR oxycodone (SMD 0.14, 95% CI 0.01 to 0.27; n = 882 in 7 studies; low-certainty evidence). This SMD is equivalent to a difference of 0.27 points on the Brief Pain Inventory scale (0-10 numerical rating scale), which is not clinically significant. Pooled analyses also suggested that there may be little to no difference in the proportion of participants achieving complete or significant pain relief (RR 1.02, 95% CI 0.95 to 1.10; n = 1249 in 13 studies; low-certainty evidence). The RR for constipation (RR 0.75, 95% CI 0.66 to 0.86) may be lower after treatment with CR oxycodone than after CR morphine. Pooled analyses showed that, for most of the adverse events, the CIs were wide, including no effect as well as potential benefit and harm: drowsiness/somnolence (RR 0.88, 95% CI 0.74 to 1.05), nausea (RR 0.93, 95% CI 0.77 to 1.12), and vomiting (RR 0.81, 95% CI 0.63 to 1.04) (low or very low-certainty evidence). No data were available for quality of life. The evidence is very uncertain about the treatment effects on treatment acceptability and participant preference. Other comparisons The remaining studies either compared oxycodone in various formulations or compared oxycodone to different alternative opioids. None found any clear superiority or inferiority of oxycodone for cancer pain, neither as an analgesic agent nor in terms of adverse event rates and treatment acceptability. The certainty of this evidence base was limited by the high or unclear risk of bias of the studies and by imprecision due to low or very low event rates or participant numbers for many outcomes.
AUTHORS' CONCLUSIONS
The conclusions have not changed since the previous version of this review (in 2017). We found low-certainty evidence that there may be little to no difference in pain intensity, pain relief and adverse events between oxycodone and other strong opioids including morphine, commonly considered the gold standard strong opioid. Although we identified a benefit for pain relief in favour of CR morphine over CR oxycodone, this was not clinically significant and did not persist following sensitivity analysis and so we do not consider this important. However, we found that constipation and hallucinations occurred less often with CR oxycodone than with CR morphine; but the certainty of this evidence was either very low or the finding did not persist following sensitivity analysis, so these findings should be treated with utmost caution. Our conclusions are consistent with other reviews and suggest that, while the reliability of the evidence base is low, given the absence of important differences within this analysis, it seems unlikely that larger head-to-head studies of oxycodone versus morphine are justified, although well-designed trials comparing oxycodone to other strong analgesics may well be useful. For clinical purposes, oxycodone or morphine can be used as first-line oral opioids for relief of cancer pain in adults.
Topics: Adult; Analgesics, Opioid; Cancer Pain; Constipation; Humans; Morphine; Nausea; Neoplasms; Oxycodone; Pain; Quality of Life; Reproducibility of Results; Sleepiness; Vomiting
PubMed: 35679121
DOI: 10.1002/14651858.CD003870.pub7 -
Journal of Dentistry Oct 2022Dental pain is a commonly managed presentation in medicine and dentistry, where oxycodone is often prescribed. The aim of this systematic review and meta-analysis was to... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVES
Dental pain is a commonly managed presentation in medicine and dentistry, where oxycodone is often prescribed. The aim of this systematic review and meta-analysis was to determine and quantify the effectiveness of oxycodone for acute dental pain.
DATA
Randomised controlled trials, controlled trials and comparative studies were included involving patients >12 years, where oxycodone was trialled for dental pain.
SOURCES
Three databases were searched: Medline Ovid, Embase Ovid and Web of Science. Two authors independently screened title and abstracts for relevance, extracted data and performed bias assessments.
STUDY SELECTION
Of 148 potentially relevant studies, 13 articles met the inclusion criteria for the systematic review and of the 13, nine studies were included in the meta-analysis. All studies were single-dose analgesia for surgical third molar extractions.
CONCLUSIONS
Oxycodone produced more effective analgesia in combination with paracetamol. In the meta-analysis, monotherapy etoricoxib and rofecoxib showed significant pain relief compared to combination oxycodone/paracetamol (SPID6 mean difference=-2.13, CI=-3.29, -0.98; TOTPAR6 mean difference=-2.98, CI=-4.90, -1.06). Non-steroidal anti-inflammatory drugs (NSAIDs) were more effective than oxycodone/paracetamol combinations, however, the evidence would become weak in a future study with a similar patient setting due to substantial statistical heterogeneity (SPID6 and TOTPAR6 prediction interval -4.471, 0.207 and -7.28, 1.32 respectively).
CLINICAL SIGNIFICANCE
Non-steroidal anti-inflammatory drugs were superior than oxycodone/paracetamol combinations, although some patient populations may experience similar effects to the combined oxycodone/paracetamol combination.
Topics: Acetaminophen; Analgesics, Opioid; Anti-Inflammatory Agents, Non-Steroidal; Etoricoxib; Humans; Oxycodone; Pain, Postoperative
PubMed: 35977697
DOI: 10.1016/j.jdent.2022.104254 -
The Cochrane Database of Systematic... Aug 2021This is an update of the original Cochrane Review first published in Issue 10, 2016. For people with advanced cancer, the prevalence of pain can be as high as 90%.... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
This is an update of the original Cochrane Review first published in Issue 10, 2016. For people with advanced cancer, the prevalence of pain can be as high as 90%. Cancer pain is a distressing symptom that tends to worsen as the disease progresses. Evidence suggests that opioid pharmacotherapy is the most effective of these therapies. Hydromorphone appears to be an alternative opioid analgesic which may help relieve these symptoms.
OBJECTIVES
To determine the analgesic efficacy of hydromorphone in relieving cancer pain, as well as the incidence and severity of any adverse events.
SEARCH METHODS
We searched CENTRAL, MEDLINE, Embase and clinical trials registers in November 2020. We applied no language, document type or publication status limitations to the search.
SELECTION CRITERIA
We included randomised controlled trials (RCTs) that compared hydromorphone with placebo, an alternative opioid or another active control, for cancer pain in adults and children. Primary outcomes were participant-reported pain intensity and pain relief; secondary outcomes were specific adverse events, serious adverse events, quality of life, leaving the study early and death.
DATA COLLECTION AND ANALYSIS
Two review authors independently extracted data. We calculated risk ratio (RR) and 95% confidence intervals (CI) for binary outcomes on an intention-to-treat (ITT) basis. We estimated mean difference (MD) between groups and 95% CI for continuous data. We used a random-effects model and assessed risk of bias for all included studies. We assessed the evidence using GRADE and created three summary of findings tables.
MAIN RESULTS
With four new identified studies, the review includes a total of eight studies (1283 participants, with data for 1181 participants available for analysis), which compared hydromorphone with oxycodone (four studies), morphine (three studies) or fentanyl (one study). All studies included adults with cancer pain, mean age ranged around 53 to 59 years and the proportion of men ranged from 42% to 67.4%. We judged all the studies at high risk of bias overall because they had at least one domain with high risk of bias. We found no studies including children. We did not complete a meta-analysis for the primary outcome of pain intensity due to skewed data and different comparators investigated across the studies (oxycodone, morphine and fentanyl). Comparison 1: hydromorphone compared with placebo We identified no studies comparing hydromorphone with placebo. Comparison 2: hydromorphone compared with oxycodone Participant-reported pain intensity We found no clear evidence of a difference in pain intensity (measured using a visual analogue scale (VAS)) in people treated with hydromorphone compared with those treated with oxycodone, but the evidence is very uncertain (3 RCTs, 381 participants, very low-certainty evidence). Participant-reported pain relief We found no studies reporting participant-reported pain relief. Specific adverse events We found no clear evidence of a difference in nausea (RR 1.13 95% CI 0.74 to 1.73; 3 RCTs, 622 participants), vomiting (RR 1.18, 95% CI 0.72 to 1.94; 3 RCTs, 622 participants), dizziness (RR 0.91, 95% CI 0.58 to 1.44; 2 RCTs, 441 participants) and constipation (RR 0.92, 95% CI 0.72 to 1.19; 622 participants) (all very low-certainty evidence) in people treated with hydromorphone compared with those treated with oxycodone, but the evidence is very uncertain. Quality of life We found no studies reporting quality of life. Comparison 3: hydromorphone compared with morphine Participant-reported pain intensity We found no clear evidence of a difference in pain intensity (measured using the Brief Pain Inventory (BPI) or VAS)) in people treated with hydromorphone compared with those treated with morphine, but the evidence is very uncertain (2 RCTs, 433 participants; very low-certainty evidence). Participant-reported pain relief We found no clear evidence of a difference in the number of clinically improved participants, defined by 50% or greater pain relief rate, in the hydromorphone group compared with the morphine group, but the evidence is very uncertain (RR 0.99, 95% CI 0.84 to 1.18; 1 RCT, 233 participants; very low-certainty evidence). Specific adverse events At 24 days of treatment, morphine may reduce constipation compared with hydromorphone, but the evidence is very uncertain (RR 1.56, 95% CI 1.12 to 2.17; 1 RCT, 200 participants; very low-certainty evidence). We found no clear evidence of a difference in nausea (RR 0.94, 95% CI 0.66 to 1.30; 1 RCT, 200 participants), vomiting (RR 0.87, 95% CI 0.58 to 1.31; 1 RCT, 200 participants) and dizziness (RR 1.15, 95% CI 0.71 to 1.88; 1 RCT, 200 participants) (all very low-certainty evidence) in people treated with hydromorphone compared with those treated with morphine, but the evidence is very uncertain. Quality of life We found no studies reporting quality of life. Comparison 4: hydromorphone compared with fentanyl Participant-reported pain intensity We found no clear evidence of a difference in pain intensity (measured by numerical rating scale (NRS)) at 60 minutes in people treated with hydromorphone compared with those treated with fentanyl, but the evidence is very uncertain (1 RCT, 82 participants; very low-certainty evidence). Participant-reported pain relief We found no studies reporting participant-reported pain relief. Specific adverse events We found no studies reporting specific adverse events. Quality of life We found no studies reporting quality of life.
AUTHORS' CONCLUSIONS
The evidence of the benefits and harms of hydromorphone compared with other analgesics is very uncertain. The studies reported some adverse events, such as nausea, vomiting, dizziness and constipation, but generally there was no clear evidence of a difference between hydromorphone and morphine, oxycodone or fentanyl for this outcome. There is insufficient evidence to support or refute the use of hydromorphone for cancer pain in comparison with other analgesics on the reported outcomes. Further research with larger sample sizes and more comprehensive outcome data collection is required.
Topics: Adult; Analgesics, Opioid; Cancer Pain; Child; Humans; Hydromorphone; Male; Middle Aged; Morphine; Neoplasms; Oxycodone
PubMed: 34350974
DOI: 10.1002/14651858.CD011108.pub3 -
Cancer Treatment Reviews Apr 2024Cancer-related pain often requires opioid treatment with opioid-induced constipation (OIC) as its most frequent gastrointestinal side-effect. Both for prevention and... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Cancer-related pain often requires opioid treatment with opioid-induced constipation (OIC) as its most frequent gastrointestinal side-effect. Both for prevention and treatment of OIC osmotic (e.g. polyethylene glycol) and stimulant (e.g. bisacodyl) laxatives are widely used. Newer drugs such as the peripherally acting µ-opioid receptor antagonists (PAMORAs) and naloxone in a fixed combination with oxycodone have become available for the management of OIC. This systematic review and meta-analysis aims to give an overview of the scientific evidence on pharmacological strategies for the prevention and treatment of OIC in cancer patients.
METHODS
A systematic search in PubMed, Embase, Web of Science and the Cochrane Library was completed from inception up to 22 October 2022. Randomized and non-randomized studies were systematically selected. Bowel function and adverse drug events were assessed.
RESULTS
Twenty trials (prevention: five RCTs and three cohort studies; treatment: ten RCTs and two comparative cohort studies) were included in the review. Regarding the prevention of OIC, three RCTs compared laxatives with other laxatives, finding no clear differences in effectivity of the laxatives used. One cohort study showed a significant benefit of magnesium oxide compared with no laxative. One RCT found a significant benefit for the PAMORA naldemedine compared with magnesium oxide. Preventive use of oxycodone/naloxone did not show a significant difference in two out of three other studies compared to oxycodone or fentanyl. A meta-analysis was not possible. Regarding the treatment of OIC, two RCTs compared laxatives, of which one RCT found that polyethylene glycol was significantly more effective than sennosides. Seven studies compared an opioid antagonist (naloxone, methylnaltrexone or naldemedine) with placebo and three studies compared different dosages of opioid antagonists. These studies with opioid antagonists were used for the meta-analysis. Oxycodone/naloxone showed a significant improvement in Bowel Function Index compared to oxycodone with laxatives (MD -13.68; 95 % CI -18.38 to -8.98; I = 58 %). Adverse drug event rates were similar amongst both groups, except for nausea in favour of oxycodone/naloxone (RR 0.51; 95 % CI 0.31-0.83; I = 0 %). Naldemedine (NAL) and methylnaltrexone (MNTX) demonstrated significantly higher response rates compared to placebo (NAL: RR 2.07, 95 % CI 1.64-2.61, I = 0 %; MNTX: RR 3.83, 95 % CI 2.81-5.22, I = 0 %). With regard to adverse events, abdominal pain was more present in treatment with methylnaltrexone and diarrhea was significantly more present in treatment with naldemedine. Different dosages of methylnaltrexone were not significantly different with regard to both efficacy and adverse drug event rates.
CONCLUSIONS
Magnesium oxide and naldemedine are most likely effective for prevention of OIC in cancer patients. Naloxone in a fixed combination with oxycodone, naldemedine and methylnaltrexone effectively treat OIC in cancer patients with acceptable adverse events. However, their effect has not been compared to standard (osmotic and stimulant) laxatives. More studies comparing standard laxatives with each other and with opioid antagonists are necessary before recommendations for clinical practice can be made.
Topics: Humans; Laxatives; Analgesics, Opioid; Narcotic Antagonists; Constipation; Oxycodone; Opioid-Induced Constipation; Magnesium Oxide; Cohort Studies; Naloxone; Polyethylene Glycols; Neoplasms; Drug-Related Side Effects and Adverse Reactions; Quaternary Ammonium Compounds; Naltrexone
PubMed: 38452708
DOI: 10.1016/j.ctrv.2024.102704 -
PloS One 2020To evaluate the efficacy, safety and cost-effectiveness of Oxycodone Hydrochloride Controlled-release Tablets (CR oxycodone) and Morphine Sulfate Sustained-release... (Comparative Study)
Comparative Study Meta-Analysis
OBJECTIVE
To evaluate the efficacy, safety and cost-effectiveness of Oxycodone Hydrochloride Controlled-release Tablets (CR oxycodone) and Morphine Sulfate Sustained-release Tablets (SR morphine) for moderate to severe cancer pain titration.
METHODS
Randomized controlled trials meeting the inclusion criteria were searched through Medline, Cochrane Library, Pubmed, EMbase, CNKI,VIP and WanFang database from the data of their establishment to June 2019. The efficacy and safety data were extracted from the included literature. The pain control rate was calculated to eatimate efficacy. Meta-analysis was conducted by Revman5.1.4. A decision tree model was built to simulate cancer pain titration process. The initial dose of CR oxycodone and SR morphine group were 20mg and 30mg respectively. Oral immediate-release morphine was administered to treat break-out pain. The incremental cost-effectiveness ratio was performed with TreeAge Pro 2019.
RESULTS
19 studies (1680 patients)were included in this study. Meta-analysis showed that the pain control rate of CR oxycodone and SR morphine were 86% and 82.98% respectively. The costs of CR oxycodone and SR morphine were $23.27 and $13.31. The incremental cost-effectiveness ratio per unit was approximate $329.76. At the willingness-to-pay threshold of $8836, CR oxycodone was cost-effective, while the corresponding probability of being cost-effective at the willingness-to-pay threshold of $300 was 31.6%. One-way sensitivity analysis confirmed robustness of results.
CONCLUSIONS
CR oxycodone could be a cost-effective option compared with SR morphine for moderate to severe cancer pain titration in China, according to the threshold defined by the WHO.
Topics: Cancer Pain; Cost-Benefit Analysis; Decision Trees; Delayed-Action Preparations; Economics, Pharmaceutical; Humans; Morphine; Oxycodone; Publication Bias; Risk; Treatment Outcome
PubMed: 32302346
DOI: 10.1371/journal.pone.0231763 -
International Journal of Molecular... Aug 2023The pharmacological treatment of postherpetic neuralgia (PHN) is unsatisfactory, and there is a clinical need for new approaches. Several drugs under advanced clinical...
The pharmacological treatment of postherpetic neuralgia (PHN) is unsatisfactory, and there is a clinical need for new approaches. Several drugs under advanced clinical development are addressed in this review. A systematic literature search was conducted in three electronic databases (Medline, Web of Science, Scopus) and in the ClinicalTrials.gov register from 1 January 2016 to 1 June 2023 to identify Phase II, III and IV clinical trials evaluating drugs for the treatment of PHN. A total of 18 clinical trials were selected evaluating 15 molecules with pharmacological actions on nine different molecular targets: Angiotensin Type 2 Receptor (AT2R) antagonism (olodanrigan), Voltage-Gated Calcium Channel (VGCC) α2δ subunit inhibition (crisugabalin, mirogabalin and pregabalin), Voltage-Gated Sodium Channel (VGSC) blockade (funapide and lidocaine), Cyclooxygenase-1 (COX-1) inhibition (TRK-700), Adaptor-Associated Kinase 1 (AAK1) inhibition (LX9211), Lanthionine Synthetase C-Like Protein (LANCL) activation (LAT8881), N-Methyl-D-Aspartate (NMDA) receptor antagonism (esketamine), mu opioid receptor agonism (tramadol, oxycodone and hydromorphone) and Nerve Growth Factor (NGF) inhibition (fulranumab). In brief, there are several drugs in advanced clinical development for treating PHN with some of them reporting promising results. AT2R antagonism, AAK1 inhibition, LANCL activation and NGF inhibition are considered first-in-class analgesics. Hopefully, these trials will result in a better clinical management of PHN.
Topics: Humans; Drugs, Investigational; Nerve Growth Factor; Neuralgia, Postherpetic; Pregabalin; Randomized Controlled Trials as Topic
PubMed: 37629168
DOI: 10.3390/ijms241612987 -
Journal of Opioid Management 2022To determine equianalgesic potency ratios for opioids with an -evidence-based approach without the use of pre-existing potency tables. (Meta-Analysis)
Meta-Analysis
OBJECTIVE
To determine equianalgesic potency ratios for opioids with an -evidence-based approach without the use of pre-existing potency tables.
DESIGN
Frequentist network meta-analysis (NMA) of randomized controlled trials (RCTs) comparing opioids in patient-controlled analgesia (PCA).
SETTING
A systematic review.
DATA SOURCES
A systematic search of MEDLINE, EMBASE, the Cochrane Library (CENTRAL), and Web of Science identified relevant RCTs from start of recording to 2019.
ELIGIBILITY CRITERIA
RCTs comparing opioids via intravenous PCA in acute pain, with comparable resulting pain scores and identical treatment with coanalgesics at study level. The quality of studies was assessed using the Cochrane risk of bias tool with six items.
RESULTS
52 RCTs were identified with data for 16 opioids. Primary endpoint was the inverted ratio of means of the total consumption administered via PCA, which resembles the analgesic potency. The calculated analgesic potencies were sufentanil 423 [95 percent CI 334.99; 532.96], fentanyl 58 [48.22; 68.60], buprenorphine 37 [26.66; 50.81], remifentanil 13 [9.37; 19.13], alfentanil 7 [4.02; 11.01], hydromorphone 6 [4.96; 8.43], oxymorphone 6 [4.46; 8.84], butorphanol 4.5 [3.05; 6.73], diamorphine 2.2 [1.16; 4.10], morphine 1, oxycodone 0.9 [0.65; 1.34], piritramide 0.9 [0.55; 1.56], nalbuphine 0.7 [0.54; 0.95], pethidine 0.12 [0.10; 0.15], meptazinol 0.08 [0.03; 0.20], and tramadol 0.08 [0.07; 0.10].
CONCLUSIONS
The results in part contradict the values from the literature, which have been criticized for their imprecision. From clinical experience however, our findings seem very plausible. Short-acting opioids are less potent compared to longer acting drugs, eg, morphine, probably due to shorter intervals for -readministration.
Topics: Humans; Analgesia, Patient-Controlled; Analgesics, Opioid; Network Meta-Analysis; Tramadol; Morphine
PubMed: 36523208
DOI: 10.5055/jom.2022.0751 -
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