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Prehospital opioid dose and myocardial injury in patients with ST elevation myocardial infarction.
Fernando, H, Nehme, Z, Peter, K, Bernard, S, Stephenson, M, Bray, J, Cameron, P, Ellims, A, Taylor, A, Kaye, DM, et al
Open heart. 2020;(2)
Abstract
OBJECTIVE To characterise the relationship between opioid dose and myocardial infarct size in patients with ST elevation myocardial infarction (STEMI). METHODS Patients given opioid treatment by emergency medical services with confirmed STEMI were included in this secondary, retrospective cohort analysis of the Air versus Oxygen in Myocardial Infarction (AVOID) study. Patients with cardiogenic shock were excluded. The primary endpoint was comparison of cardiac biomarkers as a measure of infarct size based on opioid dose (low ≤8.75 mg, intermediate 8.76-15 mg and high >15 mg of intravenous morphine equivalent dose). RESULTS 422 patients were included in the analysis. There was a significantly higher proportion of patients with Thrombolysis in Myocardial Infarction (TIMI) 0 or 1 flow pre-percutaneous coronary intervention (PCI) (94% vs 81%, p=0.005) and greater use of thrombus aspiration catheters (59% vs 30%, p<0.001) in the high compared with low-dose opioid group. After adjustment for potential confounders, every 1 mg of intravenous morphine equivalent dose was associated with a 1.4% (95% CI 0.2%, 2.7%, p=0.028) increase in peak creatine kinase; however, this was no longer significant after adjustment for TIMI flow pre-PCI. CONCLUSIONS Our study suggests no benefit of higher opioid dose and a dose-dependent signal between opioid dose and increased myocardial infarct size. Prospective randomised controlled trials are required to establish causality given that this may also be explained by patients with a greater ischaemic burden requiring higher opioid doses due to more severe pain. Future research also needs to focus on strategies to mitigate the opioid-P2Y12 inhibitor interaction and non-opioid analgesia to treat ischaemic chest pain.
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Breakthrough pain in patients with head & neck cancer. A secondary analysis of IOPS MS study.
Mercadante, S, Masedu, F, Valenti, M, Aielli, F
Oral oncology. 2019;:87-90
Abstract
AIM: To characterize breakthrough pain (BTcP) in patients with Head and neck (H&N) cancer. METHODS This was a secondary analysis of multicenter study of BTcP. Background pain intensity and opioid dose were recorded. The number of BTcP episodes, their intensity, predictability, onset, duration and interference with daily activities were collected. Opioids used for BTcP, and the mean time to meaningful pain relief after taking medication, were assessed. The presence of mucositis was also assessed. RESULTS 205 patients with H&N cancer were examined. The mean number of BTcP episodes was 2.8/day, which was higher than in general population. The mean intensity of BTcP was 7.4. BTcP was more predictable in H&N cancer than in other tumors. The main trigger of predictable BTcP was the ingestion of food (76.5%). BTcP onset was fast in 148 patients (72.2%). The mean time to meaningful pain relief after taking a BTcP medication was 15.3 min and BTcP interference with daily activity was relevant in most patients (89.2%). Transdermal drugs and nasal fentanyl preparations were more frequently used for background pain and BTcP, respectively. A consistent number of patients with H&N cancer (38.5%) exhibited different levels of oral mucositis. CONCLUSION BTcP in patients with H&N cancer is characterized by a larger number of episodes/day and the predictability, particularly with ingestion of food. The use of drugs for background analgesia and BTcP were conditioned by the possible interference with swallowing or local mucosal damage.
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Use of prescribed opioids before and after bariatric surgery: prospective evidence from a U.S. multicenter cohort study.
King, WC, Chen, JY, Belle, SH, Courcoulas, AP, Dakin, GF, Flum, DR, Hinojosa, MW, Kalarchian, MA, Mitchell, JE, Pories, WJ, et al
Surgery for obesity and related diseases : official journal of the American Society for Bariatric Surgery. 2017;(8):1337-1346
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Abstract
BACKGROUND Limited evidence suggests bariatric surgery may not reduce opioid analgesic use, despite improvements in pain. OBJECTIVE To determine if use of prescribed opioid analgesics changes in the short and long term after bariatric surgery and to identify factors associated with continued and postsurgery initiated use. SETTING Ten U.S. hospitals. METHODS The Longitudinal Assessment of Bariatric Surgery-2 is an observational cohort study. Assessments were conducted presurgery, 6 months postsurgery, and annually postsurgery for up to 7 years until January 2015. Opioid use was defined as self-reported daily, weekly, or "as needed" use of a prescribed medication classified as an opioid analgesic. RESULTS Of 2258 participants with baseline data, 2218 completed follow-up assessment(s) (78.7% were female, median body mass index: 46; 70.6% underwent Roux-en-Y gastric bypass). Prevalence of opioid use decreased after surgery from 14.7% (95% CI: 13.3-16.2) at baseline to 12.9% (95% CI: 11.5-14.4) at month 6 but then increased to 20.3%, above baseline levels, as time progressed (95% CI: 18.2-22.5) at year 7. Among participants without baseline opioid use (n = 1892), opioid use prevalence increased from 5.8% (95% CI: 4.7-6.9) at month 6 to 14.2% (95% CI: 12.2-16.3) at year 7. Public versus private health insurance, more pain presurgery, undergoing subsequent surgeries, worsening or less improvement in pain, and starting or continuing nonopioid analgesics postsurgery were significantly associated with higher risk of postsurgery initiated opioid use. CONCLUSION After bariatric surgery, prevalence of prescribed opioid analgesic use initially decreased but then increased to surpass baseline prevalence, suggesting the need for alternative methods of pain management in this population.
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Dexketoprofen/tramadol: randomised double-blind trial and confirmation of empirical theory of combination analgesics in acute pain.
Moore, RA, Gay-Escoda, C, Figueiredo, R, Tóth-Bagi, Z, Dietrich, T, Milleri, S, Torres-Lagares, D, Hill, CM, García-García, A, Coulthard, P, et al
The journal of headache and pain. 2015;:541
Abstract
BACKGROUND Combination analgesics are effective in acute pain, and a theoretical framework predicts efficacy for combinations. The combination of dexketoprofen and tramadol is untested, but predicted to be highly effective. METHODS This was a randomised, double-blind, double-dummy, parallel-group, placebo-controlled, single-dose trial in patients with moderate or severe pain following third molar extraction. There were ten treatment arms, including dexketoprofen trometamol (12.5 mg and 25 mg) and tramadol hydrochloride (37.5 mg and 75 mg), given as four different fixed combinations and single components, with ibuprofen 400 mg as active control as well as a placebo control. The study objective was to evaluate the superior analgesic efficacy and safety of each combination and each single agent versus placebo. The primary outcome was the proportion of patients with at least 50 % max TOTPAR over six hours. RESULTS 606 patients were randomised and provided at least one post-dose assessment. All combinations were significantly better than placebo. The highest percentage of responders (72%) was achieved in the dexketoprofen trometamol 25 mg plus tramadol hydrochloride 75 mg group (NNT 1.6, 95% confidence interval 1.3 to 2.1). Addition of tramadol to dexketoprofen resulted in greater peak pain relief and greater pain relief over the longer term, particularly at times longer than six hours (median duration of 8.1 h). Adverse events were unremarkable. CONCLUSIONS Dexketoprofen trometamol 25 mg combined with tramadol hydrochloride 75 mg provided good analgesia with rapid onset and long duration in a model of moderate to severe pain. The results of the dose finding study are consistent with pre-trial calculations based on empirical formulae. TRIAL REGISTRATION EudraCT (2010-022798-32); Clinicaltrials.gov (NCT01307020).
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Diuretic, opiate and nitrate use in severe acidotic acute cardiogenic pulmonary oedema: analysis from the 3CPO trial.
Gray, A, Goodacre, S, Seah, M, Tilley, S
QJM : monthly journal of the Association of Physicians. 2010;(8):573-81
Abstract
BACKGROUND Drug treatments for acute cardiogenic pulmonary oedema (ACPO) have not been rigorously evaluated and recent observational data suggests some agents are related to poorer outcome. AIM: We aimed to examine the effect of treatment with diuretics, nitrates and opiates on 7-day mortality, acidosis and respiratory distress in UK Emergency Department (ED) patients with severe acidotic pulmonary oedema. DESIGN Analysis of data from the 3CPO trial; a multicentre randomized controlled trial. METHODS Data were analysed from patients recruited with severe acidotic pulmonary oedema to the 3CPO trial in 26 UK EDs between 2003 and 2007. The effects of these treatments on 7-day mortality, improvement in acidosis (pH change between baseline and 1 h) and improvement in respiratory distress (patient measured breathlessness using a Visual Analogue Score between baseline and 1 h) were tested using univariate logistic regression analysis, and a regression model used to adjust for confounding baseline differences. RESULTS Nitrates were given to 947/1048 (90.4%) patients, diuretics to 934/1049 (89.0%) patients and opiates to 541/1052 patients (51.4%). Adjusted analysis showed that opiate treatment was associated with less improvement in acidosis [difference in improvement in pH -0.022, 95% confidence interval (CI) -0.014 to -0.030, P < 0.001], but no difference in mortality or improvement in respiratory distress. We found no evidence that nitrate or diuretic use were associated with any difference in mortality, improvement in acidosis or respiratory distress. CONCLUSION Opiate use is associated with less improvement in acidosis during initial treatment and may attenuate effective treatment of severe acidotic ACPO.
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Randomized controlled trial comparing the effectiveness and safety of intranasal and intramuscular naloxone for the treatment of suspected heroin overdose.
Kerr, D, Kelly, AM, Dietze, P, Jolley, D, Barger, B
Addiction (Abingdon, England). 2009;(12):2067-74
Abstract
AIMS: Traditionally, the opiate antagonist naloxone has been administered parenterally; however, intranasal (i.n.) administration has the potential to reduce the risk of needlestick injury. This is important when working with populations known to have a high prevalence of blood-borne viruses. Preliminary research suggests that i.n. administration might be effective, but suboptimal naloxone solutions were used. This study compared the effectiveness of concentrated (2 mg/ml) i.n. naloxone to intramuscular (i.m.) naloxone for suspected opiate overdose. METHODS This randomized controlled trial included patients treated for suspected opiate overdose in the pre-hospital setting. Patients received 2 mg of either i.n. or i.m. naloxone. The primary outcome was the proportion of patients who responded within 10 minutes of naloxone treatment. Secondary outcomes included time to adequate response and requirement for supplementary naloxone. Data were analysed using multivariate statistical techniques. RESULTS A total of 172 patients were enrolled into the study. Median age was 29 years and 74% were male. Rates of response within 10 minutes were similar: i.n. naloxone (60/83, 72.3%) compared with i.m. naloxone (69/89, 77.5%) [difference: -5.2%, 95% confidence interval (CI) -18.2 to 7.7]. No difference was observed in mean response time (i.n.: 8.0, i.m.: 7.9 minutes; difference 0.1, 95% CI -1.3 to 1.5). Supplementary naloxone was administered to fewer patients who received i.m. naloxone (i.n.: 18.1%; i.m.: 4.5%) (difference: 13.6%, 95% CI 4.2-22.9). CONCLUSIONS Concentrated intranasal naloxone reversed heroin overdose successfully in 82% of patients. Time to adequate response was the same for both routes, suggesting that the i.n. route of administration is of similar effectiveness to the i.m. route as a first-line treatment for heroin overdose.
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Morphine analgesia and gastrointestinal morbidity in preterm infants: secondary results from the NEOPAIN trial.
Menon, G, Boyle, EM, Bergqvist, LL, McIntosh, N, Barton, BA, Anand, KJ
Archives of disease in childhood. Fetal and neonatal edition. 2008;(5):F362-7
Abstract
OBJECTIVE To investigate the influence of morphine therapy and other factors on the attainment of full enteral feeds and on acquired gastrointestinal pathology in preterm infants. DESIGN Secondary data analysis from a randomised, placebo controlled trial. SETTING 16 neonatal intensive care units in USA, Sweden, France and UK. PATIENTS 898 infants (treatment group 449, control 449). Gestation (median (range)): 27 (23-32) weeks; birth weight (median (range)): 985 (420-2440) g. INTERVENTIONS Morphine (M) or placebo (Pl) given pre-emptively by intravenous loading dose (100 microg/kg of morphine) and infusion (10-30 microg/kg/h depending on gestation) while infants were ventilated, for up to 14 days. "Open-label" morphine (A) could be given if clinically indicated. MAIN OUTCOME MEASURES Age at full enteral feeds and major acquired gastrointestinal pathology. RESULTS The group randomised to morphine was later in attaining full feeds (median days (quartiles): M 20 (13-29), Pl 17 (12-26); p = 0.003), and in starting feeds (median days (quartiles): M 5 (3-8), Pl 4 (2-7)). In a linear regression model, age at full feeds was independently associated with birth weight, a score of neonatal morbidities, neonatal dexamethasone use and cumulative morphine dose. There was no relationship between morphine use and acquired gastrointestinal pathology (M 9/449, Pl 8/449; chi2 p = 0.81). CONCLUSIONS Morphine delays the attainment of full enteral feeds, partly by delaying the start of feeding, but does not discernibly increase gastrointestinal complications. The attainment of full feeds is influenced by morphine dose, but other factors seem to be important, including birth weight and neonatal morbidity.