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Pain and Therapy Jun 2019Optimal pain management is crucial to the postoperative recovery process. We aimed to evaluate the efficacy and safety of intravenous oxycodone with intravenous... (Review)
Review
INTRODUCTION
Optimal pain management is crucial to the postoperative recovery process. We aimed to evaluate the efficacy and safety of intravenous oxycodone with intravenous fentanyl, morphine, sufentanil, pethidine, and hydromorphone for acute postoperative pain.
METHODS
A systematic literature search of PubMed, Cochrane Library, and EMBASE databases was performed for randomized controlled trials published from 2008 through 2017 (inclusive) that evaluated the acute postoperative analgesic efficacy of intravenous oxycodone against fentanyl, morphine, sufentanil, pethidine, and hydromorphone in adult patients (age ≥ 18 years). Outcomes examined included analgesic consumption, pain intensity levels, side effects, and patient satisfaction.
RESULTS
Eleven studies were included in the review; six compared oxycodone with fentanyl, two compared oxycodone with morphine, and three compared oxycodone with sufentanil. There were no eligible studies comparing oxycodone with pethidine or hydromorphone. Overall, analgesic consumption was lower with oxycodone than with fentanyl or sufentanil. Oxycodone exhibited better analgesic efficacy than fentanyl and sufentanil, and comparable analgesic efficacy to morphine. In terms of safety, there was a tendency towards more side effects with oxycodone than with fentanyl, but the incidence of side effects with oxycodone was comparable to morphine and sufentanil. Where patient satisfaction was evaluated, higher satisfaction levels were observed with oxycodone than with sufentanil and comparable satisfaction was noted when comparing oxycodone with fentanyl. Patient satisfaction was not evaluated in the studies comparing oxycodone with morphine.
CONCLUSIONS
Our findings suggest that intravenous oxycodone provides better analgesic efficacy than fentanyl and sufentanil, and comparable efficacy to morphine with less adverse events such as sedation. No studies comparing intravenous oxycodone with pethidine or hydromorphone were identified in this review. Better alignment of study methodologies for future research in this area is recommended to provide the best evidence base for a meta-analysis.
FUNDING
Mundipharma Singapore Holding Pte Ltd, Singapore.
PubMed: 31004317
DOI: 10.1007/s40122-019-0122-4 -
Journal of Perianesthesia Nursing :... Dec 2018Intravenous (IV) opioids are administered for management of acute postoperative pain in the postanesthesia care unit. The benefits of parenteral oxycodone for acute pain...
PURPOSE
Intravenous (IV) opioids are administered for management of acute postoperative pain in the postanesthesia care unit. The benefits of parenteral oxycodone for acute pain management are understudied. The purpose of this review was to evaluate the effectiveness of IV oxycodone for acute postoperative pain.
DESIGN
A systematic review of quantitative studies using the Joanna Briggs Institute approach.
METHODS
A search for randomized controlled trials was conducted, revealing 314 potentially relevant studies. These were compared with the inclusion criteria. Those that met these criteria were critically appraised.
FINDINGS
Participants (N = 506) in eight trials were included in this review. Four studies supported the use of IV oxycodone as patient-controlled analgesia and IV bolus. The remaining studies showed equipotent effects between oxycodone and control. Higher incidences of adverse effects were associated with IV oxycodone.
CONCLUSIONS
IV oxycodone can be considered as effective analgesia for acute postoperative pain with careful regards to its adverse effects.
Topics: Acute Pain; Administration, Intravenous; Analgesia, Patient-Controlled; Analgesics, Opioid; Humans; Oxycodone; Pain, Postoperative; Randomized Controlled Trials as Topic
PubMed: 30449435
DOI: 10.1016/j.jopan.2017.05.010 -
Anesthesia and Analgesia Oct 2019Side effects of opioids used for the treatment of acute pain frequently limit their analgesic quality. Many studies have compared opioid side effects in... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Side effects of opioids used for the treatment of acute pain frequently limit their analgesic quality. Many studies have compared opioid side effects in patient-controlled analgesia (PCA), but it remains unclear whether there are specific side effect profiles that can be exploited when choosing an opioid for a patient. In this review, we wanted to determine the risk ratios (RRs) for the most common side effects when using different opioids for intravenous PCA in equianalgesic doses and rank the substances accordingly.
METHODS
A search of MEDLINE, EMBASE, the Cochrane Library (CENTRAL), and Web of Science identified 63 randomized controlled trials comparing opioids under equianalgesic conditions. Inclusion criteria were comparable pain stimulus between groups, equal coanalgesic treatment, and comparable resulting pain scores. Quality of studies was assessed using the Cochrane risk of bias tool with 6 items. Frequentistic network meta-analysis was conducted with morphine as the comparator. This method not only summarizes all estimated effects from direct comparisons of different interventions but also allows for indirect comparisons between interventions that can be linked via the common comparator, in which case the indirect evidence can be used to enhance the precision of the direct comparisons. Primary end points of this study were RRs for nausea and vomiting, pruritus, and events of sedation, as well as mean differences for scores of sedation. Events of respiratory depression were counted. Secondary end point was patient satisfaction (mean difference). The study protocol was registered at PROSPERO (CRD42017062355).
RESULTS
Sixteen opioid interventions were compared in the largest network (nausea and vomiting outcome) and 7 opioid interventions in the smallest network (sedation events outcome). Most interventions did not differ from morphine on the primary outcomes (side effects), with some exceptions. Buprenorphine had a significantly higher RR of nausea and vomiting, whereas fentanyl had a lower RR of nausea and vomiting. Nalbuphine, butorphanol, methadone, and pethidine/meperidine had a lower risk of pruritus. Respiratory depression was rare (22 of 2452 patients). Pethidine/meperidine, fentanyl, and oxymorphone caused significantly lower sedation scores. Tramadol caused significantly lower satisfaction scores, whereas oxycodone, alfentanil, remifentanil, fentanyl, and pethidine/meperidine caused significantly higher satisfaction scores.
CONCLUSIONS
The opiate chosen for treatment most likely has little effect on the incidence of pruritus and nausea/vomiting, although considerable differences exist in terms of better and worse opioids in the presented rankings. Larger differences between drugs were observed with regard to sedation and patient satisfaction, and choosing the appropriate opioid may help to improve PCA in this regard.
Topics: Acute Pain; Administration, Intravenous; Analgesia, Patient-Controlled; Analgesics, Opioid; Consciousness; Dose-Response Relationship, Drug; Humans; Network Meta-Analysis; Pain Measurement; Pain, Postoperative; Postoperative Nausea and Vomiting; Pruritus; Randomized Controlled Trials as Topic; Respiratory Insufficiency; Risk Assessment; Risk Factors; Treatment Outcome
PubMed: 30418234
DOI: 10.1213/ANE.0000000000003887 -
Journal of Palliative Medicine Jan 2019Opioids are the foundation of treatment for cancer pain but can cause side-effects, one of the most common being nausea and vomiting, which can impair quality of life.
BACKGROUND
Opioids are the foundation of treatment for cancer pain but can cause side-effects, one of the most common being nausea and vomiting, which can impair quality of life.
OBJECTIVE
To evaluate the evidence for the management of opioid-induced nausea and vomiting. This systematic review was undertaken as part of an update of the European Association for Palliative Care's opioid guidelines.
DESIGN
Searches of MEDLINE (1966-2017) and EMBASE (1980-2017) were done. Key eligibility criteria were: randomized controlled trials conducted in patients with cancer. The Grading of Recommendations Assessment Development and Evaluations system was applied to formulate recommendations.
RESULTS
Fifteen studies were eligible (1524 patients). The studies were grouped as follows: opioid switching (n = 8); the use of antiemetics to treat opioid-induced nausea and vomiting (n = 4); and change of route of administration of the opioid (n = 3). Three recommendations were formulated: A weak recommendation for switching from morphine to oxycodone in cancer patients with nausea (quality D); a weak recommendation for switching from tramadol to either codeine or hydrocodone for pain in cancer patients with nausea (quality D); and a weak recommendation for switching from morphine/oxycodone to methadone using the three-day switch method in patients with increasing pain considered untreatable with further opioid titration and/or with opioid-related side effects (quality C).
CONCLUSIONS
This systematic review can make only weak recommendations for the management of opioid-induced nausea and vomiting. There remains a need for high-quality studies before strong recommendations on the management of opioid-induced nausea and vomiting can be made.
Topics: Adolescent; Adult; Analgesics, Opioid; Antiemetics; Cancer Pain; Humans; Nausea; Neoplasms; Practice Guidelines as Topic; Quality of Life; Randomized Controlled Trials as Topic; Vomiting; Young Adult
PubMed: 30239277
DOI: 10.1089/jpm.2018.0260 -
Pain Management Sep 2018Tapentadol is a novel atypical opioid. Anecdotal evidence suggests that tapentadol has a lower toxicity than conventional opioids. (Review)
Review
BACKGROUND
Tapentadol is a novel atypical opioid. Anecdotal evidence suggests that tapentadol has a lower toxicity than conventional opioids.
OBJECTIVES
To evaluate all single-drug mortality due to tapentadol and assess serious adverse events caused by tapentadol.
METHODS
The Preferred Reporting Items for Systematic review and Meta-Analysis Protocols (PRISMA-P) reporting guidelines, an evidence-based minimum set of items for reporting in systematic reviews, were followed in this systematic review.
RESULTS
24 peer-reviewed papers were identified. They indicate that tapentadol toxicity can cause mortality and serious adverse effects.
CONCLUSION(S)
At least four confirmed fatalities, and serious adverse effects have been documented for individuals abusing or using tapentadol as prescribed. Serious adverse effects of tapentadol use may include respiratory depression, confusion, coma, hallucination/delusion, seizures, tachycardia, hypertension, agitation, tremor, miosis, hypotension, dyspnea, electrolyte abnormality, atrial fibrillation or severe upper abdominal pain. Tapentadol is unlikely to cause serotonin syndrome. The toxicity of tapentadol is significantly less than pure mu opioids, such as oxycodone.
Topics: Analgesics, Opioid; Drug-Related Side Effects and Adverse Reactions; Humans; Phenols; Tapentadol
PubMed: 30079795
DOI: 10.2217/pmt-2018-0027 -
The Cochrane Database of Systematic... Jun 2018Opioid-induced bowel dysfunction (OIBD) is characterised by constipation, incomplete evacuation, bloating, and gastric reflux. It is one of the major adverse events of... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Opioid-induced bowel dysfunction (OIBD) is characterised by constipation, incomplete evacuation, bloating, and gastric reflux. It is one of the major adverse events of treatment for pain in cancer and in palliative care, resulting in increased morbidity and reduced quality of life.This is an update of two Cochrane reviews. One was published in 2011, Issue 1 on laxatives and methylnaltrexone for the management of constipation in people receiving palliative care; this was updated in 2015 and excluded methylnaltrexone. The other was published in 2008, Issue 4 on mu-opioid antagonists (MOA) for OIBD. In this updated review, we only included trials on MOA (including methylnaltrexone) for OIBD in people with cancer and people receiving palliative care.
OBJECTIVES
To assess the effectiveness and safety of MOA for OIBD in people with cancer and people receiving palliative care.
SEARCH METHODS
We searched the Cochrane Central Register of Controlled Trials, MEDLINE, Embase, CINAHL, and Web of Science to August 2017. We also searched clinical trial registries and regulatory websites. We contacted manufacturers of MOA to identify further data.
SELECTION CRITERIA
We included randomised controlled trials (RCTs) that assessed the effectiveness and safety of MOA for OIBD in people with cancer and people at a palliative stage irrespective of the type of terminal disease they experienced.
DATA COLLECTION AND ANALYSIS
Two review authors assessed risk of bias and extracted data. The appropriateness of combining data from the trials depended upon sufficient homogeneity across the trials. Our primary outcomes were laxation, impact on pain relief, and adverse events. Impact on pain relief was a primary outcome because a possible adverse effect of MOAs is a reduction in pain relief from opioids. We assessed the evidence on these outcomes using GRADE.
MAIN RESULTS
We identified four new trials for this update, bringing the total number included in this review to eight. In total, 1022 men and women with cancer irrespective of stage or at a palliative care stage of any disease were randomised across the trials. The MOAs evaluated were oral naldemedine and naloxone (alone or in combination with oxycodone), and subcutaneous methylnaltrexone. The trials compared with MOA with a placebo or with the active intervention administered at different doses or in combination with other drugs. The trial of naldemedine and the two of naloxone in combination with oxycodone were in people with cancer irrespective of disease stage. The trial on naloxone alone was in people with advanced cancer. The four trials on methylnaltrexone were undertaken in palliative care where most participants had cancer. All trials were vulnerable to biases; four were at a high risk as they involved a sample of fewer than 50 participants per arm.In the trial of naldemedine compared to placebo in 225 participants, there were more spontaneous laxations over the two-week treatment for the intervention group (risk ratio (RR) 1.93, 95% confidence intervals (CI) 1.36 to 2.74; moderate-quality evidence). In comparison with higher doses, lower doses resulted in fewer spontaneous laxations (0.1 mg versus 0.2 mg: RR 0.73, 95% CI 0.55 to 0.95; 0.1 mg versus 0.4 mg: RR 0.69, 95% CI 0.53 to 0.89; moderate-quality evidence). There was moderate-quality evidence that naldemedine had no effect on opiate withdrawal. There were five serious adverse events. All were in people taking naldemedine (low-quality evidence). There was an increase in the occurrence of other (non-serious) adverse events in the naldemedine groups (RR 1.36, 95% CI 1.04 to 1.79, moderate-quality evidence). The most common adverse event was diarrhoea.The trials on naloxone taken either on its own, or in combination with oxycodone (an opioid) compared to oxycodone only did not evaluate laxation response over the first two weeks of administration. There was very low-quality evidence that naloxone alone, and moderate-quality evidence that oxycodone/naloxone, had no effect on analgesia. There was low-quality evidence that oxycodone/naloxone did not increase the risk of serious adverse events and moderate-quality evidence that it did not increase risk of adverse events.In combined analysis of two trials of 287 participants, we found methylnaltrexone compared to placebo induced more laxations within 24 hours (RR 2.77, 95% CI 1.91 to 4.04. I² = 0%; moderate-quality evidence). In combined analysis, we found methylnaltrexone induced more laxation responses over two weeks (RR 9.98, 95% CI 4.96 to 20.09. I² = 0%; moderate-quality evidence). The proportion of participants who had a rescue-free laxation response within 24 hours of the first dose was 59.1% in the methylnaltrexone arms and 19.1% in the placebo arm. There was moderate-quality evidence that the rate of opioid withdrawal was not affected. Methylnaltrexone did not increase the likelihood of a serious adverse event; there were fewer in the intervention arm (RR 0.59, 95% CI 0.38 to 0.93; I² = 0%; moderate-quality evidence). There was no difference in the proportion of participants experiencing an adverse event (RR 1.17, 95% CI 0.94 to 1.45; I² = 74%; low-quality evidence). Methylnaltrexone increased the likelihood of abdominal pain and flatulence.Two trials compared differing methylnaltrexone schedules of higher doses with lower doses. For early laxation, there was low-quality evidence of no clear difference between doses on analgesia and adverse events. Both trials measured laxation response within 24 hours of first dose (trial one: RR 0.82, 95% CI 0.41 to 1.66; trial two: RR 1.07, 95% CI 0.81 to 1.42).
AUTHORS' CONCLUSIONS
In this update, the conclusions for naldemedine are new. There is moderate-quality evidence to suggest that, taken orally, naldemedine improves bowel function over two weeks in people with cancer and OIBD but increases the risk of adverse events. The conclusions on naloxone and methylnaltrexone have not changed. The trials on naloxone did not assess laxation at 24 hours or over two weeks. There is moderate-quality evidence that methylnaltrexone improves bowel function in people receiving palliative care in the short term and over two weeks, and low-quality evidence that it does not increase adverse events. There is a need for more trials including more evaluation of adverse events. None of the current trials evaluated effects in children.
Topics: Constipation; Defecation; Female; Gastrointestinal Agents; Humans; Intestinal Diseases; Male; Nalbuphine; Naloxone; Naltrexone; Narcotic Antagonists; Neoplasms; Opioid-Related Disorders; Oxycodone; Palliative Care; Piperidines; Quaternary Ammonium Compounds; Randomized Controlled Trials as Topic; Receptors, Opioid, mu
PubMed: 29869799
DOI: 10.1002/14651858.CD006332.pub3 -
BMC Cancer May 2018Inter-patient variability in response to opioids is well known but a comprehensive definition of its pathophysiological mechanism is still lacking and, more importantly,...
BACKGROUND
Inter-patient variability in response to opioids is well known but a comprehensive definition of its pathophysiological mechanism is still lacking and, more importantly, no studies have focused on children. The STOP Pain project aimed to evaluate the risk factors that contribute to clinical response and adverse drug reactions to opioids by means of a systematic review and a clinical investigation on paediatric oncological patients.
METHODS
We conducted a systematic literature search in EMBASE and PubMed up to the 24th of November 2016 following Cochrane Handbook and PRISMA guidelines. Two independent reviewers screened titles and abstracts along with full-text papers; disagreements were resolved by discussion with two other independent reviewers. We used a data extraction form to provide details of the included studies, and conducted quality assessment using the Quality Assessment Tool for Observational Cohort and Cross-Sectional Studies.
RESULTS
Young age, lung or gastrointestinal cancer, neuropathic or breakthrough pain and anxiety or sleep disturbance were associated to a worse response to opioid analgesia. No clear association was identified in literature regarding gender, ethnicity, weight, presence of metastases, biochemical or hematological factors. Studies in children were lacking. Between June 2011 and April 2014, the Italian STOP Pain project enrolled 87 paediatric cancer patients under treatment with opioids (morphine, codeine, oxycodone, fentanyl and tramadol).
CONCLUSIONS
Future studies on cancer pain should be designed with consideration for the highlighted factors to enhance our understanding of opioid non-response and safety. Studies in children are mandatory.
TRIAL REGISTRATION
CRD42017057740 .
Topics: Age Factors; Analgesics, Opioid; Biological Variation, Population; Cancer Pain; Child; Humans; Longitudinal Studies; Neoplasms; Pain Measurement; Risk Factors; Treatment Outcome
PubMed: 29776346
DOI: 10.1186/s12885-018-4478-3 -
Deutsches Arzteblatt International Mar 2018Rotating several different WHO level III opioid drugs is a therapeutic option for patients with chronic cancer-related pain who suffer from inadequate analgesia and/or...
BACKGROUND
Rotating several different WHO level III opioid drugs is a therapeutic option for patients with chronic cancer-related pain who suffer from inadequate analgesia and/or intolerable side effects. The evidence favoring opioid rotation is controversial, and the current guidelines in Germany and other countries contain only weak recommendations for it.
METHODS
This review is based on pertinent publications retrieved by a systematic review of the literature on opioid rotation for adult patients with chronic cancerrelated pain who are regularly taking WHO level III opioids by the oral or trans - dermal route.
RESULTS
9 individual studies involving a total of 725 patients were included in the analysis, and 3 previous systematic reviews of studies involving a total of 2296 patients were also analyzed. Morphine, oxycodone, fentanyl, hydromorphone, and buprenorphine were used as first-line opioid drugs, and hydromorphone, bupre - norphine, tapentadol, fentanyl, morphine, oxymorphone, and methadone were used as second-line opioid drugs. In all of the studies, pain control was achieved for 14 days after each rotation. In most of them, the dose of the new drug introduced in each rotation needed to be increased above the dose initially calculated from a rotation ratio, with the exception of rotations to methadone. The frequency of side effects was only rarely lessened, but patients largely considered the result of opioid rotation to be positive. No particular opioid drug was found to be best.
CONCLUSION
Opioid rotation can improve analgesia and patient satisfaction. The success of opioid rotation appears to depend on the magnitude of the initial dose, among other factors. Tables of equianalgesic doses should be considered no more than a rough guide for determining the dose of the new drug. Rotations to methadone should be carried out under clinical supervision in experienced hands.
Topics: Analgesics, Opioid; Buprenorphine; Cancer Pain; Chronic Pain; Fentanyl; Germany; Humans; Hydromorphone; Morphine; Neoplasms; Oxycodone; Pain Management
PubMed: 29563006
DOI: 10.3238/arztebl.2018.0135 -
BMJ Supportive & Palliative Care Jun 2018To assess the efficacy, tolerability and acceptability of oxycodone for cancer pain in adults METHODS: We searched CENTRAL, MEDLINE, MEDLINE In-Process, Embase, SCI,... (Review)
Review
OBJECTIVES
To assess the efficacy, tolerability and acceptability of oxycodone for cancer pain in adults METHODS: We searched CENTRAL, MEDLINE, MEDLINE In-Process, Embase, SCI, Conference Proceedings Citation Index-Science, BIOSIS, PsycINFO and four trials registries to November 2016.
RESULTS
We included 23 randomised controlled trials with 2144 patients analysed for efficacy and 2363 for safety. Meta-analyses showed no significant differences between controlled-release (CR) and immediate-release oxycodone in pain intensity or adverse events but did show significantly better pain relief after treatment with CR morphine compared with CR oxycodone. However, sensitivity analysis did not corroborate this result. Meta-analyses of the adverse events showed a significantly lower risk of hallucinations after treatment with CR oxycodone compared with CR morphine, but no other differences. 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 in pain relief or adverse events. The quality of this evidence base was limited by the high/unclear risk of bias of the studies and the low event rates for many outcomes.
CONCLUSIONS
Oxycodone offers similar levels of pain relief and adverse events to other strong opioids. However, hallucinations occurred less with CR oxycodone than with CR morphine, but the quality of this evidence was very low, so this finding should be treated with utmost caution. Our conclusions are consistent with other reviews and suggest that oxycodone can be used first line as an alternative to morphine. However, because it is cheaper, morphine generally remains the first-line opioid of choice.
Topics: Analgesics, Opioid; Cancer Pain; Humans; Oxycodone; Pain Management; Patient Preference; Quality of Life; Randomized Controlled Trials as Topic; Treatment Outcome
PubMed: 29331953
DOI: 10.1136/bmjspcare-2017-001457 -
Journal of Opioid Management 2017We performed a systematic review to answer the question, "Does the introduction of an opioid analgesic with abuse deterrent properties result in reduced overall abuse of... (Review)
Review
OBJECTIVE
We performed a systematic review to answer the question, "Does the introduction of an opioid analgesic with abuse deterrent properties result in reduced overall abuse of the drug in the community?"
DESIGN
We included opioid analgesics with abuse deterrent properties (hydrocodone, morphine, oxycodone) with results restricted to the metasearch term "delayed onset," English language, use in humans, and publication years 2009-2016. All articles that contained data evaluating misuse, abuse, overdose, addiction, and death were included. The results were categorized using the Bradford-Hill criteria.
RESULTS
We included 44 reports: hydrocodone (n = 7), morphine (n = 5), or oxycodone (n = 32) with Food and Drug Administration-approved Categories 1, 2, or 3 abuse deterrent labeling. The data currently available support the Hill criteria of strength (effect size), consistency (reproducibility), temporality, plausibility, and coherence. There was insufficient or no information available for the criteria of biological gradient, experiment, and analogy. We also assessed confounding factors and bias, which indicated that both were present and substantial in magnitude.
CONCLUSIONS
Our analysis found that only oxycodone extended release (ER) had information available to evaluate abuse deterrence in the community. In Australia, Canada, and the United States, reformulation of oxycodone ER was followed by marked reduction in measures of abuse. The precise extent of reduced abuse cannot be calculated because of heterogeneous data sets, but the reported reductions ranged from 10 to 90 percent depending on the measure and the duration of follow-up.
Topics: Abuse-Deterrent Formulations; Analgesics, Opioid; Delayed-Action Preparations; Drug Compounding; Humans; Opioid-Related Disorders; Protective Factors; Risk Factors; Time Factors
PubMed: 29308584
DOI: 10.5055/jom.2017.0415