Use Of Morphine Research Articles

Impact of morphine use on mortality in STEMI patients treated with primary PCI – results from a new registry

Abstract Background Opioids decrease the effect of P2Y12 receptor inhibitors in vitro and observational reports suggest that morphine use may be associated with larger infarct size. Our research group showed previously, using a prospective single-centre registry, that periprocedural morphine use may have no impact on long-term mortality in STEMI patients treated with primary PCI and clopidogrel. Purpose We aimed to study this in vitro interaction on clinical outcomes in patients who were predominantly treated with the novel P2Y12 inhibitors prasugrel or ticagrelor, according to the current guidelines. Methods From May 2020 through February 2021, we collected demographic, anamnestic, procedural and laboratory data of 297 consecutive STEMI cases who were treated with primary PCI at our tertiary centre. Of them 126 patients (42.4%) received IV morphine during the periprocedural period. Outcome measure was time to all-cause mortality. The median follow-up time was 147 days (IQR 71–242 days), with 39 events. To adjust for confounding, a 1:1 propensity score-matching analysis (PSM) was performed using 186 cases. Absolute difference in survival was analysed using Kaplan-Meier survival curves and the logrank test, whereas the relative change was assessed by univariable Cox regression. Results An adequate balance on baseline covariates was achieved by the propensity score-matching. Kaplan-Meier analysis showed no statistically significant difference in all-cause mortality of the treatment groups neither in the original nor in the propensity score-matched population (p=0.220 and 0.762 respectively). In the matched population we found no difference in survival as the HR (Morphine/No Morphine) was 0.88 (95% confidence interval [CI]: 0.39–2.00), p=0.76. Conclusion Our preliminary data suggest that morphine may have no impact on mortality in STEMI patients treated with primary PCI and medical therapy according to the current guidelines including novel P2Y12 antagonists. Funding Acknowledgement Type of funding sources: Public grant(s) – National budget only. Main funding source(s): The research was supported by the Ministry of Innovation and Technology NRDI Office within the framework of the Artificial Intelligence National Laboratory Program. Kaplan-Meier curves: Original populationKaplan-Meier curves: PSM population

Preoperative Paravertebral Block and Chronic Pain after Breast Cancer Surgery: A Double-blind Randomized Trial.

The effectiveness of paravertebral block in preventing chronic pain after breast surgery remains controversial. The primary hypothesis of this study was that paravertebral block reduces the incidence of chronic pain 3 months after breast cancer surgery. In this prospective, multicenter, randomized, double-blind, parallel-group, placebo-controlled study, 380 women undergoing partial or complete mastectomy with or without lymph node dissection were randomized to receive preoperative paravertebral block with either 0.35 ml/kg 0.75% ropivacaine (paravertebral group) or saline (control group). Systemic multimodal analgesia was administered in both groups. The primary endpoint was the incidence of chronic pain with a visual analogue scale (VAS) score greater than or equal to 3 out of 10, 3 months after surgery. The secondary outcomes were acute pain, analgesic consumption, nausea and vomiting, chronic pain at 6 and 12 months, neuropathic pain, pain interference, anxiety, and depression. Overall, 178 patients received ropivacaine, and 174 received saline. At 3 months, chronic pain was reported in 93 of 178 (52.2%) and 83 of 174 (47.7%) patients in the paravertebral and control groups, respectively (odds ratio, 1.20 [95% CI, 0.79 to 1.82], P = 0.394). At 6 and 12 months, chronic pain occurred in 104 of 178 (58.4%) versus 79 of 174 (45.4%) and 105 of 178 (59.0%) versus 93 of 174 (53.4%) patients in the paravertebral and control groups, respectively. Greater acute postoperative pain was observed in the control group 0 to 2 h (area under the receiver operating characteristics curve at rest, 4.3 ± 2.8 vs. 2.9 ± 2.8 VAS score units × hours, P < 0.001) and when maximal in this interval (3.8 ± 2.1 vs. 2.5 ± 2.5, P < 0.001) but not during any other interval. Postoperative morphine use was 73% less in the paravertebral group (odds ratio, 0.272 [95% CI, 0.171 to 0.429]; P < 0.001). Paravertebral block did not reduce the incidence of chronic pain after breast surgery. Paravertebral block did result in less immediate postoperative pain, but there were no other significant differences in postoperative outcomes.

Comparison of Ultrasound-Guided Pecto-intercostal Fascial Block and Transversus Thoracic Muscle Plane Block for Acute Poststernotomy Pain Management After Cardiac Surgery: A Prospective, Randomized, Double-Blind Pilot Study

The objective of the present study was to evaluate morphine consumption and pain scores 24 hours postoperatively to compare the effects of a bilateral pectointercostal fascial block (PIFB) with those of a transversus thoracic muscle plane block (TTMPB) on acute poststernotomy pain in cardiac surgery patients who have undergone median sternotomy. Prospective, randomized, double-blinded. The operating room, intensive care unit, and patient ward at a university hospital. Thirty-nine American Society of Anesthesiologists II-to-III patients aged 18- to-80 years, scheduled for elective cardiac surgery via median sternotomy. Patients randomly were allocated to groups scheduled to receive bilateral ultrasound-guided PIFB or TTMPB. The primary outcome was postoperative morphine use within the first 24 hours. Secondary outcomes were the numerical pain rating scale (NRS) scores at rest and during coughing, time of first analgesic demand from the patient-controlled analgesia (PCA) device, and rescue analgesia use. The nausea/vomiting scores, time to extubation, length ofstays in intensive care and the hospital, patient satisfaction scores, and complications were also recorded. The first 24-hour morphine use did not significantly differ between the PIFB and TTMPB groups (mean ± standard deviation [95% CI], 13.89 ± 6.80 [10.83-16.95] mg/24 h and 15.08 ± 7.42 [11.83-18.33] mg/24 h, respectively, p=0.608). No significant difference between the two groups in the NRS scores at rest and during coughing was observed; the groups had similar requirements for rescue analgesia in the first 24 hours (n [%], three [15.8] and seven [35], p=0.273, respectively). The time from PCA to the first analgesia request was longer in the PIFB than in the TTMPB group (median [interquartile range], 660 [540-900] minutes, and 240 [161-525] minutes, respectively, p=0.002). PIFB and TTMPB showed similar effectiveness for morphine consumption within 24 hours postoperatively and in pain scores in cardiac surgery patients.

Enteral feeding and the microbiome in critically ill children: a narrative review

ObjectiveThis narrative review summarizes our current knowledge on the interplay between enteral nutrition (EN) and gut microbiota in critically ill children, using examples from two commonly encountered diagnoses in the pediatric intensive care unit (PICU): severe sepsis and acute respiratory distress syndrome (ARDS). This review will also highlight potential areas of therapeutic interventions that should be explored in future studies.BackgroundCritically ill children display extreme dysbiosis in their gut microbiome. Factors within the PICU that are often associated with dysbiosis include the use of broad-spectrum antibiotics, proton-pump inhibitors (PPIs), intravenous morphine, and fasting. Dysbiosis can potentially lead to adverse clinical outcomes (e.g., nosocomial infection, and prolonged hospitalization). EN may modulate dysbiosis. The gut microbiota is involved in the breaking down of macronutrients, mainly carbohydrates and proteins. Fermentation of undigestible carbohydrate (e.g., inulin and oligosaccharides), and amino acids by large intestine microbiota produces short chain fatty acids (SCFAs). SCFAs serve as the main fuel source for enterocytes and help to maintain healthy gut lining. Changes to selected components of macronutrients can result in alterations in gut microbiome and have potentially beneficial effects in patients in the PICU.MethodsA comprehensive search of the MEDLINE, Cochrane Library and Google Scholar databases was conducted using appropriate MESH terms and keywords. In this narrative review, we provide a summary of current knowledge on effect of EN on gut microbiota in pediatric studies, but also describes animal- and lab-based, as well as adult studies where relevant.ConclusionsThe gut microbiome can be altered by dietary modifications and common PICU practices and treatment. Although there are strong associations in restoring eubiosis and improvement in clinical outcomes, proving causality remains challenging. Further microbiome research is needed to provide mechanistic insights into the impact of the ever changing gut microbiome. In the future, new microbiota targeted therapies could potentially be the treatment of challenging PICU conditions and restore homeostasis in these children.

Association of anesthetic and surgical risk factors with outcomes of initial diagnostic biopsies in a current cohort of children with anterior mediastinal masses

BackgroundDiagnostic biopsies of pediatric anterior mediastinal masses (AMMs) are high-risk procedures in which general anesthesia (GA) is traditionally avoided. However, awareness of historically recognized risk factors and corresponding perioperative management...

Comparison of the effect of dexmedetomidine with remifentanil on pain after lumbar laminectomy in patients under general anesthesia

Backgrounds and objectives: Acute postoperative pain is still an issue in patients undergoing lumbar laminectomy surgery. We compared the effects of remifentanil and dexmedetomidine on pain intensity as well as the analgesic requirements in patients undergoing spinal surgery. Methods: This randomized clinical trial study was conducted on 60 patients in the age range of 20 to 60 years with ASA class one and two of the American Anesthesia Association under elective lumbar vertebrae laminectomy. Patients were divided into two groups: Remifentanil (group R) and Dexmedetomidine (group D). Before induction of anesthesia in R group patients, 0.01 می g / kg / min remifentanil was used. In group D, 0.3 dexmedetomidine was injected from µg / min / 50kg using a syringe pump. Postoperative pain score, nausea, and vomiting, mean arterial blood pressure, and heart rate at recovery times, 6, 12, and 24 hours after surgery were recorded. Results: The propofol infusion rate was significantly lower in the DEX group than in group R (P = 0.001). Pain scores except for 6h after surgery was significantly lower in group DEX. Analgesic consumption was significantly lower in group DEX (P=0.021). Mean arterial pressure during surgery, after laryngoscopy, and recovery was significantly lower in group DEX (P&lt;0.05). The mean heart rate after laryngoscopy was significantly lower in group DEX (P=0.033). Conclusion: Intraoperative infusion of DEX improved hemodynamic parameters during surgery and decreased pain score, morphine use after lumbar laminectomy surgery.

Efficacy and safety of intrathecal morphine in total knee arthroplasty: A systematic review and meta-analysis.

Morphine is a potent analgesic used to manage the pain following total knee arthroplasty (TKA). We aim to assess the safety and efficacy of intrathecal morphine (ITM) compared with placebo following TKA. We systematically searched four databases for trials that study the safety and efficacy of ITM in TKA. From relevant studies, data were extracted and pooled as mean difference (MD) or standardized mean difference (SMD) with 95 percent confidence interval (CI) using Review Manager software (Version 5.3). We included six randomized controlled trials in our study. ITM significantly reduced pain scores at 4 hours (SMD = -0.82, 95 percent CI [-1.52, -0.12], p = 0.02) and 24 hours (MD = -2.01, 95 percent CI [-2.93, -1.09], p = 0.0001) after surgery compared to placebo. No statistically significant difference in cumulative morphine use or nausea episodes was observed after 24 hours. ITM in-creased the risk of pruritus more than placebo (relative risk [RR] = 4.82, 95 percent CI [2.34, 9.93], p < 0.0001). ITM reduces pain at 4 and 24 hours post-operatively with no effect on cumulative morphine consumption. The only feared side effect is pruritus.

Towards identifying nicomorphine administration in doping control: synthesis of metabolites.

Aim: Nicomorphine is rapidly metabolized mainly to the biologically active 6-nicotinoyl morphine and morphine. In sport, morphine and nicomorphine use is prohibited whereas codeine use is permitted. Accredited laboratories routinely test for morphine hence must be able to distinguish morphine, as a metabolite of a prohibited substance, from that whose use is permitted. Results: Here we show a relatively simple method to synthesize the nicomorphine metabolites, 3-nicotinoyland 6-nicotinoyl morphine, and indicate how they may be used to identify nicomorphine administration. Conclusion: This approach should help confirm that it is not codeine, an allowable analgesic in sport, that has been administered.

Significance of Metabolite Ratios in the Interpretation of Segmental Hair Testing Results-Differentiation of Single from Chronic Morphine Use in a Case Series.

In morphine intoxication cases, forensic toxicologists are frequently confronted with the question of if the individual was opioid-tolerant or opioid-naïve, which can be investigated by hair analysis. However, interpretation of results can be challenging. Here, we report on hair testing for morphine and its metabolite hydromorphone following morphine intoxication without tolerance and upon chronic use. Two consecutive hair samples were collected after a non-fatal intoxication. Analysis comprised short hair segments and their initial wash water solutions. In the intoxications, morphine and hydromorphone levels were 3.3 to 56 pg/mg and at maximum 9.8 pg/mg, respectively. Both levels and hydromorphone to morphine ratios were significantly lower compared to chronic morphine use. In the non-fatal intoxication, the highest hydromorphone to morphine ratio was obtained in the segment corresponding to the time of intoxication. Morphine ratios of wash to hair were significantly higher in the intoxications compared to chronic use, being indicative of sweat/sebum contamination. We recommend including the analysis of hydromorphone and the initial wash solution in cases of morphine intoxications. Our study demonstrates that hydromorphone to morphine ratios can help in distinguishing single from chronic morphine use and in estimating the period of exposure when a consecutive hair sample can be collected in survived intoxications.

MPalliative Care Link: Examination of a Mobile Solution to Palliative Care Coordination Among Tanzanian Patients With Cancer.

PURPOSELate-stage cancer patient symptom control is a national priority in Tanzania. Mobile health promises to improve the reach of a limited pool of palliative care specialists through interprofessional, community-based care coordination. This work assessed the effectiveness of a smartphone- or Web-based app, mPalliative Care Link (mPCL), to extend specialist access via shared data and communication with local health workers. Central to mPCL is the African Palliative care Outcome Scale (POS), adapted for automated mobile symptom assessment and response.METHODSAdult patients with incurable cancer were randomly assigned at hospital discharge to mPCL versus phone-contact POS collection. Sociodemographic, clinical, and POS data were obtained at baseline. Twice-weekly POS responses were collected and managed via mPCL or phone contact with clinician study personnel for up to 4 months, on the basis of study arm assignment. Patient end-of-study care satisfaction was assessed via phone survey.RESULTSForty-nine patients per arm participated. Comparison of baseline characteristics showed an insignificant trend toward more women (P = .07) and higher discharge morphine use (P = .09) in the mPCL group compared with phone-contact and significant between-group differences in cancer types (P = .003). Proportions of deaths were near equal between groups (mPCL: 27%; phone-contact: 29%). Overall symptom severity was significantly lower in the phone-contact group (P < .0001), and symptom severity decreased over time in both groups (P = .0001); however, between-group change in overall symptoms over time did not vary significantly (P = .34). Care satisfaction was generally high in both groups.CONCLUSIONHigher symptom severity scores in the mPCL arm likely reflect between-group sociodemographic and clinical differences and clinical support of phone-contact arm participants. Similar rates of care satisfaction in both groups suggest that mPCL may support symptom-focused care coordination in a more efficient and scalable manner than phone contact. A broader study of mPCL's cost efficiency and utility in Tanzania is needed.

The Effect of Facilitated Tucking on the Pain Intensity Induced by Chest Tube Removal in Infants.

Removal of a chest tube is a painful procedure for infants. Medications, including narcotics, are used to control pain, but nonpharmacologic interventions are also effective in reducing pain during this procedure and are not associated with adverse effects. To evaluate the additive effect of facilitated tucking to the use of morphine on infant pain associated at the time of chest tube removal. This was a prospective, randomized control study. Sixty infants were randomized into 2 equal groups utilizing a coin flip. All infants received 0.05-mg/kg morphine 20 minutes before chest tube removal. The intervention group received facilitated tucking and the control group received standard care. Infant pain was measured using the Neonatal Infant Pain Scale. Pain was assessed at 3 time points by 2 independent evaluators: 5 minutes before, during, and 5 minutes after removal of the chest tube. Mann-Whitney and Fisher's exact (Chi-square) tests were used to compare the intervention and control groups. Pain scores were increased during chest tube removal for both the intervention and the control groups. Compared with the control group, pain scores for infants in the intervention group were less before, during, and after chest tube removal. Facilitated tucking combined with morphine administration can be an effective additive intervention for pain control in infants during chest tube removal. Evaluate the effect of the facilitated tucking on pain induced by chest tube removal in preterm infants. Preterm infants may respond differently to pain.

P135. Does a dedicated scoliosis team and surgical standardization improve outcomes in adolescent idiopathic scoliosis surgery and is it reproducible?

<h3>BACKGROUND CONTEXT</h3> Expedited recovery after surgery protocols and the perioperative surgical home are two initiatives that address the need for increased efficiency in patient care. In 2011, we implemented a standardized approach including a "scoliosis team" of dedicated anesthesiologists, operating room nurses, surgical technicians, and neurophysiologists. We also implemented a standardized preoperative work-up, specific intraoperative protocols including the use of anti-fibrinolytics and intrathecal morphine, and a multidisciplinary postoperative care model. <h3>PURPOSE</h3> The purpose of this study is to determine if standardization improves AIS surgery outcomes and whether it is transferrable between institutions. <h3>STUDY DESIGN/SETTING</h3> Retrospective multicenter review. <h3>PATIENT SAMPLE</h3> Adolescent Idiopathic Scoliosis patients that underwent surgery between 2009 and 2018. <h3>OUTCOME MEASURES</h3> Surgical outcomes including operative time and length of stay. <h3>METHODS</h3> In each institution, a non-standardized group (NST) and a standardized group (ST), were compared. Demographics and perioperative outcomes were recorded. In 2015, the surgeons changed institutions (to IB). Reproducibility was determined between institutions (IA vs IB). Median (IQR), Kruskal-Wallis, and Fisher's exact test were used. <h3>RESULTS</h3> A total of 325 AIS patients were collected from the database. The non-standardized group (NST) included 44 patients, while the standardized group (ST) included 281 patients. Age (p=0.21), BMI (p=0.48), preoperative Cobb angle (p=0.48), levels fused (p=0.42), and correction percentage (p=0.39) were all similar. Standardized protocol patients had lower estimated blood loss (EBL) (700 ml vs 325 ml, p<0.001), shorter anesthesia time (437 min vs 384 min, p=0.004), shorter surgical time (310 min vs 248 min, p<0.001), and shorter length of stay (LOS) (7 days vs 5 days, p<0.001). IA (n=101) and IB (n=105) were compared. Age (p=0.21), BMI (p=0.48) and preoperative Cobb angle (p=0.48) were similar. EBL (p<0.001), anesthesia time (p<0.001), surgical time (p<0.001), and LOS (p<0.001) were significantly lower in IB. <h3>CONCLUSIONS</h3> A standardized AIS approach including a dedicated operative team, preoperative work up, postoperative multidisciplinary management, and streamlined surgical steps improves outcomes and efficiency. <h3>FDA DEVICE/DRUG STATUS</h3> This abstract does not discuss or include any applicable devices or drugs.

Morphine restores and naloxone-precipitated withdrawal depresses wheel running in rats with hindpaw inflammation

Opioids such as morphine are the most effective treatment for pain, but termination of opioid use can produce severe withdrawal symptoms. The present study models this process by using home cage wheel running to assess well-being as a result of pain, morphine analgesia, and opioid withdrawal. Injection of CFA into the right hindpaw caused a dramatic decrease in wheel running and body weight. Implantation of two morphine pellets (75 mg each) resulted in an increase in body weight on Day 1 of administration and a more gradual restoration of wheel running that was only evident during the dark phase of the circadian cycle on Days 3 and 4 of morphine administration. Continuous morphine administration decreased wheel running during the relatively inactive light phase. These findings are consistent with the clinical goal of pain therapeutics to restore normal activity during the day and facilitate sleep at night. Administration of naloxone (1 mg/kg) on Day 5 of morphine administration depressed wheel running for approximately 4 h and caused an increase in wet dog shakes. Naloxone-precipitated changes were no longer evident 6 h after administration. These findings demonstrate that the use of morphine to treat pain does not protect against opioid withdrawal. Moreover, this study provides additional support for the use of home cage wheel running as a method to assess changes in well-being as a result of pain, analgesia, and opioid withdrawal.

Profiling the Effects of Repetitive Morphine Administration on Motor Behavior in Rats.

Efficient repetitive clinical use of morphine is limited by its numerous side effects, whereas analgesic tolerance necessitates subsequent increases in morphine dose to achieve adequate levels of analgesia. While many studies focused on analgesic tolerance, the effect of morphine dosing on non-analgesic effects has been overlooked. This study aimed to characterize morphine-induced behavior and the development and progression of morphine-induced behavioral tolerance. Adult male Sprague–Dawley rats were repetitively treated with subcutaneous morphine for 14 days in two dose groups (A: 5 mg/kg/day (b.i.d.) → 10 mg/kg/day; B: 10 mg/kg/day (b.i.d.) → 20 mg/kg/day). Motor behavior was assessed daily (distance traveled, speed, moving time, rearing, rotation) in an open-field arena, before and 30 min post-injections. Antinociception was measured using tail-flick and hot-plate assays. All measured parameters were highly suppressed in both dosing groups on the first treatment day, followed by a gradual manifestation of behavioral tolerance as the treatment progressed. Animals in the high-dose group showed increased locomotor activity after 10 days of morphine treatment. This excitatory phase converted to an inhibition of behavior when a higher morphine dose was introduced. We suggest that the excitatory locomotor effects of repetitive high-dose morphine exposure represent a signature of its behavioral and antinociceptive tolerance.

Activation of the spinal EGFR signaling pathway in a rat model of cancer-induced bone pain with morphine tolerance

Cancer-induced bone pain (CIBP) is considered to be one of the most difficult pain conditions to treat. Morphine, an analgesic drug, is widely used in clinical practice, and long-term use of morphine can lead to drug tolerance. Recent reports have suggested that inhibitors of epidermal growth factor receptor (EGFR) may have analgesic effects in cancer patients suffering from pain. Therefore, we sought to determine whether EGFR signaling was involved in morphine tolerance (MT) in a rat model of cancer-induced bone pain. In this study, Walker 256 mammary gland carcinoma cells were inoculated into the tibias of rats to provoke cancer-induced bone pain. Then, morphine was intrathecally administered twice daily for seven consecutive days to induce drug tolerance. We observed sustained increased in the protein levels of EGFR, p-EGFR, ERK1/2, and p-ERK1/2 during the development of morphine tolerance in rats with cancer-induced bone pain by western blotting. The EGFR level was significantly increased in the MT and CIBP + MT groups, and EGFR was colocalized with markers of microglia and neurons in the spinal cords of rats. Inhibition of EGFR by a small molecule inhibitor markedly attenuated the degree of morphine tolerance and decreased the number of microglia, and the protein levels of EGFR, p-EGFR, ERK1/2, and p-ERK1/2 were also reduced. In summary, our results suggest that the activation of the EGFR signaling pathway in spinal microglia plays an important modulatory role in the development of morphine tolerance and that inhibition of EGFR may provide a new therapeutic option for cancer-induced bone pain.

Cost-effectiveness and cost-benefit analysis of oliceridine in the treatment of acute pain.

Aim: Oliceridine, a new class of μ-opioid receptor agonist, is selective for G-protein signaling (analgesia) with limited recruitment of β-arrestin (associated with adverse outcomes) and may provide a cost-effective alternative versus conventional opioid morphine for postoperative pain. Patients & methods: Using a decision tree with a 24-h time horizon, we calculated costs for medication and management of three most common adverse events (AEs; oxygen saturation <90%, vomiting and somnolence) following postoperative oliceridine or morphine use. Results: Using oliceridine, the cost for managing AEs was US$528,424 versus $852,429 for morphine, with a net cost savings of $324,005. Conclusion: Oliceridine has a favorable overall impact on the total cost of postoperative care compared with the use of the conventional opioid morphine.

Treatment with dopamine \u03b2-hydroxylase (DBH) inhibitors prevents morphine use and relapse-like behavior in rats

BackgroundOpioid use disorders are serious contributors to the harms associated with the drug use. Unfortunately, therapeutic interventions for opioid addicts after detoxification have been limited and not sufficiently effective. Recently, several studies have led to promising results with disulfiram (DSF), a dopamine β-hydroxylase (DBH) inhibitor, showing that it is a potent agent against not only alcohol but also addiction to various drugs.Materials and methodsThis study was designed to examine whether DSF and nepicastat (NEP; another DBH inhibitor) modify morphine intake and reinstatement of seeking-behavior using the rat model of intravenous morphine self-administration. Additionally, we intended to estimate the effects of both inhibitors on the locomotor activity as well as on extracellular dopamine and its metabolite levels in the nucleus accumbens using microdialysis in naive rats.ResultsWe demonstrated that both DBH inhibitors reduced responding to morphine self-administration. Moreover, DSF and NEP administered acutely before reinstatement test sessions consistently attenuated the reinforcing effects of morphine and a morphine-associated conditioned cue. The observed effects for lower doses (6.25–25 mg/kg; ip) of both DBH inhibitors seem to be independent of locomotor activity reduction and dopamine level in the nucleus accumbens. Neither DSF nor NEP administered daily during morphine abstinence with extinction training sessions had any effect on active lever-responding and changed the reinstatement induced by morphine priming doses. Reinstatement of drug-seeking behavior induced by a conditioned cue previously associated with morphine delivery was attenuated following repeated administration of DSF or NEP during the abstinence period.ConclusionThese results seem to point to the significance of DBH inhibition as a potential pharmacotherapy against morphine use disorders.Graphic abstract

The safety of morphine in patients with acute heart failure: A systematic review and meta-analysis.

While morphine has long been widely used in treating acute heart failure (AHF) due to its vasodilatory properties and anticipated anxiolysis, it remains unclear whether the application of morphine to those patients is reasonable. We aim to conduct a systematic review and meta‐analysis to assess the safety of morphine in patients with AHF. We searched PubMed, Cochrane Library, and Embase electronic databases from inception through March 2020. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were used to estimate the outcomes. Seven studies with 172, 226 patients were included. The results showed that morphine usage was not associated with increased in‐hospital mortality (OR: 1.94; 95% CI 0.93 to 4.03; p = 0.08). However, the use of morphine significantly increased the risk of invasive ventilation (OR: 2.72; 95% CI 1.09 to 6.80; p = 0.03). Furthermore, the subgroup analysis indicated that the application of morphine was not associated with increased 7‐day all‐cause mortality in patients with AHF (OR: 1.69; 95% CI 0.80 to 3.22; p = 0.11) but significantly increased the risk of 30‐day all‐cause mortality (OR: 1.59; 95% CI 1.16 to 2.17; p = 0.004). Based on current evidence, our results suggested that although morphine therapy did not significantly increase the risk of short‐term death (in the hospital or within 7 days) in patients with AHF, the risk of long‐term death and invasive ventilation were significantly increased. This result needs to be further confirmed by an ongoing randomized control trial.

Opioid treatment for opioid withdrawal in newborn infants.

Opioid treatment for opioid withdrawal in newborn infants.

Morphine use in AHF increases ventilator use and 30-day mortality

Morphine use in AHF increases ventilator use and 30-day mortality